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We were interested to read the article by Al-Ahmad and colleagues (1)regarding the prognostic value of impaired renal function and anemia in patients with left ventricular (LV) dysfunction, published in the Journal of the American College of Cardiology. The investigators report that reduced kidney function and a low hematocrit are independent risk factors for increased all-cause mortality in patients with LV dysfunction, with there being a synergistic relationship between the two parameters. The results from this study, together with other work in the field (2), may have important clinical implications for the management of patients with chronic heart failure (CHF). However, we believe several points deserve further consideration.
The prognostic benefits of treating anemia in CHF and whether there is an optimal range of hematocrit for survival are not known. In the Framingham study, the impact of hematocrit on all-cause death as well as morbidity and mortality due to cardiovascular disease was shown to follow a U-shaped curve (3). Other prospective epidemiological studies of healthy populations have shown that the lowest mortality rate correlates with a mid-range hematocrit level in both genders and at all ages (4). Al-Ahmad et al. (1)assessed survival in patients subdivided according to hematocrit values <35%, 35% to 39%, and ≥40%. It is not clear why the investigators grouped all patients with a hematocrit value of ≥40% (n = 5,128, 77%) into one category. According to data from Europe and North America, the normal range of hematocrit for males is 40% to 53% and that of females 36% to 48% (5). Therefore, it would have been more appropriate to further subdivide patients with a hematocrit above 40%, enabling the impact of polycythemia on survival to be assessed. Heart failure is a procoagulant state, even for patients in sinus rhythm, and hence polycythemic patients are likely to be at particular risk of thrombotic events and would be expected to have a higher mortality.
In vitro studies have shown that angiotensin-converting enzyme inhibitors can lower hematocrit levels via the inhibition of erythropoietin synthesis. It would have been interesting to have assessed whether enalapril treatment resulted in a clinically significant change in hematocrit over time. Although Al-Ahmad et al. excluded patients with severe pulmonary disease from their study, whether patients with coexisting chronic obstructive pulmonary disease (COPD) were also excluded is not reported. This may be an important confounding factor as COPD is a well-recognized cause of secondary polycythemia.
The study by Al-Ahmad and colleagues (1)mostly investigated male (86%) and asymptomatic (62%) patients. The use of erythropoietin for the treatment of anemia in CHF is likely to benefit only symptomatic patients, particularly those with more advanced heart failure. Although the findings of Al-Ahmad et al. are clearly of significance, further studies are required to establish which patients should be targeted for erythropoietin therapy and whether there is an optimal range of hematocrit (or hemoglobin) for which one should aim.
- American College of Cardiology Foundation
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