Eric B. Rimm

VITAMIN E CONSUMPTION AND THE RISK OF CORONARY HEART DISEASE IN MEN

BACKGROUND The oxidative modification of low-density lipoproteins increases their incorporation into the arterial intima, an essential step in atherogenesis. Although dietary antioxidants, such as vitamin C, carotene, and vitamin E, have been hypothesized to prevent coronary heart disease, prospective epidemiologic data are sparse. METHODS In 1986, 39,910 U.S. male health professionals 40 to 75 years of age who were free of diagnosed coronary heart disease, diabetes, and hypercholesterolemia completed detailed dietary questionnaires that assessed their usual intake of vitamin C, carotene, and vitamin E in addition to other nutrients. During four years of follow-up, we documented 667 cases of coronary disease. RESULTS After controlling for age and several coronary risk factors, we observed a lower risk of coronary disease among men with higher intakes of vitamin E (P for trend = 0.003). For men consuming more than 60 IU per day of vitamin E, the multivariate relative risk was 0.64 (95 percent confidence interval, 0.49 to 0.83) as compared with those consuming less than 7.5 IU per day. As compared with men who did not take vitamin E supplements, men who took at least 100 IU per day for at least two years had a multivariate relative risk of coronary disease of 0.63 (95 percent confidence interval, 0.47 to 0.84). Carotene intake was not associated with a lower risk of coronary disease among those who had never smoked, but it was inversely associated with the risk among current smokers (relative risk, 0.30; 95 percent confidence interval, 0.11 to 0.82) and former smokers (relative risk, 0.60; 95 percent confidence interval, 0.38 to 0.94). In contrast, a high intake of vitamin C was not associated with a lower risk of coronary disease. CONCLUSIONS These data do not prove a causal relation, but they provide evidence of an association between a high intake of vitamin E and a lower risk of coronary heart disease in men. Public policy recommendations with regard to the use of vitamin E supplements should await the results of additional studies.

Association Between Passive and Active Smoking and Incident Type 2 Diabetes in Women

OBJECTIVE Accumulating evidence has identified a positive association between active smoking and the risk of diabetes, but previous studies had limited information on passive smoking or changes in smoking behaviors over time. This analysis examined the association between exposure to passive smoke, active smoking, and the risk of incident type 2 diabetes among women. RESEARCH DESIGN AND METHODS This is a prospective cohort study of 100,526 women in the Nurses’ Health Study who did not have prevalent diabetes in 1982, with follow-up for diabetes for 24 years. RESULTS We identified 5,392 incident cases of type 2 diabetes during 24 years of follow-up. Compared with nonsmokers with no exposure to passive smoke, there was an increased risk of diabetes among nonsmokers who were occasionally (relative risk [RR] 1.10 [95% CI 0.94–1.23]) or regularly (1.16 [1.00–1.35]) exposed to passive smoke. The risk of incident type 2 diabetes was increased by 28% (12–50) among all past smokers. The risk diminished as time since quitting increased but still was elevated even 20–29 years later (1.15 [1.00–1.32]). Current smokers had the highest risk of incident type 2 diabetes in a dose-dependent manner. Adjusted RRs increased from 1.39 (1.17–1.64) for 1–14 cigarettes per day to 1.98 (1.57–2.36) for ≥25 cigarettes per day compared with nonsmokers with no exposure to passive smoke. CONCLUSIONS Our study suggests that exposure to passive smoke and active smoking are positively and independently associated with the risk of type 2 diabetes.

Obesity, fat distribution, and weight gain as risk factors for clinical diabetes in men.

