How well does the CRP test compare with other novel and emerging risk factors for vascular disease? This issue was directly addressed in the Women's Health Study, in this direct comparison of ten putative risk factors for vascular disease. In each case, the point estimate is based on being in the top versus bottom quartile for that particular analyte, and the horizontal bars represent the 95% confidence intervals for that effect. Starting from the top, we see that lipoprotein(a) screening was not a statistically significant predictor of risk, and below that, homocysteine screening, while statistically significant, was only of modest predictive value. This plot also indicates that the predictive value for LDL cholesterol, while highly statistically significant, sits approximately midway in terms of our overall risk prediction models. Interestingly, plasma levels of soluble intercellular adhesion molecule 1 (ICAM-1), a molecular marker associated with the adhesion and transmigration of leukocytes across the endothelial wall, as well as serum amyloid A (SAA), a nonspecific marker of inflammation, were in fact better markers of risk than was the LDL cholesterol or the total cholesterol level. Also of note from a clinical perspective, the best lipid marker was the total cholesterol:HDL cholesterol ratio. This finding is highly consistent with many prior epidemiologic studies and in fact is why many preventive practices prefer to use the ratio rather than any single lipid marker. However, the critical observation in this study was that plasma levels of hs-CRP on their own were actually the single strongest predictor for future vascular events, and those data are shown in the second line from the bottom. On its own, hs-CRP screening was associated with a 4.4-fold increase in risk for future vascular events among these otherwise healthy, middle-aged women. But again, the important issue is to consider combining the inflammatory screening with the lipid screening, and that is shown in the bottom line of data on the slide, suggesting that the combination of CRP level with total cholesterol: HDL cholesterol ratio provides the best overall risk estimate.

Reference:
Ridker PM, Hennekens CH, Buring JE, Rifai N. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med 2000;342:836-843.
WebsiteRidker PM et al. N Engl J Med 2000;342:836-843.