Reverse cholestrol transport substantially influences the individual risk of coronary heart disease in hypercholesterolaemic patients.

See page 465 for the article to which this Editorial refers The current extensive interest in research of infectious disease or, more generally, participation of the immune response in the pathogenesis of coronary atherosclerosis may partly be as a result of the role played by traditional risk factors in this disease. Although there is no doubt the multifactorial atherogenic process includes numerous pathogenic effects, a high intravascular concentration of LDL-particles, their accelerated inflow into the subendothelial space of the arterial wall, progressive chemical modification, and scavenger pathways of these modified particles by monocytes and foam cells play a crucial role in the development of coronary atherosclerosis. The monogenic defect in the LDL receptor locus — familial hypercholesterolaemia — is the best evidence supporting the lipid theory of atherosclerosis. Homozygotes with this defect develop vulnerable coronary plaques within the first years of life in the absence of any other coronary heart disease risk factor. Although coronary atherosclerosis develops in the heterozygous form much more slowly, the fact that their frequency in this form is more than a 1000-times higher compared to the homozygous form, constitutes a common feature of young myocardial infarction survivors. Molecular genetics of familial hypercholesterolaemia has expanded the body of our knowledge of this autosomal dominant disease, and about 300 different defects in the LDL receptor gene locus have been described to date. ‘Null mutations’ generating no LDL-receptor protein are associated with high LDLcholesterol concentrations and, probably, more frequent myocardial infarction in young age compared to other point mutations. Despite this, a proportion of patients with the heterozygous form of familial hypercholesterolaemia survived to the 7th or 8th decade of life even before the ‘statin era’, and no explanation for this discrepancy, between high intravascular LDL concentrations and the absence of clinical complications, has been proposed as yet.