Reassessing alcohol consumption and cardiovascular disease by addressing bias in observational data: results from the Multi-Ethnic Study of Atherosclerosis

Abstract Background Alcohol and its relationship with cardiovascular disease (CVD) remains contentious. Several observational studies have found cardio-protective associations, while Mendelian Randomization studies have found null or harmful effects of moderate drinking. Biases, including abstainer misclassification and sick quitter effects, may obscure true associations. It is widely understood that former drinkers are often sick quitters. However, removal of former drinkers from analyses addresses bias in the abstainer group but fails to account for induced survivorship among current drinkers. This study sought to determine whether adjusting for biases altered the association between alcohol and CVD by comparing conventional models with those using (1) occasional drinkers as the reference group instead of lifetime abstainers and (2) intention-to-treat (ITT) reallocation of former drinkers based on past drinking patterns. Methods The Multi-Ethnic Study of Atherosclerosis (MESA) is a prospective cohort study of 6,814 participants aged 45-84 years between 2000-2002 without baseline CVD. 6,755 participants were included after excluding those with missing data. Alcohol consumption was self-reported and classified as lifetime abstainer, former, or current drinker (occasional ≤1 drink/week, light 2-7 drinks/week, moderate 8-14 drinks/week, heavy 14 drinks/week). Outcomes included Coronary Artery Calcium (CAC) (0, 1-100, 101-300, and 300), and clinical events (MI, stroke, cardiovascular mortality, composite MACE, and heart failure). Results Of 6,755 participants, 20.6% were lifetime abstainers, 24.1% former drinkers, and 55.3% current drinkers. Adjusting for biases altered the observed relationship between alcohol and CVD, showing increased harm with light drinking, decreased protection with moderate drinking, and a dose-response relationship between alcohol and CAC, particularly CAC 300 in adjusted models. Protective associations between moderate drinking and MI (HR: 0.64, 95% CI: 0.38-1.06) and cardiovascular mortality (HR: 0.81, 95% CI: 0.53-1.25) were attenuated and became non-significant. Light drinking shifted from null to increased risk for MI (HR: 1.46, 95% CI: 1.11-1.92), stroke (HR: 1.54, 95% CI: 1.17-2.03), MACE (HR: 1.33, 95% CI: 1.12-1.57), and heart failure (HR: 1.42, 95% CI: 1.10-1.84). Conclusions Associations between alcohol and CVD in observational studies are sensitive to methodologic variation. Results from models correcting for abstainer/sick-quitter biases may help explain discrepant results from previous studies.