Low hemoglobin levels associated with worse outcome in ACS patients

April 14, 2005

Boston, MA - Anemia is a powerful and independent predictor of major adverse cardiovascular events in ACS patients, according to a new analysis of data from the TIMI studies published online April 11, 2005 in Circulation.[1]

The researchers, led by Dr Marc Sabatine (Brigham and Women's Hospital, Boston, MA), say that a randomized trial is now needed to identify the level at which anemia should be treated in these patients.

In the paper, the researchers note that in animal models, higher hemoglobin concentrations prevent ischemia in the setting of significant coronary artery stenosis, and in human studies, anemia has been shown to be an independent risk factor for adverse cardiovascular outcomes in community cohorts, patients with heart failure, and patients undergoing PCI. However, few studies have specifically examined anemia in patients with ACS.

To gather information on the ACS population, Sabatine et al used data from almost 40 000 ACS patients included in various TIMI trials and examined the association between baseline hemoglobin concentration and a range of cardiovascular clinical outcomes.

After adjustment for differences in baseline characteristics and index hospitalization treatments, they found a strong association between lower hemoglobin values and major adverse cardiovascular events. In patients with ST-elevation MI, cardiovascular mortality increased as hemoglobin levels fell below 14 g/dL, with an odds ratio of 1.21 for each 1-g/dL decrement. In patients with non-ST-elevation ACS, the likelihood of cardiovascular death, MI, or recurrent ischemia increased as the hemoglobin fell below 11 g/dL, with an OR of 1.45 for each 1-g/dL decrement.

Reverse J-shaped curve

But the researchers also report the observation of a reverse J-shaped curve, with hemoglobin levels above a certain level (17 g/dL for MI patients and 16 g/dL for ACS patients) also associated with an increased risk of an adverse outcome.

Sabatine et al point out that anemia reduces oxygen delivery to the myocardium downstream of coronary stenosis, and it also increases the myocardial oxygen demand necessary to maintain adequate systemic oxygen delivery, which together may explain the relationship between worse outcomes with lower hemoglobin concentrations.

They suggest that the different thresholds for risk for STEMI and non-STEMI patients may reflect differences in the mechanisms by which anemia predisposes to adverse cardiovascular events in the two types of ACS: in STEMI, even mildly reduced hemoglobin concentrations at the abrupt onset of the coronary occlusion may be enough to affect the ability of collateral flow from nearby patent vessels to limit the extent of myocardial necrosis; whereas for non-STEMI ACS, in which the vessel is only partially occluded, a more profound degree of anemia may be necessary to predispose a patient to recurrent ischemic events.

The finding that very high hemoglobin levels were also associated with a greater risk for cardiovascular events can be explained by an increased blood viscosity, which leads to increased coronary vascular resistance and reduced coronary blood flow, they say.

Randomized trial needed

Sabatine told heart wire that AHA/ACC guidelines already recommend that ACS patients should be screened and treated for anemia, but no thresholds are given.

He explained that this study probably did not provide enough evidence to use the thresholds they observed, as the data were nonrandomized and should thus be considered hypothesis generating. "It is very hard to sort out at what level we should start transfusing patients without a randomized trial," he commented. He added, "Now clinicians make their own decisions. There is a gut instinct that says we like to keep hemoglobin levels above about 9 or 10 in patients with active coronary disease. That may be okay, or it may need to be a bit higher. It would therefore be a good idea to conduct a randomized trial in which patients receive transfusions at either x or y level of hemoglobin and see whether there is a difference in clinical outcome."

Long-term treatment may be needed

He also pointed out that a transfusion of red blood cells may not be sufficient to increase hemoglobin levels in the long term and that other treatments may need to be investigated. "There is the question of how quickly an infusion of red blood cells will work. It may be too late for a STEMI patient. We can't predict when a patient will have an ACS, but we know that if they come in with a low hemoglobin they are at higher risk, so for both STEMI and non-STEMI ACS patients, the aim should be to keep the hemoglobin level up long-term. To do this, we may need to give a red-blood-cell transfusion for the acute situation and then supplement this with something that will stimulate the red-blood-cell count, such as erythropoietin."

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