Risk Of Peripheral Arterial Disease Research Articles

Evaluation of vascular risk in patients with migraine with and without aura treated with erenumab: Post hoc analysis of pooled long‐term clinical trial data

To assess cardiovascular (CV) safety of erenumab in clinical trial patients associated with degree of CV risk. Hypertension has been considered a theoretical risk associated with the inhibition of the calcitonin gene-related peptide pathway in migraine management, particularly in a patient population with pre-existing CV risk factors. Data pooled from four double-blind, randomized trials were used to assess blood pressure (BP) changes and CV safety in patients grouped based on 10-year risk of cardiac, cerebrovascular, and peripheral artery disease as no-risk-factors, low-risk (>0% to ≤10%), moderate-risk (>10% to ≤20%), and high-risk (>20%) categories. CV safety was assessed as ischemic cardiovascular and cerebrovascular adverse events (ICCAE). There was no apparent difference between placebo- (N=1032) and erenumab-treatment groups (70 mg, N=885; 140 mg, N=504) in clinical worsening of BP category from baseline to Months 1-3 (14% [143/1032] placebo vs. 13% [114/885] and 14% [71/504] for erenumab 70 and 140 mg, respectively) regardless of baseline BP category. The adverse event (AE) profile of erenumab was similar across CV risk categories throughout the long-term analysis. Erenumab-treated patients with high and moderate 10-year CV risk (N=107) did not experience any ICCAEs during the double-blind treatment period; there was a single ICCAE (a cerebral dural venous sinus thrombosis) observed in the low-risk erenumab group (N=273). There were no increases in AEs during the long-term extensions of up to 5 years (N= 2499; 3482 patient-years of exposure to erenumab) with exposure-adjusted incidence rates of cardio/cerebrovascular disorder AEs of 0.4, 0.5, 0.0, and 1.1 (per 100 patient-years) for no risk factor (N= 1805), low (N= 492), moderate (N= 121), and high (N= 81) 10-year CV risk groups, respectively. Ischemic CV and cerebrovascular AEs were uncommon and the incidence rates were similar across the 10-year CV risk categories. This analysis helps provide more detail on the CV safety of erenumab.

Abstract P155: Modifiable Lifestyle Factors, Genetic Risk, and Incident Peripheral Artery Disease Among Individuals With Type 2 Diabetes: A Prospective Study

Background: Individuals with type 2 diabetes (T2D) are at elevated risk of developing peripheral artery disease (PAD). Whether healthy lifestyle can reduce this risk, particularly in individuals genetically predisposed to PAD, is unknown. Aims: To evaluate the association between modifiable lifestyle factors with incident PAD among individuals with T2D, both overall and stratified by genetic risk of PAD. Methods: We included 19,368 individuals with T2D from the UK Biobank, who were free of PAD and cardiovascular disease. We defined a low-risk lifestyle score with 1 point assigned for each of the following: non-current smoking, regular physical activity, adhering to a high-quality diet, moderate alcohol consumption, maintaining a normal waist-hip ratio, sleeping 7-8 hours/day. A polygenic risk score (PRS) including 19 single nucleotide polymorphisms was constructed. Multivariable-adjusted Cox models were used to calculate the hazard ratio (HR) and 95% confidence interval (CI). Results: After a median 7.6 years of follow-up, 325 incident cases of PAD were documented. There was an inverse association between the low-risk lifestyle score and incident PAD, with HR (95%CI) of 0.73 (0.54, 1.03), 0.43 (0.30, 0.60), and 0.42 (0.30, 0.60) for 2, 3, and ≥4 compared with ≤1. The PRS was associated with an increased risk of PAD, with HR (95%CI) of 1.16 (1.03, 1.31) per-SD increment. A more favorable lifestyle was able to partially mitigate the risk of increased genetic susceptibility to PAD ( Figure 1 ). In mediation analysis, 42.4% of the association could be attributable to risk factors including inflammation, atherogenic lipoproteins, and impaired hepatic/renal function. Conclusion: A combined set of modifiable lifestyle factors was associated with a substantially lower risk of incident PAD among individuals with T2D and may be able to partially mitigate an underlying genetic predisposition for PAD. Our findings highlight the importance of improving adherence to these factors in the primary prevention of PAD among individuals with T2D.

