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Anemia and Iron Deficiency Linked to Mortality in HF

— Both common in heart failure, British study finds

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Anemia is common in chronic heart failure (HF), and along with iron deficiency is associated with increased mortality, a study showed.

Among patients referred to a single outpatient clinic for suspected HF, by the World Health Organization definition, of the University of Hull in England, and colleagues reported online in

That proportion with anemia rose among those actually diagnosed with HF (versus 13.4% in those without):

  • 33.3% among patients with confirmed left ventricular systolic dysfunction (LVSD)
  • 32.8% in HF with preserved ejection fraction (HFpEF) type 1
  • 34.0% in HFpEF type 2

The proportion with iron deficiency by liberal criteria was 75.5%.

The results also demonstrated an association with higher rates of all-cause mortality, "mostly driven by cardiovascular deaths," for both lower hemoglobin levels (HR 0.92, 95% CI 0.89-0.95; P<.001) and lower serum iron concentrations (HR 0.98, 95% CI 0.97-0.99; P=0.007).

Based on a range consisting of conservative to liberal criteria for low serum iron concentration or transferrin saturation, patients who had anemia were more likely to have low transferrin saturation (43.2%-68%), when compared with patients who did not have anemia (14.7%-35.2%).

Anemia and iron deficiency are both potential therapeutic targets among patients with HF, the researchers noted, because "anemia, regardless of its cause, will increase cardiac demand, which could have a deleterious effect on symptoms and prognosis. Iron deficiency may also be important in HF because it is an essential component of myoglobin and the mitochondrial respiratory chain."

Notably, they added, "Elimination of iron or hemoglobin from the multivariable model strengthened the association of the other with outcome. Therefore, it is likely that both the severity of anemia and iron deficiency contribute to an adverse outcome in patients with HF."

Participants who were recruited for the research had been referred to a community-based outpatient clinic in England because of suspected HF, and had an average age 73. Out of the 4,456 participants, 60.5% were male.

They were required to complete a questionnaire, and to undergo a clinical exam, an electrocardiograph, and an echocardiogram. Patients were tracked by electronic records for as many as 10 years following baseline data collection; but all but 294 patients were followed up for at least 3 years.

While specific causes of anemia are difficult to identify, the authors offered a few possible explanations. These included but were not limited to worsening congestion, renal dysfunction leading to reduced red blood cell mass, and impaired nutrition. They also noted that some pharmacologic therapies for HF have been linked to decreases in hemoglobin concentration.

The authors noted that the varying definitions for HF, anemia, and iron deficiency make the outcomes more difficult to assess. Additional limitations mentioned were that patients were only recruited from a single center and that the majority of the participants were white.

These results can be used in the future by helping researchers create clinical trials aimed at treating anemia, iron deficiency, or both through specific interventions.

Disclosures

Support for the research was provided by the National Heart Service, the U.K. government, and Vifor Pharma and Amgen.

Cleland reported receiving research support from Amgen, which manufactures darbepoetin alfa, and Vifor Pharma, which manufactures IV formulations of iron.

Primary Source

JAMA Cardiology

Cleland J, et al "Prevalence and outcomes of anemia and hematinic deficiencies in patients with chronic heart failure" JAMA Cardiol 2016; DOI: 10.1001/jamacardio.2016.1161,