Risk Of Peripheral Arterial Disease Research Articles

APOE and vascular disease: Sequencing and genotyping in general population cohorts

Background and aimsThe apolipoprotein E(APOE) ϵ2/ϵ3/ϵ4 polymorphism plays a central role in lipid metabolism, vascular disease and dementia. The impact of the full range of structural genetic variation in APOE for lipids, lipoproteins and apolipoproteins and for vascular disease in the general population is not known. MethodsWe systematically sequenced APOE in 10,296 individuals from the Copenhagen City Heart Study and genotyped nine rare variants (frequency≥2/10,296) in 95,227 individuals from the Copenhagen General Population Study. The UK Biobank was used for validation of common APOE variants. ResultsRare mutations in APOE, predicted to be deleterious, are present in 1 in 257 individuals in the general population. In the meta-analysis, multifactorially adjusted hazard ratios (95% confidence intervals) for ϵ44 and ϵ22 versus ϵ33 were 1.15 (1.04–1.26) and 1.02 (0.83–1.24) for ischemic cerebrovascular disease (ICVD), 1.11 (1.04–1.19) and 0.94 (0.83–1.08) for ischemic heart disease (IHD) and 1.03 (0.89–1.17) and 1.49 (1.20–1.87) for peripheral arterial disease (PAD). A multifactorially and ϵ2/ϵ3/ϵ4 adjusted weighted allele score on the continuous scale including all common and rare structural variants showed that for individuals with genetically predicted high plasma apoE and remnant cholesterol the risk for PAD was increased. ConclusionsAPOE variants with high apoE, triglycerides, and remnant cholesterol are associated with PAD, whereas common APOE variants with high LDL cholesterol, triglycerides and remnant cholesterol are associated with IHD. APOE variants with low apoE are associated with increased risk of ICVD. These findings highlight that both rare and common structural variations in APOE play a role in vascular disease.

High lipoprotein(A) increases risk of peripheral arterial disease, abdominal aortic aneurysms, and major adverse limb events

High lipoprotein(A) increases risk of peripheral arterial disease, abdominal aortic aneurysms, and major adverse limb events

Admixture mapping of peripheral artery disease in a Dominican population reveals a putative risk locus on 2q35.

Peripheral artery disease (PAD) is a form of atherosclerotic cardiovascular disease, affecting ∼8 million Americans, and is known to have racial and ethnic disparities. PAD has been reported to have a significantly higher prevalence in African Americans (AAs) compared to non-Hispanic European Americans (EAs). Hispanic/Latinos (HLs) have been reported to have lower or similar rates of PAD compared to EAs, despite having a paradoxically high burden of PAD risk factors; however, recent work suggests prevalence may differ between sub-groups. Here, we examined a large cohort of diverse adults in the BioMe biobank in New York City. We observed the prevalence of PAD at 1.7% in EAs vs. 8.5% and 9.4% in AAs and HLs, respectively, and among HL sub-groups, the prevalence was found at 11.4% and 11.5% in Puerto Rican and Dominican populations, respectively. Follow-up analysis that adjusted for common risk factors demonstrated that Dominicans had the highest increased risk for PAD relative to EAs [OR = 3.15 (95% CI 2.33-4.25), p < 6.44 × 10-14]. To investigate whether genetic factors may explain this increased risk, we performed admixture mapping by testing the association between local ancestry and PAD in Dominican BioMe participants (N = 1,813) separately from European, African, and Native American (NAT) continental ancestry tracts. The top association with PAD was an NAT ancestry tract at chromosome 2q35 [OR = 1.96 (SE = 0.16), p < 2.75 × 10-05) with 22.6% vs. 12.9% PAD prevalence in heterozygous NAT tract carriers versus non-carriers, respectively. Fine-mapping at this locus implicated tag SNP rs78529201 located within a long intergenic non-coding RNA (lincRNA) LINC00607, a gene expression regulator of key genes related to thrombosis and extracellular remodeling of endothelial cells, suggesting a putative link of the 2q35 locus to PAD etiology. Efforts to reproduce the signal in other Hispanic cohorts were unsuccessful. In summary, we showed how leveraging health system data helped understand nuances of PAD risk across HL sub-groups and admixture mapping approaches elucidated a putative risk locus in a Dominican population.

Association of Glaucoma with the Risk of Peripheral Arterial Occlusive Disease: A Retrospective Population-Based Cohort Study.

