Persistent inflammatory residual risk despite aggressive cholesterol-lowering therapy: further evidence fuelling the dual target concept

Extract

This editorial refers to ‘Comparison of interleukin-6, C-reactive protein, and low-density lipoprotein cholesterol as biomarkers of residual risk in contemporary practice: secondary analyses from the Cardiovascular Inflammation Reduction Trial’^†, by P.M. Ridker et al., on page 2952.

Inflammation and atherosclerosis: convincing evidence from vascular biology, genetic, epidemiological, and clinical studies

Over the last 30 years, vascular biology has provided unequivocal evidence that inflammatory processes play a significant role during the initiation of the atherosclerotic process, through the build up of the plaque up to the ultimate full-blown rupture or fissuring and potentially the erosion of a plaque, with the consequence of a clinical ischaemic syndrome. Various cells, in particular monocytes/macrophages that ultimately turn into foam cells, are known to produce a large number of various pro-inflammatory biomarkers that enhance plaque growth and weaken the plaque cap, thus contributing to the vulnerability of a plaque.¹

In addition, since the mid 1990s, numerous large-scale, long-term, well-controlled population-based studies in apparently healthy participants and clinical studies in patients with manifest atherosclerotic disease have clearly demonstrated that elevated concentrations of various cytokines, chemokines, acute phase proteins, and further molecules representing various pathways potentially playing a significant role in atherosclerosis have been found to be independently associated with cardiovascular outcomes, some of them also with non-vascular endpoints. Undoubtedly, the largest database for a systemic marker of inflammation exists for C-reactive protein (CRP) measured by a high-sensitivity (hs) assay. After a seminal paper published in 1997 from the Physicians’ Health Study² had clearly demonstrated that hsCRP could predict cardiovascular events independent of conventional risk factors, such an association has been confirmed in a large number of other population-based cohorts showing that a 1 SD increase in hsCRP concentration in multivariable analysis was associated with a 37% increased risk for coronary heart disease (CHD), which was as strong as or even stronger than that found for conventional risk factors.³