Concomitant Peripheral Arterial Disease Research Articles

Favorable Trends in Mortality among Patients with Concomitant Peripheral Arterial Disease and Diabetes Mellitus over Past Two Decades

BackgroundThis study examines the temporal trends in diabetes and peripheral artery disease (PAD)-related mortality in the United States, considering sociodemographic and regional factors, using data from death certificates in a national public database. MethodsData were extracted from the CDC WONDER (Centers for Disease Control and Prevention Wide Ranging Online Data for Epidemiologic Research) database from 1999 to 2020. Age-adjusted mortality rates (AAMR) per 100,000 individuals and annual percent changes (APC) with 95% confidence intervals (CI) were calculated. ResultsBetween 1999 and 2020, there were 2,252,252 PAD-related and 5,413,811 diabetes-related deaths, with 469,699 deaths involving both conditions. The overall AAMR for PAD and diabetes-related mortality (aged ≥ 25 years) decreased from 7.97 in 1999 to 6.37 in 2020, with a notable decline from 2001 to 2010 (APC: -6.16, 95% CI: -7.07, -5.23). The AAMR for PAD-related mortality fell from 40.25 to 30.56, while the AAMR for diabetes-related deaths rose from 76.71 to 93.63. Males and non-Hispanic (NH) Black individuals had higher AAMRs than females and other racial groups. The highest crude mortality rate (CMR) was in the 80-84 age group. Non-metropolitan areas consistently reported higher AAMRs than metropolitan areas, and states like Ohio, Vermont, District of Columbia, and West Virginia had significantly higher rates. ConclusionOver two decades, PAD and diabetes-related mortality trends show a positive overall reduction in AAMR. However, disparities persist, with higher rates among males, NH Black individuals, and residents of non-metropolitan areas. Significant state-level variations highlight the need for targeted interventions and tailored healthcare strategies.

Correlation and risk factors of peripheral and cervicocephalic arterial atherosclerosis in patients with ischemic cerebrovascular disease

Patients with ischemic cerebrovascular disease (ICVD) frequently develop concomitant peripheral artery disease (PAD) or renal artery stenosis (RAS), and multiterritorial atherosclerotic patients usually have a worse prognosis. We aimed to evaluate the status of peripheral atherosclerosis (AS) and cervicocephalic AS (CAS) in ICVD patients with AS, their correlation, and related risk factors contributing to coexisting cervicocephalic-peripheral AS (CPAS). Based on the severity and extent of AS evaluated by computed tomography angiography and ultrasound, the degree of AS was triple categorized to assess the correlation between CAS and PAD/RAS. CAS and PAD/RAS were defined as the most severe stenosis being ≥ 50% luminal diameter in cervicocephalic or lower limb arteries, and a peak systolic velocity at the turbulent site being ≥ 180 cm/s in the renal artery. Among 403 patients with symptom onset within 30 days, CAS, PAD, and RAS occurrence rates were 68.7%, 25.3%, and 9.9%, respectively. PAD was independently associated with the degree of extracranial and intracranial CAS (p = 0.042, OR = 1.428, 95% CI 1.014–2.012; p = 0.002, OR = 1.680, 95% CI 1.206–2.339), while RAS was independently associated with the degree of extracranial CAS (p = 0.001, OR = 2.880, 95% CI 1.556–5.329). Independent CPAS risk factors included an ischemic stroke history (p = 0.033), increased age (p < 0.01), as well as elevated fibrinogen (p = 0.021) and D-dimer levels (p = 0.019). In conclusion, the occurrence rates of RAS and PAD in ICVD patients with AS is relatively high, and with the severity of RAS or PAD increase, the severity of CAS also increase. Strengthening the evaluation of peripheral AS and controlling elevated fibrinogen might be crucial for preventing and delaying the progression of multiterritorial AS in ICVD patients with AS, thereby improving risk stratification and promoting more effective prevention and treatment strategies.

