Sex Differences in Protein Biomarkers and Measures of Fat Distribution

Sex differences in obesity and fat distribution may in part explain differences in cardiovascular risk in men versus women. We sought to examine sex differences in the associations of obesity and adiposity measures with cardiovascular disease-related protein biomarkers.

In a cross-sectional observational cohort study, we examined whether the association of obesity (body mass index [BMI] and waist circumference) and adiposity measures (visceral adipose tissue) with biomarkers demonstrates effect modification by sex using multiplicative interaction terms in multivariable linear regression models. Among 3143 participants (mean age, 50 years; 49% women), sex modified the association of BMI, waist circumference, and visceral adipose tissue with cardiovascular disease-related protein biomarkers (7 for BMI, 3 for waist circumference, and 23 for visceral adipose tissue, false discovery rate [FDR]-q_int<0.05 for all). For example, higher BMI was associated with lower α₁-microglobulin levels in men but not in women (ß, -0.113; SE, 0.028; P<0.001 in men versus ß, -0.007; SE, 0.024; P=0.78 in women). By contrast, higher BMI was associated with higher adipsin levels in men and women, but the association was more pronounced in women (ß, 0.287; SE, 0.023; P<0.001 in women versus ß, 0.189; SE, 0.026; P<0.001 in men). The associations of higher visceral adipose tissue with biomarkers representing adiposity, inflammation, and fibrosis were more pronounced in women versus men.

We found that sex modified the associations of obesity and adipose traits with cardiovascular risk ascertained by cardiovascular disease-related biomarkers including markers of adiposity, inflammation, and fibrosis. These findings highlight potential biological pathways that may underlie some of the observed differences in obesity-related cardiovascular disease between women and men.