Peripheral Arterial Disease

6. Hirsch AT, Haskal ZJ, Hertzer NR, Bakal CW, Creager MA, Halperin JL, Hiratzka LF, Murphy WRC, Olin JW, Puschett JB, et al: ACC/AHA Guidelines for the Management of Patients with Peripheral Arterial Disease (Lower Extremity, Renal, Mesenteric, and Abdominal Aortic): A Collaborative Report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interven- tions, Society of Interventional Radiology, Society for Vascular Medicine and Biology, and the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arte- rial Disease). Washinhton DC, USA: American College of Cardiology; 2005 7. Muir RL. Peripheral arterial disease: pathophysiology, risk factors, diagno-

The ABPI is defi ned as the ratio of the highest systolic pressure at the ankle divided by the brachial systolic pres- sure (Naylor et al 1988). It has been widely accepted that an ABPI of less than 0.9 is up to 95% sensitive and 99% specifi c in detecting peripheral arterial disease that would be detected on angiography (Dormandy and Rutherford 2000; Aronow 2004). This non-invasive bedside test is a reliable tool in assessing the presence and severity of PAD rather than relying solely on a clinical diagnosis. An ABPI of less than 0.9 is associated with an increased risk of cardiovascular and cerebrovascular events (Newman et al 1999). The benefi t of early diagnosis by screening for asymptomatic PAD (defi ned by a ABPI of 0.9), is debated but remains to be established (Beckman et al 2006).

under diagnosed, undertreated, poorly understood, primary care practices across the United States, 29% of patients who are older than 70 years or who are older than 50 years with a history of smoking (i)To assess prevalence of lower limb rterial disease in patients with angiographically proven coronary artery disease, (ii) to see the relation between severity of coronary artery disease and peripheral arterial disease, and (iii) to coronary artery disease. Methodology: This was a prospective hospital based study conducted in the Department of Cardioogy at SKIMS, Soura, Srinagar, Kashmir. All the patients who were taken for coronary angiography in the Department of Srinagar were evaluated in terms of complete relevant history, clinical examination and laboratory investigation. The clinical symptoms like intermittent claudication, resting, pain, feeling of cold or numbness in toes were enquired. To ascertain the presence of intermittent claudication Edinburgh Claudication Questionnaire (ECQ) was administered. Results: There were 69 males and 33 females with male female ratio of 2.1:1. Mean age of population was was 13.7% as documented by peripheral angiography. Claudication was the only relevant symptom present in two patients (14.3%) with peripheral arterial disease as compared to none without peripheral arterial disease. Hypertensive o have peripheral arterial disease as it6 was present in 71.4% among patients with peripheral arterial disease. Diabetics were more likely to have peripheral arterial disease as it was present in 42.9% among patients with peripheral arterial disease. Family history of coronary Conclusion: Coronary artery disease evaluation should be considered in patients with lower extremity PAD having diabetes, multi-cardiovascular risk

Defining the ideal treatment for peripheral arterial disease remains an ongoing endeavor. The initial treatment standard of balloon angioplasty and stenting has produced suboptimal long-term outcomes due to in-stent restenosis and the subsequent need for revascularization. Yet, the field of endovascular medicine has seen an explosion of new technologies, which have yielded promising early and mid-term results. Anti-restenotic drug therapies have the potential to reduce neointimal hyperplasia, in-stent restenosis, and improve vessel patency in femoro-popliteal arteries. We discuss herein current and future drug eluting technologies across various delivery methods and platforms.

