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Clogged Artery Predictor Less Relevant as BMI Rises

Association between CRP and multiple measures of atherosclerosis was diminished and largely not significant in obese individuals.

The relationship between C-reactive protein and multiple measures of atherosclerosis is weakened as body mass index increases, researchers found.

Rising high-sensitivity CRP levels were associated with increased rates of coronary artery calcification in normal-weight and overweight men and in normal-weight women, but not in obese individuals of either sex, according to Amit Khera, MD, of the University of Texas Southwestern Medical Center in Dallas, and colleagues.

The findings, reported online in the Journal of the American College of Cardiology, were similar for two other measures of atherosclerosis — aortic wall thickness and aortic plaque burden.

CRP levels are known to be influenced by obesity. The inflammatory biomarker is primarily produced in the liver in response to interleukin-6, a cytokine released not only by atherosclerotic plaques, but also by adipose tissue.

“Thus,” Khera and colleagues wrote, “the predictive value of CRP for cardiovascular disease may be diminished in obese individuals, in whom the CRP signal from adipose tissue may predominate over the signal from underlying atherosclerotic disease.”

They noted also that the greater burden of risk factors in obese individuals may mask the cardiovascular risk signal of CRP.

The researchers examined data from 1,600 women and 1,299 men ages 30 to 65 (mean age 44 in men and 45 in women) participating in the Dallas Heart Study.

Coronary artery calcification was measured using CT and was defined as an Agatston score greater than 10 units. Aortic wall thickness and aortic plaque burden were assessed using MRI.

Using the traditional BMI cutoff 30 kg/m2 or greater, 38 percent of the men and 53 percent of the women in the study were obese.

In addition to the nonsignificant relationships between CRP levels and the three measures of atherosclerosis in obese individuals, the generally poor predictive ability of CRP for subclinical atherosclerosis overall tended to become even worse as BMI increased.

For both men and women, the c-statistics of CRP for the measures of atherosclerosis ranged from 0.552 to 0.643 in normal-weight individuals and from 0.509 to 0.595 in obese individuals.

In contrast, the Framingham risk score predicted all three measures of atherosclerosis, regardless of BMI.

The JUPITER trial, presented in 2008, concluded that CRP added to traditional risk factors was more accurate. The trial enrolled patients with a high baseline CRP and found that they benefitted from taking rosuvastatin in terms of a reduction of cardiovascular events.

BMI was not part of inclusion or exclusion criteria in JUPITER. However, the overall mean BMI was 27.4 ±5. In the group with low CRP (less than 2 mg/L), the mean BMI was 26 ±4. In the group with elevated CRP (≥2 mg/L), the mean BMI was 29.1 ±5. These mean figures are close to the BMI cutoff of 30 kg/m2 or greater used in the study by Khera and colleagues.

What the current findings mean in terms of past or future studies using CRP as a marker of atherosclerosis risk remains to be seen, particularly because the current work was not a randomized controlled study.

The authors acknowledged other limitations of the study, including the possibility that the reduced accuracy of CRP as a marker of atherosclerosis could reflect imprecision of the atherosclerosis measures in obese individuals, leading to misclassification bias.

In addition, they noted, the findings of the current study cannot be extrapolated to cardiovascular events.

“Because CRP may be a better marker of plaque instability than plaque presence, additional studies with clinical events are needed to clarify the relationship between CRP and cardiovascular outcomes in obese individuals,” they wrote.

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