This study aimed to investigate the potential association between glaucoma and peripheral arterial occlusive disease. The study recruited patients, including 101,309 with glaucoma and 1,860,528 without a glaucoma diagnosis, from a population of 2 million patients in the Longitudinal Health Insurance Database. Propensity score matching was performed between the two groups, matching for age, sex, and comorbidities. In total, 95,575 patients with glaucoma and 95,575 patients without glaucoma were analyzed for their risk of developing peripheral arterial occlusive disease. The analysis of the data revealed that the glaucoma group had a higher incidence density (ID = 4.13) of peripheral arterial occlusive disease than the non-glaucoma group (ID = 3.42). The relative risk for the glaucoma group was 1.21 (95% C.I. = 1.15-1.28). Cox proportional hazard model analysis indicated that the glaucoma group had a higher risk of developing peripheral arterial occlusive disease (HR = 1.18; 95% C.I. = 1.12-1.25). The subgroup analysis of the risk of PAOD showed that the glaucoma group had a higher risk of developing peripheral arterial occlusive disease in the age group of 20 to 39 (p for interaction = 0.002). In conclusion, patients with glaucoma were associated with a higher risk of subsequent peripheral arterial occlusive disease compared with those without a diagnosis of glaucoma.

Peripheral artery disease and markers of endothelial dysfunction and platelet activation in people with HIV.

People with HIV (PWH) have increased risk of peripheral artery disease (PAD), but the pathogenesis is unknown. We aimed to determine associations between markers of endothelial dysfunction and platelet activation and both PAD at baseline and de novo PAD in PWH. 1012 PWH from the longitudinal Copenhagen Comorbidity in HIV Infection (COCOMO) study and 57 age- and sex-matched population controls were included. Plasma samples were collected at baseline and analyzed for soluble thrombomodulin, syndecan-1 and CD40 ligand (sCD40L). Ankle-brachial index was measured at baseline and two-year follow-up in PWH. Logistic and Poisson regression models were used to test associations. PWH had higher concentrations of soluble thrombomodulin (P=0.03) and syndecan-1 (P<0.001), and lower concentrations of sCD40L (P<0.001) compared to controls. High concentration of soluble thrombomodulin, but not syndecan-1 or sCD40L, was associated with lower odds of PAD in PWH at baseline after adjustments (adjusted odds ratio: 0.50 [0.28, 0.90], P=0.02). None of the markers were associated with de novo PAD. PWH had higher concentrations of soluble thrombomodulin and syndecan-1 and lower concentration of sCD40L compared to controls. Soluble thrombomodulin was associated with lower odds of PAD at baseline. Further studies are needed to elucidate the pathogenesis of PAD in people with HIV.

Chronic Venous Disease and Its Intersections With Diabetes Mellitus.

Chronic venous disease (CVD) is a vascular disorder in which blood return is severely compromised and CVD is usually characterized by venous hypertension. Along with obesity and diabetes mellitus, CVD is one of the most common civilization diseases. In general, the estimated prevalence of CVD ranges from 60-80 %. Early diagnosis and adequate treatment are important for preventing progression to more severe stages of the disease like venous leg ulcers. Clinical manifestations of CVD in initial stages of the disease are often asymptomatic. However, as CVD progresses, symptoms begin to develop. Treatment of CVD could be divided into conservative and surgical. Conservative therapy consists of compression, pharmacological treatment and lifestyle change. In cases where conservative therapy is ineffective, surgical or endovascular treatment may be required. The intersections between diabetes mellitus (DM) and CVD are not to be underestimated. CVD and DM have often the same risk factors. Symptoms of CVD can be modified by late complications of DM, but the incidence of different CVD degrees seems to be the same as in diabetics as in non-diabetics population. We are particularly concerned in diabetics about worse compliance with treatment due to their often-poorer adherence to treatment of DM and lifestyle changes. Moreover, there exist a higher risk of CVD and peripheral arterial disease in diabetics patients. Patients with CVD should always be inspected for the presence of DM, considering its presence can have a bearing on CVD symptoms, diagnostic procedures, and therapeutic strategies.

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.

Heart Failure and Major Adverse Cardiovascular Events in Atrial Fibrillation Patients: A Retrospective Primary Care Cohort Study.

