C-Reactive Protein, Fibrinogen, and Cardiovascular Disease Prediction

Study Questions:

What is the value of assessing levels of C-reactive protein (CRP) or fibrinogen, markers of inflammation, for the prediction of first cardiovascular events (CVEs)?


The Emerging Risk Factors Collaboration (ERFC) group reviewed 52 prospective studies that included 246,669 participants without a history of cardiovascular disease (CVD) to investigate the value of adding CRP or fibrinogen levels to conventional risk factors for the prediction of cardiovascular risk. Discrimination and reclassification were determined during follow-up with modeling of the clinical implications of initiation of statin therapy after the assessment of CRP or fibrinogen.


In the 52 studies, mean age was 61 years, and 56% were men. The CRP was available in 67% of participants, among whom 12% had a first CVE (2/3rd coronary 1/3rd stroke) with a median of 6.7 years to first outcome. The addition of information on high-density lipoprotein cholesterol (HDL-C) to a prognostic model for CVD that included age, sex, smoking status, blood pressure, history of diabetes, and total cholesterol level, increased the C-index, a measure of risk discrimination, by 0.0050. The further addition to this model of information on CRP or fibrinogen increased the C-index by 0.0039 and 0.0027, respectively (p < 0.001), and yielded a net reclassification improvement of 1.52% and 0.83%, respectively, for the predicted 10-year risk categories of “low” (<10%), “intermediate” (10% to <20%), and “high” (≥20%) (p < 0.02 for both comparisons). It was estimated that among 100,000 adults 40 years of age or older, 15,025 persons would initially be classified as being at intermediate risk for a CVE if conventional risk factors alone were used to calculate risk. Assuming that statin therapy would be initiated in accordance with Adult Treatment Panel III guidelines (i.e., for persons with a predicted risk of ≥20% and for those with certain other risk factors, such as diabetes, irrespective of their 10-year predicted risk), additional targeted assessment of CRP or fibrinogen levels in the 13,199 remaining participants at intermediate risk could help prevent approximately 30 additional CVEs over the course of 10 years.


In persons without known CVD, it is estimated that under current treatment guidelines, assessment of the CRP or fibrinogen level in those at intermediate risk for a CVE could help prevent one additional event over a period of 10 years for every 400-500 people screened.


While not the major focus of this report, the minimal effect of HDL-C on the C-statistic for predicting outcome in the model is hard to understand in light of previous studies by the same group. In a publication regarding the relative value of cholesterol, HDL-C, and apolipoproteins, the ERFC group concluded that in 68 studies involving >300,000 patients without pre-existing CVD, HDL-C was strongly and inversely related to CVE (JAMA, 2009). Each 1-standard deviation in HDL-C (15 mg/dl) was related to a 22% decrease in coronary heart disease risk. The various international guidelines for prescribing statins for preventing first CVEs have been increasingly more (albeit modestly) enthusiastic about measuring the CRP in the intermediate-risk group. I don’t think this analysis will change many opinions.

Clinical Topics: Arrhythmias and Clinical EP, Dyslipidemia, Prevention, Atrial Fibrillation/Supraventricular Arrhythmias, Lipid Metabolism, Nonstatins, Novel Agents, Statins, Smoking

Keywords: Inflammation, Stroke, Follow-Up Studies, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Lipoproteins, Coronary Disease, Risk Factors, Blood Pressure, Smoking, Primary Prevention, Prognosis, Cholesterol, C-Reactive Protein, Biological Markers, Cardiovascular Diseases, Atrial Fibrillation, Fibrinogen, Diabetes Mellitus

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