Abstract P624: Peripheral Artery Disease and Long-Term Risk of Femur Fracture Among Older Adults: The Atherosclerosis Risk in Communities Study

Introduction: Femur fracture can have devastating consequences in older patients. Lower extremity peripheral artery disease (PAD) reduces physical function, which can in turn increase the risk of falls. However, less is known regarding the association of PAD with incident femur fracture in older adults. Hypothesis: PAD is associated with a higher risk of incident femur fracture independent of potential confounders. Methods: We included 5,276 participants from ARIC Visit 5 (2011-2013) (mean age 76 [standard deviation: 5] years, 57% women and 22% self-identified Black race). Femur fractures were defined as an outpatient encounter or hospitalization with ICD-9 codes: 820-821 or ICD-10 codes: S72. We quantified the association of PAD status at baseline, based on ankle-brachial index (ABI) ≤0.9 or clinical history of PAD, with incident femur fracture using multivariable Cox regression and follow-up until 2019. Results: There were 224 incident femur fractures over a median follow-up of 7.2 [IQI 5.6-7.8] years. The incidence rate of femur fracture was almost 2-times higher in participants with PAD compared to those without a history of PAD and ABI 1.11-1.20 (reference group) (10.5 [7.5-14.8] vs. 5.5 [4.3-6.9] per 1,000 person-years). This association persisted after accounting for demographic (hazards ratio [HR]: 1.86 [95% CI 1.23-2.84] in Model 1) and other confounders (HR 1.59 [1.04-2.46] in Model 2) (Table). When we excluded participants with a clinical history of PAD, low ABI (≤0.9) remained significantly associated with incident femur fracture compared to the reference group (HR 1.94 [1.18-3.19]). Our findings were consistent in demographic and clinical subgroups (e.g., by sex and diabetes status). Conclusions: In community-dwelling older adults, PAD, even when not clinically diagnosed, was associated with an increased risk of femur fracture. Clinicians and patients should be aware of this complication of PAD and consider preventive measures to avoid falls (e.g., exercise counseling, and making home safer).

Abstract P105: Peripheral Artery Disease and Subsequent Risk of Cancer: The Atherosclerosis Risk in Communities (ARIC) Study

Introduction: Cardiovascular disease (CVD) and cancer share risk factors, including smoking and obesity. Indeed, an increased cancer risk was reported among patients with CVD, such as myocardial infarction. Lower extremity peripheral artery disease (PAD) has also been explored in this context, but most previous studies included only Whites, had follow-up <10 years, or did not account for key confounders like smoking. Hypothesis: PAD is independently associated with long-term cancer risk in a bi-racial cohort. Methods: We studied 13,102 ARIC participants without prevalent cancer at visit 1 (1987-89) (mean age 54 [SD 6] years, 54% women, and 26% Black) (funding: NHLBI, NCI, and NPCR). Incident cancer was ascertained by linkage to cancer registries and medical record review. We categorized PAD status at visit 1 into symptomatic PAD (intermittent claudication or a history of lower extremity revascularization), asymptomatic PAD (ankle brachial index [ABI] ≤0.9), and other ABI categories of >0.9-1.0, >1.0-1.1, >1.1-1.2, >1.2-1.3 and >1.3. We ran multivariable Cox models. Results: During the median follow-up of 25 years (IQI 15-27 years), there were 4,142 incident cancer cases. 25-year cumulative cancer incidence was 48% in symptomatic PAD, 39% in asymptomatic PAD, and 31-34% in the other categories. When we adjusted for demographic factors, both symptomatic and asymptomatic PAD showed significant hazard ratios for incident cancer (1.79 [95%CI 1.33-2.43] and 1.39 [1.18-1.63], respectively, vs. ABI 1.1-1.2, Model 1 in Table ). After adjusting for additional potential confounders, including smoking and diabetes, these associations were somewhat attenuated but remained consistent (Models 2-4 in Table ). Conclusion: Both symptomatic and asymptomatic PAD were associated with an increased risk of cancer independently of smoking and diabetes. Although potential mechanisms should be explored, clinicians should be aware of this excess cancer risk among patients with PAD when considering cancer prevention and screening.

Remnant cholesterol is independently asssociated with an increased risk of peripheral artery disease in type 2 diabetic patients.

Remnant cholesterol (RC) has been correlated with a higher risk of atherosclerosis. It has been confirmed that in the general population, an elevated RC level is related to a 5-fold higher risk of peripheral arterial disease (PAD). Diabetes is one of the strongest risk factors for PAD development. However, the association between RC and PAD in the specific population of type 2 diabetes mellitus (T2DM) has not been investigated. Herein, the correlation was investigated between RC and PAD in T2DM patients. In the retrospective study, the hematological parameter data of 246 T2DM patients without PAD (T2DM - WPAD) and 270 T2DM patients with PAD (T2DM - PAD) was collected. Differences in RC levels between the two groups were compared, and the association between RC and PAD severity was examined. Multifactorial regression was used to determine whether RC was a significant contributor to the development of T2DM - PAD. The diagnostic potential of RC was tested using receiver operating characteristic (ROC) curve. The RC levels in T2DM - PAD individuals were considerably greater than in T2DM - WPAD individuals (P < 0.001). RC had a positive correlation with disease severity. Further, multifactorial logistic regression analyses found that elevated RC levels were a major contributor to T2DM - PAD (P < 0.001). The area under the curve (AUC) of the RC for T2DM - PAD patients was 0.727. The cut-off value of RC was 0.64 mmol/L. The RC levels were higher in T2DM - PAD patients, and were independently linked with its severity. Diabetic patients with RC levels > 0.64 mmol/L had an elevated risk of developing PAD.

