• Assess relative risk of cardiovascular disease (CVD)

• Assess risk of a recurrent cardiovascular event in patients with coronary heart disease (CHD)

C-reactive protein (CRP) is a non-specific acute-phase protein produced by the liver in response to tissue injury, infection, and inflammation. Measurement of serum levels, which rise as much as 1,000-fold after an acute event, has traditionally been used to diagnose and monitor acute inflammatory states. However, mild CRP elevation (within the normal, non-acute-phase range) has recently emerged as a valuable marker of cardiovascular risk.¹

Mildly elevated CRP (eg, ≤10 mg/L) has been linked with risk for CVD, including first and recurrent coronary events¹ and stroke;² vascular events after stroke;³ myocardial infarction or angina in patients with peripheral vascular disease;⁴ poor outcome in acute coronary syndromes^1,5 and congestive heart failure;⁶ restenosis after coronary angioplasty;⁷ sudden cardiac death;⁸ hypertension;⁹ dementia;¹⁰ and type 2 diabetes mellitus.¹¹ Prospective studies with highly sensitive assays such as Cardio CRP have consistently shown CRP to be a strong predictor of increased cardiovascular risk in both men and women.¹ The predictive value of CRP is independent of other established risk factors, including LDL-cholesterol, and screening with both CRP and LDL may provide a better risk assessment than using either test alone.¹² Additionally, evidence suggests patients with high CRP/normal LDL are at greater risk than those with normal CRP/high LDL.¹²

Many therapies aimed at reducing cardiovascular risk act through anti-inflammatory pathways. Aspirin and statins both yield the greatest preventive effect in patients with the highest CRP levels.^1,13 Statin therapy reduces the risk of first acute coronary events¹⁴ and stroke¹⁵ associated with elevated CRP, and recent evidence suggests patients who have low CRP levels after statin therapy have better clinical outcomes regardless of the resultant LDL level.¹⁶ Statin therapy also appears to reduce the risk of major adverse cardiac events after stent implantation in patients with elevated CRP levels.¹⁷ Furthermore, evidence from multiple studies indicate that intensive statin therapy leads to an early reduction in cardiac events, sustained for over 2 years, in patients with acute coronary syndrome.¹⁸ Such reduction is likely related to diminished inflammation as evidenced by greater decreases in CRP levels observed after statin therapy than observed after placebo.¹⁹ Weight loss²⁰ and regular physical activity,²¹ both associated with reduced cardiovascular risk, appear to have anti-inflammatory effects as well (ie, reduced CRP, fibrinogen, and white blood cell levels).

• Individuals without a previous history of CHD, especially those with intermediate CHD risk (10-year risk = 10% to 20% according to Framingham global risk scoring system^1,22)

• Patients with stable or acute coronary disease

1 mL room temperature serum (0.5 mL minimum); refrigerated or frozen serum also acceptable. Alternatively, heparin or EDTA plasma may be submitted.

Overnight fasting prior to specimen collection is preferred to avoid excess turbidity due to lipemia. Samples should be collected 2 or more weeks after resolution of any acute inflammatory disease.

• Nephelometric method utilizing latex particles coated with CRP monoclonal antibodies

• Standardized against the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC)/ Bureau Communautaire de Référence (BCR)/College of American Pathologists (CAP) CRP reference preparation

• Analytical sensitivity: 0.2 mg/L

• Cardio CRP results are reported in mg/L with an interpretive comment regarding the risk for CHD

• Synonyms: high-sensitivity C-reactive protein; highly sensitive C-reactive protein

• CPT code*: 86141

Ideally, CRP levels should be measured twice, 2 weeks apart, and the average of the 2 values used for risk assessment.

The reference ranges listed above are derived from a study of more than 40,000 adults from various populations.¹ CRP values in the range of 3.1 to 10 mg/L indicate an approximate 2.0 relative risk of CVD compared with those in the lowest tertile. 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 later, after the inflammatory response has resolved.¹

The following are associated with increased CRP levels: 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. Moderate alcohol intake, physical activity, weight loss, and medications including statins, fibrates, and niacin are associated with decreased levels.¹