The 5-year risk of death after onset of heart failure (HF) is about 50%. Although previous studies have shown beneficial effects of light-to-moderate alcohol consumption and risk of cardiovascular diseases and mortality, it is unclear whether moderate alcohol consumption is associated with a lower risk of death in subjects with HF. We investigated whether alcohol consumption and type of alcohol preference are associated with the risk of total mortality in 449 US male physicians with prevalent HF. Alcohol consumption was assessed through food frequency questionnaire, and mortality was ascertained through annual follow-up questionnaires and adjudicated by an Endpoint Committee. The mean age of subjects was 75.7 ± 8.2 years with an average follow-up of 7 years. We found evidence of a J-shaped relation between alcohol consumption and mortality (hazard ratio [95% confidence interval] 1.00 [reference], 0.85 [0.61 to 1.20], 0.60 [0.40 to 0.88], and 0.71 [0.42 to 1.21] for alcohol intake of none, <1 drink/day, 1 to 2 drinks/day, and 3+ drinks/day, respectively [p for quadratic trend = 0.058]). There was no relation between beverage preference (beer, wine, or liquor) and mortality. In conclusion, our data showed a J-shaped association between alcohol intake and mortality in patients with HF.
The lifetime risk of developing heart failure (HF) at 40 years is estimated to be 1 in 5. Although survival after HF has improved over time, approximately 50% of patients with HF diagnosis will die within 5 years. A variety of healthy lifestyle factors, including moderate alcohol intake, are related to a lower risk of HF. In addition, it has been shown that moderate alcohol intake is associated with lower mortality. Limited data exist on the relation of alcohol intake and mortality in subjects with HF. In addition, little is known about the relation of alcoholic beverage preference (beer, liquor, or wine) with mortality in subjects with HF. A recent European study showed a 29% increase in long-term mortality with moderate alcohol intake in older participants with previously diagnosed HF. However, this study only included wine drinkers and only evaluated ≤250 ml/day of alcohol intake. Thus, in the present study, we examined whether alcohol consumption and type of alcoholic beverage consumed are associated with mortality in US male physicians with prevalent HF.
Methods
The present study used data from the Physicians’ Health Study (PHS) I and II. A detailed description of PHS studies has been previously published. Briefly, the PHS I was a completed, randomized, double-blind placebo-controlled trial designed to study low-dose aspirin and β carotene for the primary prevention of cardiovascular disease and cancer in US male physicians that began in 1982 and ended in 1995. The PHS II recruited 7,000 new physicians and re-enrolled 7,641 members of the PHS I from 1997 to 2001. All members of the PHS I who were still alive have been prospectively followed with annual questionnaires, on trial completion. All physicians who completed the food frequency questionnaire (FFQ) from 1999 to 2001 and had an HF diagnosis before the FFQ were eligible to be included in the analysis (n = 449). Each participant gave written informed consent, and the Institutional Review Board at the Brigham and Women’s Hospital approved the study protocol.
Information on alcohol consumption was self-reported using an FFQ administered from 1999 to 2001. Participants were asked to provide their average use for each of beer (1 glass, bottle, or can), wine (4 oz glass), and liquor (e.g., whiskey, gin, and so on, 1 drink or shot). Possible response categories were “never or <1/month,” “1 to 3/month,” “1/week,” “2 to 4/week,” “5 to 6/week,” “1/day,” “2 to 3/day,” “4 to 5/day,” and “6+/day.” Response categories were converted to median number of drinks for beer, wine, and liquor per day and added together. Total alcohol consumption was characterized as none, <1 drink/day, 1 to 2 drinks/day, and 3+ drinks/day.
Alcoholic preference was classified as consuming no alcohol if a participant indicated “never or <1/month” for all 3 alcoholic beverage types. A participant was classified as preferring beer, wine, or liquor if >50% of average consumption was from a single source. If a participant consumed <50% of total alcohol from either beer, wine, or liquor, then the participant was classified as having no preference.
Incidence of death and morbidities, including HF, was determined using annual follow-up questionnaires. Specifically, a questionnaire was mailed to each participant to obtain information on the occurrence of new medical diagnoses. When participants died, death certificates were obtained for confirmation and review of cause of death. Additional information was obtained from the participants’ next of kin and from medical records. A detailed description of HF validation in the PHS using a review of medical records in a subsample has been published elsewhere. Demographic and lifestyle informations were self-reported at baseline. Diet information was obtained through FFQ.
