Exertional Limb Pain Research Articles

Abstract 2124: Genetic Variation Associated With Progression And Severity Of Peripheral Artery Disease

Background: Peripheral Artery Disease (PAD) is a major source of cardiovascular morbidity and mortality, affecting >230 million individuals worldwide. While PAD may initially cause exertional limb pain (claudication), progression leads to chronic limb threatening ischemia (CLTI; rest pain and/or tissue loss) and amputation, which are associated with high rates of hospitalization and death. Genetic variants associated with PAD susceptibility have been identified using genome-wide association studies (GWAS). However, the role of genetic variation in the progression of PAD and disease severity remains poorly understood. Methods: GWAS of progression to CLTI were performed among individuals with PAD in the VA Million Veteran Program (MVP) and Copenhagen Hospital Biobank (CHB), accounting for age, sex, and genetic principal components. GWAS were first performed among genetically inferred ancestry subpopulations (EUR: European; AFR: African; AMR: admixed American), and combined using fixed-effects meta-analysis. SlopeHunter was used to account for index-event bias using a GWAS of prevalent PAD. Genetic associations with PAD severity (claudication, CLTI, amputation) were evaluated using multinomial logistic regression. Results: Up to 21.1 million genetic variants were tested for association with CLTI (17,641 individuals) in comparison to PAD (75,133 individuals). A total of 3 genetic loci were associated with progression to CLTI (p < 5x10 -8 ). The strongest association with CLTI was rs6025 (OR 1.25, 95% CI 1.18 to 1.34, p = 4.62x10 -12 ), a common missense variant (p.Arg534Gln) encoding Factor V Leiden, with consistent effects accounting for index-event bias. Compared to 489,538 individuals without PAD in MVP, rs6025 was associated with increased risk of non-specific PAD (OR 1.15, 95% CI 1.1 to 1.2, p = 5x10 -8 ), claudication (OR 1.14, 95% CI 1.1 to 1.2, p = 1x10 -4 ), CLTI (OR 1.42, 95% CI 1.3 to 1.6, p = 7x10 -23 ), and amputation (OR 1.54, 95% CI 1.4 to 1.8, p = 2x10 -10 ). Conclusion: Our results implicate F5 p.Arg534Gln as a risk factor for PAD progression and severe PAD manifestations including CLTI and amputation. This result provides genetic support for a potential role of anticoagulation as a treatment to prevent PAD progression and severe outcomes.

Combination of Exercise Testing Criteria to Diagnose Lower Extremity Peripheral Artery Disease.

Objectives: Nothing is known about the interest of the combination of exercise tests to diagnose Lower-extremity Peripheral Artery Disease (LEPAD). The aim of this study was to assess if combining exercise testing criteria [post-exercise Ankle-Brachial Index (ABI) + exercise-oximetry (exercise-TcPO2)] improves the detection of lower limbs arterial stenoses as compared with post-exercise ABI using American Heart Association (AHA) criteria, or exercise-TcPO2 alone.Material and Methods: In a prospective monocentric study, consecutive patients with exertional-limb pain and normal resting-ABI referred to our vascular center (Rennes, France) were assessed from May 2016 to February 2018. All included patients had a computed tomography angiography (CTA), a resting-ABI, a post-exercise ABI and an exercise-TcPO2. AHA post-exercise criteria, new validated post-exercise criteria (post-exercise ABI decrease ≥18.5%, post-exercise ABI decrease <0.90), and Delta from Rest of Oxygen Pressure (Total-DROP) ≤-15mmHg (criterion for exercise-TcPO2) were used to diagnose arterial stenoses ≥50%. For the different combinations of exercise testing criteria, sensitivity or specificity or accuracies were compared with McNemar's test.Results: Fifty-six patients (mean age 62 ± 11 years old and 84% men) were included. The sensitivity of the combination of exercise testing criteria (post-exercise ABI decrease ≥18.5%, or post-exercise ABI decrease <0.90 or a Total-DROP ≤-15mmHg) was significantly higher (sensitivity = 81% [95% CI, 71–92]) than using only one exercise test (post-exercise AHA criteria (sensitivity = 57% [43–70]) or exercise-TcPO2 alone (sensitivity = 59% [45–72]).Conclusions: Combination of post-exercise ABI with Exercise-TcPO2 criteria shows better sensitivity to diagnose arterial stenoses compared with the AHA post-exercise criteria alone or Exercise-TcPO2 criteria used alone. A trend of a better accuracy of this combined strategy was observed but an external validation should be performed to confirm this diagnostic strategy.

