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Background Four large trials have shown cholesterol-reduction therapy to be effective for primary prevention of coronary heart disease (CHD). Methods To determine the generalizability of these trials to a community-based sample, we compared the total cholesterol and high-density lipoprotein cholesterol (HDL-C) distributions of patients in the 4 trials with those of Framingham Heart Study subjects. Lipid profiles that have not been studied were identified. Twelve-year rates of incident CHD were compared between subjects who met eligibility criteria and those who did not. Results The Framingham sample included 2498 men and 2870 women aged 30 to 74 years. Among Framingham men, 23.4% to 42.0% met eligibility criteria for each of the 4 trials based on their lipid levels; 60.2% met eligibility criteria for at least 1 trial. For the 1 trial that included women, 20.2% of Framingham women met eligibility criteria. In general, subjects with desirable total cholesterol levels and lower HDL-C levels and subjects with average total cholesterol levels and average to higher HDL-C levels have not been included in these trials. Among subjects who developed incident CHD during follow-up, 25.1% of men and 66.2% of women would not have been eligible for any trial. Most ineligible subjects who developed CHD had isolated hypertriglyceridemia (>2.25 mmol/L [>200 mg/dL]). Conclusions In our sample, 40% of men and 80% of women had lipid profiles that have not been studied in large trials to date. We observed a large number of CHD events in "ineligible" subjects in whom hypertriglyceridemia was common. Further studies are needed to define the role of lipid-lowering therapy vs other strategies for primary prevention in the general population.

Context We devised a risk appraisal function to assess the hazard of heart failure in persons who are predisposed by coronary disease, hypertension, or valvular heart disease. Objective To provide general practitioners and internists with a cost-effective method to select people at high risk who are likely to have impaired left ventricular systolic function and may therefore require further evaluation and aggressive preventive measures. Methods The routinely measured risk factors used in constructing the heart failure profile include age, electrocardiographic left ventricular hypertrophy, cardiomegaly on chest x-ray film, heart rate, systolic blood pressure, vital capacity, diabetes mellitus, evidence of myocardial infarction, and valvular disease or hypertension. Based on 486 heart failure cases during 38 years of follow-up, 4-year probabilities of failure were computed using the pooled logistic regression model for each sex; a simple point score system was employed. A multivariate profile was also produced without the vital capacity or chest x-ray film because these may not be readily available in some clinical settings. Results Using the risk factors that make up the multivariate risk formulation—derived from ordinary office procedures—the probability of developing heart failure can be estimated and compared with the average risk for persons of the same age and sex. Using this risk profile, 60% of events in men and 73% in women occurred in subjects in the top quintile of multivariate risk. Conclusions Using this multivariate risk formulation, it is possible to identify high-risk candidates for heart failure who are likely to have a substantial yield of positive findings when tested for objective evidence of presymptomatic left ventricular dysfunction. The risk profile may also identify candidates who are at high risk for heart failure because of multiple, marginal risk factor abnormalities that might otherwise be overlooked.

The degree of clustering for common metabolic coronary disease risk factors is not well known, the antecedents of clustering are not well studied, and the impact of such clusters on coronary risk has not been assessed systematically.Prospective community sample of 2406 men and 2569 women aged 18 to 74 years at baseline. The 6 metabolically linked risk factors considered were the lowest sex-specific quintile of high-density lipoprotein cholesterol and the highest quintiles of body mass index, systolic blood pressure, triglycerides, glucose, and serum total cholesterol.At baseline the risk factor sum, represented as integer values, ranged from 0 to 6, and clusters of 3 or more risk factors occurred at twice the rate predicted by chance. After adjustment for age and obesity level, a 2.25-kg (5-lb) weight increase over 16 years was associated with an increased risk factor sum in men (+20%; P=.002) and women (+37%; P.001), and a 2.25-kg weight loss was associated with a decreased risk factor sum in men (-48%; P.001) and women (-40%; P.001). Clusters of 3 or more risk factors were associated with a 2.39 (95% confidence interval, 1.56-3.36) and 5.90 (95% confidence interval, 2.54-13.73) times greater risk of coronary heart disease in men and women, respectively (both P.001).Atherogenic risk factor clustering is common in both sexes, worsens with weight gain, and is associated with greatly increased risk of coronary disease risk in both sexes.

Background Elevated fasting total homocysteine (tHcy) levels were recently shown to confer an independent risk for all-cause and cardiovascular disease (CVD) mortality among selected Norwegian patients with confirmed coronary heart disease. We examined whether elevated fasting plasma tHcy levels were predictive of all-cause and CVD mortality in a large, population-based sample of elderly US women and men. Methods Nonfasting plasma tHcy levels were determined in 1933 elderly participants (mean age, 70 ± 7 years; 58.9% women) from the original Framingham Study cohort, examined between 1979 and 1982, with follow-up through 1992. Unadjusted and adjusted (ie, for age, sex, diabetes, smoking, systolic blood pressure, total and high-density lipoprotein cholesterol, and creatinine) relative risk estimates (with 95% confidence intervals [CIs]) for total and CVD mortality were generated by proportional hazards modeling, with tHcy levels (quartiles) as the independent variable. Results There were 653 total deaths and 244 CVD deaths during a median follow-up of 10.0 years. Proportional hazards modeling revealed that tHcy levels of 14.26 µmol/L or greater (the upper quartile), vs less than 14.26 µmol/L (the lower three quartiles), were associated with relative risk estimates of 2.18 (95% CI, 1.86-2.56) and 2.17 (95% CI, 1.68-2.82) for all-cause and CVD mortality, respectively. The relative risk estimates after adjustment for age, sex, systolic blood pressure, diabetes, smoking, and total and high-density lipoprotein cholesterol levels attenuated these associations, but they remained significant: 1.54 (95% CI, 1.31-1.82) for all-cause mortality; 1.52 (95% CI, 1.16-1.98) for CVD mortality. Conclusion Elevated nonfasting plasma tHcy levels are independently associated with increased rates of all-cause and CVD mortality in the elderly.