The Joint Link of the rs1051730 and rs1902341 Polymorphisms and Cigarette Smoking to Peripheral Artery Disease and Atherosclerotic Lesions of Different Arterial Beds.

Genome-wide association studies (GWAS) have discovered numerous single nucleotide polymorphisms (SNP) contributing to peripheral artery disease (PAD), but their joint effects with risk factors like cigarette smoking (CS) on disease susceptibility have not been systematically investigated. The present study looked into whether CS mediates the effects of GWAS loci on the development of PAD and atherosclerotic lesions in different arterial beds. DNA samples from 1263 unrelated individuals of Slavic origin including 620 PAD patients and 643 healthy subjects were genotyped by the MassArray-4 system for rs1051730, rs10134584, rs1902341, rs10129758 which are known as PAD-associated GWAS loci. The rs1051730 polymorphism was strongly associated with an increased risk of PAD (p = 5.1 × 10-6), whereas rs1902341 did not show an association with disease risk. The rs1051730 polymorphism was associated with increased plasma levels of LDL cholesterol (p = 0.001), and conferred a greater risk of PAD in cigarette smokers than in nonsmokers (p < 0.01). Interestingly, the rs1902341T allele was associated with an increased risk of PAD in smokers and a decreased disease risk in nonsmokers. SNPs and CS were both linked to unilateral and/or bilateral atherosclerotic lesions of peripheral vessels, as well as the abdominal aorta, coronary, and cerebral arteries. The studied polymorphisms exert pleiotropic and cigarette smoking-mediated effects on atherosclerotic lesions of different arterial beds.

The Association Between Metabolic Dysfunction-Associated Fatty Liver Disease and Peripheral Arterial Disease in the Chinese Population.

Emerging evidence suggested that metabolic dysfunction-associated fatty liver disease (MAFLD) was significantly associated with atherosclerotic diseases. Atherosclerosis in the peripheral arteries is the most common cause of peripheral arterial disease (PAD), which has not been substantially controlled in the past. We aimed to investigate the association between MAFLD and PAD in the Chinese population. This observational study covered 102,115 participants who underwent health checkups with detailed examinations for PAD and MAFLD. PAD was measured by ankle-brachial index, and MAFLD was diagnosed by abdominal ultrasound. The generalized linear mixed models and random-effects Cox proportional hazards models were used to analyze the relationship between MAFLD and PAD. The baseline characteristics showed that patients with MAFLD had higher prevalence of PAD compared with those without MAFLD (2.7% vs 2.2%). Compared to non-MAFLD, the individuals with MAFLD were associated with a higher risk of the presence of PAD (adjusted odds ratio: 1.30, 95% confidence interval (CI): 1.19-1.42, P < 0.001). In the prospective cohort study, 6833 participants underwent a follow-up of 2.76 (standard deviation: 1.36) years, and MAFLD at baseline was a higher risk of associated with incident PAD (adjusted hazards ratio: 1.67, 95% CI: 1.17-2.38, P = 0.005). Moreover, with the accumulation of metabolic abnormalities, the risk of the PAD was increased in the individuals with MAFLD. Furthermore, MAFLD attributed risk of PAD was more evident in participants without metabolic comorbidities. MAFLD was associated with a significantly higher risk for the prevalence and incidence of PAD in the Chinese population. The finding suggested that individuals with MAFLD are not only have a higher risk of coronary heart diseases but also have an increased risk of atherosclerosis in peripheral arteries.

Non-esterified fatty acids and risk of peripheral artery disease in older adults: The cardiovascular health study

Background and aimsNon-esterified fatty acids have been implicated in the pathogenesis of diabetes and cardiovascular disease. No longitudinal study has assessed their effects on peripheral artery disease (PAD). We determined the relationships between NEFAs and incident clinical PAD and abnormal ankle-brachial index (ABI) in a population-based cohort of older persons. MethodsWe evaluated 4575 community living participants aged >65 years who underwent measurement of circulating NEFAs in fasting specimens and ABI in 1992–1993. Participants were assessed annually for clinical PAD until 2015 and underwent repeat ABI in 1998–1999. We used Cox proportional hazards regression to model the associations between NEFAs and risk of clinical PAD and logistic regression to model the associations of NEFAs with incident abnormal ABI. ResultsMean age was 74.8 years, 59% were female, and 17% were Black. NEFAs were associated with higher risk of clinical PAD in unadjusted and adjusted models. The adjusted hazard ratios for incident clinical PAD were 1.51 (95%CI = 1.06–2.13, p = 0.02) across extreme tertiles, and 1.14 (95%CI = 0.99–1.31, p = 0.08) per standard deviation higher NEFA. The corresponding odds ratios for abnormal ABI were 0.95 (95%CI = 0.69–1.32, p = 0.76) across extreme tertiles, and 1.03 (95%CI = 0.89–1.20, p = 0.68) per standard deviation higher NEFA. Relationships appeared similar irrespective of sex, race, or pre-existing cardiovascular disease, but were stronger later than earlier in follow-up. ConclusionsHigher serum levels of NEFAs are significantly associated with increased likelihood of clinical PAD over long-term follow-up but not with 6-year decline in ABI. NEFAs may offer a potential target for intervention against clinical PAD.

