Peripheral Arterial Disease In Individuals Research Articles

Liraglutide for Lower Limb Perfusion in People With Type 2 Diabetes and Peripheral Artery Disease

Peripheral artery disease (PAD) in diabetes may lead to diabetic foot ulcer and lower-extremities amputation. Glucagon-like peptide 1 receptor agonists have proven cardiovascular benefits in trials of people with type 2 diabetes at high cardiovascular risk. To examine the effect of liraglutide on peripheral perfusion measured as peripheral transcutaneous oxygen pressure (TcPo2) in individuals with type 2 diabetes and PAD. This open-label randomized clinical trial was conducted between February 1, 2021, and June 30, 2022, with a final follow-up on December 30, 2022, at University of Campania "Luigi Vanvitelli," Naples, Italy. Fifty-five individuals with type 2 diabetes, PAD, and TcPo2 between 30 and 49 mm Hg were included. Patients were randomized to receive 1.8 mg of subcutaneous liraglutide or conventional treatment of cardiovascular risk factors (control group) for 6 months. Coprimary outcomes were the change from baseline of peripheral perfusion between groups and the comparison of the proportion of individuals who reached 10% increase of TcPo2 from baseline in each group. Fifty-five participants (mean [SD] age, 67.5 [8.5] years; 43 [78%] male) were randomized (27 to the liraglutide group and 28 to the control group) and analyzed. Participants had a median (IQR) hemoglobin A1c level of 6.9% (6.5%-7.8%) and a mean (SD) TcPo2 of 40.3 (5.7) mm Hg. Transcutaneous Po2 increased over time in both groups, with significant differences favoring the liraglutide group after 6 months (estimated treatment difference, 11.2 mm Hg; 95% CI, 8.0-14.5 mm Hg; P < .001). The 10% increase of TcPo2 occurred in 24 participants (89%) in the liraglutide group and 13 (46%) in the control group (relative risk, 1.91; 95% CI, 1.26-2.90; P < .001). Compared with the control group, individuals in the liraglutide group had a significant reduction of C-reactive protein (-0.4 mg/dL; 95% CI, -0.7 to -0.07 mg/dL; P = .02), urinary albumin to creatinine ratio (-119.4 mg/g; 95% CI, -195.0 to -43.8 mg/g; P = .003), and improvement of 6-minute walking distance (25.1 m; 95% CI, 21.8-28.3 m; P < .001). In this randomized clinical trial of people with type 2 diabetes and PAD, liraglutide increased peripheral perfusion detected by TcPo2 measurement during 6 months of treatment. These results support the use of liraglutide to prevent the clinical progression of PAD in individuals with type 2 diabetes. ClinicalTrials.gov Identifier: NCT04881110.

Risk Factors for and Risk of Peripheral Artery Disease in Swedish Individuals With Type 2 Diabetes: A Nationwide Register-Based Study.

To investigate to what extent having control of peripheral artery disease (PAD) risk factors is associated with the risk of incident PAD in individuals with type 2 diabetes. A total of 148,096 individuals with type 2 diabetes in the Swedish National Diabetes Register between 2005 and 2009 were included and matched with 320,066 control subjects on the basis of age, sex, and county. A few control subjects who developed type 2 diabetes after recruitment, during wash-in (<0.2%), were not censored but instead matched with two new control subjects. Individuals with type 2 diabetes were evaluated according to the number of PAD risk factors beyond recommended guideline levels at baseline, including LDL cholesterol, blood pressure, smoking, glycated hemoglobin, and estimated glomerular filtration rate. Incident PAD events were ascertained from 2006 to 2019. A graded association was observed between the number of PAD risk factors not at target and incident PAD in individuals with type 2 diabetes. The adjusted hazard ratio for PAD was 1.41 (95% CI 1.23-1.63) for those with type 2 diabetes with all PAD risk factors within target compared with control subjects matched for sex, age, and county but not risk factor status, in contrast with 9.28 (95% CI 3.62-23.79) for those with all five PAD risk factors not at target. A graded association was observed between increasing number of PAD risk factors not at target and incident PAD in individuals with type 2 diabetes.