Atrial fibrillation (AF) is a common cardiac arrhythmia that is associated with an increased risk of major adverse cardiovascular events (MACE). The main goal was to analyze the links and associations between AF and MACE. A multicenter, observational, retrospective, community-based study of a cohort (n = 40,297) of the general population aged 65-95 years between 1 January 2015 and 31 December 2021 without a previous diagnosis of AF or MACE in the Primary Care setting. 2574 people (6.39%) developed a first AF event, resulting in an overall incidence of 8.9/1000 people-years [CI95% 8.6-9.2]. The incidence of MACE among those with AF was 75.1/1000 people-years [CI95% 70.8-79.5], whereas among those without AF, it was 20.6/1000 people-years [CI 95% 20.2-21.1], resulting in a rate ratio of 3.65 [CI 95% 3.43-3.88, p < 0.001]. Besides, the incidence of HF with AF was 40.1 people-years [CI 95% 37.1-43.2], while in the group without AF, it was 8.3 people-years [CI 95% 7.9-8.6, p < 0.001], with a rate ratio of 4.85 [CI 95% 4.45-55.3, p < 0.001]. Before an AF diagnosis, there is already a higher risk of chronic kidney disease, ischemic cardiopathy, and peripheral artery disease. A higher risk of poor nutritional status was detected among those with MACE (49.7% vs. 26.6%, p < 0.001). AF diagnosis increases the incidence of heart failure fourfold. Additional information is required to establish the connection between AF, major adverse cardiovascular events, and nutritional status.

ABO Blood Group Type and the Risks of Peripheral Artery Disease in Type II Diabetes Mellitus

ABO Blood Group Type and the Risks of Peripheral Artery Disease in Type II Diabetes Mellitus

Association between psoriasis and peripheral artery occlusive disease: a population-based retrospective cohort study.

Psoriasis (PSO) is a chronic skin condition that affects a variety of disorders, especially the cardiovascular system. This study investigated the association between PSO and peripheral arterial disease (PAOD). A retrospective cohort study design was carried out between 2000 and 2018. The exposure subject was a newly diagnosed PSO. The diagnosis of PSO was never elaborated as a comparison subject. Balanced heterogeneity of the two groups was used by propensity score matching. The cumulative incidence of PAOD between the two groups was performed using Kaplan-Meier analysis. The Cox proportional hazard model was used to measure the risk of PAOD risk hazard ratio. After matching the 1: 1 propensity score, 15,696 subjects with PSO and the same number of subjects without the diagnosis of PSO were recruited. The PSO subject had a higher risk of PAOD than the non-PSO subject (adjusted HR = 1.25; 95% CI = 1.03-1.50). In the 40-64-year-old subgroup, the subject of PSO exhibited an increased risk of PAOD than the subject without PSO. Psoriasis is associated with an increased risk of peripheral arterial disease and curative care is necessary to reduce the risk of PAOD..

Monitoring Muscle Perfusion in Rodents During Short-Term Ischemia Using Power Doppler Ultrasound.

The aim of this work was to evaluate the reliability of power Doppler ultrasound (PD-US) measurements made without contrast enhancement to monitor temporal changes in peripheral blood perfusion. On the basis of pre-clinical rodent studies, we found that combinations of spatial registration and clutter filtering techniques applied to PD-US signals reproducibly tracked blood perfusion in skeletal muscle. Perfusion is monitored while modulating hindlimb blood flow. First, in invasive studies, PD-US measurements in deep muscle with laser speckle contrast imaging (LSCI) of superficial tissues made before, during and after short-term arterial clamping were compared. Then, in non-invasive studies, a pressure cuff was employed to generate longer-duration hindlimb ischemia. Here, B-mode imaging was also applied to measure flow-mediated dilation of the femoral artery while, simultaneously, PD-US was used to monitor downstream muscle perfusion to quantify reactive hyperemia. Measurements in adult male and female mice and rats, some with exercise conditioning, were included to explore biological variables. PD-US methods are validated through comparisons with LSCI measurements. As expected, no significant differences were found between sexes or fitness levels in flow-mediated dilation or reactive hyperemia estimates, although post-ischemic perfusion was enhanced with exercise conditioning, suggesting there could be differences between the hyperemic responses of conduit and resistive vessels. Overall, we found non-contrast PD-US imaging can reliably monitor relative spatiotemporal changes in muscle perfusion. This study supports the development of PD-US methods for monitoring perfusion changes in patients at risk for peripheral artery disease.

