Peripheral arterial disease development

Peripheral arterial occlusion can be the initial manifestation of cardiac or systemic disease. At times, patients with chronic stable claudication may experience abrupt shortening of the distance at which claudication occurs, and this may be the only symptomatic evidence of an acute arterial occlusion either by embolization of by thrombus formation on a pre-existing arterial stenosis. The situation is not chronic and stable any more, but acute and unstable. As ischemia becomes more severe, the patient with chronic peripheral arterial disease develops ischemic pain at rest. The pathophysiologic mechanisms and the clinical presentation parallel the evolution of chronic stable angina pectoris to unstable angina and acute coronary syndromes. 

In addition to coronary sclerosis, evidence is accumulating that high Lp(a) levels may be important in the development of cerebrovascular and peripheral arterial disease, as well (J6, T8, U2). Lp(a) levels not only correlated well with clinical endpoints such as transient ischemic attack and cerebral infarction, but also were associated with the extent and severity of carotid atherosclerosis, as assessed by bidirectional Doppler ultrasound (K23, M33, Z2). 

It is well-established that an elevated level of cholesterol, particnlarly that carried largely in the form of LDLs, is an independent risk factor for the development of atherosclerosis and its sequelae, including coronary artery disease (leading to heart attacks), strokes, and peripheral arterial disease. 

Compared to normotensives, hypertensive persons develop a marked excess of the major cardiovascular diseases. In the age group 45-74, they develop at least twice as much occlusive peripheral artery disease, about three times as much coronary disease, more than four times as much congestive [heart] failure and over seven times the incidence of brain infarction as normotensives. 

A 62-year-old hypertensive man with renal artery stenosis, an adrenal adenoma, peripheral artery disease, and an abdominal aortic aneurysm developed a hypertensive crisis with chest pain. He was treated with nitrates, heparin, aspirin, and nicardipine, which were afterwards replaced by diltiazem 200 mg/day, because of persistent chest pain. He developed atrioventricular block 2 hours after the second dose of diltiazem, and was successfully treated with a pacemaker. 

Chronic inflammation is an important component in the development and progression of atherosclerosis, and numerous epidemiological studies have demonstrated, that increased serum CRP concentrations are positively associated with a risk of future coronary events, such as coronary artery disease, cerebrovascular disease, or peripheral arterial disease/ " It has also been shown to be predictive of future events in patients with acute coronary syndromes and in patients with stable angina and coronary artery stents. 

McCully made the first connection between homocysteine levels and cardiovascular disease in 1969. Since then there have been many studies showing that higher plasma homocysteine levels are associated with a higher risk of cardiovascular, cerebrovascular and peripheral arterial disease. (This topic is developed in the chapter Cardiovascular effects of B vitamins and folate in the context of fortification ). 

This chapter will review the available studies that report the incidence and prevalence of peripheral vascular disease in both type 1 and type 2 diabetic patients. It will focus not only on risk factors associated with the development of peripheral arterial disease, but also touch on pathophysiologic changes that may help to account for some epidemiologic trends. Lastly, it will highlight differences between diabetic and nondiabetic subjects concerning localization of disease and its association with mortality and limb loss. 

Risk Factors for Accelerated Development of Peripheral Artery Disease in Diabetic Subjects... 

These studies all demonstrate unequivocally that hypercholesterolemia, especially in a diabetic individual, predisposes to acceleration of peripheral arterial disease. Smoking in these individuals will accelerate this process (22). Lastly, presence of systolic hypertension while contributing to the development of peripheral arterial disease, in most studies has not been shown to markedly accelerate its development. Therefore, clinical studies focusing on the mechanism of arterial wall injury from low-density lipoproteins as well as growth factor homeostasis of vessel injury repair, need to be performed in high-risk individuals so that the progression of this process can be attenuated. 

