Peripheral Arterial Disease Research Articles

Exploring the Genetic Relationship Between Type 2 Diabetes and Cardiovascular Disease: A Large-Scale Genetic Association and Polygenic Risk Score Study

Type 2 diabetes (T2D) is often comorbid with cardiovascular diseases (CVDs). The direction of causation between T2D and CVD is difficult to determine; however, there may be a common underlying pathway attributable to shared genetic factors. We aimed to determine whether there is a shared genetic susceptibility to T2D and CVD. This study utilizes large-scale datasets from the UK Biobank (UKB) and DIAGRAM consortium to investigate the genetic association between T2D and CVD through phenotypic association analyses, linkage disequilibrium score (LDSC) analysis, and polygenic risk score (PRS) analysis. LDSC analysis demonstrates significant genetic associations between T2D and various CVD subtypes, including angina, heart failure (HF), myocardial infarction (MI), peripheral vascular disease (PVD), and stroke. Although the genetic association between T2D and atrial fibrillation (AF) was not significant, individuals in the high-T2D PRS group had a significantly increased risk of CVD. These findings suggest a common genetic basis and suggest that genetic susceptibility to T2D may be a potential predictor of CVD risk.

Mediating effect of fasting blood glucose and peripheral arterial disease on the relationship between sexual functioning and health-related quality of life among Nigerians with type 2 diabetes

Mediating effect of fasting blood glucose and peripheral arterial disease on the relationship between sexual functioning and health-related quality of life among Nigerians with type 2 diabetes

Associations of Metabolic Dysfunction-Associated Fatty Liver Disease With Peripheral Artery Disease: Prospective Analysis in the UK Biobank and ARIC Study.

There is currently limited evidence comparing the association between metabolic dysfunction-associated fatty liver disease (MAFLD), nonalcoholic fatty liver disease (NAFLD), and the risk of peripheral artery disease (PAD). This study aims to analyze the associations of MAFLD and NAFLD with incident PAD. Two longitudinal studies, the UKB (UK Biobank) study (n=372 216) and the ARIC (Atherosclerosis Risk in Communities) study (n=4681), categorized participants into MAFLD/non-MAFLD groups and NAFLD/non-NAFLD groups. Subsequently, participants were classified into 4 groups: non-fatty liver disease, MAFLD-only, NAFLD-only, and both MAFLD and NAFLD groups. Cox proportional hazard model estimated associations of MAFLD/NAFLD status, subtypes, and liver fibrosis severity with PAD risk. The MAFLD group had a higher risk of incident PAD compared with the non-MAFLD group, and similarly, the NAFLD group had a higher risk compared with the non-NAFLD group. Among these 4 groups, the MAFLD-only group had the strongest association with the risk of incident PAD, while the NAFLD-only group was not independently associated. Diabetic MAFLD subtype was significantly associated with increased PAD risk, and higher level of liver fibrosis scores correlated with elevated PAD risk. Both MAFLD and NAFLD are significantly associated with an increased incidence of PAD, with stronger associations in MAFLD and diabetic MAFLD population. These findings emphasize that the need for screening and prevention strategies for PAD in this high-risk population is warranted. The assessment of MAFLD and its subtypes should be considered as an integral component of cardiovascular risk assessment.

Trends in Peripheral Artery Disease, Lower Extremity Revascularization, and Lower Extremity Amputation in Incident Type 2 Diabetes: A Danish Population-Based Cohort Study.

To examine trends in peripheral artery disease (PAD), lower-extremity (LE) revascularization, and LE amputation in patients with incident type 2 diabetes. This cohort study included patients in Denmark diagnosed with type 2 diabetes in 1996-2015 and followed until 2020. Patients were age and sex matched with as many as three general population individuals. Outcomes comprised 5-year cumulative incidences of first-time PAD, LE revascularization, and LE amputation. Age- and sex-adjusted hazard ratios (aHRs) were computed using Cox regression. The cohort comprised 349,454 patients with incident type 2 diabetes (53% male; median age 62 years) and 1,025,054 general population individuals. Among patients with diabetes, decreases in 5-year cumulative incidence of PAD (from 6.2 to 3.4%; aHR 0.55 [95% CI 0.52-0.57]), LE revascularization (from 0.8 to 0.6%; aHR 0.80 [95% CI 0.71-0.90]), and LE amputation (from 1.0 to 0.4%; aHR 0.45 [95% CI 0.40-0.51]) occurred from 1996-2000 to 2011-2015. LE amputation decreased at all amputation levels (hip/thigh, knee/lower leg, and ankle/foot/toe) during the study period. In the general population, 5-year cumulative incidence remained stable (1.2-1.5% for PAD, ∼0.4% for LE revascularization, and ∼0.2% for LE amputation). However, the relative rates of all outcomes were two- to threefold higher in patients with diabetes than matched individuals in 2011-2015. In recent decades, the cumulative incidence of LE complications substantially decreased in patients with incident type 2 diabetes while remaining stable in the general population.

