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Peripheral arterial disease (PAD) is a common condition associated with an increased risk of coronary heart disease, myocardial infarction and stroke. It follows that PAD merits aggressive preventive treatment that includes lipid lowering drugs (mainly statins). This review summarises the current knowledge concerning the use and mechanisms of action of statins in patients with PAD. Statins not only lower the risk of vascular events, but they also improve the symptoms associated with PAD. There is also evidence that statins reduce surgical mortality and improve graft patency and limb salvage. Because of the high risk, a more aggressive goal [i.e. low density lipoprotein cholesterol (LDL-C) of 70 mg/dl; 1.8 mmol/l] [National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III), revised guidelines 2004] should be considered to maximally reduce the atheroma burden and related events. Not all statins can achieve this LDL-C target. Furthermore, there may be a need to use an additional lipid lowering drug so as to achieve the LDL-C goal and benefit from the different modes of action. Statins exert beneficial pleiotropic effects on haemostasis, the vasculature and inflammatory markers. There is also evidence that statins improve renal function (the plasma creatinine level is considered as an emerging vascular risk factor). Since PAD patients often take several drugs, there is a need to carefully consider their selection so as to maximize benefits and minimize adverse effects. Patients with PAD often do not receive adequate lipid lowering treatment. This situation needs to change.
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PMID:Peripheral arterial disease: a missed opportunity to administer statins so as to reduce cardiac morbidity and mortality. 1572 Feb 52

Peripheral arterial disease (PAD) is underdiagnosed and undertreated. This is despite the high vascular morbidity and mortality rates associated with PAD. There is also evidence that quitting smoking, improving the lipid profile, lowering the blood pressure, and administering antiplatelet drugs reduce the risk of vascular events in these patients. Secondary prevention for patients with PAD is yet to meet the standard of care for those with ischemic heart disease. The authors surveyed 200 claudicants attending a vascular clinic with additional follow-up in a risk modification clinic. After a median follow-up of 28 months (range: 6-65) there was a significant (p = 0.001) improvement in walking distance; 34 patients (17%) had a vascular ischemic event. Of those, 11 patients (5.5%) had worsening intermittent claudication and 9 had a stroke/transient ischemic attack; 9 events (4.5%) were fatal. The lipid targets were met in 76% the patients. Half the smokers quit smoking and 94% of the patients were taking antiplatelet drugs or anticoagulants. Blood pressure reached the accepted target in 87% of the patients. Secondary prevention in patients with PAD may reduce the risk of vascular events. Aggressive risk modification is therefore recommended.
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PMID:Risk modification in patients with peripheral arterial disease: a retrospective survey. 1588 95

Peripheral arterial disease (PAD) is a common, progressive manifestation of atherothrombotic vascular disease, which should be managed no different to cardiac disease. Indeed, there is growing evidence that PAD patients are a high risk group, although still relatively under-detected and under treated. This is despite the fact that PAD patients are an increased mortality rate comparable to those with pre-existing or established cardiovascular disease [myocardial infarction, stroke]. With a holistic approach to atherothrombotic vascular disease, our management of PAD can only get better.
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PMID:Peripheral arterial disease: a high risk - but neglected - disease population. 1597 99

Peripheral arterial disease (PAD) is associated with platelet hyperaggregability as well as an increase in morbidity and mortality from myocardial infarction (MI) and stroke. Purinergic signaling has been shown, both experimentally and clinically, to play an important role in the activation of platelets. Platelets express three different purinergic receptors: P2Y1, P2Y12 and P2X1. We assessed the hypothesis that the hyperaggregability associated with PAD is partly due to an increased P2 receptor expression at the transcriptional and/or translational level. Patients with PAD (n=8) and controls (n=8) were studied. Using a high-resolution channelyzer, platelet shape change (PSC) was assessed by measuring the median platelet volume (MPV). The fall in free platelet count following the addition of ADP was also assessed. Real-time PCR was used to quantify the mRNA expression and Western blots to quantify the protein expression of P2 receptors in platelets. The median (and range) fall in free platelet count after adding ADP was significantly (P=0.02) greater for patients [11% (5-24); n=8] than for controls [0.5% (0-10); n=8] despite using a lower concentration of ADP for the patient samples. The MPV did not differ significantly. The mRNA levels for the three P2 receptors were similar in PAD patients and controls. Western blot detected no significant differences in protein expression between these groups. Thus, platelets from PAD patients show an increased activation after stimulation with ADP (even though all patients were on aspirin). This hyperactivity was neither due to an obvious up-regulation of the mRNA levels nor to altered protein levels of P2 receptors in the platelets. It is suggested that the increased sensitivity to ADP in PAD is caused by post-receptor mechanisms.
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PMID:Increased platelet purinergic sensitivity in peripheral arterial disease--a pilot study. 1601 76

