From Medscape Medical News
Laurie Barclay, MD
September 22, 2009 — An Expert Panel of the Infectious Diseases Society of America (IDSA) has prepared updated, evidence-based guidelines for immunization of infants, children, adolescents, and adults. The new guidelines, which are published in the September 15 issue of Clinical Infectious Diseases, replace the previous IDSA clinical practice guideline for quality standards for immunization, published in 2002
"The IDSA updates its guidelines when new data or publications change prior recommendations or when the Expert Panel decides that clarification or additional guidance is warranted," write Larry K. Pickering, from the National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, and colleagues. "For the 2009 guidelines, vaccine licensure, approval, recommendations, safety, financing, barriers, and implementation issues were reviewed. This report does not include issues involving vaccines and autism and other potential adverse events."
These guidelines are intended to assist clinicians who care for either immunocompetent or immunocompromised people of all ages to provide recommended vaccinations. Since the previous clinical practice guideline was published in 2002, there have been significant improvements in the ability to prevent more infectious diseases.
New Vaccines, Recommendations
New vaccines that have been licensed since 2002 include human papillomavirus vaccine; live, attenuated influenza vaccine; meningococcal conjugate vaccine; rotavirus vaccine; tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine; and zoster vaccine. New combination vaccines that have become available are measles, mumps, rubella, and varicella vaccine; tetanus, diphtheria, and pertussis and inactivated polio vaccine; and tetanus, diphtheria, and pertussis and inactivated polio/Haemophilus influenzae type b vaccine.
For young children, hepatitis A vaccines are now universally recommended.
All children aged 6 months through 18 years and adults who are 50 years or older should receive annual administration of influenza vaccines.
The routine childhood and adolescent immunization schedule now includes a second dose of varicella vaccine.
The adolescent and adult immunization schedules have expanded to accommodate many of these new recommendations.
Other areas highlighted in the updated guidelines include the need to remove barriers to immunization, to eliminate racial and ethnic disparities in access to and compliance with vaccine recommendation, to address issues regarding vaccine safety, and to fund the cost of implementing recommended vaccinations.
The updated guidelines also provide specific recommendations for vaccination of special groups, including healthcare providers, immunocompromised patients, pregnant women, international travelers, and internationally adopted children.
Specific vaccine recommendations for infants, children, adolescents, and adults, and their accompanying level of evidence rating, are as follows:
Infants, children, adolescents, and adults should be given all age-appropriate vaccines as recommended by the Advisory Committee on Immunization Practices, the American Academy of Family Physicians, and the American Academy of Pediatrics
When a vaccine dose is not given at the recommended age, it should be given at any subsequent medical visit when indicated and feasible, without restarting the series
For people who have delayed immunizations or who want to accelerate their vaccination schedule, recommendations for the minimum interval between doses should still be followed
All indicated vaccines should be administered simultaneously when appropriate and feasible
Licensed combination vaccines may be given provided the following conditions apply: any components of the combination are indicated, other components are not contraindicated, and the US Food and Drug Administration (FDA) has licensed the vaccine for that dose of the series (
For childcare, schools and colleges, and nursing homes, specific immunization requirements should be followed
Vaccinations delivery should be coordinated with other preventive healthcare services recommended for children, adolescents, and adults
Storage and administration of all vaccines should follow recommendations of the manufacturer and licensing requirements from the FDA
Clin Infect Dis. 2009;49:817–840. Abstract
Friday, September 25, 2009
Monday, September 14, 2009
Aerobic Exercise May Reduce Risk for Fatty Liver Disease
From Medscape Medical News
Deborah Brauser
September 11, 2009 — Obese individuals with a sedentary lifestyle can lower their risk for nonalcoholic fatty liver disease (NAFLD) by engaging in routine physical activities, according to results of a small randomized study published online June 15 in Hepatology.
In addition, this lower risk was not contingent upon weight loss, but was a direct result of the increased exercise program.
"These data provide the first direct experimental evidence demonstrating that regular aerobic exercise reduces hepatic lipids in obesity even in the absence of body-weight reduction," write Nathan A. Johnson, from the Discipline of Exercise and Sport Science and the Institute of Obesity, Nutrition and Exercise at the University of Sydney in Australia, and colleagues.
"Physical activity should be strongly promoted for the management of fatty liver," add the study authors.
The location of body fatness, particularly visceral adipose tissue (VAT), is increasingly recognized as being of greater importance in determining the metabolic and cardiovascular consequences of excess adiposity, the authors report.
In addition, evidence is emerging that excessive storage of hepatocellular triglyceride is a common feature of obesity, with hepatic steatosis (or NAFLD) possibly affecting 30% of the adult population and the majority of obese individuals.
However, there is a paucity of evidence regarding the effects of diet and exercise interventions on reducing hepatic triglyceride concentration (HTGC), and no definitive pharmacotherapy exists for it.
Strategies Besides Those Aimed at Weight Loss Are Needed
"Although intervention aimed at weight loss is advocated, reductions in weight by dietary restriction are typically modest and are increasingly viewed as an unsustainable outcome of lifestyle modification," write the study authors. "Therefore, appropriate therapeutic strategies for reducing HTGC, which are not contingent upon weight loss, are needed."
Although the effect of aerobic exercise on liver fat independent of weight loss has not been clarified, the investigators sought to assess its effect on hepatic, blood, abdominal, and muscle lipids for this study.
Dr. Johnson and his team enrolled 23 obese adults who had a body mass index of 30 kg/m2 or higher and who reported a sedentary lifestyle and low alcohol intake (0-20 g/day).
Baseline measurements were performed to determine HTGC and saturation index, abdominal VAT and subcutaneous adipose tissue (SAT) area and volume, intramyocellular triglyceride concentration, cardiorespiratory fitness, anthropometry, and blood biochemistry.
A total of 19 patients were then randomly allocated to receive either 4 weeks of supervised aerobic exercise training (n = 12) made up of 3 cycle ergometer sessions (30–45 minutes each) per week or 4 weeks of a sham intervention (placebo, n = 7). Those in the placebo group received 1 supervised stretching session at treatment initiation and were then directed to perform the stretches 3 times per week at home.
The investigators measured HTGC with noninvasive proton magnetic resonance spectroscopy and measured abdominal lipids by magnetic resonance imaging. Cardiorespiratory fitness was assessed using the Physical Work Capacity test undertaken on a cycle ergometer. All measurements for both groups were repeated at completion of the allocated exercise programs.
After 4 weeks of aerobic cycling exercise, VAT volume was significantly reduced by 12% (P < .01) and HTGC was reduced by 21% (P < .05).
The aerobic exercise regime was also associated with a significant (14%) reduction in plasma free fatty acids (P < .05).
Exercise training did not alter body weight, vastus lateralis intramyocellular triglyceride, abdominal SAT volume, magnetic resonance spectroscopy-measured hepatic lipid saturation, or homeostasis model assessment of insulin resistance (P > .05).
First Direct Evidence
"Using a short-term aerobic cycling training intervention in previously sedentary obese adults, we provide the first direct experimental evidence demonstrating that regular aerobic exercise training reduces hepatic lipids without concurrent changes in body weight or abdominal SAT content," write the study authors. "Thus, regular exercise may mitigate the metabolic and cardiovascular consequences of obesity, including fatty liver."
"Our observation of a beneficial effect of regular exercise itself . . . should refocus the debate, and hence policy, on the role of physical activity in the prevention and management of obesity and NAFLD. In other words, physical activity should be strongly promoted for the management of fatty liver," conclude the study authors.
Hepatology. 2009;50:000-000. Abstract
Deborah Brauser
September 11, 2009 — Obese individuals with a sedentary lifestyle can lower their risk for nonalcoholic fatty liver disease (NAFLD) by engaging in routine physical activities, according to results of a small randomized study published online June 15 in Hepatology.
In addition, this lower risk was not contingent upon weight loss, but was a direct result of the increased exercise program.
"These data provide the first direct experimental evidence demonstrating that regular aerobic exercise reduces hepatic lipids in obesity even in the absence of body-weight reduction," write Nathan A. Johnson, from the Discipline of Exercise and Sport Science and the Institute of Obesity, Nutrition and Exercise at the University of Sydney in Australia, and colleagues.
"Physical activity should be strongly promoted for the management of fatty liver," add the study authors.
The location of body fatness, particularly visceral adipose tissue (VAT), is increasingly recognized as being of greater importance in determining the metabolic and cardiovascular consequences of excess adiposity, the authors report.
In addition, evidence is emerging that excessive storage of hepatocellular triglyceride is a common feature of obesity, with hepatic steatosis (or NAFLD) possibly affecting 30% of the adult population and the majority of obese individuals.
However, there is a paucity of evidence regarding the effects of diet and exercise interventions on reducing hepatic triglyceride concentration (HTGC), and no definitive pharmacotherapy exists for it.
Strategies Besides Those Aimed at Weight Loss Are Needed
"Although intervention aimed at weight loss is advocated, reductions in weight by dietary restriction are typically modest and are increasingly viewed as an unsustainable outcome of lifestyle modification," write the study authors. "Therefore, appropriate therapeutic strategies for reducing HTGC, which are not contingent upon weight loss, are needed."
Although the effect of aerobic exercise on liver fat independent of weight loss has not been clarified, the investigators sought to assess its effect on hepatic, blood, abdominal, and muscle lipids for this study.
Dr. Johnson and his team enrolled 23 obese adults who had a body mass index of 30 kg/m2 or higher and who reported a sedentary lifestyle and low alcohol intake (0-20 g/day).
Baseline measurements were performed to determine HTGC and saturation index, abdominal VAT and subcutaneous adipose tissue (SAT) area and volume, intramyocellular triglyceride concentration, cardiorespiratory fitness, anthropometry, and blood biochemistry.
A total of 19 patients were then randomly allocated to receive either 4 weeks of supervised aerobic exercise training (n = 12) made up of 3 cycle ergometer sessions (30–45 minutes each) per week or 4 weeks of a sham intervention (placebo, n = 7). Those in the placebo group received 1 supervised stretching session at treatment initiation and were then directed to perform the stretches 3 times per week at home.
The investigators measured HTGC with noninvasive proton magnetic resonance spectroscopy and measured abdominal lipids by magnetic resonance imaging. Cardiorespiratory fitness was assessed using the Physical Work Capacity test undertaken on a cycle ergometer. All measurements for both groups were repeated at completion of the allocated exercise programs.
After 4 weeks of aerobic cycling exercise, VAT volume was significantly reduced by 12% (P < .01) and HTGC was reduced by 21% (P < .05).
The aerobic exercise regime was also associated with a significant (14%) reduction in plasma free fatty acids (P < .05).
Exercise training did not alter body weight, vastus lateralis intramyocellular triglyceride, abdominal SAT volume, magnetic resonance spectroscopy-measured hepatic lipid saturation, or homeostasis model assessment of insulin resistance (P > .05).
First Direct Evidence
"Using a short-term aerobic cycling training intervention in previously sedentary obese adults, we provide the first direct experimental evidence demonstrating that regular aerobic exercise training reduces hepatic lipids without concurrent changes in body weight or abdominal SAT content," write the study authors. "Thus, regular exercise may mitigate the metabolic and cardiovascular consequences of obesity, including fatty liver."
"Our observation of a beneficial effect of regular exercise itself . . . should refocus the debate, and hence policy, on the role of physical activity in the prevention and management of obesity and NAFLD. In other words, physical activity should be strongly promoted for the management of fatty liver," conclude the study authors.
Hepatology. 2009;50:000-000. Abstract
Saturday, September 12, 2009
Baldness and Myocardial Infarction in Men?
From American Journal of Epidemiology
The Atherosclerosis Risk in Communities Study
Eyal Shahar; Gerardo Heiss; Wayne D. Rosamond; Moyses Szklo
Abstract
Because hair loss may be a surrogate measure of androgenic activity -- possibly a determinant of coronary atherosclerosis -- several studies have explored the presence and magnitude of an association between male pattern baldness and myocardial infarction (MI). In particular, vertex baldness, but not frontal baldness alone, was strongly associated with incident MI in a large, hospital-based, case-control study.
The authors examined these associations in a cross-sectional sample of 5,056 men aged 52-75 years, of whom 767 had a history of MI. The sample was derived from the Atherosclerosis Risk in Communities (ARIC) Study (1987-1998).
As compared with a baldness-free reference group, the estimated odds ratios for prevalent MI from a multivariable model were 1.28 (frontal baldness), 1.02 (mild vertex baldness), 1.40 (moderate vertex baldness), and 1.18 (severe vertex baldness). Other regression models have yielded similar results, including the absence of a monotonic "dose-response relation" between the extent of vertex baldness and prevalent MI.
The authors also examined the relation of baldness pattern to carotid intimal-medial thickness, a measure of atherosclerosis, among those who were free of clinical cardiovascular disease. The estimated mean differences in carotid intimal-medial thickness between groups of men with various types of baldness and their baldness-free counterparts were all close to zero.
The results of this study suggest that male pattern baldness is not a surrogate measure of an important risk factor for myocardial infarction or asymptomatic atherosclerosis.
http://www.medscape.com/viewarticle/578402
The Atherosclerosis Risk in Communities Study
Eyal Shahar; Gerardo Heiss; Wayne D. Rosamond; Moyses Szklo
Abstract
Because hair loss may be a surrogate measure of androgenic activity -- possibly a determinant of coronary atherosclerosis -- several studies have explored the presence and magnitude of an association between male pattern baldness and myocardial infarction (MI). In particular, vertex baldness, but not frontal baldness alone, was strongly associated with incident MI in a large, hospital-based, case-control study.
The authors examined these associations in a cross-sectional sample of 5,056 men aged 52-75 years, of whom 767 had a history of MI. The sample was derived from the Atherosclerosis Risk in Communities (ARIC) Study (1987-1998).
As compared with a baldness-free reference group, the estimated odds ratios for prevalent MI from a multivariable model were 1.28 (frontal baldness), 1.02 (mild vertex baldness), 1.40 (moderate vertex baldness), and 1.18 (severe vertex baldness). Other regression models have yielded similar results, including the absence of a monotonic "dose-response relation" between the extent of vertex baldness and prevalent MI.
The authors also examined the relation of baldness pattern to carotid intimal-medial thickness, a measure of atherosclerosis, among those who were free of clinical cardiovascular disease. The estimated mean differences in carotid intimal-medial thickness between groups of men with various types of baldness and their baldness-free counterparts were all close to zero.
The results of this study suggest that male pattern baldness is not a surrogate measure of an important risk factor for myocardial infarction or asymptomatic atherosclerosis.
http://www.medscape.com/viewarticle/578402
Haze & Your Heart
Hi everyone who has to put up with the haze the last few weeks,
Do be careful if you have had heart attacks before.
Air Pollution Can Induce Arrhythmias (irregular heart beat) in Some MI Patients
From Reuters Health Information
Aug 07 - A history of myocardial infarction can increase the risk of ventricular arrhythmias when patients are exposed to airborne particulate matter, according to Italian researchers. Failure to take beta-blockers appears to make these patients more prone to autonomic dysregulation.
As reported in the July issue of the European Heart Journal, Dr. Antonio F. Folino of the University of Padua and colleagues assessed the impact of air pollution on arrhythmias and autonomic function in 39 patients with a prior myocardial infarction.
"We accurately assessed the exposure to air pollution...by means of personal samplers worn by the subjects in backpacks for 24 hours, analyzing the particulate matter to which they were exposed," Dr. Folino told Reuters Health.
At the same time as air pollution monitoring, all of the subjects underwent continuous ECG recording. Thirty-two of the patients were taking beta blockers.
Overall, there was no correlation between heart rate variability and exposure to particulate matter. However, there was a negative correlation between heart rate variability and exposure to PM-0.25 in the patients not taking beta-blockers. More severe ventricular arrhythmias were observed at the highest concentrations of PM-10 and PM-2.5.
"We showed a direct negative influence of particulate matter on the cardiovascular system," Dr. Folino said. "In particular, the inhalation of the larger particles has been correlated with increased arrhythmias, while the ultrafine (particles) induced an increase in sympathetic autonomic activity, a negative factor in the prognosis of patients with heart disease."
