Anemia Associated With Increased Mortality Risk Up to 12 Months After Stroke

Deborah Brauser

August 24, 2016

Anemia not only is highly prevalent in older adult patients with acute stroke but can also increase the risk for post-stroke mortality by twofold, new research suggests.

A database study of more than 8000 stroke patients in the United Kingdom (UK) showed that 25% had anemia upon hospitalization. In addition, there was a significant association between the condition and increased mortality risk for up to 1 year after an ischemic or hemorrhagic stroke.

An additional systematic review of 20 studies, with a total population of almost 30,000 stroke patients, showed that the odds of dying within 12 months of having had a hemorrhagic stroke were 1.5 times greater for those with anemia than those without. And the mortality odds were twice as great for patients with anemia who had had an ischemic stroke.

"What is surprising is the magnitude of effect we see from the impact of anemia as a potentially modifiable risk factor," principal investigator, Phyo K. Myint, MD, professor of medicine of old age at the University of Aberdeen, Scotland, told Medscape Medical News via email.

"Clinicians should be aware of this new knowledge and appropriately manage stroke patients with anemia," said Dr Myint.

Dr Phyo K. Myint

He added that because it isn't currently known whether "simply correcting the anemia in stroke" can improve outcomes, clinicians will need to decide the best management strategy for their individual patients.

The database study also showed that elevated levels of hemoglobin were significantly associated with increased mortality risk, especially during the first month after stroke.

"This suggested a U-shaped relationship between hemoglobin levels and short-term mortality," write the investigators.

All of the findings were published online August 17 in the Journal of the American Heart Association.

UK Stroke Register

The researchers first analyzed records from a UK Regional Stroke Register for 8013 patients (52.4% women; mean age, 77.8 years; 86.7% with ischemic stroke) who were admitted to a hospital between January 2003 and May 2015.

At admission, 26.7% of the men and 22.5% of the women had anemia, defined as hemoglobin levels less than 13 or 12 g/dL for the men and women, respectively. Elevated hemoglobin was defined as levels greater than 17 or 15.5 g/dL, respectively.

Associations between anemia and hemoglobin levels with mortality were evaluated at several time points, including 1, 3, and 6 months and 1 year after a stroke had occurred. The overall inpatient mortality rate was 21.3%.

In the men with ischemic stroke, those with anemia had increased mortality rates at all time measures compared with those with "normal" levels of hemoglobin (13.8 to 14.6 g/dL). The odds ratio (OR) for mortality was 1.8 at admission and climbed steadily to 2.3 at 1 year.

Among the men with hemorrhagic stroke and anemia, their mortality rate was significantly greater than that among men in the normal hemoglobin group at 1 year (OR, 1.8).

The mortality ORs among female ischemic stroke patients with anemia ranged from 1.3 at the 1-month follow-up to 1.5 at the 1-year point compared with the women who had normal hemoglobin levels.

The association between mortality and anemia was also significant at all time points for the women with hemorrhagic stroke, with ORs ranging from 1.8 to 2.1.

The following table shows the association between elevated hemoglobin and 1-month mortality ORs vs normal hemoglobin levels for the patient groups.

Table. Association Between Elevated Hemoglobin and 1-Month Mortality vs Normal Hemoglobin

Patient/Stroke Type OR for Elevated Hemoglobin (95% Confidence Interval)
Male, ischemic 1.79 (1.00-3.20)
Male, hemorrhagic 2.90 (1.08-7.75)
Female, ischemic 1.49 (1.00-2.21)
Female, hemorrhagic 2.11 (0.92-4.82)

 

The investigators then evaluated 20 trials on anemia and mortality from the Embase and MEDLINE databases conducted up to December 2014. They combined these stroke populations with the earlier study's population for a total of 29,943 stroke patients assessed.

When the meta-analysis examined the studies that focused on ischemic stroke, the pooled OR for mortality for those with anemia upon hospitalization was 1.97 (95% confidence interval [CI], 1.57 - 2.47; overall effect, P < .00001).

In the studies that focused on hemorrhagic stroke, the OR for mortality for the patients with anemia was 1.46 (95% CI, 1.23 - 1.74; overall effect, P < .0001).

In other words, "stroke patients with anemia were 1.5 to 2 times more likely to die," said Dr Myint.

This second part of their research "provided robust evidence to support the findings of our primary database study," he added.

That said, the investigators note that the "optimal treatment option in this patient group is unclear." Therefore, more studies are needed to assess the "cost-effectiveness of interventions in this patient population in an acute stroke setting."

"Brings More Data to the Table"

"I think this is a great starting point and nicely synthesizes the data," said Philip B. Gorelick, MD, professor of translational science and molecular medicine at Michigan State University College of Human Medicine, Grand Rapids, and medical director of the Mercy Health Hauenstein Neuroscience Center, when invited to comment.

Dr Philip B. Gorelick

"We know that anemia in and of itself has not been recognized as a well-documented risk factor for stroke, with the exception of sickle cell disease. Most people don't have that disease but quite a few people, especially as they get older, have anemia," he said.

"This new paper brings a lot more data to the table, which I think is important."

Dr Gorelick, who is a past chair of the International Stroke Conference, was not involved with this research.

He noted that the finding that one fourth of the database study patients had anemia at admission wasn't surprising, and he pointed out that this older population "had their share of other risk factors," such as coronary heart disease (in 30% of the men with anemia and 24% of the women), atrial fibrillation (21% vs 22%, respectively), and hypertension (42% of each group).

As for the association between increased mortality risk and higher levels of hemoglobin, Dr Gorelick echoed the investigators, calling this a U-shaped relationship. "As often shown in epidemiology, not enough or too much of something may not be a good thing in a population."

When asked what he thinks is the study's overall take-away message, he said that "we should put our practitioners on alert that anemia should be considered as a possible predictor of stroke."

"There might be something here. But because we don't yet know whether treating the anemia with red blood cells or other means will reduce stroke, I'd say: let's look for the cause of the anemia, correct that, and then hopefully the anemia will go away," Dr Gorelick concluded.

The study was funded by the Norfolk and Norwich University Hospital (NNUH) NHS Foundation Trust Stroke Services and by the NNUH Research and Development Department. Dr Myint reports having once received honorarium of less than £1000 from ViForPharma as an advisory panel member. The other study authors and Dr Gorelick have disclosed no relevant financial relationships.

J Am Heart Assoc. Published online August 17, 2016. Full text

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