Test Code: 91737, 10124

Clinical use

• Assess relative risk of cardiovascular disease (CVD)
• Assess risk of a recurrent cardiovascular event in patients with coronary heart disease (CHD)
• Reclassify patients with intermediate CVD risk into a high-risk category
• Guide therapeutic decisions for patients with borderline or intermediate CVD risk

Clinical background

C-reactive protein (CRP) is a nonspecific acute-phase protein produced by the liver in response to tissue injury, infection, and inflammation. CRP levels rise as much as 1,000-fold after an acute event; these high levels can be used to diagnose and monitor acute inflammatory states. Levels within the normal, nonacute-phase range (≥10 mg/L) can help assess cardiovascular risk. The high-sensitivity CRP (hs-CRP) test is used for this purpose because it can accurately determine CRP levels in the low range of 1 to 10 mg/L.

Mildly elevated CRP levels have been linked to increased risk for various cardiovascular-related disorders, including coronary heart disease (CHD), peripheral artery disease (PAD), stroke, and sudden cardiac death.1 The predictive value of hs-CRP for cardiovascular events is independent of other established risk factors, including low-density lipoprotein cholesterol (LDL-C).2 Mildly elevated hs-CRP levels also predict recurrent CHD events and poor prognosis in some patients, including those who have PAD.3

Because hs-CRP levels are associated with cardiovascular risk, they can contribute to risk stratification. Recommendations on the clinical utility of hs-CRP test results are divided, however. The American Association of Clinical Endocrinologists supports using hs-CRP as part of the Reynold’s Risk Score for predicting CHD events.4 The US Preventive Services Task Force similarly found that adding hs-CRP to traditional risk factors provides more accurate risk assessment, but found that more evidence was required to support that measuring hs-CRP improves clinical outcomes.5

The American College of Cardiology/American Heart Association Task Force recommends using hs-CRP test results as a possible “risk enhancer” for risk-based treatment decisions.6 For patients with “borderline” or “intermediate” CVD risk (as determined by a quantitative risk assessment based on the pooled cohort equations for evaluating the 10-year risk of a CVD event ), hs-CRP results may help determine if a moderate intensity statin treatment is appropriate.6

Furthermore, data support using hs-CRP levels as potential targets for intervention, beyond LDL-C. One study combined data from 3 randomized clinical trials involving over 30,000 patients on statin therapy; hazard ratios, calculated using the top and bottom quartiles for both hs-CRP levels and LDL-C levels, were significantly higher (P<.0001) for hs-CRP vs LDL-C for incident major adverse cardiovascular event (1.3 vs 1.1), cardiovascular mortality (2.7 vs 1.3), and all-cause mortality (2.4 vs 1.2).7 These data suggest that patients on statin therapy with increased hs-CRP levels may benefit from supplemental anti-inflammatory drugs (eg, oral colchicine as demonstrated in a separate meta-analysis8).

Note that this test is not intended for the diagnosis or monitoring of acute inflammatory states. A standard (conventional) CRP test is available for those purposes (test code 4420).

Interpretive information

Ideally, the average of 2 hs-CRP measurements, done 2 weeks apart, should be used when interpreting hs-CRP values. hs-CRP values in the range of 3.1 to 10 mg/L indicate an approximate 2-fold increased risk of CVD compared with values <1.0 mg/L. Levels persistently above 10 mg/L may indicate an acute inflammatory process; sources of infection or inflammation should be sought and the test repeated at least 2 weeks after the inflammatory response has resolved.9

In a patient with borderline 10-year CVD risk (5% to <7.5%), hs-CRP levels ≥2 mg/L support considering moderate intensity statin treatment. 6 In a patient with intermediate 10-year CVD risk (7.5% to 20%), hs-CRP levels ≥2 mg/L support initiating moderate intensity statin treatment.6

Increased CRP levels are also associated with elevated blood pressure, elevated body mass index, cigarette smoking, metabolic syndrome, diabetes, low HDL levels, high triglyceride levels, use of estrogen or progesterone, and chronic infections or inflammation. Decreased levels are associated with moderate alcohol intake, physical activity, weight loss, and medications including statins, fibrates, and niacin.9

hs-CRP testing is offered with (CardioIQ® hs-CRP, test code 91737) or without (hs-CRP, test code 10124) enhanced reporting, which includes color-coding to display progressive risk.