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.

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.

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.

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.

The effects of dietary flaxseed on cardiac arrhythmias and claudication in patients with peripheral arterial disease 1.

Patients with peripheral artery disease (PAD) are at increased risk for cardiovascular events, and higher susceptibility for cardiac arrhythmias may be involved. The objectives of this double-blinded randomized controlled FLAX-PAD trial were to determine whether daily consumption of a diet supplemented with 30 g of milled flaxseed (or placebo) over 1 year by PAD patients has effects on the prevalence of cardiac arrhythmias and exercise capacity. Cardiac arrhythmias were assessed on a cardiac stress test and at rest. At baseline, the PAD patients had a high incidence of cardiac arrhythmias (48% in the flaxseed group and 32% in the placebo group). After 1 year, the presence of cardiac arrhythmias in the flaxseed group decreased by 2% and increased by 12% in the placebo group (P > 0.05). Electrocardiographic variables (P, PR, QRS, QT, and QTc) did not change in either group during the trial. Patients from both groups improved initial and absolute claudication distances but the intergroup difference was also not statistically significant. In summary, the prevalence of cardiac arrhythmias and physical capacity trended in a positive direction for patients ingesting flaxseed but either a larger sample size or a longer intervention with flaxseed may be required to show statistically significant differences.

Association of arterial calcification with chronic limb ischemia in patients with peripheral artery disease.

OBJECTIVE: Arterial calcification is associated with an increased risk of limb events, including amputation. The association between calcification in lower extremity arteries and the severity of ischemia, however, has not been assessed. We thus sought to determine whether the extent of peripheral artery calcification (PAC) was correlated with Rutherford chronic ischemia categories and hypothesized that it could independently contribute to worsening limb status. METHODS: We retrospectively reviewed all patients presenting with symptomatic peripheral artery disease who underwent evaluation by contrast and noncontrast computed tomography scan of the lower extremities as part of their assessment. Demographic and cardiovascular risk factors were recorded. Rutherford ischemia categories were determined based on history, physical examination, and noninvasive testing. PAC scores and the extent of occlusive disease were measured on noncontrast and contrast computed tomography scans, respectively. Spearman's correlation testing was used to assess the relationship between occlusive disease and calcification scores. Multivariable logistic regression was used to identify factors associated with increasing Rutherford ischemia categories. RESULTS: There were 116 patients identified, including 75 with claudication and 41 with critical limb ischemia. In univariate regression, there was a significant association between increasing Rutherford ischemia category and age, diabetes duration, hypertension, the occlusion score, and PAC. There was a moderate correlation between the extent of occlusive disease and PAC scores (Spearman's R = 0.6). In multivariable analysis, only tobacco use (odds ratio [OR], 3.1; 95% confidence interval [CI], 1.2-8.3), diabetes duration (OR, 1.04; 95% CI, 1.01-1.08), and the calcification score (OR, 2.1; 95% CI, 1.4-3.2) maintained an association with increasing ischemia categories after adjusting for relevant cardiovascular risk factors and the extent of occlusive disease. CONCLUSIONS: PAC is independently associated with increased ischemia categories in patients with peripheral artery disease. Further research aimed at understanding the relationship between arterial calcification and worsening limb ischemia is warranted.

Age-dependent effects of homocysteine and dimethylarginines on cardiovascular mortality in claudicant patients with lower extremity arterial disease.

The association among serum homocysteine (HCY), symmetric dimethylarginine (SDMA), and asymmetric dimethylarginine (ADMA) is of interest in endothelial dysfunction, although the underlying pathology is not fully elucidated. We investigated the relationship of HCY with SDMA and ADMA regarding their long-time outcome and the age dependency of HCY, SDMA, and ADMA values in claudicant patients with lower extremity arterial disease. 120 patients were included in a prospective observational study (observation time 7.96 ± 1.3 years) with cardiovascular mortality as the main outcome parameter. Patients with intermittent claudication prior to their first endovascular procedure were included. HCY, SDMA, and ADMA were measured by high-performance liquid chromatography. Cutoff values for HCY (≤/>15 µmol/l), SDMA (≤/>0.75 µmol/l), and ADMA (≤/>0.8 µmol/l) differed significantly regarding cardiovascular mortality (p < 0.001, p < 0.001, p = 0.017, respectively). Age correlated significantly with HCY (r = 0.393; p < 0.001), SDMA (r = 0.363; p < 0.001), and ADMA (r = 0.210; p = 0.021). HCY and SDMA (r = 0.295; p = 0.001) as well as SDMA and ADMA (r = 0.380; p < 0.001) correlated with each other, while HCY and ADMA did not correlate (r = 0.139; p = 0.130). Patients older than 65 years had higher values of HCY (p < 0.001) and SDMA (p = 0.01), but not of ADMA (p = 0.133). In multivariable linear regression, age was the only significant independent risk factor for cardiovascular death (beta coefficient 0.413; 95% CI 0.007-0.028; p = 0.001). Age correlated significantly with HCY, SDMA, and ADMA. However, only age was an independent predictor for cardiovascular death. Older patients have higher values of HCY and SDMA than younger subjects suggesting age-adjusted cutoff values of HCY and SDMA due to strong age dependency.