Assessment and Diagnosis of Peripheral Artery Disease in Patients with Diabetes

Peripheral artery disease (PAD) is a chronic circulatory condition that occurs when the arteries that supply blood to the legs and feet are narrowed or blocked, leading to reduced blood flow to these areas. PAD is a common complication of type 2 diabetes, affecting up to 1 in 3 individuals with the condition. Assessment of PAD in individuals with diabetes typically involves a physical exam, ankle-brachial index (ABI) measurement, and imaging tests such as Doppler ultrasound or angiography. The ABI is a noninvasive measure that compares the blood pressure in the ankles and arms, with a lower ABI indicating a higher risk of PAD. Management of PAD in type 2 diabetes involves a multifaceted approach, including lifestyle modifications, medication, and revascularization procedures. Lifestyle changes such as smoking cessation and regular exercise can improve PAD symptoms and reduce the risk of disease progression. Medications such as antiplatelet agents, statins, and blood pressure-lowering drugs help to manage PAD and its associated risk factors. Revascularization procedures such as angioplasty or bypass surgery may be necessary in severe cases of PAD to restore blood flow to the affected limbs. In addition, these procedures should be considered in the feet of patients with diabetes if there is evidence of ischemia. Early detection and management of PAD in type 2 diabetes are critical to preventing complications such as non-healing wounds, infections, and amputations. Individuals with type 2 diabetes should undergo regular screening for PAD and work with their healthcare providers to develop a personalized treatment plan.

The Plasma Oxylipidome Links Smoking Status to Peripheral Artery Disease.

Peripheral artery disease (PAD) is prevalent among individuals with a history of tobacco smoking. Although oxidation of lipids may contribute to atherogenesis in vascular disease, enzymatically and nonenzymatically produced oxidized lipids can have varying and contrasting physiological effects. The underlying mechanisms of atherogenic vulnerability can be better elucidated with the recent advances in oxylipidome quantification using HPLC-MS/MS technology. In a randomized, controlled clinical trial, the plasma oxylipidome was analyzed in participants living with PAD by smoking status (n = 98) and in nonsmoking comparators without chronic disease (n = 20). Individuals with PAD had approximately a four-fold higher level of total plasma oxylipins versus the comparator. Cessation of smoking in individuals with PAD was associated with significantly lower levels of linoleic acid-derived TriHOMEs, greater levels of omega-3 fatty acid-derived oxylipins, and greater levels of nonfragmented oxidized phosphatidylcholines (OxPCs). Individuals living with PAD but without a history of smoking, exhibited higher levels of the putative atherogenic fragmented OxPCs versus individuals who currently or previously smoked. These data implicate the plasma oxylipidome in PAD and that smoking cessation is associated with a less inflammatory profile. Furthermore, fragmented OxPCs may play a more significant role in the pathophysiology of PAD in individuals without a history of smoking.

Should We Screen for Peripheral Artery Disease in Individuals With Venous Insufficiency?

The prevalence of lower extremity chronic venous insufficiency and peripheral artery disease (PAD) increase with age. Clinically, it is unclear how often a patient ultrasound-determined venous insufficiency (UDVI) has concurrent PAD and whether this is a higher risk group that may benefit from PAD screening.

Sortilin/Omentin-1 ratio in peripheral artery disease: A cross-sectional study on 295 unselected elderly patients

BackgroundThe role of sortilin and omentin-1 in the pathogenesis of atherosclerosis and vascular disease is an emerging topic in recent years. These molecules can be found circulating in the blood. Recent studies have shown how these biomarkers appear to correlate with the severity of PAD. The levels of these molecules appear to be inversely proportional to each other. Their relationship may provide further insight into the management of the very old diabetic patients with PAD. This study aimed to assess the possible role of sortilin/omentin-1 ratio as easy-to-measure marker in peripheral artery disease (PAD) in type-2 diabetic patients. MethodsThis study analyzed the association between sortilin and omentin-1 serum levels and the presence of clinically significant lower limb PAD in diabetic individuals. We enrolled 295 diabetic patients, including 179 with PAD. Serum levels were collected and correlated with clinical characteristics of the patients. ResultsSortilin concentration was significantly higher in the latter group compared to the former and there was a trend toward increased sortilin levels as disease severity increased. Omentin-1 serum levels were significantly lower in diabetic patients with PAD than in diabetic controls and the levels gradually decreased in proportion to disease severity. The ratio of sortilin to omentin-1 was significantly higher in patients with PAD compared to the other group. ConclusionThe sortilin to omentin-1 ratio appears to be a predictive factor for PAD in patients with type-2 diabetes and it may be a promising marker for clinically significant atherosclerosis of the lower limbs. Further studies are needed to confirm this finding and to evaluate its clinical usefulness.

