Predictive value of creatinine/cystatin C ratio and physical activity for all-cause mortality risk in hypertensive patients

Abstract

Physical activity (PA) is a cornerstone of hypertension management, but whether muscle mass influences its survival benefits remains unclear. The serum creatinine-to-cystatin C ratio (CCR) has been proposed as a surrogate marker of muscle mass, although it is also affected by renal function, nutritional status, and inflammation. This study examined the association between CCR and mortality in hypertensive adults and explored the role of PA intensity. This retrospective cohort study included 2,432 adults with essential hypertension from the National Health and Nutrition Examination Survey (NHANES). Hypertension was defined as systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥90 mmHg, or use of antihypertensive medication. Muscle mass was estimated using CCR, and PA was classified as inactive, moderate, or vigorous. All-cause mortality was obtained through linkage with the National Death Index. Covariates included age, sex, race/ethnicity, education, smoking status, body mass index (BMI), albumin, C-reactive protein (CRP), lipid profile, and estimated glomerular filtration rate (eGFR). Kaplan–Meier analyses and multivariable Cox regression models were used. Low CCR was associated with older age, female sex, higher CRP, and lower albumin levels. In multivariable analyses, low CCR independently predicted all-cause mortality and outperformed indicators such as BMI and lipid measures. Stratified analyses suggested a stronger association between low CCR and mortality among participants performing vigorous PA (HR 1.95) than among those with moderate PA (HR 1.20) or inactivity (HR 1.29), although the interaction between CCR and PA was not significant (p-interaction = .21). Exercise was associated with survival in those with higher CCR. CCR is an independent predictor of mortality in hypertensive adults and adds value beyond conventional markers. Low CCR may be associated with reduced survival benefits from vigorous PA, although this finding requires confirmation. Incorporating CCR into risk assessment may help identify patients who could benefit from muscle-preserving strategies and resistance training.