Abstract 14613: Sex Differences in Protein Biomarkers and Measures of Fat Distribution

Abstract

Background: Sex differences in obesity and fat distribution have been well described and may explain differences in subsequent cardiovascular risk in men vs women. Underlying mechanisms are not fully elucidated and warrant further investigation. Objective: This study aims to examine sex differences in the associations of obesity and fat distribution measures with cardiovascular disease (CVD) protein biomarkers reflecting key pathways including inflammation, adiposity, fibrosis, and neurohormonal regulation. Methods: We measured 71 circulating protein biomarkers in 3,143 participants with available computed tomography measures of adiposity in the Framingham Heart Study. We examined whether sex modified the association of obesity (body mass index [BMI] and waist circumference [WC]) and fat distribution measures (visceral adipose tissue [VAT]) with protein biomarkers using multiplicative interaction terms in multivariable linear regression models. Sex-stratified analyses were performed as appropriate. Results: Among 3,143 participants (mean age 50 years, 48.7% women), we found that sex modified the association of BMI with 8 protein biomarkers including AGP-1, adipsin, IGFBP-1, IGFBP-2, ADM, KLKB1, MCP-1, and ucMGP (FDR-q int < 0.05 for all, Figure 1 ). For example, BMI was associated with higher MCP-1 levels in women, but not in men (ß 0.132, SE 0.025, p < 0.0001 in women vs ß 0.036, SE 0.028, p = 0.20 in men, FDR-q int 0.03). We found that sex also modified the association of WC and VAT with key CVD protein biomarkers including AGP-1 and A1M. Conclusions: We found that sex modified the association of obesity and adipose traits with cardiovascular risk as ascertained using biomarkers of CVD. These findings highlight potential biological pathways that may contribute to obesity-related cardiometabolic disease uniquely in men versus women.