Implications of fasting plasma glucose variability on the risk of incident peripheral artery disease in a population without diabetes: a nationwide population-based cohort study

BackgroundDiabetes have been known as a traditional risk factor of developing peripheral artery disease (PAD). However, the study evaluating the impact of long-term glycemic variability on the risk of developing PAD is limited, especially in a general population without diabetes.MethodsWe included 152,931 individuals without diabetes from the Korean National Health Insurance Service–Health Screening Cohort. Fasting plasma glucose (FPG) variability was measured using coefficient variance (FPG-CV), standard deviation (FPG-SD), and variability independent of the mean (FPG-VIM).ResultsA total of 16,863 (11.0%) incident cases of PAD were identified during a median follow-up of 8.3 years. Kaplan–Meier curves showed a progressively increasing risk of PAD in the higher quartile group of FPG variability than in the lowest quartile group (log rank P < 0.001). Multivariable Cox proportional hazard analysis showed the hazard ratio for PAD prevalence as 1.11 (95% CI 1.07–1.16, P < 0.001) in the highest FPG-CV quartile than in the lowest FPG-CV quartile after adjusting for confounding variables, including mean FPG. Similar degree of association was shown in the FPG-SD and FPG-VIM. In sensitivity analysis, the association between FPG variability and the risk of developing PAD persisted even after the participants were excluded based on previously diagnosed diseases, including stroke, coronary artery disease, congestive heart failure, chronic kidney disease, or current smokers or drinkers. Subgroup analysis demonstrated that the effects of FPG variability on the risk of PAD were more powerful in subgroups of younger age, regular exercisers, and those with higher income.ConclusionsIncreased long-term glycemic variability may have a significant prognostic effect for incident PAD in individuals without diabetes.Graphical

Profile of Peripheral Arterial Disease in Type 2 Diabetes Mellitus - A Hospital-based observational study in Coastal Karnataka

Introduction: Ankle Brachial Index (ABI) is one of the common non-invasive diagnostic tools available for diagnosing Peripheral Arterial Disease (PAD). However, it has been observed that for an individual diagnosed with both PAD and Type 2 Diabetes Mellitus (T2DM), ABI tends to give false diagnostic value because of the calcification of the major lower limb arteries. Therefore, the health care professionals are at times misled for the diagnosis of PAD. To overcome this another diagnostic tool Toe Brachial Index (TBI) was suggested to perform. However, there is limited literature on performing both ABI and TBI in the given population in a single study.Aim:The main focus of this study is to report the profile of ABI and TBI along with classical symptoms like claudication pain, palpation of pulse and history of T2DM for the screening and diagnosis of PAD in T2DM.Materials And Methods: In this cross-sectional observational study, a total of 121 participants diagnosed with T2DM were recruited for the study as per the inclusion criteria. Detailed demographic details of the participants were noted. Diagnostic tool including both ABI and TBI were performed for all the participants and the data was analysed.Results:Among 121 participants, only 3 participants had both ABI and TBI positive indicating positive diagnostic test for PAD and 106 participants had both ABI and TBI negative. However, in the remaining 12 participants, 10 showed TBI positive but ABI negative and 2 had ABI positive but TBI negative.Conclusions: Based on our study we have reported the profile of PAD in T2DM individuals, which is found to be 10.75.%. Therefore, it can be concluded that ABI and TBI both should be performed to rule out any complication. This will be beneficial in early screening and detection of neuro ischemic changes in foot and subsequently to prevent amputation.

PCSK9 loss of function is protective against extra-coronary atherosclerotic cardiovascular disease in a large multi-ethnic cohort.

