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.