Predictive factors of extremity graft occlusion after endovascular repair of abdominal aortic aneurysm: A 13-year single center experience

Aim: Graft leg thrombosis (GLT) after Endovascular Aortic Repair (EVAR) is an important problem affecting morbidity/mortality. In addition to anatomical factors such as aortic neck angle and diameter in graft leg thrombosis; we aimed to convey the roles of graft extension to the external iliac artery and the effect of graft type selection on the results. Material and Methods: Analysis of 512 patients who underwent EVAR between 2010 and 2023 was performed. The effects of anatomical factors, graft material, underlying diseases, age and gender on the development of graft leg thrombosis were evaluated. Anatomical measurements were evaluated in terms of their predictive power for graft leg thrombosis by Receiver Operating Characteristic (ROC) analysis. Results: The prevalence of graft leg occlusion was significantly associated with some anatomical factors, especially increased aortic neck angle (OR=1.07, p<0.001) and descent to the external iliac artery (OR=13.43, p<0.001). Poliytetrafluoroethylene (PTFE) grafts were associated with a reduced risk of graft leg occlusion (OR=0.26, p=0.002). ROC analysis showed that aortic neck angle had the highest predictive accuracy for GLT (AUC=0.817, p<0.001). There were no significant differences in age, gender, smoking status, diabetes, and hypertension as comorbidities. Peripheral artery disease was shown to increase the risk. Conclusion: Our findings highlight the role of aortic anatomy and graft material selection in the risk of graft leg thrombosis. The use of PTFE grafts appears to be protective against graft leg thrombosis. This information highlights the importance of personalized surgical planning and postoperative management to optimize patient outcomes. Future research should focus on developing models that include these factors.

Identification of Metabolic Patterns in Korean Patients with Type 2 Diabetes Mellitus and their Association with Diabetes-Related Complications.

Resolving metabolic heterogeneity in patients with type 2 diabetes mellitus (T2DM) gives them access to precision medicine. Despite ethnic diversity in pathophysiological processes in individuals with T2DM, studies on subtypes of diabetes related to clinical characteristics in Asians are insufficient. This study aims to identify metabolic patterns in middle-aged patients with T2DM in Republic of Korea (Korea) and determine the incidence of diabetes-related complications according to patterns. We analyzed 6,603 patients with T2DM aged 30 to 64 who visited three centers of general hospital in Korea. Three metabolic patterns were derived: Obesity and Hypertension pattern (OH-P), Liver Function-related HyperGlycemia pattern (LFHG-P), and Decreased Kidney Function pattern (DKF-P). The highest tertile of the OH-P score was associated with an increased risk of peripheral vascular disease compared to the lowest tertile (HR = 1.26, 95% CI = 1.02-1.57). The highest tertile of the LFHG-P score was associated with an increased risk of myocardial infarction (HR = 1.79, 95% CI = 1.13-2.82) and atrial fibrillation (HR = 1.54, 95% CI = 1.07-2.23). No association with complications was found in the DKF-P. This study suggests the need for proper management and treatment according to metabolic patterns in patients with T2DM.

Candida associated infra-inguinal prosthetic vascular graft infection: A case report

Prosthetic vascular grafts (PVG) are artificial vascular materials used for revascularization in the treatment of vascular diseases. Due to increase in life expectancy, the number of individuals requiring PVGs is increasing and encountering the PVGI is also more frequent. We presented an interesting case operated because of infected graft in which Candida albicans grew. The patient had been operated twice for peripheral artery disease in another hospital before. We performed femoro-popliteal bypass by using great saphenous vein after removal of infected graft. In peripheric bypass surgery performed with PTFE (polytetrafluoroethylene) graft, growth of Candida albicans in graft material is a rare condition and this situation has a high mortality rate. In the patients with comorbidities and who will undergo redo-surgery, excessive care should be given in terms of graft infections.

