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Am Fam Physician. 2004;69(5):1245-1247

Markers of systemic inflammation can predict future cardiovascular events in healthy persons and patients with coronary artery disease. Measurement of certain inflammatory markers can help identify high-risk patients, monitor disease activity, and provide a therapeutic guide for reducing the inflammatory component of the disease. Fibrinogen and high-sensitivity C-reactive protein (CRP) are the inflammatory markers most extensively studied for their relation to cardiovascular risk. Rosenson and Koenig reviewed the effectiveness of fibrinogen and high-sensitivity CRP measurement in evaluating and managing cardiovascular disease risk.

Coronary artery inflammation is involved in all stages of atherosclerotic plaque formation. Plaque rupture and erosions precipitate thrombosis in patients with acute myocardial infarction (MI), unstable angina, stenosis, total vessel occlusion, and sudden death. The thin, fibrous cap overlying the lipid-rich core of unstable plaques contains inflammatory cells that include proteins such as fibrinogen and CRP, which are important determinants of plaque rupture.

Fibrinogen and CRP are associated independently with a variety of cardiovascular end points in unhealthy and apparently healthy patients. Fibrinogen is involved directly in coagulation, and CRP is a sensitive marker of inflammation and tissue damage. In patients with stable angina, fibrinogen and CRP levels are predictors of cardiac events. A CRP level of at least 3 mg per L (28.6 nmol per L) predicts more ischemic episodes and the need for revascularization procedures; fibrinogen also has prognostic value in this circumstance.

Clinical risk factorMarker association
Cigarette smokingTwofold higher concentrations of fibrinogen and CRP than in nonsmokers
Obesity, overweightSignificantly higher hs-CRP levels than in normal-weight persons
Insulin resistanceCorrelates with hs-CRP and fibrinogen
Metabolic syndromeLinear relation with CRP
Type 2 diabetesHs-CRP predicts development.

Certain cardiovascular risk factors are associated ciated with elevated fibrinogen or high-sensitivity CRP levels, decreasing the prognostic value of these markers (see accompanying table). Treatments that reduce cardiovascular risk also affect these inflammatory markers. Aspirin and clopidogrel have the greatest relative risk reduction in patients with elevated CRP levels. Statin therapy does not affect fibrinogen levels as do nicotinic acid and some fibrates, although statins have been shown to reduce the risk for coronary artery disease associated with systemic inflammation or to lower levels of circulating high-sensitivity CRP.

Measuring fibrinogen and high-sensitivity CRP levels can identify patients at increased risk for coronary events. High-sensitivity CRP levels are a better measure and more reproducible than fibrinogen levels. The Clopidogrel in Unstable Angina to Prevent Recurrent Events Trial demonstrated that combined therapy with aspirin (75 to 325 mg per day) and clopidogrel was more effective than aspirin alone in preventing cardiovascular events, and this combination may be considered, especially in patients with coronary artery disease and elevated high-sensitivity CRP levels.

The authors conclude that high-sensitivity CRP measurement is appropriate in high-risk cardiovascular patients, and that patients with elevated levels should be given more intense treatment, including weight reduction, exercise and, when indicated by low-density lipoprotein cholesterol levels, an increased dosage of statins, or lipid-lowering therapy combined with niacin or a fibrate.

editor's note: The American Heart Association (AHA) and Centers for Disease Control and Prevention (CDC)1 have studied the effectiveness of inflammatory markers in clinical cardiac care and prevention. CRP appears to have the strongest association with cardiovascular disease, especially when the high-sensitivity CRP assay is used. Inflammatory marker measurements can vary with specific patient characteristics. The conclusion of the AHA/CDC report is that high-sensitivity CRP is probably the best supported inflammatory marker and should be measured twice (optimally, two weeks apart). Results less than 1.0 mg per dL (9.5 nmol per L) represent low risk; 1.0 to 3.0 mg per dL (9.5 to 28.6 nmol per L), average risk; and greater than 3.0 mg per dL, high risk. Results greater than 10 mg per dL (95.2 nmol per L) may represent a chronic inflammatory or infectious process. Testing may be useful to identify patients without known cardiovascular disease who may be at higher risk than is estimated by major risk factors and patients at intermediate risk who require further evaluation or therapy, and to motivate moderate- or high-risk patients to improve their lifestyles. The use of high-sensitivity CRP levels to screen for cardiovascular disease risk in the entire adult population is not recommended. Future studies will clarify the utility and cost-effectiveness of these measurements.—r.s.

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