Risk Factors for Coronary Heart Disease in Men 18 to 39 Years of Age

Coronary heart disease remains the leading cause of death in the United States (1). Autopsy studies (2-5) show that coronary atherosclerosis begins as early as 20 years of age, and a recent study found severely stenotic coronary arteries (narrowing 40%) in 19% of men in their early thirties (6). On the basis of these observations, the National Cholesterol Education Program recommended cholesterol screening in all adults 20 years of age or older (7). Similarly, the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure recommends screening for hypertension in all persons 18 years of age or older (8). However, guidelines on prevention of coronary heart disease in young adults have not been uniformly accepted, in part because data on risk prediction and coronary disease prevention in adults younger than 40 years of age are limited (9-12). Numerous studies in middle-aged (40 to 65 years of age) and, to a lesser extent, older persons have shown that the major risk factors for coronary heart disease (which include cholesterol level, blood pressure, and cigarette smoking) are predictive of long-term outcomes in these age groups (13-16). In addition, primary and secondary prevention trials have convincingly shown benefits of reduction of certain risk factors, such as dyslipidemia and hypertension, in middle-aged and older adults (7, 8, 17-19). However, equally compelling data from observational studies or clinical trials are almost nonexistent in young adults (4, 5, 13, 20). The Chicago Heart Association Detection Project in Industry, one of the largest and longest cardiovascular disease studies, is a unique resource. The study cohort comprises 11 016 young men 18 to 39 years of age at baseline (mean age, 29 years), and more than 20 years of follow-up have been completed for coronary and all-cause mortality. We report data on risk prediction in young men from the Project. We hypothesized that the risk factors typically related to death from coronary heart disease in middle-aged cohorts are also related to death from coronary disease in younger cohorts. Methods Study Sample The Chicago Heart Association Detection Project in Industry is a prospective cohort study of long-term risks for coronary, total cardiovascular, and all-cause mortality. Demographic characteristics of participants, selection criteria, and standardized methods have been reported elsewhere (14, 21, 22). Briefly, approximately 75 000 employees of 84 Chicago-area companies and organizations were invited to participate in assessments of cardiovascular risk factors; the response rate was 53%. The cohort screened between November 1967 and January 1973 included 39 573 men and women 18 to 74 years of age from various ethnic backgrounds (white, Asian, African American, Hispanic, and other). Our report focuses on the 11 016 men who were 18 to 39 years of age at baseline. All age-eligible participants were included in the analyses, except diabetic persons; at that young age, fewer than 1% of the cohort members had diabetes, and those who did were presumed to have type 1 diabetes. A group of nondiabetic men who were 40 to 59 years of age at baseline was used for comparison. The study has been reviewed on a regular basis by the institutional review board at Northwestern University and has repeatedly received approval for ongoing follow-up. Because the study participants are not contacted directly in follow-up and are never identified by name in any report, this research has been granted an exemption from the need to obtain informed consent of the participants after the baseline examination. Risk Factor Assessment Baseline screening for risk factors was performed by trained personnel. Questionnaires were used to record age, sex, ethnicity, years of education, number of cigarettes smoked per day, medical history, and history of medical treatment for diabetes or hypertension. Measurements included height and weight to calculate body mass index, a single measurement of supine casual blood pressure obtained by using a standard stethoscope and mercury sphygmomanometer, resting electrocardiography, and a single measurement of total serum cholesterol. Standardized methods were used for laboratory determinations of total serum cholesterol (22), uric acid (23), and plasma glucose (24). Criteria from the Pooling Project (25) and Hypertension Detection and Follow-up Program (26) were used to classify electrocardiographic abnormalities as minor (such as nonspecific ST or T-wave abnormalities) or major (such as major Q-wave or ventricular hypertrophy). Outcomes Death from coronary heart disease was the primary outcome of interest. Before 1979, vital status was ascertained by periodic follow-up by using both local records and the Social Security Administration; from 1979 onward, the National Death Index was used. Ascertainment of vital status is more than 99% complete for all study participants. Death