Estimated glomerular filtration rate in a population with normal to mildly reduced renal function as predictor of cardiovascular disease

Background: While moderate and severe chronic kidney disease is an established independent risk factor for cardiovascular disease (CVD), the association of estimated glomerular filtration rate (eGFR) differences within the normal to mildly reduced range (from 60 to >90 ml/min/1.73m²) and CVD is less clear. Our aim was to examine the association of eGFR with incident CVD in a cohort of predominantly healthy subjects with normal to mildly reduced renal function. Design: Retrospective cohort study. Methods: We collected demographic, clinical, and laboratory parameters of subjects free of diabetes mellitus or CVD who attended annual medical screening examinations between 2001 and 2009. Main outcome measures were a new diagnosis of coronary artery disease (CAD) or cerebrovascular events (CVE). Results: During a median follow up of 4.3 years, among 10,909 subjects (mean eGFR 78.5±12.2 ml/min/1.73m²), 10.3% were diagnosed with CAD (n=1025) or CVE (n=94). Compared with subjects in the highest eGFR quintile (7≥88.8 ml/min/1.73m²), subjects in the lowest quintile (≤68.2 ml/min/1.73m²) had a hazard ratio (HR) of 1.64 (95% CI 1.35-2.00; p<0.001) for a CAD outcome, but this association was no longer significant after adjustment for age and other confounders (adjusted HR 1.08; p=0.55). Similar findings were obtained for the association of eGFR with CVE. Conclusions: In a predominantly healthy population with normal to mildly reduced renal function, lower eGFR is associated with higher risk for CVD; however, this association is not independent but merely reflects the association of age and other cardiovascular risk factors with reduced eGFR.