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Anemia as a Risk Factor for Cardiovascular Disease and All-Cause Mortality in Diabetes: The Impact of Chronic Kidney Disease

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

^* Nephrology, Clinical Care Research, ^|| Cardiology, Tufts-New England Medical Center, Boston, Massachusetts; and Pfizer Inc., New York, New York

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: 617-636-8329; E-mail: msarnak{at}tufts-nemc.org

Received for publication March 1, 2005. Accepted for publication July 27, 2005.

Anemia is a potential nontraditional risk factor for cardiovascular disease (CVD). This study evaluated whether anemia is a risk factor for adverse outcomes in people with diabetes and whether the risk is modified by the presence of chronic kidney disease (CKD). Persons with diabetes from four community-based studies were pooled: Atherosclerosis Risk in Communities, Cardiovascular Health Study, Framingham Heart Study, and Framingham Offspring Study. Anemia was defined as a hematocrit <36% in women and <39% in men. CKD was defined as an estimated GFR of 15 to 60 ml/min per 1.73 m². Study outcomes included a composite of myocardial infarction (MI)/fatal coronary heart disease (CHD)/stroke/death and each outcome separately. Cox regression analysis was used to study the effect of anemia on the risk for outcomes after adjustment for potential confounders. The study population included 3015 individuals: 30.4% were black, 51.6% were women, 8.1% had anemia, and 13.8% had CKD. Median follow-up was 8.6 yr. There were 1215 composite events, 600 MI/fatal CHD outcomes, 300 strokes, and 857 deaths. In a model with a CKD-anemia interaction term, anemia was associated with the following hazard ratios (95% confidence intervals) in patients with CKD: 1.70 (1.24 to 2.34) for the composite outcome, 1.64 (1.03 to 2.61) for MI/fatal CHD, 1.81 (0.99 to 3.29) for stroke, and 1.88 (1.33 to 2.66) for all-cause mortality. Anemia was not a risk factor for any outcome in those without CKD (P > 0.2 for all outcomes). In persons with diabetes, anemia is primarily a risk factor for adverse outcomes in those who also have CKD.

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