Unveiling sex-specific cardiometabolic and adiposity risk profiles for precision prevention

Cardiometabolic diseases (CMDs) are the leading global cause of mortality, driven by interrelated metabolic and cardiovascular factors. Sex differences significantly shape risk. We investigated sex-specific differences in cardiometabolic risk factors through univariate analyses and multivariate principal component analysis (PCA), with the goal of identifying meaningful patterns and potential biomarkers to support tailored prevention strategies.

A cross-sectional study was conducted on 1715 individuals (929F/786 M; 58.1 ± 13.5 years). Clinical and biochemical variables were compared by sex, including markers of metabolic, atherogenic cardiovascular, and renal risk. All parameters were measured using certified and standardized methods to ensure reproducibility. PCA was applied to explore underlying patterns of association.

Correlation analyses revealed significant associations only between insulin resistance markers and atherogenic cardiovascular risk indices, suggesting largely independent effects of other parameters. In contrast, PCA identified coherent clusters: lipid/atherogenic markers, glycemic and insulin-resistance indices, and adiposity measures, while renal function emerged as a distinct domain. Sex differences were evident, with men displaying a less favorable cardiometabolic profile. PCA showed that in females, variance was mainly explained by triglyceride-related indices (TG, TG/HDL, AIP), adiposity measures, and blood pressure, whereas in males, lipid and atherogenic markers (TC, LDL, CRI indices, non-HDL, LCI) predominated, with adiposity and blood pressure forming separate clusters in both sexes. Lifestyle variables (smoking, alcohol consumption, fatigue) also modulated risk, whereas family history of diabetes and hypertension showed weak associations.

Overall, cardiometabolic risk emerges as a multidimensional construct shaped by distinct yet overlapping biological and behavioral domains, with sex and lifestyle exerting specific influences, underscoring the need for individualized, sex-specific prevention strategies.

The study protocol was registered in ClinicalTrials.gov (ID: NCT0642756).