Asymptomatic Peripheral Arterial Disease Among Jordanian Patients With Diabetic Foot Ulcer

Asymptomatic Peripheral Arterial Disease Among Jordanian Patients With Diabetic Foot Ulcer

Transcutaneous osseointegrated prosthetic system (TOPS) with an intramedullary prosthesis : Management of the femoral stump with concurrent total hip arthroplasty

Simultaneous implantation of aTOPS (transcutaneous osseointegrated prosthetic system) and THA (total hip arthroplasty) or staged approach. Patients with aTOPS who have coxarthrosis. Patients with an existing THA who have required above-knee amputation and need aTOPS. Patients with an existing TOPS who sustain amedial femoral neck fracture and are not stabilizable with osteosynthesis. Atypical anatomy, osteomyelitis, radiation or chemotherapy to the affected limb in the last 18months, peripheral occlusive arterial disease with critical ischemia, diabetes mellitus with polyneuropathy, local dermal or systemic infection, immunocompromised state or use of immunosuppressants, cognitive impairment or lack of compliance for the system, other significant physical impairments. Individualized preoperative planning based on CT data. Access similar to conventional THA for existing TOPS. Implantation of an artificial acetabulum with amatching inlay. Similar approach for medial femoral neck fractures without reconstructive options. For existing THA and prior above-knee amputation, removal of existing shaft and potentially neck component for modular prosthesis. Subsequent implantation of TOPS stem in conventional manner. Additional THA requires appropriate rehabilitation following endoprosthesis guidelines, tailored to the TOPS situation. For simultaneous implantation of TOPS and THA the patients' load-bearing capacity and mobilization depend on the duration of the implanted stem. Only 4patients have been treated at BGU Murnau making statistical analysis not feasible. Three of the 4patients experienced significant pain relief and improved mobility shortly after surgery. One patient remained as immobile postoperatively as preoperatively due to inability to achieve pain-free full weight-bearing.

Endovascular abdominal aortic aneurysm repair (EVAR) outcomes of unibody and single/double docking limb endografts in Medicare beneficiaries between 2012 and 2018.

The evaluation of perioperative and long term outcomes for endovascular aneurysm repair (EVAR) of abdominal aortic aneurysms (AAA) using anatomic (unibody) and proximal neck fixated (docking limbs) endografts across consecutive time cohorts. This study compares the outcomes of EVAR in Medicare patients stratified by mode of fixation. All patients who underwent EVAR between 2012 and 2018 were identified in the Medicare database. Anatomic fixation (AF) and proximal fixation (PF) grafts were differentiated using Current Procedural Terminology (CPT) codes. The AF population was divided into three-time cohorts based on iterative changes in graft design: Cohort 1: (01/01/2012-20/07/2014); Cohort 2: (21/07/2014-09/05/2016); and Cohort 3: (10/05/2016-31/12/2017). The PF cohort was similarly divided into these three periods. Outcomes were evaluated through 31/12/2020 and included all-cause mortality, aortic rupture, and aortic-related reintervention. 32,031 patients underwent EVAR during the study period; 4729 were AF and 27,302 were PF. There were more women (p < .001) and patients with peripheral vascular disease (PVD) (p < .001) in the AF group. There were no group differences in perioperative outcomes. In Cohort 1, there was a higher rate of reintervention (11.9% vs 7.6%; p < .001) and aortic rupture (5.3% vs 4.0%; p = .019) in the AF group compared to the PF group. In Cohort 2, reintervention, aortic rupture, and reintervention rates were similar between the two groups (p = NS). In Cohort 3, the reintervention and aortic rupture rates were similar between the two groups (p = NS). The higher rates of aortic rupture and reintervention seen in the AF group in Cohort 1 when compared with the PF group did not persist in Cohorts 2 and 3. This suggests that improvements in graft design may have led to durability which is similar to that of PF grafts. However, late aneurysm related complications are inherent risks after EVAR and long-term surveillance remains necessary.