The hidden side of calf claudication: Hemodynamic and clinical results of treadmill testing in 584 patients complaining of isolated exertional calf pain

Background and aimsCalf pain is the most frequent symptom of arterial claudication. We hypothesized that patients with self-reported isolated calf claudication have frequent exertional non-calf symptoms during objective laboratory testing, and that many would show not only distal, but also proximal ischemia. MethodsWe retrospectively analyzed the patients referred since 2016 for exercise transcutaneous oxygen pressure (Ex-tcpO2). The Edinburgh Claudication Questionnaire (ECQ) was self-completed before and during a treadmill test. For calf and non-calf (buttock and thigh) Ex-tcpO2, a lowest decrease of rest of oxygen pressure (DROP) < −15 mmHg was indicative of ischemia. We selected the patients that reported calf claudication only and analyzed minimal DROP and per-test ECQ observations. ResultsExertional symptoms on a treadmill occurred in 526 (90.1%) of the 584 patients analyzed (65.6 ± 11.4 years old), with 391 (74.3%) of these symptoms affecting only the calf. Isolated calf ischemia with or without symptoms was found in only 139 (23.8%) patients. Overall, among the 584 patients self-reporting isolated calf symptoms, a perfect concordance between symptoms on a treadmill and Ex-tcpO2 (i.e. calf symptoms associated to calf ischemia) was observed in only 114 (19.5%) cases. ConclusionsOur study demonstrated that patients self-reporting exertional limb pain strictly limited to the calf may also have non-calf claudication on a treadmill and frequently show not-only-calf ischemia. These observations are important when planning reeducation or when studying the tissue consequences of ischemia in patients with claudication.

Exercise testing criteria to diagnose lower extremity peripheral artery disease assessed by computed-tomography angiography.

BackgroundThe sensitivity and specificity of exercise testing have never been studied simultaneously against an objective quantification of arterial stenosis. Aims were to define the sensitivity and specificity of several exercise tests to detect peripheral artery disease (PAD), and to assess whether or not defined criteria defined in patients suspected of having a PAD show a difference dependent on the resting ABI.MethodsIn this prospective study, consecutive patients with exertional limb pain referred to our vascular center were included. All patients had an ABI, a treadmill exercise-oximetry test, a second treadmill test (both 10% slope; 3.2km/h speed) with post-exercise pressures, and a computed-tomography-angiography (CTA). The receiver-operating-characteristic curve was used to define a cut-off point corresponding to the best area under the curve (AUC; [CI95%]) to detect arterial stenosis ≥50% as determined by the CTA.ResultsSixty-three patients (61+/-11 years-old) were included. Similar AUCs from 0.72[0.63–0.79] to 0.83[0.75–0.89] were found for the different tests in the overall population. To detect arterial stenosis ≥50%, cut-off values of ABI, post-exercise ABI, post-exercise ABI decrease, post-exercise ankle pressure decrease, and distal delta from rest oxygen pressure (DROP) index were ≤0.91, ≤0.52, ≥43%, ≥20mmHg and ≤-15mmHg, respectively (p<0.01). In the subset of patients with an ABI >0.91, cut-off values of post-exercise ABI decrease (AUC = 0.67[0.53–0.78]), and DROP (AUC = 0.67[0.53–0.78]) were ≥18.5%, and ≤-15mmHg respectively (p<0.05).ConclusionResting ABI is as accurate as exercise testing in patients with exertional limb pain. Specific exercise testing cut-off values should be used in patients with normal ABI to diagnose PAD.

Don't Just Blame it on the Veins: An Update on Vascular Exertional Limb Pain.

Exertional limb pain is a common problem encountered in recreational and competitive athletes. Affecting both the upper and lower extremities, this broad entity can be musculoskeletal, vascular, neurologic, oncologic, or infectious in origin. This article focuses on the vascular causes of exercise-related extremity pain, which encompass a cadre of elusive diagnoses. Specifically, we examine arterial endofibrosis, popliteal artery entrapment syndrome, and chronic exertional compartment syndrome of both the upper and lower extremities. For each of these conditions, we offer updates regarding the respective epidemiology, common signs and symptoms, worthwhile diagnostic modalities, and pertinent treatment options, all based on evidence and reports published over the past year.