Association of Race and Neighborhood Socioeconomic Disadvantage with Incident Peripheral Artery Disease and Chronic Limb-threatening Ischemia

There are disparities in peripheral artery disease (PAD) outcomes according to both race and socioeconomic disadvantage separately. However, few studies have investigated the association of race and socioeconomic deprivation together with risk of PAD. We aimed to investigate the association of race and socioeconomic disadvantage with risk of incident PAD and incident chronic limb-threatening ischemia (CLTI). We included all non-Hispanic white and non-Hispanic Black adults in the Maryland Health Services Cost Review Commission from January 2013 through December 2019 without prevalent PAD or CLTI at their index visit. PAD and CLTI were defined by inpatient and outpatient diagnosis codes. Socioeconomic disadvantage was determined by the area deprivation index (ADI), a comprehensive measure of socioeconomic deprivation, using nine-digit zip codes. Patients living in neighborhoods with greater socioeconomic deprivation (ADI 3 and 4) were categorized as high ADI, while patients living in neighborhoods with lower socioeconomic deprivation (ADI 1 and 2) were categorized as low ADI. We estimated the cumulative incidence of PAD and CLTI and quantified hazard ratios (HR) using multivariable Cox proportional hazards models across four race and ADI groups after correcting for traditional demographic and cardiovascular risk factors. A total of 5,592,650 adult patients without PAD or CLTI at baseline (51.6% ≥65 years of age, 37.9% Black, 31.2% with high ADI) were followed for a median of 10.71 years (interquartile range, 5-31 years). The overall cumulative incidence of PAD and CLTI was 22% and 6%, respectively, and varied significantly by race and ADI (Figs 1 and 2). After adjusting for baseline differences between groups, the risk of incident PAD was highest for the Black-high ADI group (hazard ratio [HR], 1.40; 95% confidence interval [CI], 1.38-1.43), followed by White-high ADI (HR, 1.22; 95% CI, 1.20-1.24) and Black-low ADI (HR, 1.00; 95% CI, 0.99- 1.01) compared to White-low ADI (Table). Similarly, the risk of incident CLTI was highest for the Black-high ADI group (HR, 1.52; 95% CI, 1.48-1.57), followed by White-high ADI (HR, 1.38; 95% CI, 1.33-1.42), then Black-low ADI (HR, 1.14; 95% CI, 1.11-1.17) compared to White-low ADI. Previously reported racial differences in risk of PAD and CLTI are largely explained by socioeconomic deprivation, as characterized by ADI. Adults living in areas with higher socioeconomic deprivation are at higher risk of incident PAD and CLTI than their less socioeconomically deprived counterparts.Fig 2Cumulative Incidence Function Curves of Incident CLTI in health Services Cost Review Commission Database from 2013 through 2019 Stratified by Race and ADI.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

A Pilot Program to Educate High-School Students Regarding Vascular Disease: The Western New York Model

Public education and awareness are critical to addressing issues related to vascular health and disease. However, to date, little work has been done at the community level with regard to outreach to at-risk populations and to address these knowledge gaps. We describe an intervention to educate high-school students regarding vascular disease with aims to improve community knowledge and to also promote further inquiry into the field of vascular surgery. An educational initiative was commenced in three public high schools. A team of vascular surgeons, vascular residents/fellows, medical students, and vascular lab technicians provided in-class education sessions for the length of a class period (approximately 50 minutes). During each session, there was an interactive presentation on risk factors, presentation, and treatment of peripheral arterial disease, stroke, and abdominal aortic aneurysms. This was followed by hands-on stations where students were introduced to endovascular tools and 3D-printed aortic models, as well as a station where students performed ultrasound examinations of their own carotid arteries and abdominal aortas, and ankle brachial indexes were performed. Before and after each session, substantive quizzes regarding vascular disease were administered, and results of the quizzes were tracked. A total of 155 students completed pre-educational session quizzes, and 132 students completed postsession quizzes (Table). Five questions were included on the pre- and postsession quizzes: peripheral arterial disease risk factors (question 1), smoking-related risks (question 2), abdominal aortic aneurysm symptoms (question 3), stroke symptoms (question 4), and smoking pathophysiology (question 5). An improvement was seen in the aggregate number of correct responses for each question (Table). There was also an increase in the total number of students who scored four correct: 7 (4.5%) presession to 20 (15.2%) postsession, and those who scored five correct: 0 (0%) presession to 11 (8.3%) postsession. Targeted programs aimed at high-school students by vascular surgeons, trainees, and staff can provide a sustainable model for public education and awareness of vascular disease that increases knowledge and may also spur interest in vascular surgery. Further work is needed to determine if these interventions can increase knowledge not only in students in the community at large but also in populations at risk surrounding these schools.TablePre- and posteducational session quiz resultsPresession correct responses, No. (%)Postsession correct responses, No. (%)Question 1: risk for developing PAD106 (68.4)101 (76.5)Question2: smoking-related risks59 (38.1)59 (44.7)Question3: most common AAA symptom12 (7.7)45 (34.1)Question 4: signs of stroke33 (21.3)44 (33.3)Question 5: smoking pathophysiology75 (48.4)75 (56.8)Total N = 155Total N = 132Total no. of correct responses 018 (11.6)9 (6.8) 144 (28.4)31 (23.5) 248 (31.0)32 (24.2) 338 (24.5)29 (22.0) 47 (4.5)20 (15.2) 50 (0)11 (8.3)AAA, Abdominal aortic aneurysm; PAD, peripheral arterial disease. Open table in a new tab

