ORLANDO, FLA. — The presence of inflammatory markers, a low hemoglobin, or both is superior to traditional cardiovascular risk factors for predicting adverse cardiovascular outcomes in women under evaluation for suspected myocardial ischemia, Christopher B. Arant, M.D., said at the annual meeting of the American College of Cardiology.
The standard cardiovascular (CV) risk factors appear to considerably underestimate the true risk of CV events in women presenting with chest pain, added Dr. Arant, a cardiologist at the University of Florida, Gainesville.
He reported on 595 women, mean age 58 years, who underwent coronary angiography as part of an evaluation for suspected myocardial ischemia in the National Heart, Lung, and Blood Institute-sponsored Women and Ischemia Syndrome Evaluation (WISE).
During a mean 3.6 years of follow-up, all-cause mortality among the women was 7%, and the rate of an MI, heart failure, stroke, another vascular event, or death was 20%. Yet the predicted 10-year risk of a CV event in WISE participants based on their Framingham Risk Score was a mere 4.6%. This underestimate shows the need for better methods of recognizing women at high risk.
Inflammation plays a key role in atherosclerosis and its complications, perhaps even more so in women than in men. Dr. Arant and his coinvestigators previously examined the predictive power of three inflammatory markers—C-reactive protein, interleukin-6, and serum amyloid A—and showed they were strong predictors of CV risk in the WISE cohort. They also established that hemoglobin level was an independent predictor of adverse CV outcomes.
In their new study, they showed that adding a hemoglobin level below 12 g/dL to the three inflammatory markers created a four-biomarker combination that incrementally and independently predicted CV events in the WISE study women.
In a Cox multivariate regression analysis, the only traditional risk factors that predicted CV events were diabetes, associated with a 79% increase in risk, and obstructive coronary artery disease on angiography, which increased risk by 65%.
In contrast, the presence of any one of the four biomarkers was associated with a 90% increased risk of CV events during follow-up. Two positive biomarkers conferred a 192% increased risk. Women with three had a 368% increased risk, and those with four abnormal biomarkers had a 550% increased risk.
The same graded relationship held true between abnormal biomarkers and all-cause mortality. The risk of death increased 4.5-fold in women with one abnormal biomarker, compared with those with none, and 19.2-fold in those with four biomarkers.
The mean hemoglobin in the WISE cohort was 12.9 g/dL. Why a modest reduction to below 12 g/dL was predictive of CV events in the WISE population remains speculative. Hemoglobin is not an obvious marker of inflammation. Previous data have suggested hemoglobin is an independent predictor of CV events and acute MI.
A possibility is that mild anemia may reflect bone marrow underproduction of red blood cells due to systemic inflammation. However, the observation that adding hemoglobin to the three inflammatory markers yielded an incremental increase in event risk in WISE suggests a low hemoglobin may be acting directly to increase risk.
Studies of sickle cell anemia patients suggest that hemoglobin may be important in the transport of nitric oxide, known to play a key role in endothelial function.
A clinical pearl from the WISE chest pain registry is that women with cardiac ischemia have a very high prevalence of atypical angina. “We like to say any pain above the waist in women who have risk factors requires a good history and physical exam and really needs to be considered as an anginal equivalent,” he said.