Abstract

Background: We previously reported that functional iron deficiency, assessed by low mean corpuscular hemoglobin concentration (MCHC), has been associated with adverse outcomes in non-anemic patients with HF. Yet, the effect of change in MCHC levels on outcomes has not been studied before. Methods: We prospectively enrolled 1,579 subjects with HF undergoing coronary angiography, with 5-year follow-up. Blood indices [hemoglobin (Hb), MCHC, MCV, RDW] were assessed on enrollment and after 6 months of follow up by reviewing medical records. Anemia was defined as Hb levels <12 g/dL in males, and <11 g/dL in females. Results: In our population (age 66 ± 10 years, male 65%, CAD 75%), most patients were non-anemic (n=1,161, 73.5%). In non-anemic patients, mean Hb and median (IQR) MCHC were 13.3±1.2 g/dL and 34.2 (33.43-34.9) g/dL, respectively. Non-anemic HF patients with lower MCHC had higher mortality risk [Q1 vs Q4 Hazard ratio (HR) (95%CI) of 2.5(1.9-3.2), p<0.001]. Total of 552 (35%) had follow up Hb levels with a mean time between baseline and follow up levels of 169.3 ± 41.6 days. HF severity (EF, BNP), outcomes and blood indices were similar in patients with and without follow up levels, suggesting good representation of the total population. Changes in MCHC levels was studied in non-anemic patients on baseline and follow up (n=318). Most patient with low MCHC at baseline (<Q1, n=79) continued to have low MCHC on follow up (n=61), while half of the patients with high baseline MCHC (≥Q1, n=239) developed low MCHC on follow up (n=120). In comparison to patient with persistently high MCHC, patients with persistently low MCHC had a significantly increased mortality risk [HR(95%CI) of 3.5(2.1-6.1), p<0.001]. All models remained significant even after adjusting for traditional CAD risk factors, EF and baseline blood indices. Conclusion: Relative hypochromia is an independent predictor of increase mortality in patients with HF, even in the setting of normal hemoglobin levels.

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