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The epidemiology, costs, and comorbidities associated with atherosclerosis and the role of newer antiplatelet agents are reviewed. Cardiovascular disease is the leading cause of death in the United States. More than 60 million Americans have one or more types of cardiovascular disease. The total annual cost of coronary heart disease has been estimated at $95 billion. Patients with an existing atherosclerotic disease in one vascular bed are at high risk of having an ischemic vascular event in the same or another vascular bed. Peripheral arterial disease is a strong marker for underlying cerebrovascular and cardiovascular disease. The common link among these diseases is atherosclerosis leading to atherothrombosis. Platelets play an integral role in atherosclerosis and the formation of arterial thrombus as well as in subsequent acute events such as ischemic stroke, myocardial infarction, and vascular death. Arterial thrombosis can be mediated by shear-stress-induced platelet aggregation. Currently, only one third to one half of all eligible patients with stroke, myocardial infarction, or peripheral arterial disease receive antiplatelet therapy. Thienopyridines such as ticlopidine and clopidogrel are effective inhibitors of shear-stress-induced and endothelial-injury-induced platelet aggregation. Advances in antiplatelet therapy provide an opportunity to use newer antiplatelet agents in the prevention of atherosclerosis-related morbidity and mortality; therapeutic approaches should be directed toward recognizing atherosclerosis as a generalized disease process and preventing ischemic events in multiple vascular beds.
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PMID:Atherosclerosis: a unifying disorder with diverse manifestations. 978 96

The risk factors, epidemiology, diagnosis, and treatment of peripheral arterial disease are reviewed. Peripheral arterial disease is characterized by a gradual reduction in blood flow to one or more limbs secondary to atherosclerosis. Risk factors include smoking, diabetes mellitus, hyperlipidemia, and hypertension. The most common clinical manifestation is intermittent claudication. The prevalence of intermittent claudication in people over the age of 50 is 2-7% for men and 1-2% for women. The ankle:brachial pressure index (ABPI) is a useful measure of disease severity; an ABPI of 0.5-0.9 is common in intermittent claudication. The goals of therapy are to relieve or reduce ischemic symptoms, alleviate disability, improve in functional capacity, prevent progression that may result in gangrene and limb loss, and prevent cardiovascular and cerebrovascular events. Treatment includes risk-factor modification, drug therapy (primarily with antiplatelet agents), and revascularization procedures. Aspirin has been shown to be effective in reducing the associated risk of myocardial infarction and stroke. Ticlopidine appears to be a reasonable alternative for patients who are hypersensitive to aspirin. Clopidogrel has been shown to be more effective than aspirin in patients with recent myocardial infarction, recent stroke, or established peripheral arterial disease. There is controversy over the appropriate treatment for acute arterial occlusions. Risk-factor modification and antiplatelet drugs are the mainstays of therapy for patients with intermittent claudication, the most common manifestation of peripheral arterial disease.
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PMID:Management of peripheral arterial disease. 978 99

