Prognostic impact of atrial fibrillation on the outcomes of peripheral artery disease according to preoperative symptoms for endovascular revascularization.

Peripheral artery disease (PAD) and atrial fibrillation (AF) are associated with major cardiovascular and cerebrovascular events (MACCE). However, outcomes stratified according to the preoperative symptoms of PAD in patients with AF have not been sufficiently investigated. This was a retrospective study of prospectively collected data pertaining to 2237 patients (1179 patients with intermittent claudication [IC] and 1058 patients with critical limb-threatening ischemia [CLTI]) who underwent endovascular therapy at 34 hospitals between August 2014 and August 2016. AF was present in 91 (7.7%) patients with IC and 150 (14.2%) patients with CLTI. In the CLTI group, patients with AF had a higher event rate of MACCE and all-cause death than those without AF (1-year rates of freedom from MACCE: 0.66 and 0.81 in patients with and without AF, respectively, p < 0.001). In contrast, in the IC group, there was no statistically significant difference in the rates of MACCE between patients with and without AF. In the Cox multivariate analysis, AF was a significant predictor of MACCE in patients with CLTI but not in patients with IC, even after adjusting for covariates. The impact of AF on the outcome of patients with PAD was greater in those with CLTI. Further studies are needed to clarify the possible mechanisms underlying these differences.

Inflammation and Loss of Skeletal Muscle Mass in Chronic Limb Threatening Ischemia.

BACKGROUND: Lower extremity peripheral arterial disease (PAD) is an atherosclerotic disease of the lower extremities. Atherosclerosis, inflammation, and sarcopenia are independently associated and potentiate each other. Inflammation is deeply involved in the formation and progression of atherosclerosis and is also involved in the pathophysiology of sarcopenia. Sarcopenia is defined as low muscle mass, with low muscle strength. This study aims to determine the differences in skeletal muscle characteristics and in inflammatory parameters between patients with claudication and with chronic limb threatening ischemia (CLTI). METHODS: An observational, prospective study in patients with PAD was conducted from January 2018 to December 2020. The clinical characteristics and the cardiovascular risk factors were prospectively registered. The inflammatory parameters determined were: positive acute phase proteins (C-reactive Protein- CRP- and fibrinogen) and negative acute phase proteins albumin, total cholesterol and high-density lipoprotein (HDL). The skeletal muscle area and density were quantified with a computed topography (CT) scan. The strength was determined with a Jamar® hydraulic hand dynamometer. RESULTS: A total of 116 patients (mean age: 67.65 ± 9.53 years-old) 64% with claudication and 46% with CLTI were enrolled in the study. No differences were registered between patients with claudication and CLTI on age, cardiovascular risk factors (hypertension, dyslipidemia, diabetes mellitus, and smoking habits) and medication. There was a higher prevalence of men in the claudication group (88.89% vs. 71.70%, P = 0.019). Analyzing the inflammatory parameters, we noted that patients with CLTI had increased serum levels of positive acute phase proteins: CRP (37.53 ± 46.61 mg/L vs. 9.18 ± 26.12 mg/L, P = 0.000), and fibrinogen (466.18 ± 208.07 mg/dL vs. 317.37 ± 79.42 mg/dL, P = 0.000). CLTI patients had decreased negative acute phase proteins: albumin (3.53 ± 0.85 g/dL vs. 3.91 ± 0.72 g/dL, P = 0.001), total cholesterol (145.41 ± 38.59 mg/dL vs. 161.84 ± 34.94 mg/dL, P = 0.013) and HDL (38.70 ± 12.19 mg/dL vs. 51.31 ± 15.85 mg/dL, P = 0.000). We noted that patients with CLTI had lower skeletal muscle area and mass (14,349.77 ± 3,036.60 mm2 vs. 15,690.56 ± 3,183.97 mm2P = 0.013; 10.11 ± 17.03HU vs. 18.02 ± 13.63HU P = 0.013). After adjusting for the variable sex, the association between skeletal muscle density and CLTI persisted (r (97) = -0.232, P = 0.021). The groups did not differ in strength (patients with claudication: 25.39 ± 8.23 Kgf vs. CLTI: 25.17 ± 11.95 Kgf P = 0.910). CONCLUSIONS: CLTI patients have decreased skeletal muscle mass and a systemic inflammation status. Recognizing the deleterious triad of atherosclerosis, inflammation and loss of skeletal mass patients with CLTI is an opportunity to improve medical therapy and to perform a timely intervention to stop this vicious cycle.