Abstract 4121555: Integrated Polygenic Score Stratifies Risk of Peripheral Artery Disease and Major Adverse Limb Events

Background: Peripheral artery disease (PAD) is a heritable atherosclerotic condition. With growing knowledge of the genetic basis for PAD and related risk factors, there is opportunity to identify high-risk individuals for prevention and potentially intervention based on polygenic background. Aims: To develop and validate an integrated genome-wide polygenic score for PAD (GPS PAD ), evaluate association of polygenic risk with major adverse limb events (MALE), and compare predictive performance in diverse ancestral populations to previously published polygenic scores. Methods: We developed GPS PAD by integrating genetic association summary statistics for PAD and related traits stratified by ancestry. GPS PAD was trained in a sample of 96,239 European individuals from the UK Biobank, and validated in multi-ancestry cohorts, including a holdout validation UK Biobank dataset (N=304,294), and external All of Us (AoU; N=237,173) and Mass General Brigham Biobank datasets (N=37,017). GPS PAD performance was benchmarked against previously published polygenic scores and clinical risk factors. Results: GPS PAD was comprised of 603,595 variants with weights informed by association with PAD and ten PAD risk factors across five ancestry groups. GPS PAD had an OR-per SD of 1.63 in the holdout UK Biobank dataset (95% CI 1.60-1.68). GPS PAD outperformed previously published scores in non-European subgroups in the UK Biobank and achieved superior cross-population portability in external validation cohorts. GPS PAD was associated with incident PAD in the UK Biobank (HR 1.66; 95% CI 1.61-1.71) and achieved improvements in discrimination (ΔC-statistic 0.030) that were nearly equivalent to the additive performances of diabetes (ΔC-statistic 0.029) and smoking (ΔC-statistic 0.034) to the baseline model including age, sex, and 10 principal components of ancestry. Among individuals with prevalent PAD, GPS PAD was associated with incident MALE in the UK Biobank (HR 1.48; 95% CI 1.24-1.77). GPS PAD consistently identified individuals with PAD at high MALE-risk in the Mass General Brigham Biobank (HR 1.34; 95% CI 1.12-1.60), and AoU (HR 1.33; 95% CI 1.12-1.58). Conclusions: These findings contribute a polygenic score for PAD that predicts disease and MALE with cross-cohort performance and transferability to diverse ancestries. Integrated polygenic scores may be used to stratify PAD risk and target more aggressive management, lifestyle modification, and surveillance efforts.

Abstract 4147628: A Mixed Methods Analysis of Patient Knowledge in Peripheral Artery Disease

Introduction: Patient knowledge of lower extremity peripheral artery disease (PAD) is low compared to other cardiovascular diseases. Research Questions/Hypothesis: We hypothesize that demographic and socioeconomic factors impact patient knowledge of PAD. Goals/Aims: To obtain qualitative description of and identify factors associated with patient knowledge of PAD. Methods/Approach: We performed a convergent parallel mixed methods study of participants with an established PAD diagnosis. Participants completed an 87-item survey assessing demographics, awareness of PAD diagnosis, and PAD knowledge. Functional health literacy (FHL) was measured using the short Test of Functional Health Literacy Assessment. Multivariable linear regression was used to identify factors associated with PAD knowledge scores. Semi-structured interviews were used to describe understanding of PAD. Transcripts were analyzed with inductive and deductive coding, and a constant comparative approach was used to identify themes. Results/Data: There were 91 participants (77.2% response rate, 49.5% female, 29.7% Black, mean age 68.6 years). Most participants (51.7%) had chronic limb-threatening ischemia and 17.6% had a previous major amputation. While 21.3% had poor FHL and 24.4% were unaware of their PAD diagnosis, the average knowledge score was 79.1%. On bivariate analysis, non-White race, non-ambulatory status, poor FHL, lack of awareness of PAD diagnosis, and not knowing the chronicity of diagnosis were inversely associated with knowledge score. Multivariate linear regression showed that poor FHL, non-White race, and not knowing the chronicity of PAD diagnosis were independently associated with low PAD knowledge. Qualitative analysis of 22 participants revealed that patients have difficulty understanding the name “PAD”, confuse PAD with other comorbidities, and have incorrect beliefs about PAD despite high knowledge scores. Conclusions: Knowledge of PAD is associated with health literacy. However, patients have incorrect beliefs and difficulty understanding the terminology associated with PAD despite a high average knowledge score. Knowledge scores may not adequately reflect understanding. Future research will focus on optimizing patient education, identifying strategies to appropriately gauge patient understanding, and understanding the association between knowledge and behavior in PAD.