Association of Smokeless Tobacco Use With Incident Peripheral Artery Disease: Results From the Atherosclerotic Risk in Communities Study

Cigarette smoking is associated with an increased risk for peripheral artery disease. It is unknown whether smokeless tobacco, a noncombustible form of tobacco exposure, is also associated with increased peripheral artery disease risk. Using data from the Atherosclerosis Risk in Communities study, we tested the hypothesis that the use of smokeless tobacco is associated with a higher risk of developing peripheral artery disease. Participants with peripheral artery disease at baseline were excluded. Smokeless tobacco use was assessed 3 times from 1987 to 1995, and peripheral artery disease events accrued from 1987 to 2018. Smokeless tobacco was modeled as a time-dependent exposure in Cox regression models. Analyses were completed in 2021. This study included 14,344 participants with a baseline mean (SD) age of 54.1 (5.7) years; 54.8% were female, and 26.4% were Black. There were 635 incident peripheral artery disease events over a median follow-up of 27.6 years (maximum of 32.1 years). The peripheral artery disease incidence rate was 4.44 per 1,000 person-years among those who used smokeless tobacco compared with 1.74 per 1,000 person-years for those who did not. The hazard ratio for current versus never smokeless tobacco use was 1.94 (95% CI=1.31, 2.88) after adjustment for sociodemographic characteristics and cigarette smoking. Peripheral artery disease incidence rate among those currently using smokeless tobacco was similar to that of those who currently smoke cigarette (3.39 per 1,000 person-years). Current smokeless tobacco use was associated with high rates of peripheral artery disease, similar to cigarette smoking. Future research should evaluate the effect of cessation of noncombustible tobacco on incident peripheral artery disease.

The Impact Of HIV On The Prevalence And Characterization Of Peripheral Arterial Disease In Kigali, Rwanda: A Pilot Study

No studies have estimated the prevalence of peripheral arterial disease (PAD) in Rwanda, especially when accounting for the increased rate of human immunodeficiency virus (HIV), which is often associated with an increased risk of PAD. This study sought to estimate the prevalence of PAD stratified by HIV status in Kigali.

High Prevalence of Lower Extremity Medial Arterial Calcification in HIV-infected Patients With and Without Chronic Renal Disease: A Vascular Ultrasound Cross-sectional Study

Background: The association between HIV infection and increased risk of atherosclerotic peripheral artery disease (PAD) has been documented. Still, the relationship between HIV infection and lower extremity medial arterial calcification (MAC) is unknown. Objective: We performed a cross-sectional study to compare the frequency of MAC diagnosed by vascular ultrasound in PAD-asymptomatic people living with HIV (PLWH) with and without chronic kidney disease (CKD) compared to HIV-uninfected participants as a control group. Methods: MAC was defined as smooth, linear, and non-stenotic hyperechogenicity in the arterial wall compared to the surrounding tissues. We studied 191 patients: 50 PLWH (25 with an estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73m2 and 25 with an eGFR &lt;60 mL/min/1.73m2) and 141 HIV-uninfected patients (68 with eGFR&lt;60 ml/min/1.73m2). Results: MAC was most frequently found in PLWH with CKD (76%). The prevalence of MAC among PLWH was 54.0% (95% confidence interval [CI], 40.4-67.0%), whereas, in HIV-uninfected, it was 34.0% (95% CI, 26.7-42.2%, P=0.013). Age and CKD were consistently associated with MAC in our multivariable models, and there was also a sign that PLWH had higher odds of having MAC. Conclusion: We found a higher prevalence of MAC in PAD-asymptomatic PLWH compared to HIV-uninfected ones and provided evidence that HIV infection could be associated with MAC.

Chronic Pancreatitis and Risk of Atherosclerotic Cardiovascular Disease: A US Cohort Propensity-Matched Study.