Effects of walking impairment on mental health burden, health risk behavior and quality of life in patients with intermittent claudication: A cross-sectional path analysis.

INTRODUCTION: Intermittent claudication is the leading symptom of peripheral artery disease (leg pain when walking). The present study investigates the extent to which walking impairment is associated with health-related quality of life, mental health and health risk behavior. METHODS: A theory-based, cross-sectional path model was empirically examined using pre-intervention baseline data from a multicenter, randomized-controlled trial of patients with intermittent claudication (PAD-TeGeCoach). Data were available from 1 696 patients who completed a battery of questionnaires between April 14, 2018 and March 12, 2019, including measures of walking impairment (Walking Impairment Questionnaire), health-related quality of life (SF-12), mental burden (GAD-7, PHQ-9), nicotine- and alcohol-related risk behavior (Fagerström-Test, AUDIT-C). Sociodemographic characteristics and comorbid conditions were included in the postulated model a priori to minimize confounding effects. RESULTS: Walking impairment was associated with an increase in depressive (ß = -.36, p < .001) and anxiety symptoms (ß = -.24, p < .001). The prevalence of depressive and anxiety symptoms was 48.3% and 35.5%, respectively, with female patients and those of younger age being at greater risk. Depressive symptoms were predictive of an increased tobacco use (ß = .21; p < .001). Walking impairment had adverse effects on physical quality of life, both directly (ß = .60, p < .001) and indirectly mediated through depressive symptoms (ß = -.16, p < .001); and indirectly on mental quality of life mediated through depressive (ß = -.43, p < .001) and anxiety symptoms (ß = -.35, p < .001). DISCUSSION: The findings underscore the need for a comprehensive treatment strategy in patients with intermittent claudication. Measures to improve walking impairment (e.g. exercise training) are key to enhance quality of life and should be the primary treatment. As a key mediator of mental quality of life, depressive and anxiety symptoms should be addressed by rigorously including mental health treatment. Risky health behaviors should be approached by promoting behavior change (e.g. smoking cessation) as a secondary prevention of peripheral artery disease.

The assessment of lower extremity peripheral artery disease impact on body mass center disorders.

BACKGROUND: Lower extremity peripheral artery disease is a problem of contemporary medicine and along with the ischemic heart disease it is considered to be a civilization disease. The risk of the disease increases significantly within a group of people reaching the age of 55 years and is closely related to co-occurring hazardous factors, such as diabetes, hyperlipidemia, hypertension or tobacco smoking. The first symptom reported by patients is intermittent claudication. Such symptoms may indicate that lower extremity peripheral artery disease does have an impact on posture disorders and motor skills. METHODS: The study covered four stages. The first stage involved medical interviews to obtain information regarding anthropometry, age, motor organ surgery, concomitant diseases and the lifestyle. In the following stage the value of the ankle brachial index for both lower limbs were calculated. In case of symptomatic patients, additionally, the location of artery stenosis/aortoiliac section, was verified. The third stage involved using a dynamometric platform for determination of the body mass center position for both studied groups. In the fourth stage a treadmill walk test was used to assess the participants for intermittent claudication. FINDINGS: Based on the obtained results, an attempt was taken to observe the relationship between the clinical characteristics of the disease and the body mass center position deviations. INTERPRETATION: The attempt was undertaken to assess whether the measurement of body mass center position might be a diagnostic parameter to evaluate the patient's condition and thus an indication for taking a decision for surgical treatment or rehabilitation.

