Abstract. Coronary heart disease (CHD) is a major cause of morbidity and mortality in patients with chronic kidney disease or anemia. The purpose of this study was to examine whether the association between renal function and risk of CHD is modified by hemoglobin (Hgb) status. Analyses were based on data from the Atherosclerosis Risk in Communities study, a community-based study of risk factors for CHD in middle-aged people. People with known CHD at baseline were excluded from the analysis. Participants were followed for 9 yr for the occurrence of CHD. Anemia was defined as Hgb Ͻ13 g/dl in men and Ͻ12 g/dl in women. Cox proportional hazards models were used to assess the relative risk (RR) of CHD occurrence according to Hgb status, after adjusting for other risk factors (demographics, lipids, diabetes, hypertension, smoking, body mass index, and carotid intima-media thickness). A total of 13,329 participants were included. The interaction between Hgb concentration and serum creatinine (Scr) was significant (P ϭ 0.02). Among people with anemia, a Scr Ն1.2 mg/dl in women or Ն1.5 mg/dl in men was associated with a higher risk of CHD (RR, 2.74; 95% confidence interval, 1.42 to 5.28) than those with normal Scr. In contrast, among those without anemia, this association was not noted (RR, 1.20; 95% confidence interval, 0.86 to 1.67). In conclusion, this study indicates that high Scr is associated with almost a threefold risk of CHD among middle-aged people with anemia, whereas no increased risk is found in people with high Scr in the absence of anemia.Cardiovascular disease (CVD) mortality rates in ESRD are approximately 15 times higher than in the general population (1). Many studies examining the association between ESRD and cardiovascular mortality (2,3) have found that ESRD is an independent predictor of cardiovascular death. However, it is unclear whether moderate renal insufficiency is also associated with cardiovascular events. Previous studies conducted in patients at high risk of CVD have suggested that mild renal insufficiency may be an independent risk factor for cardiovascular events (4 -8). However, in analyses of population-based cohorts (9,10), there was no independent association between moderate renal insufficiency and cardiovascular mortality or nonfatal cardiovascular events after adjustment for traditional risk factors.Anemia is a frequent complication of chronic kidney disease (CKD) and is primarily due to failure of erythropoietin production to respond to decreased hemoglobin (Hgb) concentration (11,12). In chronic anemia, long-lasting flow/volume overload and increased cardiac work lead to progressive cardiac enlargement and left ventricular hypertrophy (13). The risk of coronary heart disease (CHD) increases when the anemia is not treated, and recent studies have indicated that anemia in patients with CKD may predispose to ischemic heart disease, heart failure, and premature death (14 -16). Therefore, the risk of CHD may be distinctly higher in people with renal insufficiency and concomitant ane...