Alcohol Consumption and Risk for Coronary Heart Disease among Men with Hypertension

Context Heavy alcohol consumption may increase risk for hypertension, but does it increase risk for cardiovascular disease? Contributions In this 16-year prospective study, 11711 male health professionals with hypertension reported their average alcohol consumption every 4 years. Compared with men who abstained from alcohol, men who consumed 10 to 14 g/d (about 1 drink per day), 15 to 29 g/d, 30 to 49 g/d, and more than 49 g/d of alcohol had decreased risk for myocardial infarction. Alcohol intake seemed unrelated to total death or death due to cardiovascular disease. Cautions Alcohol intake and hypertension were self-reported. Few outcomes limited ability to determine precise relationships between alcohol and stroke. The Editors Hypertension is a major public health burden in the United States. In 1999, 65 million adults had the condition, an approximately 30% increase from 1991 (1). Hypertension is associated with a doubled risk for cardiovascular disease (CVD) and may account for 30% of events associated with CVD (2). Moderate alcohol consumption is inversely associated with CVD and total death (3, 4). However, intake of more than 30 grams of alcohol (that is, more than 2 drinks) per day is associated with an increased risk for hypertension (5, 6). Guidelines for alcohol consumption among patients with hypertension range from a limit of 2 to 3 drinks per day to complete abstention from alcohol (79). These contradictory recommendations may reflect the paucity of information on the relation between alcohol consumption and risk for CVD among patients with hypertension. To our knowledge, only 3 studies have addressed the relationship of alcohol intake and death due to CVD among patients with hypertension (1012). Although the studies reported lower numbers of death due to CVD with moderate alcohol consumption, none assessed specific incidence of MI. Of importance, the studies were limited to alcohol consumption assessed after diagnosis of hypertension and were unable to account for changes of alcohol consumption after the diagnosis. To address these issues, we investigated whether alcohol consumption is inversely associated with CVD and death among 11711 men with hypertension participating in the Health Professionals Follow-Up Study (HPFS), a prospective cohort of male health professionals in the United States. Methods The HPFS enrolled 51529 male dentists, veterinarians, optometrists, pharmacists, osteopathic physicians, and podiatrists from the United States who were 40 to 75 years of age and who returned a mailed questionnaire about diet and medical history in 1986. Follow-up questionnaires were sent biennially to update information on exposures and newly diagnosed illnesses. Hypertensive status was determined from the biennial questionnaires. In 1986, participants were asked if they had ever been diagnosed with hypertension and, if so, when. On subsequent questionnaires, participants reported whether they had been diagnosed with hypertension in the past 2 years and, if so, the year of diagnosis. For this analysis, we included 9016 men with hypertension whose condition was diagnosed during follow-up (that is, men with incident hypertension) and 2695 men with hypertension at baseline whose condition was diagnosed between 1975 and 1986 and who reported not changing their alcohol consumption during that time (that is, men with prevalent hypertension). From the full cohort of 51529 men, we excluded 4397 who reported a baseline history of cardiovascular disease, stroke, or cancer (other than nonmelanoma skin cancer); 81 with hypertension diagnosed after a CVD event; 1653 who had missing or implausible nutritional information at baseline (including missing alcohol consumption,70 missing food items, or estimated daily energy intake 800 or 4200 kcal [only 438 of these participants were actually hypertensive]); 271 with missing information for smoking, physical activity, or body mass index (BMI); and 95 whose initial questionnaire had other technical problems. We also excluded 6548 men at baseline because we could not determine their drinking history, because hypertension was diagnosed before 1975, or because they reported substantially changing their alcohol consumption within 10 years before enrollment. Of the remaining men, we identified 11711 patients with hypertension at baseline or during follow-up who were eligible for analysis. Although our sample size was set by the size of the original HPFS cohort assembled in 1986, a sample size calculation showed that 1700 participants in the abstaining and moderate-drinking categories would detect a relative risk of 0.6, as observed by Malinski and colleagues (10), with 80% power and accepting a false-positive rate of 0.05. We assessed alcohol consumption by using a 131-item semiquantitative food-frequency questionnaire with separate items for beer, white wine, red wine, and liquor. We specified standard portions as a