Prevalence of chronic opioid use in patients with peripheral arterial disease undergoing revascularization.

OBJECTIVE: Opiate use, dependence, and the associated morbidity and mortality are major current public health problems in the United States. Little is known about patterns of opioid use in patients with peripheral arterial disease (PAD). The purpose of this study was to identify the prevalence of chronic preoperative and postoperative prescription opioid use in patients with PAD. A secondary aim was to determine the demographic, comorbid conditions, and operative characteristics associated with chronic opioid use. METHODS: Using a single-institution database of patients with PAD undergoing open or endovascular lower extremity intervention from 2013 to 2014, data regarding opiate use and associated conditions were abstracted for analysis. Patients were excluded if they did not live in North Carolina or surgery was not for PAD. Preoperative (PreCOU) and postoperative chronic opioid use (PostCOU) were defined as consistent opioid prescription filling in the 3 months before and after the index procedure, respectively. Opioid prescription filling was assessed using the North Carolina Controlled Substance Reporting System. Demographics, comorbid conditions, other adjunct pain medication data, and operative characteristics were abstracted from our institutional electronic medical record. Associations with PreCOU were evaluated using the t test, Wilcoxon test, or two-sample median test (continuous), or the χ2 or Fisher exact tests (categorical). RESULTS: A total of 202 patients undergoing open (108; 53.5%) or endovascular (94; 46.5%) revascularization for claudication or critical limb ischemia were identified for analysis. The mean age was 64.6 years, and 36% were female. Claudication was the indication for revascularization in 26.7% of patients, and critical limb ischemia was the indication in 73.3% of patients. The median preoperative ankle-brachial index (ABI) was 0.50. Sixty-eight patients (34%) met the definition for PreCOU. PreCOU was associated with female gender, history of chronic musculoskeletal pain, benzodiazepine use, and self-reported illicit drug use. Less than 50% of patients reported use of non-opiate adjunct pain medications. No association was observed between PreCOU and pre- or postoperative ABI, or number of prior lower extremity interventions. Following revascularization, the median ABI was 0.88. PreCOU was not associated with significant differences in postoperative complications, length of stay, or mortality. Overall, 71 patients (35%) met the definition for PostCOU, 14 of whom had no history of preoperative chronic opiate use. Ten patients with PreCOU did not demonstrate PostCOU. CONCLUSIONS: Chronic opiate use was common in patients with PAD with a prevalence of approximately 35%, both prior to and following revascularization. Revascularization was associated with a termination of chronic opiate use in less than 15% of patients with PreCOU. Additionally, 10% of patients who did not use opiates chronically before their revascularization did so afterwards. Patients with PAD requiring intervention represent a high-risk group with regards to chronic opiate use. Increased diligence in identifying opioid use among patients with PAD and optimizing the use of non-narcotic adjunct pain medications may result in a lower prevalence of chronic opiate use and its attendant adverse effects.

Evaluation of functional capacity and muscle metabolism in individuals with peripheral arterial disease with and without diabetes.

OBJECTIVE: Peripheral arterial disease (PAD) is characterized by intermittent claudication, which interferes with walking and leads to worsening of functional capacity. This mechanism has not been clearly defined in PAD. Thus, the aim of our study was to identify the muscular metabolism and vascular function variables using near-infrared spectroscopy (NIRS) and their possible associations with functional capacity in individuals with PAD and secondly to verify the differences in these variables between persons with PAD and diabetes mellitus (DM) and those with PAD without DM. METHODS: A total of 39 participants with intermittent claudication were enrolled, 14 of whom had DM. They were assessed for functional capacity by the total distance covered in the treadmill test with the speed and grade constant and for muscle function and metabolism using near-infrared spectroscopy at rest and during the treadmill test. The Spearman correlation coefficient was computed to assess the presence of an association between the variables, and multiple linear regression analysis was performed, considering the total test distance as the dependent variable. The assessment between groups was performed using the independent t test or Mann-Whitney U test. RESULTS: The near-infrared spectroscopy variables related to tissue oxygen saturation in the test recovery phase were correlated with the functional performance during the treadmill test. Thus, those with a longer or slower recovery time and those with greater tissue deoxygenation had walked a shorter distance. A significant difference (P = .049) was noted between those with PAD stratified by DM in the reoxygenation time required for an occlusion. CONCLUSIONS: These findings reinforce the hypothesis that peripheral factors related to vascular function and muscular metabolism can affect the walking capacity of persons with PAD and that microvascular dysfunction is more prevalent among those with PAD and DM.