Ankle brachial index is equally predictive of exercise-induced limb ischemia in diabetic and non-diabetic patients with walking limitation

BackgroundIn diabetic patients, arterial stiffness may impair compressibility of vessels and result in higher ankle to brachial index (ABI) than in non-diabetic subjects. MethodsWe studied 1972 non-diabetic and 601 diabetic patients, with suspected peripheral artery disease, Exercise transcutaneous oxygen pressure (Ex-tcpO2), expressed in DROP index (limb tcpO2 change minus chest tcpO2 change), is insensitive to arterial stiffness and can estimate exercise-induced regional blood flow impairment (RBFI). A minimal DROP <−15 mm Hg indicates the presence of RBFI (positive test). ABI was simplified to a category variable (ABIc) by rounding ABI to the closest first decimal. ResultsIn the ABIc range 0.4 to 1.1 linear regression for mean DROP values were: y = 34 x - 53; (R2 = 0.211) and y = 33 x - 52; (R2 = 0.186) in diabetic and Non-diabetic patients, respectively. Both Db and non-D patients showed a high proportion of positive Ex-tcpO2 tests for ABIc in the normal range (ABIc: 1.0 and over) from 27.1 to up to 58%. More than half of patients with borderline ABI (ABIc = 0.9) had RBFI during exercise. it was 65.6% in diabetic and 58.5% non-diabetic patients. ConclusionsResting ABI was not a better predictor of exercise-induced RBFI in non-Db than in Diabetic patients. Our results highlights the interest of still measuring resting-ABI in diabetic patients to argue for the vascular origin of exertional limb pain, but also of performing exercise tests in patients with walking impairment.

Exercise transcutaneous oximetry significantly modifies the diagnostic hypotheses and impacts scheduled investigations or treatments of patients with exertional limb pain

IntroductionIn lower extremity peripheral artery disease (PAD), transcutaneous oximetry at exercise (Ex-TcpO2) has been largely validated in research practice, but evidence of routine practice in various vascular laboratories is missing. We hypothesized that Ex-TcPO2 would change the diagnosis hypotheses, investigations and treatments for patients referred for exertional limb pain. Material & methodsA multicenter prospective trial was conducted in nine different referral centers. Investigators performed Ex-TcpO2 and recorded investigations and treatments already scheduled for the patient. We encoded referral physician's diagnostic hypothesis. Before Ex-TcpO2, vascular physicians were asked to give their diagnosis hypotheses. A minimal decrease from rest of oxygen pressure (DROP)<minus 15mmHg defined the presence of exercise-induced ischemia on the area of interest. After Ex-TcPO2, we recorded post-test diagnostic hypothesis and investigations and treatments to be cancelled or performed. We compared the diagnosis hypotheses, scheduled investigations and treatments, before and after the Ex-TcpO2. ResultsWe included 603 patients (485 males: 80.4%), aged 64.7±9.8years. The post-test diagnosis hypothesis differed in 266 patients (44.1%; p<0.0001) and in 96 patients (15.9%) from the pre-test hypothesis of referring and vascular physician, respectively. This led to the recommendation to cancel 27 scheduled investigations or treatments of a total cost of ~130,000 euros. DiscussionEx-TcPO2 in patients with exertional limb pain is applicable in various vascular institutions, and significantly modifies the diagnostic hypotheses and impacts scheduled investigations or treatments of patients with exertional limb pain.

Discharge Destination after Elective Femoropopliteal Bypass in Patients without Critical Ischemia

Femoropopliteal bypass (FPB) remains a widely accepted treatment option for symptomatic leg ischemia, even in patients without features of critical limb ischemia (CLI). These patients are revascularized to improve symptoms of exertional limb pain and the goal of such treatment is to increase their ability to ambulate within the community. Therefore, the anticipated initial discharge disposition for a patient without CLI undergoing FPB is back to their home. This study examined the disposition at initial discharge of such patients. Data from the 2012 National Surgical Quality Improvement Program registry was queried for all elective FPB performed in patients without CLI. Analysis was limited to patients surviving to initial discharge who were living independently at home before surgery. Initial disposition was defined as to HOME or to a FACILITY (either rehabilitation or skilled nursing); these constituting the study groups. Univariate analysis and multivariable logistic regression were performed to identify patient risk factors for failure to discharge to home. In-hospital and postoperative events were also recorded and compared. Significance was defined at P ≤ 0.05. In National Surgical Quality Improvement Program 2012, 1060 cases of elective FPB in patients without CLI were found. The mean± SD age of the population was 65 ± 9 years; 359 (34%) of patients were female; 198 (19%) had a reported race other than white; and most (893, 84%) had hypertension. 60 (6%) patients failed to discharge to home (26 to rehabilitation, 34 to skilled nursing). On univariate analysis, age (FACILITY 68 ± 11 years vs HOME 65 ± 9 years, P = 0.009), female gender (55% vs 37%, P < 0.001), nonwhite race (30% vs 18%, P = 0.007), and a history of diabetes (48% vs 33%, P = 0.01), dialysis (5% vs 1.3%, P = 0.02) congestive heart failure (5% vs 1.1%, P = 0.01), or a stroke (cerebrovascular accident, 5% vs 2.6%, P = 0.01) were found to predict failure to discharge to home. On multivariate analysis, female gender [odds ratio (OR) = 2.4, 95% confidence interval = 1.4-4.1, P = 0.002], and a history of congestive heart failure (OR = 4.7, 1.2-18, 0.03] or cerebrovascular accident (OR = 3.4, 1.9-9.4, 0.02) independently predicted failure to discharge to home. FACILITY patients had higher rates of infectious complications (8.3% vs 1.4%, P < 0.001), myocardial infarction (3.3% vs 0.8%, P = 0.05), operative transfusion (22% vs 5.8%, P < 0.001), and unplanned reoperation (17% vs 2.4%, P < 0.001) during their initial hospitalization. Elective FPB results in a low but not negligible failure of initial return to the community in patients without CLI. Female gender and serious comorbidities predict initial discharge to a facility, which is associated with a complicated hospital course. Careful patient selection is important to achieve good outcomes in this population and furthermore study into the specific preoperative functional and socioeconomic factors predicting failure of early return to the community is warranted.

