NHLBI Workshop on C-Reactive Protein: Basic and Clinical Research Needs
July 10-11, 2006

CRP and Lifestyle Factors: How Modifiable is CRP by Changes in Adiposity and Lifestyle Behaviors?
JoAnn E. Manson

C-reactive protein (CRP) levels are highly correlated with several lifestyle factors and responsive to behavioral changes. In particular, obesity and degree of adiposity are major determinants of CRP levels and weight loss has been shown to reduce these levels. In the large-scale Women's Health Study, women in the top quartile of body mass index (BMI) were 12 times more likely than women in the lowest quartile to have elevated levels of hsCRP (RR 12.2, 95% CI 6.44-23.0) after adjustment for other measured risk factors. There is moderately strong evidence that abdominal adiposity is more highly correlated with CRP levels than lower body obesity. Several randomized clinical trials of weight loss provide compelling evidence that weight reduction leads to favorable changes in CRP levels. Moreover, weight loss following gastric bypass surgery in morbidly obese patients has been linked to reductions in CRP. Although weight loss and reduced adiposity are associated with lower CRP levels, it remains unclear whether any of the favorable effects of weight loss on insulin resistance and other cardiovascular risk factors are directly mediated by the CRP changes.

The relationship between physical activity and CRP is less clear than that for adiposity. Several observational studies indicate that men and women who engage in regular physical activity have lower CRP levels, but the contribution of differences in adiposity remains controversial. Although most analyses control for BMI or other measures of body fatness, the possibility of residual confounding by this variable cannot be excluded. Several studies suggest a much stronger association of CRP with adiposity than with physical activity level. In a recent systematic review of studies of physical activity and CRP, the authors concluded that exercise produces a short-term inflammatory response (an acute phase response, particularly after strenuous exercise) but a longer-term "anti-inflammatory" response with longitudinal exercise training and habitual physical activity. The contribution of adiposity changes to the latter response has not been fully elucidated.

Several other lifestyle factors influence CRP levels, including smoking (and smoking cessation), alcohol consumption, and multiple dietary factors. CRP levels are clearly higher in smokers than in nonsmokers, and past smokers have CRP levels that are lower than those of current smokers and only marginally higher than those of never smokers. In terms of alcohol, CRP levels appear to be lower in moderate drinkers than in nondrinkers, but the relationship may be U-shaped. A limited body of research on diet and CRP suggests that certain dietary factors, including oleic acid, a-linolenic acid, and RRR-a-alpha tocopherol, reduce CRP and other biomarkers of inflammation. Conflicting data have been reported for saturated and trans fatty acids, marine omega-3 fatty acids, cholesterol, high glycemic-load diets, and soy. Finally, several medications including estrogen therapy, statins and other lipid-modulating agents, anti-inflammatory medications, hypoglycemic agents, and many other pharmacologic interventions appear to modify levels of CRP.

In view of the strong association between several lifestyle and behavioral factors and levels of CRP, it is important to understand whether CRP is an important mediator of related pathophysiology or a non-causal correlate. Reduced adiposity and favorable changes in cardiovascular risk factors may be related to lower CRP levels, but whether CRP changes can directly impact insulin resistance and cardiovascular risk remains a subject of ongoing debate.

References

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  3. Kasapis C, Thompson PD. The effects of physical activity on serum C-reactive protein and inflammatory markers. J Am Coll Cardiol 2005;45:1563-9.
  4. Nicklas BJ, You T, Pahor M. Behavioural treatments for chronic systemic inflammation: effects of dietary weight loss and exercise training. CMAJ 2005;172:1199-1209. (also for obesity/weight loss)
  5. Plaisance EP, Grandjean PW. Physical activity and high-sensitivity C-reactive protein. Sports Med 2006;36:443-58.
  6. Okita K, Nishijima H, Murakami T, et al. Can exercise training with weight loss lower serum C-reactive protein levels? Arterioscler Thromb Vasc Biol 2004;24:1868-73.
  7. The Diabetes Prevention Program Research Group. Intensive lifestyle intervention or Metformin on inflammation and coagulation in participants with impaired glucose tolerance. Diabetes 2005;54:1566-72.
  8. Basu A, Devaraj S, Jialal I. Dietary factors that promote or retard inflammation. Arterioscler Thromb Vasc Biol 2006;26:995-1001.
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