Mechanisms of Atherosclerosis in Peripheral Arterial Diseases

Atherosclerosis is the major cause of death and disability in the United States, accounting annually for approximately 750,000 deaths, largely due to myocardial infarction (MI) and stroke (respectively, the first and third major causes of mortality). Other vascular events, such as rupture of vascular aneurysms, catastrophic atheroembolization, and mesenteric and renal ischemia also contribute to the morbidity of this disease. The elevation in ADMA probably explains the observation that administration of L-arginine to individuals with atherosclerosis (or risk factors for atherosclerosis) restores endothelial vasodilator function and can even reduce symptoms of coronary or peripheral arterial disease (PAD). In the Physician’s Health Study, an elevated C-reactive protein was a risk factor for the development of symptomatic PAD and also a risk for peripheral revascularization. There is a circadian pattern of acute MI and sudden death, with most heart attacks occurring in the morning during arousal from sleep or shortly thereafter.