Peripheral arterial disease (PAD) is an under-recognized and underestimated complication of diabetes. Prevalence of PAD in diabetic patients is 25-30%. The main reason for underreporting is the largely asymptomatic nature of PAD in diabetes. It is important to diagnose PAD as soon as possible because PAD is an important marker for systemic atherosclerosis. Patients with claudication have approximately a 30% five-year mortality rate. PAD patients die 10 years earlier than patients without this atherothrombotic disease. About 70% of the PAD patients die from coronary heart disease, 5-11% die from stroke. PAD and diabetes are comorbid conditions and are associated with the risk of death from coronary artery bypass graft surgery. The prevalence of diabetes in patients who undergo cardiac surgery is 30% and the prevalence of PAD is 18%. The presence of PAD in diabetic patients had a similar 2-fold increase in the annual incidence of death compared with diabetic patients without PAD. The theory that diabetes and PAD together is associated with small vessel disease may play a role in the cause of the higher long-term mortality seen in at least two studies (Circulation 2004; suppl II: II/41-II/44).
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PMID:[Diabetes, heart surgery and the peripheral arteries]. 1659 51

Peripheral arterial disease in the legs represents a subset of atherosclerosis that manifests a particularly sinister profile. A predominance of sympathetic activity in the periphery favors the development of neurogenic atherosclerosis. Atherosclerosis may then produce flow derangements and decreased physical activity that serves to escalate sympathetic bias in a vicious cycle. Restoration of normal flow in peripheral arterial disease may not only produce local benefit due to improved perfusion, but also represent a gateway to correcting many systemic conditions that may at first glance appear unrelated but share a common etiology of autonomic dysfunction, such as gout, acute coronary syndromes, stroke, sleep apnea, arrhythmias, depression, erectile dysfunction, inflammation, hypercoagulability, sleep disorders, bowel dysfunction, renal failure, and aging.
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PMID:Peripheral arterial disease: a manifestation of evolutionary dislocation and feed-forward dysfunction. 1670 60

Atherothrombosis involves the mutually interactive dual mechanistic processes of atherosclerotic plaque progression and thrombus formation. In the setting of acute plaque rupture, resultant thrombus formation precipitates acute ischemic events such as acute coronary syndromes (ACS), stroke, and transient ischemic attack. Peripheral arterial disease is also a manifestation of atherothrombotic disease, and occurs both acutely and as a result of underlying disease progression. Atherothrombotic disease is highly prevalent and imposes a substantial burden on the community. For example, coronary artery disease was the single greatest cause of mortality among men and women in the US and accounted for an estimated US dollars 142.1 billion in health costs in 2005. Activated platelets are the prime mediators of arterial thrombus formation. This review discusses the evidence supporting the use of oral antiplatelet agents with other risk prevention strategies in the long-term secondary prevention of atherothrombotic disease. The most widely used oral antiplatelet agent is aspirin (acetylsalicylic acid), and both aspirin and clopidogrel have proven roles in the management of atherothrombotic disease. Clopidogrel should also be used in combination with aspirin in patients with non-ST-segment elevation ACS and those undergoing percutaneous coronary intervention. Recent data suggest that clopidogrel may have a significant role, with or without fibrinolytic therapy, in the immediate management of ST-segment elevation ACS.
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PMID:The role of oral antiplatelet agents in atherothrombotic disease. 1678 Mar 88

