Faculty, Staff and Student Publications
Publication Date
11-16-2023
Journal
BMC Medicine
Abstract
BACKGROUND: Metabolite signatures of long-term alcohol consumption are lacking. To better understand the molecular basis linking alcohol drinking and cardiovascular disease (CVD), we investigated circulating metabolites associated with long-term alcohol consumption and examined whether these metabolites were associated with incident CVD.
METHODS: Cumulative average alcohol consumption (g/day) was derived from the total consumption of beer, wine, and liquor on average of 19 years in 2428 Framingham Heart Study Offspring participants (mean age 56 years, 52% women). We used linear mixed models to investigate the associations of alcohol consumption with 211 log-transformed plasma metabolites, adjusting for age, sex, batch, smoking, diet, physical activity, BMI, and familial relationship. Cox models were used to test the association of alcohol-related metabolite scores with fatal and nonfatal incident CVD (myocardial infarction, coronary heart disease, stroke, and heart failure).
RESULTS: We identified 60 metabolites associated with cumulative average alcohol consumption (p < 0.05/211 ≈ 0.00024). For example, 1 g/day increase of alcohol consumption was associated with higher levels of cholesteryl esters (e.g., CE 16:1, beta = 0.023 ± 0.002, p = 6.3e - 45) and phosphatidylcholine (e.g., PC 32:1, beta = 0.021 ± 0.002, p = 3.1e - 38). Survival analysis identified that 10 alcohol-associated metabolites were also associated with a differential CVD risk after adjusting for age, sex, and batch. Further, we built two alcohol consumption weighted metabolite scores using these 10 metabolites and showed that, with adjustment age, sex, batch, and common CVD risk factors, the two scores had comparable but opposite associations with incident CVD, hazard ratio 1.11 (95% CI = [1.02, 1.21], p = 0.02) vs 0.88 (95% CI = [0.78, 0.98], p = 0.02).
CONCLUSIONS: We identified 60 long-term alcohol consumption-associated metabolites. The association analysis with incident CVD suggests a complex metabolic basis between alcohol consumption and CVD.
Keywords
Humans, Female, Middle Aged, Male, Cardiovascular Diseases, Prospective Studies, Alcohol Drinking, Coronary Disease, Diet, Risk Factors, Alcohol consumption, Metabolites
DOI
10.1186/s12916-023-03149-2
PMID
37968697
PMCID
PMC10652547
PubMedCentral® Posted Date
11-16-2023
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Included in
Cardiology Commons, Cardiovascular Diseases Commons, Medical Genetics Commons, Public Health Education and Promotion Commons