medRxiv · Feb 3, 2026
Alcohol Consumption and ALDH2 Polymorphism Jointly Modify the Association Between HDL Cholesterol and Coronary Artery Calcium Score in Older Adults
By Chuang SYCSY, Chuang SYCSY, Wu MT et al.
Abstract Importance The 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. Objective To 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 Participants Retrospective analysis of 819 community-dwelling older adults aged ≥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. Exposures Serum HDL-C levels, alcohol consumption status, and ALDH2 rs671 genotype. Main Outcomes and Measures CAC 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. Results HDL-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 (β = –0.019, P = .003) were independently associated with higher CAC scores. The inverse association between HDL-C and CAC was significant among drinkers (β = –0.028, P = 0.005) and non-drinkers with ALDH2 GG (β = –0.020, P = 0.0479) but not among non-drinkers without ALDH2 GG (β = −0.005, P = 0.6106), with a significant interaction ( P = 0.0276). Conclusions and Relevance Higher 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.