Abstract 2114: Differences In The Circulating Transcriptome Between Peripheral Artery Disease And Coronary Artery Disease

Introduction: Despite common risk factors, peripheral artery disease (PAD) and coronary artery disease (CAD) exhibit distinct pathological presentations. Previous gene expression profiling of blood from CAD and PAD patients shows alterations in inflammatory and immune related transcripts relative to controls. Studies have not directly compared gene expression in PAD versus CAD. Here, we aimed to use whole-blood RNA sequencing to investigate transcriptomic differences between PAD and CAD. Methods: Whole blood from subjects age 40-65 years with symptomatic PAD (n=20, mean age 59, 75% male, 35% white) and CAD (n=51, mean age 52, 82% male, 78% white) was collected into PAXgene tubes. Patients with concomitant CAD and PAD were excluded. RNA was isolated, sequenced and analyzed to investigate differential circulating gene expression between PAD and CAD subjects adjusting for age, sex, and race/ethnicity. Cell type deconvolution method dtangle was applied to characterize cell type proportions in the whole blood transcriptome. Results: Between PAD and CAD subjects, 106 transcripts were differentially expressed (adjP &lt; 0.1), of which 38 were enriched in PAD and 68 were enriched in CAD. Gene set enrichment analysis (GSEA) revealed 29 pathways differentially expressed (FDR 0.05) between PAD and CAD, of which 8 were enriched in PAD and 21 enriched in CAD. The top enriched pathways in PAD were “specific granule” (Normalized enrichment score [NES] = 2.1, q value = 2.5 x 10 -5 ) and “secretory granule membrane” (NES = 1.9, q = 1.0 x 10 -4 ). Top enriched pathways in CAD were “T cell receptor complex” (NES = 3.1, q = 2.2 x 10 -7 ) and “response to interferon-alpha” (NES = 3.1, q = 2.2 x 10 -9 ). Cellular deconvolution using dtangle showed increased CD8 T-cells (p=0.01) and CD4 Naïve T-cells (p=0.007) in subjects with CAD versus PAD. Conclusion: Whole blood transcriptomics revealed significant differences in the circulating transcriptome between patients presenting with PAD and CAD. Our data suggest upregulation of pathways related to secretory granules in PAD, and enrichment of CD8 and CD4 Naïve T-cells and pathways related to T-cell signaling in CAD. Differences in the circulating transcriptome may help explain pathological and clinical differences between PAD and CAD.

Risk factors for and risk of all-cause and atherosclerotic cardiovascular disease mortality in people with type 2 diabetes and peripheral artery disease: an observational, register-based cohort study

BackgroundType 2 diabetes (T2D) and peripheral artery disease (PAD) are recognized as independent risk factors contributing to excess mortality. Contemporary observational studies exploring the associations of risk factors, and risk of all-cause and atherosclerotic cardiovascular disease mortality in persons with T2D following the onset of incident peripheral artery disease are limited. The objectives of this study were to investigate the associations of risk factors, and assess mortality risks in people with T2D compared with controls without T2D after the onset of PAD.MethodsAll persons with T2D (n = 150,215) registered in the Swedish National Diabetes Register between 2005 and 2009 were included, along with 346,423 controls without T2D matched for sex and age. Data were retrieved from several national registries, capturing information on risk factors, onset of incident peripheral artery disease, other comorbidities, socioeconomic factors, and outcomes. To compare persons with T2D and controls following the onset of peripheral artery disease regarding the risk of all-cause, and atherosclerotic cardiovascular disease mortality, Cox proportional hazard models and Kaplan-Meier curves were employed. A gradient-boosting model was utilized to estimate the relative statistical contribution of risk factors to the modeling of incident mortality risk in people with both T2D and peripheral artery disease.ResultsCrude rates of incident all-cause mortality were higher in individuals with T2D compared with controls, following the onset of PAD (600.4 (95% CI, 581.4-619.8) per 10,000 person-years versus 549.1 (95% CI, 532.1-566.5) per 10,000 person-years). Persons with T2D had an adjusted hazard ratio (HR) for all-cause mortality of 1.12 (95% CI, 1.05–1.19, P < 0.01) compared with controls after onset of incident PAD. The comparable adjusted HR for cardiovascular mortality was 1.13 (95% CI, 1.07–1.19, P < 0.01). High age and hyperglycemia at baseline played a significant role in contributing to the predictive models for incident all-cause and cardiovascular mortality among individuals with both T2D and PAD.ConclusionsThe presence of T2D with concomitant PAD is related to an increased risk of both all-cause and cardiovascular mortality compared with individuals with only PAD. This argues for implementing optimized and intensive treatment strategies for individuals with both conditions.