High Apolipoprotein E Levels Predict Adverse Limb Events in Patients with Peripheral Artery Disease Due to Peripheral Artery Disease Undergoing Endovascular Treatment and On-Statin Treatment.

Little is known about the association between limb prognosis in peripheral artery disease and apolipoprotein E (apoE). We evaluated the long-term impact of apoE on adverse limb events in patients with intermittent claudication receiving statin treatment.A total of 218 consecutive patients (mean age, 73 ± 8 years; 81% men) with intermittent claudication who underwent their first intervention between 2009 and 2020 were included in this study. All patients had achieved LDL-C < 100 mg/dL on statin treatment and were divided into two groups based on the apoE value (≥ 4.7 or < 4.7 mg/dL). We evaluated the incidence of major adverse limb events (MALEs), including vessel revascularization and limb ischemia development.A total of 39 and 179 patients were allocated to the higher and lower apoE groups, respectively. Compared to the lower apoE group, the higher apoE group had a significantly higher total cholesterol level, triglyceride level, and non-high-density lipoprotein cholesterol level. During the median follow-up period of 3.6 years, 30 patients (13.8%) developed MALEs. Kaplan-Meier analysis revealed that the cumulative incidence of MALEs in the higher apoE group was significantly higher than that in the lower apoE group (44.0% versus 21.6%, log-rank test, P = 0.002). During multivariable Cox hazard analysis, higher apoE level (≥ 4.7 mg/dL) (hazard ratio, 2.61; 95% confidence interval, 1.18-5.70, P = 0.019) was the only strong independent predictor of MALEs.ApoE levels could be a strong predictor and residual risk for long-term limb prognosis in patients with intermittent claudication and achieving LDL-C < 100 mg/dL with statin treatment.

Gait variability is affected more by peripheral artery disease than by vascular occlusion.

BACKGROUND: Patients with peripheral artery disease with intermittent claudication (PAD-IC) have altered gait variability from the first step they take, well before the onset of claudication pain. The mechanisms underlying these gait alterations are poorly understood. AIMS: To determine the effect of reduced blood flow on gait variability by comparing healthy older controls and patients with PAD-IC. We also determined the diagnostic value of gait variability parameters to identify the presence of PAD. METHODS: A cross-sectional cohort design was used. Thirty healthy older controls and thirty patients with PAD-IC walked on a treadmill at their self-selected speed in pain free walking (normal walking for healthy older controls; prior to claudication onset for PAD) and reduced blood flow (post vascular occlusion with thigh tourniquet for healthy older controls; pain for PAD) conditions. Gait variability was assessed using the largest Lyapunov exponent, approximate entropy, standard deviation, and coefficient of variation of ankle, knee, and hip joints range of motion. Receiver operating characteristics curve analyses of the pain free walking condition were performed to determine the optimal cut-off values for separating individuals with PAD-IC from those without PAD-IC. RESULTS AND DISCUSSION: Patients with PAD-IC have increased amount of variability for knee and hip ranges of motion compared with the healthy older control group. Regarding the main effect of condition, reduced blood flow demonstrated increased amount of variability compared with pain free walking. Significant interactions between group and condition at the ankle show increased values for temporal structure of variability, but a similar amount of variability in the reduced blood flow condition. This demonstrates subtle interactions in the movement patterns remain distinct between PAD-IC versus healthy older controls during the reduced blood flow condition. A combination of gait variability parameters correctly identifies PAD-IC disease 70% of the time or more. CONCLUSIONS: Gait variability is affected both by PAD and by the mechanical induction of reduced blood flow. Gait variability parameters have potential diagnostic ability, as some measures had 90.0% probability of correctly identifying patients with PAD-IC.

