Early stages of cardiorenometabolic syndrome in young adults: a sex-specific analysis

BACKGROUND: Sex-specific differences in the early cardiorenometabolic risk profile of young adults remain poorly characterized. The majority of existing studies pool men and women without sex-stratified analysis, limiting personalized assessment of risk at the preclinical stage. AIM: To examine sex-specific associations between cardiorenometabolic risk factors, cardiac structural and functional parameters, and markers of renal dysfunction in young adults. METHODS: A single-center, observational, cross-sectional, case-control study was conducted between 2022 and 2023 at the Consultative Diagnostic Center, Kazan. Eligible participants were adults aged 25–44 years with CMDS stages I–III, providing written informed consent. Individuals with established type 2 diabetes, coronary artery disease, heart failure, atrial fibrillation, chronic kidney disease, autoimmune, oncological, and acute infectious diseases, endocrine disorders, pregnancy, and lactation were excluded. A total of 169 participants were enrolled (89 women, 80 men); median age 34.0 [30.0; 39.0] years; the two groups were comparable in age (p = 0.423). Cardiorenometabolic risk factors and parameters of renal dysfunction were assessed alongside echocardiographic parameters and types of left ventricular remodeling. RESULTS: Men more frequently had elevated blood pressure, hypertriglyceridemia, and hyperuricemia, and had higher serum levels of cystatin C and creatinine (p = 0.003–0.004); women more frequently had abdominal obesity (p = 0.005), higher body fat values, and elevated high-sensitivity C-reactive protein (hs-CRP), leptin, and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels (p 0.001–0.009). No significant sex differences were identified in estimated glomerular filtration rate (eGFR) or in the distribution of left ventricular remodeling types (p = 0.258–0.848). Correlation analysis revealed sex-specific associations: in women, obesity and inflammation parameters correlated with cystatin C content, whereas in men, they correlated with serum creatinine. On multiple linear regression, cystatin C-based eGFR in women was independently associated with hs-CRP and visceral fat level (R² = 0.283; p 0.001); creatinine-based eGFR in men was independently associated with visceral fat level and leptin (R² = 0.166; p = 0.029). CONCLUSION: In young adults without manifest cardiorenometabolic disease, sex differences in cardiorenometabolic risk factors were established. Sex-specific features were identified in the association of renal dysfunction indices with cardiometabolic parameters: in women, a closer relationship was shown for cystatin C and cystatin C-based eGFR, while in men—for creatinine and creatinine-based eGFR. These findings indicate the advisability of considering sex when selecting a renal biomarker for early cardiorenal risk stratification.