Sex Differences in Early Stages of Cardiorenometabolic Syndrome in Young Adults

Cardiorenometabolic diseases represent a significant global health burden. Data highlight an alarming rise in cardiorenometabolic risk factors, such as adiposity, arterial hypertension, insulin resistance, elevated body mass index (BMI), dyslipidemia, and early renal dysfunction among adults. However, studies evaluating the sex-stratified burden, especially in young adults, are limited. The aim of this study was to investigate the differences between sexes in the early stages of cardiorenometabolic syndrome in young adults.

This cross-sectional study included 169 patients (89 female and 80 male participants). We conducted patient interviews along with comprehensive laboratory and instrumental analyses. Studied cardiorenometabolic parameters included anthropometry, body composition analysis, blood pressure measurements, lipid, glycemic and renal profiles, and factors constituting residual risk and echocardiographic parameters. Non-parametric statistical tests were performed.

The median age of participants was 34 (30-39) years. Abdominal obesity, hyperleptinemia, elevated high-sensitivity C-reactive protein (hsCRP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, and elevated heart rate were more common in female participants. Male participants exhibited a higher frequency of elevated systolic and diastolic blood pressure (BP). Furthermore, hypertriglyceridemia, hyperuricemia, elevated cystatin C levels, and urine albumin to creatinine ratio were significantly more common in male participants. A similar trend was observed while evaluating the median values. Stratification by sex and cystatin C tertiles revealed that in women, higher cystatin C tertiles were associated with increasing BMI, waist circumference (WC), visceral fat, and glucose, hsCRP, and leptin levels. Notably, a statistically significant decline in estimated glomerular filtration rate (eGFR), based on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) cystatin C formula (eGFR_cysC), was observed in both female and male participants. However, apart from this finding, no significant trends were observed among male participants. Key sex-specific significant interactions were identified for BMI, WC, waist-hip ratio, body fat percentage, visceral fat level, BP, high-density lipoprotein cholesterol, uric acid, eGFR_cysC, hsCRP, leptin, NT-proBNP, and heart rate. Correlation analysis revealed that eGFR derived from cystatin C in female participants and creatinine in male participants demonstrated stronger and more extensive correlations with cardiometabolic and echocardiographic parameters than their respective individual biomarkers. The regression models further clarified these relationships. In female participants, eGFR based on cystatin C was independently predicted by hsCRP, visceral fat, systolic BP, and insulin. In male participants, eGFR based on creatinine was inversely associated with visceral fat level and positively associated with leptin.

This study underscores profound sex differences in cardiorenometabolic risk profiles among young adults, with female participants exhibiting adiposity-driven inflammation and male participants displaying early renal and vascular perturbations. While cystatin C and creatinine emerged as sensitive markers of cardiometabolic-renal crosstalk, cystatin C-based eGFR and creatinine-based eGFR better captured risks in females and males, respectively.