Peripheral arterial disease (PAD) is a manifestation of widespread atherosclerosis. Lipid modification (especially with statins) is a component of the treatment of patients with PAD since this condition is considered a coronary heart disease equivalent. This review considers the mechanism of action of statins in PAD. Statins have been shown to reduce the incidence of new coronary events in patients with PAD. However, surveys suggest that many such patients remain undertreated. Statins can also increase walking distance in patients with PAD. There is also evidence that statins can improve renal function in these patients. Several other actions of statins are considered in this review. PAD patients have an increased morbidity and mortality, largely due to myocardial infarction and stroke. Recognizing and treating these high-risk patients as early as possible should be a priority.
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PMID:Statins and peripheral arterial disease: potential mechanisms and clinical benefits. 1684 Dec 71

Under the auspices of the Agency for Healthcare Research and Quality, the United States Preventive Services Task Force (USPSTF) recently released an update to its 1996 Peripheral Arterial Disease (PAD) Screening Recommendation Statement. The USPSTF recommended against PAD screening, giving the practice a "D" level recommendation. This level suggests that little or no benefit could accrue from PAD screening and that screening-associated harm could occur. The present commentary disputes the Task Force's recommendation. The USPSTF statement omitted important peer-reviewed data on the prevalence, screening efficacy, and short-term adverse prognosis of patients with PAD and failed to consider the beneficial outcomes that probably would result from timely diagnosis and treatment of this important manifestation of atherosclerosis. The Task Force implied that screening may lead to unnecessary tests, including increased risk associated with use of contrast angiographic studies. However, most patients with PAD have neither classic symptoms of leg claudication nor threatened limbs but have an extraordinarily high rate of adverse cardiovascular events, such as myocardial infarction, stroke, and death--events that should serve as a key rationale for screening. Medical therapy, including risk factor modification and antiplatelet medications, is known to reduce cardiovascular morbidity and mortality rates in these patients. The Task Force's recommendation against PAD detection may itself adversely result in inadequate recognition and treatment of PAD, with adverse public health consequences. We encourage the USPSTF to reevaluate the extant data, add vascular specialty expertise to its review group, and reconsider its recommendation.
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PMID:The United States preventive services task force recommendation statement on screening for peripheral arterial disease: more harm than benefit? 1732 50

Peripheral arterial disease (PAD) is a well-established risk factor for clinical cardiovascular disease (CVD). The impact of a low ankle-brachial index (ABI), higher than the generally recognized 0.9 cutpoint for PAD, on CVD risk is not well characterized. We analyzed data from the 1999 to 2002 National Health and Nutrition Examination Survey (n = 4,895), a nationally representative sample of United States adults, to determine the prevalence of PAD (ABI <0.90), borderline PAD (ABI 0.90 to 0.99), a low-normal ABI (1.00 to 1.09), and a normal ABI (1.10 to 1.29), and the association of these ABI levels with CVD. The prevalence of PAD, borderline PAD, a low-normal ABI, and a normal ABI was 5.0%, 8.7%, 27.8%, and 54.8%, respectively. After age, race/ethnicity, and gender adjustment, the odds ratios of a 10-year coronary heart disease (CHD) risk of >or=20%, CHD, stroke, and CVD were higher at lower ABI levels (each p trend <0.01). After additional adjustment for potential confounders, the odds ratios associated with a low-normal ABI, borderline PAD, and PAD, compared with those with a normal ABI, were 1.24 (95% confidence interval [CI] 0.91 to 1.70), 1.34 (95% CI 0.99 to 1.83), and 1.87 (95% CI 1.29 to 2.73), respectively (p trend <0.001) for CVD and 1.20 (95% CI 0.82 to 1.77), 1.45 (95% CI 0.80 to 2.63), and 2.02 (95% CI 1.20 to 3.39), respectively (p trend = 0.015) for a 10-year risk of CHD of >or=20%. In contrast, a trend was not present for CHD and stroke after multivariate adjustment. In conclusion, subjects with a low-normal ABI or with borderline PAD need screening for CVD risk factors, and interventions may be appropriate to prevent cardiovascular events.
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PMID:Relation of borderline peripheral arterial disease to cardiovascular disease risk. 1705 34


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