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CVD Risk Assessment and Risk Prediction: What does CRP add?
Peter Wilson

The relation between levels of C-reactive protein (CRP) and vascular disease risk has been investigated in several completed and ongoing projects from the Framingham Heart Study.

  • Rost et al (2001) assessed risk for stroke in the original cohort and found that elevated CRP levels were predictive of increased risk for ischemic cerebrovascular disease and the risk was increased for persons in the top quartile of CRP (RR =1.6 men, RR=2.1 women) after multivariable adjustment.
  • Rutter et al (2004) investigated the interaction between CRP and the metabolic syndrome and found that CRP levels were significantly related to the number of components of the metabolic syndrome that were present in both sexes. In a statistical model that predicted incident CVD events the top quartile of CRP and presence of the metabolic syndrome were both statistically associated with an increased risk for events.
  • Wilson et al (2005) estimated risk of vascular events according to level of CRP and found that CRP levels > 3.0 mg/L were associated with a significantly increased risk of Major CHD (RR=1.68, 95% CI 1.14-2.49) and Major CVD (RR=1.60, 95% CI 1.19-2.14) events in age- and sex-adjusted models, but the CRP>3.0 mg/L effects were no longer statistically significant for Major CHD (RR=1.22, 95% CI 0.81-1.84) or Major CVD (RR=1.22, 95% CI 0.90-1.66) in multivariable models. No increase in the area under the Receiver Operating Characteristic Curve was seen when CRP information was added to a prediction model that used traditional variables.
  • Wilson et al (2006, unpublished) assessed the role of hs-CRP and homocysteine (Hcys) levels on cardiovascular disease (CVD) risk in 3090 Framingham Offspring participants followed for 12 years and in an age-adjusted model that included both sexes and used CRP <1.00 mg/L as the referent level the relative risk for CVD and its components hard CHD (MI and CHD death), CHD (hard CHD and angina pectoris), and hard CVD (hard CHD and stroke) were increased for all outcomes in the category CRP > 3.0 mg/L. In a multivariable analysis of risk that also included age, sex, systolic blood pressure, total/HDL cholesterol ratio, diabetes mellitus, current smoking, hypertension treatment and homocysteine, a CRP level > 3.0 mg/L was associated with a 1.51 (95% confidence interval [C.I.] 1.12-2.04) relative risk for developing CVD. In a similar multivariable analysis the relative risk (RR) was increased for Hard CHD RR=1.63 (95% CI 1.03-2.59), CHD RR=1.31 (95% CI 0.92-1.89), and Hard CVD RR=1.74 (95%CI 1.15-2.63).
  • Wilson et al (2006, unpublished) examined the relation between CRP, other markers of inflammation, and risk of intermittent claudication for the Framingham Offspring with 8 years of follow up. The top tertile of CRP was associated with an increased risk of claudication (RR=3.58, 95% CI1.47-8.75) in analyses that were adjusted by age and sex and also increased in models that were adjusted for sex and Framingham Risk Score (RR=2.81, 95% CI 1.15-6.88).

In conclusion, these CRP results from Framingham Heart Study men and women show consistent but modestly greater relative risk for CVD and CHD events with increasing levels of CRP, but there is little evidence of improved discrimination, and there are stronger risks associated with incidence of cerebrovascular disease and intermittent claudication.

References

  1. Rost NS, Wolf PA, Kase CS, Kelly-Hayes M, Silbershatz H, Massaro JM, D'Agostino RB, Franzblau C, Wilson PW. Plasma Concentration of C-Reactive Protein and Risk of ischemic stroke and transient ischemic attack: The Framingham Study. Stroke 2001; 32(11):2575-2579.
  2. Rutter MK, Meigs JB, Sullivan LM, D'Agostino RB, Sr., Wilson PW. C-reactive protein, the metabolic syndrome, and prediction of cardiovascular events in the Framingham Offspring Study. Circulation 2004; 110(4):380-385.
  3. Wilson PW, Nam BH, Pencina M, D'Agostino RB, Sr., Benjamin EJ, O'Donnell CJ. C-reactive protein and risk of cardiovascular disease in men and women from the Framingham Heart Study. Arch Intern Med 2005; 165(21):2473-2478.

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