Systemic Lupus Erythematosus and Cardiovascular Diseases: A Systematic Review.

Systemic lupus erythematosus (SLE) is an autoimmune condition characterized by multi-organ involvement. The clinical presentation often varies from mild to moderate to severe. The cardiovascular system may also be affected, often portending a poor prognosis for patients. Although the relationship between SLE and cardiovascular disorders has been extensively explored through case reports and literature reviews, few systematic reviewsexplicitly focusing on this association have been conducted. In light of this, this systematic review aims to analyze the extent of the association between SLE and cardiovascular diseases (CVDs), by exploring therisk of developing CVDs, including myocardial infarction (MI), atherosclerosis, myocarditis, pericarditis and arrhythmias, in SLE patients vs. non-SLE patients. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to perform the systematic review. A detailed search was done covering the period from March 2003 to March 2023 using three databases: PubMed, Google Scholar, and Cochrane. The PubMed search identified 597 articles, while Google Scholar and Cochrane searches yielded 559 and three articles, respectively. Of the 1159 articles retrieved, we chose eight for final consideration, after excluding papers that did not discuss the role of SLE in CVDs, papers published earlier than 2003, and papers with incomplete data. The eight studies chosen included two narrative reviews, two systematic reviews, and four observational studies. In this systematic review, SLE was proven to have a strong relationship with diverse CVDs, including rare ones scarcely discussed in the literature, such as vasculitis and aortic dissection. All eight of the final papers indicated a connection between SLE and CVDs, based on the systematic analysis of thesearticles, which revealed that most recent research supports a higher risk of peripheral arterial occlusive disease (PAOD), MI, pericarditis, myocarditis, and other cardiovascular disorders in individuals with SLE. These associations may have certain gray areas, as patient characteristics and comorbidities often affect the extent of illness and long-term prognosis. Larger-scale studies are required to probe this relationship further and research the etiopathogenesis involved in order to improve patient outcomes. The effects of SLE on the heart are, however, unequivocal.

Association of diabetic retinopathy with risk of developing cardiovascular diseases in patients undergoing hemodialysis: A population-based cohort study

Background and aimsWhile patients undergoing dialysis have substantially increased cardiovascular event rates compared with the general population, predicting individual risk remains difficult. Whether diabetic retinopathy (DR) is associated with cardiovascular diseases in this population is unclear. Methods and resultsWe conducted a nationwide cohort study of 27,686 incident hemodialysis patients with type 2 diabetes who were enrolled in Taiwan's National Health Insurance Research Database between January 1, 2010, and December 31, 2014, and had follow-up data until December 31, 2015. The primary outcome was a composite of macrovascular events, including acute coronary syndrome (ACS), acute ischemic stroke, and peripheral artery disease (PAD). A total of 10,537 (38.1%) patients had DR at baseline. We matched 9164 patients without DR (mean age, 63.7 years; 44.0% women) to 9164 patients with DR (mean age, 63.5 years; 43.8% women) by propensity score. During a median follow-up of 2.4 years, 5204 patients in the matched cohort experienced a primary outcome. The presence of DR was associated with a higher risk of a primary outcome (subdistribution hazard ratio [sHR] 1.07; 95% CI, 1.01–1.13), which reflected a higher risk of acute ischemic stroke (sHR 1.26; 95% CI, 1.14–1.39) and PAD (sHR 1.14; 95% CI, 1.05–1.25) but not ACS (sHR 0.99; 95% CI, 0.92–1.06). ConclusionsThe presence of DR signifies an increased risk of acute ischemic stroke and PAD in hemodialysis patients with type 2 diabetes, independent of the known risk factors. These results highlight the need for more comprehensive cardiovascular assessment and management in hemodialysis patients with DR.

