Role of C-reactive protein in coronary risk reduction: focus on primary prevention

Given the limitations of current risk assessment strategies, adjunctive markers are needed to improve the prediction of a first coronary event. Research into the inflammatory nature of atherosclerosis suggests that inflammatory-response proteins may serve as potential predictors of clinical events. One in particular, C-reactive protein, has been the focus of much attention. Epidemiologic studies have shown a fairly consistent independent association between high-sensitivity C-reactive protein (hs-CRP) elevations and coronary risk, although a causal relation has not yet been established. Given this association, current guidelines recommend the optional use of hs-CRP to predict enhanced absolute risk in selected patients. The use of a marker in general clinical practice should be based on statistical measures that show incremental benefit over established risk factors and on randomized clinical trials in which therapy initiated as a result of marker screening improves patient outcomes. Thus far, statistical evidence concerning the incremental benefit of hs-CRP is not conclusive. Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) is now being conducted to compare the efficacy of statin therapy versus placebo in subjects considered to be at increased risk on the basis of hs-CRP elevations, despite low to normal levels of low-density lipoprotein cholesterol. In conclusion, although epidemiologic studies suggest that low-grade C-reactive protein elevations are independently associated with coronary risk, more complete evidence is needed to validate the use of hs-CRP as a risk assessment tool in general practice and as a target for therapy in individual patients.