We used the Cox proportional hazards analysis to calculate the multivariable adjusted hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). Proportional hazards assumption was tested by including an interaction with logarithmic person-time in the model. Person-time was measured from return of FFQ until death or date with last available participant information. We initially assessed confounding by age (<65, 65 to <70, 70 to <75, 75 to <80, and 80+ years), race (white vs nonwhite), body mass index (continuous), smoking (never, past, or current), exercise (never, 1 to 2 days/week, and 3 to 7 days/week), and prevalent atrial fibrillation (yes/no). We then considered coronary heart disease (yes/no), diabetes (yes/no), and hypertension (yes/no) as potential mediators and did not adjust for them in the multivariable model. We obtained p for linear and quadratic trend by creating a new variable that was assigned median alcohol intake in each category and fitted that new variable and its quadratic term in the regression. For beverage preference analyses, we created indicator variables and used nondrinkers as the reference group. Analysis was completed using SAS, version 9.3 (SAS Institute, Cary, North Carolina). All p values were 2 tailed, and the significance level was set at an alpha of 0.05.
Results
The characteristics at baseline of the 449 HF cases in the PHS are presented in Table 1 according to alcohol consumption. The mean age of participants was 75.7 ± 8.2 years (range 50.6 to 97.0). During an average follow-up of 7 years, 206 deaths occurred. The crude incidence rates of mortality were 82.7, 61.1, 55.1, and 61.5 deaths per 1,000 person-years for alcohol consumption of none, <1 drink/day, 1 to 2 drinks/day, and 3+ drinks/day, respectively. In a multivariable adjusted Cox regression, there was a J-shaped association between alcohol intake and the risk of mortality with HRs (95% CI) of 1.00 (reference), 0.85 (0.61 to 1.20), 0.60 (0.40 to 0.88), and 0.71 (0.42 to 1.21), for alcohol intake of none, <1 drink/day, 1 to 2 drinks/day, and 3+ drinks/day, respectively (p for quadratic trend = 0.058; Table 2 ). Adding potential mediators (prevalent hypertension, coronary heart disease, and diabetes) to the model did not attenuate the associations. In secondary analysis, we did not find evidence for an effect of beverage preference on mortality: compared with nondrinkers in multivariable adjusted models, HR (95% CI) for mortality was 0.88 (0.51 to 1.53) for beer preference, 0.82 (0.56 to 1.20) for wine preference, and 0.73 (0.49 to 1.11) for liquor preference. Subjects without a beverage preference had a 43% lower risk of mortality compared with nondrinkers (95% CI 10% to 64%; Figure 1 ).
| Characteristics | Frequency of Alcohol Intake | |||
|---|---|---|---|---|
| Never (n = 136) | <1/Day (n = 159) | 1–2/Day (n = 103) | >2/Day (n = 51) | |
| Age (years) | 76.6 ± 8.5 | 74.3 ± 8.5 | 76.8 ± 7.5 | 75.4 ± 7.8 |
| Body mass index (kg/m 2 ) | 25.2 ± 4.1 | 26.8 ± 3.9 | 26.0 ± 3.8 | 26.3 ± 3.9 |
| White | 130 (96%) | 147 (92%) | 101 (98%) | 49 (96%) |
| Cigarette use | ||||
| Never | 72 (53%) | 54 (34%) | 31 (30%) | 9 (18%) |
| Past | 57 (42%) | 98 (62%) | 68 (66%) | 39 (77%) |
| Current | 7 (5%) | 7 (4%) | 4 (4%) | 3 (6%) |
| Exercise frequency | ||||
| None | 66 (50%) | 80 (50%) | 43 (42%) | 22 (45%) |
| 1–2 days/week | 11 (8%) | 16 (10%) | 15 (15%) | 7 (14%) |
| 3+ days/week | 56 (42%) | 63 (40%) | 44 (43%) | 20 (41%) |
| Atrial fibrillation | 58 (43%) | 78 (49%) | 50 (49%) | 30 (59%) |
| Hypertension | 93 (68%) | 112 (70%) | 75 (73%) | 34 (67%) |
| Diabetes mellitus | 39 (29%) | 40 (25%) | 26 (25%) | 11 (22%) |
| Coronary heart disease | 78 (57%) | 93 (58%) | 62 (60%) | 26 (51%) |
| Frequency of Alcoholic Drinks Per Day | Cases/Person-Time | Crude Incidence Rate (Per 1000 Person-Years) | Hazard Ratios (95% CI) | |
|---|---|---|---|---|
| Age Adjusted | Model 1 ∗ | |||
| None | 72/870.7 | 82.69 | 1.00 | 1.00 |
| <1 | 70/1145.2 | 61.13 | 0.84 (0.60–1.17) | 0.85 (0.61–1.20) |
| 1–2 | 43/780.0 | 55.13 | 0.61 (0.42–0.89) | 0.60 (0.40–0.88) |
| >2 | 21/341.5 | 61.50 | 0.77 (0.47–1.26) | 0.71 (0.42–1.21) |
| p for linear trend | 0.110 | 0.069 | ||
| p for quadratic trend | 0.046 | 0.058 | ||
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