Most arterial occlusive disease is produced by atherosclerosis. Atherosclerosis is a generalized response of the artery wall to injury. Atherosclerotic plaques are characterized by smooth muscle migration into the intima and subsequent proliferation and extracellular lipid deposition. Complex lesions are composed of a fibrous cap containing smooth muscle and inflammatory cells overlying a central core of lipid-rich necrotic debris. Clinical symptoms are produced by progressive stenosis, calcification, intraplaque hemorrhage, distal embolization, and luminal thrombosis after cap rupture. Atherosclerosis is a systemic disease, associated with some degree of involvement of all major arteries, but its most common clinical manifestations involve a limited number of arteries at areas of turbulent flow and low sheer stress: the carotid bifurcation, the infrarenal aorta and the iliac, superficial femoral, and tibial arteries, and the ostia of the renal and visceral arteries.

Most arterial aneurysms are classified as atherosclerotic or degenerative, because atheromas are found in the aneurysm wall and many patients have typical atherosclerotic risk factors. Both occlusive disease and aneurysms may be present in the same individual. However, the exact role of atherosclerosis in the causation of aneurysms is poorly defined. An imbalance of tissue metalloproteinases and metalloproteinase inhibitors is responsible for elastin and collagen degradation. Genetic predisposition, inflammation, and hemodynamic factors may also play a permissive role in aneurysm formation.

Atherosclerosis has been associated with increasing age, hypercholesterolemia, diabetes mellitus, smoking, a positive family history, hypertension, elevated levels of lipoprotein(a) and C-reactive protein, sedentary lifestyle, obesity, and homocystinuria. Control of risk factors by use of antihypertensive and lipid-lowering medications, regulation of blood sugar, tobacco cessation, and regular exercise remain the mainstays of treatment. Aspirin and clopidogrel (and potentially glycoprotein IIb/IIIa inhibitors) may prevent microemboli by impairing platelet aggregation; clopidogrel reduces the relative risk of stroke, myocardial infarction, and vascular death by 24% over aspirin alone in at-risk patients. Preliminary studies suggest that antioxidants, particularly dietary vitamin E, may also be beneficial in slowing the progression of disease. More recently, research has focused on the use of macrolide antibiotics in atherosclerotic disease, based on the finding of Chlamydia pneumoniae in symptomatic atheromas. Gene transfer of vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthetase (eNOS), as well as specifically targeted gene therapy for risk factor management, represent active areas of investigation.

Frangos SG et al: Vascular drugs in the new millennium. J Am Coll Surg 2000;191:76.

Hodis HN et al: Estrogen in the prevention of atherosclerosis: a randomized, double-blind, placebo-controlled trial. Ann Intern Med 2001;135:939.

Khurana R et al: Gene therapy for cardiovascular disease: a case for cautious optimism. Hypertension 2001;38:1210.

Kilaru S et al: Nicotine: a review of its role in atherosclerosis. J Am Coll Surg 2001;193:538.

Lusis AJ et al: Atherosclerosis. Nature 2000;407:233.

McQuillan BM et al: Antioxidant vitamins and the risk of carotid atherosclerosis. J Am Coll Cardiol 2001;38:1788.

Ridker PM et al: Novel risk factors for systemic atherosclerosis. JAMA 2001;285:2481.