These results, he concluded, show that "patients with coronary artery disease are particularly vulnerable to the effect of air pollution and that the effects of air pollutants can worsen the prognosis of these subjects."
Eur Heart J 2009;30:1614-1620.
Do be careful if you have had heart attacks before.
Air Pollution Can Induce Arrhythmias (irregular heart beat) in Some MI Patients
From Reuters Health Information
Aug 07 - A history of myocardial infarction can increase the risk of ventricular arrhythmias when patients are exposed to airborne particulate matter, according to Italian researchers. Failure to take beta-blockers appears to make these patients more prone to autonomic dysregulation.
As reported in the July issue of the European Heart Journal, Dr. Antonio F. Folino of the University of Padua and colleagues assessed the impact of air pollution on arrhythmias and autonomic function in 39 patients with a prior myocardial infarction.
"We accurately assessed the exposure to air pollution...by means of personal samplers worn by the subjects in backpacks for 24 hours, analyzing the particulate matter to which they were exposed," Dr. Folino told Reuters Health.
At the same time as air pollution monitoring, all of the subjects underwent continuous ECG recording. Thirty-two of the patients were taking beta blockers.
Overall, there was no correlation between heart rate variability and exposure to particulate matter. However, there was a negative correlation between heart rate variability and exposure to PM-0.25 in the patients not taking beta-blockers. More severe ventricular arrhythmias were observed at the highest concentrations of PM-10 and PM-2.5.
"We showed a direct negative influence of particulate matter on the cardiovascular system," Dr. Folino said. "In particular, the inhalation of the larger particles has been correlated with increased arrhythmias, while the ultrafine (particles) induced an increase in sympathetic autonomic activity, a negative factor in the prognosis of patients with heart disease."
These results, he concluded, show that "patients with coronary artery disease are particularly vulnerable to the effect of air pollution and that the effects of air pollutants can worsen the prognosis of these subjects."
Eur Heart J 2009;30:1614-1620.
Friday, September 11, 2009
DASH-Style Diet May Help Protect Against Kidney Stones
From Medscape Medical News
Laurie Barclay, MD
August 18, 2009 — The Dietary Approaches to Stop Hypertension (DASH) diet may help protect against kidney stones, according to the results of a prospective study reported online August 13 in the Journal of the American Society of Nephrology.
"Despite previously observed associations between individual dietary factors and kidney stone risk, relatively few studies have examined the impact of overall diet or dietary patterns on risk," write Eric N. Taylor, MD, from Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, and colleagues.
"The [DASH] diet, which is high in fruits and vegetables, moderate in low-fat dairy products, and low in animal protein represents a novel potential means of kidney stone prevention. The consumption of fruits and vegetables increases urinary citrate, an important inhibitor of calcium stone formation, and a diet with normal to high calcium content but low in animal protein and sodium decreases the risk of calcium oxalate stone recurrence by 51%," the researchers state.
The investigators studied the association between a DASH-style diet and incident kidney stones in the Health Professionals Follow-up Study (n = 45,821 men; 18 years of follow-up), Nurses' Health Study I (n = 94,108 older women; 18 years of follow-up), and Nurses' Health Study II (n = 101,837 younger women; 14 years of follow-up).
To determine degree of compliance with the DASH-style diet, the investigators constructed a DASH score based on 8 components: high consumption of fruits, vegetables, nuts and legumes, low-fat dairy products, and whole grains, and low consumption of sodium, sweetened beverages, and red and processed meats. Cox hazards regression allowed adjustment for age, body mass index (BMI), fluid intake, and other clinical factors.
During a combined follow-up of 50 years, there were 5645 incident kidney stones. Intakes of calcium, potassium, magnesium, oxalate, and vitamin C were higher in participants with higher DASH scores, and sodium intakes were lower.
The observed reductions in kidney stone risk were independent of age, BMI, fluid intake, and other factors. Even in participants with lower calcium intake, higher DASH scores predicted lower risk for kidney stones. The findings were unaffected by excluding participants with hypertension.
"Consumption of a DASH-style diet is associated with a marked decrease in kidney stone risk," the study authors write. "In contrast to our previous studies of individual dietary factors and kidney stone risk in these populations, the impact of a DASH-style diet was similar in men and women, in older and younger individuals, and in participants with both low and high BMI."
Limitations of this study include lack of data on stone composition reports from all stone formers, failure to examine the effect of DASH score on 24-hour urine calcium, poor measurement of sodium intake, and limited generalizability.
"Although we think it reasonable for calcium oxalate stone formers with high levels of urinary oxalate to avoid intake of some individual foods very high in oxalate (such as spinach and almonds), our data do not support the common practice of dietary oxalate restriction in calcium stone formers, particularly if such advice results in lower intake of fruits, vegetables, and whole grains. Because of the adverse side effect profile of many current medical therapies for nephrolithiasis, a randomized trial is needed to determine the efficacy of a DASH-style diet compared with medical intervention for the secondary prevention of calcium oxalate kidney stones."
J Am Soc Nephrol. Published online August 13, 2009.
Laurie Barclay, MD
August 18, 2009 — The Dietary Approaches to Stop Hypertension (DASH) diet may help protect against kidney stones, according to the results of a prospective study reported online August 13 in the Journal of the American Society of Nephrology.
"Despite previously observed associations between individual dietary factors and kidney stone risk, relatively few studies have examined the impact of overall diet or dietary patterns on risk," write Eric N. Taylor, MD, from Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, and colleagues.
"The [DASH] diet, which is high in fruits and vegetables, moderate in low-fat dairy products, and low in animal protein represents a novel potential means of kidney stone prevention. The consumption of fruits and vegetables increases urinary citrate, an important inhibitor of calcium stone formation, and a diet with normal to high calcium content but low in animal protein and sodium decreases the risk of calcium oxalate stone recurrence by 51%," the researchers state.
The investigators studied the association between a DASH-style diet and incident kidney stones in the Health Professionals Follow-up Study (n = 45,821 men; 18 years of follow-up), Nurses' Health Study I (n = 94,108 older women; 18 years of follow-up), and Nurses' Health Study II (n = 101,837 younger women; 14 years of follow-up).
To determine degree of compliance with the DASH-style diet, the investigators constructed a DASH score based on 8 components: high consumption of fruits, vegetables, nuts and legumes, low-fat dairy products, and whole grains, and low consumption of sodium, sweetened beverages, and red and processed meats. Cox hazards regression allowed adjustment for age, body mass index (BMI), fluid intake, and other clinical factors.
During a combined follow-up of 50 years, there were 5645 incident kidney stones. Intakes of calcium, potassium, magnesium, oxalate, and vitamin C were higher in participants with higher DASH scores, and sodium intakes were lower.
The observed reductions in kidney stone risk were independent of age, BMI, fluid intake, and other factors. Even in participants with lower calcium intake, higher DASH scores predicted lower risk for kidney stones. The findings were unaffected by excluding participants with hypertension.
"Consumption of a DASH-style diet is associated with a marked decrease in kidney stone risk," the study authors write. "In contrast to our previous studies of individual dietary factors and kidney stone risk in these populations, the impact of a DASH-style diet was similar in men and women, in older and younger individuals, and in participants with both low and high BMI."
Limitations of this study include lack of data on stone composition reports from all stone formers, failure to examine the effect of DASH score on 24-hour urine calcium, poor measurement of sodium intake, and limited generalizability.
"Although we think it reasonable for calcium oxalate stone formers with high levels of urinary oxalate to avoid intake of some individual foods very high in oxalate (such as spinach and almonds), our data do not support the common practice of dietary oxalate restriction in calcium stone formers, particularly if such advice results in lower intake of fruits, vegetables, and whole grains. Because of the adverse side effect profile of many current medical therapies for nephrolithiasis, a randomized trial is needed to determine the efficacy of a DASH-style diet compared with medical intervention for the secondary prevention of calcium oxalate kidney stones."
J Am Soc Nephrol. Published online August 13, 2009.
Thursday, September 10, 2009
Adherence to a Low-Fat, High-Fiber Diet Lowers Risk of Polyp Recurrence
From Reuters Health Information
Sep 04 - Patients who strictly follow a low-fat, high-fiber, and high-fruit and -vegetable diet have a lower risk of colon adenoma recurrence.
"The Polyp Prevention Trial was designed to test the effect of (this) dietary intervention on the recurrence of adenomas in the colon," Dr. Leah B. Sansbury of the National Cancer Institute, Bethesda, Maryland, and colleagues write in the September issue of the American Journal of Epidemiology.
The authors note that the goals of the dietary intervention were to limit fat to 20% of energy intake and to consume at least 18 g of fiber and 3.5 servings of fruits and vegetables per 1000 kcal.
"After 4 years of the trial, no difference in the rate of adenoma recurrence between the intervention group and the control group was observed," they note. "The number of dietary goals met by the intervention group varied greatly; thus, it is possible that lack of adherence in fully attaining the intervention goals may account for the lack of observed effect."
The researchers examined data from the Polyp Prevention Trial to determine whether strict adherence to the low-fat, high-fiber, and high-fruit and -vegetable intervention goals influenced the risk of adenoma recurrence. Included were 1095 subjects recruited between 1991 and 1994 (control group, n = 947; intervention group, n = 958). Annual food-frequency questionnaires were used to assess dietary intake and supplement use.
Colonoscopies were performed at baseline, the 1-year visits, and the end of the trial intervention.
Of 821 participants in the intervention group who completed the study, 245 (29.8%) were classified as poor compliers, 366 (44.6%) as inconsistent compliers, and 210 (25.6%) as super compliers. Subjects classified as super compliers consistently reported that they met or exceeded each of the dietary goals at all four annual visits.
In unadjusted analyses, super compliers had a 30% statistically significant decreased odds of adenoma recurrence compared with controls (odds ratio = 0.69). The association remained unchanged in fully adjusted models. Strict compliance to the intervention over the entire 4 years led to a nearly 50% statistically significant decreased odds of multiple adenomas. A nonsignificant inverse association was observed for multiple and advanced adenoma recurrence.
"To focus on testing the biologic effects of an intervention or treatment on the trial, future dietary and treatment trials could target and randomize individuals most likely to comply," Dr. Sansbury and associates conclude. "Findings from such trials would enhance the validity of our own findings."
Am J Epidemiol 2009;170:576-584.
Sep 04 - Patients who strictly follow a low-fat, high-fiber, and high-fruit and -vegetable diet have a lower risk of colon adenoma recurrence.
"The Polyp Prevention Trial was designed to test the effect of (this) dietary intervention on the recurrence of adenomas in the colon," Dr. Leah B. Sansbury of the National Cancer Institute, Bethesda, Maryland, and colleagues write in the September issue of the American Journal of Epidemiology.
The authors note that the goals of the dietary intervention were to limit fat to 20% of energy intake and to consume at least 18 g of fiber and 3.5 servings of fruits and vegetables per 1000 kcal.
"After 4 years of the trial, no difference in the rate of adenoma recurrence between the intervention group and the control group was observed," they note. "The number of dietary goals met by the intervention group varied greatly; thus, it is possible that lack of adherence in fully attaining the intervention goals may account for the lack of observed effect."
The researchers examined data from the Polyp Prevention Trial to determine whether strict adherence to the low-fat, high-fiber, and high-fruit and -vegetable intervention goals influenced the risk of adenoma recurrence. Included were 1095 subjects recruited between 1991 and 1994 (control group, n = 947; intervention group, n = 958). Annual food-frequency questionnaires were used to assess dietary intake and supplement use.
Colonoscopies were performed at baseline, the 1-year visits, and the end of the trial intervention.
Of 821 participants in the intervention group who completed the study, 245 (29.8%) were classified as poor compliers, 366 (44.6%) as inconsistent compliers, and 210 (25.6%) as super compliers. Subjects classified as super compliers consistently reported that they met or exceeded each of the dietary goals at all four annual visits.
In unadjusted analyses, super compliers had a 30% statistically significant decreased odds of adenoma recurrence compared with controls (odds ratio = 0.69). The association remained unchanged in fully adjusted models. Strict compliance to the intervention over the entire 4 years led to a nearly 50% statistically significant decreased odds of multiple adenomas. A nonsignificant inverse association was observed for multiple and advanced adenoma recurrence.
"To focus on testing the biologic effects of an intervention or treatment on the trial, future dietary and treatment trials could target and randomize individuals most likely to comply," Dr. Sansbury and associates conclude. "Findings from such trials would enhance the validity of our own findings."
Am J Epidemiol 2009;170:576-584.
What If Regular Exercise Were as Good as a Stent for Stable Angina?
From Heartwire
Shelley Wood
Medscape Conference Coverage, based on selected sessions at the:
European Society of Cardiology (ESC) Congress 2009
September 8, 2009 (Barcelona, Spain) - Investigators for the multicenter PET study were keen to build on the surprising findings from their pilot trial: that 12 months of exercise training was just as good as PCI for myocardial perfusion and symptom relief in patients with stable angina and even better in terms of preventing cardiovascular events. Those hopes, however, were dashed when the multicenter PET study ground to a halt due to a lack of enthusiasm among patients and enrolling centers.
But in new findings presented by Dr Rainer Hambrecht (Klinikum Links der Weser, Bremen, Germany) at the European Congress of Cardiology 2009 Congress, combined data from the PET pilot study and the aborted PET multicenter trial suggest that regular exercise training is superior to PCI at preventing subsequent cardiovascular events.
The original PET study [1] randomized 102 patients to either exercise or PCI and reexamined patients after 12 months using coronary angiography, technetium-99m scintigraphy, and ergospirometry, as well as a range of clinical end points. Results, which were published in Circulation in 2004, showed clear and comparable improvements in symptoms and myocardial perfusion from baseline with both treatment strategies, and a trend toward better event-free survival in the training group at both 12 and 48 months.
"Our expectation was that exercise training would not be inferior to PCI; however, what we saw after 12 months was a clear, significant improvement in exercise over PCI in patients with stable CAD," Hambrecht told heartwire .
Exercise benefits
Inspired by the PET pilot, Hambrecht et al launched the PET multicenter trial at four hospitals in Germany, Austria, Switzerland, and Romania. By design, patients were randomized either to PCI or to two weeks of a supervised exercise training program every day, made up of five short periods of exercise daily. Patients were then given bicycles at home and asked to exercise on them every day, plus attend a supervised exercise program one or two times per week. The bikes, Hambrecht told heartwire , were equipped with sensors that monitored the amount and duration of exercise and ensured that it was actually the study participant--and not another family member--who was using the equipment.
But according to Hambrecht, the trial had major problems recruiting and was halted with just over 100 of the original 400 patients it had hoped to enroll. The study had plenty of funding; enrollment problems lay with both the recruiting centers and the patients themselves, he said. "There was some reluctance among the centers to join us in performing this study and also difficulties recruiting patients for the study" and explaining the randomization process. "If you get the stent you are free of symptoms within a few minutes, [whereas] in the training group, you have to work a lot, for several months, to reduce the angina threshold."
As with the pilot study, there were striking improvements with both PCI and exercise training in angina class and improvements in event-free survival that were nonsignificantly better for the training patients.
However, when the patients from both the multicenter and pilot studies were combined for a total of 202 patients with two-year follow-up, investigators achieved the statistical significance not met in the multicenter trial, Hambrecht reported. In a pooled analysis of event-free survival, 21 events occurred in the training group as opposed to 32 events in the PCI group (p=0.039). The differences speak to the direct benefits of exercise on the cardiovascular system globally, as opposed to the palliative, more localized benefits of PCI. Whereas both strategies improve myocardial perfusion, angina threshold, and exercise capacity, only exercise improves endothelial function and slows disease progression, he noted. Moreover, he stressed, improvements in both arms were seen on top of optimal medical therapy.
Forces work against exercise
In an interview with heartwire , Hambrecht acknowledged that there are multiple forces working against a scenario in which regular exercise is prescribed instead of stenting. For one, patients are not motivated to take responsibility for improving their own cardiovascular health--even if it means better event-free survival. For another, encouraging exercising is financially less appealing for hospitals, Hambrecht observed: "That was my feeling, that hospitals were reluctant to participate in this study, because they derive revenue from PCI procedures."
Hambrecht believes his data support calls to take the time between the diagnostic angiogram and the revascularization procedure to discuss the options with the patient, rather than stenting every patient.