Frailty Is Associated with an Increased Risk of Major Adverse Cardiac Events in Patients with Stable Claudication.

BACKGROUND: Frailty, a syndrome characterized by decreased physiologic reserves and resistance to stressors, is associated with disability, poor surgical outcomes, and mortality. We evaluated the impact of frailty on cardiovascular disease (CVD) events in peripheral arterial disease (PAD) patients with intermittent claudication. METHODS: We conducted a retrospective review of patients with stable intermittent claudication enrolled in the OMEGA-PAD study between 2010 and 2015. The modified frailty index (mFI) is a retrospectively validated index of frailty derived from the Canadian Study of Health and Aging and was used in this study to categorize frailty as low, medium, or high. Our outcome was time to occurrence of a major adverse cardiac event (MACE), defined as a composite endpoint of myocardial infarction, coronary revascularization, stroke, or CVD-related death. Cox proportional hazards models were used to calculate relative hazards ratio. RESULTS: There were 129 subjects with a mean age of 67 years, 97% were men, 36% were diabetic, and 33% had known coronary heart disease. When the mFI criteria were applied, 38 subjects were "low" frailty, 72 were "medium" frailty, and 19 were "high" frailty. During the median follow-up period of 34 months (interquartile range: 25-43), 29 subjects experienced a MACE. When compared to the lowest mFI, patients with medium frailty were 2.8 times more likely to have an event (95% confidence interval [CI]: 0.95-8.46, P = 0.06), whereas patients with a high mFI were 4.8 times as likely (95% CI: 1.43-15.8, P = 0.01). In a model adjusted for age, smoking status, and presence of diabetes, those with a medium mFI were 4.3 times more likely to have an event (95% CI: 1.37-13.7, P = 0.01) and those with a high mFI were 9.2 times as likely (95% CI: 2.6-32.4, P = 0.001). CONCLUSIONS: Higher mFI category is associated with a significantly increased risk of MACE in PAD patients with stable claudication. Frailty may serve as a useful adjunct for assessment of overall cardiac risk, particularly as treatment options are being contemplated.

Edinburgh questionnaire in the screening for peripheral artery disease in type 2 diabetic patients.

AIM: to analyze Edinburgh questionnaire (EQ) screening performance for peripheral artery disease (PAD) in type 2 diabetic patients. METHODS: Cross sectional study including 150 type 2 diabetic patients without PAD history. All patients responded to EQ and had peripheral pulse checkup and measurement of the ankle/brachial index (ABI). PAD was considered to be present when the ABI was ≤ 0.9 Results: Participants mean age was 57.46 ± 8.04 years and sex-ratio (men/women) was 1.3. EQ has revealed intermittent claudication in 18 patients (12%). On examination, 42 patients (28%) had at least one weakened or abolished pulse in upper limbs. ABI has revealed the presence of PAD in 16% of patients. The EQ sensibility specificity, positive and negative predictivevalueswere 29, 91,39 and 87%, respectively. Among patients with false negative results (n=17), nine had peripheral neuropathy. CONCLUSION: In diabetic patients, EQ had a very low sensibility for the PAD screening. In fact, the important false negative rate, due to the coexisting of peripheral neuropathy, had limited the use of this questionnaire.

Amputation Rates, Mortality, and Pre-operative Comorbidities in Patients Revascularised for Intermittent Claudication or Critical Limb Ischaemia: A Population Based Study.

