• 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 levels (eg, ≤10 mg/L) have consistently been linked to increased risk for various cardiovascular-related disorders, including first and recurrent coronary events,¹ stroke,² peripheral artery disease,³ sudden cardiac death,⁴ hypertension,⁵ and type 2 diabetes mellitus.⁶ 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.⁷ Evidence suggests patients with high CRP/normal LDL are at greater risk than those with normal CRP/high LDL.⁷ Furthermore, elevated CRP levels predict poor prognosis and recurrent coronary events in patients after acute coronary syndrome (ACS),^1,8 stroke,⁹ congestive heart failure,¹⁰ or restenosis.¹¹

Patients with systemic autoimmune diseases including rheumatoid arthritis (RA) and systemic
lupus erythematosus (SLE) are at increased risk of CVD. For patients with RA, CRP levels ≥5 mg/L were associated with a 3.3 relative risk of cardiovascular death in a prospective study with over
500 patients.¹² Similarly for patients with SLE, levels >9 mg/L were associated with increased cardiovascular events (odds ratio = 2.6).¹³

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.^1,14 When CRP levels are elevated, statin therapy reduces the risk of first acute coronary events, even in apparently healthy individuals, and the risk of stroke.^15-17 The risk of adverse cardiac events after
stent implantation¹⁸ or with ACS¹⁹ is also reduced with statin treatment, regardless of the resultant LDL-cholesterol level.²⁰ In patients with ACS, such reduction may be sustained over 2 years and is likely related to diminished inflammation as evidenced by greater decreases in CRP levels observed after statin therapy than observed after placebo.²¹ Thus, high-sensitivity CRP monitoring of ACS patients during statin therapy can significantly add to prediction of death or acute coronary events.²²

• 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^1,23)

• 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 after the inflammatory response has resolved.¹ In patients with active RA or SLE, persistent elevations are associated with increased risk of CVD (see references 12 and 13).

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