"We have enough evidence from several studies, including COURAGE and our PET studies, comparing PCI vs more conservative strategies, and the data are quite convincing that PCI is not superior" in stable angina, he concluded.
Shelley Wood
Medscape Conference Coverage, based on selected sessions at the:
European Society of Cardiology (ESC) Congress 2009
September 8, 2009 (Barcelona, Spain) - Investigators for the multicenter PET study were keen to build on the surprising findings from their pilot trial: that 12 months of exercise training was just as good as PCI for myocardial perfusion and symptom relief in patients with stable angina and even better in terms of preventing cardiovascular events. Those hopes, however, were dashed when the multicenter PET study ground to a halt due to a lack of enthusiasm among patients and enrolling centers.
But in new findings presented by Dr Rainer Hambrecht (Klinikum Links der Weser, Bremen, Germany) at the European Congress of Cardiology 2009 Congress, combined data from the PET pilot study and the aborted PET multicenter trial suggest that regular exercise training is superior to PCI at preventing subsequent cardiovascular events.
The original PET study [1] randomized 102 patients to either exercise or PCI and reexamined patients after 12 months using coronary angiography, technetium-99m scintigraphy, and ergospirometry, as well as a range of clinical end points. Results, which were published in Circulation in 2004, showed clear and comparable improvements in symptoms and myocardial perfusion from baseline with both treatment strategies, and a trend toward better event-free survival in the training group at both 12 and 48 months.
"Our expectation was that exercise training would not be inferior to PCI; however, what we saw after 12 months was a clear, significant improvement in exercise over PCI in patients with stable CAD," Hambrecht told heartwire .
Exercise benefits
Inspired by the PET pilot, Hambrecht et al launched the PET multicenter trial at four hospitals in Germany, Austria, Switzerland, and Romania. By design, patients were randomized either to PCI or to two weeks of a supervised exercise training program every day, made up of five short periods of exercise daily. Patients were then given bicycles at home and asked to exercise on them every day, plus attend a supervised exercise program one or two times per week. The bikes, Hambrecht told heartwire , were equipped with sensors that monitored the amount and duration of exercise and ensured that it was actually the study participant--and not another family member--who was using the equipment.
But according to Hambrecht, the trial had major problems recruiting and was halted with just over 100 of the original 400 patients it had hoped to enroll. The study had plenty of funding; enrollment problems lay with both the recruiting centers and the patients themselves, he said. "There was some reluctance among the centers to join us in performing this study and also difficulties recruiting patients for the study" and explaining the randomization process. "If you get the stent you are free of symptoms within a few minutes, [whereas] in the training group, you have to work a lot, for several months, to reduce the angina threshold."
As with the pilot study, there were striking improvements with both PCI and exercise training in angina class and improvements in event-free survival that were nonsignificantly better for the training patients.
However, when the patients from both the multicenter and pilot studies were combined for a total of 202 patients with two-year follow-up, investigators achieved the statistical significance not met in the multicenter trial, Hambrecht reported. In a pooled analysis of event-free survival, 21 events occurred in the training group as opposed to 32 events in the PCI group (p=0.039). The differences speak to the direct benefits of exercise on the cardiovascular system globally, as opposed to the palliative, more localized benefits of PCI. Whereas both strategies improve myocardial perfusion, angina threshold, and exercise capacity, only exercise improves endothelial function and slows disease progression, he noted. Moreover, he stressed, improvements in both arms were seen on top of optimal medical therapy.
Forces work against exercise
In an interview with heartwire , Hambrecht acknowledged that there are multiple forces working against a scenario in which regular exercise is prescribed instead of stenting. For one, patients are not motivated to take responsibility for improving their own cardiovascular health--even if it means better event-free survival. For another, encouraging exercising is financially less appealing for hospitals, Hambrecht observed: "That was my feeling, that hospitals were reluctant to participate in this study, because they derive revenue from PCI procedures."
Hambrecht believes his data support calls to take the time between the diagnostic angiogram and the revascularization procedure to discuss the options with the patient, rather than stenting every patient.
"We have enough evidence from several studies, including COURAGE and our PET studies, comparing PCI vs more conservative strategies, and the data are quite convincing that PCI is not superior" in stable angina, he concluded.
Hoarseness
Otolaryngol Head Neck Surg. 2009;141:S1-S31.
Clinical Context
Hoarseness is a common presenting symptom in many different practice settings, affecting approximately one third of individuals at some point during their lifetime, but many people in the United States are unaware of the possible causes and appropriate treatment of hoarseness. Although most patients with hoarseness have benign, self-limiting conditions, persistent hoarseness may be a warning signal of underlying cancer.
A multidisciplinary panel convened by the AAO-HNSF developed a practical clinical guideline for management of hoarseness, targeting consumers as well as all clinicians who are likely to diagnose and treat patients with hoarseness. Dysphonia, or hoarseness, is characterized by altered vocal quality, pitch, volume, or vocal effort that hinders communication or decreases voice-related quality of life.
Study Highlights
The history and physical examination of the patient with hoarseness should identify factors that may affect management.
These risk factors may include recent surgery on the neck or in the recurrent laryngeal nerve territory, recent endotracheal intubation, neck radiation therapy, history of tobacco abuse, and occupation as a singer or vocal performer.
Although most causes of hoarseness are benign or self-limiting conditions, laryngeal tumor or other serious underlying condition should be ruled out, as well as adverse effects of medication.
The examining physician or consultant should perform laryngoscopy in the office to visualize the larynx if hoarseness persists for more than 3 months or if the underlying cause is not easily diagnosed or is thought to be serious.
Laryngoscopy is considered the primary diagnostic modality for hoarseness and should be done before any other imaging procedures.
Imaging studies, such as computed tomography or magnetic resonance imaging scans, should not be done before the larynx is visualized with laryngoscopy in patients whose primary complaint is hoarseness.
Unless there are signs or symptoms of significant gastroesophageal reflux disease, hoarseness should not be treated with antireflux medications. These may be prescribed when laryngoscopy suggests chronic laryngitis.
The clinician should not routinely prescribe antibiotics or oral corticosteroids to treat hoarseness.
Voice therapy is recommended for patients of all ages diagnosed with hoarseness that decreases voice-related quality of life.
Laryngoscopy should be performed before voice therapy is started, and the speech-language pathologist should be informed of the findings.
The usual regimen for voice therapy is 1 to 2 sessions per week for 4 to 8 weeks.
Most causes of hoarseness do not require surgery, but it may be indicated for suspected cancer, other tumors or growths, abnormal vocal cord movement, or abnormal vocal cord muscle tone.
For hoarseness caused by adductor spasmodic dysphonia, the clinician should prescribe, or refer the patient to a clinician who can prescribe, botulinum toxin injections.
Clinical Implications
Although most causes of hoarseness are benign or self-limiting conditions, laryngeal tumor or other serious underlying condition should be ruled out, as well as adverse effects from medication. Laryngoscopy is considered the primary diagnostic modality for hoarseness and should be done before any other imaging procedures.
Unless there are signs or symptoms of significant gastroesophageal reflux disease, or chronic laryngitis, hoarseness should not be treated with antireflux medications. Antibiotics or oral corticosteroids are not routinely recommended. Voice therapy is recommended for patients of all ages diagnosed with hoarseness that decreases voice-related quality of life.
http://cme.medscape.com/viewarticle/708571?sssdmh=dm1.526917&src=nldne&uac=71630FV
Clinical Context
Hoarseness is a common presenting symptom in many different practice settings, affecting approximately one third of individuals at some point during their lifetime, but many people in the United States are unaware of the possible causes and appropriate treatment of hoarseness. Although most patients with hoarseness have benign, self-limiting conditions, persistent hoarseness may be a warning signal of underlying cancer.
A multidisciplinary panel convened by the AAO-HNSF developed a practical clinical guideline for management of hoarseness, targeting consumers as well as all clinicians who are likely to diagnose and treat patients with hoarseness. Dysphonia, or hoarseness, is characterized by altered vocal quality, pitch, volume, or vocal effort that hinders communication or decreases voice-related quality of life.
Study Highlights
The history and physical examination of the patient with hoarseness should identify factors that may affect management.
These risk factors may include recent surgery on the neck or in the recurrent laryngeal nerve territory, recent endotracheal intubation, neck radiation therapy, history of tobacco abuse, and occupation as a singer or vocal performer.
Although most causes of hoarseness are benign or self-limiting conditions, laryngeal tumor or other serious underlying condition should be ruled out, as well as adverse effects of medication.
The examining physician or consultant should perform laryngoscopy in the office to visualize the larynx if hoarseness persists for more than 3 months or if the underlying cause is not easily diagnosed or is thought to be serious.
Laryngoscopy is considered the primary diagnostic modality for hoarseness and should be done before any other imaging procedures.
Imaging studies, such as computed tomography or magnetic resonance imaging scans, should not be done before the larynx is visualized with laryngoscopy in patients whose primary complaint is hoarseness.
Unless there are signs or symptoms of significant gastroesophageal reflux disease, hoarseness should not be treated with antireflux medications. These may be prescribed when laryngoscopy suggests chronic laryngitis.
The clinician should not routinely prescribe antibiotics or oral corticosteroids to treat hoarseness.
Voice therapy is recommended for patients of all ages diagnosed with hoarseness that decreases voice-related quality of life.
Laryngoscopy should be performed before voice therapy is started, and the speech-language pathologist should be informed of the findings.
The usual regimen for voice therapy is 1 to 2 sessions per week for 4 to 8 weeks.
Most causes of hoarseness do not require surgery, but it may be indicated for suspected cancer, other tumors or growths, abnormal vocal cord movement, or abnormal vocal cord muscle tone.
For hoarseness caused by adductor spasmodic dysphonia, the clinician should prescribe, or refer the patient to a clinician who can prescribe, botulinum toxin injections.
Clinical Implications
Although most causes of hoarseness are benign or self-limiting conditions, laryngeal tumor or other serious underlying condition should be ruled out, as well as adverse effects from medication. Laryngoscopy is considered the primary diagnostic modality for hoarseness and should be done before any other imaging procedures.
Unless there are signs or symptoms of significant gastroesophageal reflux disease, or chronic laryngitis, hoarseness should not be treated with antireflux medications. Antibiotics or oral corticosteroids are not routinely recommended. Voice therapy is recommended for patients of all ages diagnosed with hoarseness that decreases voice-related quality of life.
http://cme.medscape.com/viewarticle/708571?sssdmh=dm1.526917&src=nldne&uac=71630FV
Wednesday, September 9, 2009
Where do Eggs Fit in a Heart-healthy Diet?
Role of Eggs in the American Diet
From American Journal of Lifestyle Medicine
Joanne Curran Celentano PhD
Abstract
Eggs make up a relatively small contribution to the energy consumption of the average American, in part because of the perception that the cholesterol content makes them a for-bidden food for a heart-healthy diet. The relationship between egg cholesterol, blood cholesterol, and cardiovascular disease risk is complex and not clearly understood. In addition, eggs provide many valuable and bioavailable nutrients. Thus, the place of eggs in meal planning should be reconsidered while keeping in mind the diet and lifestyle recommendations of the American Heart Association.
Introduction
As far as single-component foods are concerned, there are few more nutrient dense than eggs. Yet this food category accounts for a very limited amount of energy consumption (1.3%) by the average American.[1] The perception of eggs as a forbidden food can be traced back to the 1970s recommendation by the American Heart Association to reduce the consumption of eggs and other sources of dietary cholesterol to lower the risk of cardiovascular disease (CVD).[2]
Since that time, compelling research suggests that the relationship between eggs and heart disease risk is not so simple, especially when examining free-living populations. There are responders and nonresponders to dietary cholesterol and, in some cases, paradoxical responses including lower cholesterol in egg consumers and/or elevated cholesterol with no change in the CVD risk ratio. The question of where eggs fit in a heart-healthy diet gets more interesting when considering the potential benefits of eggs in the diet, especially for infants and elderly persons. Eggs are a good or excellent source of many essential nutrients, are relatively low cost, and serve as an effective vehicle for functional ingredients in the diet.
Does Eating Eggs Increase Serum Cholesterol and Heart Disease Risk?
The relationship of dietary cholesterol to serum cholesterol has been demonstrated most clearly in experimental feeding studies. Such studies have shown that the consumption of an additional egg per day will lead to a modest increase (1%–3%) in serum cholesterol.[2] However, population studies examining the association between egg consumption and serum cholesterol concentration have not been so convincing.[3] Several large epidemiological studies have examined the association of egg consumption and serum cholesterol. The Framingham Heart Study[4] examined the serum cholesterol in high versus low egg consumption and found no significant difference in either men or women. The association between self-reported dietary intake of eggs and serum cholesterol was examined in a population of 12 000 men in the Multiple Risk Factor Intervention Trial. Paradoxically, those consuming more eggs had lower serum cholesterol than those men consuming fewer eggs.[5] Similarly, in the Third National Health and Nutrition Examination Survey (NHANES III), the diets of 20 000 participants were evaluated, and participants consuming less than 1 egg per week had a higher average serum cholesterol than those consuming more than 4 eggs per week.[6]
Recently, the association between egg consumption and the risk of CVD and mortality was investigated using data from the Physician's Health Study.[7] In this prospective cohort study, egg consumption was assessed using an abbreviated food-frequency questionnaire. In an average follow-up of 20 years, there was no association between egg consumption and myocardial infarct or stroke. However, egg consumption was positively related to all-cause mortality in a dose-dependent way, and this relationship was stronger among diabetic subjects. The researchers concluded from these data that infrequent egg consumption did not influence the risk of CVD in male physicians. The relationship of egg consumption with all-cause mortality required further investigation. A possible explanation for this finding was offered in a letter to the editor.[8] It was suggested that a nonadherer bias might be responsible for the association because there is no biological basis for an increased association of noncardio-vascular causes of death with high egg consumption. It was suggested that such bias is a limitation of observational studies. For example, high egg consumers tend to smoke more, and egg consumption is often associated with other high-fat foods such as bacon and butter. The "guilt by association" has to be parsed out in such studies to ensure that eggs are not inadvertently associated with risk.
Heart failure (HF) represents a subtype of CVD and may be underrepresented in studies investigating associations of diet and CVD, especially in younger cohorts with lower incidence of this subtype.[9] Little dietary-related research specific to HF is available; however, as the population ages, HF is increasingly adding to the health care burden and affecting the quality of life.[10] A recent study examined the association between egg consumption and risk of HF in a prospective cohort study of 21 275 male physicians.[11] Egg consumption up to 6 times per week was not associated with incident HF; however, consumption equal to or greater than 7 times per week was associated with increased risk of HF in male physicians. The Atherosclerosis Risk in Communities study evaluated incident HF and diet in a longitudinal cohort study including 14 153 African American and white men and women aged 45 to 64 years. During the 13-year follow-up, there were 1140 cases of HF. Whole-grain intake was associated with lower HF risk, whereas intake of eggs and high-fat dairy was associated with a greater risk of incident HF.[9]
Responders versus Nonresponders
Despite extensive research, the link between egg consumption and risk for coronary heart disease (CHD) is not clearly established. The relationship is likely influenced by variability in individual responses to dietary cholesterol. This variability was examined in relation-ship to the blood cholesterol response to egg consumption.[12,13] For some individuals, consuming eggs did cause a rise in blood cholesterol. These individuals are considered hyperresponders to a cholesterol challenge. However, 70% of the population experience little to no change in blood cholesterol following consumption of dietary cholesterol (hyporesponders). In addition, the egg cholesterol increased both circulating low-density lipoprotein (LDL-C) and high-density lipoprotein (HDL-C) in those individuals who experience changes in blood cholesterol following egg consumption. Moreover, eggs have been shown to promote the formation of large LDL particles, shifting individuals to a less atherogenic lipid profile. Such individual variations in the response to dietary cholesterol can be attributed to a variety of factors, including ethnicity, body mass index, and hormone status.[14] Genetics certainly has a role. Recently, it was reported that polymorphism in the ATP-binding cassette G (ABCG5) is thought to influence the response to dietary cholesterol.[15] In this study, 40 men and 51 postmenopausal women were randomly assigned to consume eggs (equivalent to 640 mg/d additional dietary cholesterol) or placebo for 30 days in a crossover design. It was found that genotype influenced the response to cholesterol, with one specific group experiencing a greater increase in LDL-C in response to the cholesterol challenge. Although this study was small, the results suggest that genetic makeup influences an individual response to cholesterol and may explain some of the controversy surrounding the questions and recommendations about dietary cholesterol in relationship to blood cholesterol and disease risk.