OBJECTIVES: The aims of this population based study were to describe mid- to long-term amputation risk, cumulative incidence of death or amputation, and differences in pre-operative comorbidities in patients revascularised for lower limb peripheral artery disease (PAD). METHODS: This was an observational cohort study. Data from the Swedish National Quality Registry for Vascular Surgery (Swedvasc) were combined with mandatory national health care registries and patient medical records. All patients who underwent revascularisation in Sweden between May 2008 and May 2013 for intermittent claudication (IC) or critical limb ischaemia (CLI), aged 50 years and older, were identified through the Swedvasc database. The mandatory national health care registries and medical records provided data on comorbidities, mortality, and major amputations. RESULTS: A total of 16,889 patients with PAD (IC, n = 6272; CLI, n = 10,617) were studied. The incidence of amputations in IC patients was 0.4% (range 0.3%-0.5%) per year. Among CLI patients, the amputation rate during the first 6 months following revascularisation was 12.0% (95% CI 11.3-12.6). Thereafter, the incidence declined to approximately 2% per year. The cumulative combined incidence of death or amputation 3 years after revascularisation was 12.9% (95% CI 12.0-13.9) in IC patients and 48.8% (95% CI 47.7-49.8) in CLI patients. Among CLI patients, compared with IC patients, the prevalence of diabetes, ischaemic stroke, heart failure, and atrial fibrillation was approximately doubled and renal failure was nearly tripled, even after age standardisation. CONCLUSION: The risk of amputation is particularly high during the first 6 months following revascularisation for CLI. IC patients have a benign course in terms of limb loss. Mortality in both IC and CLI patients is substantial. Revascularised CLI patients have different comorbidities from IC patients.

Peripheral Vascular Disease: The Beneficial Effect of Exercise in Peripheral Vascular Diseases Based on Clinical Trials.

Intermittent claudication (IC) due to peripheral artery diseases (PAD) is one of the disabling disease that can affect quality of life (QOL) and functional status of capacity. It is characterized by cramping pain which develops with exercise and eliminated by rest secondary to decrease blood flow to the muscles. The annual incidence rate is increased with age. Exercise rehabilitation has a great impact in improving the functional capacity and prevent the functional disability. The available evidences from current studies have showed that exercise therapy is considered the primary treatment in PAD, which in consequently improves the QOL. In this chapter we will illustrate the current available evidences which support exercise benefit and outcomes in PAD with IC.

Pathology of Neointimal Calcification in Very Late Restenosis After Bare Metal Stent Implantation for Superficial Femoral Artery.

A 60-year-old man, who had claudication in his right limb due to total occlusion of the right superficial femoral artery, received bare metal stents. Although the bare metal stents in the superficial femoral artery did not show restenosis 5 years after stent implantation, angiography revealed significant in-stent restenosis when he developed right critical limb ischemia at 8 years post implantation. Ballooning for in-stent lesions did not result in full expansion. His right limb was amputated above the knee due to progressive limb ischemia. In the pathological findings in the superficial femoral artery, marked calcification was observed in the entire circumference of the luminal surface of the neointima. However, lipid core formation was not identified in the neointima. Although several cracks following balloon angioplasty were observed at the superficial calcified layers, injury to neointimal tissue such as compression was not observed. The neointima exhibited heavy calcification in the very late phase of in-stent restenosis after bare metal stent implantation in superficial femoral artery. Therefore, balloon angioplasty in the very late phase of in-stent restenosis potentially results in underexpansion.

Impact of coexisting aneurysms on open revascularization for aortoiliac occlusive disease.

OBJECTIVE: National data evaluating outcomes for occlusive abdominal aortic reconstructions are well described. The relative effect of operative indication as well as the presence of concomitant abdominal aortic aneurysm (AAA) on in-hospital mortality is not well defined. METHODS: The Nationwide Inpatient Sample was queried to identify patients who underwent open aortic surgery (2003-2010). Indication for surgery was classified by International Classification of Diseases, Ninth Revision diagnostic codes to identify isolated occlusive indications as well as combined occlusive disease and AAA. Primary outcome was in-hospital mortality. Secondary outcomes were complications and discharge disposition. RESULTS: Overall, 56,374 underwent aortic reconstruction, 48,591 for occlusive disease (86.2%) and 7783 for combined occlusive disease with AAA (13.8%). Intermittent claudication was the most common indication for intervention (60.9%), whereas 39.7% underwent intervention for critical limb ischemia (22.2% rest pain, 17.6% gangrene). Patients with intermittent claudication had more concomitant AAAs (17.3%) than did patients with critical limb ischemia (8.4%). The baseline characteristics for those with occlusive disease and combined occlusive with AAA disease were similar in terms of obesity (4.8% vs 4.2%; P = .27) and congestive heart failure (6.6% vs 6.3%; P = .65) but differed by age (62.2 years vs 68.4 years; P < .0001) and hypertension (65.4% vs 69.1%; P = .005). Patients with combined occlusive and AAA disease had higher mortality than those with occlusive disease alone (3.9% vs 2.7%; P = .01). On multivariable regression, factors associated with in-hospital mortality included gangrene with AAA compared with gangrene alone (odds ratio [OR], 2.8; 95% confidence interval [CI], 1.6-4.7; P < .0002), age >65 years age (OR, 3.1; 95% CI, 2.4-4.1; P < .0001), renal failure (OR, 2.7; 95% CI, 1.9-3.8; P < .0001), and concurrent lower extremity revascularization (OR, 1.3; 95% CI, 1.1-1.7; P < .02). CONCLUSIONS: Intermittent claudication or critical limb ischemia with concomitant AAA carries a higher mortality than intermittent claudication or critical limb ischemia alone, especially in older patients with gangrene requiring revascularization and renal insufficiency. Preoperative risk stratification strategies should focus on the indication for surgery as well as the presence of concomitant AAA.

