C-Reactive Protein: How Has JUPITER Impacted Clinical Practice?

Abstract

Inflammation plays a pivotal role in all phases of atherosclerosis. High-sensitivity C-reactive protein (hsCRP), the best characterized biomarker of inflammation, is an independent predictor of future cardiovascular (CV) events and can add further insight to risk stratification. Assessment of hsCRP levels in clinical practice is feasible and inexpensive. Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) was a landmark primary prevention trial that enrolled 17,802 apparently healthy men and women with low-density lipoprotein cholesterol levels of less than 130 mg/dL and hsCRP levels of 2 mg/L or higher and randomly assigned them to rosuvastatin, 20 mg daily, or placebo. The trial demonstrated that treatment with statin was associated with significant lowering of hsCRP (37%), with 44% reduction in incident CV and 20% reduction in all-cause mortality. These compelling data from the JUPITER trial should encourage changes in our approach toward primary prevention of CV disease and lipid-lowering therapy, as these data shift the focus toward a link between inflammation, statin therapy, and prevention of atherosclerotic CV diseases.

Keywords: C-reactive protein; Cardiovascular disease; JUPITER; coronary artery disease; risk factor.

Figure 1

Age-adjusted relative risk of future cardiovascular events according to baseline C-reactive protein levels (solid bars) and low-density lipoprotein (LDL) cholesterol levels (open bars). (Reproduced with permission from Ridker PM, Rifai N, Rose L, Buring JE, Cook NR. N Engl J Med 2002; 347:1557–1565.11)

Figure 2

Cumulative incidence of cardiovascular events according to study group. Panel A shows the cumulative incidence of the primary end point (nonfatal myocardial infarction, nonfatal stroke, arterial revascularization, hospitalization for unstable angina, or confirmed death from cardiovascular causes). The hazard ratio for rosuvastatin, as compared with placebo, was 0.56 (95% confidence interval [CI], 0.46–0.69; P < .00001). Panel B shows the cumulative incidence of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes, for which the hazard ratio in the rosuvastatin group was 0.53 (95% CI, 0.40–0.69; P < .00001). Panel C shows the cumulative incidence of arterial revascularization or hospitalization for unstable angina, for which the hazard ratio in the rosuvastatin group was 0.53 (95% CI, 0.40–0.70; P < .00001). Panel D shows the cumulative incidence of death from any cause, for which the hazard ratio in the rosuvastatin group was 0.80 (95% CI, 0.67–0.97; P  =  .02). (Reproduced with permission from Ridker PM, Danielson E, Fonseca FA, et al. N Engl J Med 2008; 359: 2195–2207.12)

Figure 3

Median changes in high-sensitivity C-reactive protein (hsCRP) in patients undergoing cardiac rehabilitation and in control subjects with coronary artery disease (CAD). (Reproduced with permission from Milani RV, Lavie CJ, Mehra MR. J Am Coll Cardiol 2004; 43: 1056–1061.40)