Abstract 4139141: Predicted efficacy of inclisiran on cardiovascular outcomes in lower extremity peripheral artery disease: results of the In Silico Sirius study

Introduction: Symptomatic lower extremity peripheral artery disease (PAD) patients have the highest risk of cardiovascular (CV) outcomes among patients with established atherosclerotic cardiovascular disease (ASCVD). Inclisiran, an siRNA targeting PCSK9 mRNA, reduces LDL-C levels. In SIRIUS in silico trial (NCT05974345), inclisiran was predicted to lower CV events in ASCVD patients. Research question/Hypothesis: SIRIUS in silico study aims to predict the efficacy of inclisiran on CV outcomes in subgroups of patients with or without PAD. Methods: The SIRIUS in silico trial was conducted using a knowledge-based mechanistic computational model of ASCVD applied to a virtual ASCVD population with LDL-C ≥ 70 mg/dL. Each virtual patient is its own control. This model was previously calibrated and validated before running the trial. SIRIUS compared the efficacy of inclisiran vs placebo on top of High Intensity (HI) statins with or without ezetimibe on 3-Point-MACE defined as a composite of time to first occurrence of CV death, nonfatal myocardial infarction (MI) or nonfatal ischemic stroke (IS) over 5 years. Occurrence of major acute limb events (MALE) was also individually assessed in time-to-first-event analyses. Results: Among 204, 691 virtual SIRIUS ASCVD patients, 28,072 (13.7%) had PAD. At 5 years, the mean predicted percentage reduction in LDL-C with inclisiran as compared to placebo was -49.3% and -49.8% in patients with or without PAD, respectively. The predicted rate of 3P-MACE in the inclisiran arm was consistently lower than in the placebo arm in patients with PAD (17.62% vs 22.88%; Hazard Ratio (HR): 0.75 medium uncertainty) and in patients without PAD (10.33% vs 13.64%; HR: 0.75 low uncertainty). Compared to placebo, inclisiran was also predicted to consistently reduce MALE in patients with or without PAD (2.71% vs 4.11%; HR: 0.65 medium uncertainty and 0.19% vs 0.29%; HR: 0.66 high uncertainty respectively). Conclusion: Pending the results of ORION-4 and VICTORION-2-P, this first In Silico trial in virtual PAD patients predicted a potential effect of inclisiran on 3P-MACE and MALE reductions over 5 years follow-up.

Abstract 4132769: Carnosine Supplementation Improves Walking Ability of Peripheral Arterial Disease Patients

Introduction: Peripheral artery disease (PAD) is a significant cause of cardiovascular morbidity and mortality, characterized by atherosclerosis in the skeletal muscle. Currently no mechanism-based therapeutics are available for this diseased population. In the muscle, histidyl dipeptides, such as carnosine (ranging between 5-10 mM) possess the abilities to bind with toxic lipid peroxidation products, such as acrolein. Preclincial studies show carnosine is depleted in the ischemic leg, increasing intramuscular carnosine improves angiogenesis, and blood flow in the ischemic leg. In humans, carnosine levels are increased in the muscle with carnosine supplementation. However, little is known whether carnosine levels are affected in PAD patients and its effect on their walking ability. Hypothesis: Carnosine supplementation will improve walking ability of PAD patients. Methods: We recruited normal (males: n=48; females: n=52; age: 50 ±10 years) and PAD subjects (males: n=52; females: n=41; age: 67±8 years; ankle brachial index (ABI): 0.65±0.18 measured urinary histidyl dipeptides, histidyl dipeptide-aldehyde conjugates, and oxidative stress markers: N-Acetyl-S-(3-hydroxypropyl)-L-Cysteine (3-HPMA) and N-acetyl-S-(2-carboxyethyl)-L-cysteine (CEMA), both are acrolein metabolites. PAD subjects (n=7; n=5 females and n=2 males; ABI: 0.68±0.08, age: 63±8 years) were supplemented with carnosine 2 g/day for 3 months, measured distance covered in a six-minute walk test (6MWT), ABI, blood profile at baseline and after completion. Results: In PAD subjects urinary carnosine was decreased (normal: 20±29 vs PAD:11±14 nmoles/mg creatinine, p&lt;0.024), carnosine aldehdye conjugates were increased (carnosine propanal: 1.46±1.27 vs normal 0.56±1.08 nmoles/mg creatinine, p&lt;0.0001; and carnosine propanol: 4.66±2.80 vs normal 1.52±1.21 nmoles/mg creatinine, p&lt;0.0001). Oxidative stress markers were increased in the PAD subjects (CEMA: 341±210 vs normal: 119±86 ng/mg creatinine, p&lt;0.0004 and 3HPMA: 6.57±6.32 ng/mg protien vs normal: 5.49±5.28 ng/mg creatinine, p&lt;0.001). Following carnosine supplementation, blood profile was unchanged. Distance covered in 6MWT increased by 166±204 feet (before: 577±129 vs 743±152 feet after, p&lt;0.048) and there was an increasing trend in ABI (before: 0.68±0.08 vs 0.80±0.19; after, p&lt;0.18). Conclusion: Urinary carnosine could serve as a biomarker to evaluate PAD pathology and carnosine supplementation may improve walking ability of PAD patients.