Worldwide prevalence of chronic pancreatitis (CP) has risen in recent years, with data suggesting an increased risk of atherosclerotic cardiovascular disease (ASCVD) in these patients. We assessed the incidence and risk of ASCVD in patients with CP. We compared the risk of ischemic heart disease, cerebrovascular accident, and peripheral arterial disease between CP and non-CP cohorts after propensity matching of known risk factors of ASCVD using TriNetX, a multi-institutional database. We also evaluated the risk of outcomes of ischemic heart disease including acute coronary syndrome, heart failure, cardiac arrest, and all-cause mortality between CP and non-CP cohorts. Chronic pancreatitis cohort was also found to have an increased risk of ischemic heart disease (adjusted odds ratio [aOR], 1.08; 95% confidence interval [CI], 1.03-1.12), cerebrovascular accident (aOR, 1.12; 95% CI, 1.05-1.20), and peripheral arterial disease (aOR, 1.17; 95% CI, 1.1-1.24). Chronic pancreatitis patients with ischemic heart disease were also found to have an increased risk of acute coronary syndrome (aOR, 1.16; 95% CI, 1.04-1.30), cardiac arrest (aOR, 1.24; 95% CI, 1.01-1.53), and mortality (aOR, 1.60; 95% CI, 1.45-1.77). Chronic pancreatitis patients are at a higher risk of ASCVD when compared with the general population, matched for confounding etiological, pharmacological, and comorbid variables.

Influence of atherosclerosis risk factors on the anatomical distribution of peripheral arterial disease in patients with chronic limb-threatening ischemia: a cross-sectional study.

Atherosclerosis risk factors can have different impacts on cardiovascular diseases and on the anatomical distribution of Peripheral Arterial Disease (PAD). To study the influence of atherosclerosis risk factors on the anatomical distribution of PAD in patients with chronic limb-threatening ischemia (CLTI). We performed an observational, cross-sectional, and analytical study that included 476 hospitalized patients with CLTI due to PAD. We compared the presence of atherosclerosis risk factors (age, gender, diabetes mellitus, smoking, and hypertension) in patients with PAD involving three different anatomic areas (aortoiliac, femoropopliteal, and infrapopliteal). Multivariate analysis was performed to identify associations between atherosclerosis risk factors and PAD distribution. The mean age of the 476 patients was 69 years, 249 (52%) were men, and 273 (57%) had diabetes. Seventy-four percent (353) had minor tissue loss. Multivariate analysis identified three risk factors associated with PAD anatomical distribution (gender, smoking, and DM). Women had a 2.7 (CI: 1.75-4.26) times greater chance of having femoropopliteal disease. Smokers had a 3.6-fold (CI: 1.54-8.30) greater risk of aortoiliac disease. Diabetic patients were 1.8 (CI: 1.04-3.19) times more likely to have isolated infrapopliteal occlusive disease. The study showed that gender, DM, and smoking impact on the anatomical distribution of PAD in patients with CLTI. Diabetic patients were more likely to have only infrapopliteal disease, women had a greater risk of femoropopliteal PAD, and smokers had a greater risk of aortoiliac occlusive disease.

Risk profiles, access to care, and outcomes in Hispanics hospitalized for lower extremity peripheral artery disease.

Previous studies have shown that Hispanics have worse clinical outcomes for lower extremity peripheral artery disease (PAD) than non-Hispanic White (NHWs). Using a national database, this study aimed to document the contemporary burden of PAD in Hispanics by evaluating their risk profiles, access to care, and outcomes compared with NHWs. Hospitalizations of Hispanics and NHWs with a primary diagnosis of PAD were identified using 2011-2017 National Inpatient Sample data. Patient sociodemographic characteristics, comorbidities, whether the admission was through the emergency department (ED) or elective, length of stay, and costs accrued were compared by ethnicity. Temporal trends in revascularizations, amputations, and ED admissions by year were evaluated with the Cochran-Mantel-Haenszel test and stratified by ethnicity. Data were combined across years and multivariable logistic regression was used to evaluate the association of ethnicity with inpatient revascularization, amputation, and mortality, adjusting for sociodemographic and cardiovascular risk factors. From 2011 to 2017, there were a total of 1,018,220 PAD hospitalizations among Hispanics (13.9%) and NHWs (86.1%) between 2011 and 2017. Hispanics were more often low income and uninsured and presented with higher burden of comorbidities including diabetes, renal failure, prior amputations, and chronic limb-threatening ischemia compared with NHWs. Most Hispanics were admitted via the ED compared with NHWs (58.0% vs 36.7%; d= 0.48), and median length of stay was almost a day longer (4.5days vs 3.7days). Hispanic ethnicity was associated with lower odds of surgical (odds ratio [OR], 0.62; 95% confidence interval [CI], 0.57-0.67) and endovascular revascularization (OR, 0.94; 95% CI, 0.89-0.996) and mortality (OR, 0.83; 95% CI, 0.75-0.93), but higher odds of minor (OR, 1.25; 95% CI, 1.20-1.31) and major (OR, 1.08; 95% CI, 1.03-1.14) amputation. Two tiers of health care consumption for inpatient PAD care and outcomes manifested among Hispanics and NHWs. First, Hispanics with PAD had a more vulnerable socioeconomic profile and presented with more severe PAD than NHWs. Second, they sought care more disproportionately through the ED and underwent more amputations than NHWs. To eradicate these inequities in PAD care and risk, strategies that improve access to outpatient care and expand health care coverage, as well as targeted management of risk factors in these vulnerable minority groups are needed.