OBJECTIVE To investigate the relation between obesity, fat distribution, and weight gain through adulthood and the risk of non-insulin-dependent diabetes melli-tus (NIDDM). RESEARCH DESIGN AND METHODS We analyzed data from a cohort of 51,529 U.S. male health professionals, 40-75 years of age in 1986, who completed biennial questionnaires sent out in 1986, 1988, 1990, and 1992. During 5 years of follow-up (1987-1992), 272 cases of NIDDM were diagnosed among men without a history of diabetes, heart disease, and cancer in 1986 and who provided complete health information. Relative risks (RRs) associated with different anthropometrie measures were calculated controlling for age, and multivariate RRs were calculated controlling for smoking, family history of diabetes, and age. RESULTS We found a strong positive association between overall obesity as measured by body mass index (BMI) and risk of diabetes. Men with a BMI of ≥35 kg/m2 had a multivariate RR of 42.1 (95% confidence interval [CI] 22.0-80.6) compared with men with a BMI <23.0 kg/m2. BMI at age 21 and absolute weight gain throughout adulthood were also significant independent risk factors for diabetes. Fat distribution, measured by waist-to-hip ratio (WHR), was a good predictor of diabetes only among the top 5%, while waist circumference was positively associated with the risk of diabetes among the top 20% of the cohort. CONCLUSIONS These data suggest that waist circumference may be a better indicator than WHR of the relationship between abdominal adiposity and risk of diabetes. Although early obesity, absolute weight gain throughout adulthood, and waist circumference were good predictors of diabetes, attained BMI was the dominant risk factor for NIDDM; even men of average relative weight had significantly elevated RRs.

Dietary Fiber, Glycemic Load, and Risk of NIDDM in Men

OBJECTIVE Intake of carbohydrates that provide a large glycemic response has been hypothesized to increase the risk of NIDDM, whereas dietary fiber is suspected to reduce incidence. These hypotheses have not been evaluated prospectively. RESEARCH DESIGN AND METHODS We examined the relationship between diet and risk of NIDDM in a cohort of 42,759 men without NIDDM or cardiovascular disease, who were 40–75 years of age in 1986. Diet was assessed at baseline by a validated semiquantitative food frequency questionnaire. During 6-years of follow-up, 523 incident cases of NIDDM were documented. RESULTS The dietary glycemic index (an indicator of carbohydrates ability to raise blood glucose levels) was positively associated with risk of NIDDM after adjustment for age, BMI, smoking, physical activity, family history of diabetes, alcohol consumption, cereal fiber, and total energy intake. Comparing the highest and lowest quintiles, the relative risk (RR) of NIDDM was 1.37 (95% CI, 1.02–1.83, P trend = 0.03). Cereal fiber was inversely associated with risk of NIDDM (RR = 0.70; 95% CI, 0.51–0.96, P trend = 0.007; for > 8.1 g/day vs. < 3.2 g/day). The combination of a high glycemic load and a low cereal fiber intake further increased the risk of NIDDM (RR = 2.17, 95% CI, 1.04–4.54) when compared with a low glycemic load and high cereal fiber intake. CONCLUSIONS These findings support the hypothesis that diets with a high glycemic load and a low cereal fiber content increase risk of NIDDM in men. Further, they suggest that grains should be consumed in a minimally refined form to reduce the incidence of NIDDM.

Moderate alcohol intake and lower risk of coronary heart disease: meta-analysis of effects on lipids and haemostatic factors

Abstract Objective: To summarise quantitatively the association between moderate alcohol intake and biological markers of risk of coronary heart disease and to predict how these changes would lower the risk. Design: Meta-analysis of all experimental studies that assessed the effects of moderate alcohol intake on concentrations of high density lipoprotein cholesterol, apolipoprotein A I, fibrinogen, triglycerides, and other biological markers previously found to be associated with risk of coronary heart disease. Participants: Men and women free of previous chronic disease and who were not dependent on alcohol Studies were included in which biomarkers were assessed before and after participants consumed up to 100 g of alcohol a day. Interventions: Alcohol as ethanol, beer, wine, or spirits. Main outcome measures: Changes in concentrations of high density lipoprotein cholesterol, apolipoprotein A I, Lp(a) lipoprotein, triglycerides, tissue type plasminogen activator activity, tissue type plasminogen activator antigen, insulin, and glucose after consuming an experimental dose of alcohol for 1 to 9 weeks; a shorter period was accepted for studies of change in concentrations of fibrinogen, factor VII, von Willebrand factor, tissue type plasminogen activator activity, and tissue type plasminogen activator antigen. Results: 61 data records were abstracted from 42 eligible studies with information on change in biological markers of risk of coronary heart disease. An experimental dose of 30 g of ethanol a day increased concentrations of high density lipoprotein cholesterol by 3.99 mg/dl (95% confidence interval 3.25 to 4.73), apolipoprotein A I by 8.82 mg/dl (7.79 to 9.86), and triglyceride by 5.69 mg/dl (2.49 to 8.89). Several haemostatic factors related to a thrombolytic profile were modestly affected by alcohol On the basis of published associations between these biomarkers and risk of coronary heart disease 30 g of alcohol a day would cause an estimated reduction of 24.7% in risk of coronary heart disease. Conclusions: Alcohol intake is causally related to lower risk of coronary heart disease through changes in lipids and haemostatic factors. Key messages Results from observational studies provide strong evidence that moderate alcohol intake lowers risk of coronary heart disease Short term trials of alcohol intake show significant changes in concentrations of lipids and clotting factors The changes in concentrations of high density lipoprotein cholesterol, fibrinogen, and triglycerides associated with an intake of 30 g of alcohol a day should reduce risk of coronary disease by 24.7% Alcohol intake may be causally related to lower risk of coronary heart disease through changes in lipids and haemostatic factors