ABI: ankle-arm index; CHF: congestive heart failure; CI: confidence interval; COPD: chronic obstructive pulmonary disease; CRP: C-reactive protein; CVs: coefficients of variability; FBG: fasting blood glucose; IDIS: Iowa Drug Information Service; IL-10: interleukin-10; IL-6SR: IL-6 soluble receptor; LCBR: Laboratory for Cytokine Biochemistry; MrOS: Osteoporotic Fractures in Men Study; MV: multivariable; OR: odds ratio; PAD: peripheral arterial disease; PASE: Physical Activity Scale for the Elderly; TNF α : tumor-necrosis factor- α ; TNF α SRII: soluble receptor-II

How patients with peripheral arterial disease (PAD) communicate their knowledge about the illness and treatment was influenced by their information-seeking behaviour. They navigated through uncertainty, beliefs and facts about their illness and treatment with a discernible need of further knowledge about vascular disease and strategies for risk factor prevention. The short time spent with patients following endovascular treatment requires evidenced-based and innovative guid- ance in clinical practice in order to meet individual needs. It is, however, important to consider different as- pects of health literacy and how it may affect the pa- tient’s choice in actively or passively participating in the understanding and management of PAD. Hence, further research should focus on the implementation and evalu- ation of structured education programmes, perhaps sup- ported by modern technology as a complement to oral communication. This strategy may facilitate patients’ ability to participate and be involved in their own health and treatment.

Arteriography has been regarded as the main investigation for peripheral arterial disease and it is the traditional gold standard for peripheral arterial diagnosis. Its major drawback is that the information it provides is morphological, from which the haemodynamic impact of individual occlusive lesions has to be inferred. Knowing that most atherosclerotic plaques are eccentric, it is recognised that using uniplanar views for arteriography could result in missed or occasionally underestimated arterial stenoses^^ ‘“ . Although advances in the technique of arteriography and contrast materials, this procedure is still with associated complications. Egglin et al^^^ recently reported that the arteriography is associated with 2% complications. These may be due to contrast reaction, contrast induced renal failure, vascular injury (haematoma, dissection, false aneurysm, and distal embolisation), and wound complications.

3. Hirsch AT, Haskal ZJ, Hertzer NR, et al. ACC/AHA 2005 Practice guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease): endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation. Circulation. 2006 Mar 21;113(11): e463–e654.

1. Hirsch AT, Haskal ZJ, Hertzer NR, et al; for American Association for Vascular Surgery/Society for Vascular Surgery; Society for Cardiovascular Angiography and Interventions; Society for Vascular Medicine and Biology; Society of Interventional Radiology; ACC/ AHA Task Force on Practice Guidelines. ACC/AHA Guidelines for the Management of Patients with Peripheral Arterial Disease (lower extremity, renal, mesenteric, and abdominal aortic): a collaborative report from the American Associations for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (writing committee to develop guidelines for the management of patients with peripheral arterial disease); summary of recommendations. J Vasc Interv Radiol. 2006;17(9):1383–1397.

Peripheral arterial disease (PAD) is stenosis or occlusion of peripheral arterial vessels by atherosclerotic plaque. It may present as intermittent claudication, rest pain and impotence. PAD of the lower limbs is the third most important site of atherosclerotic disease after coronary heart disease and cerebrovascular disease. Increasing age, family history, smoking, hypertension, dyslipidemia and more decisively diabetes are significant risk factors. PAD is a clinical condition that has often been neglected, underdiagnosed, undertreated and has a serious outcome. It may lead to nonhealing wounds, gangrene and amputation of the lower limbs. Hence, early identification of patients at risk of PAD and timely referral to the vascular surgeon in severe cases is crucial.

10. Cotter G, Cannon CP, McCabe CH. Prior peripheral arterial disease and cerebrovascular disease are independent predictors of adverse outcome in patients with acute coronary syndromes: are we doing enough? Results from the orbofiban in patients with unstable coronary syndromes- thrombolysis in myocardial infarction (OPUS-TIMI) 16 study. Am Heart J. 2003;145(4):622-7.

