A Test in Context: High-Sensitivity C-Reactive Protein

Ridker PM.
A Test in Context: High-Sensitivity C-Reactive Protein. J Am Coll Cardiol 2016;67:712-723.

The following are key points to remember from this review of high-sensitivity C-reactive protein (hs-CRP):

  1. Inflammation is an integral component of the atherosclerotic process and acute coronary syndromes, and is reflected by the serum biomarker hs-CRP measured in mg/L. The median in the United States is about 2 mg/L in the absence of infection, arthritis, chronic inflammatory disorders, and recent trauma.
  2. Hs-CRP levels are elevated in the metabolic syndrome likely mediated from inflammatory cytokines in visceral fat, correlate with number and severity of the criteria, predict vascular event risk, and may have a role in the development of diabetes. Recent studies confirm the predictive value of hs-CRP for cardiovascular (CV) events, but do not support a causal role in the disease expression.
  3. Based on evidence from several statin trials including JUPITER (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin), the best clinical outcomes were in those in whom treatment lowered the low-density lipoprotein cholesterol (LDL-C) <70 mg/dl and hs-CRP to <2 mg/dl. In the JUPITER trial, healthy men and women selected only by an hs-CRP >2 mg, and LDL-C <130 mg/dl (mean 108 mg/dl), as compared to placebo, 20 mg of rosuvastatin reduced major CV endpoints by about 50% and all-cause mortality by 20% (each significant).
  4. The magnitude of the relative risk for coronary heart disease and CV mortality is similar to the total cholesterol, high-density lipoprotein cholesterol (HDL-C), and blood pressure. Unlike with the coronary artery calcium score, the relationship of hs-CRP with coronary disease is more related to event rates than atherosclerosis per se.
  5. Hs-CRP is a Class IIb indication for screening with the main indication the intermediate-risk group for deciding statin therapy. Considering that the JUPITER trial included persons with a very low LDL-C, hs-CRP should be cost-effective in this subset regardless of which statin is used if the targets of LDL-C <70 mg/dl and hs-CRP <2 mg/L are reached.
  6. Placebo-controlled trials with endpoints of CV events and diabetes are in progress using anti-inflammatory agents including low-dose methotrexate, canakinumab, colchicine, and salsalate.

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