Theories of intimal injury leading to plaque formation include platelet adhesion and production of
growth factors,
hypercholesterolemia, smooth muscle cell proliferation, macrophage activity, defective utilization of
low-density lipoproteins via deficient receptors, and deficiency in cellular lysosomal
enzymes. High levels of
low-density lipoproteins and
intermediate-density lipoproteins, as well as their
apoproteins, are strong risk factors for cardiovascular disease. The lowering of the
cholesterol level has been shown to produce significant regression of atherosclerotic lesions. Data also suggest an interaction between
lipids and platelets, although the role of coagulation disorders as an independent risk factor for
atherosclerosis is difficult to assess. Although much of the data are controversial, there is evidence that platelet survival time is a strong predictor of severe vessel damage. In addition, some studies have reported decreased activity of
antithrombin III with
coronary artery disease, and there appears to be a direct correlation between
fibrinogen and
cholesterol levels. Finally,
diabetes mellitus (both types I and II) is a significant independent risk factor for
atherosclerosis. The risk is not related to the severity or duration of diabetes, and it appears to be greater in women than in men.