glass, bottle, or can of beer; a 4-ounce glass of wine; and a shot of liquor. For each beverage, participants were asked how often on average over the past year they consumed that amount. We calculated ethanol intake by multiplying the frequency of consumption of each beverage by the alcohol content of the specified portion size (12.8 g for beer, 11.0 g for wine, and 14.0 g for liquor) and summing across beverages (13). This process was repeated for the years 1990, 1994, and 1998, with an added item about light beer in 1994. In 1986, men also reported the number of days per week that they typically drank any form of alcohol. We examined associations between alcohol consumption estimated by using the food-frequency questionnaire with consumption estimated by using 2 one-week dietary records collected approximately 6 months apart from 136 participants residing in eastern Massachusetts (14, 15). The Spearman correlation coefficient between these 2 measures was 0.86. Estimated mean alcohol intake was 12.8 grams per day using dietary records and 12.5 grams per day using the food-frequency questionnaire, with no evidence of systematic bias. The correlation coefficient for drinking frequency between our questionnaire and diet records was 0.79. Outcomes and Measurements Our primary end points were incident nonfatal MI and fatal coronary heart disease or stroke. Myocardial infarction and stroke were first identified by self-reports on biennial questionnaires and then confirmed by medical records with World Health Organization or National Survey of Stroke criteria (16). Fatal MI and stroke were confirmed by medical records or autopsy reports. All end points were confirmed by a physician blinded to exposure status. Approximately 80% of participants had MI that was considered definite; the remaining patients had MI that was considered probable and were excluded as end points in sensitivity analyses. Further details of the confirmation of end points are published elsewhere (17, 18). Other end points were total death; death due to CVD; and death augmented by alcohol intake, including cirrhosis, alcohol-related types of cancer, accidents and other external causes, cancer of the colon and rectum, pneumonia, and hemorrhagic stroke according to Thun and colleagues (19). Covariate information was derived from biennial questionnaires. Nutritional information was derived from food-frequency questionnaires. Participants self-reported cardiovascular risk factors (self-report of physician-diagnosed diabetes and hypercholesterolemia, cigarette smoking, physical activity, and weight) every 2 years. Aspirin use included use of aspirin and aspirin-containing products at least twice weekly. Regular use of lipid-lowering therapy and several categories of antihypertensive medication (for example, diuretics, -blockers, calcium-channel blockers, and -blockers) was also recorded biennially. Nutritional variables, anthropomorphic measures, aspirin use, and self-reported CVD risk factors have been validated (2025). We calculated person-years of follow-up from the date of return of the 1986 questionnaire (for men with hypertension at baseline) or date of diagnosis of hypertension (for incident cases of hypertension) to the date of the first CVD event, the date of death, or 31 January 2002. We used Cox proportional hazards models with time-varying covariates to estimate hazard ratios for categories of alcohol intake relative to abstainers (26). We simultaneously controlled for age; smoking (never, former, 1 to 14 cigarettes per day, 15 to 24 cigarettes per day, and 25 cigarettes per day); BMI (in quintiles); diabetes; hypercholesterolemia; parental history of MI; aspirin use; lipid-lowering therapy; 5 categories of leisure-time physical activity; quintiles of energy intake; and quintiles of energy-adjusted intake of saturated fat, trans fatty acids, folate, vitamin E, magnesium, sodium, potassium, -3 fatty acids, and dietary fiber. Alcohol consumption and dietary variables were updated every 4 years; other potential confounders were updated every 2 years. We stopped updating participants alcohol use if they developed cancer (other than nonmelanoma skin cancer) for all analyses. In secondary analyses for coronary heart disease outcomes, we censored participants when they developed cancer. To examine possible confounding by sociodemographic status, we adjusted for marital and employment status (full-time, part-time, or retired), profession, and ethnicity in the multivariate model. We conducted tests of linear trend across categories of increasing alcohol consumption by treating the midpoints of consumption in categories as a continuous variable. The possibility of a nonlinear relation between alcohol consumption and risk for MI was examined with restricted cubic splines (27) and tested with the likelihood ratio test, comparing models with only the linear term to models with linear and cubic spline terms. None of the nonlinear models provided a statistically significantly better model-fit than lin