High sensitivity C-reactive protein for predicting cardiovascular disease: an inflammatory hypothesis

Hyperlipidaemia is present in only half of all patients who develop coronary heart disease. Over the past several years evidence has accumulated that inflammatory mechanisms play a pivotal role in the genesis of atherosclerosis and its complications. Attention has thus focused on whether circulating markers of inflammation can provide a new method to improve cardiovascular risk prediction. These markers include high sensitivity C-reactive protein, serum amyloid A, interleukin-6, heat shock protein 65 and soluble intercellular adhesion molecule type 1. Of these inflammatory markers, high sensitivity C-reactive protein has been the best studied. Produced in the liver in response to interleukin-6, high sensitivity C-reactive protein has been shown to predict myocardial infarction, stroke and vascular death in a variety of clinical settings. High sensitivity C-reactive protein also appears to have predictive value in both stable and unstable angina as well as in the chronic phase after myocardial infarction, an intriguing finding in light of the emerging role of inflammation in determining plaque stability. Lack of standardization of assays, inconsistency of prospective data and concern about variation in levels have led to doubts regarding the clinical utility of inflammatory markers. Also, data supporting the hypothesis, that inflammatory markers could improve upon traditional lipid screening, are few and mainly derived from studies of C-reactive protein in middle-aged men. A recent analysis from the Women’s Health Study sought to address these issues. This prospective, nested case-control study among 28 263 apparently healthy post-menopausal women sought to determine the risk of cardiovascular events associated with baseline levels of a variety of inflammatory and other markers. Incident cardiovascular events included death from coronary heart disease, non-fatal myocardial infarction or stroke, or the need for coronary revascularization procedures. The mean follow-up period was 3 years and the markers assessed at baseline included high sensitivity C-reactive protein, serum amyloid A, interleukin-6, sICAM-1, homo-