Serum adiponectin concentrations as a risk factor for cardiovascular complications in type 1 diabetes

AimBy analyzing data from DCCT/EDIC study, we investigated the associations of serum adiponectin concentrations with macrovascular complications and cardiovascular events in T1D. Materials and MethodsAdiponectin concentrations were measured in EDIC year 8. The participants (n = 1040) were divided into four groups by quartiles of adiponectin concentrations. The association of macrovascular complications and cardiovascular events were analyzed by using multivariable regression and Cox proportional hazards models. ResultsHigh adiponectin concentrations were associated with decreased risk of peripheral artery disease represented by ankle brachial index (ORs (95% CI): 0.22 (0.07–0.72), 0.48 (0.18–1.25), and 0.38 (0.14–0.99) in fourth, third, and second quartiles compared with first quartile), with reduced carotid intima-media thickness, and with increased LVEDV index. Moreover, high adiponectin concentrations were also associated with increased risk of any cardiovascular events (HRs (95% CI): 2.59 (1.10–6.06), 2.03 (0.90–4.59), and 1.22 (0.52–2.85)) and major atherosclerotic cardiovascular events (HRs (95% CI): 11.37 (2.04–63.43), 5.68 (1.04–31.07), and 3.76 (0.65–21.77) in fourth, third, and second quartiles compared with first quartile), however, after adjustments with LVEDV index, these associations were diminished. ConclusionsAdiponectin may protect carotid atherosclerosis and peripheral artery disease in T1D. It may be associated with increased cardiovascular events, depending on cardiac structural changes.

Supervised exercise training improves cardiorespiratory fitness and reduces perioperative risk in peripheral artery disease patients with intermittent claudication.

This study examined to what extent supervised aerobic and resistance exercise combined with continued unsupervised exercise training improves cardiorespiratory fitness and corresponding perioperative risk in peripheral artery disease (PAD) patients with intermittent claudication. A total of 106 patients (77% male) were enrolled into the study, alongside 155 healthy non-PAD control participants. Patients completed supervised exercise therapy (aerobic and resistance exercises of the upper and lower limbs) twice a week for 10 weeks. Thereafter, 52 patients completed 12 weeks of an unsupervised tailored home-based exercise. Pain-free walking distance (PWD), maximum walking distance (MWD), peak oxygen uptake ([Formula: see text]) and perioperative risk were assessed before and after both exercise interventions. Patients were highly unconditioned relative to healthy controls ([Formula: see text]=11.9 vs 24.2ml/kg/min, p=<0.001) with 91% classified as high perioperative risk (peak oxygen uptake <15ml/kg/min). Supervised exercise increased PWD (+44±81m, p=<0.001), MWD (+44±71m, p=<0.001) and [Formula: see text] (+1.01±1.63ml/kg/min, p=<0.001) and lowered perioperative risk (91% to 85%, p=<0.001). When compared with supervised exercise, the improvements in PWD were maintained following unsupervised exercise (+11±91m vs supervised exercise, p=0.572); however, MWD and [Formula: see text] decreased (-15±48m, p=0.030 and -0.34±1.11ml/kg/min, p=0.030, respectively) and perioperative risk increased (+3%, p=<0.001) although still below baseline (p=<0.001). Supervised aerobic and resistance exercise training and, to a lesser extent, unsupervised tailored exercise improves walking capacity and cardiorespiratory fitness and reduces perioperative risk in PAD patients with intermittent claudication.

Circulating proteins and peripheral artery disease risk: observational and Mendelian randomization analyses.

