The Time for Cardiovascular Inflammation Reduction Trials Has Arrived

Abstract

Inflammation is a major determinant of atherothrombosis, and based on more than a decade of consistent prospective epidemiological evidence, the inflammatory biomarker highsensitivity C-reactive protein (hsCRP) is in clinical use an independent determinant of cardiovascular risk, even when levels of LDL-C are low.1 Guidelines for use of hsCRP as an adjunct to global risk prediction were issued by the American Heart Association in 2003,2 and risk algorithms incorporating hsCRP such as the Reynolds Risk Score have been developed and validated.3 Increased hsCRP levels not only predict future risk of myocardial infarction, stroke, and cardiovascular death, but are intimately associated with metabolic syndrome and incident diabetes. 4,5 As a result of interrelationships with insulin resistance, leptin, adiponectin, cytokine function, endothelial dysfunction, and impaired fibrinolysis, CRP has been hypothesized to present a common link in pathways connecting vascular inflammation, diabetes, and premature atherothrombosis.6 There appears to be an underlying genetic basis for these relationships; in a genome wide association study of more than 6000 women, unsuspected genetic determinants of CRP have been found that include polymorphism in the leptin receptor gene LEPR and in 2 loci that are more commonly considered genes associated with maturity onset diabetes of the young, GCKR and HNF1.7