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. 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 ( = 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. Lower eGFR of 15 mL/min/1.73 m was associated with higher ASCVD risk [ = -2.7% (95% confidence interval: -3.7, -1.8%), P < 0.001], higher IMT [ = 0.05 mm (0.03, 0.08 mm), P < 0.001] and lower FMD [ = -0.87% (-1.64, -0.11%), P = 0.026]. Compared with eGFR ≥90 mL/min/1.73 m, those with eGFR 60-89 mL/min/1.73 m 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, lower eGFR is associated with a greater 10-year risk for first ASCVD event, higher IMT and relatively impaired FMD.