Relation of Alcohol Consumption and Coronary Heart Disease in Hypertensive Male Physicians (from the Physicians' Health Study)
Article Outline
Alcohol has diverse effects on the cardiovascular system. Moderate drinking is associated with a decreased risk of cardiovascular disease, yet increasing amounts of alcohol consumption are known to increase blood pressure. These opposing effects have led to interest in the effect of moderate alcohol consumption on the risk of coronary heart disease (CHD) in patients with hypertension. To test the hypothesis that moderate alcohol consumption decreases the risk of myocardial infarction (MI) in patients with hypertension, we used data on 5,164 participants in the Physicians' Health Study who were apparently healthy and free of CHD at baseline. Incident MI was ascertained by annual follow-up questionnaires and validated through review of medical records. Cox proportional hazard model was used to compute multivariable-adjusted hazard ratios with corresponding 95% confidence intervals. From 1982 to 2008, 623 cases of MI occurred. Compared to subjects consuming <1 drink per week, hazard ratios for MI were 1.05 (95% confidence interval 0.85 to 1.28), 0.78 (95% confidence interval 0.64 to 0.97), and 0.57 (95% confidence interval 0.35 to 0.95) for alcohol consumption of 1 to 4, 5 to 7, and >8 drinks per week adjusted for age, body mass index, smoking, exercise, diabetes, multivitamin use, vegetable intake, breakfast cereal intake, and cholesterol (p for trend <0.0022). Similar inferences could be made for the secondary outcomes of angina pectoris and any CHD (which included MI, angina pectoris, and previous revascularization). In conclusion, our data demonstrated an inverse relation between moderate alcohol consumption and CHD in hypertensive men.
Only limited data have been published on the association between alcohol consumption and coronary heart disease (CHD) in patients with hypertension.1, 2 Thus, we sought to prospectively evaluate whether alcohol consumption is associated with a decreased risk of myocardial infarction (MI) in hypertensive participants of the Physicians' Health Study (PHS), a large cohort with >20 years of follow-up. In secondary analyses, we sought to assess the association between moderate alcohol consumption and angina pectoris and any CHD (including MI, angina pectoris, coronary artery bypass surgery, and percutaneous coronary intervention).
Methods
The present study analyzed data from the PHS, a randomized trial used to study low-dose aspirin and β-carotene for the primary prevention of cardiovascular disease and cancer in 22,071 United States men physicians without a history of MI at baseline. A description of the PHS has been previously published.3 For the present study, we included patients with prevalent self-reported hypertension at baseline. Subjects were asked to report their current blood pressure and whether they had ever received drug treatment for hypertension. Prevalent hypertension was defined as a systolic blood pressure ≥140 mm Hg, diastolic blood pressure ≥90 mm Hg, or self-reported treatment for hypertension. Of 5,236 subjects with prevalent hypertension at baseline, we excluded 72 subjects for missing covariate data, leaving a final sample of 5,164 subjects.
Subjects' usual alcohol consumption was self-reported on a standard questionnaire with subjects being asked, “How often do you usually consume alcoholic beverages?” Responses included rarely/never, 1 time to 3 times/month, 1 time/week, 2 to 4 times/week, 5 to 6 times/week, daily, and ≥2 times/day. The response was interpreted as the number of alcoholic drinks consumed during the specified period. A detailed description of alcohol assessment in the PHS has been previously published.3, 4
Ascertainment of outcomes in the PHS has been obtained through yearly questionnaires and has been previously described.5 Specifically, a questionnaire was mailed to each participant every 6 months during the first year and annually thereafter. An end-point committee reviewed medical records to confirm the diagnosis of CHD. MI was validated using World Health Organization criteria.6 Our primary outcome was MI. Secondary outcomes included angina pectoris and total CHD (angina pectoris, MI, coronary artery bypass surgery, or percutaneous coronary intervention).
Demographic data were collected at baseline. Information on co-morbid illness was been collected through annual follow-up. Self-reported information on age, physical activity, cigarette smoking, multivitamin use, body mass index, vegetable intake, breakfast cereal consumption, and total cholesterol was obtained at baseline. Each subject gave written informed consent, and the institutional review board at Brigham and Women's Hospital (Boston, Massachusetts) approved the study protocol.
