The Effect of Fruit and Vegetable Intake on Risk for Coronary Heart Disease

In several studies, many nutrients in fruits and vegetables, such as dietary fiber, potassium, and antioxidants, have been associated with reduced risk for cardiovascular disease (1-5). However, as reviewed elsewhere (6), most prospective studies that have specifically examined intake of fruits and vegetables in relation to risk for cardiovascular disease have been small, and their results have been inconsistent. Dietary assessments were often crude and available only at baseline, and few studies have examined the effects of specific types of vegetables or fruits. In a recent report (7), we evaluated the association between fruit and vegetable intake and risk for ischemic stroke. We found that persons in the highest quintile of fruit and vegetable intake had a relative risk of 0.69 (95% CI, 0.52 to 0.92) compared with the lowest quintile of intake; moreover, a 1-serving/d increase in fruit or vegetable intake was associated with a 6% lower risk for ischemic stroke, after controlling for standard cardiovascular risk factors. In the current study, we sought to evaluate the association between intake of overall and specific fruits and vegetables and incidence of coronary heart disease. Methods Study Sample The samples for this analysis consisted of participants in the Nurses' Health Study (8) and Health Professionals' Follow-Up Study (1). The two studies have similar designs; in both, participants complete mailed questionnaires about medical history, health behaviors, and occurrence of cardiovascular and other outcomes every 2 years. The Nurses' Health Study began in 1976, when 121 700 female registered nurses 30 to 55 years of age were recruited; diet was first assessed in 1980. Health Professionals' Follow-up Study participants were recruited in 1986 and comprise 51 529 male health professionals, including dentists, veterinarians, pharmacists, optometrists, osteopaths, and podiatrists, 40 to 75 years of age. Sample for Analysis We excluded participants with incomplete dietary assessments or with previously diagnosed cancer, diabetes or cardiovascular disease that was reported before the first dietary assessment. We followed 84 251 eligible women during 14 years of follow-up and 42 148 eligible men during 8 years follow-up for incidence of coronary heart disease. The rate of follow-up for nonfatal events was 97% of the total potential person-years of follow-up in both cohorts. Assessment of Coronary Heart Disease End Points Our primary end point was nonfatal myocardial infarction or fatal coronary disease occurring after return of the 1980 questionnaire but before 1 June 1994 in women and after return of the 1986 questionnaire but before 1 January 1994 in men. We sought to review medical records for all such reports. Records were reviewed by physicians who were blinded to the participants' risk factor status. Myocardial infarction was confirmed by using World Health Organization criteria: symptoms plus either diagnostic electrocardiographic changes or elevated levels of cardiac enzymes (9). Infarctions that required hospital admission and for which confirmatory information was obtained by interview or letter, but for which no medical records were available, were designated as probable. We included all confirmed and probable cases in our analyses because results were the same after probable cases were excluded. Deaths were identified by using state vital records and the National Death Index or were reported by next of kin and the U.S. postal system. Follow-up for deaths was more than 98% complete [10]. Death certificates along with medical records were used to ascertain cause of death. Fatal coronary disease was categorized as definite if 1) it was confirmed by hospital record or autopsy or 2) coronary disease was listed as the cause of death on the certificate, this was the underlying and most plausible cause, and evidence of previous coronary disease was available. We did not rely on the statement of the cause of death on the death certificate alone as providing sufficient confirmation of death due to coronary heart disease. If no medical records were available, we categorized persons in whom coronary heart disease was the underlying cause on the death certificate as presumed coronary heart disease. Analyses limited to confirmed cases yielded results very similar to those obtained when all cases were included, although with less precision. Persons who experienced sudden death within 1 hour of onset of symptoms and had no plausible cause other than coronary disease were categorized as coronary heart disease cases. Fatal cases of coronary heart disease constituted 30% of all cases of coronary heart disease among women and 33% among men. Dietary Assessment Diet was assessed in the Nurses' Health Study in 1980, 1984, 1986, and 1990. A 61-item semi-quantitative food-frequency questionnaire that included 6 fruit items, 11 vegetable items, and 3 potato items was used in 1980. In 