Estimated Glomerular Filtration Rate Within the Normal or Mildly Impaired Range and Incident Cardiovascular Disease. The American Journal of Medicine, 2015. 128(9): p. 1015-22.e2.
Eisen A, Hoshen M, Balicer RD, Reges O, Rabi Y, Leibowitz M, Iakobishvili Z, Hasdai D.
Background: The association between lower estimated glomerular filtration rate (eGFR) and incident cardiovascular disease is less clear within the normal or mildly impaired range.
Methods: 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 m(2) < eGFR < 130 mL/min/1.73 m(2), without prior cardiovascular disease, and with and without proteinuria.
Results: 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 m(2) < eGFR < 130 mL/min/1.73 m(2) 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).
Conclusion: 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 m(2) < eGFR < 130 mL/min/1.73 m(2) range, indicating that eGFR, especially using the CKD-EPI formula, may be an independent risk marker for incident cardiovascular disease.