Ten-year mortality after treating obstructive coronary atherosclerosis with contemporary stents in patients with or without concomitant peripheral arterial disease

Background and aimsPrevious studies in percutaneous coronary intervention (PCI) patients showed a higher 3-year adverse event risk, including all-cause mortality, in those with concomitant peripheral arterial disease (PADs). Ten-year data of mortality and causes of death are scarce. This analysis assessed PCI patients, treated with contemporary drug-eluting stents, the impact of concomitant PADs on very long-term mortality, and causes of death. MethodsWe assessed PCI all-comers from our center who participated in the TWENTE and DUTCH PEERS trials (clinicaltrials.gov:NCT01066650, NCT01331707), comparing patients with versus without PADs. Life status was checked in the Dutch Personal Records Database; causes of death were obtained from medical records. ResultsOf 2705 study patients, 668 (24.7%) died during follow-up: 88/212 (41.5%) patients with PADs and 580/2493 (23.1%) without PADs. In PADs patients, the 10-year rate of all-cause mortality was about twice as high as in patients without PADs (41.5% vs.23.1%, HR: 2.05, 95%-CI: 1.64–2.57, p<0.001). For both groups, the rates of patients dying from various causes of death were: cardiac (14.1% vs.6.8%), vascular (2.8% vs. 1.1%), non-cardiovascular (17.4% vs. 9.8%), and unclear causes (7.1% vs. 5.3%), without a statistically significant between-group difference. When multivariate analysis was adjusted for between-group differences in cardiovascular risk profile, PADs remained predictor of all-cause mortality (adjusted HR: 1.38, 95%-CI: 1.08–1.75, p=0.01). ConclusionsThe 10-year all-cause mortality rate in PCI patients with concomitant PADs was almost twice as high as in those without PADs. Age and other traditional cardiovascular risk factors were higher in patients with PADs, but after correction for these confounders PADs still accounted for almost 40% increase in mortality.

Ticagrelor with or without aspirin following percutaneous coronary intervention in high-risk patients with concomitant peripheral artery disease: A subgroup analysis of the TWILIGHT randomized clinical trial

The optimal antiplatelet regimen after percutaneous coronary intervention (PCI) in patients with peripheral artery disease (PAD) is still debated. This analysis aimed to compare the effect of ticagrelor monotherapy versus ticagrelor plus aspirin in patients with PAD undergoing PCI. In the TWILIGHT trial, patients at high ischemic or bleeding risk that underwent PCI were randomized after 3 months of dual antiplatelet therapy (DAPT) to aspirin or matching placebo in addition to open-label ticagrelor for 12 additional months. In this post-hoc analysis, patient cohorts were examined according to the presence or absence of PAD. The primary endpoint was Bleeding Academic Research Consortium (BARC) 2, 3, or 5 bleeding. The key secondary endpoint was a composite of all-cause death, myocardial infarction (MI), or stroke. Endpoints were assessed at 12 months after randomization. Among 7,119 patients, 489 (7%) had PAD and were older, more likely to have comorbidities, and multivessel disease. PAD patients had more bleeding or ischemic complications than no-PAD patients. Ticagrelor monotherapy compared to ticagrelor plus aspirin was associated with less BARC 2, 3, or 5 bleeding in PAD (4.6% vs 8.7%; HR 0.52; 95%CI 0.25-1.07) and no-PAD patients (4.0% vs 7.0%; HR 0.56; 95%CI 0.45-0.69; interaction P-value .830) and a similar risk of death, MI, or stroke in these 2 groups (interaction P-value .446). Despite their higher ischemic and bleeding risk, patients with PAD undergoing PCI derived a consistent benefit from ticagrelor monotherapy after 3 months of DAPT in terms of bleeding reduction without any relevant increase in ischemic events. CLINICAL TRIAL REGISTRY INFORMATION:: https://www. gov/study/NCT02270242.

ABC as in Arteriopathy, Bleeding, and Coronary disease: Disentangling the prognostic conundrum of patients undergoing percutaneous coronary intervention with concomitant peripheral artery disease.

Key points The prognosis of patients undergoing percutaneous coronary intervention can be informed by attentive appraisal of bleeding risk and peripheral artery disease. While the predictive interplay between bleeding risk and peripheral artery disease is quite complex, the former prognostic factor seems more potent and capable of better guiding decision‐making. Future research is warranted to gauge the benefits of individualized antithrombotic and antiatherosclerotic regimens to improve long‐term prognosis in patients undergoing percutaneous coronary intervention.

Hypertension Management in Peripheral Artery Disease: A Mini Review.