BackgroundTherapeutic inhibition of PCSK9 protects against coronary artery disease (CAD) and ischemic stroke (IS). The impact on other diseases remains less well characterized.MethodsWe created a genetic risk score (GRS) for PCSK9 using four single nucleotide polymorphisms (SNPs) at or near the PCSK9 locus known to impact lower LDL-Cholesterol (LDL-C): rs11583680, rs11591147, rs2479409, and rs11206510. We then used our GRS to calculate weighted odds ratios reflecting the impact of a genetically determined 10 mg/dL decrease in LDL-C on several pre-specified phenotypes including CAD, IS, peripheral artery disease (PAD), abdominal aortic aneurysm (AAA), type 2 diabetes, dementia, chronic obstructive pulmonary disease, and cancer. Finally, we used our weighted GRS to perform a phenome-wide association study.ResultsGenetic and electronic health record data that passed quality control was available in 312,097 individuals, (227,490 White participants, 58,907 Black participants, and 25,700 Hispanic participants). PCSK9 mediated reduction in LDL-C was associated with a reduced risk of CAD and AAA in trans-ethnic meta-analysis (CAD OR 0.83 [95% CI 0.80–0.87], p = 6.0 x 10−21; AAA OR 0.76 [95% CI 0.68–0.86], p = 2.9 x 10−06). Significant protective effects were noted for PAD in White individuals (OR 0.83 [95% CI 0.71–0.97], p = 2.3 x 10−04) but not in other genetic ancestries. Genetically reduced PCSK9 function associated with a reduced risk of dementia in trans-ethnic meta-analysis (OR 0.86 [95% CI 0.78–0.93], p = 5.0 x 10−04).ConclusionsGenetically reduced PCSK9 function results in a reduction in risk of several important extra-coronary atherosclerotic phenotypes in addition to known effects on CAD and IS, including PAD and AAA. We also highlight a novel reduction in risk of dementia, supporting a well-recognized vascular component to cognitive impairment and an opportunity for therapeutic repositioning.

Impact of LDL Cholesterol on Microvascular Versus Macrovascular Disease: A Mendelian Randomization Study

BackgroundLow-density lipoprotein cholesterol (LDL-C) is causally associated with a high risk of coronary artery disease. Whether this also holds for a spectrum of peripheral vascular diseases is unknown. ObjectivesThe purpose of this study was to determine whether high LDL-C causally relates to risk of retinopathy, neuropathy, chronic kidney disease (CKD), and peripheral arterial disease (PAD) in the general population. MethodsOne-sample Mendelian randomization (MR) of 116,419 Danish individuals, 2-sample MR on summary-level data from the Global Lipid Genetics Consortium (GLGC) (n = 94,595) and the UK Biobank (n = 408,455), and meta-analysis of randomized statin trials (n = 64,134) were performed. ResultsObservationally, high LDL-C did not associate with high risk of retinopathy or neuropathy. There were stepwise increases in risk of CKD and PAD with higher LDL-C (both p for trend <0.001), with hazard ratios of 1.05 (95% confidence interval [CI]: 0.97 to 1.13) for CKD, and 1.41 (95% CI: 1.23 to 1.62) for PAD in individuals with LDL-C above the 95th percentile versus below the 50th percentile. In genetic, causal analyses in the Copenhagen studies, the risk ratio of disease for a 1 mmol/l higher LDL-C was 1.06 (95% CI: 0.24 to 4.58) for retinopathy, 1.05 (95% CI: 0.64 to 1.72) for neuropathy, 3.83 (95% CI: 2.00 to 7.34) for CKD, and 2.09 (95% CI: 1.30 to 2.38) for PAD. Summary-level data from the GLGC and the UK Biobank for retinopathy, neuropathy, and PAD gave similar results. For CKD, a 1-mmol/l lower LDL-C conferred a higher eGFR of 1.95 ml/min/1.73 m2 (95% CI: 1.88 to 2.02 ml/min/1.73 m2) observationally, 5.92 ml/min/1.73 m2 (95% CI: 4.97 to 6.86 ml/min/1.73 m2) genetically, and 2.69 ml/min/1.73 m2 (95% CI: 1.48 to 3.94 ml/min/1.73 m2) through statin therapy. ConclusionsHigh LDL-C was not causally associated with risk of retinopathy and neuropathy; however, high LDL-C was observationally and genetically associated with high risks of PAD and CKD, suggesting that LDL-C is causally involved in the pathogenesis of these diseases.

