CRP provides another reason to lose weight and gain heart health

February 04, 2002

DALLAS, Feb. 5 - Losing weight may lower blood levels of the inflammatory marker called C-reactive protein (CRP), a factor associated with an increased risk of heart disease, according to a report in today's Circulation: Journal of the American Heart Association.

On average, CRP levels were reduced by 32.3 percent, from 3.06 to 1.63 micrograms per milliliter (m/ml), after a weight loss of approximately 15 kilograms (33 pounds), reports primary researcher André Tchernof, Ph.D., formerly from the department of medicine at the University of Vermont, Burlington. Tchernof now works in the molecular endocrinology lab in Quebec City, Canada.

Researchers measured CRP levels before and after a weight-loss study conducted in the greater Burlington, Vt., area. The study included 61 obese postmenopausal women, average age 56. Obesity is defined as a body mass index higher than 30 kg/m2. Body mass index assesses body weight relative to height. All the women in the study were physically inactive, nonsmokers and nondiabetic.

Before and after the weight-loss protocol, researchers measured body composition and body fat distribution using radiological and imaging techniques. Blood samples were taken to obtain lipid profiles, estrogen measurements and plasma CRP levels.

"Other studies have shown that obese patients are usually characterized by increased plasma CRP, possibly because fat tissue releases a factor called interleukin-6, which in turn stimulates CRP production in the liver," says Tchernof. "Based on these previous studies, we hypothesized that a reduction in fat tissue mass would lower plasma CRP levels in obese women." Twenty-five women participated in the weight-loss portion of the study. They underwent a weight stabilization period before and after the program. A registered dietitian who helped the women choose their food, with or without using a fasting supplement, supervised the weight-loss program. The weight was lost over an average of 13.9 months, including the stabilization period before metabolic testing. The women were encouraged not to change their level of physical activity during the weight-loss program. Average weight loss was 14.5 kg (a 15.6 percent reduction), including an average loss of 10.4 kg in fat mass (a 25 percent reduction). Abdominal fat was reduced by 36.1 percent, and subcutaneous (under the skin) fat dropped 23.7 percent. Glucose disposal, an index for insulin sensitivity, increased by 33.2 percent. "During the weight-loss protocol, total body fat loss was a better predictor of plasma CRP changes than abdominal fat loss. Thus, from our results, we cannot determine whether plasma CRP levels are related more closely to abdominal fat distribution or total body fatness," says Tchernof.

"The women also lost approximately 3 kg in muscle mass. However, the loss of muscle mass was not related to the change in CRP," he says. "It really looks like fat loss is the best predictor of CRP changes."

The reduction in CRP was proportional to the magnitude of fat loss. In response to the weight loss, insulin sensitivity and the cardiovascular disease risk profile of the women improved significantly. The plasma CRP reduction was apparently not related to estrogen levels or the use of cholesterol-lowering drugs or aspirin, which are known to affect CRP levels. The mechanisms correlating the degree of obesity to circulating CRP levels have yet to be determined, but Tchernof says one theory is particularly compelling.

"The hypothesis that inflammatory factors (particularly interleukin-6 and TNF-alpha) mediate the link between fat accumulation and plasma CRP levels has been put forth by several other investigators," he says. The team is examining whether estrogen and menopausal status can affect the release of interleukin-6 in fat tissue.

Researchers from Italy reported in the Jan. 15 rapid access publication of Circulation: Journal of the American Heart Association a study that found weight gain, particularly in the abdominal area, appears to raise the amount of cytokines and other inflammatory substances that can contribute to artery clogging, increasing the risk for heart disease.

The new study provides more evidence that weight loss may be an effective way to reduce inflammation and thus reduce heart attack risk, says Tchernof.

Co-authors of the study include Amy Nolan, R.D.; Cynthia K. Sites, M.D.; Philip A. Ades, M.D.; and Eric T. Poehlman, Ph.D. The work was funded in part by the National Institutes of Health.
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