We classified each hypertensive subject into categories of alcohol consumption as described earlier. Subjects who described their alcohol consumption as rarely/never were used as the reference group for all analyses. We calculated person-time of follow-up from baseline until the first occurrence of (1) outcome of interest, (2) death, or (3) censoring date (date of receipt of the last follow-up questionnaire, 2008). Within each alcohol category, we calculated the incidence rate by dividing the number of cases of MI by the corresponding person-time of follow-up. We used Cox proportional hazards model to compute multivariable-adjusted hazard ratios with corresponding 95% confidence intervals. We assessed confounding using a 10% change in hazard ratio. Assumptions for proportional hazards models were tested by including main effects and product terms of covariates and time factor. These assumptions were met because all p values were >0.05. The initial model was adjusted only for age (continuous). The parsimonious model was adjusted for age, body mass index (kilograms per square meter, continuous), smoking (never, previous, current), exercise (<1 and 1 time/week, and 2 to 4 and ≥5 times/week), and diabetes (yes/no). The fully adjusted model also controlled for multivitamin use (never, previous, current), vegetable consumption (<3, 3 to 4, 5 to 6, 7 to 13, and ≥14 servings/day), breakfast cereal intake (0, <1, 2 to 6, and ≥7), randomization arm (aspirin vs placebo), and treatment for hypercholesterolemia. To explore whether the phenomenon of “sick quitters” might inflate the hazard ratios, we repeated the analysis excluding nondrinkers and using current drinkers of 5 to 7 drinks/week as the reference group. In secondary analyses, we examined the relation between alcohol consumption in hypertensive men and angina pectoris and total CHD. All analyses were completed using SAS 9.2 (SAS Institute, Cary, North Carolina). The significance level was set at 0.05.
Results
Of the 5,164 participants who reported prevalent hypertension at baseline, mean age at randomization was 58.1 years; 14.9% of subjects were nondrinkers, and 25.8% of participants reported alcohol consumption of 7 drinks/week, and only 4.3% reported drinking ≥2 drinks/day. Table 1 presents baseline characteristics of study participants according to alcohol consumption. During an average follow-up of 17.9 years, 623 new cases of MI, 1,249 cases of angina pectoris, and 1,441 cases of total CHD occurred. In multivariable Cox regression model, alcohol consumption was associated with a lower risk for MI in a dose-dependent manner (p for linear trend = 0.0022; Table 2). Repeating the analysis using current drinkers of 5 to 7 drinks/week as the reference group did not change the relation between alcohol consumption and risk of MI. In addition, examination of the effect of alcohol consumption on angina pectoris and total CHD demonstrated a similar protective relation (Table 3).
Table 1. Baseline characteristics of 5,164 hypertensive male physicians according to alcohol consumption
| Characteristics | Alcohol Consumption | |||
|---|---|---|---|---|
| <1/wk (n = 1,315) | 1–4/week (n = 1,668) | 5–7/wk (n = 1,959) | ≥8/wk (n = 222) | |
| Age (years) | 58.1 ±10.1 | 56.5±9.8 | 59.3±9.8 | 59.8±9.5 |
| Body mass index (kg/m2) | 25.9±3.4 | 25.6±2.9 | 25.3±2.9 | 25.8±3.6 |
| Vegetable intake (servings/d) | 7.9±5.1 | 8.5±4.9 | 8.7±4.8 | 8.3±5.8 |
| Current multivitamins | 23.5% | 19.6% | 25.7% | 27.7% |
| Current smokers | 9.5% | 9.7% | 13.5% | 26.1% |
| Exercise >1 time/week | 63.0% | 71.0% | 72.3% | 60.6% |
| Diabetes mellitus | 10.1% | 4.9% | 4.1% | 5.9% |
| Total cholesterol >240 mg/dl or treated | 16.4% | 16.2% | 18.0% | 17.5% |