Abstract: Peripheral arterial disease (PAD) is an increasingly recognized disorder that is associated with functional impairment, quality-of-life deterioration, increased risk of cardio- vascular ischemic events, and increased risk of total and cardiovascular mortality. Although earlier studies suggested that PAD was more common in men, recent reports based on more sensitive tests have shown that the prevalence of PAD in women is at least the same as in men, if not higher. PAD tends to present itself asymptomatically or with atypical symptoms more frequently in women than in men, and is associated with comorbidities or situations particularly or exclusively found in the female sex, such as osteoporosis, hypothyroidism, the use of oral contraceptives, and a history of complications during pregnancy. Fat-distribution patterns and differential vascular characteristics in women may influence the interpretation of diagnostic methods, whereas sex-related vulnerability to drugs typically used in subjects with PAD, dif- ferences in risk-factor distribution among sexes, and distinct responses to revascularization procedures in men and women must be taken into account for proper disease management. All these issues pose important challenges associated with PAD in women. Of note, this group has classically been underrepresented in research studies. As a consequence, several sex-related challenges regarding diagnosis and management issues should be acknowledged, and research gaps should be addressed in order to successfully deal with this major health issue.

Objective: Symptomatic peripheral arterial disease (PAD) is associated with impaired walking endurance in patients with chronic obstructive pulmonary disease (COPD).. However,[r]

Abstract: Peripheral arterial disease (PAD) is frequently diagnosed after permanent damage has occurred, resulting in a high rate of morbidity, amputation, and loss of life. Early and ongoing diagnosis and treatment is required for this progressive disease. Lifestyle modifications can prevent or delay disease progression and improve symptoms. Limb-sparing endovascular interventions can restore circulation based on appropriate diagnostic testing to pinpoint vascular targets, and intervention must occur as early as possible to ensure optimal clinical outcomes. An algorithm for the diagnosis and management of PAD was developed to enable a collaborative approach between the family practice and primary care physician or internist and various special- ists that may include a diabetologist, endocrinologist, smoking cessation expert, hypertension and lipid specialist, endovascular interventionalist, vascular surgeon, orthopedist, neurologist, nurse practitioner, podiatrist, wound healing expert, and/or others. A multidisciplinary team working together has the greatest chance of providing optimal care for the patient with PAD and ensuring ongoing surveillance of the patient’s overall health, ultimately resulting in better quality of life and increased longevity for patients with PAD.

IWGDF guidelines recommend the use of ABPI meas- urement in the assessment of the diabetic foot. They rec- ommend considering ABPI measurements of less than 0.9 as abnormal and those between 0.9–1.3 as largely exclud- ing PAD (GRADE recommendation: strong; Quality of evidence: low) [21]. Although, it is widely accepted that low values (< 0.9) are useful in detecting arterial disease, evidence suggests that high values (0.9–1.3 or > 1.3) cannot reliably exclude PAD in the presence of diabetes [29, 30]. This is because measurements can be falsely ele- vated due to the presence of incompressible calcified blood vessels [29]. Although this is acknowledged in the rationale for the IWGDF recommendation, confusingly it has still been retained in the guidance that a value be- tween 0.9–1.3 can exclude PAD. Participants in our survey demonstrated poor knowledge of ABPI interpretation with 44.3% either falsely considering that ABPI is a reliable method to exclude PAD in diabetes or being uncertain. They also demonstrated poor knowledge of the usefulness of ABPI with only 26% of respondents routinely perform- ing it in clinical practice. These results suggest that IWGDF guidance may need to be reviewed in order to clarify this issue.

An important anti-inflammatory athero-protective transcription factor, Kruppel-Like Factor 4 (KLF4), was recently reported to be down regulated in regions of disturbed flow (Table 3). In vitro investigations suggested that disturbed flow leads to increased CpG island methylation in KLF4 leading to increased expression of downstream KLF4 transcription target genes such as endothelial nitric oxide (eNOS), thrombomodulin, and monocyte chemotactic protein-1 (MCP-1) [62]. Arterial tissue isolated from regions of disturbed flow in pigs had significantly lower expression of KLF4 and eNOS, and a hypermethylated myocyte enhancer factor-2 binding site in the KLF4 promoter [62]. Recently, it was also shown that disturbed flow regulates genome-wide DNA methylation patterns in a DNMT-dependent manner in studies using a partial carotid ligation murine model [19]. The reduction of DNMT1 activity by 5Azacytidine (5-Aza) or siRNA markedly attenuated endothelial inflammation. Furthermore, disturbed flow resulted in hypermethylation of several crucial mechano-sensitive genes, including HoxA5 and KLF3 whose expression was subsequently restored by 5-Aza administration [19]. These data suggest that disturbed flow controls the epigenetic phenotype of the vascular endothelium and thereby promotes atherosclerosis.