Peripheral arterial disease has received less attention from epidemiologists than coronary and cerebrovascular disease. Prevalence and incidence data typically show that peripheral arterial disease increases with age, is more common in men than women, and that symptomatic disease is only the tip of the iceberg. Studies concerning the prevalence of peripheral arterial disease rely mainly on the Rose questionnaire, which is used to screen for intermittent claudication, and on the ankle/brachial index, used to detect asymptomatic disease. Although there is a certain parallel between the 2 sets of data, the figures for asymptomatic disease consistently surpass those for clinical disease, and there is a wide variation between frequencies obtained in individual studies. In general, the prevalence of peripheral arterial disease is estimated to be under 2% for men aged less than 50 years, increasing to over 5% in those aged more than 70 years. Women reach these rates almost 10 years after men, although this gender difference decreases with increasing age. Figures for incidence follow a similar trend. The incidence of chronic critical ischaemia is estimated to be between 0.05% and 0.1% of the population. Asymptomatic disease detected with noninvasive tests is 3 to 4 times more frequent than intermittent claudication: its prevalence increases from under 5% for individuals aged less than 50 years to over 20% for individuals aged more than 70 years. The classical risk factors for atherosclerosis also apply to peripheral arterial disease, although their order of importance may be different from that for coronary and carotid disease. Several studies have shown that peripheral arterial disease correlates most strongly with cigarette smoking. Smoking is also the single greatest predictor of the progression of peripheral arterial disease. Other risk factors include hypertension, raised lipid levels (cholesterol and triglycerides for severe disease), diabetes, increased plasma viscosity, fibrinogen and homocysteine levels. Divergent views have been expressed in individual epidemiological studies with regard to the respective contribution of these risk factors to the development and progression of peripheral arterial disease. The natural history of peripheral arterial disease is characterised by a relatively benign local evolution. It can be estimated that, in general, 3 of 4 men presenting with intermittent claudication will never have a serious problem necessitating vascular intervention, and that no more than 5% are ever likely to require a major amputation. However, the underlying atherosclerotic pathology progresses with time: nondiseased arteries become obliterated and disease with an initially unilateral pattern frequently progresses to become bilateral. In addition, the few patients who do progress to critical ischaemia are at a significantly higher risk of amputation. The general prognosis for patients with peripheral arterial disease is particularly negative. There is a high prevalence of coronary heart disease and cerebrovascular disease in such patients, although the exact percentages depend on the patient population selected and on the method used for their evaluation. Coronary heart disease is detected in 40 to 60% of patients through a medical history combined with electrocardiography, while systematic coronary angiography detects coronary heart disease in 90% of those undergoing surgery. Although few patients with peripheral arterial disease have a history of stroke, in studies of surgical patients almost 30% appear to have significant extracranial disease. Patients with peripheral arterial disease have a poor life expectancy: the mortality rate is 3 to 5% per year in those with intermittent claudication and 20% per year in those with critical ischaemia. Coronary heart disease accounts for half of the total mortality, while vascular disease in general accounts for almost two-thirds.
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PMID:[Epidemiology and prognosis of peripheral obliterative arteriopathy]. 984 97

Peripheral arterial disease of the lower limbs is a manifestation of atherosclerosis, and may also affect other vascular territories such as the coronary and cerebral arteries. Progressive narrowing of the vessels up to total occlusion can present as intermittent claudication or pain at rest, with or without cutaneous lesions. Patients with intermittent claudication are at a low risk of amputation, and the symptom has to be regarded as a warning signal for myocardial infarction and stroke. Nevertheless, if the patient's walking distance is too limited to allow a near-normal life, symptomatic treatment to improve quality of life should be considered. Treatment may consist of walking exercise, surgical or interventional radiological revascularisation, or, in some cases, administration of vasoactive drugs. Antiplatelet agents should be administered in an attempt to limit disease progression and prevent cardiac and cerebrovascular complications, together with active measures to reduce established risk factors such as smoking, diabetes, hyperlipidaemia, and arterial hypertension. The presence of pain at rest indicates that a lower limb is jeopardised, especially when the criteria for critical ischaemia have also been met. These criteria include the presence of chronic (lasting for more than 2 weeks) symptoms of ischaemia at rest and a systolic blood pressure less than 50 mm Hg or 30 mm Hg at the ankle or big toe, respectively. In such a situation, revascularisation should be attempted whenever possible. If this is not possible or if the procedure has failed, prostacyclin administered intravenously for days or weeks is an alternative. After revascularisation, early reocclusion may be prevented by administering anticoagulants and late reocclusion by antiplatelet agents, in conjunction with eradication of risk factors. In all situations, therapeutic decision-making should be undertaken in a multidisciplinary setting and should include the following: specialists in angiology (an internist) and interventional radiology; a vascular surgeon; an orthopaedic surgeon, if necessary; and diabetes and infectious disease specialists.
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PMID:[Drug treatment strategies for peripheral obliterative arteriopathy]. 984 99

