Alcohol Consumption Over Time and Risk of Death: A Systematic Review and Meta-analysis

Harindra Jayasekara; Dallas R. English; Robin Room; Robert J. MacInnis

Disclosures

Am J Epidemiol. 2014;179(9):1049-1059. 

In This Article

Results

Characteristics of Studies

The numbers of articles identified in each database using the search strategy are given in Figure 1. Fifty-two full-text articles were selected after excluding the others on the basis of their titles or abstracts. Of these, 40 were excluded because they did not report a measure of association between alcohol consumption over time and all-cause mortality risk (Web Appendix available at http://aje.oxfordjournals.org/. This left 12 articles that fulfilled the eligibility criteria.[23–34] The article by Wannamethee et al.[34] was excluded because Emberson et al.[28] reported more comprehensive data from the same study cohort. King et al.[31] did not report estimates that could be included in a meta-analysis; attempts to obtain further information from the authors were unsuccessful. Paganini-Hill et al.[30] reported estimates for variation in intake but not for average intake over time. Thus, the meta-analysis included 9 independent cohort studies published between 1991 and 2010 (Table 1). These studies included 10,490 deaths and 62,950 study participants. Five studies were conducted in Europe and 4 in the United States. Friesema et al.[32] measured lifetime alcohol consumption retrospectively for different periods of life, whereas others[23–29,33] assessed current intake more than once over time. Four studies reported separate relative risks for men and women,[23,25,26,32] 1 reported combined relative risk for both sexes,[27] and 4 included men only.[24,28,29,33] Beulens et al.[29] studied men with hypertension.

Figure 1.

Flow diagram describing selection of studies for inclusion in a meta-analysis of alcohol consumption measured over time and mortality risk, 1966–2012. A manual search added 1 additional article to the electronic search. CINAHL, Cumulative Index to Nursing and Allied Health Literature.

The relative risks and their 95% confidence intervals for categories of alcohol intake from each study are given in Table 2. Lazarus et al.[23] and Fillmore et al.[25] defined alcohol intake over time by comparing intakes at baseline and follow-up assessment (e.g., abstainer-to-moderate) and included both stable and varying drinkers in their model. Goldberg et al.[24] reported relative risks for stable and varying (e.g., abstainer-to-light/moderate) drinkers separately using consistent abstainers as the reference category. Gronbaek et al.,[27] Emberson et al.,[28] Beulens et al.,[29] and Britton et al.[33] used intake categories defined solely by average intake over time. Wellmann et al.[26] and Friesema et al.[32] included both stable and varying drinkers in their models, as well as categories of stable drinkers by the level of intake.

Association Between Alcohol Intake Over Time and Mortality Risk in Men

Using relative risks reported by Lazarus et al.,[23] Goldberg et al.,[24] Fillmore et al.,[25] Emberson et al.,[28] Beulens et al.,[29] and Britton et al.,[33] we observed a nonlinear association between average alcohol consumption over time and mortality risk (P for nonlinearity = 0.02), characterized by little evidence for an inverse association at low levels of intake but higher mortality risk at intakes over 40 g/day compared with abstention for men (Figure 2). Between-study heterogeneity of study-specific trends was defined by the coefficients of the first (I2 = 35%) and second (I2 = 54%) spline transformations of alcohol consumption. The dose-response relationship did not change appreciably when we excluded the study by Beulens et al.,[29] which was restricted to men with hypertension (P for nonlinearity < 0.01; for the first spline transformation, I2 = 45%; for the second spline transformation, I2 = 53%), or when we included the relative risk for men and women combined by Gronbaek et al.[27] (P for nonlinearity = 0.01; for the first spline transformation, I 2 = 52%; for the second spline transformation, I 2 = 60%).

Figure 2.

Adjusted relative risk of death associated with average alcohol consumption over time in a meta-analysis of published studies for men, 1966–2012. The vertical axis is on a log scale. Bold line, spline model; long dashed lines, upper and lower confidence limits of spline model; short dashed line, linear model.

The reported relative risks for men, mapped onto the defined intake categories used to derive pooled relative risks for comparable categories of intake, are given in Table 3 (number and percent of men in each intake category are available in Web Table 1). We derived the following pooled relative risks by intake category: for 1–29 g/day, 0.90 (95% confidence interval (CI): 0.81, 0.99); for 30–59 g/day, 1.19 (95% CI: 0.89, 1.58); and for 60 or more g/day, 1.52 (95% CI: 0.78, 2.98) (Figure 3 compared with abstention. Visual inspections of the forest plot and funnel plot (Figure 4 for men did not show marked publication bias. Egger's test results confirmed this finding: for 1–29 g/day, P = 0.31; for 30–59 g/day, P = 0.65; and for 60 or more g/day, P = 0.54. The inverse association for an intake of 1–29 g/day did not change much when the analysis was repeated excluding 1 study at a time (excluding Lazarus et al.,[23] relative risk (RR) = 0.90, 95% CI: 0.80, 1.02; excluding Goldberg et al.,[24] RR = 0.88, 95% CI: 0.77, 1.01; excluding Emberson et al.,[28] RR = 0.90, 95% CI: 0.80, 1.00; excluding Beulens et al.,[29] RR = 0.88, 95% CI: 0.77, 1.00; excluding Britton et al.,[33] RR = 0.94, 95% CI: 0.87, 1.01; and excluding Fillmore et al.,[25] RR = 0.87, 95% CI: 0.78, 0.97).

Figure 3.

Forest plot displaying random-effects meta-analyses of the associations of all-cause mortality risk with categories of alcohol consumption over time compared with nondrinking for men using risk estimates from selected studies that reported levels of average intake over time, 1966–2012. Midpoint of box representing each study indicates relative risk (RR), and area of box indicates weight given to the study; diamonds, pooled relative risks. CI, confidence interval.

Figure 4.

Funnel plot with pseudo 95% confidence limits for the associations of all-cause mortality risk with categories of alcohol consumption over time compared with nondrinking using risk estimates from selected studies that reported levels of average alcohol intake over time for men, 1966–2012. Circles, 1–29 g/day; triangles, 30–59 g/day; squares, ≥60 g/day; continuous line, no effect; dashed lines, upper and lower confidence limits.

Association Between Alcohol Intake Over Time and Mortality Risk in Women

The small number of studies reporting relative risks for women did not permit meta-analyses. The relative risks reported by Friesema et al.[32] for a stable intake of 1–14.9 g/day over time and by Fillmore et al.[25] for moderate-to-moderate drinking were 0.63 (95% CI: 0.25, 1.59) and 1.1 (95% CI: 0.9, 1.3), respectively (Table 2 Wellmann et al.[26] reported a relative risk of 0.94 (95% CI: 0.49, 1.81) for a constant intake of 20 or more g/day (Table 2).

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