Physical activity and incidence of non-insulin-dependent diabetes mellitus in women

The potential role of physical activity in the primary prevention of non-insulin-dependent diabetes mellitus (NIDDM) is largely unknown. We examined the association between regular vigorous exercise and the subsequent incidence of NIDDM in a prospective cohort of 87,253 US women aged 34-59 years and free of diagnosed diabetes, cardiovascular disease, and cancer in 1980. During 8 years of follow-up, we confirmed 1303 cases of NIDDM. Women who engaged in vigorous exercise at least once per week had an age-adjusted relative risk (RR) of NIDDM of 0.67 (p less than 0.0001) compared with women who did not exercise weekly. After adjustment for body-mass index, the reduction in risk was attenuated but remained statistically significant (RR = 0.84, p = 0.005). When analysis was restricted to the first 2 years after ascertainment of physical activity level and to symptomatic NIDDM as the outcome, age-adjusted RR of those who exercised was 0.5, and age and body-mass index adjusted RR was 0.69. Among women who exercised at least once per week, there was no clear dose-response gradient according to frequency of exercise. Family history of diabetes did not modify the effect of exercise, and risk reduction with exercise was evident among both obese and nonobese women. Multivariate adjustments for age, body-mass index, family history of diabetes, and other variables did not alter the reduced risk found with exercise. Our results indicate that physical activity may be a promising approach to the primary prevention of NIDDM.

Cardiovascular Morbidity and Mortality in Women Diagnosed With Rheumatoid Arthritis

Background—Rheumatoid arthritis may be associated with an increased risk of cardiovascular disease. We compared the incidence rates of myocardial infarction and stroke in subjects with and without rheumatoid arthritis. Methods and Results—A prospective cohort study was conducted among the 114 342 women participating in the Nurses’ Health Study who were free of cardiovascular disease and rheumatoid arthritis at baseline in 1976. All self-reported cases of rheumatoid arthritis were confirmed by medical record review. Fatal and nonfatal myocardial infarctions and strokes were similarly confirmed. Multivariate pooled logistic regression was used to adjust for potential cardiovascular risk factors. Five hundred twenty-seven incident cases of rheumatoid arthritis and 3622 myocardial infarctions and strokes were confirmed during 2.4 million person-years of follow-up. The adjusted relative risk of myocardial infarction in women with rheumatoid arthritis compared with those without was 2.0 (95% confidence interval [CI], 1.23 to 3.29). For stroke, the adjusted relative risk was 1.48 (95% CI, 0.70 to 3.12). Women who had rheumatoid arthritis for at least 10 years had a risk for myocardial infarction of 3.10 (95% CI, 1.64 to 5.87). Conclusion—In this large prospective cohort of women, participants with rheumatoid arthritis had a significantly increased risk of myocardial infarction but not stroke compared with those without rheumatoid arthritis. If these data are confirmed, aggressive coronary heart disease prevention strategies should be tested for persons with rheumatoid arthritis.

Prospective study of alcohol consumption and risk of coronary disease in men

Although an inverse association between alcohol consumption and risk of coronary artery disease has been consistently found in several types of studies, some have argued that the association is due at least partly to the inclusion in the non-drinking reference group of men who abstain because of pre-existing disease. The association between self-reported alcohol intake and coronary disease was studied prospectively among 51,529 male health professionals. In 1986 the participants completed questionnaires about food and alcohol intake and medical history, heart disease risk factors, and dietary changes in the previous 10 years. Follow-up questionnaires in 1988 sought information about newly diagnosed coronary disease. 350 confirmed cases of coronary disease occurred. After adjustment for coronary risk factors, including dietary intake of cholesterol, fat, and dietary fibre, increasing alcohol intake was inversely related to coronary disease incidence (p for trend less than 0.001). Exclusion of 10,302 current non-drinkers or 16,342 men with disorders potentially related to coronary disease (eg, hypertension, diabetes, and gout) which might have led men to reduce their alcohol intake, did not substantially affect the relative risks. These findings support the hypothesis that the inverse relation between alcohol consumption and risk of coronary disease is causal.