Surprisingly, no clinical trials have specifically addressed the contribution of hypertension to the development of peripheral arterial disease. Most of the data comes from multiple regression analysis of many parameters looking for correlations, or subgroup analysis of trials designed primarily to look at coronary artery disease. However, Kannel cidA.. (6) has shown that epidemiological data analyzed in this way accurately predicts disease risk in a variety of American population samples, and in elderly as well as young coronary candidates. 

Not all epidemiological studies, however, confirm hypertension as a consistent risk factor for the development of peripheral vascular disease. Fowkes et al. (4) designed a retrospective study to assess risk factors in the general population that might be more powerful for the prediction of the development of peripheral arterial disease rather than coronary artery... 

A 64-year-old woman with familial hypercholesterolemia, peripheral arterial disease and recent coronary bypass surgery developed Achilles tendon xanthomas within several months of adding immediate-release niacin and cholestyramine to rosuvastatin [80]. 

Peripheral artery disease (PAD) has also been reported to be a risk factor. A study investigated the influence of PAD on the frequency of CIN after heart catheterisation. Four hundred and twelve included in the study were divided into three groups 251 patients with coronary heart disease (CHD), 77 patients with PAD and 84 patients without CHD and PAD. Forty-nine patients developed CIN. The study found that patients with PAD had a statistically significant higher rate of CIN after heart catheterisation compared to patients without PAD (32.7 vs 16.8%, p = 0.008) [29 ]. 

In order to minimise the risks, it is advised that strodium ranelate should not be used in patients with ischaemic heart disease, peripheral arterial disease, cerebrovascular disease or in patients with xmcontroUed hypertension. Finally, prescribers are advised of the patient s risk of developing cardiovascular disease before starting treatment and thereafter at regular intervals. 

Tools to improve cardiovascular health are of great importance in countries where life expectancy is significantly increasing and where the prevalence of lifestyle-related diseases such as cardiovascular disease and type II diabetes is constantly growing. Atherosclerosis is still the leading cause of mortality and morbidity in affluent societies. By changing diet and lifestyle the risk factors for cardiovascular mortality and morbidity can be lowered. Among these risk factors, the importance of total cholesterol and low-density lipoprotein (LDL) cholesterol levels in blood semm is well established. An elevated serum concentration of cholesterol and especially of LDL cholesterol is a key risk factor for the development of atherosclerosis and its clinical manifestations, which include coronary heart disease and cerebrovascular and peripheral artery diseases. 

Intermittent claudication is a group of symptoms characterized by pain in the calf muscle of one or both legp, caused by walking and relieved by rest. It is a manifestation of peripheral vascular disease, in which atherosclerotic lesions develop in the femoral artery, diminishing blood supply to the lower leg. Cilostazol is used to treat intermittent claudication. 

Contrary to LDL, high-density lipoproteins (HDL) prevent atherosclerosis, and therefore, their plasma levels inversely correlate with the risk of developing coronary artery disease. HDL antiatherogenic activity is apparently due to the removal of cholesterol from peripheral tissues and its transport to the liver for excretion. In addition, HDL acts as antioxidants, inhibiting copper- or endothelial cell-induced LDL oxidation [180], It was found that HDL lipids are oxidized easier than LDL lipids by peroxyl radicals [181]. HDL also protects LDL by the reduction of cholesteryl ester hydroperoxides to corresponding hydroperoxides. During this process, HDL specific methionine residues in apolipoproteins AI and All are oxidized [182]. 

Reduction in risk of Ml, stroke, and death from cardiovascular causes - In patients 55 years of age or older at high risk of developing a major cardiovascular event because of a history of coronary artery disease, stroke, peripheral vascular disease, or diabetes that is accompanied by at least 1 other cardiovascular risk factor (eg, hypertension, elevated total cholesterol levels, low FIDL levels, cigarette smoking, documented microalbuminuria). 

In a retrospective analysis of 63 patients treated with arginine vasopressin for catecholamine resistant vasodila-tory shock, 30% developed ischemic skin lesions (23). Pre-existing peripheral arterial occlusive disease and septic shock were independent susceptibility factors. 

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