Prevalence and associated risk factors of peripheral artery disease in virologically suppressed HIV-infected individuals on antiretroviral therapy in Kwara state, Nigeria: a cross sectional study

BackgroundThe association between HIV and cardiovascular disease (CVD) has been reported in several studies. However, there is paucity of information on the prevalence of subclinical disease as well as its associated risk factors in sub-Saharan African population. The aim of this study was to determine the prevalence and associated risk factors of peripheral artery disease (PAD) among virologically suppressed HIV-infected participants in Kwara State, Nigeria.MethodsThis study was conducted between July 2018 and December 2018. A total of 150 HIV-infected participants aged between 20 and 55 years and 50 HIV non-infected age-matched controls were randomly recruited in the study. Sociodemographic, anthropometric and clinical data were collected using a well-structured questionnaire. Ankle brachial index (ABI) was measured, PAD was defined as ABI of < 0.9. Cryopreserved serum was used to evaluate lipid profile parameters. Student’s t-test and Chi-square were used to compare continuous and categorical variables. Associations of CVD risk factors and clinical data, and lipid profile with low ABI were assessed using logistic regression analysis.ResultsThe study participants had a mean age of 43.73 ± 8.74, majority were females (72.7%) with a mean duration on ART of 7.73 ± 3.52 years. Hypertension was present in 15.9%, diabetes 4%, family history of CVD 8.6% and metabolic syndrome 17.3% in the study group. The study participants recorded significantly lower mean values for ABI, HDL-C and significantly higher mean values of TG (P < 0.05) compared to the control group. The prevalence of low ABI (14.6%) was higher in the study group compared to the control group (2%). A significantly negative correlation between ABI and duration on ART (r = − 0.163, P = 0.041) and a positive correlation between viral load and TG were observed in the study group. TC (OR 1.784, P = 0.011), LDL-C (OR 1.824, P = 0.010) and CD4 cell count < 200 cells/mm3 (OR 2.635, P = 0.364) were associated with low ABI in the participants.ConclusionViral suppression with combined antiretroviral therapy and long term treatment is associated with dyslipidaemia, with increased risk of PAD. Prevalence of PAD in virologically-suppressed individuals does not differ from the controls in the population studied.

Prevalence and Pattern of Peripheral Arterial Disease among Diabetic Individual in Al-jouf Region

Introduction: Peripheral arterial disease (PAD) is a common vascular disorder in Saudi Arabia where diabetes mellitus, hypertension and smoking are common risks. As this disease carries significant morbidity and mortality. Objective: This study aimed to screen for PAD in the community among diabetics, determining its prevalence, severity and associated risk factors. Patients and Methods: This study was done at 3 primary health care centers (PHCCs) at Domat Aljandal and two centers at Quraiat, Aljouf region. The included patients were 149, all were diabetic, 114 males and 35 females. The sociodemographic data, special habits, symptoms of peripheral ischemia and biochemical profiles [including blood lipids and fasting sugar] were extracted from the medical files and asked during interview. After clinical assessment, the ankle brachial index (ABI) was bilaterally determined on supine position using 8 MHz vascular Doppler. PAD was diagnosed if an ABI was 0.05 for each). The frequency of low ABI was significantly more frequent among patients with history of vascular surgery (P=0.001). Patients with PAD had significantly higher mean ages (P=0.048) and non- significantly higher mean of duration of DM. If patients known to have PAD are excluded, new diagnosis of PAD was made in 30 of 128 naive patients (23.4%). Conclusion: The prevalence of PAD in diabetic individuals in the community is high, probably due to the high frequency of other risks such as smoking and hypertension. These finding warrants activation of the nationwide screening program for prevention of cardiovascular diseases to decrease the morbidity and mortality of this diabetic complication.

High Serum Leptin Level is Associated with Peripheral Artery Disease in Geriatric Individuals

Summary Background Leptin contributes to the pathogenesis of atherosclerosis, endothelial dysfunction, and thrombosis. Peripheral arterial disease (PAD) is a common manifestation of atherosclerosis and is expected to prevail among geriatric individuals. The present study aimed to determine whether serum leptin level is associated with PAD in a geriatric group. Methods Blood samples were obtained from 60 participants in the study who were >65 years of age. Ankle-brachial index (ABI) values were measured using the automated oscillometric method. PAD was considered to be present if the left or right ABI values were less than 0.90, and these participants were included in the low ABI group. Serum leptin levels were measured using a commercial enzyme immunoassay kit. Results Of these geriatric participants, ten (16.7%) were in the low ABI group. Compared with the elderly participants in the normal ABI group, those in the low ABI group were current smokers (p = 0.048) and had higher serum C-reactive protein (CRP, p = 0.018) and leptin levels (p = 0.005). Multivariate logistic regression analysis of the factors significantly associated with PAD demonstrated that leptin (odds ratio: 1.078, 95% confidence interval: 1.021–1.138, p = 0.006) was an independent predictor of PAD. Female (p = 0.001), body mass index (p = 0.008), and a logarithmically transformed CRP (log-CRP, p = 0.035) were found to be associated with serum log-leptin levels among geriatric participants after multivariate forward stepwise linear regression analysis. Conclusion High serum leptin level is a risk marker for PAD in geriatric individuals.