| Aspirin arm | 49.7% | 51.9% | 48.8% | 50.0% |
| Breakfast cereal ≥2 servings/week | 44.9% | 42.3% | 39.6% | 30.6% |
Table 2. Incidence rates and hazard ratios (95% confidence intervals) for myocardial infarction according to alcohol consumption
| Alcohol Consumption (drinks/week) | Cases | Hazard Ratio (95% Confidence Intervals) | ||
|---|---|---|---|---|
| Age Adjusted | Model 1⁎ | Model 2† | ||
| <1 | 172 | 1.0 | 1.0 | 1.0 |
| 1–4 | 223 | 1.03(0.84–1.26) | 1.08(0.88–1.32) | 1.05(0.85–1.28) |
| 5–7 | 211 | 0.78(0.64–0.95) | 0.81(0.66–1.00) | 0.78(0.64–0.97) |
| >8 | 17 | 0.62(0.37–1.02) | 0.58(0.35–0.96) | 0.57(0.35–0.95) |
| p value for linear trend | 0.0021 | 0.0046 | 0.0022 | |
⁎Adjusted for age, body mass index, smoking, exercise, and diabetes. |
†Adjusted for age, body mass index, smoking, exercise, diabetes, multivitamin use, vegetable intake, breakfast cereal intake, and cholesterol. |
Table 3. Hazard ratios (95% confidence intervals) for angina pectoris and total coronary heart disease (myocardial infarction, angina, or revascularization)
| Alcohol Use (drinks/wk) | Hazard Ratio (95% Confidence Intervals) for Angina Pectoris | Hazard Ratio (95% Confidence Intervals) for Total CHDs | ||||
|---|---|---|---|---|---|---|
| Age Adjusted | Model 1⁎ | Model 2† | Age Adjusted | Model 1⁎ | Model 2† | |
| <1 | 1.0 | 1.0 | 1.0 | 1.0 | 1.0 | 1.0 |
| 1–4 | 0.92(0.80–1.06) | 0.94(0.82–1.08) | 0.92(0.80–1.07) | 0.95(0.83–1.08) | 0.97(0.85–1.11) | 0.95(0.83–1.09) |
| 5–7 | 0.71(0.62–0.82) | 0.73(0.63–0.85) | 0.71(0.62–0.83) | 0.72(0.63–0.82) | 0.74(0.65–0.85) | 0.72(0.63–0.83) |
| >8 | 0.63(0.46–0.88) | 0.63(0.45–0.87) | 0.62(0.44–0.86) | 0.65(0.48–0.88) | 0.63(0.47–0.86) | 0.62(0.45–0.84) |
| p value for trend | <0.0001 | <0.0001 | <0.0001 | <0.0001 | <0.0001 | <0.0001 |
⁎Adjusted for age, body mass index, smoking, exercise, and diabetes. |
†Adjusted for age, body mass index, smoking, exercise, diabetes, multivitamin use, vegetable intake, breakfast cereal intake, and cholesterol. |
Discussion
In this cohort of United States men physicians, our results confirm the beneficial effect of judicious alcohol use on the risk of MI. Furthermore, our secondary analysis suggests that this benefit extends to all patients with CHD (patients with angina pectoris and previous revascularization in addition to MI). These findings suggest that the effects of moderate alcohol consumption on the cardiovascular system lead to a net benefit. Although alcohol has been shown to increase blood pressure, the relatively modest increase in blood pressure7, 8 is likely countered by the effect of alcohol consumption on insulin sensitivity,9 inflammation,10 high-density lipoprotein cholesterol,11 and platelet aggregation12 in moderate drinkers. However, it is important to emphasize the decrease in cardiovascular disease with moderate alcohol consumption in hypertensive subjects in no way decreases the importance of blood pressure control regardless of drinking habits.13
Previous studies have shown that moderate alcohol consumption decreases the risk of cardiovascular disease in otherwise healthy subjects14, 15 and may confer an advantage in cardiovascular and overall survival.16, 17 Our findings expand on this and are consistent with previously published data suggesting a decreased risk of cardiovascular disease with moderate alcohol consumption even in patients with known hypertension. Previous work with the PHS cohort suggested an association between light to moderate alcohol consumption in hypertensive men and a decreased risk of total and cardiovascular mortality.2 In addition, Beulens et al1 demonstrated a decrease in the risk of fatal and nonfatal MI in hypertensive patients with moderate alcohol consumption.
