ABSTRACT
Th ere is increasing interest in the roles of infl ammation and of pro-infl ammatory cytokines in cardiovascular disease (CVD), including coronary heart disease (CHD), stroke, peripheral arterial disease (PAD) and venous thromboembolism. Worldwide, inter-individual diff erences in CVD risk are largely explained by well-established cardiovascular risk factors. Th ese may be non-modifi able (age, male sex) or modifi able (tobacco smoke exposure, arterial blood pressure, blood cholesterol, obesity, diabetes, psychosocial factors). We have hypothesized that the eff ects of these risk factors on CVD may be partly mediated by pro-infl ammatory cytokines and their eff ects on atherosclerosis, thrombosis and blood rheology. In this chapter, we review large epidemiological studies of the associations of their circulating levels (and their functional genotypes) with risk factors, and with risk of CVD. Most published information is available for circulating interleukin-6 (IL-6), levels of which are associated with most risk factors, risk of CHD, outcome of stroke, progression of PAD, and blood viscosity. Th ese associations of IL-6 may partly explain the associations of circulating “downstream” infl ammatory markers-C-reactive protein (CRP), fi brinogen, white cell count, erythrocyte sedimentation rate (ESR), blood viscosity-with risk of CVD: a hypothesis that can be tested by Mendelian randomization studies, or by randomized controlled trials of cytokineantagonist drugs. Less epidemiological information is currently available for other
pro-infl ammatory cytokines such as interleukin-18 (IL-18), tumour necrosis factor alpha (TNFα), matrix metalloproteinase-9 (MMP-9) and leptin, and antiinfl ammatory cytokines such as adiponectin and interleukin-10 (IL-10). Ongoing studies should clarify their associations with risk factors and with risk of CVD and, where appropriate, assess their causality.
