Board Review

A 58-year-old man is evaluated during a routine appointment and asks for advice on cardiac risk assessment. He does not have any current cardiac symptoms, exercises 4 days per week, and has never smoked. He has no chronic health issues and takes no medications. He has no known drug allergies. Results of the physical examination are normal.

Cardiovascular risk calculation using the Pooled Cohort Equations predicts a 6% risk of a myocardial infarction or coronary death in the next 10 years.

Which of the following tests should be performed next?

A) Adenosine cardiac magnetic resonance (CMR) imaging

B) Cardiac CT angiography

C) Fractionated lipoprotein profile

D) High-sensitivity C-reactive protein assay

E) Stress echocardiography

Answer: D - High-sensitivity C-reactive protein assay

Objective: Use high-sensitivity C-reactive protein level to guide treatment and cardiac risk stratification in a patient at intermediate risk of cardiovascular disease.

Key Point

In patients with an intermediate risk of cardiovascular disease, the measurement of high-sensitivity C-reactive protein (hsCRP) has been proved to be useful for guiding primary prevention strategies, with as many as 30% of patients being reclassified as either low risk or high risk based on the hsCRP measurement.

The most appropriate management of this patient is to obtain high-sensitivity C-reactive protein (hsCRP) levels. He has an intermediate risk of myocardial infarction and coronary death (5% to below 7.5% as defined by the Pooled Cohort Equations). The measurement of hsCRP has been proved to be useful for guiding primary prevention strategies in intermediate-risk patients, with as many as 30% of patients being reclassified as either low risk or high risk based on hsCRP measurement.

When used for this purpose, the CRP assay should be able to detect levels to at least 0.03 mg/L (high sensitivity); a single test is appropriate in patients with levels below 1.0 mg/L, but testing should be repeated in 2 weeks for values of 1.0 mg/L or higher to assess for persistent elevation. Patients with hsCRP measurement below 1.0 mg/L are considered at a low relative risk for coronary heart disease and those with levels of 3.0 mg/L or higher are considered at a high relative risk. A meta-analysis from the Emerging Risk Factors Collaboration in 2010 found that hsCRP levels have a strong linear association with both ischemic stroke and vascular mortality. Although evidence is not strong that modification of risk can occur with treatment after hsCRP measurement, the JUPITER study randomized patients with serum LDL cholesterol levels below 130 mg/dL (3.37 mmol/L) and hsCRP levels greater than or equal to 2.0 mg/L to rosuvastatin or placebo. Patients were followed for the occurrence of death, myocardial infarction, stroke, or a composite of first major cardiovascular event for 5 years. In addition to lowering serum LDL cholesterol levels from 108 to 55 mg/dL (2.80 to 1.42 mmol/L) and hsCRP from 4.2 to 2.2 mg/L, rosuvastatin significantly reduced the incidence of major cardiovascular events.

Because this patient is asymptomatic, adenosine cardiac magnetic resonance (CMR) imaging, cardiac CT angiography, and stress echocardiography are not indicated and have not been associated with reduction in cardiovascular events.

There is currently no role for the evaluation of lipid particle size and number (fractionated lipoprotein profiling). No studies to date have shown that treatment targeted to lipoprotein particle size and number affects outcomes, and the use of these tests is not addressed in current cholesterol management guidelines.

Ridker PM, Danielson E, Fonseca FA, et al; JUPITER Study Group. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008 Nov 20;359(21):2195-207. Link Out