Abstract 4139186: Bempedoic Acid and Limb Outcomes in Statin-Intolerant Patients with Peripheral Artery Disease

Introduction: Patients with peripheral artery disease (PAD) are at high risk of major adverse limb events (MALE) and CV events and have high rates of recurrence of these events. Recently, bempedoic acid was shown to reduce MACE in primary and secondary prevention patients. Whether bempedoic acid reduces the risk of MALE is unknown. Methods: CLEAR Outcomes randomized 13,970 patients to bempedoic acid 180 mg or placebo. A clinical history of PAD was reported by investigators at baseline. Two blinded vascular medicine specialists independently adjudicated all adverse events for limb outcomes including worsening PAD symptoms leading to revascularization, chronic limb threatening ischemia, and acute limb ischemia events with the composite defined as MALE. Outcomes were assessed as time to first event as well as total (including recurrent) events using a negative binomial approach. Results: A total of 1,624 of the enrolled patients had PAD at baseline. Over a median of 41.1 months the rate of first and total MALE events in patients with PAD in the placebo group were 8.3% and 13.7% respectively. Bempedoic acid reduced first MALE events by 36% (HR 0.64, 95% CI 0.44-0.93) with an absolute risk reduction (ARR) of 2.5% and number needed to treat (NNT) of 40, compared to placebo (figure, panel A). Similarly, when considering total events, bempedoic acid reduced MALE by 45% (RR 0.55, 95% CI 0.35 – 0.85, figure panel b). Consistent benefits were observed for MALE in the overall population as well as composites of MACE and MALE in both populations (Figure panel b). There was no evidence of effect modification for the benefit of bempedoic acid for MALE on the basis of PAD at baseline (p-interaction 0.09). Conclusions: Bempedoic acid significantly reduces MALE. Benefits appear potentially greater when considering total (i.e. recurrent) events. These findings support the importance of LDL-C lowering therapy in patients with PAD. In addition, these findings support the early use of therapies with proven MALE benefit, including bempedoic acid, to optimize outcomes in PAD.

Abstract 4122008: Bayesian modeling to forecast mortality due to Ischemic Heart Disease, Stroke, and Peripheral Artery Disease in Brazil until 2040

Introduction: Atherosclerotic cardiovascular disease, specifically ischemic heart disease (IHD), stroke, and peripheral artery disease (PAD) together are among the leading causes of cardiovascular mortality in Brazil. As the obesity, hypertension, and diabetes rates in the Brazil continue to increase, projecting mortality rates related to these conditions are important for guiding health policy. Hypothesis: We hypothesized that there are differences in the future trends of IHD, stroke and PAD in Brazil. Aims: We sought to forecast the trends in IHD, stroke, and PAD in Brazil until 2040 to fill in this important knowledge gap and inform public health policy development. Methods: We collected the annual death counts for IHD, stroke, and PAD and the mid-year population estimates in 5-year age brackets (40 – 79 years) between 1990 and 2019 from the Global Burden of Disease. We calculated the annual crude and age-standardized mortality rates (per 100 000 residents) for IHD, stroke and PAD between 1990 and 2019. Using this observed data, we estimated the projected mortality rates for these conditions till 2040 using Bayesian age-period-cohort (BAPC) models. Results: Brazil`s population (aged 40-79 years) will increase by 237.5% between 1990 and 2040. Nationally, compared to 2019, the age standardized IHD mortality is projected to reduce by 31.66 % [2019: 131.13, 2040:89.6 (IQR: 65.83, 113.37)] and stroke rates are estimated to reduce by 16.75% [2019: 91.09, 2040: 75.83 (IQR: 51.68, 99.98)]. However, PAD rates are projected to increase by 1.2% in the same period [2019: 1.58, 2040: 1.66 (IQR: 1.24, 2.07)]. The age standardized IHD and stroke mortality rates will reduce in males and females. However, the age standardized PAD rates will increase in females [2019: 1.33, 2040: 1.48 (IQR: 1.06, 1.89), 11.28% difference] and remain reasonably constant among males. Conclusion: In Brazil, the age standardized rates for IHD and stroke mortality are projected to decline till 2040. However, PAD related mortality is likely to be an important issue among females. Our findings highlight the need for early and targeted interventions to address these potential cardiovascular health disparities.