The data from the NHANES III (1988–1994) were examined to assess the nutritional contribution of eggs in the American diet and to estimate the strength of the association between egg consumption and serum cholesterol. Nutrient intake from 24-hour recall and egg intake from food-frequency questionnaires were used to group 27 378 participants into egg consumers and nonconsumers. Egg consumers had considerably greater nutrient density contributing vitamin A, E, folate, and B12. The results also indicated that egg consumption was negatively correlated with serum cholesterol. In this population, those who reported eating 4 or more eggs per week had significantly lower mean serum cholesterol than those who reported eating less than or equal to 1 egg per week. In this cross-sectional and population-based study, egg consumption made important nutritional contributions to the American diet and was not associated with high serum cholesterol concentrations.[6]
Thus, it is important to look at eggs as more than a cholesterol-delivery sys-tem. Eggs are an inexpensive and low-calorie source of high-quality protein and other nutrients, including folate, riboflavin, selenium, choline, and vitamins B12 and A, D, and K.[15] In addition, the lipid matrix of the egg yolk enhances the bio-availability of valuable carotenoid pigments, including lutein and zeaxanthin.[16] Thus, the positive contribution of eggs to a healthy diet should be considered in the risk–benefit analysis.[17]
This may be particularly true for elderly persons. The incidence of age-related diseases will continue as our population ages. By the year 2020, the number of people older than 60 years is expected to top 1 billion.[18] The burden of treating chronic disease is significant both in dollars spent and lost productivity. The need to identify risk factors for disease must be evaluated along with diet and lifestyle factors that promote healthy aging.
For elderly persons, it has been suggested that the widely accepted risk factors for CHD may not be applicable.[19] Whereas elevated total cholesterol and LDL-C values are considered predictive of CHD risk in the middle years, this may not be relevant for the elderly population. In this population, a low-fat diet prescription may actually lead to a diet pattern that increases CHD risk. A higher carbohy-drate, especially simple carbohydrate, diet is associated with elevated triglycerides, low HDL-C, and the production of small, dense LDL particles. In cases in which fat/ cholesterol restriction is practiced over energy restriction, a high-carbohydrate diet may have the net effect of promoting insulin resistance.[14] To promote energy restriction instead, eggs may provide a low-calorie and nutrient-dense option for meal planning. In addition, the protein quality of eggs reflects its balanced amino acid profile, and the high-quality egg protein may be helpful in avoiding the loss of muscle mass associated with aging.[20]
While not typically recommended, carbohydrate-restricted diets (CRD) have been popular for rapid weight loss and are associated with lower glucose and insulin levels and improve dyslipidemia. Studies have shown that the improved lipid profile (elevated HDL-C and lower triglycerides) are associated with a higher intake of dietary cholesterol.[21] Eggs have been shown to modulate the inflammatory response to CRD. Daily egg consumption along with CRD in overweight men was associated with decrease in C-reactive protein and increased adiponectin compared with CRD without eggs.[20]
Egg Carotenoids and Eye Health
The leading cause of irreversible blind-ness in the United States is age-related macular degeneration (AMD).[22] Although the causes of AMD are complex and multifaceted, a lifetime exposure to oxidative damage is clearly implicated. Although both light and oxygen are essential for normal vision, the accumulated by-products from oxidative metabolism in the retina over time can cause damage. Lutein and zeaxanthin (L/Z) accumulate in the macular region of the retina and are collectively referred to as macular pigment (MP). Because of its antioxidant and light-filtering properties, the MP may protect the retina and reduce the risk of developing AMD. Studies have shown that individuals who consume foods rich in L/Z have a lower risk for AMD,[23] higher blood levels of L/Z,[24,25] and higher MP density.[26–28]
Several studies have shown that eggs provide a highly bioavailable source of L/Z.[16,24,29] While the average content of L/Z in the yolk is ~200 to 300 μg, the lipid matrix allows for efficient uptake of these pigments. As little as 1 egg per day or 6 eggs per week have been shown to increase serum L/Z and MP, respectively.[16,29] The concentration of L/Z in the egg yolk can be easily modified by alterations in the animal diet, and the difference in the L/Z content of grocery store eggs varies widely depending on the type and care of the animal.[16] Many local egg producers allow their animals to graze in appropriate weather, and their egg yolks may range from pale yellow to deep orange depending on the L/Z avail-able in the diet. Consumers can identify lutein as associated with eye health, reflecting the media's attention in magazine articles and advertisements. For example, a recent article titled "Eat for Your Eyes"[30] discussed 5 food strategies to help you "see more clearly." The inclusion of eggs in the diet was one of the recommendations, citing a study in which consuming 2 eggs per day was associated with increased circulating L/Z with no change in blood LDL-C. The recommendation was to "go ahead and enjoy eggs regularly unless advised otherwise by your doctor." The article did include the caveat to stay within the American Heart Association guidelines, as noted below.
Current Recommendations
The American Heart Association[31,32] Diet and Lifestyle Recommendations for Cardiovascular Disease Risk Reduction are listed in Table 1. The current recommendations reflect a shift toward looking at dietary patterns and overall diet quality rather than focusing on specific nutrients and a diet based more on inclusion of a wide range of foods and less on avoidance of particular foods or ingredients. Whereas there was previously a stated recommendation to limit eggs to 4 yolks per week, this food-specific recommendation is not in the current guidelines. The American Heart Association recommendation is to limit dietary cholesterol to <300 mg/d. The average egg yolk contains on average 213 mg of cholesterol.
If eggs are judged on their nutritional content, convenience, and cost, the positive contributions of eggs may outweigh the potential risk associated with the cholesterol. This may be particularly true for healthy elderly individuals whose cholesterol risk and nutritional needs differ from earlier years. For individuals with diabetes or major risk factors for CHD, the recommendation to limit dietary cholesterol to <200 mg/d[33] allows for less frequent use of unmodified egg products. Along with the numerous modified egg products on the market today (eg, Egg Beaters), there will likely be additional egg and egg products with higher lutein and lower cholesterol in the future.[34,35]
From American Journal of Lifestyle Medicine
Joanne Curran Celentano PhD
Abstract
Eggs make up a relatively small contribution to the energy consumption of the average American, in part because of the perception that the cholesterol content makes them a for-bidden food for a heart-healthy diet. The relationship between egg cholesterol, blood cholesterol, and cardiovascular disease risk is complex and not clearly understood. In addition, eggs provide many valuable and bioavailable nutrients. Thus, the place of eggs in meal planning should be reconsidered while keeping in mind the diet and lifestyle recommendations of the American Heart Association.
Introduction
As far as single-component foods are concerned, there are few more nutrient dense than eggs. Yet this food category accounts for a very limited amount of energy consumption (1.3%) by the average American.[1] The perception of eggs as a forbidden food can be traced back to the 1970s recommendation by the American Heart Association to reduce the consumption of eggs and other sources of dietary cholesterol to lower the risk of cardiovascular disease (CVD).[2]
Since that time, compelling research suggests that the relationship between eggs and heart disease risk is not so simple, especially when examining free-living populations. There are responders and nonresponders to dietary cholesterol and, in some cases, paradoxical responses including lower cholesterol in egg consumers and/or elevated cholesterol with no change in the CVD risk ratio. The question of where eggs fit in a heart-healthy diet gets more interesting when considering the potential benefits of eggs in the diet, especially for infants and elderly persons. Eggs are a good or excellent source of many essential nutrients, are relatively low cost, and serve as an effective vehicle for functional ingredients in the diet.
Does Eating Eggs Increase Serum Cholesterol and Heart Disease Risk?
The relationship of dietary cholesterol to serum cholesterol has been demonstrated most clearly in experimental feeding studies. Such studies have shown that the consumption of an additional egg per day will lead to a modest increase (1%–3%) in serum cholesterol.[2] However, population studies examining the association between egg consumption and serum cholesterol concentration have not been so convincing.[3] Several large epidemiological studies have examined the association of egg consumption and serum cholesterol. The Framingham Heart Study[4] examined the serum cholesterol in high versus low egg consumption and found no significant difference in either men or women. The association between self-reported dietary intake of eggs and serum cholesterol was examined in a population of 12 000 men in the Multiple Risk Factor Intervention Trial. Paradoxically, those consuming more eggs had lower serum cholesterol than those men consuming fewer eggs.[5] Similarly, in the Third National Health and Nutrition Examination Survey (NHANES III), the diets of 20 000 participants were evaluated, and participants consuming less than 1 egg per week had a higher average serum cholesterol than those consuming more than 4 eggs per week.[6]
Recently, the association between egg consumption and the risk of CVD and mortality was investigated using data from the Physician's Health Study.[7] In this prospective cohort study, egg consumption was assessed using an abbreviated food-frequency questionnaire. In an average follow-up of 20 years, there was no association between egg consumption and myocardial infarct or stroke. However, egg consumption was positively related to all-cause mortality in a dose-dependent way, and this relationship was stronger among diabetic subjects. The researchers concluded from these data that infrequent egg consumption did not influence the risk of CVD in male physicians. The relationship of egg consumption with all-cause mortality required further investigation. A possible explanation for this finding was offered in a letter to the editor.[8] It was suggested that a nonadherer bias might be responsible for the association because there is no biological basis for an increased association of noncardio-vascular causes of death with high egg consumption. It was suggested that such bias is a limitation of observational studies. For example, high egg consumers tend to smoke more, and egg consumption is often associated with other high-fat foods such as bacon and butter. The "guilt by association" has to be parsed out in such studies to ensure that eggs are not inadvertently associated with risk.
Heart failure (HF) represents a subtype of CVD and may be underrepresented in studies investigating associations of diet and CVD, especially in younger cohorts with lower incidence of this subtype.[9] Little dietary-related research specific to HF is available; however, as the population ages, HF is increasingly adding to the health care burden and affecting the quality of life.[10] A recent study examined the association between egg consumption and risk of HF in a prospective cohort study of 21 275 male physicians.[11] Egg consumption up to 6 times per week was not associated with incident HF; however, consumption equal to or greater than 7 times per week was associated with increased risk of HF in male physicians. The Atherosclerosis Risk in Communities study evaluated incident HF and diet in a longitudinal cohort study including 14 153 African American and white men and women aged 45 to 64 years. During the 13-year follow-up, there were 1140 cases of HF. Whole-grain intake was associated with lower HF risk, whereas intake of eggs and high-fat dairy was associated with a greater risk of incident HF.[9]
Responders versus Nonresponders
Despite extensive research, the link between egg consumption and risk for coronary heart disease (CHD) is not clearly established. The relationship is likely influenced by variability in individual responses to dietary cholesterol. This variability was examined in relation-ship to the blood cholesterol response to egg consumption.[12,13] For some individuals, consuming eggs did cause a rise in blood cholesterol. These individuals are considered hyperresponders to a cholesterol challenge. However, 70% of the population experience little to no change in blood cholesterol following consumption of dietary cholesterol (hyporesponders). In addition, the egg cholesterol increased both circulating low-density lipoprotein (LDL-C) and high-density lipoprotein (HDL-C) in those individuals who experience changes in blood cholesterol following egg consumption. Moreover, eggs have been shown to promote the formation of large LDL particles, shifting individuals to a less atherogenic lipid profile. Such individual variations in the response to dietary cholesterol can be attributed to a variety of factors, including ethnicity, body mass index, and hormone status.[14] Genetics certainly has a role. Recently, it was reported that polymorphism in the ATP-binding cassette G (ABCG5) is thought to influence the response to dietary cholesterol.[15] In this study, 40 men and 51 postmenopausal women were randomly assigned to consume eggs (equivalent to 640 mg/d additional dietary cholesterol) or placebo for 30 days in a crossover design. It was found that genotype influenced the response to cholesterol, with one specific group experiencing a greater increase in LDL-C in response to the cholesterol challenge. Although this study was small, the results suggest that genetic makeup influences an individual response to cholesterol and may explain some of the controversy surrounding the questions and recommendations about dietary cholesterol in relationship to blood cholesterol and disease risk.
The data from the NHANES III (1988–1994) were examined to assess the nutritional contribution of eggs in the American diet and to estimate the strength of the association between egg consumption and serum cholesterol. Nutrient intake from 24-hour recall and egg intake from food-frequency questionnaires were used to group 27 378 participants into egg consumers and nonconsumers. Egg consumers had considerably greater nutrient density contributing vitamin A, E, folate, and B12. The results also indicated that egg consumption was negatively correlated with serum cholesterol. In this population, those who reported eating 4 or more eggs per week had significantly lower mean serum cholesterol than those who reported eating less than or equal to 1 egg per week. In this cross-sectional and population-based study, egg consumption made important nutritional contributions to the American diet and was not associated with high serum cholesterol concentrations.[6]
Thus, it is important to look at eggs as more than a cholesterol-delivery sys-tem. Eggs are an inexpensive and low-calorie source of high-quality protein and other nutrients, including folate, riboflavin, selenium, choline, and vitamins B12 and A, D, and K.[15] In addition, the lipid matrix of the egg yolk enhances the bio-availability of valuable carotenoid pigments, including lutein and zeaxanthin.[16] Thus, the positive contribution of eggs to a healthy diet should be considered in the risk–benefit analysis.[17]
This may be particularly true for elderly persons. The incidence of age-related diseases will continue as our population ages. By the year 2020, the number of people older than 60 years is expected to top 1 billion.[18] The burden of treating chronic disease is significant both in dollars spent and lost productivity. The need to identify risk factors for disease must be evaluated along with diet and lifestyle factors that promote healthy aging.
For elderly persons, it has been suggested that the widely accepted risk factors for CHD may not be applicable.[19] Whereas elevated total cholesterol and LDL-C values are considered predictive of CHD risk in the middle years, this may not be relevant for the elderly population. In this population, a low-fat diet prescription may actually lead to a diet pattern that increases CHD risk. A higher carbohy-drate, especially simple carbohydrate, diet is associated with elevated triglycerides, low HDL-C, and the production of small, dense LDL particles. In cases in which fat/ cholesterol restriction is practiced over energy restriction, a high-carbohydrate diet may have the net effect of promoting insulin resistance.[14] To promote energy restriction instead, eggs may provide a low-calorie and nutrient-dense option for meal planning. In addition, the protein quality of eggs reflects its balanced amino acid profile, and the high-quality egg protein may be helpful in avoiding the loss of muscle mass associated with aging.[20]
While not typically recommended, carbohydrate-restricted diets (CRD) have been popular for rapid weight loss and are associated with lower glucose and insulin levels and improve dyslipidemia. Studies have shown that the improved lipid profile (elevated HDL-C and lower triglycerides) are associated with a higher intake of dietary cholesterol.[21] Eggs have been shown to modulate the inflammatory response to CRD. Daily egg consumption along with CRD in overweight men was associated with decrease in C-reactive protein and increased adiponectin compared with CRD without eggs.[20]
Egg Carotenoids and Eye Health
The leading cause of irreversible blind-ness in the United States is age-related macular degeneration (AMD).[22] Although the causes of AMD are complex and multifaceted, a lifetime exposure to oxidative damage is clearly implicated. Although both light and oxygen are essential for normal vision, the accumulated by-products from oxidative metabolism in the retina over time can cause damage. Lutein and zeaxanthin (L/Z) accumulate in the macular region of the retina and are collectively referred to as macular pigment (MP). Because of its antioxidant and light-filtering properties, the MP may protect the retina and reduce the risk of developing AMD. Studies have shown that individuals who consume foods rich in L/Z have a lower risk for AMD,[23] higher blood levels of L/Z,[24,25] and higher MP density.[26–28]
Several studies have shown that eggs provide a highly bioavailable source of L/Z.[16,24,29] While the average content of L/Z in the yolk is ~200 to 300 μg, the lipid matrix allows for efficient uptake of these pigments. As little as 1 egg per day or 6 eggs per week have been shown to increase serum L/Z and MP, respectively.[16,29] The concentration of L/Z in the egg yolk can be easily modified by alterations in the animal diet, and the difference in the L/Z content of grocery store eggs varies widely depending on the type and care of the animal.[16] Many local egg producers allow their animals to graze in appropriate weather, and their egg yolks may range from pale yellow to deep orange depending on the L/Z avail-able in the diet. Consumers can identify lutein as associated with eye health, reflecting the media's attention in magazine articles and advertisements. For example, a recent article titled "Eat for Your Eyes"[30] discussed 5 food strategies to help you "see more clearly." The inclusion of eggs in the diet was one of the recommendations, citing a study in which consuming 2 eggs per day was associated with increased circulating L/Z with no change in blood LDL-C. The recommendation was to "go ahead and enjoy eggs regularly unless advised otherwise by your doctor." The article did include the caveat to stay within the American Heart Association guidelines, as noted below.