Outcomes of Vascular Intervention in Diabetic Patients with Peripheral Arterial Disease

BACKGROUND: Peripheral arterial disease (PAD) is more prevalent and often presents as more severe in patients with diabetes mellitus (DM) compared with those without DM. Although some patients may be asymptomatic, symptoms ranging from exertional leg heaviness and fatigue to acute limb loss are possible. PAD has significant physical and psychiatric health consequences, thus management with medical therapy and lifestyle changes are indicated. However, peripheral vascular intervention (PVI) is an increasingly popular method used in patients failing conservative management. The association of PVI with health status in diabetic patients has yet to be determined.&#x0D; &#x0D; METHODS: We analyzed the clinical response to PVI in DM (n=203, 52%) compared with non-DM patients (n=183, 48%), using the Peripheral Arterial Questionnaire (PAQ) for patients during baseline and a maximum 6 months after PVI. 502 patients participated with an exclusion of 116 patients from our analysis due to progression of acute limb ischemia and incomplete data collection. Our finalized study population comprised 386 consecutive patients with symptomatic PAD who had also received PVI treatment during the aforementioned time frame. Our patient population received PVI treatment in the year 2012 at the St. John Hospital and Medical Center in Detroit, MI. We used the PAQ summary score, which summarizes the patients’ level of physical and social function, patient symptoms, and overall quality of life before and after the procedure. This represented the PAD-related Quality of Health (QOH). Our score range is between 0 (lowest health quality) and 100 (highest health quality). &#x0D; &#x0D; RESULTS: Compared with non-DM patients, those with DM were more likely to have a history of prior PVI, an increased prevalence of PAD risk factors, and significantly lower QOH scores at baseline (32.7 +/- 20 vs 37.5 +/- 20.6, p=0.02). After adjustment for baseline confounding, neither the baseline, the change, nor the final summary scores were significantly different between groups. This suggests similar symptomatic and functional improvement in non-DM and DM patients post-PVI. &#x0D; &#x0D; CONCLUSIONS: Following PVI, PAD-specific health status showed a similar improvement in patients with and without DM, illustrating that use of this strategy among patients with multiple comorbidities or diffuse PAD as useful. &#x0D; &#x0D; Key Words: peripheral arterial disease, peripheral vascular intervention, diabetes mellitus, quality of life &#x0D; &#x0D; Figure or Table: &#x0D; Table 5. Comparison of the Summary Score of 6 PAQ Domains Using Median Scores from Mann Whitney U Test of DM and Non-DM Patients in Detroit, MI, USA&#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; PAQ domain&#x0D; &#x0D; &#x0D; DM&#x0D; &#x0D; &#x0D; Non-DM&#x0D; &#x0D; &#x0D; P-Value&#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; Physical limitation&#x0D; &#x0D; &#x0D; 16.6 (75.4)&#x0D; &#x0D; &#x0D; 25.0 (79.8)&#x0D; &#x0D; &#x0D; 0.06&#x0D; &#x0D; &#x0D; &#x0D; &#x0D; Symptoms&#x0D; &#x0D; &#x0D; 23.6 (75.4)&#x0D; &#x0D; &#x0D; 27.7 (79.8)&#x0D; &#x0D; &#x0D; 0.24&#x0D; &#x0D; &#x0D; &#x0D; &#x0D; Symptom stability&#x0D; &#x0D; &#x0D; 25.0 (75.4)&#x0D; &#x0D; &#x0D; 25.0 (79.8)&#x0D; &#x0D; &#x0D; 0.28&#x0D; &#x0D; &#x0D; &#x0D; &#x0D; Social limitation&#x0D; &#x0D; &#x0D; 16.6 (75.4)&#x0D; &#x0D; &#x0D; 25.0 (79.8)&#x0D; &#x0D; &#x0D; 0.07&#x0D; &#x0D; &#x0D; &#x0D; &#x0D; Treatment satisfaction&#x0D; &#x0D; &#x0D; 0.0 (75.4)&#x0D; &#x0D; &#x0D; 0.0 (79.8)&#x0D; &#x0D; &#x0D; 0.42&#x0D; &#x0D; &#x0D; &#x0D; &#x0D; Quality of life&#x0D; &#x0D; &#x0D; 16.6 (75.4)&#x0D; &#x0D; &#x0D; 25.0 (79.8)&#x0D; &#x0D; &#x0D; 0.06&#x0D; &#x0D; &#x0D; &#x0D; &#x0D; Summary score&#x0D; &#x0D; &#x0D; 18.7 (75.4)&#x0D; &#x0D; &#x0D; 26.0 (79.8)&#x0D; &#x0D; &#x0D; 0.049&#x0D; &#x0D; &#x0D; &#x0D; &#x0D;

Development and validation of a nomogram to predict the risk of peripheral artery disease in patients with type 2 diabetes mellitus.

