The association between lower estimated glomerular filtration rate (eGFR) and incident cardiovascular disease is less clear within the normal or mildly impaired range.

Using the Chronic Kidney Disease EPIdemiology collaboration (CKD-EPI) and the Modification of Diet in Renal Disease (MDRD) eGFR formulas, we analyzed outpatients ≥ 22 years old from 2004-2006 with 60 mL/min/1.73 m² < eGFR < 130 mL/min/1.73 m², without prior cardiovascular disease, and with and without proteinuria.

During a median follow-up of 96 months and > 10 million patient-years of follow-up, 103,506 and 104,315 cardiovascular events were recorded using CKD-EPI (n = 1,341,400, mean age 49.2 years, 42.6% male) and MDRD (n = 1,284,762, mean age 50.2 years, 43.4% male) formulas, respectively (incident event rates 4.4% and 4.6%, respectively). Adjusting for age, sex, and major cardiovascular risk factors, a 10-unit eGFR increase was independently associated with a mean decrease of 3.0% and 1.0% in incident cardiovascular events, using CKD-EPI and MDRD, respectively (P < .001 for both), with a sharp decrease in events in the 100-mL/min/1.73 m² < eGFR < 130 mL/min/1.73 m² range in the CKD-EPI, but not the MDRD, cohort. Using net reclassification analysis, CKD-EPI was more accurate in predicting events than MDRD (Net Reclassification Improvement 0.39, P < .001 stratifying patients to eGFR deciles and 0.64, P < .001 as a continuous variable). Using both formulas, eGFR was predictive of incident cardiovascular disease for patients without proteinuria, but not for the 2.4% with proteinuria (P < .001 for interaction).

Higher eGFR is associated with fewer cardiovascular events in adults without prior cardiovascular disease and without proteinuria, particularly in the 100-mL/min/1.73 m² < eGFR < 130 mL/min/1.73 m² range, indicating that eGFR, especially using the CKD-EPI formula, may be an independent risk marker for incident cardiovascular disease.