Efficacy and Safety of Adjunctive Cilostazol to Clopidogrel-Treated Diabetic Patients With Symptomatic Lower Extremity Artery Disease in the Prevention of Ischemic Vascular Events.

Background Type 2 diabetes mellitus is a risk factor for lower extremity arterial disease. Cilostazol expresses antiplatelet, anti-inflammatory, and vasodilator actions and improves the claudication intermittent symptoms. We investigated the efficacy and safety of adjunctive cilostazol to clopidogrel-treated patients with type 2 diabetes mellitus exhibiting symptomatic lower extremity arterial disease, in the prevention of ischemic vascular events and improvement of the claudication intermittent symptoms. Methods and Results In a prospective 2-arm, multicenter, open-label, phase 4 trial, patients with type 2 diabetes mellitus with intermittent claudication receiving clopidogrel (75 mg/d) for at least 6 months, were randomly assigned in a 1:1 ratio, either to continue to clopidogrel monotherapy, without receiving placebo cilostazol (391 patients), or to additionally receive cilostazol, 100 mg twice/day (403 patients). The median duration of follow-up was 27 months. The primary efficacy end point, the composite of acute ischemic stroke/transient ischemic attack, acute myocardial infarction, and death from vascular causes, was significantly reduced in patients receiving adjunctive cilostazol compared with the clopidogrel monotherapy group (sex-adjusted hazard ratio [HR], 0.468; 95% CI, 0.252-0.870; P=0.016). Adjunctive cilostazol also significantly reduced the stroke/transient ischemic attack events (sex-adjusted HR, 0.38; 95% CI, 0.15-0.98; P=0.046) and improved the ankle-brachial index and pain-free walking distance values (P=0.001 for both comparisons). No significant difference in the bleeding events, as defined by Bleeding Academic Research Consortium criteria, was found between the 2 groups (sex-adjusted HR, 1.080; 95% CI, 0.579-2.015; P=0.809). Conclusions Adjunctive cilostazol to clopidogrel-treated patients with type 2 diabetes mellitus with symptomatic lower extremity arterial disease may lower the risk of ischemic events and improve intermittent claudication symptoms, without increasing the bleeding risk, compared with clopidogrel monotherapy. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02983214.

Unusual presentation of moyamoya disease with popliteal involvement: case report and review of the literature / Apresentação incomum de doença de moyamoya com envolvimento poplíteo: relato de caso e revisão da literatura

Abstract Moyamoya disease is a rare disorder that involves the cerebrovascular system. Usually, it leads to occlusion of the arteries of the cerebral system and causes cerebral circulatory complaints. A 48-year-old female patient was admitted to our clinic with intermittent claudication in both legs. Biphasic and monophasic waveform patterns were detected bilaterally in distal (trifurcation arteries) lower extremities with Doppler sonography. The patient therefore underwent systemic vascular examination. Computed tomography angiography revealed bilateral carotid occlusion at the level of supraclinoid segments, and opacifications were detected at the distal segments of the bilateral anterior cerebellar and middle cerebellar arteries. The patient was diagnosed with moyamoya disease, and anticoagulant treatment was started. In conclusion, most previous reports have presented the cerebrovascular involvement of moyamoya disease. However, this disease can involve different peripheral vascular systems and careful and systemic vascular examination is necessary for an exact diagnosis.