Total Contact Casting Remains an Effective Modality for Treatment of Diabetic Foot Ulcers.

Total contact casting (TCC) is used to promote wound closure in diabetic foot ulcers (DFUs); however, this technique is underused today. This study aims to further evaluate the efficacy of TCC in a large cohort, including patients with peripheral artery disease (PAD). This was a retrospective analysis of patients with DFUs who underwent TCC from 2017 to 2021. PAD was defined as absence of pedal pulse or ABI <0.9. Demographic data, DFU characteristics, and peripheral arterial intervention were evaluated. Outcomes included complete healing, healing time, and rate of major amputation. Subgroup analysis was performed on patients undergoing peripheral intervention. 152 patients underwent TCC. Mean age was 58.8 ± 12.1years, 79.6% were male, and 26.3% had PAD. Mean DFU size was 8.27 ± 9.9cm2, with mean depth 0.61 ± 0.49cm. 112 patients had palpable pedal pulses on the affected extremity (73.7%). Average ABI was 1.12 ± 0.22 (n = 90). Complete healing was observed in 122 (80.3%) patients, with average healing time of 81.5 ± 57.1days. Thirteen (8.6%) patients eventually required amputation (3 major). When compared to patients with healed DFUs, those without healing had higher rates of amputation (39.1% vs 3.1%, P < .001), intervention (43.4% vs 17.8%, P = .006), and noncompliance (39.1% vs 20.2%, P = .046). Thirty-three patients underwent revascularization, undergoing angioplasty (81.8%), atherectomy (63.6%), stent (15.2%), and/or bypass (9.1%). Interventions were performed in aortoiliac (3.0%), femoropopliteal (45.5%), and tibial (72.7%) segments. Twenty-two (66.7%) patients who underwent revascularization completely healed. Patients requiring revascularization were more likely to have previous intervention (57.6% vs 13.4%, P < .0001) and incompressible vessels (36.4% vs 7.6%, P < .00001), with lower ABIs (0.94 ± 0.25 vs 1.17 ± 0.18, P = .0008) compared to patients without intervention. TCC remains an effective option for treatment of DFUs, as most were completely healed. Patients with PAD may benefit from TCC and revascularization, however, healing rates are lower in this cohort, necessitating the need for close observation.

Abstract 4138246: Differences in Major Adverse Cardiovascular and Lower Limb Events and Guideline-Directed Medical Therapy Among Males and Females Within an Integrated Healthcare System

Background: Health disparities based on gender have been recognized as having a detrimental impact on care delivery and early identification of disease processes. Peripheral arterial disease (PAD) is the third leading cause of atherosclerotic disease mortality. It is unclear what role, if any, gender plays in the diagnosis, treatment, and outcomes of PAD. Hypotheses: Females are less likely to have guideline-directed medical therapy (GDMT) and more likely to have major adverse cardiovascular events (MACE) and major adverse lower limb events (MALE) than males. Methods: The Intermountain Health electronic database was queried for patients meeting the following criteria: ≥18-years of age, PAD diagnosis between Jan 2006 to Dec 2021, seen at least once within the 18-months following initial PAD diagnosis, and had a symptom of PAD (see table). Follow-up GDMT, based on the 2016 AHA/ACC PAD guidelines, was determined by medication and procedures. Time to outcomes of MACE (all-cause death, MI, stroke, or unstable angina hospitalization) and MALE (limb ischemia, limb revascularization, or limb amputation) were examined using Cox-proportional hazard adjusted for GDMT, age, and prior CAD. Results: A total of 7522 patients had a symptomatic PAD diagnosis, with 38% female and 62% male. Females tended to be older (70.1±13.0 vs 68.6±11.7), more likely to be obese (25% v 21%), and less likely to have Afib (21% v. 24%), CAD (30% v 41%), MI (11% v 16%), renal failure (19% v 22%) but more likely to have a bleeding history (30% v 26%) (all p&lt;0.01). Females were slightly less likely to have all the GDMT and yet had similar rates of referrals to specialists but higher rates to primary care providers (Table). After adjustment, females were less likely to have MACE (HR=0.94; 95% CI: 0.88, 0.99) and MALE (HR=0.85; 95% CI: 0.80, 0.92). Conclusion: Females had lower rates of MALE, driven by lower limb revascularization or amputation rates, and slightly lower rates, after adjustment, for MACE. This was observed despite the high rates of GDMT for both females and males (~80% in any category), with females having slightly less GDMT.