Assessment of ulceration risk in diabetic individuals.

To identify the risk factors for foot ulceration through the tracing of diabetic peripheral neuropathy and peripheral arterial disease in individuals with type I and II diabetes, who were assisted in reference centers of the Federal District, Brazil. a cross-sectional and analytical study, with the assessment of 117 individuals in outpatient clinics of the Federal District. Continuous variables were compared through Mann-Whitney test, and categorized variables, through Chi-square test for univariate analysis and Logistics regression test for multivariate analysis. painful diabetic peripheral neuropathy was present in 37 (75.5%) of the individuals with neuropathy. Deformities and loss of protective plant sensibility were related to neuropathy (p=0.014 and p=0.001, respectively). Of the 40 (34.2%) individuals in the sample who presented peripheral arterial disease, 26 (65%) presented calcification risk. signs of painful peripheral polyneuropathy, peripheral arterial disease, deformities, loss of protective plantar sensibility, and dry skin were identified as risk factors for ulceration.

Abstract 11579: Physical Activity versus Body Mass Index and Prevalence of Peripheral Arterial Disease

Introduction: Physical activity and body mass index (BMI) are independently associated with peripheral arterial disease (PAD). However, their relative significance and combined association with PAD remain unclear. Hypothesis: We hypothesize that physical activity is associated with a lower odds of PAD across the BMI spectrum and that physical activity attenuates the prevalence of PAD in obese patients. Methods: We studied 3,250,350 U.S. adults who self-referred for PAD screening from 2003-2008 (Life Line Screening Inc., Independence, Ohio). Subjects completed a medical/lifestyle questionnaire. They were categorized into physically active or physically inactive based on their response in the questionnaire to whether they engaged in any type of vigorous leisure time exercise on a regular basis. All subjects were evaluated for PAD by ankle brachial index, with &lt;0.9 considered abnormal. We divided participants into standardized BMI categories: underweight (&lt; 18.5), normal weight (18.5-24.9), overweight (25-29.9), obese class I (30-34.9), class II (35-39.9), and class III (&gt; 40). Multivariable logistic regression was used to estimate the odds of PAD among the BMI categories, based on physical activity. Results: Overall, mean age was 63.1 ± 10.5 years, 65.5% were female, and mean BMI was 27.7 ± 5.8 kg/m 2 . 41.5% were physically inactive. Average BMI was higher in the physically inactive versus physically active group (28.9 ± 6.3 vs. 27.0 ± 5.3, P&lt;0.0001). Prevalence of PAD initially decreased and then increased with BMI and was attenuated with physical activity. Following multivariable adjustment, physical activity was independently associated with lower odds of PAD across the BMI spectrum (Table). Conclusion: Physical activity is associated with lower odds of PAD in underweight, normal weight, overweight and obese individuals. The higher prevalence of PAD with increasing BMI is attenuated with physical activity.

Effectiveness of bedside investigations to diagnose peripheral artery disease among people with diabetes mellitus: a systematic review.