Potential identification of a claudicant group vulnerable to acute kidney injury.

This observational study aimed to investigate the relationship between renal injury, endothelial function and oxidative stress in claudicants undergoing maximal treadmill exercise. Twenty patients with claudication were identified in whom the urinary N-acetyl-ß-D-glucosaminidase (ß-NAG)/creatinine ratio, plasma oxidative state and endothelial function were tested pre- and post-maximal treadmill walking exercise. Of the 20 participants in this study, the urinary NAG/creatinine (Cr) rose from a pre-exercise level of 8.9, 6.7 to 14.3 (µmol/L/mmol Cr; median, IQR) to 12.9, 9.1 to 17.7 post exercise (p = 0.0003, Mann Whitney U test). Of the 20 participants, eight participants had a rise of the NAG/Cr ratio post exercise whereas 12 did not. Participants with a rise in the NAG/Cr ratio post exercise had a greater ability to increase endothelial reactivity (%; median, IQR; 2.56, 0.1 to 3.7) cf. (0.1, -4.8 to 0.9, p = 0.03); they also walked further (metres; median, IQR; 415, 208 to 908) cf. (170, 100 to 315, p = 0.04), had a lower pre-exercise H2O2 (median, IQR; 1.9, 1.4 to 2.3 cf. 2.7, 2.1 to 3.3; p = 0.04) and a greater rise in H2O2 post exercise (18.8, -1.5 to 129.7 cf., -7.7, -13.9 to -2.0, p = 0.04). The mechanism by which the phenotypically distinct sub-group of patients with intermittent claudication who experience a NAG/Cr rise involves complex interactions between systemic oxidative stress and endothelial function. Implications on cardiovascular risk in this group requires further investigation.

Safety of supervised exercise therapy in patients with intermittent claudication.

BACKGROUND: Supervised exercise therapy (SET) is recommended as the primary treatment for patients with intermittent claudication (IC). However, there is concern regarding the safety of performing SET because IC patients are at risk for untoward cardiovascular events. The Dutch physical therapy guideline advocates cardiac exercise testing before SET, if indicated. Perceived uncertainties concerning safety may contribute to the underuse of SET in daily practice. The objective of this review was to analyze the safety of supervised exercise training in patients with IC. METHODS: Two authors independently studied clinical trials investigating SET. Data were obtained from MEDLINE, EMBASE, and The Cochrane Central Register of Controlled Trials. Complication rates were calculated and expressed as number of events per number of patient-hours. The usefulness of cardiac screening before SET was evaluated in a subanalysis. RESULTS: Our search strategy revealed 2703 abstracts. We selected 121 articles, of which 74 met the inclusion criteria. Studies represent 82,725 hours of training in 2876 IC patients. Eight adverse events were reported, six of cardiac and two of noncardiac origin, resulting in an all-cause complication rate of one event per 10,340 patient-hours. CONCLUSIONS: SET can safely be prescribed in patients with IC because an exceedingly low all-cause complication rate was found. Routine cardiac screening before commencing SET is not required. Our results may diminish perceived uncertainties regarding safety and will possibly increase the use of SET in daily practice.

Association of dual-antiplatelet therapy with reduced major adverse cardiovascular events in patients with symptomatic peripheral arterial disease.