Current Recommendations
The American Heart Association[31,32] Diet and Lifestyle Recommendations for Cardiovascular Disease Risk Reduction are listed in Table 1. The current recommendations reflect a shift toward looking at dietary patterns and overall diet quality rather than focusing on specific nutrients and a diet based more on inclusion of a wide range of foods and less on avoidance of particular foods or ingredients. Whereas there was previously a stated recommendation to limit eggs to 4 yolks per week, this food-specific recommendation is not in the current guidelines. The American Heart Association recommendation is to limit dietary cholesterol to <300 mg/d. The average egg yolk contains on average 213 mg of cholesterol.
If eggs are judged on their nutritional content, convenience, and cost, the positive contributions of eggs may outweigh the potential risk associated with the cholesterol. This may be particularly true for healthy elderly individuals whose cholesterol risk and nutritional needs differ from earlier years. For individuals with diabetes or major risk factors for CHD, the recommendation to limit dietary cholesterol to <200 mg/d[33] allows for less frequent use of unmodified egg products. Along with the numerous modified egg products on the market today (eg, Egg Beaters), there will likely be additional egg and egg products with higher lutein and lower cholesterol in the future.[34,35]
Saturday, September 5, 2009
Passive Smoking Tied to Masked Hypertension
From Reuters Health Information
NEW YORK (Reuters Health) Aug 20 - Ambulatory blood pressure testing suggests that people with passive domestic or work exposure to tobacco smoke are at increased risk of masked hypertension, Greek researchers report in the August issue of the American Journal of Hypertension.
"Our findings," investigator Dr. Costas Thomopoulos told Reuters Health, "demonstrate that passive smoking may be a 'hidden partner' of out-of-clinic hypertension and especially of masked hypertension."
Dr. Thomopoulos of Elena Venizelou Hospital, Athens, and colleagues came to this conclusion after studying 154 patients with regular passive smoke exposure and another 100 without exposure. All were self-referred to the hospital's outpatient hypertensive unit for blood pressure evaluation.
The subjects had blood pressure measures taken on 3 separate visits to the clinic and also underwent 24-hour ambulatory monitoring on a work day.
Compared to those who were not exposed, the passive smokers showed higher 24 hour systolic BP (126 versus 122 mm/Hg), diastolic BP (89 versus 84 mm/Hg) and clinic heart rate (79 versus 73 beats per minute) (p<0.05 for all). In addition, passive smokers had a higher prevalence of masked hypertension (23% versus 8%; p<0.01).
On multivariate analysis, passive smoking was an independent predictor of masked hypertension, as were weekly duration and intensity of passive smoke exposure, younger age, clinic heart rate, low physical activity, and standing/sitting differences in diastolic BP and heart rate.
Further studies are needed, Dr. Thomopoulos said, but these findings point in "the direction of including passive smoking evaluation in (routine) clinical practice."
Am J Hypertens 2009;22:853-859.
NEW YORK (Reuters Health) Aug 20 - Ambulatory blood pressure testing suggests that people with passive domestic or work exposure to tobacco smoke are at increased risk of masked hypertension, Greek researchers report in the August issue of the American Journal of Hypertension.
"Our findings," investigator Dr. Costas Thomopoulos told Reuters Health, "demonstrate that passive smoking may be a 'hidden partner' of out-of-clinic hypertension and especially of masked hypertension."
Dr. Thomopoulos of Elena Venizelou Hospital, Athens, and colleagues came to this conclusion after studying 154 patients with regular passive smoke exposure and another 100 without exposure. All were self-referred to the hospital's outpatient hypertensive unit for blood pressure evaluation.
The subjects had blood pressure measures taken on 3 separate visits to the clinic and also underwent 24-hour ambulatory monitoring on a work day.
Compared to those who were not exposed, the passive smokers showed higher 24 hour systolic BP (126 versus 122 mm/Hg), diastolic BP (89 versus 84 mm/Hg) and clinic heart rate (79 versus 73 beats per minute) (p<0.05 for all). In addition, passive smokers had a higher prevalence of masked hypertension (23% versus 8%; p<0.01).
On multivariate analysis, passive smoking was an independent predictor of masked hypertension, as were weekly duration and intensity of passive smoke exposure, younger age, clinic heart rate, low physical activity, and standing/sitting differences in diastolic BP and heart rate.
Further studies are needed, Dr. Thomopoulos said, but these findings point in "the direction of including passive smoking evaluation in (routine) clinical practice."
Am J Hypertens 2009;22:853-859.
Friday, September 4, 2009
Only Three Cigarettes a Day Significantly Increases Cardiovascular Disease Risk
From Heartwire
Martha Kerr
September 3, 2009 (Provo, Utah) — Exposure to relatively low levels of fine particulate matter (PM) significantly increases the risk of cardiovascular disease [1]. The risk trajectory levels off with higher levels of exposure, researchers report, in a study published online August 31, 2009 in Circulation. The study will appear in the September 15 issue.
Risk of cardiovascular disease increased 64% by smoking three cigarettes a day. Risk doubled by smoking a pack a day, according to data on more than one million adults prospectively collected by the American Cancer Society, as part of the Cancer Prevention Study II of 1982.
Using this database, Dr C Arden Pope (Brigham Young University Provo, UT) and colleagues calculated adjusted relative risks of mortality according to an estimated average daily dose of fine PM from active cigarette-smoke inhalation, as well as the PM doses from secondhand cigarette-smoke exposure and from exposure to air pollution.
"There were substantially increased cardiovascular mortality risks at very low levels of active cigarette smoking and smaller but significant excess risks even at the much lower exposure levels associated with secondhand cigarette smoke and ambient air pollution," the researchers report.
"The results indicate that it is fundamentally implausible that the relationship between cardiovascular mortality and fine particulate pollution from cigarette smoke and ambient air pollution can be characterized as linked by a simple linear dose-response relationship," the authors write. "Rather, our results suggest that the exposure-response function is relatively steep at very low levels of exposure, flattening out at high exposure levels."
Pope and colleagues note several limitations of the study, among them the large exposure gap between ambient air pollution, secondhand-smoke exposure, and active smoking. And, the authors say, there are no prospective cohort or related studies of long-term exposure across the range of exposure that would fill this gap.
Even with its limitations, the study findings have important public-health implications, Pope's team comments. Most studies of the effects of fine PM on cardiovascular disease risk have been conducted in areas where the annual average PM concentrations rarely exceed 30 µg/m3. Recent estimates indicate average concentrations of particulate air pollution in urban areas of China, India, and other developing countries often exceed 100 µg/m3
Martha Kerr
September 3, 2009 (Provo, Utah) — Exposure to relatively low levels of fine particulate matter (PM) significantly increases the risk of cardiovascular disease [1]. The risk trajectory levels off with higher levels of exposure, researchers report, in a study published online August 31, 2009 in Circulation. The study will appear in the September 15 issue.
Risk of cardiovascular disease increased 64% by smoking three cigarettes a day. Risk doubled by smoking a pack a day, according to data on more than one million adults prospectively collected by the American Cancer Society, as part of the Cancer Prevention Study II of 1982.
Using this database, Dr C Arden Pope (Brigham Young University Provo, UT) and colleagues calculated adjusted relative risks of mortality according to an estimated average daily dose of fine PM from active cigarette-smoke inhalation, as well as the PM doses from secondhand cigarette-smoke exposure and from exposure to air pollution.
"There were substantially increased cardiovascular mortality risks at very low levels of active cigarette smoking and smaller but significant excess risks even at the much lower exposure levels associated with secondhand cigarette smoke and ambient air pollution," the researchers report.
"The results indicate that it is fundamentally implausible that the relationship between cardiovascular mortality and fine particulate pollution from cigarette smoke and ambient air pollution can be characterized as linked by a simple linear dose-response relationship," the authors write. "Rather, our results suggest that the exposure-response function is relatively steep at very low levels of exposure, flattening out at high exposure levels."
Pope and colleagues note several limitations of the study, among them the large exposure gap between ambient air pollution, secondhand-smoke exposure, and active smoking. And, the authors say, there are no prospective cohort or related studies of long-term exposure across the range of exposure that would fill this gap.
Even with its limitations, the study findings have important public-health implications, Pope's team comments. Most studies of the effects of fine PM on cardiovascular disease risk have been conducted in areas where the annual average PM concentrations rarely exceed 30 µg/m3. Recent estimates indicate average concentrations of particulate air pollution in urban areas of China, India, and other developing countries often exceed 100 µg/m3
Hong Kong Health Care Workers Leery of H1N1 Vaccine
From Reuters Health Information
NEW YORK (Reuters Health) Aug 26 - Even though testing has so far raised no "red flags" regarding safety of vaccines against the novel H1N1 influenza virus, surveys and focus groups show that healthcare workers and members of the public may be leery of being inoculated when supplies become available this fall.
Writing in the August 26 issue of BMJ Online First, Dr. Paul K. S. Chan and associates at the Chinese University of Hong Kong note that "in nearly all countries with a (pandemic) preparedness plan, healthcare workers are listed as the priority group for mass vaccination."
In May of this year when the WHO pandemic influenza alert level had been raised to phase 5, the researchers distributed 810 questionnaires to public hospital workers, primarily doctors and nurses.
A tally of the 389 questionnaires that were returned indicated that less than half (48%) intended to accept pre-pandemic H1N1 vaccination. The most common reason for refusal was worry over side effects, follow by questions about the vaccine's efficacy and the conviction that it was "not yet the right time to be vaccinated."
"This is particularly surprising in a city where the SARS outbreak had such a huge impact," Dr. Chan's team points out.
The strongest associations with willingness to be vaccinated, the report indicates, were a history of seasonal flu vaccination and the perception that they were likely to be infected.
In a linked commentary, Dr. Rachel Jordan, from the University of Birmingham, and Dr. Andrew Hayward, from the University College of London, advise that in order to maximize vaccine uptake, "use of convenient mobile systems, monitoring and feedback systems, and 'opt-out' systems (where healthcare workers need to indicate their reasons for not accepting the vaccine) show promise."
In a separate article published online in the Emerging Health Threats Journal, Dr. Natalie Henrich of the University of British Columbia and Dr. Bev J. Holmes at Simon Fraser University, both in Vancouver, describe findings from 11 focus groups conducted with the public in Vancouver, Canada, in 2006 and 2007 to explore their willingness to use novel vaccines in a pandemic.
The researchers asked the 85 participants how willing they would be to accept a new vaccine in the event of a pandemic. Very few people said they or their children would definitely get vaccinated, the authors report. Participants' concerns centered around the risk of infection versus the risks involved in using newly developed vaccines.
"Participants were hesitant to use the novel vaccines (due to) concern that unsafe pharmaceuticals may be rushed to market during the health crisis," the authors said.
Instead, many individuals believed they could protect themselves through their own behavior, including frequent handwashing, staying away from crowded places and sick people, and eating well to maintain their strong immune system.
BMJ 2009;339:b3391.
Emerging Health Threats Journal 2009.
NEW YORK (Reuters Health) Aug 26 - Even though testing has so far raised no "red flags" regarding safety of vaccines against the novel H1N1 influenza virus, surveys and focus groups show that healthcare workers and members of the public may be leery of being inoculated when supplies become available this fall.
Writing in the August 26 issue of BMJ Online First, Dr. Paul K. S. Chan and associates at the Chinese University of Hong Kong note that "in nearly all countries with a (pandemic) preparedness plan, healthcare workers are listed as the priority group for mass vaccination."
In May of this year when the WHO pandemic influenza alert level had been raised to phase 5, the researchers distributed 810 questionnaires to public hospital workers, primarily doctors and nurses.
A tally of the 389 questionnaires that were returned indicated that less than half (48%) intended to accept pre-pandemic H1N1 vaccination. The most common reason for refusal was worry over side effects, follow by questions about the vaccine's efficacy and the conviction that it was "not yet the right time to be vaccinated."
"This is particularly surprising in a city where the SARS outbreak had such a huge impact," Dr. Chan's team points out.
The strongest associations with willingness to be vaccinated, the report indicates, were a history of seasonal flu vaccination and the perception that they were likely to be infected.
In a linked commentary, Dr. Rachel Jordan, from the University of Birmingham, and Dr. Andrew Hayward, from the University College of London, advise that in order to maximize vaccine uptake, "use of convenient mobile systems, monitoring and feedback systems, and 'opt-out' systems (where healthcare workers need to indicate their reasons for not accepting the vaccine) show promise."
In a separate article published online in the Emerging Health Threats Journal, Dr. Natalie Henrich of the University of British Columbia and Dr. Bev J. Holmes at Simon Fraser University, both in Vancouver, describe findings from 11 focus groups conducted with the public in Vancouver, Canada, in 2006 and 2007 to explore their willingness to use novel vaccines in a pandemic.
The researchers asked the 85 participants how willing they would be to accept a new vaccine in the event of a pandemic. Very few people said they or their children would definitely get vaccinated, the authors report. Participants' concerns centered around the risk of infection versus the risks involved in using newly developed vaccines.
"Participants were hesitant to use the novel vaccines (due to) concern that unsafe pharmaceuticals may be rushed to market during the health crisis," the authors said.
Instead, many individuals believed they could protect themselves through their own behavior, including frequent handwashing, staying away from crowded places and sick people, and eating well to maintain their strong immune system.
BMJ 2009;339:b3391.
Emerging Health Threats Journal 2009.
Thursday, September 3, 2009
Importance of Exercise and Physical Activity in Older Adults Reviewed
From Medscape Medical News CME
Laurie Barclay, Désirée Lie,
July 8, 2009 — The American College of Sports Medicine has issued a position stand providing an overview of issues critical to understanding the importance of exercise and physical activity in older adult populations. The review and guidelines are published in the July issue of Medicine & Science in Sports & Exercise.
"The 2008 Physical Activity Guidelines for Americans affirms that regular physical activity reduces the risk of many adverse health outcomes," write Wojtek J. Chodzko-Zajko, PhD, and colleagues from the American College of Sports Medicine. "The guidelines state that all adults should avoid inactivity, that some physical activity is better than none, and that adults who participate in any amount of physical activity gain some health benefits. However, the guidelines emphasize that for most health outcomes, additional benefits occur as the amount of physical activity increases through higher intensity, greater frequency, and/or longer duration."
The reviewers conclude that no amount of physical activity can stop biological aging but that evidence to date affirms that by limiting the development and progression of chronic disease and disabling conditions, regular exercise can reduce the physiologic harms of an otherwise sedentary lifestyle and improve active life expectancy. Older adults who engage in regular exercise may also experience significant psychological and cognitive benefits.
The position stand recommends that all older adults participate in regular physical activity and avoid an inactive lifestyle and that exercise prescription for older adults include aerobic, muscle-strengthening, and flexibility exercises
Benefits of Physical Activity and Exercise
The following are some specific evidence statements regarding the benefits of physical activity and exercise, and their accompanying level of evidence rating(see "Note" at end of article for explanation of the ratings):
Vigorous, long-term participation in aerobic exercise training (AET) improves cardiovascular reserve and skeletal muscle adaptations, allowing trained older persons to sustain a submaximal exercise load with less cardiovascular stress and muscular fatigue than their untrained peers. Prolonged AET may also reduce age-related accumulation of central body fat, thereby protecting the heart (level of evidence, B).