To develop and validate a nomogram for predicting the risk of peripheral artery disease (PAD) in patients with type 2 diabetes mellitus (T2DM) and assess its clinical application value. Clinical data were retrospectively collected from 474 patients with T2DM at the Air Force Medical Center between January 2019 and April 2022. The patients were divided into training and validation sets using the random number table method in a ratio of 7:3. Multivariate logistic regression analysis was performed to identify the independent risk factors for PAD in patients with T2DM. A nomogram prediction model was developed based on the independent risk factors. The predictive efficacy of the prediction model was evaluated using the consistency index (C-index), area under the curve (AUC), receiver operating characteristic (ROC) curve, Hosmer-Lemeshow (HL) test, and calibration curve analysis. Additionally, decision curve analysis (DCA) was performed to evaluate the prediction model's performance during clinical application. Age, disease duration, blood urea nitrogen (BUN), and hemoglobin (P<0.05) were observed as independent risk factors for PAD in patients with T2DM. The C-index and the AUC were 0.765 (95% CI: 0.711-0.819) and 0.716 (95% CI: 0.619-0.813) for the training and validation sets, respectively, indicating that the model had good discriminatory power. The calibration curves showed good agreement between the predicted and actual probabilities for both the training and validation sets. In addition, the P-values of the HL test for the training and validation sets were 0.205 and 0.414, respectively, indicating that the model was well-calibrated. Finally, the DCA curve indicated that the model had good clinical utility. A simple nomogram based on three independent factors-duration of diabetes, BUN, and hemoglobin levels-may help clinicians predict the risk of developing PAD in patients with T2DM.

The ankle-brachial index for assessing the prevalence of peripheral artery disease and cardiovascular risk in patients with type 2 diabetes mellitus

Background and aimsType 2 diabetes mellitus (T2DM) is an important risk factor for peripheral artery disease (PAD). Ankle-Brachial Index (ABI) was found associated with a higher cardiovascular (CV) risk and mortality. The main goals of this study were to establish the prevalence of PAD in a T2DM population, and assess the relationship between PAD and the CV risk calculated with the CUORE Project score (CPS) (https://www.cuore.iss.it/). The association between the ABI, the main risk factors for PAD and T2DM complications was also investigated. Methods and resultsTwo hundred patients were consecutively enrolled. The prevalence of PAD in this population was 17%. The CV risk tended to be higher (p = 0.0712) in the group with a pathological ABI than in the group with a normal ABI. Glycated hemoglobin (r = −0.1591; p = 0.0244), total cholesterol (r = −0.1958; p = 0.0054), LDL cholesterol (r = −0.1708; p = 0.0156) and systolic blood pressure (r = −0.1523; p = 0.0313) correlated significantly and inversely with the left ABI. The frequency of diabetic retinopathy was significantly higher in the group with a pathological ABI (p = 0.0316). ConclusionsThe data reveal a high prevalence of PAD in patients with T2DM. The CPS confirmed that patients with a pathological ABI have tendency to a higher CV risk. The results point to the importance of an accurate CV assessment – also measuring individuals’ ABI and calculating their CPS - to better pinpoint those at high risk of PAD, especially among patients with T2DM.

Abstract 11954: Metabolomic Profiles Differentiate Arterial and Venous Polygenic Risk

Introduction : Genome-wide association studies reveal genetic correlations between venous and arterial cardiovascular phenotypes, such as venous thromboembolism (VTE), coronary artery disease (CAD), and peripheral arterial disease (PAD). The extent to which these diseases share metabolomic signatures has not been established. Methods : Polygenic risk scores (PRS) for CAD, PAD, and VTE were constructed using PRS-CS with external summary statistics and tested on ~120,000 UK Biobank participants with metabolomic profiling. Linear regression adjusted for age, sex, genotyping array, the first five principal components of ancestry, and statin prescription estimated the effect of polygenic disease risk on 249 metabolites among participants free of prevalent cardiovascular disease. For all metabolomic associations common to at least two diseases, bidirectional two-sample Mendelian randomization tested the causal relationship between metabolite and phenotype. Results : We found 206, 201, and 116 metabolites were associated with genetic risk for CAD, PAD, and VTE, respectively, at an adjusted p-value of 0.001 ( Figure ). Metabolomic profiles were similar between CAD and PAD (R = 0.75, P = 1.25E-46) and CAD and VTE (R = 0.76, P = 8.27E-49), but not between VTE and PAD (R = 0.24, P = 1.21E-4). Mendelian randomization revealed 28 metabolites that increased risk for both CAD and PAD and 2 metabolites that increased risk for CAD but decreased risk for VTE. There were no metabolites with shared causal relationship between PAD and VTE. Conclusions : Polygenic risks for arterial and venous disease are associated with unique metabolomic profiles. Mendelian randomization reveals overlap in causal metabolites between CAD and PAD but little overlap between VTE and either CAD or PAD despite moderate genetic correlation.