25-Hydroxyvitamin D and Risk of Myocardial Infarction in Men: A Prospective Study

BACKGROUND Vitamin D deficiency may be involved in the development of atherosclerosis and coronary heart disease in humans. METHODS We assessed prospectively whether plasma 25-hydroxyvitamin D (25[OH]D) concentrations are associated with risk of coronary heart disease. A nested case-control study was conducted in 18,225 men in the Health Professionals Follow-up Study; the men were aged 40 to 75 years and were free of diagnosed cardiovascular disease at blood collection. The blood samples were returned between April 1, 1993, and November 30, 1999; 99% were received between April 1, 1993, and November 30, 1995. During 10 years of follow-up, 454 men developed nonfatal myocardial infarction or fatal coronary heart disease. Using risk set sampling, controls (n = 900) were selected in a 2:1 ratio and matched for age, date of blood collection, and smoking status. RESULTS After adjustment for matched variables, men deficient in 25(OH)D (<or=15 ng/mL [to convert to nanomoles per liter, multiply by 2.496]) were at increased risk for MI compared with those considered to be sufficient in 25(OH)D (>or=30 ng/mL) (relative risk [RR], 2.42; 95% confidence interval [CI], 1.53-3.84; P < .001 for trend). After additional adjustment for family history of myocardial infarction, body mass index, alcohol consumption, physical activity, history of diabetes mellitus and hypertension, ethnicity, region, marine omega-3 intake, low- and high-density lipoprotein cholesterol levels, and triglyceride levels, this relationship remained significant (RR, 2.09; 95% CI, 1.24-3.54; P = .02 for trend). Even men with intermediate 25(OH)D levels were at elevated risk relative to those with sufficient 25(OH)D levels (22.6-29.9 ng/mL: RR, 1.60 [95% CI, 1.10-2.32]; and 15.0-22.5 ng/mL: RR, 1.43 [95% CI, 0.96-2.13], respectively). CONCLUSION Low levels of 25(OH)D are associated with higher risk of myocardial infarction in a graded manner, even after controlling for factors known to be associated with coronary artery disease.

Review of moderate alcohol consumption and reduced risk of coronary heart disease: is the effect due to beer, wine, or spirits?

Abstract Objectives: To review the effect of specific types of alcoholic drink on coronary risk. Design: Systematic review of ecological, case-control, and cohort studies in which specific associations were available for consumption of beer, wine, and spirits and risk of coronary heart disease. Subjects: 12 ecological, three case-control, and 10 separate prospective cohort studies. Main outcome measures: Alcohol consumption and relative risk of morbidity and mortality from coronary heart disease. Results: Most ecological studies suggested that wine was more effective in reducing risk of mortality from heart disease than beer or spirits. Taken together, the three case-control studies did not suggest that one type of drink was more cardioprotective than the others. Of the 10 prospective cohort studies, four found a significant inverse association between risk of heart disease and moderate wine drinking, four found such an association for beer, and four for spirits. Conclusions: Results from observational studies, where alcohol consumption can be linked directly to an individuals risk of coronary heart disease, provide strong evidence that all alcoholic drinks are linked with lower risk. Thus, a substantial portion of the benefit is from alcohol rather than other components of each type of drink. Key messages Key messages We examined the relation between specific alcoholic drinks and reduction of risk of coronary heart disease by summarising published reports from ecological, case-control, and cohort studies Most ecological studies suggested that wine was more effective in reducing risk of mortality than beer or spirits, whereas the three case-control studies together did not suggest that one type of drink was more cardioprotective than others Of the 10 prospective cohort studies, four found a significant inverse association between risk of heart disease and moderate wine drinking, four found the association for beer, and four found it for spirits. The evidence suggests that all alcoholic drinks are linked with lower risk, so that much of the benefit is from alcohol rather than other components of each type of drink