Prolonged participation in resistance exercise training (RET) increases muscle and bone mass and strength to a greater extent vs AET (level of evidence, B).
In healthy middle-aged and older adults, AET programs of sufficiently intense (≥ 60% of pretraining VO2max), frequency, and length (≥ 3 days/week for ≥ 16 weeks) may significantly improve VO2max (level of evidence, A).
In healthy middle-aged and older adults, 3 months or more of moderate-intensity AET are associated with cardiovascular adaptations which are apparent both at rest and in response to acute dynamic exercise (level of evidence, A/B).
Moderate-intensity AET has been shown to reduce total body fat, but not fat-free mass, in overweight middle-aged and older adults (level of evidence, A/B).
Beneficial metabolic changes associated with AET include improved glycemic control and clearance of postprandial lipids, as well as preferential utilization of fat during submaximal exercise (level of evidence, B).
In postmenopausal women, AET may counteract age-related decreases in bone mineral density (level of evidence, B).
RET may markedly increase strength and muscular power in older adults (level of evidence, A).
Older and younger adults have similar age-related increases in muscle quality, and these increases do not appear to be sex specific (level of evidence, B).
Improvements in muscular endurance have been reported after RET using moderate- to higher-intensity protocols, but not lower-intensity RET, and may improve muscular endurance (level of evidence, C).
Although the effect of exercise on physical function is poorly understood and may not be linear, RET may improve walking, chair stand, and balance activities (level of evidence, C/D).
Older adults who regularly take part in moderate- or high-intensity RET may have increased fat-free mass, decreased total body fat mass, and other beneficial changes in body composition (level of evidence, B/C).
Compared with sedentary control subjects, adults who participate in high-intensity RET have maintained or improved bone mineral density, with a direct relationship between muscle and bone adaptations (level of evidence, B).
Evidence is mixed regarding the effect of RET on metabolic variables (level of evidence, B/C).
In populations at increased risk of falling, multimodal exercise, including strength and balance exercises, and tai chi may decrease the risk for noninjurious and sometimes injurious falls (level of evidence, C).
Few controlled studies have evaluated the effect of flexibility exercise on range of motion in older adults (level of evidence, D).
Regular exercise and physical activity are linked to significant improvements in overall psychological well-being, possibly via effects on self-concept and self-esteem. Physical fitness and AET are linked to a lower risk for clinical depression or anxiety (level of evidence, A/B).
Cardiovascular fitness and higher levels of physical activity lower the risk for cognitive decline and dementia, based on epidemiologic studies. In experimental studies, AET and RET, alone or especially combined, improve some measures of cognitive functioning, especially those requiring executive control, in previously sedentary older adults (level of evidence, A/B).
Physical activity appears to be linked to some aspects of quality of life, but the precise nature of the relationship is unclear (level of evidence, D).
High-intensity RET is effective for treating clinical depression. Additional research should address the optimal intensity and frequency of RET needed to elicit specific improvements in other measures of psychological health and well-being (level of evidence, A/B).
"A combination of AET and RET activities seems to be more effective than either form of training alone in counteracting the detrimental effects of a sedentary lifestyle on the health and functioning of the cardiovascular system and skeletal muscles," the authors of the position stand conclude. "Although there are clear fitness, metabolic, and performance benefits associated with higher-intensity exercise training programs in healthy older adults, it is now evident that such programs do not need to be of high intensity to reduce the risks of developing chronic cardiovascular and metabolic disease. However, the outcome of treatment of some established diseases and geriatric syndromes is more effective with higher-intensity exercise (e.g., type 2 diabetes, clinical depression, osteopenia, sarcopenia, muscle weakness)."
Med Sci Sports Exerc. 2009;41:1510-1530.
Laurie Barclay, Désirée Lie,
July 8, 2009 — The American College of Sports Medicine has issued a position stand providing an overview of issues critical to understanding the importance of exercise and physical activity in older adult populations. The review and guidelines are published in the July issue of Medicine & Science in Sports & Exercise.
"The 2008 Physical Activity Guidelines for Americans affirms that regular physical activity reduces the risk of many adverse health outcomes," write Wojtek J. Chodzko-Zajko, PhD, and colleagues from the American College of Sports Medicine. "The guidelines state that all adults should avoid inactivity, that some physical activity is better than none, and that adults who participate in any amount of physical activity gain some health benefits. However, the guidelines emphasize that for most health outcomes, additional benefits occur as the amount of physical activity increases through higher intensity, greater frequency, and/or longer duration."
The reviewers conclude that no amount of physical activity can stop biological aging but that evidence to date affirms that by limiting the development and progression of chronic disease and disabling conditions, regular exercise can reduce the physiologic harms of an otherwise sedentary lifestyle and improve active life expectancy. Older adults who engage in regular exercise may also experience significant psychological and cognitive benefits.
The position stand recommends that all older adults participate in regular physical activity and avoid an inactive lifestyle and that exercise prescription for older adults include aerobic, muscle-strengthening, and flexibility exercises
Benefits of Physical Activity and Exercise
The following are some specific evidence statements regarding the benefits of physical activity and exercise, and their accompanying level of evidence rating(see "Note" at end of article for explanation of the ratings):
Vigorous, long-term participation in aerobic exercise training (AET) improves cardiovascular reserve and skeletal muscle adaptations, allowing trained older persons to sustain a submaximal exercise load with less cardiovascular stress and muscular fatigue than their untrained peers. Prolonged AET may also reduce age-related accumulation of central body fat, thereby protecting the heart (level of evidence, B).
Prolonged participation in resistance exercise training (RET) increases muscle and bone mass and strength to a greater extent vs AET (level of evidence, B).
In healthy middle-aged and older adults, AET programs of sufficiently intense (≥ 60% of pretraining VO2max), frequency, and length (≥ 3 days/week for ≥ 16 weeks) may significantly improve VO2max (level of evidence, A).
In healthy middle-aged and older adults, 3 months or more of moderate-intensity AET are associated with cardiovascular adaptations which are apparent both at rest and in response to acute dynamic exercise (level of evidence, A/B).
Moderate-intensity AET has been shown to reduce total body fat, but not fat-free mass, in overweight middle-aged and older adults (level of evidence, A/B).
Beneficial metabolic changes associated with AET include improved glycemic control and clearance of postprandial lipids, as well as preferential utilization of fat during submaximal exercise (level of evidence, B).
In postmenopausal women, AET may counteract age-related decreases in bone mineral density (level of evidence, B).
RET may markedly increase strength and muscular power in older adults (level of evidence, A).
Older and younger adults have similar age-related increases in muscle quality, and these increases do not appear to be sex specific (level of evidence, B).
Improvements in muscular endurance have been reported after RET using moderate- to higher-intensity protocols, but not lower-intensity RET, and may improve muscular endurance (level of evidence, C).
Although the effect of exercise on physical function is poorly understood and may not be linear, RET may improve walking, chair stand, and balance activities (level of evidence, C/D).
Older adults who regularly take part in moderate- or high-intensity RET may have increased fat-free mass, decreased total body fat mass, and other beneficial changes in body composition (level of evidence, B/C).
Compared with sedentary control subjects, adults who participate in high-intensity RET have maintained or improved bone mineral density, with a direct relationship between muscle and bone adaptations (level of evidence, B).
Evidence is mixed regarding the effect of RET on metabolic variables (level of evidence, B/C).
In populations at increased risk of falling, multimodal exercise, including strength and balance exercises, and tai chi may decrease the risk for noninjurious and sometimes injurious falls (level of evidence, C).
Few controlled studies have evaluated the effect of flexibility exercise on range of motion in older adults (level of evidence, D).
Regular exercise and physical activity are linked to significant improvements in overall psychological well-being, possibly via effects on self-concept and self-esteem. Physical fitness and AET are linked to a lower risk for clinical depression or anxiety (level of evidence, A/B).
Cardiovascular fitness and higher levels of physical activity lower the risk for cognitive decline and dementia, based on epidemiologic studies. In experimental studies, AET and RET, alone or especially combined, improve some measures of cognitive functioning, especially those requiring executive control, in previously sedentary older adults (level of evidence, A/B).
Physical activity appears to be linked to some aspects of quality of life, but the precise nature of the relationship is unclear (level of evidence, D).
High-intensity RET is effective for treating clinical depression. Additional research should address the optimal intensity and frequency of RET needed to elicit specific improvements in other measures of psychological health and well-being (level of evidence, A/B).
"A combination of AET and RET activities seems to be more effective than either form of training alone in counteracting the detrimental effects of a sedentary lifestyle on the health and functioning of the cardiovascular system and skeletal muscles," the authors of the position stand conclude. "Although there are clear fitness, metabolic, and performance benefits associated with higher-intensity exercise training programs in healthy older adults, it is now evident that such programs do not need to be of high intensity to reduce the risks of developing chronic cardiovascular and metabolic disease. However, the outcome of treatment of some established diseases and geriatric syndromes is more effective with higher-intensity exercise (e.g., type 2 diabetes, clinical depression, osteopenia, sarcopenia, muscle weakness)."
Med Sci Sports Exerc. 2009;41:1510-1530.
High-Carb, High-Fat Diets Superior to High-Protein Diets in Improving Cognitive Performance
From Medscape Medical News
Deborah Brauser
September 1, 2009 — Diets high in carbohydrates or fat can lead to significantly better cognitive-performance and inflight-testing scores in pilots than diets high in protein, according to results reported in a poster presentation at the Military Health Research Forum (MHRF) 2009 in Kansas City, Missouri.
In addition, a high-carbohydrate diet helped study pilots sleep better, and a high-fat diet appeared to lead to significantly faster short-term memory.
"We started out thinking that the high-protein diet would lead to being the sharpest afterward," said colead investigator Glenda Lindseth, RN, PhD, licensed registered dietician and professor of nursing at the University of North Dakota (UND) in Grand Forks. "But we were surprised by our findings that it was actually the high-carb or high-fat diets that were the best. Eating a diet that's high in protein just isn't going to help you perform optimally."
"As a retired air-force pilot and a pilot for over 30 years, I believe this type of study is definitely needed," said the other colead author, Paul Lindseth, PhD, professor of aviation and associate dean at the UND Odegard School of Aerospace Sciences. "This is important for pilots in the military and in combat situations, where they need to be sharp and alert."
The Lindseths report that human error has been implicated in 70% to 80% of civil- and military-aviation accidents and in up to 91% of general-aviation accidents. In addition, lack of proper nutrition was rated as the top stressor in the daily lives of professional airline pilots.
Little Research on Diet and Cognition
There is currently little research on the potential connection between dietary intake and cognition. So in this study, the investigators sought to compare diets high in carbohydrates, fat, and protein to test their effects on cognition, flight performance, and sleep patterns.
A total of 45 pilots (mean age, 20.8 years; 87% male) from the UND commercial-aviation program were enrolled in this 14-week repeated-measures crossover trial.
During the first week, participants were randomized to receive 1 of 4 diets (3 full meals and 2 snacks) for 4 days: a diet high in carbohydrates, a diet high in fat, a diet high in protein, or a control diet. After a 2-week "phase-out" period, all pilots then randomly received a different study diet. This process was repeated until all pilots had received all 4 diets.
"We made sure that each pilot, no matter which of the study plans we gave them, got what would be considered a well-balanced diet, within 95% of the US recommended daily allowances for all of the micronutrients," explained Glenda Lindseth. In addition, the pilots were tested to make sure they received the number of calories required to sustain their weight.
Worse Performance With High-Protein Diet
Flight performance scores were determined using a GATT 2 full-motion flight simulator. The Sternberg item-recognition test and the Vandenberg mental-rotation test were used to evaluate cognitive function. Sleep patterns were measured with the Actiwatch sleep watch.
Results showed that overall flight-performance scores for the pilots consuming a high-protein diet were significantly worse (P < 05) than for those consuming a high-carbohydrate or a high-fat diet. A hierarchical regression analysis indicated that this was due in part to dietary protein intakes, serotonin levels, and irritability scores.
In addition, high-carbohydrate diets produced shorter sleep latencies than the other diets, especially the control diet (P < .03). In fact, the researchers found that if the pilots ate the high-carbohydrate diet, they seemed to sleep better, fall asleep quicker, and wake up less often.
The response time on the Sternberg test of short-term memory was significantly faster for participants who ate the high-fat diet (P < .05) than for those who ate the protein and control diets, especially at higher memory loads. No significant impact was observed on the Vandenberg test.
"We're certainly not saying you always have to eat high fat," said Glenda Lindseth. "The take-away message is that a diet that is well balanced and has a lot of carbohydrates and a reasonable amount of fat in it is best for pilots to perform well cognitively."
"These results can make significant contributions to understanding the effects of diet on cognition and performance and may, therefore, decrease the number of errors due to human factors for the war fighter," she added. The investigators are planning a follow-up study to confirm their findings.
Findings Likely Generalizeable
In an interview with Medscape Psychiatry, Karen Tountas, PhD, MHRF conference chair and the event's peer-reviewed medical research program manager, said: "I think this is a very exciting study. They've focused on working with pilots but anything we can find out about diet and its relationship to cognition [will likely] translate across all people. [This study] does open up avenues of more questions to be asked." Dr. Tountas was not associated with the trial.
She said that others reading these results should take into consideration who their particular patients are. "There are a lot of other different end points. Is it cognition that [the clinician] is looking at? Is it weight? Is it a combination of those 2? I think that it would be important for [clinicians] to get a broader picture of that before making a decision for their own patient population."
"We know the brain's primary source of energy is glucose — that is sugar, just straight sugar," Captain E. Melissa Kaime, MD, director of the Congressionally Directed Medical Research Programs (CDMRP), part of the US Army Medical Research and Materiel Command, told Medscape Psychiatry.
"In some ways it shouldn't surprise us that a diet high in carbohydrates is good for the brain because that's the glucose it needs. But we all know that there are other problems in society too, such as an obesity epidemic. So we want to certainly feed the brain but we don't want to overfeed it or the rest of the body." Captain Kaime was not involved in the study.
"Pilots use higher executive-functioning parts of their brains, and this study was testing these highly trained pilots at their maximum cognitive stress," added Captain Kaime.
"This is the first look at a new way of science, of looking to see: What does the brain need? So the next step is going to be: What dose now? What schedule? If you need glucose, is it 10 minutes before the stress test of the brain or is it a continuous diet of glucose? Like all good studies, this one brings up more questions than it answers."
"We're trying so hard to keep people healthy and we want the magic bullet — the 1 pill or the 1 vaccine that fixes everything." Captain Kaime said that this study is just 1 more that says the solution "is in your diet. And that is actually good news. Because if the solutions are . . . common sense and practical and available, [something] that you don't have to go out and buy with a prescription and that is at your fingertips anyway, that just makes it all the more powerful."
This study was funded by the CDMRP of the US Department of Defense. The Lindseths, Dr. Tountas, and Captain Kaime have disclosed no relevant financial relationships.
Military Health Research Forum (MHRF) 2009: Abstract P16-9. Presented September 1, 2009.
Deborah Brauser
September 1, 2009 — Diets high in carbohydrates or fat can lead to significantly better cognitive-performance and inflight-testing scores in pilots than diets high in protein, according to results reported in a poster presentation at the Military Health Research Forum (MHRF) 2009 in Kansas City, Missouri.
In addition, a high-carbohydrate diet helped study pilots sleep better, and a high-fat diet appeared to lead to significantly faster short-term memory.
"We started out thinking that the high-protein diet would lead to being the sharpest afterward," said colead investigator Glenda Lindseth, RN, PhD, licensed registered dietician and professor of nursing at the University of North Dakota (UND) in Grand Forks. "But we were surprised by our findings that it was actually the high-carb or high-fat diets that were the best. Eating a diet that's high in protein just isn't going to help you perform optimally."
"As a retired air-force pilot and a pilot for over 30 years, I believe this type of study is definitely needed," said the other colead author, Paul Lindseth, PhD, professor of aviation and associate dean at the UND Odegard School of Aerospace Sciences. "This is important for pilots in the military and in combat situations, where they need to be sharp and alert."
