Letter by Andreotti et al Regarding Article, “Hemoglobin Level, Chronic Kidney Disease, and the Risks of Death and Hospitalization in Adults With Chronic Heart Failure: The Anemia in Chronic Heart Failure: Outcomes and Resource Utilization (ANCHOR) Study”
To the Editor:
We read with interest the study by Go and colleagues1 in which the authors report that among 59 772 adults with chronic heart failure, hemoglobin concentrations ([Hb]) <13 g/dL and glomerular filtration rates (GFR) <45 mL/min per 1.73 m2 significantly predicted an increased risk of dying during the next 7 years (independently of each other, of age, and of left ventricular systolic function) compared with [Hb] of 13.0 to 13.9 g/dL and GFR ≥60 mL/min per 1.73 m2. The adjusted hazard ratio for death ranged from 1.2 (with [Hb] of 12 to 12.9 g/dL) to 3.5 (with [Hb] <9 g/dL) and from 1.4 (with GFR of 30 to 44 mL/min per 1.73 m2) to 3.3 (with GFR <15 mL/min per 1.73 m2). The authors invoke bone marrow depression, impaired erythropoietin production or function, tissue hypoxia, nutritional deficiencies, drug-induced side effects, fluid and neurohormonal imbalances, and accelerated ventricular remodeling as possible reasons for their findings.1
We suggest an additional interpretation for the observations by Go and colleagues. Depressed progenitor cell availability, through blunted cardiovascular repair mechanisms, may contribute to explain the higher risk of death associated with low [Hb] and impaired kidney function.2 Ischemic heart disease is the most common cause of heart failure,1 and low [Hb], kidney dysfunction, and reduced circulating CD34+ progenitor cells are emerging as powerful predictors of death among ischemic heart disease patients.3,4⇓ Interestingly, endothelial nitric oxide synthase is essential for progenitor cell mobilization.2
We have investigated the relation among [Hb], GFR, and the number of circulating CD34+ in 52 hemodynamically stable ischemic heart disease patients. As expected, admission values of [Hb] were associated with GFR (P=0.002, r=0.39).4 However, only [Hb] (P=0.009, β=0.42)—and not GFR (P=0.65)—significantly predicted the number of circulating CD34+. Additionally, [Hb] predicted CD34+ in patients with GFR >45 mL/min per 1.73 m2 (n=46, P=0.02, β=0.37) and also in those with GFR <45 mL/min per 1.73 m2 (n=6, P=0.006, beta=1.01). Among 83 similar ischemic heart disease patients, we investigated the relation between [Hb] and endogenous plasma nitric oxide metabolites. On multivariable analysis, reduced nitric oxide bioavailability (P=0.01), but not C-reactive protein (P=0.33), white cell count (P=0.35), serum creatinine (P=0.25), or other potential confounders, independently predicted admission [Hb] <13 g/dL.5
We propose that low [Hb] may signal bone marrow depression, reduced CD34+ bioavailability, and impaired nitric oxide function, both in the presence and absence of kidney disease, representing a potentially powerful and integrated marker of cardiovascular risk.
Go AS, Yang J, Ackerson LM, Lepper K, Robbins S, Massie BM, Shlipak MG. Hemoglobin level, chronic kidney disease, and the risks of death and hospitalization in adults with chronic heart failure. The Anemia in Chronic Heart Failure: Outcomes and Resource Utilization (ANCHOR) Study. Circulation. 2006; 113: 2713–2723.
Andreotti F, Becker RC. Atherothrombotic disorders. New insights from hematology. Circulation. 2005; 111: 1855–1863.
Sabatine MS, Morrow DA, Giugliano RP, Burton PB, Murphy SA, McCabe CH, Gibson CM, Braunwald E. Association of hemoglobin levels with clinical outcomes in acute coronary syndromes. Circulation. 2005; 111: 2042–2049.
Andreotti F, Coluzzi G, Lavorgna A, Marzo F, Di Stasio E, Carrozza C, Zuppi C, Crea F. Relation between nitric oxide metabolites and haemoglobin concentrations in patients with ischemic heart disease. Heart. 2007; 93: 255–257.