Heavy alcohol consumption, depression, their comorbidity and risk of all-cause and cause-specific mortality: a prospective cohort study

Background Alcohol consumption and depression commonly co-occur, and most current research has focused on the associations between either alcohol consumption or depression alone with mortality risk. However, the association of the comorbidity of heavy alcohol consumption and depression on the risk of all-cause and cause-specific mortality remains unclear in the U.S. population. Aim The objective of our study was to analyze the risks of all-cause and cause-specific mortality in participants who have heavy alcohol consumption alone, depression alone, or both, by conducting a prospective cohort study with a sample in the National Health and Nutrition Examination Survey (NHANES) database. Method For this cohort study, we included 11,590 U.S. adults aged >= 20 years from a nationally representative sample. Data on depression and alcohol consumption were extracted from the NHANES conducted between 2005 and 2018, and mortality information was obtained from the NHANES Linked Mortality File through December 31, 2019. Drinking and depression were classified into four groups: only heavy alcohol consumption, only depression, both present, and neither present. By adjusting for confounding factors, we applied the Cox proportional hazards model to investigate the risk of all-cause mortality associated with alcohol consumption and depressive states, including cardiovascular disease (CVD), cancer, and other causes. The log-rank test and Kaplan-Meier (K-M) survival analysis were applied to investigate differences in survival probabilities. Additionally, we examined the correlation between heavy alcohol consumption and depression by assessing additive interaction using the synergy index (SI), the attributable proportion due to interaction (AP), and the relative excess risk due to interaction (RERI). Results The adjusted HR (aHR) for all-cause mortality, as well as mortality due to CVD, cancer, and other causes, were highest among individuals with comorbid heavy alcohol consumption and depression (HR 2.68[95%CI 1.84,3.91]; 2.64 [95%CI 1.27, 5.48]; 2.55 [95%CI 1.22,5.35]; and 2.78[95%CI 1.64, 4.71]). However, the results of additive and multiplicative interactions indicated that the synergistic effect of heavy alcohol consumption and depression on all-cause and cause-specific mortality did not reach statistical significance. Conclusions Our findings confirmed that heavy alcohol consumption or depression was associated with an increased risk of all-cause and other-cause mortality. Although the synergistic effect of comorbid heavy alcohol consumption and depression on all-cause and cause-specific mortality did not reach statistical significance, the comorbidity of heavy alcohol consumption and depression was associated with the highest risk of all-cause and cause-specific mortality. This research could provide a foundation for further investigations into the mechanisms underlying the comorbidity of heavy alcohol consumption and depression, as well as interventions for depression among heavy alcohol consumers, with significant implications for public health and clinical practice.