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Observational Study
. 2022 Mar 1;5(3):e223849.
doi: 10.1001/jamanetworkopen.2022.3849.

Association of Habitual Alcohol Intake With Risk of Cardiovascular Disease

Kiran J Biddinger  1   2   3 , Connor A Emdin  1   2 , Mary E Haas  1   2   4 , Minxian Wang  1   2 , George Hindy  1   2   4   5 , Patrick T Ellinor  1   3 , Sekar Kathiresan  1   2   6 , Amit V Khera  1   2 , Krishna G Aragam  1   2   3
Affiliations
Observational Study

Association of Habitual Alcohol Intake With Risk of Cardiovascular Disease

Kiran J Biddinger et al. JAMA Netw Open. .

Erratum in

  • Error in Abstract.
    [No authors listed] [No authors listed] JAMA Netw Open. 2022 Apr 1;5(4):e2212024. doi: 10.1001/jamanetworkopen.2022.12024. JAMA Netw Open. 2022. PMID: 35442460 Free PMC article. No abstract available.

Abstract

Importance: Observational studies have consistently proposed cardiovascular benefits associated with light alcohol consumption, while recent genetic analyses (ie, mendelian randomization studies) have suggested a possible causal link between alcohol intake and increased risk of cardiovascular disease. However, traditional approaches to genetic epidemiology assume a linear association and thus have not fully evaluated dose-response estimates of risk across different levels of alcohol intake.

Objectives: To assess the association of habitual alcohol intake with cardiovascular disease risk and to evaluate the direction and relative magnitude of cardiovascular risk associated with different amounts of alcohol consumption.

Design, setting, and participants: This cohort study used the UK Biobank (2006-2010, follow-up until 2016) to examine confounding in epidemiologic associations between alcohol intake and cardiovascular diseases. Using both traditional (ie, linear) and nonlinear mendelian randomization, potential associations between alcohol consumption and cardiovascular diseases (eg, hypertension and coronary artery disease) as well as corresponding association shapes were assessed. Data analysis was conducted from July 2019 to January 2022.

Exposures: Genetic predisposition to alcohol intake.

Main outcomes and measures: The association between alcohol consumption and cardiovascular diseases, including hypertension, coronary artery disease, myocardial infarction, stroke, heart failure, and atrial fibrillation.

Results: This study included 371 463 participants (mean [SD] age, 57.0 [7.9] years; 172 400 [46%] men), who consumed a mean (SD) 9.2 (10.6) standard drinks per week. Overall, 121 708 participants (33%) had hypertension. Light to moderate alcohol consumption was associated with healthier lifestyle factors, adjustment for which attenuated the cardioprotective epidemiologic associations with modest intake. In linear mendelian randomization analyses, a 1-SD increase in genetically predicted alcohol consumption was associated with 1.3-fold (95% CI, 1.2-1.4) higher risk of hypertension (P < .001) and 1.4-fold (95% CI, 1.1-1.8) higher risk of coronary artery disease (P = .006). Nonlinear mendelian randomization analyses suggested nonlinear associations between alcohol consumption and both hypertension and coronary artery disease: light alcohol intake was associated with minimal increases in cardiovascular risk, whereas heavier consumption was associated with exponential increases in risk of both clinical and subclinical cardiovascular disease.

Conclusions and relevance: In this cohort study, coincident, favorable lifestyle factors attenuated the observational benefits of modest alcohol intake. Genetic epidemiology suggested that alcohol consumption of all amounts was associated with increased cardiovascular risk, but marked risk differences exist across levels of intake, including those accepted by current national guidelines.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Haas reported receiving personal fees and stock and stock options from Regeneron Pharmaceuticals outside the submitted work. Dr Ellinor reported receiving grants from Bayer AG and IBM Health and personal fees from Bayer AG, MyoKardia, Quest Diagnostics, and Novartis during the conduct of the study. Dr Kathiresan reported being an employee of Verve Therapeutics; owning equity in Verve Therapeutics, Maze Therapeutics, Color Health, and Medgenome; receiving personal fees from Medgenome and Color Health; serving on the advisory boards for Regeneron Genetics Center and Corvidia Therapeutics; and consulting for Acceleron, Eli Lilly and Co, Novartis, Merck, Novo Nordisk, Novo Ventures, Ionis, Alnylam, Aegerion, Haug Partners, Noble Insights, Leerink Partners, Bayer Healthcare, Illumina, Color Genomics, MedGenome, Quest Diagnostics, and Medscape outside the submitted work. Dr Khera reported receiving personal fees from Merck, Amarin Pharmaceuticals, Amgen, Maze Therapeutics, Navitor Pharmaceuticals, Sarepta Therapeutics, Verve Therapeutics, Silence Therapeutics, Veritas International, Color Health, and Third Rock Ventures and receiving grants from IBM Research outside the submitted work. Dr Aragam reported receiving speaking fees from the Novartis Institute for Biomedical Research. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Epidemiological Associations Between Alcohol Consumption and Incident Cardiovascular Disease
Baseline Cox proportional hazards models are shown in blue, and lifestyle-adjusted models are shown in orange. Lifestyle factors were smoking, body mass index, red meat intake, vegetable intake, physical activity, and self-reported health. Associations between subcategories of alcohol consumption and incident cardiovascular diseases are presented as hazard ratios for hypertension and coronary artery disease (CAD). Alcohol consumption is reported as US standard drinks per week, equivalent to 14 g of alcohol. Error bars represent the 95% CI.
Figure 2.
Figure 2.. Genetic Associations of Alcohol Consumption With Cardiovascular Disease Phenotypes
Using fractional polynomial nonlinear mendelian randomization analyses with Alcohol Use Disorder–Restricted instrument, localized average causal effects were metaregressed against mean consumption in strata of residual alcohol intake, and exposure-outcome associations were reconstructed as the derivative of the best fit model for hypertension and coronary artery disease. Alcohol consumption is reported as US standard drinks per week, with each standard drink equivalent to 14 g of alcohol. Solid lines refer to odds ratio (OR) estimates, and shaded areas denote 95% CIs for the model.
Figure 3.
Figure 3.. Genetic Associations of Alcohol Consumption With Continuous Traits and Cardiovascular Risk Factors
Using fractional polynomial nonlinear mendelian randomization analyses with Alcohol Use Disorder–Restricted instruments, localized average causal effects were metaregressed against mean consumption in each strata of alcohol, and these plots were reconstructed as the derivative of the best fit model for γ-glutamyl transferase (GGT), low-density lipoprotein (LDL) cholesterol, systolic blood pressure (SBP), and diastolic blood pressure (DBP). Alcohol consumption is reported as US standard drinks per week, with each standard drink equivalent to 14 g of alcohol. Solid lines refer to odds ratio (OR) estimates, and shaded areas denote 95% CIs for the model.
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