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Effects of Anemia and Left Ventricular Hypertrophy on Cardiovascular Disease in Patients with Chronic Kidney Disease

Daniel E. Weiner^*, Hocine Tighiouart, Panagiotis T. Vlagopoulos^*, John L. Griffith, Deeb N. Salem, Andrew S. Levey^* and Mark J. Sarnak^*

Divisions of ^* Nephrology, Clinical Care Research, and Cardiology, Tufts-New England Medical Center, Boston, Massachusetts

Address correspondence to: Dr. Mark J. Sarnak, Division of Nephrology, Tufts-New England Medical Center, 750 Washington Street, Box 391, Boston, MA 02111. Phone: 617-636-1182; Fax: 617-636-2369; E-mail: msarnak{at}tufts-nemc.org

Received for publication July 25, 2004. Accepted for publication March 2, 2005.

Left ventricular hypertrophy (LVH) and anemia are highly prevalent in moderate chronic kidney disease (CKD). Because anemia may potentiate the adverse effects of LVH on cardiovascular outcomes, the effect of both anemia and LVH on outcomes in CKD was examined. Data from four community-based longitudinal studies were pooled: Atherosclerosis Risk in Communities Study, Cardiovascular Health Study, Framingham Heart Study, and Framingham Offspring Study. Serum creatinine levels were calibrated indirectly across studies, and GFR was estimated using the Modification of Diet in Renal Disease equation. CKD was defined as GFR between 15 and 60 ml/min per 1.73 m². LVH was based on electrocardiogram criteria. Anemia was defined as hematocrit <36% in women and 39% in men. The primary outcome was a composite of myocardial infarction, stroke, and death; a secondary cardiac outcome included only myocardial infarction and fatal coronary heart disease. Among 2423 patients with CKD, 96% had electrocardiogram and anemia data. Median follow-up was 102 mo. In adjusted analysis, LVH was associated with increased risk for composite and cardiac outcomes (hazard ratio [HR], 1.67 [95% confidence interval (CI), 1.34 to 2.07] and 1.62 [95% CI, 1.18 to 2.24], respectively), whereas anemia was associated with increased risk for the only composite outcome (HR, 1.51 [95% CI, 1.27 to 1.81]). The combination of anemia and LVH was associated with an increased risk for both study outcomes compared with individuals with neither risk factor (HR, 4.15 [95% CI, 2.62 to 6.56] and 3.92 [95% CI, 2.05 to 7.48]; P = 0.02 and 0.01 for interaction term, respectively). The combination of anemia and LVH in CKD identifies a high-risk population.

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