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Acute Decline in Renal Function, Inflammation, and Cardiovascular Risk after an Acute Coronary Syndrome

Lisa M. Mielniczuk^*, Marc A. Pfeffer, Eldrin F. Lewis, Michael A. Blazing, James A. de Lemos, Satishkumar Mohanavelu, Jean Rouleau^||, Keith Fox^¶, Terje R. Pedersen^**, and Robert M. Califf

^* University of Ottawa Heart Institute, Ottawa, Ontario, Canada; Cardiovascular Division, Brigham and Women's Hospital and Department of Medicine, Harvard Medical School, Boston, Massachusetts; Duke Clinical Research Institute, Durham, North Carolina; Donald W. Reynolds Cardiovascular Clinical Research Center, University of Texas Southwestern Medical Center, Dallas, Texas; ^|| Department of Medicine, University of Montreal, Montreal, Quebec, Canada; ^¶ Centre for Cardiovascular Sciences, University of Edinburgh, Edinburgh, United Kingdom; ^** Centre for Preventive Medicine, Ullevål University Hospital and Medical Faculty, University of Oslo, Oslo, Norway

Correspondence: Dr. Lisa M. Mielniczuk,University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, Ontario K1Y 4W7, Canada. Phone: 613-761-4059; Fax: 613-761-4877; E-mail: lmielniczuk{at}ottawaheart.ca

Background and objectives: Chronic kidney disease is associated with a higher risk of cardiovascular outcomes. The prognostic significance of worsening renal function has also been shown in various cohorts of cardiac disease; however, the predictors of worsening renal function and the contribution of inflammation remains to be established.

Design, setting, participants, & measurements: Worsening renal function was defined as a 25% or more decrease in estimated GFR (eGFR) over a 1-mo period in patients after a non-ST or ST elevation acute coronary syndromes participating in the Aggrastat-to-Zocor Trial; this occurred in 5% of the 3795 participants.

Results: A baseline C-reactive protein (CRP) in the fourth quartile was a significant predictor of developing worsening renal function (odds ratio, 2.48; 95% confidence interval, 1.49, 4.14). After adjusting for baseline CRP and eGFR, worsening renal function remained a strong multivariate predictor for the combined cardiovascular composite of CV death, recurrent myocardial infarction (MI), heart failure or stroke (hazard ratio, 1.6; 95% confidence interval, 1.1, 2.3).

Conclusions: Patients with an early decline in renal function after an acute coronary syndrome are at a significant increased risk for recurrent cardiovascular events. CRP is an independent predictor for subsequent decline in renal function and reinforces the idea that inflammation may be related to the pathophysiology of progressive renal disease.