Abstract 4135082: Small dense low-density lipoprotein cholesterol and risk of peripheral artery disease

Background: High levels of small dense low-density lipoprotein (sdLDL) is a hallmark of dyslipidemia; however, studies on sdLDL cholesterol levels and risk of peripheral artery disease are sparse and results inconclusive. Hypothesis: We tested the hypothesis that higher levels of sdLDL cholesterol are associated with increased risk of peripheral artery disease in a primary prevention setting. Methods: We studied 31,036 individuals free of lipid-lowering therapy, ischemic stroke, and myocardial infarction at study entry in 2013-2017. All had fresh sample measurements of sdLDL cholesterol. During a median follow-up on 6.2 years, 155 were diagnosed with peripheral artery disease. The association was confirmed using ankle-brachial index (ABI) ≤ 0.9 as endpoint. Lastly, as comparison across different vascular beds risk estimates for myocardial infarction and ischemic stroke were calculated. Results: Higher levels of sdLDL cholesterol were associated with higher risk of peripheral artery disease and an ABI ≤ 0.9 illustrated by cubic splines multivariable adjusted for sex, systolic blood pressure, education, body mass index (BMI), diabetes, large buoyant LDL cholesterol, and age. Per 1 mmol/L (37 mg/dL) higher sdLDL cholesterol hazard ratio for peripheral artery disease was 2.01 (95% CI: 1.41-2.85) and odds ratio for an ABI ≤ 0.9 was 1.51 (95% CI: 1.07-2.14) in multivariable adjusted models. The cumulative incidence of peripheral artery disease was respectively 1.5%, 2.5%, and 3.5% for individuals having a sdLDL cholesterol in the 1 st -50 th , 51 st -90 th , and the 91 st -100 th percentiles at age 80. For the 91 st -100 th versus the 1 st -50 th percentile a hazard ratio on 2.51 (95% CI: 1.50-4.20) for peripheral artery disease, 2.18 (95% CI: 1.58-3.01) for myocardial infarction, and 1.85 (95% CI: 1.37-2.49) for ischemic stroke was found. Furthermore, the association of higher sdLDL cholesterol with increased risk of peripheral artery disease was robust in sensitivity analyses. Conclusion: Higher levels of sdLDL cholesterol were robustly associated with increased risk of peripheral artery disease in a primary prevention setting.

Abstract 4140149: Differences in Interventional Treatment Outcomes of Peripheral Arterial Disease between African American Females, African American Males, and Caucasian Females

Introduction: Several recent publications demonstrated worse outcomes of interventional treatment of peripheral arterial disease (PAD) in patients of African American (AA) descent compared to Caucasians (C), and in female patients compared to male patients. However, studies addressing sex differences in outcomes, included predominantly white female patients. To our knowledge, there are no published studies specifically addressing outcomes of interventional treatment of PAD in female patients of African American descent. Aims: 1. To determine if the outcomes of interventional treatment of PAD in female patients of African American (FAA) descent differ from male African American patients (MAA), and Caucasian female patients (FC). If such differences exist, to identify factors associated with it. Methods: This study has a cross-sectional design with systematically retrospective data collection by the National Vascular Quality Initiative. Included in this study was data on patients treated with endovascular and open surgical options for symptomatic PAD. Statistical analysis was done using IBM Statistic SPSS V25. Results: 447,263 unique cases containing required data were available in the VQI database. Among them, 171,250 were female patients, of which 32,966 were FAA, 126,519 FC, and 39,461 MAA. This race and gender distribution is not significantly different from the US population structure (US Census Bureau 2023). 1 However, female to male ratio was higher in AA (0.83) compared to C (0.58, p&lt;0.0001). FAA were younger (65.143+/-9.59) compared to FC (69.16+/-10.32, P&lt;0.00001). Comparison of comorbidities, smoking rates, pre-interventional medications and post-interventional outcomes are listed in Table 1. Multivariate analysis confirmed higher amputation rate among FAA compared to FC and to MAA and showed no significant difference in mortality. Conclusions: FAA patients who require interventional treatment for PAD have significantly higher rate of hypertension and diabetes compared to FC and MAA patients and have higher amputation rates. It appears that differences in clinical outcomes of PAD treatment in FAA are related mostly if not entirely to poorly managed comorbidities existed prior to intervention.