Strengths of our study include the large sample, >20 years of follow-up, confirmation of CHD by review of medical records, and a large number of covariates to control for confounding. In addition, the fact that CHD diagnoses were self-reported by physicians with confirmation by medical records makes our outcome measurements very reliable. This reliability is of particular interest for angina because this end point is infrequently used in epidemiologic studies given the potential of inaccuracy in self-reported diagnosis, a problem unlikely to occur with physicians. There are certain limitations to our study. The population of the PHS is limited to men physicians who may have somewhat different behaviors than the general population as evidenced by a lower prevalence of smoking, diabetes, and obesity and a higher percentage of regular exercise. These behavior differences and the lack of women in the cohort somewhat limit generalizability and the ability to test for an interaction between gender and the beneficial effects of alcohol. In addition, misclassification bias is possible due to the identification of prevalent hypertension and alcohol consumption by self-report. However, other investigators have reported a good accuracy of self-report of blood pressure in the PHS.18 Further, no inference on the association between heavy drinking and CHD in hypertensive subjects can be made because there was a limited number of drinkers of ≥2 drinks/day in our sample (n = 222 or 4.3%).
References
- . Alcohol consumption and risk for risk for coronary heart disease among men with hypertension. Ann Intern Med. 2007;146:10–19
- . Alcohol consumption and cardiovascular disease mortality in hypertensive men. Arch Intern Med. 2004;164:623–628
- . Moderate alcohol consumption and risk for angina pectoris or myocardial infarction in U.S. male physicians. Ann Intern Med. 1997;126:372–375
- . Alcohol consumption and risk of heart failure in the Physicians' Health Study I. Circulation. 2007;115:34–39
- . Final report on the aspirin component of the ongoing Physicians' Health Study. N Engl J Med. 1989;321:129–135
- Ischaemic Heart Disease Registers: Report of the Fifth Working Group (Including a Second Revision of the Operating Protocol). Copenhagen: World Health Organization; 1971;
- . Alcohol consumption and blood pressure: Kaiser-Permanente multiphasic health examination data. N Engl J Med. 1977;296:1194–2000
- . Effects of alcohol reduction on blood pressure: a meta-analysis of randomized controlled trials. Hypertension. 2001;38:1112–1117
- . Beneficial postprandial effect of a small amount of alcohol on diabetes and cardiovascular risk factors: modification by insulin resistance. J Clin Endocrinol Metab. 2005;90:661–672
- . Moderate alcohol intake and markers of inflammation and endothelial dysfunction among diabetic men. Diabetologia. 2004;47:1760–1767
- . Moderate alcohol intake, increased levels of high-density lipoprotein and its subfractions, and decreased risk of myocardial infarction. N Engl J Med. 1993;329:1829–1834
- . Alcohol consumption and platelet activation and aggregation among women and men: the Framingham Offspring Study. Alcohol Clin Exp Res. 2005;29:1906–1912
- . Sequelae of systemic hypertension in alcohol abstainers, light drinkers, and heavy drinkers. Am J Cardiol. 2006;98:1063–1068
- . Prospective study of alcohol consumption and risk of coronary disease in men. Lancet. 1991;338:464–468
- . A prospective study of moderate alcohol consumption and the risk of coronary disease and stroke in women. N Engl J Med. 1988;319:267–273
- . Alcohol dosing and total mortality in men and women: an updated meta-analysis of 34 prospective studies. Arch Intern Med. 2006;166:2437–2445
- . Alcohol consumption and mortality among middle-aged and elderly U.S. adults. N Engl J Med. 1997;337:1705–1714
- . Alcohol consumption and the risk of hypertension in women and men. Hypertension. 2008;51:1080–1087
The Physicians' Health Study is supported by Grants CA-34944, CA-40360, CA-097193, HL-26490, and HL-34595 from the National Institute of Health, Bethesda, Maryland.
PII: S0002-9149(09)01103-5
doi:10.1016/j.amjcard.2009.05.036
Published by Elsevier Inc.