Peripheral arterial disease (PAD) in the legs, measured noninvasively by the ankle-arm index (AAI) is associated with clinically manifest cardiovascular disease (CVD) and its risk factors. To determine risk of total mortality, coronary heart disease, or stroke mortality and incident versus recurrent CVD associated with a low AAI, we examined the relationship of the AAI to subsequent CVD events in 5888 older adults with and without CVD. The AAI was measured in 5888 participants >/=65 years old at the baseline examination of the Cardiovascular Health Study. All participants had a detailed assessment of prevalent CVD and were contacted every 6 months for total mortality and CVD events (including CVD mortality, fatal and nonfatal myocardial infarction, congestive heart failure, angina, stroke, and hospitalized PAD). The crude mortality rate at 6 years was highest (32.3%) in those participants with prevalent CVD and a low AAI (P<0.9), and it was lowest in those with neither of these findings (8.7%, P<0.01). Similar patterns emerged from analysis of recurrent CVD and incident CVD. The risk for incident congestive heart failure (relative risk [RR]=1.61) and for total mortality (RR=1.62) in those without CVD at baseline but with a low AAI remained significantly elevated after adjustment for cardiovascular risk factors. Hospitalized PAD events occurred months to years after the AAI was measured, with an adjusted RR of 5.55 (95% CI, 3.08 to 9.98) in those at risk for incident events. A statistically significant decline in survival was seen at each 0.1 decrement in the AAI. An AAI of <0.9 is an independent risk factor for incident CVD, recurrent CVD, and mortality in this group of older adults in the Cardiovascular Health Study.
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PMID:Ankle-arm index as a predictor of cardiovascular disease and mortality in the Cardiovascular Health Study. The Cardiovascular Health Study Group. 1007 55

Peripheral arterial disease affects approximately 8-10 million people in the United States. Approximately one-third to one-half of these individuals are symptomatic. The risk factors that contribute to peripheral arterial disease are similar to those associated with other forms of atherosclerosis, including diabetes mellitus, cigarette smoking, hypercholesterolemia, high blood pressure, and hyperhomocysteinemia. Of these, diabetes and cigarette smoking pose the greatest risk for developing peripheral arterial disease. The prognosis of patients with these risk factors is limited because of their greater risks for myocardial infarction, stroke, and cardiovascular death. Cardiovascular mortality correlates inversely with the ankle/brachial index, and the risk of death is greatest in those with the most severe peripheral arterial disease. Treatment regimens to reduce cardiovascular morbidity and mortality in patients with peripheral arterial disease should include risk factor modification and antiplatelet therapy. The cardinal symptoms of peripheral arterial disease include intermittent claudication and rest pain, with the latter being indicative of critical limb ischemia. Therapeutic strategies that focus on improving the patient's quality of life, reducing the severity of claudication, and improving limb viability include supervised exercise training, pharmacotherapy, and revascularization. Two drugs-pentoxifylline and cilostazol-currently are approved by the Food and Drug Administration for the treatment of patients with claudication. Meta-analyses have suggested that, compared with placebo, pentoxifylline improves maximal walking distance by approximately 20-25%. Cilostazol is a phosphodiesterase type 3 inhibitor. In clinical trials, cilostazol has consistently improved maximal walking distance as compared with placebo, with the range of improvement being approximately 40-60%. Drugs that are currently under investigation include propionyl-L-carnitine, vasodilator prostaglandins, L-arginine, and the angiogenic factors, vascular endothelial growth factor and basic fibroblast growth factors.
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PMID:Medical management of peripheral arterial disease. 1140 4