We conducted observational and Mendelian randomization (MR) analyses to explore the associations between blood proteins and risk of peripheral artery disease (PAD). The observational cohort analyses included data on 257 proteins estimated in fasting blood samples from 12 136 Swedish adults aged 55-94 years who were followed up for incident PAD via the Swedish Patient Register. Mendelian randomization analyses were undertaken using cis-genetic variants strongly associated with the proteins as instrumental variables and genetic association summary statistic data for PAD from the FinnGen study (11 924 cases and 288 638 controls) and the Million Veteran Program (31 307 cases and 211 753 controls). The observational analysis, including 86 individuals diagnosed with incident PAD during a median follow-up of 6.6-year, identified 13 proteins [trefoil factor two, matrix metalloproteinase-12 (MMP-12), growth differentiation factor 15, V-set and immunoglobulin domain-containing protein two, N-terminal prohormone brain natriuretic peptide, renin, natriuretic peptides B, phosphoprotein associated with glycosphingolipid-enriched microdomains one, C-C motif chemokine 15, P-selectin, urokinase plasminogen activator surface receptor, angiopoietin-2, and C-type lectin domain family five member A] associated with the risk of PAD after multiple testing correction. Mendelian randomization analysis found associations of T-cell surface glycoprotein CD4, MMP-12, secretoglobin family 3A member 2, and ADM with PAD risk. The observational and MR associations for T-cell surface glycoprotein CD4 and MMP-12 were in opposite directions. This study identified many circulating proteins in relation to the development of incident PAD. Future studies are needed to verify our findings and assess the predictive and therapeutic values of these proteins in PAD.

C-31 | Impact of Marijuana Use on Prevalence and Interventions in Peripheral Artery Disease

The growing legalization of marijuana use warrants investigation of its various effects on the vasculature. We aim to determine whether marijuana users have an increased risk of peripheral artery disease (PAD) and subsequent surgical intervention. De-identified patient data from the National Inpatient Sample (NIS) from 2016-2019 were queried. Inclusion criteria included a diagnosis of marijuana use and peripheral artery disease. Patients were further stratified based on any percutaneous lower extremity vascular intervention. Data was analyzed using SPSS software in a binary logistic regression model, a p value <0.001 was considered statistically significant, and samples were standardized for comparison using predicted probabilities. Of the 30m+ patients in the NIS from 2016 to 2019, there were 623,768 patients diagnosed as marijuana users. These patients had an average age of 37.4 years, even distribution across genders, were more likely to be white and more likely to be elective admissions (p<0.001). Of these patients, 2,424 (0.38%) were concomitantly diagnosed with PAD. Marijuana users were at more than three times the risk of developing PAD (OR= 3.68, p<0.001) but had no statistically significant increased risk for mortality or requiring percutaneous intervention (p<0.001). Marijuana users are at a markedly increased risk of being diagnosed with PAD but are at no increased risk of requiring intervention nor mortality from their peripheral ischemia. Possible mechanisms for this increased risk may involve changes in coagulability and peripheral vascular tone from marijuana use. Vigilant monitoring for disease screening and progression should be initiated earlier in the outpatient setting in conjunction with cessation counseling.

Abstract 374: Sexual Dimorphism And Elabela Expression In Peripheral Artery Disease

Introduction: Elabela is a component of the apelinergic system known to regulate immune responses and has a cardiovascular protection role, including atherosclerosis. Peripheral artery disease (PAD) is the narrowing or blockage of larger arteries in the legs. Patients with PAD suffer from poor perfusion to their lower extremities, in addition to increased rates of cardiovascular complications. The role of sexual dimorphism in the immune system in the PAD is poorly understood. Our previous research suggests that Elabela may hold a gender-dependent protective role that can be used as immunotherapeutic. We hypothesized that in patients with PAD, expression of Elabela will be different between males and females, implicating in sexual dimorphism of the immune response, the disease outcome, and treatment. Methods: Blood samples were collected from PAD patients (n=8) and risk factor closely matched controls (n=8). PBMCs were isolated by gradient centrifugation. By flow cytometry, gating strategy on Elabela, and Elabela expressing leukocytes, using FlowJow software for analysis. Results: The results showed that there is a sexual difference in the expression of Elabela in both controls and patients with PAD. In general, males showed a high level of Elabela than females. PAD decreases Elabela expression in both males and females. Regarding Elabela expressing leukocytes, in female controls, there was no significant difference in leukocyte expression of Elabela as compared to PAD patients, while male controls demonstrated increased leukocyte expression of Elabela. Conclusions: Our findings suggest a potential role for Elabela in PAD. Importantly, these results also indicate a difference in Elabela expression based on sex dimorphism. Such differences could potentially be used as a biomarker in the diagnosis and prognosis of PAD along with therapeutic values.