Abstract 18607: Sex-specific Metabolites Associated With Incident Stroke, Incident Coronary Heart Disease, Hypertension, And Chronic Kidney Disease In The Regards Cohort

Abstract

Sex disparities continue to exist in cardiometabolic diseases. Metabolomic profiling offers the ability to gain insight into disease mechanisms. The purpose of the present analysis was to identify metabolites associated with sex and determine if sex-specific metabolites are associated with incident stoke, incident coronary heart disease (CHD), hypertension (HTN), and chronic kidney disease (CKD). Targeted metabolomics was conducted for 358 metabolites in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort. Weighted logistic regression models were used to test the association between sex and metabolites. Metabolites meeting the Bonferroni-corrected threshold were selected for replication in the Hypertension Genetic Epidemiology Network study. Cox proportional hazard models were used to calculate hazard ratios (HRs) per unit standard deviation (SD) of each replicated metabolite with incident stroke and incident CHD. Weighted logistic regression models were used to calculate odds ratios (ORs) per unit SD of each replicated metabolite with prevalent HTN and prevalent CKD. A total of 1,898 individuals were included in the analysis and 50.47% of the sample was male sex. The mean age was 68.40 ± 10.55 years and 43% of the sample was Black race. Sixteen metabolites were associated with sex, meeting the Bonferroni-adjusted p-value of 1.4 x 10 -4 . These included 8 lipids, 6 amino acids, 1 indole, and 1 quinoline. Of these 16 metabolites, none were associated with incident stroke or incident CHD. Kynurenic acid and leucine were associated with HTN in the base model adjusting for age, sex, and race (kynurenic acid: OR 1.45, 95% CI [1.19, 1.76], p=2.36 x 10 -4 ; leucine: OR 1.41, 95% CI [1.14, 1.76], p=2.03 x 10 -3 ). Indole-3-lactic acid and kynurenic acid were associated with CKD in the full model adjusting for age, sex, race, smoking, alcohol use, and BMI (indole-3-lactic acid: OR 3.83, 95% CI [2.77, 5.29], p=5.93 x 10 -16 ; kynurenic acid: OR 6.63, 95% CI [4.67, 9.41], p=1.50 x 10 -25 ). Our findings shed light on the sexual dimorphism of the metabolome and suggest that differences in biochemical pathways may contribute to sex disparities in cardiometabolic disease risk.