Novel anti-inflammatory drugs in hypertension

Abstract

Over the last years chronic low-grade inflammation has emerged as an important new cardiovascular risk factor. Inflammatory responses within the vasculature might release pro-inflammatory cytokines that increase levels of C-reactive protein (CRP). First evidence for a role of inflammation in the development of atherosclerosis comes from studies demonstrating its prognostic value in unstable angina [1]. The inflammation hypothesis was further supported by data from observational studies demonstrating that CRP is a predictor of first cardiovascular events and might be an even stronger prognostic factor than low-density lipoprotein (LDL)-Cholesterol for coronary artery disease [2,3]. CRP appears to be a stable analyte over time and has been subject to numerous recent studies. Thus, on the basis of several studies, the Centers for Disease Control and Prevention and the American Heart Association recommended using highly sensitive (hs)-CRP and implicated the relative risk categories (low, average, high), corresponding to approximate tertiles of values ( 3.0mg/l, respectively) for individual cardiovascular risk assessment, in particular for those patients presenting with an intermediate risk [4]. However, a single inflammatory marker may or may not estimate all aspects of the underlying inflammatory processes, especially as they may affect cardiovascular disease (CVD) risk, and different markers may differ in their specificity for CVD. Indeed, there are several additional markers with a potential role as useful predictors of cardiovascular risk, such as serum amyloid-A, cytokines (e.g. interleukin (IL)-6), acute phase reactants, adhesion molecules and fibrinogen. Interestingly, a recent publication demonstrated that significant gender and race differences in CRP levels exist which contribute to differences in cardiovascular outcome [5]. CRP plasma levels were assessed in 2749 white and black subjects aged 30–65 years and participating in the Dallas Heart Study. Black subjects had higher CRP levels than white subjects and women had higher CRP levels than men, suggesting that overall recommendations for CRP cut-off levels for risk assessment should be adjusted for race and gender. The clinical relevance of CRP as a significant predictor of coronary artery disease (CAD) was further challenged by Danesh et al. [6], demonstrating that CRP was a weaker marker than traditional risk factors like total cholesterol or smoking in the Reykjavik prospective study. However, in the study population, total plasma cholesterol levels were higher and CRP levels lower than those reported in the US population.