Usefulness of Relative Hypochromia in Risk Stratification for Nonanemic Patients With Chronic Heart Failure

The purpose of this study is to investigate the impact of a reduction of hemoglobin (Hb) content in the erythrocytes as estimated by mean corpuscular hemoglobin concentration (MCHC) on long-term clinical outcomes in nonanemic patients with heart failure (HF). We prospectively enrolled 1,579 subjects with HF who underwent coronary angiography enrolled in the GeneBank study with 5-year follow-up of all-cause mortality. Levels of Hb and MCHC were assessed at enrollment and after 6 months of follow-up. Anemia was defined as Hb levels <13 g/dl in men and <12 g/dl in women. In our nonanemic cohort (n = 785, 49.7%), mean Hb and median MCHC were 13.8 ± 1.1 g/dl and 34.3 g/dL (interquartile range 33.6 to 35), respectively. Nonanemic patients with heart failure with lower MCHC had higher mortality risk (quartiles 1 vs 4, hazard ratio = 2.1, 95% confidence interval 1.4 to 3.3, p = 0.001). In a subset of nonanemic patients with persistent normal Hb on follow-up (n = 206), the mean time between baseline and follow-up MCHC levels was 169.3 ± 41.6 days. In comparison with patients with levels of MCHC more than the first quartile (≥33.6 g/dl) on baseline and follow-up, patients with persistently low MCHC (<33.6 g/dl) had a significantly increased mortality risk (log rank <0.001). All models remained significant even after adjusting for traditional cardiac risk factors, left ventricular ejection fraction, baseline Hb levels, and mean corpuscular volume. In conclusion, relative hypochromia is an independent predictor of increased mortality risk in patients with HF, even in the setting of normal Hb levels.