Association between normal or mildly reduced kidney function, cardiovascular risk and biomarkers for atherosclerosis: results from the ENCORE trial

BACKGROUND: Moderate-to-severe kidney dysfunction is associated with atherosclerotic cardiovascular disease (ASCVD). Gradations of normal or mildly reduced kidney function may also associate with ASCVD risk. METHODS: We conducted a secondary analysis using baseline data from the Exercise and Nutritional Interventions for Cardiovascular Health (ENCORE) trial. Participants were sedentary, overweight and obese adults with unmedicated pre-hypertension or Stage I hypertension and an estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m(2). The Pooled Cohorts Equations were used to estimate a 10-year risk for first ASCVD event. Carotid artery intima-media thickness (IMT) and brachial artery flow-mediated dilation (FMD) were measured to assess subclinical atherosclerosis and vascular endothelial function, respectively. Using linear regression, we examined the association between eGFR and ASCVD risk, IMT and FMD. RESULTS: Participants (N = 139) were predominantly women (65%), white (60%), with a mean age of 52.0 ± 9.6 years and mean eGFR of 89.1 ± 15.0 mL/min/1.73 m(2). Lower eGFR of 15 mL/min/1.73 m(2) was associated with higher ASCVD risk [b = −2.7% (95% confidence interval: −3.7, −1.8%), P < 0.001], higher IMT [b = 0.05 mm (0.03, 0.08 mm), P < 0.001] and lower FMD [b = −0.87% (−1.64, −0.11%), P = 0.026]. Compared with eGFR ≥90 mL/min/1.73 m(2), those with eGFR 60–89 mL/min/1.73 m(2) had higher mean ASCVD risk (7.6% versus 2.7%; P < 0.001), greater mean IMT (0.74 mm versus 0.66 mm; P < 0.001) and lower mean FMD (2.0% versus 3.7%; P = 0.026). After controlling for CVD risk factors, the association between eGFR and IMT remained significant (P < 0.001), and eGFR and FMD trended toward significance (P = 0.08). CONCLUSIONS: Among overweight and obese adults with unmedicated high blood pressure and eGFR ≥60 mL/min/1.73 m(2), lower eGFR is associated with a greater 10-year risk for first ASCVD event, higher IMT and relatively impaired FMD.