A 52-year-old male called his primary care physician and asked whether he should be treated with a statin, a call prompted by a recent commercial. The primary care physician said he would review the records and get back to the him.
On review, the patient had had a recent lipid profile which demonstrated a cholesterol of 160 mg/dl, a LDL of 125 mg/dl, a HDL of 35 mg/dl, and triglycerides of 80 mg/dl. Other significant past medical history was notable for well-controlled hypertension and a family history of premature coronary disease. The physician calculated the patient’s Framingham Risk Score, which resulted in an estimated 10-year risk of cardiovascular disease of 12%. The physician decided further risk stratification was in order, and asked the patient to come in to have a C-reactive protein (CRP). This was done approximately two weeks later and the level was 12 mg/L.
Your next step would be to:
The correct answer is: D. Repeat the CRP
CRP has been found to improve risk stratification for subsequent cardiovascular disease beyond that used in addition to standard risk factor testing such as the Framingham Risk Score,(1,2) although some trials have not been able to demonstrate this.(3,4) Current recommendations give a Class IIa recommendation for measurement of CRP for men over the age of 50 and women over the age of 60 with an LDL of <130 mg/dL who are not currently treated with statins and do not have overt coronary disease, diabetes, or chronic kidney disease.(1) Given the patient's risk factors, he would be considered intermediate risk, and also meet enrollment criteria for the JUPITER Trial (low LDL, elevated CRP).(5)
However in this case, the patient’s CRP is markedly elevated. The precision in reproducibility of CRP is good with little seasonal or diurnal variation(6); however, current recommendations state that two separate measurements of CRP should be performed to classify a person’s risk to account for potential increase within individual variability.(6) Patients with evidence of active infection, systemic inflammatory processes, or trauma should not be tested until these conditions have resolved.
On further questioning by the physician, the patient stated that at the time of testing, he was getting over an episode of severe bronchitis. On repeat testing, the CRP and it returned at 1.5 mg/L. The physician discussed with the patient that he was low risk based on the low LDL and low CRP.
In this case, the elevated CRP was thought to be secondary to the patient's recent infection. A markedly elevated CRP should prompt the physician to ask the patient about potential recent infections or other causes of systemic inflammation, and should be repeated to confirm the elevation.
Greenland P, Alpert JS, Beller GA, et al. 2010 ACCF/AHA guideline for assessment of cardiovascular risk in asymptomatic adults. J Am Coll Cardiol 2010;56:e50-103.
Buckley DI, Fu R, Freeman M, Rogers K, Helfand M. C-reactive protein as a risk factor for coronary heart disease: a systematic review and meta-analyses for the U.S. Preventive Services Task Force. Ann Intern Med 2009;151:483-95.
Shah T, Casas JP, Cooper JA, et al. Critical appraisal of CRP measurement for the prediction of coronary heart disease events: new data and systematic review of 31 prospective cohorts. Int J Epidemiol 2009;38:217–231.
Wilson PW, Nam BH, Pencina M, et al. C-reactive protein and risk of cardiovascular disease in men and women from the Framingham Heart Study. Arch Intern Med 2005;165:2473–2478.
Ridker PM, Danielson E, Fonseca FA, et al for the JUPITER Study Group. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med 2008;359:2195-207.
Pearson TA, Mensah GA, Alexander RW, et al. Markers of inflammation and cardiovascular disease: application to clinical and public health practice: A statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association. Circulation 2003;107:499-511.