1984, the questionnaire was expanded to 126 items that covered 15 fruit items and 28 vegetable items plus potatoes; similar questionnaires were repeated in 1986 and 1990. In the Health Professionals' Follow-up Study, diet was assessed in 1986 and 1990 by using food-frequency questionnaires very similar to those in the 1984 Nurses' Health Study questionnaire. We excluded women who left 10 or more of the 61 items blank or who had implausible scores for total food intake (<500 or >3500 kcal/d). Men who left 70 or more of the 131 dietary questions blank or who reported daily caloric intake outside the plausible range of 800 to 4200 calories were also excluded. For each food item, a standard serving size was specified. Natural portion sizesfor example, one banana or a small glass of tomato juicewere used whenever possible; otherwise a weight or volume of that item commonly consumed by the U.S. population at one meal was used. On dietary questionnaires, participants reported their average intake of the specified portion size (serving) for each food over the past year. For each food item on the questionnaire, nine responses were possible, ranging from never or less than once per month to six or more times per day. Detailed descriptions of the reproducibility and validity of the food frequency questionnaire for men and women have been published elsewhere (11-13). Frequencies and portions for the individual food items were converted to average daily intake of each fruit and vegetable item for each participant. The average daily intakes of individual food items were combined to compute total fruit and vegetable intake and intakes of composite fruit and vegetable groups. Definitions of the composite groups (all fruits, all vegetables, citrus fruit, citrus fruit juice, cruciferous vegetables, green leafy vegetables, vitamin Crich fruits and vegetables, legumes, and potatoes) were modified for our previous study (7) by using a report by Steinmetz and colleagues (14). Vitamin Crich fruits and vegetables were defined as those containing more than 30 mg of vitamin C per serving. We did not include potatoes, tofu and soybeans, dried beans, and lentils as vegetables; in addition, condiments such as chili sauce and garlic that had very small portion sizes were not counted in total vegetables. When aggregating items to compute the composite items, we assumed that individual foods for which values were missing implied no intake (15). Statistical Analysis We found 1063 incident cases of coronary heart disease among men and 1127 among women. Person-time for each participant was calculated from the date of return of the 1980 questionnaire in the Nurses' Health Study or the 1986 questionnaire in the Health Professionals' Follow-up Study to the first coronary heart disease event, death, or the cutoff date (1 June 1994 for women and 31 January 1994 for men), whichever occurred first. We excluded participants who reported cardiovascular disease or cancer or diabetes before completion of the baseline dietary questionnaires. Each participant contributed only one end point, and the cohort at risk for each 2-year follow-up period included only those who remained free of reported coronary heart disease at the beginning of each follow-up period. The study hypotheses were defined before data were collected. The analyses were performed separately in each cohort because of differences in sex and the questionnaires administered to the two cohorts. This approach was selected to achieve better control of confounding. We used pooled logistic regression with 2-year follow-up increments (16) to estimate relative risks (incidence rate ratios) and 95% CIs within each cohort. Analyses were adjusted for age (5-year categories), smoking (never, former, or current [1 to 14 cigarettes/d, 15 to 24 cigarettes/d, or 25 cigarettes/d]), alcohol consumption (five categories in women and seven categories in men), family history of myocardial infarction (before 65 years of age in women and before 60 years of age in men), body mass index (quintiles); use of multivitamin supplements, use of vitamin E, use of aspirin, physical activity (two categories in women and quintiles in men), reported hypertension and hypercholesterolemia, total daily caloric intake (17), and time period (each 2-year follow-up period). Among women, we also controlled for postmenopausal hormone use. We updated information on diet and risk factors for coronary heart disease over time to better represent long-term patterns (8, 18). In the Nurses' Health Study, we used data from the 1980, 1984, 1986, and 1990 questionnaires, and in the Health Professionals' Follow-up Study, we used data from the 1986 and 1990 questionnaires. For each 2-year follow-up period in which events were reported, we computed intake for each composite item as a cumulative average of intake from all available food-frequency questionnaires up to the start of the follow-up period. For participants who experienced angina, coronary artery bypass graft surgery or a