certificates were acquired for known decedents and were coded by trained physicians according to the International Classification of Diseases, Eighth Revision (ICD-8) (27). Study team members who were blinded to baseline data cross-checked all coding decisions. For this report, only underlying cause of death was used. Coronary heart disease deaths were those assigned ICD-8 codes 410.0 through 414.9. Cardiovascular disease mortality was defined by ICD-8 codes 400.00 through 445.9. All-cause mortality was also assessed. Follow-up was complete at 20 years in all participants except those who were deceased and 356 participants (3.2% of the cohort) with less than 20 years of follow-up. Statistical Analysis Cox proportional-hazards regression was used to assess the association of baseline risk factors with death from coronary heart disease. Risk factors assessed were age, serum cholesterol level, systolic blood pressure, diastolic blood pressure, number of cigarettes smoked per day, body mass index, major electrocardiographic abnormalities, minor electrocardiographic abnormalities, education, and black ethnicity. To determine whether associations of each risk factor with coronary heart disease mortality differed between young and middle-aged men, an interaction model was formulated that included a dummy variable representing the middle-aged group and the interaction of each risk factor with the dummy variable. Rejection of a Wald test (28) that the interaction equaled zero indicated that the relative risks differed in the young and middle-aged groups. This part of the analysis assessed whether risk factors that are typically related to death from coronary heart disease in a middle-aged cohort are also related to death from coronary heart disease in a young cohort. To assess whether risk factors that are significantly associated with death from coronary heart disease are also accurate in predicting death from coronary heart disease in a young cohort, we constructed receiver-operating characteristic (ROC) curves for selected models in the young cohort and calculated the corresponding c-statistic, which represents the area under the ROC curve (AUC) (29). A nonparametric statistical test developed by DeLong and colleagues (30) was performed to determine whether the AUCs for various models differed significantly from one another. The ROC curve is a graphical method of depicting the trade-off between the true-positive rate (sensitivity) and the false-positive rate (1 specificity) of a test (29). The AUC represents the discriminating ability of that particular test. An AUC of 0.50 indicates that a test has no discriminatory capacity; the true-positive rate equals the false-positive rate, and the value represents the probability of prediction by chance alone. As the AUC increases and the curve migrates closer toward the upper left margin of the graph, the predictive capability of that test increases. Previous studies have used ROC curves to identify and assess the predictive capacity of risk assessment strategies in persons 30 to 74 years of age who are at risk for subsequent coronary disease (15, 31). Role of the Funding Sources The current funding source, the National Heart, Lung, and Blood Institute, has had no role in the collection, analysis, or interpretation of the data or in the decision to submit the paper for publication. Previous funding sources have included the American Heart Association of Metropolitan Chicago, which contributed personnel who were involved in data collection at baseline. The American Heart Association of Metropolitan Chicago has not been involved in analysis or interpretation of the current data or in the decision to submit the paper for publication. Results Baseline Characteristics Table 1 shows baseline characteristics of the two age groups. Mean age in the 11 016 younger men was 29.7 years; mean total serum cholesterol level in this group was 4.92 mmol/L (189.9 mg/dL), and mean systolic blood pressure was 134.6 mm Hg. Approximately half of the younger participants were current smokers, and they consumed an average of 21.2 cigarettes per day. Mean formal education was 13.8 years, and black persons made up 8.1% of participants. The prevalence of major and minor electrocardiographic abnormalities was 3.3% and 5.5%, respectively. As expected, all average values for risk factors were lower (less adverse) in younger adults than in men 40 to 59 years of age at baseline. Table 1. Baseline Characteristics of Young and Middle-Aged Men in the Chicago Heart Association Detection Project in Industry, 19671973 Cardiovascular Disease and All-Cause Mortality Four hundred fifty-five men died during 20 years of follow-up. One third of these mortality events (n = 155) were due to cardiovascular disease, and coronary heart disease was the leading cause of death (n = 123). Relative Risk for Death from Coronary Heart Disease in Young Adult Men Table 2 shows the relative risk for death from coronary heart disease over