The Lindseths report that human error has been implicated in 70% to 80% of civil- and military-aviation accidents and in up to 91% of general-aviation accidents. In addition, lack of proper nutrition was rated as the top stressor in the daily lives of professional airline pilots.
Little Research on Diet and Cognition
There is currently little research on the potential connection between dietary intake and cognition. So in this study, the investigators sought to compare diets high in carbohydrates, fat, and protein to test their effects on cognition, flight performance, and sleep patterns.
A total of 45 pilots (mean age, 20.8 years; 87% male) from the UND commercial-aviation program were enrolled in this 14-week repeated-measures crossover trial.
During the first week, participants were randomized to receive 1 of 4 diets (3 full meals and 2 snacks) for 4 days: a diet high in carbohydrates, a diet high in fat, a diet high in protein, or a control diet. After a 2-week "phase-out" period, all pilots then randomly received a different study diet. This process was repeated until all pilots had received all 4 diets.
"We made sure that each pilot, no matter which of the study plans we gave them, got what would be considered a well-balanced diet, within 95% of the US recommended daily allowances for all of the micronutrients," explained Glenda Lindseth. In addition, the pilots were tested to make sure they received the number of calories required to sustain their weight.
Worse Performance With High-Protein Diet
Flight performance scores were determined using a GATT 2 full-motion flight simulator. The Sternberg item-recognition test and the Vandenberg mental-rotation test were used to evaluate cognitive function. Sleep patterns were measured with the Actiwatch sleep watch.
Results showed that overall flight-performance scores for the pilots consuming a high-protein diet were significantly worse (P < 05) than for those consuming a high-carbohydrate or a high-fat diet. A hierarchical regression analysis indicated that this was due in part to dietary protein intakes, serotonin levels, and irritability scores.
In addition, high-carbohydrate diets produced shorter sleep latencies than the other diets, especially the control diet (P < .03). In fact, the researchers found that if the pilots ate the high-carbohydrate diet, they seemed to sleep better, fall asleep quicker, and wake up less often.
The response time on the Sternberg test of short-term memory was significantly faster for participants who ate the high-fat diet (P < .05) than for those who ate the protein and control diets, especially at higher memory loads. No significant impact was observed on the Vandenberg test.
"We're certainly not saying you always have to eat high fat," said Glenda Lindseth. "The take-away message is that a diet that is well balanced and has a lot of carbohydrates and a reasonable amount of fat in it is best for pilots to perform well cognitively."
"These results can make significant contributions to understanding the effects of diet on cognition and performance and may, therefore, decrease the number of errors due to human factors for the war fighter," she added. The investigators are planning a follow-up study to confirm their findings.
Findings Likely Generalizeable
In an interview with Medscape Psychiatry, Karen Tountas, PhD, MHRF conference chair and the event's peer-reviewed medical research program manager, said: "I think this is a very exciting study. They've focused on working with pilots but anything we can find out about diet and its relationship to cognition [will likely] translate across all people. [This study] does open up avenues of more questions to be asked." Dr. Tountas was not associated with the trial.
She said that others reading these results should take into consideration who their particular patients are. "There are a lot of other different end points. Is it cognition that [the clinician] is looking at? Is it weight? Is it a combination of those 2? I think that it would be important for [clinicians] to get a broader picture of that before making a decision for their own patient population."
"We know the brain's primary source of energy is glucose — that is sugar, just straight sugar," Captain E. Melissa Kaime, MD, director of the Congressionally Directed Medical Research Programs (CDMRP), part of the US Army Medical Research and Materiel Command, told Medscape Psychiatry.
"In some ways it shouldn't surprise us that a diet high in carbohydrates is good for the brain because that's the glucose it needs. But we all know that there are other problems in society too, such as an obesity epidemic. So we want to certainly feed the brain but we don't want to overfeed it or the rest of the body." Captain Kaime was not involved in the study.
"Pilots use higher executive-functioning parts of their brains, and this study was testing these highly trained pilots at their maximum cognitive stress," added Captain Kaime.
"This is the first look at a new way of science, of looking to see: What does the brain need? So the next step is going to be: What dose now? What schedule? If you need glucose, is it 10 minutes before the stress test of the brain or is it a continuous diet of glucose? Like all good studies, this one brings up more questions than it answers."
"We're trying so hard to keep people healthy and we want the magic bullet — the 1 pill or the 1 vaccine that fixes everything." Captain Kaime said that this study is just 1 more that says the solution "is in your diet. And that is actually good news. Because if the solutions are . . . common sense and practical and available, [something] that you don't have to go out and buy with a prescription and that is at your fingertips anyway, that just makes it all the more powerful."
This study was funded by the CDMRP of the US Department of Defense. The Lindseths, Dr. Tountas, and Captain Kaime have disclosed no relevant financial relationships.
Military Health Research Forum (MHRF) 2009: Abstract P16-9. Presented September 1, 2009.
Smoking Boosts Multiple Sclerosis Risk
From Medscape Medical News
Allison Gandey
September 2, 2009 — Evidence is mounting that people at risk for autoimmune disease are especially susceptible to the harmful effects of smoking, but a new study suggests that nicotine might not be the culprit.
Those who stopped smoking saw their risk decline quite quickly.
"Our study confirms that smoking cigarettes increases the risk of multiple sclerosis," lead investigator Anna Hedström, MD, from the Karolinska Institutet in Stockholm, Sweden, said during an interview. "We found that the more a person smokes, the greater the risk. But what is interesting is we found that those who stopped smoking saw their risk decline quite quickly, and some exsmokers were as healthy as people who never smoked."
But in a surprising twist, researchers found that smokeless tobacco did not increase this risk. "That's not to say it isn't bad for you," Dr. Hedström told Medscape Neurology. "Other studies have linked it to heart disease and cancer — particularly lip cancer." She suggests that carcinogens other than nicotine might be affecting the immune system.
Speaking on behalf of the Multiple Sclerosis Society of Canada, Aprile Royal, assistant vice president of clinical programs, said that "there are lots of reasons not to smoke; it is bad for anyone. But for people with multiple sclerosis or those at particular risk, smoking is especially dangerous."
She complimented the study design, in which a large sample of patients was drawn from multiple centers. The work is part of the Epidemiologic Investigation of Multiple Sclerosis — an extensive case–control study of more than 900 patients and 1800 control subjects.
Researchers report that the increased risk was apparent even among participants who had smoked moderately. They report: "We found clear evidence of a dose-response correlation between cumulative dose of smoking and the risk of developing the disease."
The increased risk for multiple sclerosis associated with cigarettes remained up to 5 years after a patient stopped smoking, but it later declined.
A study published in Neurology last month showed that people with multiple sclerosis who smoke have higher lesion volumes, more atrophy, and are at greater risk for blood–brain-barrier disruption (Neurology. 2009;73:504-510).
During a recent interview, lead author of that study, Robert Zivadinov, MD, from the University of New York School of Medicine and Biomedical Sciences in Buffalo, said: "Ours is the first study to demonstrate that smoking can promote brain-tissue injury in multiple sclerosis patients."
Autoimmune Disease and Smoking Don't Mix
The findings are similar to those of a study published in July (Arch Neurol. 2009;66:858-864). As previously reported by Medscape Neurology, investigators found that smoking contributes to rapid disease progression.
Asked for comment when the study was first published, Lily Jung, MD, from the Swedish Neuroscience Institute in Seattle, Washington, and member of the American Academy of Neurology, said that "this is just more ammunition for telling patients that to stop smoking is the easiest thing they can do to treat their multiple sclerosis."
During an interview, Dr. Hedström said she agrees. She also recommends that people with a family history of multiple sclerosis avoid smoking.
Neurology. 2009;73:696-701. Abstract
Allison Gandey
September 2, 2009 — Evidence is mounting that people at risk for autoimmune disease are especially susceptible to the harmful effects of smoking, but a new study suggests that nicotine might not be the culprit.
Those who stopped smoking saw their risk decline quite quickly.
"Our study confirms that smoking cigarettes increases the risk of multiple sclerosis," lead investigator Anna Hedström, MD, from the Karolinska Institutet in Stockholm, Sweden, said during an interview. "We found that the more a person smokes, the greater the risk. But what is interesting is we found that those who stopped smoking saw their risk decline quite quickly, and some exsmokers were as healthy as people who never smoked."
But in a surprising twist, researchers found that smokeless tobacco did not increase this risk. "That's not to say it isn't bad for you," Dr. Hedström told Medscape Neurology. "Other studies have linked it to heart disease and cancer — particularly lip cancer." She suggests that carcinogens other than nicotine might be affecting the immune system.
Speaking on behalf of the Multiple Sclerosis Society of Canada, Aprile Royal, assistant vice president of clinical programs, said that "there are lots of reasons not to smoke; it is bad for anyone. But for people with multiple sclerosis or those at particular risk, smoking is especially dangerous."
She complimented the study design, in which a large sample of patients was drawn from multiple centers. The work is part of the Epidemiologic Investigation of Multiple Sclerosis — an extensive case–control study of more than 900 patients and 1800 control subjects.
Researchers report that the increased risk was apparent even among participants who had smoked moderately. They report: "We found clear evidence of a dose-response correlation between cumulative dose of smoking and the risk of developing the disease."
The increased risk for multiple sclerosis associated with cigarettes remained up to 5 years after a patient stopped smoking, but it later declined.
A study published in Neurology last month showed that people with multiple sclerosis who smoke have higher lesion volumes, more atrophy, and are at greater risk for blood–brain-barrier disruption (Neurology. 2009;73:504-510).
During a recent interview, lead author of that study, Robert Zivadinov, MD, from the University of New York School of Medicine and Biomedical Sciences in Buffalo, said: "Ours is the first study to demonstrate that smoking can promote brain-tissue injury in multiple sclerosis patients."
Autoimmune Disease and Smoking Don't Mix
The findings are similar to those of a study published in July (Arch Neurol. 2009;66:858-864). As previously reported by Medscape Neurology, investigators found that smoking contributes to rapid disease progression.
Asked for comment when the study was first published, Lily Jung, MD, from the Swedish Neuroscience Institute in Seattle, Washington, and member of the American Academy of Neurology, said that "this is just more ammunition for telling patients that to stop smoking is the easiest thing they can do to treat their multiple sclerosis."
During an interview, Dr. Hedström said she agrees. She also recommends that people with a family history of multiple sclerosis avoid smoking.
Neurology. 2009;73:696-701. Abstract
Wednesday, September 2, 2009
Use of Low-Dose Aspirin in Primary Prevention of Cardiovascular Events Not Recommended
From Heartwire
Fran Lowry
Medscape Conference Coverage, based on selected sessions at the:
European Society of Cardiology (ESC) Congress 2009
August 30, 2009 (Barcelona, Spain) — The use of low-dose aspirin in the primary prevention of cardiovascular events in healthy individuals with asymptomatic atherosclerosis is currently not warranted, according to the lead researcher of a large "real-world" study presented today at the European Society of Cardiology (ESC) 2009 Congress.
In the randomized trial of 3350 subjects deemed at high risk for cardiovascular and cerebrovascular events because of a low ankle-brachial index (ABI) (<0.95), aspirin had absolutely no effect on reducing events compared with placebo, Dr Gerry Fowkes (University of Edinburgh, Scotland) reported on behalf of the Aspirin for Asymptomatic Atherosclerosis (AAA) trialists.
However, aspirin did increase the risk of major hemorrhage.
The bleeding effect "is a real obstacle," Fowkes told heartwire . "I don't think the evidence is convincing enough as yet that aspirin should be used routinely in the general population."
The results of the trial are in conflict with findings from a meta-analysis from the Antithrombotic Trialists' (ATT) collaboration, which was published earlier this year in the Lancet [1], discussant Dr Carlo Patrono (Catholic University School of Medicine, Rome, Italy) told ESC attendees. He questioned how the results of AAA could be interpreted in light of the 12% relative risk reduction in serious cardiovascular events, largely driven by a reduction in nonfatal MI, that was seen in the ATT trial.
AAA Done Where the Need for Prevention Is Great
The AAA was a pragmatic trial, Fowkes explained, conducted in a deprived population in central Scotland, where rates of coronary heart disease and related mortality are high. "We wanted to get at where the problem actually existed in the population," he said.
Between 1998 and 2001, the AAA trialists invited men and women 50 to 75 years of age to undergo screening for asymptomatic atherosclerosis by measuring their ABI. A low ABI in otherwise-healthy individuals has been shown to be related to an increased risk of future cardiovascular events. Because it is simple and noninvasive, the ABI has the potential to be used as a screening test to detect high-risk individuals, Fowkes explained.
Of the more than 166 000 invitations that were sent out, the trialists ended up screening 28 980 individuals. Of this number, 3350 had a low ABI and were thus eligible to be entered into the trial.
They were randomly allocated to 100-mg enteric coated aspirin daily or to placebo and followed for a mean of 8.2 years. The primary end point of the trial was the composite of an initial fatal or nonfatal coronary event, stroke, or revascularization. Secondary end points were all vascular events, which included a composite of initial fatal or nonfatal coronary event, stroke, or revascularization, angina, intermittent claudication, transient ischemic attack, and all-cause mortality.
Patients in both groups were matched for age (mean age 62 years), gender (roughly 30% were men), and comorbidities. One-third of the study population consisted of smokers.
Aspirin had no effect in terms of reducing cardiovascular and cerebrovascular events. In all, there were 357 events, 181 (10.8%) in the aspirin group and 176 (10.5%) in the placebo group (hazard ratio 1.03, 95% CI 0.84–1.27).
Interestingly, cancer mortality was higher in the placebo group than in the aspirin group, Fowkes noted.
Adverse events, including major hemorrhage, were greater in the aspirin group (HR 1.71, 95% CI 0.99–2.97).
Fowkes pointed out that 40% of patients were noncompliant and did not take their aspirin as prescribed over the duration of the trial. Such a low compliance rate could have affected the results. "The 60% compliance rate is the typical level of compliance that you will find in the primary-prevention setting, and obviously there are many reasons that people stop taking aspirin. So whether aspirin is beneficial in clinical practice among patients who have a low ankle-brachial index and who are fully compliant with aspirin is unknown, and so our results cannot be extrapolated to that situation," he said.
heartwire asked Fowkes what he thinks may work for primary prevention in people with asymptomatic atherosclerosis, now that aspirin appears to be ineffective. "We don't have any strong evidence about what would work, but I think that given that these are high-risk individuals, it is probably reasonable to give them a statin. I think it would prove to be cost-effective to give a statin," he said. "Obviously, there is the possibility of giving a stronger antiplatelet such as clopidogrel or some of these new drugs that are being developed, but one would have to trial those properly."
AAA Underpowered
Patrono said the AAA study may have been underpowered and suggested that was one reason for its negative findings. "The sample size would have to be about four times larger to achieve the power to show a 12% relative risk reduction," he said.
Other reasons: "The presence of peripheral arterial disease, whether symptomatic or asymptomatic, may render platelet activation more critically dependent on ATP than thromboxane release, and there is some experimental as well as clinical evidence supporting this possibility."
An accelerated platelet turnover associated with peripheral arterial disease--at least in some patients--may also be a cause for the discrepancy, Patrono said.
To try to dissect out potential explanations, Fowkes and Dr Colin Baigent (Oxford University, UK), lead author of the ATT trial, have agreed to see how the AAA study would fit into the ATT meta-analysis. When available, the results will be posted by the Clinical Trial Service Unit, Patrono said.
Fowkes told heartwire that there is no reason to think that the relative reduction in cardiovascular events created by aspirin should be different in the primary or secondary setting. It's just that the benefits in the secondary setting far outweigh the risks. "The absolute reduction is much higher in secondary prevention than in primary prevention, but the level of bleeding is the same. So in secondary prevention, you've got a big reduction in events and a small amount of bleeding. In primary prevention, you have a smaller amount of reduction of events, and the same amount of bleeding. These two have got to be counterbalanced in the primary-prevention situation, and that is where the concern is at the moment."
Fran Lowry
Medscape Conference Coverage, based on selected sessions at the:
European Society of Cardiology (ESC) Congress 2009
August 30, 2009 (Barcelona, Spain) — The use of low-dose aspirin in the primary prevention of cardiovascular events in healthy individuals with asymptomatic atherosclerosis is currently not warranted, according to the lead researcher of a large "real-world" study presented today at the European Society of Cardiology (ESC) 2009 Congress.
