Sex hormone-binding globulin and coronary heart disease: a narrative review of associations and biomarker potential.

BACKGROUND AND

OBJECTIVE

Coronary heart disease (CHD) remains the leading cause of global mortality, and traditional cardiovascular risk scores fail to accurately identify high-risk individuals in certain populations. Sex hormone-binding globulin (SHBG) has emerged as a multifunctional metabolic biomarker linking liver function to systemic vascular health. This narrative review aims to synthesize current epidemiological evidence on the association between SHBG and CHD risk, clarify the underlying biological mechanisms, and evaluate its potential clinical utility.

METHODS

A comprehensive literature search was performed in PubMed and Web of Science databases for studies published between January 1981 and August 2024. We included peer-reviewed original research (cohort, case-control, cross-sectional studies), systematic reviews, meta-analyses, and clinical guidelines investigating the SHBG-CHD relationship in human populations. Evidence synthesis was conducted using the Scale for the Assessment of Narrative Review Articles (SANRA) framework, with conflicting results critically evaluated based on study design, population characteristics, SHBG measurement methods, and confounding adjustment strategies.

KEY CONTENT AND FINDINGS: A total of 46 relevant studies were included, comprising 32 prospective cohort studies, 8 case-control studies, and 6 meta-analyses. Current evidence consistently shows that lower circulating SHBG levels are independently associated with an increased risk of CHD in both men and women, with this association partially mediated by insulin resistance, metabolic syndrome (MetS), and dyslipidemia. However, significant heterogeneity exists across studies, particularly regarding the strength of association in postmenopausal women and the impact of statin therapy on SHBG metabolism.

CONCLUSIONS

SHBG holds promise as a complementary biomarker for CHD risk assessment. Lower circulating SHBG levels are consistently associated with elevated CHD risk in both men and women, with this association partially mediated by insulin resistance and MetS. However, significant study heterogeneity (particularly in postmenopausal populations), non-standardized measurement methods, the absence of sex- and ethnicity-specific reference ranges, and unresolved causal relationships currently limit its clinical utility. Future large-scale, multicenter studies with harmonized testing protocols are needed to establish clinical reference thresholds and validate the incremental value of SHBG beyond traditional cardiovascular risk factors.