The cystatin c–to–creatinine eGFR ratio and subclinical cardiac structure and function in a population-based cohort
H Holm, H Zilic, M Magnusson, A Jujic, D Kylhammar, J Engvall, M Ohlsson, J Molvin, A Christensson, A laucyte-cibulskieneAbstract
Background
The ratio of cystatin C– to creatinine-based estimated glomerular filtration rate (eGFRcys/eGFRcr) has emerged as an integrative marker associated with adverse outcomes in patients with established heart failure. However, its associations with echocardiographic measures of cardiac structure and function in the general population remain incompletely characterized.
Methods
In an exploratory cross-sectional analysis of a population-based cohort (n=5,657; 48.1% men), associations between eGFRcys/eGFRcr-ratio and echocardiographic measures were examined. Linear regression was used for continuous outcomes and logistic regression for dichotomized echocardiographic abnormalities. Multivariable models included age, sex, systolic blood pressure, diabetes, smoking, and body mass index.
Results
In multivariable linear regression analyses, higher eGFRcys/eGFRcr ratio was associated with lower indexed left ventricular mass (LVMI; β −2.8 g/m², 95%CI(−5.1,−0.4), p=0.020) and lower interventricular septal thickness in diastole (IVSd; β −0.05 cm, 95%CI (−0.07,−0.03), p<0.001), as well as higher LVEF (β +1.0%, 95%CI(0.3,1.7), p=0.005) and stroke volume (β +6.1 mL, 95%CI(3.8,8.4), p<0.001). Higher eGFRcys/eGFRcr ratio was further associated with more favorable diastolic indices, including higher septal e′ velocity (β +0.85 cm/s, 95%CI(0.57,1.14), p<0.001) and lower LAVi (β −1.7 mL/m², 95%CI(−2.8,−0.6), p=0.002), as well as higher TAPSE (β +1.3 mm, 95%CI(0.8,1.8), p<0.001). In logistic regression analyses, higher eGFRcys/eGFRcr ratio was associated with lower odds of reduced septal e′ velocity (<7 cm/s; OR 0.37, 95%CI(0.22,0.63), p<0.001) and left atrial enlargement (LAVi >34 mL/m²; OR 0.65, 95%CI(0.45,0.95), p=0.026). Associations with left ventricular hypertrophy [MM1] and elevated E/e′ [MM2] were not statistically significant after multivariable adjustment.
Conclusions
In a large population-based cohort, higher eGFRcys/eGFRcr-ratio was independently associated with multiple favorable echocardiographic measures of cardiac structure and function, particularly indices of left ventricular remodeling and diastolic function. These findings support eGFRcys/eGFRcr as a marker of subclinical cardio–renal interactions beyond traditional measures of kidney function.