Resumo A doença de moyamoya é um distúrbio raro que envolve o sistema cerebrovascular. Normalmente, leva à oclusão das artérias do sistema cerebral e causa problemas circulatórios no cérebro. Uma mulher de 48 anos foi admitida em nossa clínica com claudicação intermitente em ambas as pernas. Na ultrassonografia com Doppler, foram detectados padrões de formato de onda bifásico e monofásico nas extremidades inferiores distais (artérias da trifurcação) de forma bilateral. Portanto, realizou-se o exame vascular sistêmico na paciente. A angiografia por tomografia computadorizada revelou oclusão carotídea bilateral no nível dos segmentos supraclinoides, e opacificações foram detectadas nos segmentos distais das artérias cerebelares anteriores e médias de forma bilateral. A paciente foi diagnosticada com doença de moyamoya, e o tratamento anticoagulante foi iniciado. Em conclusão, a maioria dos relatos anteriores apresentou o envolvimento cerebrovascular da doença de moyamoya. No entanto, essa doença pode envolver diferentes sistemas vasculares periféricos, e um exame vascular sistêmico minucioso é necessário para um diagnóstico exato.

Chronic bronchitis without airflow obstruction, asthma and rhinitis are differently associated with cardiovascular risk factors and diseases.

BACKGROUND AND OBJECTIVES: Cardiovascular and respiratory diseases can frequently coexist. Understanding their link may improve disease management. We aimed at assessing the associations of chronic bronchitis (CB), asthma and rhinitis with cardiovascular diseases and risk factors in the general population. METHODS: We used data collected in the Gene Environment Interactions in Respiratory Diseases study, an Italian multicentre, multicase-control study. Among 2463 participants (age 21-86, female 50%) who underwent standardized interviews, skin prick and lung function tests, we identified 254 cases of CB without airflow obstruction, 418 cases of asthma without CB, 959 cases of rhinitis alone, and 832 controls. The associations of respiratory diseases with reported cardiovascular risk factors (lifestyles, hypertension, dyslipidaemia), heart disorders (myocardial infarction, coronary thrombosis, angina, aorta or heart surgery) and intermittent claudication were estimated through relative risk ratios (RRR) by multinomial logistic regression models. RESULTS: Compared to controls, CB cases were more likely to be heavy smokers, alcohol consumers, physically inactive, and to suffer from hypertension or dyslipidaemia; rhinitis cases were less obese but more likely to have hypertension. Asthma was significantly associated with current smoking. After adjusting for cardiovascular risk factors, heart disorders were associated with CB (RRR[95%CI]: 1.58[1.12-2.22]) and rhinitis (1.35[0.98-1.85]) and intermittent claudication was associated with CB (3.43[2.52-4.67]), asthma (1.51[1.04-2.21]) and rhinitis (2.03[1.34-3.07]). CONCLUSIONS: CB, asthma and rhinitis were associated with cardiovascular risk factors and diseases. In particular, CB shared with cardiovascular diseases almost all risk factors and was strongly associated with a higher risk of heart disorders and intermittent claudication.

Intermittent Claudication in Physiotherapists' Practice.

Intermittent claudication is a symptom of atherosclerosis of the lower limbs (peripheral arterial disease (PAD)) and is characterized by pain and cramps of lower limb muscles during exercise. Claudication leads to a reduction in physical activity of patients. PAD is a systemic disease. Atherosclerotic lesions located in the arteries of the lower limbs not only pose the risk of the ischemic limb loss, but above all, they are an important prognostic factor. Patients with claudication are at significant risk of cardiovascular complications such as infarcts or strokes. Comprehensive rehabilitation of patients with intermittent claudication based on the current TASC II (Inter-Society Consensus for the Management of Peripheral Arterial Disease) guidelines, ESC (European Society of Cardiology) guidelines, and AHA (American Heart Association) guidelines includes supervised treadmill training, training on a bicycle ergometer, Nordic Walking, resistance exercises of lower limb muscles, and exercises of upper limbs. A trained, educated, and motivated patient has a chance to improve life quality as well as life expectancy.