Abstract 11460: Sleep Duration, Quality, and Risk of Peripheral Artery Disease: Multinational Cohort and Mendelian Randomization Studies

Introduction: Sleep duration and quality have been linked to atherosclerosis, however the effects on peripheral artery disease (PAD) specifically have not been well characterized. We conducted cohort, case-control, and Mendelian randomization analyses across three large multinational samples (Sweden, United Kingdom, United States) to evaluate associations between sleep traits and risk of PAD. Hypothesis: Abnormal sleep duration and poor sleep quality are associated with increased risk of PAD. Methods: Sleep traits (including duration, subjective quality, daytime napping, snoring, apnea, and insomnia) were assessed for associations with incident PAD using Cox proportional hazards regression within a cohort of 53,416 Swedish adults. Replication was sought in a case-control study of 28,123 PAD cases and 128,459 controls from the VA Million Veteran Program (MVP) and a cohort study of 452,028 individuals from the UK Biobank (UKB). Two-sample Mendelian randomization (MR) was used to estimate causal effects of sleep-related traits on PAD (31,307 PAD cases 211,753 controls). Results: Observational analyses demonstrated a U-shaped association between sleep duration and PAD risk. In Swedish adults, incident PAD risk was higher in those with short sleep (&lt;5 hours; hazard ratio (HR) 1.74; 95% confidence interval (CI) 1.31-2.31) or long sleep (≥8 hours; HR 1.24; 95% CI 1.08-1.43), compared to individuals with a sleep duration of 7 to &lt;8 hours/night. This finding was supported by case-control analysis in MVP and cohort analysis in UKB. Observational analysis also revealed positive associations between poor sleep quality (HR 1.81; 95% CI 1.13-2.90) and daytime napping (HR 1.32; 95% CI 1.18-1.49) with PAD. MR analysis supported an inverse association between sleep duration (odds ratio per hour increase, 0.79, 95% CI, 0.55, 0.89) and PAD, and an association between short sleep and increased PAD (odds ratio, 1.20, 95% CI, 1.04-1.38). MR also found an association between insomnia with PAD (OR 1.10; 95% CI 1.05-1.15) and a reverse association of PAD on shorter sleep (OR 1.05; 95% CI 1.01-1.10). Conclusions: Short sleep duration and measures of poor sleep quality may be causal risk factors for PAD. Maintenance of healthy sleep habits may help prevent PAD.

Abstract 14054: Monocyte Vascular Endothelial Growth Factor Receptor-1 Signaling in Peripheral Artery Disease

Introduction: Peripheral artery disease (PAD) is caused by atherosclerosis of large arteries of the leg(s). Beyond complications from poor perfusion to the legs, patients with PAD suffer higher than expected rates of heart attack and strokes. Monocytes are subdivided into three subtypes: CD14++CD16- (classical), CD14+CD16+ (intermediate), and CD14-CD16+ (non-classical). The intermediate monocyte subtype is linked to PAD. Vascular Endothelial Growth Factor receptor (VEGFR)-1 is a member of tyrosine kinase family that is expressed in monocytes and has high affinity for the VEGF-A ligand. Recent studies showed that inhibition of VEGFR1/STAT-3 signaling decreases angiogenesis in PAD. We hypothesized that in patients with PAD, intermediate monocytes would have less VEGFR1/STAT3 activation than controls. Methods: Blood samples were collected from PAD patients (n=11) and risk factor closely matched controls (n=17). PBMCs were isolated by gradient centrifugation. By flow cytometry, gating strategy on monocytes was done by excluding granulocytes (CD66b), B and T lymphocytes (CD3,CD19), and natural killer cells (CD56). Next, monocytes were subdivided into three populations (intermediate, classical, and non-classical) by gating according to their CD14/CD16 expression. Within each population, levels of p(Y1333)VEGFR1, VEGFR1, pSTAT3, and STAT3 were determined. Results: Data from flow cytometry analysis showed a significant increase in the intermediate monocyte population in PAD vs control (~1.5-fold change; p=0.01). However, there was no significant difference in the non-classical or classical monocytes between PAD and control. Within the intermediate monocytes, P(Y1333) VEGFR1/VEGFR1 was decreased (~2-fold change) and pSTAT3/STAT3 was significantly decreased (~2-fold change) in PAD vs control. In both the non-classical and classical monocytes, there was no significant difference in either phosphorylated receptor between PAD and control. Conclusions: The data confirm the intermediate monocyte is associated with PAD and suggest that VEGFR1/STAT3 signaling is decreased in intermediate monocytes in PAD vs control. Understanding the mechanism of VEGFR1 activation may prove to be a promising therapeutic target for patients with PAD.