Non-invasive tests for the detection of peripheral artery disease (PAD) among individuals with diabetes mellitus are important to estimate the risk of amputation, ulceration, wound healing and the presence of cardiovascular disease, yet there are no consensus recommendations to support a particular diagnostic modality over another and to evaluate the performance of index non-invasive diagnostic tests against reference standard imaging techniques (magnetic resonance angiography, computed tomography angiography, digital subtraction angiography and colour duplex ultrasound) for the detection of PAD among patients with diabetes. Two reviewers independently screened potential studies for inclusion and extracted study data. Eligible studies evaluated an index test for PAD against a reference test. An assessment of methodological quality was performed using the quality assessment for diagnostic accuracy studies instrument. Of the 6629 studies identified, ten met the criteria for inclusion. In these studies, the patients had a median age of 60-74 years and a median duration of diabetes of 9-24 years. Two studies reported exclusively on patients with symptomatic (ulcerated/infected) feet, two on patients with asymptomatic (intact) feet only, and the remaining six on patients both with and without foot ulceration. Ankle brachial index (ABI) was the most widely assessed index test. Overall, the positive likelihood ratio and negative likelihood ratio (NLR) of an ABI threshold <0.9 ranged from 2 to 25 (median 8) and <0.1 to 0.7 (median 0.3), respectively. In patients with neuropathy, the NLR of the ABI was generally higher (two out of three studies), indicating poorer performance, and ranged between 0.3 and 0.5. A toe brachial index <0.75 was associated with a median positive likelihood ratio and NLRs of 3 and ≤ 0.1, respectively, and was less affected by neuropathy in one study. Also, in two separate studies, pulse oximetry used to measure the oxygen saturation of peripheral blood and Doppler wave form analyses had NLRs of 0.2 and <0.1. The reported performance of ABI for the diagnosis of PAD in patients with diabetes mellitus is variable and is adversely affected by the presence of neuropathy. Limited evidence suggests that toe brachial index, pulse oximetry and wave form analysis may be superior to ABI for diagnosing PAD in patients with neuropathy with and without foot ulcers. There were insufficient data to support the adoption of one particular diagnostic modality over another and no comparisons existed with clinical examination. The quality of studies evaluating diagnostic techniques for the detection of PAD in individuals with diabetes is poor. Improved compliance with guidelines for methodological quality is needed in future studies.

Prevalence of lower extremity peripheral arterial disease in individuals with chronic immune mediated inflammatory disorders.

To compare the prevalence of lower extremity peripheral artery disease (PAD) and to assess whether age-associated progression in ankle-brachial index (ABI) differs between individuals with chronic immune-mediated inflammatory diseases (CIID) and the general population. Pooled analysis with data from individuals aged 50 years and older with ABI measurements, obtained from population-based cross-sectional studies conducted in Catalonia (Spain). Information on three CIID diagnoses (i.e., inflammatory bowel disease, systemic connective tissue disorders, and inflammatory polyarthropathies and spondylopathies, considered as one entity for purposes of analysis) was obtained from electronic medical records. To ascertain the statistical association between PAD and CIID, logistic regression models were fitted and adjusted for age, sex, and cardiovascular risk factors. We tested the interaction between age and CIID diagnosis for ABI values. We included 8799 individuals, 312 (3.6%) with CIID. The age-standardized prevalence of PAD was higher in the CIID group (12% vs. 6% in general population, p = 0.001), and the model adjusted for age, sex, and cardiovascular risk factors also showed higher risk in individuals with CIID [Odds Ratio (95% confidence interval) = 1.65 (1.15-2.38); p = 0.007]. The inflammatory polyarthropathies/spondylopathies diagnosis was significantly associated with PAD in the fully adjusted model [1.80 (1.18-2.75); p = 0.006]. The atherosclerotic process was accelerated in individuals with CIID, compared to the general population (p for interaction<0.001). In individuals with CIID, age-standardized prevalence of PAD was significantly higher than in the general population and the atherosclerotic process was accelerated. However, only inflammatory polyarthropathies/spondylopathies was associated with significant risk of PAD.

Abstract 358: Genetic Determinants of Lower-Extremity Claudication in South Asians

OBJECTIVES: The prevalence of peripheral arterial disease (PAD) in South Asian populations is less than that reported in populations of Western descent despite higher rates of MI and diabetes. This suggests that there may be a different underlying genetic predisposition to PAD in South Asian individuals. This study was designed to investigate the genetic determinants of PAD in a large Pakistani cohort. METHODS: We examined the association between single nucleotide polymorphisms (SNPs) and clinical symptoms of claudication in participants of the Pakistan Risk of Myocardial Infarction Study (PROMIS), a multicenter case-control study of MI in Pakistan, using its 1000-Genome imputed data set. RESULTS: 724 (4.8%) of the 15,570 individuals enrolled in PROMIS had symptoms of claudication. These subjects had an average (SD) age of 56 (9.7) years and 536 (74%) were male. To assess the role of known MI risk loci, 250 kBP regions flanking the 45 reported MI risk SNPs were examined for their association with claudication. No SNP in any of the known MI risk loci met the pre-determined Bonferroni p-value threshold for significance (&lt;1x10-5). Likewise, a composite risk score based on reported MI risk related SNPs was not associated with claudication symptoms despite a highly significant correlation with MI (p=4.7x10-34). In genome wide analysis no SNP achieved significance with a p-value &lt;5 x 10-8. There were, however, three SNPs with p-values &lt;5 x 10-7, suggestive of potential associations with claudication: rs7580101 (p=1.1 x 10-7), rs4655022 (p=1.4 x 10-7), and rs57859654 (p=2.1 x 10-7). Interestingly, rs7580101 occurs within an intron of the gene for CD59, a complement inhibitor that has been demonstrated to modulate atherosclerosis in multiple mouse models. The CD59 gene has not been previously reported as a MI or PAD risk locus. CONCLUSIONS: These findings argue for a different genetic risk profile for PAD and CAD in South Asians, supporting the differences in PAD prevalence between this population and those of Western descent. Additionally, they identify numerous novel potential risk loci for PAD. Replication studies are currently underway to validate these findings.