Lower extremity peripheral artery disease (PAD) affects over 230 million adults globally, with hypertension being one of the major risk factors for the development of PAD. Despite the high prevalence, patients with hypertension who have concomitant PAD are less likely to receive adequate therapy. Through this review, we present the current evidence underlying hypertension management in PAD, guideline-directed therapies, and areas pending further investigation. Multiple studies have shown that both high and relatively lower blood pressure levels are associated with worse health outcomes, including increased morbidity and mortality. Hence, guideline-directed recommendation involves cautious management of hypertensive patients with PAD while ensuring hypotension does not occur. Although any antihypertensive medication can be used to treat these patients, the 2017 American Heart Association/American College of Cardiology (AHA/ACC), 2017 European Society of Cardiology (ESC), and 2022 Canadian guidelines favor the use of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) as the initial choice. Importantly, data on blood pressure targets and treatment of hypertension in PAD are limited and largely stem from sub-group studies and post-hoc analysis. Large randomized trials in patients with PAD are required in the future to delineate hypertension management in this complex patient population.

Impact of pain and adverse health outcomes on long-term US testicular cancer survivors.

No study has quantified the impact of pain and other adverse health outcomes on global physical and mental health in long-term US testicular cancer survivors or evaluated patient-reported functional impairment due to pain. Testicular cancer survivors given cisplatin-based chemotherapy completed validated surveys, including Patient-Reported Outcomes Measurement Information System v1.2 global physical and mental health, Patient-Reported Outcomes Measurement Information System pain questionnaires, and others. Multivariable linear regression examined relationships between 25 adverse health outcomes with global physical and mental health and pain-interference scores. Adverse health outcomes with a β^ of more than 2 are clinically important and reported below. Among 358 testicular cancer survivors (median age = 46 years, interquartile range [IQR] = 38-53 years; median time since chemotherapy = 10.7 years, IQR = 7.2-16.0 years), median adverse health outcomes number was 5 (IQR = 3-7). A total of 12% testicular cancer survivors had 10 or more adverse health outcomes, and 19% reported chemotherapy-induced neuropathic pain. Increasing adverse health outcome numbers were associated with decreases in physical and mental health (P < .0001 each). In multivariable analyses, chemotherapy-induced neuropathic pain (β^ = -3.72; P = .001), diabetes (β^ = -4.41; P = .037), obesity (β^ = -2.01; P = .036), and fatigue (β^ = -8.58; P < .0001) were associated with worse global mental health, while being married or living as married benefited global mental health (β^ = 3.63; P = .0006). Risk factors for pain-related functional impairment included lower extremity location (β^ = 2.15; P = .04) and concomitant peripheral artery disease (β^ = 4.68; P < .001). Global physical health score reductions were associated with diabetes (β^ = -3.81; P = .012), balance or equilibrium problems (β^ = -3.82; P = .003), cognitive dysfunction (β^ = -4.43; P < .0001), obesity (β^ = -3.09; P < .0001), peripheral neuropathy score (β^ = -2.12; P < .0001), and depression (β^ = -3.17; P < .0001). Testicular cancer survivors suffer adverse health outcomes that negatively impact long-term global mental health, global physical health, and pain-related functional status. Clinically important factors associated with worse physical and mental health identify testicular cancer survivors requiring closer monitoring, counseling, and interventions. Chemotherapy-induced neuropathic pain must be addressed, given its detrimental impact on patient-reported functional status and mental health 10 or more years after treatment.

Abstract 16776: Recurrent Admission of Acute Decompensated Heart Failure Among Patients With and Without PAD and Its Significance in the CKD Population: The ARIC Cohort Study

Introduction: Peripheral artery disease (PAD) and chronic kidney disease (CKD) are common comorbidities in patients with heart failure (HF). Importantly, CKD is associated with a greater risk of incident PAD and is a known risk factor for worse outcomes in HF patients. However, it is unclear whether the concomitant existence of PAD and CKD increases the risk of recurrent hospitalization for acute decompensated heart failure (ADHF). Methods: Since 2005, the Atherosclerosis Risk in Communities (ARIC) study has conducted hospital surveillance of ADHF with events verified by physician review. Demographics, comorbidities, laboratory data, and medications were abstracted from medical record by trained personnel. Hazard ratios of ADHF readmissions were analyzed using repeat-events Cox regression. Models were adjusted for age, race, sex, year and hospital of admission, coronary artery disease (CAD), COPD, and diabetes mellitus. CKD was defined by glomerular filtration rate [GFR] ≤60 mL/min/1.73m 2 . Results: From 2005-2018, there were 1049 index hospitalizations for ADHF (mean age 77 years, 66% white) with measured creatinine, who were discharged alive. Of these, 155 (15%) had a diagnosis of PAD and 66% had CKD stage 3a or worse (GFR ≤60 mL/min/1.73m 2 ). Patients with PAD had a greater prevalence of smoking, CAD, myocardial infarction, and stroke. The 1-year ADHF readmission rate tended to be higher in patients with PAD, irrespective of CKD stage, compared to those without PAD ( Figure 1 ). After adjustments, PAD was associated with greater hazards of 1-year ADHF readmissions, both in patients with CKD stage 3a or worse (HR, 1.71; 95% CI: 1.25 - 2.32) and without CKD (HR, 1.84; 95% CI: 1.07-3.15). Conclusion: Patients with ADHF and concomitant PAD have a higher prevalence of cardiovascular comorbidities and higher likelihood of 1-year ADHF readmission, irrespective of the CKD status. Focused strategies to prevent ADHF readmission in this high-risk group are warranted.