English

Peripheral arterial occlusive disease (PAOD) is a prevalent atherosclerotic disorder characterized by exertional limb pain, loss of limband a high mortality rate.All the aspects of health status, life style, life satisfaction, mental state or well-being together reflect the multi-dimensional nature of Quality of Life in an individual. MATERIAL &METHODS:A cross sectional study was conducted over a period of 6 months from October 2012 to march 2013.Patients with signs and symptoms of peripheral arterial occlusive disease were referred for further evaluation byColor Doppler Ultrasonography to the Department of Radiodiagnosis. The evaluation of QOL in respondents with PAOD was performed, by means of WHOQOL-BREF questionnaire, after obtaining clearance from the Institution's Ethics Committee.RESULTS:-The mean scores in each of the four domains for both men and women were found to be similar. The difference between men and women was not found to be statistically significant for any of the four domains.The mean scores of the gangrene absent groups and gangrene present groups were found to differ significantly inthedomainsof physical (p=0.025), psychological (p=0.031), environmental(p=0.048)and social relations (p=0.017). The mean scores of the age groups of 70 years were found to differ significantly in the domains of physical (p=0.046), psychological (p=0.037).The mean scores, of thegroups according to the Stage of PAD in accordance with Fontaine classification, were found to differ significantly in thedomains of physical (p=0.0316), psychological (p=0.0241), environmental(p=0.0472)and social relations (p=0.0126).

The Effect of Selected Health, Demographic and Psychosocial Aspects on Quality of Life in Patients with Peripheral Arterial Occlusive Disease – a Prospective Analysis

Peripheral arterial occlusive disease (PAOD) is a prevalent atherosclerotic disorder characterized by exertional limb pain, loss of limb, and a high mortality rate. Because of its chronic nature, it often has a negative impact on a patient quality of life (QoL). Aims. To evaluate the effect of selected health, demographic and psychosocial aspects on QoL in respondents with PAOD. The study is a prospective and cross-sectional. It was carried out at the 2nd Department of Medicine of Charles University Hospital at the Faculty of Medicine in Hradec Králové, Czech Republic. Forty two respondents with PAOD (28 male, 14 female) were evaluated. All the respondents had involvement of femoral and popliteal arterial circulation. The number of all respondents in accordance with Fontaine classification was as follows: intermittent claudication: stage IIa - 4, stage IIb (<200 m) - 16, stage IIb (<50 m) - 9, chronic limb ischaemia: stage III - 6, stage IV - 7. The average age of all respondents was 65,4 years old (age range 45-79 years old). The study evaluates the effect of health aspects (stage of PAOD in accordance with Fontaine classification, diabetes mellitus, arterial hypertension, hyperlipidaemia, obesity, smoking), demographic (age, sex) and psychosocial aspects (level of education, marital status, religion) on QoL in respondents with PAOD. The Czech version of the International Generic European Quality of Life Questionnaire - EQ-5D was used. The statistical evaluation presents statistically a significant dependence of QoL in respondents with PAOD on age (p < 0,01) and the stage of PAOD in accordance with the Fontaine classification (p < 0,01). The effect of other health, demographic and psychosocial aspects was statistically insignificant. The results had shown that with an increasing age and with a serious stage of PAOD in accordance with Fontaine classification, the QoL declines. The global QoL in respondents with PAOD is low.