Peripheral arterial disease (PAD) is a major risk marker for systemic ischaemic events. The understanding of PAD has moved from PAD as an organ-specific disease to PAD as the lower-limb localization of a multifocal disease, i.e. atherothrombosis. Blood platelet activation and aggregation is a common denominator in atherothrombotic events, and use of antiplatelet agents in patients with PAD can inhibit thrombus formation and reduce the occurrence of myocardial infarction (MI), ischaemic stroke (IS) and vascular death. Many studies have investigated various antiplatelet regimens for preventing acute cardiovascular events in patients with a prior ischaemic event, although many of these studies had a number of limitations. The Antiplatelet Trialists' Collaboration performed a meta-analysis of 23 stroke trials and found an average odds risk reduction of 25% for a combined endpoint of stroke, MI or vascular death. The concept of atherothrombosis as a multifocal disease was challenged by the Clopidogrel versus Aspirin in Patients at Risk of Ischaemic Events (CAPRIE) trial. This study showed an 8.7% decrease in the relative risk reduction for further atherothrombotic events with clopidogrel over aspirin (p = 0.043) for the overall population, in terms of the combined endpoint of IS, Ml or vascular death.
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PMID:Rationale for the use of platelet aggregation inhibitors in PAD patients. 1178 61

Peripheral arterial disease (PAD) is a very common manifestation of atherosclerosis and is associated with a high risk of cardiovascular morbidity and mortality. Despite the magnitude of the problem, PAD is often under-recognized in clinical practice until its limb manifestations are severe or heart attack or stroke supervene. The PAD Awareness, Risk and Treatment: New Resources for Survival (PARTNERS) program, recently completed in the USA, had five aims: (1) creation of a method for detection of PAD in primary care practice; (2) assessment of the awareness of the PAD diagnosis in both patients and physicians; (3) assessment of the magnitude of the atherosclerotic risk factor burden and intensity of treatment of atherosclerotic risk factors in PAD patients; (4) assessment of the disease-specific and general quality of life of PAD patients in their communities; and (5) provision of an educational intervention to foster improved community-prescribed medical interventions for patients with PAD. Lack of public and physician interest in PAD contrasts with the high prevalence and poor medical prognosis of PAD. The intention of PARTNERS was to create a community-based program to measure current rates of PAD awareness, physician recognition and treatment intensity. Data obtained will form the basis of future clinical investigations to improve clinical care for PAD patients in the USA.
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PMID:PAD awareness, risk, and treatment: new resources for survival--the USA PARTNERS program. 1178 64

Peripheral arterial disease (PAD) is associated with platelet hyperaggregability as well as an increase in morbidity and mortality from myocardial infarction and stroke. Enhanced platelet activation in PAD may substantially contribute to these adverse outcomes. A relative resistance to aspirin therapy has been reported in patients with PAD. Therefore, clopidogrel may be superior to aspirin in treatment of PAD. Furthermore, the aspirin + clopidogrel combination could be more effective than monotherapy but its risk-benefit ratio has yet to be evaluated. Clopidogrel is preferable to ticlopidine because of its safer profile and the convenience of once-daily administration. The glycoprotein (Gp) IIb/IIIa inhibitors may also find a place as short-term therapy after peripheral angioplasty. There is a need to consider the use of clopidogrel in patients who cannot tolerate aspirin. Patients who have an event while taking aspirin also present a problem. One possibility here is to substitute aspirin with clopidogrel or to add clopidogrel to the aspirin. Although these options are currently not evidence based in patients with PAD, there is emerging evidence showing that they are realistic choices.
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PMID:The role of platelets in peripheral arterial disease: therapeutic implications. 1197 62

Peripheral arterial disease (PAD) is a common but under-recognized problem affecting older patients. Intermittent claudication is the most frequent symptom of PAD, although the diagnosis of PAD is often overlooked until the patient presents with limb-threatening ischemia. Importantly, PAD is a marker for generalized atherosclerosis and is closely associated with coronary and cerebrovascular disease. The severity of PAD has been correlated with an increased risk of myocardial infarction, stroke, and cardiovascular death. The recognition and diagnosis of PAD, combined with its appropriate medical management, may well reduce the overall risk of cardiovascular morbidity. When diagnosed early, both exercise and pharmacotherapy can ameliorate symptoms of claudication, augment functional performance, and improve quality of life.
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PMID:Peripheral arterial disease: medical care and prevention of complications. 1209 54


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