In the randomized trial of 3350 subjects deemed at high risk for cardiovascular and cerebrovascular events because of a low ankle-brachial index (ABI) (<0.95), aspirin had absolutely no effect on reducing events compared with placebo, Dr Gerry Fowkes (University of Edinburgh, Scotland) reported on behalf of the Aspirin for Asymptomatic Atherosclerosis (AAA) trialists.
However, aspirin did increase the risk of major hemorrhage.
The bleeding effect "is a real obstacle," Fowkes told heartwire . "I don't think the evidence is convincing enough as yet that aspirin should be used routinely in the general population."
The results of the trial are in conflict with findings from a meta-analysis from the Antithrombotic Trialists' (ATT) collaboration, which was published earlier this year in the Lancet [1], discussant Dr Carlo Patrono (Catholic University School of Medicine, Rome, Italy) told ESC attendees. He questioned how the results of AAA could be interpreted in light of the 12% relative risk reduction in serious cardiovascular events, largely driven by a reduction in nonfatal MI, that was seen in the ATT trial.
AAA Done Where the Need for Prevention Is Great
The AAA was a pragmatic trial, Fowkes explained, conducted in a deprived population in central Scotland, where rates of coronary heart disease and related mortality are high. "We wanted to get at where the problem actually existed in the population," he said.
Between 1998 and 2001, the AAA trialists invited men and women 50 to 75 years of age to undergo screening for asymptomatic atherosclerosis by measuring their ABI. A low ABI in otherwise-healthy individuals has been shown to be related to an increased risk of future cardiovascular events. Because it is simple and noninvasive, the ABI has the potential to be used as a screening test to detect high-risk individuals, Fowkes explained.
Of the more than 166 000 invitations that were sent out, the trialists ended up screening 28 980 individuals. Of this number, 3350 had a low ABI and were thus eligible to be entered into the trial.
They were randomly allocated to 100-mg enteric coated aspirin daily or to placebo and followed for a mean of 8.2 years. The primary end point of the trial was the composite of an initial fatal or nonfatal coronary event, stroke, or revascularization. Secondary end points were all vascular events, which included a composite of initial fatal or nonfatal coronary event, stroke, or revascularization, angina, intermittent claudication, transient ischemic attack, and all-cause mortality.
Patients in both groups were matched for age (mean age 62 years), gender (roughly 30% were men), and comorbidities. One-third of the study population consisted of smokers.
Aspirin had no effect in terms of reducing cardiovascular and cerebrovascular events. In all, there were 357 events, 181 (10.8%) in the aspirin group and 176 (10.5%) in the placebo group (hazard ratio 1.03, 95% CI 0.84–1.27).
Interestingly, cancer mortality was higher in the placebo group than in the aspirin group, Fowkes noted.
Adverse events, including major hemorrhage, were greater in the aspirin group (HR 1.71, 95% CI 0.99–2.97).
Fowkes pointed out that 40% of patients were noncompliant and did not take their aspirin as prescribed over the duration of the trial. Such a low compliance rate could have affected the results. "The 60% compliance rate is the typical level of compliance that you will find in the primary-prevention setting, and obviously there are many reasons that people stop taking aspirin. So whether aspirin is beneficial in clinical practice among patients who have a low ankle-brachial index and who are fully compliant with aspirin is unknown, and so our results cannot be extrapolated to that situation," he said.
heartwire asked Fowkes what he thinks may work for primary prevention in people with asymptomatic atherosclerosis, now that aspirin appears to be ineffective. "We don't have any strong evidence about what would work, but I think that given that these are high-risk individuals, it is probably reasonable to give them a statin. I think it would prove to be cost-effective to give a statin," he said. "Obviously, there is the possibility of giving a stronger antiplatelet such as clopidogrel or some of these new drugs that are being developed, but one would have to trial those properly."
AAA Underpowered
Patrono said the AAA study may have been underpowered and suggested that was one reason for its negative findings. "The sample size would have to be about four times larger to achieve the power to show a 12% relative risk reduction," he said.
Other reasons: "The presence of peripheral arterial disease, whether symptomatic or asymptomatic, may render platelet activation more critically dependent on ATP than thromboxane release, and there is some experimental as well as clinical evidence supporting this possibility."
An accelerated platelet turnover associated with peripheral arterial disease--at least in some patients--may also be a cause for the discrepancy, Patrono said.
To try to dissect out potential explanations, Fowkes and Dr Colin Baigent (Oxford University, UK), lead author of the ATT trial, have agreed to see how the AAA study would fit into the ATT meta-analysis. When available, the results will be posted by the Clinical Trial Service Unit, Patrono said.
Fowkes told heartwire that there is no reason to think that the relative reduction in cardiovascular events created by aspirin should be different in the primary or secondary setting. It's just that the benefits in the secondary setting far outweigh the risks. "The absolute reduction is much higher in secondary prevention than in primary prevention, but the level of bleeding is the same. So in secondary prevention, you've got a big reduction in events and a small amount of bleeding. In primary prevention, you have a smaller amount of reduction of events, and the same amount of bleeding. These two have got to be counterbalanced in the primary-prevention situation, and that is where the concern is at the moment."
Use of Low-Dose Aspirin in Primary Prevention of Cardiovascular Events Not Recommended
From Heartwire
Fran Lowry
Medscape Conference Coverage, based on selected sessions at the:
European Society of Cardiology (ESC) Congress 2009
August 30, 2009 (Barcelona, Spain) — The use of low-dose aspirin in the primary prevention of cardiovascular events in healthy individuals with asymptomatic atherosclerosis is currently not warranted, according to the lead researcher of a large "real-world" study presented today at the European Society of Cardiology (ESC) 2009 Congress.
In the randomized trial of 3350 subjects deemed at high risk for cardiovascular and cerebrovascular events because of a low ankle-brachial index (ABI) (<0.95), aspirin had absolutely no effect on reducing events compared with placebo, Dr Gerry Fowkes (University of Edinburgh, Scotland) reported on behalf of the Aspirin for Asymptomatic Atherosclerosis (AAA) trialists.
However, aspirin did increase the risk of major hemorrhage.
The bleeding effect "is a real obstacle," Fowkes told heartwire . "I don't think the evidence is convincing enough as yet that aspirin should be used routinely in the general population."
The results of the trial are in conflict with findings from a meta-analysis from the Antithrombotic Trialists' (ATT) collaboration, which was published earlier this year in the Lancet [1], discussant Dr Carlo Patrono (Catholic University School of Medicine, Rome, Italy) told ESC attendees. He questioned how the results of AAA could be interpreted in light of the 12% relative risk reduction in serious cardiovascular events, largely driven by a reduction in nonfatal MI, that was seen in the ATT trial.
AAA Done Where the Need for Prevention Is Great
The AAA was a pragmatic trial, Fowkes explained, conducted in a deprived population in central Scotland, where rates of coronary heart disease and related mortality are high. "We wanted to get at where the problem actually existed in the population," he said.
Between 1998 and 2001, the AAA trialists invited men and women 50 to 75 years of age to undergo screening for asymptomatic atherosclerosis by measuring their ABI. A low ABI in otherwise-healthy individuals has been shown to be related to an increased risk of future cardiovascular events. Because it is simple and noninvasive, the ABI has the potential to be used as a screening test to detect high-risk individuals, Fowkes explained.
Of the more than 166 000 invitations that were sent out, the trialists ended up screening 28 980 individuals. Of this number, 3350 had a low ABI and were thus eligible to be entered into the trial.
They were randomly allocated to 100-mg enteric coated aspirin daily or to placebo and followed for a mean of 8.2 years. The primary end point of the trial was the composite of an initial fatal or nonfatal coronary event, stroke, or revascularization. Secondary end points were all vascular events, which included a composite of initial fatal or nonfatal coronary event, stroke, or revascularization, angina, intermittent claudication, transient ischemic attack, and all-cause mortality.
Patients in both groups were matched for age (mean age 62 years), gender (roughly 30% were men), and comorbidities. One-third of the study population consisted of smokers.
Aspirin had no effect in terms of reducing cardiovascular and cerebrovascular events. In all, there were 357 events, 181 (10.8%) in the aspirin group and 176 (10.5%) in the placebo group (hazard ratio 1.03, 95% CI 0.84–1.27).
Interestingly, cancer mortality was higher in the placebo group than in the aspirin group, Fowkes noted.
Adverse events, including major hemorrhage, were greater in the aspirin group (HR 1.71, 95% CI 0.99–2.97).
Fowkes pointed out that 40% of patients were noncompliant and did not take their aspirin as prescribed over the duration of the trial. Such a low compliance rate could have affected the results. "The 60% compliance rate is the typical level of compliance that you will find in the primary-prevention setting, and obviously there are many reasons that people stop taking aspirin. So whether aspirin is beneficial in clinical practice among patients who have a low ankle-brachial index and who are fully compliant with aspirin is unknown, and so our results cannot be extrapolated to that situation," he said.
heartwire asked Fowkes what he thinks may work for primary prevention in people with asymptomatic atherosclerosis, now that aspirin appears to be ineffective. "We don't have any strong evidence about what would work, but I think that given that these are high-risk individuals, it is probably reasonable to give them a statin. I think it would prove to be cost-effective to give a statin," he said. "Obviously, there is the possibility of giving a stronger antiplatelet such as clopidogrel or some of these new drugs that are being developed, but one would have to trial those properly."
AAA Underpowered
Patrono said the AAA study may have been underpowered and suggested that was one reason for its negative findings. "The sample size would have to be about four times larger to achieve the power to show a 12% relative risk reduction," he said.
Other reasons: "The presence of peripheral arterial disease, whether symptomatic or asymptomatic, may render platelet activation more critically dependent on ATP than thromboxane release, and there is some experimental as well as clinical evidence supporting this possibility."
An accelerated platelet turnover associated with peripheral arterial disease--at least in some patients--may also be a cause for the discrepancy, Patrono said.
To try to dissect out potential explanations, Fowkes and Dr Colin Baigent (Oxford University, UK), lead author of the ATT trial, have agreed to see how the AAA study would fit into the ATT meta-analysis. When available, the results will be posted by the Clinical Trial Service Unit, Patrono said.
Fowkes told heartwire that there is no reason to think that the relative reduction in cardiovascular events created by aspirin should be different in the primary or secondary setting. It's just that the benefits in the secondary setting far outweigh the risks. "The absolute reduction is much higher in secondary prevention than in primary prevention, but the level of bleeding is the same. So in secondary prevention, you've got a big reduction in events and a small amount of bleeding. In primary prevention, you have a smaller amount of reduction of events, and the same amount of bleeding. These two have got to be counterbalanced in the primary-prevention situation, and that is where the concern is at the moment."
Fran Lowry
Medscape Conference Coverage, based on selected sessions at the:
European Society of Cardiology (ESC) Congress 2009
August 30, 2009 (Barcelona, Spain) — The use of low-dose aspirin in the primary prevention of cardiovascular events in healthy individuals with asymptomatic atherosclerosis is currently not warranted, according to the lead researcher of a large "real-world" study presented today at the European Society of Cardiology (ESC) 2009 Congress.
In the randomized trial of 3350 subjects deemed at high risk for cardiovascular and cerebrovascular events because of a low ankle-brachial index (ABI) (<0.95), aspirin had absolutely no effect on reducing events compared with placebo, Dr Gerry Fowkes (University of Edinburgh, Scotland) reported on behalf of the Aspirin for Asymptomatic Atherosclerosis (AAA) trialists.
However, aspirin did increase the risk of major hemorrhage.
The bleeding effect "is a real obstacle," Fowkes told heartwire . "I don't think the evidence is convincing enough as yet that aspirin should be used routinely in the general population."
The results of the trial are in conflict with findings from a meta-analysis from the Antithrombotic Trialists' (ATT) collaboration, which was published earlier this year in the Lancet [1], discussant Dr Carlo Patrono (Catholic University School of Medicine, Rome, Italy) told ESC attendees. He questioned how the results of AAA could be interpreted in light of the 12% relative risk reduction in serious cardiovascular events, largely driven by a reduction in nonfatal MI, that was seen in the ATT trial.
AAA Done Where the Need for Prevention Is Great
The AAA was a pragmatic trial, Fowkes explained, conducted in a deprived population in central Scotland, where rates of coronary heart disease and related mortality are high. "We wanted to get at where the problem actually existed in the population," he said.
Between 1998 and 2001, the AAA trialists invited men and women 50 to 75 years of age to undergo screening for asymptomatic atherosclerosis by measuring their ABI. A low ABI in otherwise-healthy individuals has been shown to be related to an increased risk of future cardiovascular events. Because it is simple and noninvasive, the ABI has the potential to be used as a screening test to detect high-risk individuals, Fowkes explained.
Of the more than 166 000 invitations that were sent out, the trialists ended up screening 28 980 individuals. Of this number, 3350 had a low ABI and were thus eligible to be entered into the trial.
They were randomly allocated to 100-mg enteric coated aspirin daily or to placebo and followed for a mean of 8.2 years. The primary end point of the trial was the composite of an initial fatal or nonfatal coronary event, stroke, or revascularization. Secondary end points were all vascular events, which included a composite of initial fatal or nonfatal coronary event, stroke, or revascularization, angina, intermittent claudication, transient ischemic attack, and all-cause mortality.
Patients in both groups were matched for age (mean age 62 years), gender (roughly 30% were men), and comorbidities. One-third of the study population consisted of smokers.
Aspirin had no effect in terms of reducing cardiovascular and cerebrovascular events. In all, there were 357 events, 181 (10.8%) in the aspirin group and 176 (10.5%) in the placebo group (hazard ratio 1.03, 95% CI 0.84–1.27).
Interestingly, cancer mortality was higher in the placebo group than in the aspirin group, Fowkes noted.
Adverse events, including major hemorrhage, were greater in the aspirin group (HR 1.71, 95% CI 0.99–2.97).
Fowkes pointed out that 40% of patients were noncompliant and did not take their aspirin as prescribed over the duration of the trial. Such a low compliance rate could have affected the results. "The 60% compliance rate is the typical level of compliance that you will find in the primary-prevention setting, and obviously there are many reasons that people stop taking aspirin. So whether aspirin is beneficial in clinical practice among patients who have a low ankle-brachial index and who are fully compliant with aspirin is unknown, and so our results cannot be extrapolated to that situation," he said.
heartwire asked Fowkes what he thinks may work for primary prevention in people with asymptomatic atherosclerosis, now that aspirin appears to be ineffective. "We don't have any strong evidence about what would work, but I think that given that these are high-risk individuals, it is probably reasonable to give them a statin. I think it would prove to be cost-effective to give a statin," he said. "Obviously, there is the possibility of giving a stronger antiplatelet such as clopidogrel or some of these new drugs that are being developed, but one would have to trial those properly."
AAA Underpowered
Patrono said the AAA study may have been underpowered and suggested that was one reason for its negative findings. "The sample size would have to be about four times larger to achieve the power to show a 12% relative risk reduction," he said.
Other reasons: "The presence of peripheral arterial disease, whether symptomatic or asymptomatic, may render platelet activation more critically dependent on ATP than thromboxane release, and there is some experimental as well as clinical evidence supporting this possibility."
An accelerated platelet turnover associated with peripheral arterial disease--at least in some patients--may also be a cause for the discrepancy, Patrono said.
To try to dissect out potential explanations, Fowkes and Dr Colin Baigent (Oxford University, UK), lead author of the ATT trial, have agreed to see how the AAA study would fit into the ATT meta-analysis. When available, the results will be posted by the Clinical Trial Service Unit, Patrono said.
Fowkes told heartwire that there is no reason to think that the relative reduction in cardiovascular events created by aspirin should be different in the primary or secondary setting. It's just that the benefits in the secondary setting far outweigh the risks. "The absolute reduction is much higher in secondary prevention than in primary prevention, but the level of bleeding is the same. So in secondary prevention, you've got a big reduction in events and a small amount of bleeding. In primary prevention, you have a smaller amount of reduction of events, and the same amount of bleeding. These two have got to be counterbalanced in the primary-prevention situation, and that is where the concern is at the moment."
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