Alcohol Consumption and ALDH2 Polymorphism Jointly Modify the Association Between HDL Cholesterol and Coronary Artery Calcium Score in Older Adults

ImportanceThe association between high-density lipoprotein cholesterol (HDL-C) and coronary artery calcium (CAC) burden remains unclear, and the potential modifying effects of lifestyle and genetic factors are not well characterized. ObjectiveTo clarify the relationship between HDL-C and CAC scores in older adults and examine whether alcohol consumption and the ALDH2 rs671 genetic variant modify this association. Design, Setting, and ParticipantsRetrospective analysis of 819 community-dwelling older adults aged [&ge;]55 years (378 men; 441 women) without a history of coronary stent placement, enrolled in the Healthy Aging Longitudinal Study in Taiwan. Baseline alcohol consumption and metabolic profiles were collected during 2014-2019; CAC scores were assessed in 2023 using low-dose computed tomography. ExposuresSerum HDL-C levels, alcohol consumption status, and ALDH2 rs671 genotype. Main Outcomes and MeasuresCAC scores calculated using the Agatston method. Linear and logistic regression models assessed associations between HDL-C and CAC, adjusting for demographic and cardiometabolic risk factors. Interaction terms tested effect modification by alcohol consumption and ALDH2 genotype. ResultsHDL-C was inversely associated with log-transformed CAC scores after adjusting for age and sex (R = -0.228, P < .001). In multivariable models, older age, male sex, higher systolic blood pressure, elevated HbA1c, and lower HDL-C levels ({beta} = -0.019, P = .003) were independently associated with higher CAC scores. The inverse association between HDL-C and CAC was significant among drinkers ({beta} = -0.028, P = 0.005) and non-drinkers with ALDH2GG ({beta} = -0.020, P = 0.0479) but not among non-drinkers without ALDH2GG ({beta} = -0.005, P = 0.6106), with a significant interaction (P = 0.0276). Conclusions and RelevanceHigher HDL-C levels were independently and inversely associated with CAC scores in older adults, with the relationship significantly modified by both alcohol consumption and ALDH2 genotype. These findings highlight a gene-environment interaction that may inform precision cardiovascular prevention strategies, particularly in populations with low prevalence of ALDH2 deficiency.