[Lower limb arterial disease in patients with diabetes]. / Artériopathie chez le patient diabétique.

Lower limb arteriopathy is a frequent and potentially serious complication of diabetes. In fact, it largely explains the high incidence of lower limb amputations in diabetic patients as well as a significant impairment of quality of life in the case of intermittent claudication or decubitus pain. The severity of the disease is also based on the associated cardiovascular morbidity and mortality. The diagnosis is primarily made by the clinical examination, completed by functional hemodynamic tests (ankle/brachial index, transcutaneous oxygen pressure and toe pressure) and possibly imaging tests (arterial Doppler and arteriography of the lower limbs). The treatment of lower limbs arterial disease will depend on the vascular symptomatology, the severity of the vascular lesions evaluated by the hemodynamic tests and by the anatomical characteristics of the vascular lesions.

ARTÉRIOPATHIE CHEZ LE PATIENT DIABÉTIQUE. L'artérite des membres inférieurs est une complication fréquente et potentiellement grave du diabète. En effet, elle explique en grande partie l'incidence élevée des amputations des membres inférieurs chez les patients diabétiques ainsi qu'une altération importante de la qualité de vie en cas de claudication intermittente ou de douleurs de décubitus. La gravité de la maladie repose également sur la morbi-mortalité cardiovasculaire associée. Le diagnostic est porté avant tout par l'examen clinique, complété par des tests hémodynamiques fonctionnels (indice de pression systolique à la cheville, pression transcutanée en oxygène et pression d'orteil) et éventuellement des examens d'imagerie (Doppler artériel des membres inférieurs et artériographie). Le traitement de l'artériopathie dépend de la symptomatologie vasculaire, de la sévérité des lésions vasculaires évaluée par les tests hémodynamiques fonctionnels et par les caractéristiques anatomiques des lésions vasculaires.

The progression rate of peripheral arterial disease in patients with intermittent claudication: a systematic review.

BACKGROUND: Intermittent claudication (IC) is the most common symptom of peripheral arterial disease and is generally treated conservatively due to limited prognostic evidence to support early revascularisation in the individual patient. This approach may lead to the possible loss of opportunity of early revascularisation in patients who are more likely to deteriorate to critical limb ischaemia. The aim of this review is to evaluate the available literature related to the progression rate of symptomatic peripheral arterial disease. METHODS: We conducted a systematic review of the literature in PubMed and MEDLINE, Cochrane library, Elsevier, Web of Science, CINAHL and Opengrey using relevant search terms to identify the progression rate of peripheral arterial disease in patients with claudication. Outcomes of interest were progression rate in terms of haemodynamic measurement and time to development of adverse outcomes. Two independent reviewers determined study eligibility and extracted descriptive, methodologic, and outcome data. Quality of evidence was evaluated using the Cochrane recommendations for assessing risk of bias and was reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: Seven prospective cohort studies and one retrospective cohort study were identified and included in this review with the number of participants in each study ranging from 38 to 1244. Progression rate reports varied from a yearly decrease of 0.01 in ankle-brachial pressure index (ABPI) to a yearly decrease ABPI of 0.014 in 21% of participants. Quality of evidence ranged from low to moderate mostly due to limited allocation concealment at recruitment and survival selection bias. CONCLUSIONS: Progression of PAD in IC patients is probably underestimated in the literature due to study design issues. Predicting which patients with claudication are likely to deteriorate to critical limb ischaemia is difficult since there is a lack of evidence related to lower limb prognosis. Further research is required to enable early identification of patients at high risk of progressing to critical ischaemia and appropriate early revascularisation to reduce lower limb morbidity.

Unmet medical needs in intermittent Claudication with diabetes and coronary artery disease-A "real-world" analysis on 21 197 PAD patients.

