Figure 2.

Sex differences in blood-based biomarkers and potential clinical implications. (A) Biologic determinants of sex differences in blood-based biomarkers can be broadly classified into internal and external factors. Internal factors that contribute to sex differences in biomarkers include genes and sex chromosomes, sex hormones, tissue distribution, and inflammatory milieu. External factors include social/cultural and environmental factors. (B) Sex differences in biomarkers can manifest in two ways. First, a given biomarker may portend a similar risk of CVD in men and women, yet inherent differences in circulating baseline levels of biomarkers in men vs women may contribute to sex differences in disease risk. Second, sex may modify the effect of a biomarker on a disease outcome. In other words, the same biomarker increment may portend a differential risk in men vs women, resulting in sex differences in disease. (C) The clinical applications of sex-based differences in blood-based biomarkers remain unclear, but sex differences can translate to sex-specific biomarker cutoffs for improved diagnosis of CVD, improved risk prediction and prognosis for men and women, and sex-specific targeted therapies.