Screening for peripheral arterial disease

In the general population, up to 10% of people younger than 70 years and 15% to 20% of people older than 70 years have peripheral arterial disease (PAD). Symptomatic and asymptomatic PAD has an estimated prevalence of 13% in the over 50 years age group. However, asymptomatic PAD can account for up to 75% of PAD patients and only 10% of PAD patients have typical intermittent claudication. People with PAD are at an increased risk of death, heart and cerebrovascular disease and are recommended to receive treatment to manage their cardiac risk. They suffer from significant functional limitations in their daily activities and the most severely affected are at risk of limb loss. Many people with PAD do not have any symptoms. Only some people have discomfort or pain in the lower legs when walking, so PAD often goes undetected. Given the high incidence of asymptomatic and undiagnosed PAD, it is important to determine the effectiveness of a screening intervention in preventing cardiovascular adverse outcomes, both fatal and non-fatal. To determine the effectiveness of screening for PAD in asymptomatic and undiagnosed individuals in terms of reduction of all-cause mortality, cardiovascular events (for example myocardial infarction and stroke), morbidity from PAD (intermittent claudication, amputation, reduced walking distance) and improvement in quality of life. The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched November 2013) and CENTRAL (2013, Issue 10). All published and unpublished randomised controlled trials (RCTs) of screening for PAD were sought without language restriction. Studies identified for potential inclusion in the review were independently assessed by both review authors. We planned to conduct data collection and analysis in accordance with the Cochrane Handbook for Systematic Review of Interventions. No RCTs were identified that met the inclusion criteria. Unfortunately, no randomised controlled trial data are available regarding screening for PAD. Therefore, we are unable to determine the effects of screening for PAD in order to guide decision making by healthcare providers and planners. High quality randomised controlled trials evaluating the effectiveness of screening for PAD in asymptomatic and undiagnosed individuals in terms of reduction of all-cause mortality, cardiovascular events (for example myocardial infarction and stroke), morbidity from PAD (intermittent claudication, amputation, reduced walking distance) and improvement in quality of life are needed.

Co-Existence of Carotid Artery Disease, Renal Artery Stenosis, and Lower Extremity Peripheral Arterial Disease in Patients With Coronary Artery Disease

In atherosclerosis, carotid artery stenosis (CAS), renal artery stenosis (RAS), lower extremity peripheral arterial disease (PAD), and coronary artery disease (CAD) are common pathologic lesions; their interrelationship is, however, unclear. We studied concomitant multiple atherosclerotic lesions in patients with CAD to understand their prevalence and relations. A cross-sectional analysis was performed on data from consecutive patients who underwent nonemergent coronary angiography. Simultaneous carotid and renal artery Doppler studies and ankle-brachial systolic pressure measurements were reviewed to diagnose concomitant lesions and their severity. The study included 1,734 patients (aged 71 ± 9 years; 70% men), with prevalences of CAS, RAS, lower extremity PAD, and CAD of 6%, 7%, 13%, and 72%, respectively. In patients with CAD (n = 1,253), the prevalences of CAS, RAS, and lower extremity PAD were 7%, 9%, and 16%, respectively; 24% CAD patients had ≥1 additional atherosclerotic lesion. Significant interactions among the prevalences of these lesions were found. In addition, the extent of CAD and the prevalences of CAS, RAS, and lower extremity PAD were significantly correlated. Multivariate analysis supported these relationships. In conclusion, the prevalences of CAS, RAS, lower extremity PAD, and CAD were strongly interrelated in the study population; CAD severity was related to that of other atherosclerotic lesions. Additional systematic screening of other concomitant atherosclerotic lesions is recommended, especially in CAD patients having multivessel disease, left main disease, and/or already diagnosed with other concomitant atherosclerotic lesions.