Coronary heart disease: pathophysiological events and risk factors

Summary Cardiovascular disease remains the major cause of morbidity and mortality in the UK, causing more than 110 000 deaths per annum. Coronary risk is multifactorial, being a composite of genetic and environmental determinants. Its major risk factors include hypertension, dyslipidaemia, obesity, plasma clotting factor concentrations, smoking and diabetes mellitus. The overall heritability of coronary heart disease has been estimated to be between 15 and 50%, and hence, there is a substantial potential role for environmental factors, including diet, to modify coronary risk. Studies in experimental animal models have permitted a more detailed analysis of the cellular events by which atherosclerosis is initiated and progresses. This work has identified the endothelium as a primary site of injury, leading to endothelial dysfunction. Detailed histological and radiological studies in man have led to the identification of features of atherosclerotic plaques that make them more vulnerable to abrupt rupture. The possible role of infection and inflammation in this process is supported by epidemiological data. These new insights into the pathogenesis of atherosclerosis have been accompanied by the identification of a new generation of risk factors.