The Case for More High-sensitivity C-Reactive Protein Testing

Cholesterol  and blood pressure measurements are routine tools in the armamentarium for  treating cardiovascular disease, but few  internists and cardiologists utilize high-sensitivity C-reactive  protein (hsCRP) testing even though it is an important prognostic tool in both  primary and secondary cardiac risk prevention, according to an international  team of experts led by Paul Ridker, MD, a leading authority and researcher on  the role of inflammation in cardiovascular disease.

Physicians  hesitant to use hsCRP measurements aren’t availing themselves of the latest scientific findings, wrote  Ridker and his colleagues in an editorial in the European Heart Journal (EHJ). “This  reluctance is neither evidence based nor in the best interest of patient  care,” they asserted,  pointing to studies that demonstrated the value of hsCRP as a risk prediction  tool in the primary prevention setting. “Measurement of hsCRP adds as much to  risk prediction as does evaluation of [high-density lipoprotein] or total  cholesterol, both of which are universally recommended in current European  prevention guidelines,” they wrote.

“Multiple trials have shown that the benefits of statin therapy  relate to both lipid lowering and inhibition of inflammation, with on-treatment  hsCRP levels as important a prognostic factor as on-treatment levels of LDL  [low-density lipoprotein] cholesterol. Very recent data suggest that low levels  of hsCRP but not low levels of LDL cholesterol are protective for  stroke,” they added. One  study, the JUPITER trial, challenges the claim that treatment options for  patients with elevated hsCRP simply don’t exist in primary prevention. The  findings indicated that patients with hsCRP levels of >2 mg/L do in fact  benefit from statin therapy “even in the absence of overt hyperlipidaemia,” Ridker and his colleagues  noted.Other  key clinical trials illustrate the significance of measuring hsCRP levels in  secondary prevention. The CANTOS trial “provided proof of principle that targeting innate immunity, at  least with a monoclonal antibody that reduces the critical  interleukin-1β to  interleukin-6 to CRP pathway, significantly lowers recurrent rates of myocardial  infarction and cardiovascular death among patients already treated with  high-intensity statins,” they  summarized.

The  editorial also highlighted a recent study that included more than 7,000 patients with percutaneous coronary  artery intervention who underwent serial hsCRP measurements at Mount Sinai  Hospital in New York from 2009 and 2016. Among these patients, “38% had persistently high residual  inflammatory risk (hsCRP >2 mg/L) despite high-quality care, and another 10%  developed residual inflammatory risk over time,”  the editorialists summarized. Following these patients  for more than a year afterward, investigators found that for those with hsCRP  above 2 mg/L, rates of recurrent myocardial infarction and all-cause mortality  were 7.5% and 2.6% respectively, compared with much lower rates of 4.3% and 0.7%  found in patients with lower hsCRP. Investigators in subgroup analyses also  found a link between elevated hsCRP and poor outcomes in both men and women, and  among those with LDL cholesterol levels above and below 70  mg/dL.

“Physicians can only address the biological processes they  measure,” the  editorialists wrote, adding, “Without measuring hsCRP, it is unclear how we will effectively  identify and manage residual inflammatory risk.”  While some reject the idea of using hsCRP as a  screening tool, this controversy “has resulted in less than optimal preventive care for millions of  high-risk European patients,” they concluded.