BACKGROUND: Peripheral artery disease (PAD) is frequently co-prevalent with coronary artery disease (CAD) and diabetes (DM). The study aims to define the burden of CAD and/ or DM in PAD patients at moderate stages and further to evaluate its impact on therapy and outcome. METHODS: Study is based on health insurance claims data of the BARMER reflecting an unselected "real-world" scenario. Retrospective analyses were based on 21 197 patients hospitalized for PAD Rutherford 1-3 between 1 January 2009 to 31 December 2011, including a 4-year follow-up (median 775 days). RESULTS: In PAD patients, CAD is prevalent in 25.3% (n = 5355), DM in 23.5% (n = 4976), and both CAD and DM in 8.2% (n = 1741). Overall, in-hospital mortality was 0.4%, being increased if CAD was present (CAD alone: OR 1.849; 95%-CI 1.066-3.208; DM alone: OR 1.028; 95%-CI 0.520-2.033; CAD and DM: OR 3.115; 95%-CI 1.720-5.641). Both, CAD and DM increased long-term mortality (CAD alone: HR 1.234; 95%-CI 1.106-1.376; DM alone: HR 1.260; 95%-CI 1.125-1.412; CAD and DM: HR 1.76; 95%-CI 1.552-1.995). DM further increased long-term amputation risk (DM alone: HR 2.238; 95%-CI 1.849-2.710; DM and CAD: HR 2.199; 95%-CI 1.732-2.792), whereas CAD (alone) did not. CONCLUSIONS: In a greater perspective, the data identify also mild to modest stage PAD patients at particular risk for adverse outcomes in presence of CAD and/or DM. CAD and DM both are related with a highly increased risk of long-term mortality even in intermittent claudication, and DM independently increased amputation risk.

Cardiovascular Disease: Lower Extremity Peripheral Artery Disease.

Lower extremity peripheral artery disease (PAD) refers to atherosclerotic disease that involves the iliac, femoral, or more distal arteries of the lower extremities. This condition affects 8 to 12 million Americans. Risk factors include advanced age, hypertension, dyslipidemia, diabetes, and cigarette smoking. Approximately 10% to 30% of patients with PAD present with the classic symptom of intermittent claudication. Some patients experience symptoms such as pallor, hair loss, or nonhealing wounds, and up to half of patients are asymptomatic. There are differing recommendations from various organizations for screening of asymptomatic patients. If PAD is suspected, the ankle-brachial index is the preferred first test. Further tests, including duplex ultrasonography or angiography, may be warranted depending on the clinical situation. Therapy for patients with PAD consists of lifestyle modifications, which include diet modification, exercise programs, and smoking cessation. Medical therapy consists of antiplatelet and statin therapies for secondary prevention of vascular complications, and consideration of drugs such as cilostazol for symptom control. Patients with acute limb ischemia should be referred emergently for evaluation and possible revascularization. Patients with lifestyle-limiting claudication despite lifestyle modification and medical therapy and patients with chronic limb ischemia (eg, nonhealing wounds) should be considered for revascularization.

Exercise and Chronic Wound Healing.

The calf muscles have been called the body's "second heart," improving blood circulation when exercised, usually by walking. Structured exercise training (SET) increases calf muscle pump function, lower limb circulation, and walking capacity for those with limited ambulation due to peripheral arterial disease (PAD)1 or venous insufficiency.2 This resulted in the Centers for Medicare and Medicaid Services (CMS) decision to reimburse up to thirty-six 30- to 60-minute, properly supervised hospital outpatient or office-based SET sessions over 12 weeks to treat intermittent claudication for patients with PAD. Exercise improves acute wound healing in diabetic mice3 and healthy elderly humans,4 but insufficient evidence supports its healing efficacy on ischemic ulcers,1 venous leg ulcers (VLUs),5 and diabetic foot ulcers (DFUs).6 This month's Evidence Corner examines 2 recent randomized controlled trials (RCTs) testing the effects of foot exercises that activate calf muscles on chronic VLUs7 and DFUs.8.