OBJECTIVE: This study was conducted to determine whether there is additive benefit of dual-antiplatelet therapy (DAPT) with aspirin (acetylsalicylic acid [ASA]) and clopidogrel compared with ASA monotherapy among patients with symptomatic peripheral arterial disease. METHODS: This was an observational cohort analysis that included 629 patients with claudication or critical limb ischemia. The prevalence of patients taking ASA monotherapy vs DAPT was assessed monthly for up to 3 years. A propensity model was constructed to adjust for baseline demographic characteristics and to assess the effect of DAPT on major adverse cardiovascular events (MACEs) and major adverse limb events. RESULTS: At baseline, 348 patients were taking DAPT and 281 were taking ASA monotherapy. During 3 years of follow-up, 50 events (20%) occurred in the DAPT group vs 59 (29%) in the ASA monotherapy group. After propensity weighting, DAPT use was associated with a decreased risk of MACEs (adjusted hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.44-0.96) and overall mortality (adjusted HR, 0.55; 95% CI, 0.35-0.89). No association was found between DAPT use and the risk of major amputation (adjusted HR, 0.69; 95% CI, 0.37-1.29). In a subgroup of 94 patients who underwent point-of-care platelet function testing, 21% had decreased response to ASA and 55% had a decreased response to clopidogrel. No association was found between a reduced response to ASA or clopidogrel and adverse events at 1 year. CONCLUSIONS: DAPT may be associated with reduced rates of MACEs and death among patients with symptomatic peripheral arterial disease.

Comparison between walking test and treadmill test for intermittent claudication associated with lumbar spinal canal stenosis.

PURPOSE: To clarify the priorities of the walking test and the treadmill test for intermittent claudication of lumbar canal stenosis. METHODS: The study population comprised 45 subjects, with a mean age of 72.6 years. An investigator walked with the subjects during the walking test or watched the subjects walking on the treadmill machine in the treadmill test. RESULTS: The pain scales became significantly worse after the walking test. Ten patients who were diagnosed as root symptom type or cauda equine symptoms were subsequently diagnosed as mixed type by the walking test. The numbers of patients who experienced muscle weakness that was not revealed at rest were eight with the walking test and seven with the treadmill test. The numbers of patients who experienced sensory disturbance that was not observed at rest were seven with the walking test and two with the treadmill test. CONCLUSIONS: The walking test detected significantly more symptoms that were not detected at rest than the treadmill test.

Influence of regular exercise on body fat and eating patterns of patients with intermittent claudication.

This study examined the impact of regular supervised exercise on body fat, assessed via anthropometry, and eating patterns of peripheral arterial disease patients with intermittent claudication (IC). Body fat, eating patterns and walking ability were assessed in 11 healthy adults (Control) and age- and mass-matched IC patients undertaking usual care (n = 10; IC-Con) or supervised exercise (12-months; n = 10; IC-Ex). At entry, all groups exhibited similar body fat and eating patterns. Maximal walking ability was greatest for Control participants and similar for IC-Ex and IC-Con patients. Supervised exercise resulted in significantly greater improvements in maximal walking ability (IC-Ex 148%-170% vs. IC-Con 29%-52%) and smaller increases in body fat (IC-Ex -2.1%-1.4% vs. IC-Con 8.4%-10%). IC-Con patients exhibited significantly greater increases in body fat compared with Control at follow-up (8.4%-10% vs. -0.6%-1.4%). Eating patterns were similar for all groups at follow-up. The current study demonstrated that regular, supervised exercise significantly improved maximal walking ability and minimised increase in body fat amongst IC patients without changes in eating patterns. The study supports the use of supervised exercise to minimize cardiovascular risk amongst IC patients. Further studies are needed to examine the additional value of other lifestyle interventions such as diet modification.

Prediction of coronary artery disease in patients with lower extremity peripheral artery disease.

Coronary artery disease (CAD) is a major determinant of long-term prognosis in patients with peripheral artery disease (PAD). We investigated the predictors of CAD in patients with lower extremity PAD.A total of 107 patients with PAD who underwent peripheral and simultaneous coronary angiography were reviewed. PAD was defined as (≥ 50%) stenosis associated with claudication or critical limb ischemia. PAD was divided into proximal and distal lesions. CAD was defined as angiographically significant (≥ 50%) stenosis of coronary arteries.The prevalence of CAD in patients with PAD was 62% (67/107), and of this 62%, only 13% (9/67) had angina and 72% (48/67) had multi-vessel disease. Diabetes significantly increased the risk of CAD in patients with PAD and the odds ratio of having multi-vessel CAD was 2.5 (1.1-5.9, P = 0.037) in multivariate regression analysis. The patients with multi-vessel CAD had more cardiovascular risk factors than those with normal, minimal and single CAD (P = 0.032). Interestingly, the prevalence of proximal PAD was higher in the normal or single CAD group than the multi-vessel CAD group, whereas both proximal and distal involvement of PAD was higher in the multi-vessel CAD group.Diabetes, multi-cardiovascular risk factors, and involvement of both proximal and distal lesions significantly increased the risk of multi-vessel CAD. Therefore, simultaneous CAD evaluation should be considered in patients with lower extremity PAD having diabetes, multi-cardiovascular risk factors, or multi-level disease.