Journal of Aging Research 7 Table 7: Hazard ratios of CVD mortality stratiﬁed by types of alcohol beveragea, Aerobics Center for Longitudinal Study (ACLS), 1974–2002. Alcohol consumption (drinks/week) Non Drinkers Quartile 1 Quartile 2 Quartile 3 Quartile 4 Beer (n = 23, 728) No. 4870 3854 4876 5779 4349 No. of Cases 128 43 104 64 75 Hazard ratios 1.00 (referent) 0.71 (0.50, 1.02) 0.76 (0.57, 1.01) 0.72 (0.52, 0.995) 1.06 (0.78, 1.45) Wine (n = 21, 997) No. 4870 4091 4999 4175 3862 No. of Cases 128 55 104 55 64 Hazard ratios 1.00 (referent) 0.76 (0.55, 1.05) 0.70 (0.53, 0.93) 0.74 (0.53, 1.04) 0.89 (0.64, 1.23) Liquor (n = 20, 416) No. 4870 3111 5022 3562 3851 No. of Cases 128 36 112 74 144 Hazard ratios 1.00 (referent) 0.74 (0.51, 1.07) 0.71 (0.55, 0.93) 0.69 (0.50, 0.93) 0.98 (0.75, 1.27) a Adjusted for age (in years), year of examination, BMI (kg/m2), smoking (current smoker or not), family history of CVD (yes or no), maximal treadmill time (min), and remaining type of alcohol. consumption. Beulens et al. [37] also found that liquor drinkers had the strongest association with decreased risk of myocardial infarction. There have been inconsistencies, however, when comparing the types of alcohol on mortality. While several epidemiologic studies, including the current study, have found no diﬀerences in risk between types of alcohol consumed [1, 43, 48, 49], others have suggested unique cardioprotection from wine [50]. Experimental stud- ies have shown the ethanol in wine to have additional protection compared to dealcoholized red wine [51]. The diﬀerential eﬀects may depend on gender. Compared to de- alcoholized beverages, women had increased adiponectin (an anti-inﬂammatory factor also shown to be associated with improved insulin sensitivity) after drinking red wine, while men had increased levels after drinking liquor and beer [52]. 4.6. Strengths and Limitations. Strengths of this study are inclusion of several potential confounders including mea- sures of ﬁtness and psychological variables, lengthy follow- up in a large cohort, exploration of relationships by health risk factors, and stratiﬁcation by alcohol types. The lim- itations include that the sample was only men from the Cooper Clinic in Dallas, Tex, USA, predominantly white, and of middle to high incomes, limiting generalizations to entire populations. However, the homogenous population does eliminate potential confounding from gender [4] and race [5, 28], both of which have been shown to inﬂuence the relationship between alcohol and mortality. Additionally, this regional population is similar in physiologic variables to other North American populations [53]. The mean age of 43 at baseline with an average follow-up time of 16 years makes these ﬁndings particularly relevant for an aging American population. When stratiﬁed by age, we did not ﬁnd a signiﬁcant association in the older men, but this may have been due to a small sample of men above 60. Future studies are needed to conﬁrm the lower levels of alcohol consumption found to be protective in this study population. Clearly, more work will be required in populations that diﬀer in racial and ethnic composition to that of the ACLS. While self-reported alcohol consumption has been val- idated [23], under or overreporting could have inﬂuenced the trends in risk reduction in either direction. The format of response did not allow assessment of varied drinking patterns including daily frequency of alcohol consumption. Studies have suggested that alcohol should be consumed in small amounts over multiple occasions for health beneﬁts rather than binge drinking [54]. In the sensitivity analyses, it was not possible to isolate single types of drinkers due to low prevalence of single alcohol-type drinkers. Despite adjustment for many confounders, confounding may still exist in this and other prospective studies. One potential confounder not adjusted for was diet, particularly fat intake, which plays an established role in cardiovascular outcomes. We did, however, measure and control for blood cholesterol levels which is associated with dietary fat intake [55]. Consistent with previous studies, we used nondrinkers as the referent group [5, 43, 56]. Some researchers have argued against using nondrinkers as the referent group due to confounding predisposing conditions or other latent vari- ables contributing to diﬀerential mortality risk independent of alcohol consumption [10]. Mukamal et al. [14] found that nondrinkers are more likely to be in poor health, obese, of low income, or physically inactive; however, they did not exclude or report whether the participants had preexisting vascular disease. In contrast, when adjusted for preexisting disease (excluded or controlled for in our model), Wannamethee and Shaper [10] found ex-drinkers and life- long nondrinkers had equal CVD mortality and almost equal all-cause mortality. When Hart and Smith [56] examined the health status of nondrinkers to drinkers, they did not diﬀer substantially. Friesema et al. [57] found that the inverse relationship between alcohol consumption and mortality could not be explained by health status alone. Potential confounding would have a less likely eﬀect on CVD mortality