the control group (23.7 ± 20.3 mL/min) was relatively lower than that of the non-PAD group undergoing dialy- sis (32.7 ± 15.5 mL/min) (Additional file 1: Figure S1c). One reason for this could have been that 53.1% of dialy- sis patients were treated with calcium antagonists and 27.3% of patients were treated with angiotensin- converting enzyme (ACE) inhibitors/angiotensin recep- tor blocker (ARB) drugs (Table 1). Debbabi et al. [35] re- ported that skin blood flow using a laser Doppler device was increased in patients with hypertension who were treated with ACE inhibitors compared with that in the control group and in patients with hypertension who were treated with other drugs. Our results showed that LDF-Plantar-Qb of dialysis patients in the non-PAD group was increased compared with that of the healthy control group; however, it is unknown whether ACE/ ARB drug administration affected this result. Another potential reason is that small capillary shunting in the peripheral skin area would be disrupted by aging, uremia, hypertension, diabetes, dyslipidemia, and athero- sclerosis. If the terminal arteriole and postcapillary ven- ule shunt at the peripheral skin area are disrupted by these factors, then blood flow would increase compared with that of a younger, healthy patient. Another reason for speculation is that LDF measurements were per- formed for dialysis patients, and it was suspected that the systemic body fluid increased more than that in the non-dialysis control group. In terms of the fluid volume, it was reported that skin blood flow was affected by hemodialysis [15]. According to the development of fluid removal, LDF blood flow in the plantar area of the foot decreased when systolic blood pressure decreased, sug- gesting that LDF blood flow is reflective of systemic blood flow or fluid volume.

Diagnosing PAD is of clinical impor- tance for two reasons. The first is to identify a patient who has a high risk of subsequent MI or stroke regardless of whether symptoms of PAD are present. The second is to elicit and treat symp- toms of PAD, which may be associated with functional disability and limb loss. PAD is often more subtle in its presenta- tion in patients with diabetes than in those without diabetes. In contrast to the focal and proximal atherosclerotic lesions of PAD found typically in other high-risk patients, in diabetic patients the lesions are more likely to be more diffuse and distal. Importantly, PAD in individuals with diabetes is usually accompanied by peripheral neuropathy with impaired sensory feedback. Thus, a classic history of claudication may be less common. However, a patient may elicit more subtle symptoms, such as leg fatigue and slow walking velocity, and simply attribute it to getting older. It has been reported that patients with PAD and diabetes experience worse lower- extremity function than those with PAD alone. 9 Also, diabetic patients who have

The term peripheral arterial disease (PAD) generally refers to a disorder that obtained the blood supply to lower or uper extremities. It is frequently associated with cerebral and coronary atherosclerosis. While studying diabetic patients with cardiovascular diseases Warren S et al found that peripheral arterial disease in diabetic patients is similar to that found in control subjects but it begins at an early age, advances more rapidly and is more common. 1

Materials and methods: Of 28 patients with peripheral arterial disease, who had successfully undergone stent implantation, 15 received cilostazol and 13 received ticlopidine. Primary patency rates were retrospectively analyzed by means of Kaplan–Meier survival curves, with differences between the two medication groups compared by log-rank test. A multivariate Cox proportional haz- ards model was applied to assess the effect of cilostazol versus ticlopidine on primary patency. Results: The cilostazol group had significantly better primary patency rates than the ticlopi- dine group. Cumulative primary patency rates at 12 and 24 months after stent placement were, respectively, 100% and 75% in the cilostazol group versus 39% and 30% in the ticlopidine group (P = 0.0073, log-rank test). In a multivariate Cox proportional hazards model with adjustment for potentially confounding factors, including history of diabetes, cumulative stent length, and poor runoff, patients receiving cilostazol had significantly reduced risk of restenosis (hazard ratio 5.4; P = 0.042).