Coronary Artery Disease Mortality Predicted by Anemia

Findings reported in the American Journal of Medicine reveal that low hemoglobin levels independently predict mortality in patients with stable coronary artery disease (CAD).1

Anemia is both a general risk factor for cardiovascular disease and a predictor of adverse outcomes in patients with acute coronary syndrome.2 It is possible that anemia could influence CAD progression via increased inflammation.3 “However, coexisting conditions (cardiovascular and other) are also intricately related to both inflammation and hemoglobin levels and it remains uncertain as to whether anemia is causally implicated in adverse outcomes or whether it is a marker of other, or advanced, disease” such as heart failure, the researchers wrote.

Researchers from multiple international universities analyzed data from the Prospective Observational Longitudinal Registry of Patients With Stable Coronary Artery Disease (CLARIFY) to examine the relationship between hemoglobin levels over time and 4-year mortality, cardiovascular events, and major bleeding. The 21,829 participants with baseline hemoglobin levels were divided into groups based on anemic (A) or normal (N) status at baseline and follow-up: N/N, A/N, N/A, and A/A.

The mean age of participants (77.4% male) was 64±10 years. Mean hemoglobin was 14.0±1.5 g/dL, and 11% of men and 13.1% of women were anemic at baseline. The following results were observed.

  • Low hemoglobin levels at baseline independently predicted all-cause, cardiovascular, and noncardiovascular mortality; the composite of cardiovascular death, myocardial infarction, or stroke; and major bleeds (all P <.001; unadjusted models).
  • Anemia detected at follow-up was independently associated with all-cause mortality (hazard ratio [HR], 1.90; 95% CI, 1.55-2.33 for A/A and HR, 1.87; 95% CI, 1.54- 2.28 for N/A; both P <.001) and cardiovascular and noncardiovascular mortality (P =.001 and P <.001, respectively).
  • Patients who had anemia at baseline but not at follow-up did not show an increased risk of mortality (HR, 1.02; 95% CI, 0.77-1.35), although they did demonstrate a higher risk of major bleeding (HR, 2.06; 95% CI, 1.23-3.44; P =.013).

“Persisting or new onset anemia is a powerful predictor of cardiovascular and noncardiovascular mortality,” the researchers wrote. Further research should aim to elucidate the cause of low hemoglobin in these cases and the potential to improve outcomes by increasing hemoglobin levels.

“In current clinical practice hemoglobin level should be considered an important marker in terms of assessment of prognosis and bleeding risk,” the investigators noted.


Funding for this research was supported by grants from Servier.

Drs Kaira, Danchin, Ferrari, Tardif, Tendera, Fox, and Steg report receiving personal and other fees from Servier. Ms Greenlaw and Mr Ford also report receiving fees from Servier. Study researchers also report financial relationships with several other pharmaceutical companies, including Amgen, Bayer, Boehringer Ingelheim, Eli Lilly, Novartis, and Novo Nordisk, among others. 

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  1. Kalra PR, Greenlaw N, Ferrari R, et al; for the CLARIFY Investigators. Hemoglobin and change in hemoglobin status predict mortality, cardiovascular events and bleeding in stable coronary artery disease [published online January 18, 2017].  Am J Med. doi:10.1016/j.amjmed.2017.01.002
  2. Ang DS, Kao MP, Noman A, Lang CC, Struthers AD. The prognostic significance of early and late anaemia in acute coronary syndrome. QJM. 2012;105(5):445-454. doi:10.1093/qjmed/hcr258

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