Pre-participation Withdrawal and Noncompletion of Cardiac Rehabilitation in Peripheral Artery Disease: MATCHED COMPARISONS TO CORONARY ARTERY DISEASE.

Despite the mortality benefit of cardiac rehabilitation (CR) participation, as well as its cost-effectiveness for people with peripheral artery disease (PAD), there are limited data on adherence and completion of CR in those with and without concomitant coronary artery disease (CAD). The objective of this study was to compare CR pre-participation withdrawal and noncompletion between patients with PAD and concomitant PAD and CAD (PAD/CAD) versus matched and unmatched patients with CAD (uCAD). Consecutively referred patients between 2006-2017 with PAD (n = 271) and PAD/CAD (n = 610) were matched to CAD by age, sex, diabetes, smoking status, and referral year. The uCAD (n = 14 487) group was included for comparison. Reasons for withdrawal were ascertained by interview. There were no significant differences in pre-participation withdrawal between PAD and matched CAD (46 vs 43%, P = .49), nor in noncompletion (22 vs 18%, P = .28). Results were similar for PAD/CAD and matched CAD (withdrawal: 36 vs 34%, P = .37) and (noncompletion: 25 vs 23%, P = .46). A smaller proportion of patients with uCAD withdrew (28%) than patients with PAD ( P < .001) and PAD/CAD ( P < .001), with no difference in noncompletion ( P > .40, both). There were no differences between PAD and PAD/CAD and their matched counterparts for medical and nonmedical reasons for withdrawal and noncompletion ( P ≥ .25, all). Pre-participation withdrawal rates were similar between patients with PAD, PAD/CAD, and their matched cohorts but greater than patients with uCAD. Once patients started CR, there were similar completion rates among all groups. Reports that patients with PAD are less likely to start CR may be related to their complex medical profile rather than PAD alone. Strategies to improve participation among patients with PAD should focus on the immediate post-referral period.

Outcome of percutaneous coronary intervention using ultrathin-strut biodegradable polymer sirolimus-eluting versus thin-strut durable polymer zotarolimus-eluting stents in patients with comorbid peripheral arterial disease: a post-hoc analysis from two randomized trials.

In patients with peripheral arterial disease (PADs), who underwent percutaneous coronary intervention (PCI), little is known about the potential impact of using different new-generation drug-eluting stents (DES) on outcome. In PCI all-comers, the results of most between-stent comparisons-stratified by strut thickness-suggested some advantage of coronary stents with ultrathin-struts. The current post-hoc analysis aimed to assess outcomes of PCI with ultrathin-strut biodegradable polymer sirolimus-eluting stents (BP-SES) vs. thin-strut durable polymer zotarolimus-eluting stents (DP-ZES) in patients with PADs. We pooled 3-year patient-level data from two large-scale randomized all-comer trials to compare Orsiro ultrathin-strut BP-SES vs. Resolute-type thin-strut DP-ZES in trial participants with concomitant PADs. BIO-RESORT (December 2012 to August 2015) and BIONYX (October 2015 to December 2016) included all-comer patients who were aged 18 years or older, capable of providing informed consent, and required a PCI. The trials had web-based randomization, with block sizes of 4 and 8, performed in a 1:1:1 or 1:1 fashion. Assessors, research staff, and patients were blinded to the type of stent used. We assessed the composite main clinical endpoint target vessel failure [TVF: cardiac death, target vessel related myocardial infarction (MI), or clinically indicated target vessel revascularization (TVR)], its components, and stent thrombosis. Of 4,830 trial participants, 360 had PADs: 177 (49.2%) were treated with BP-SES and 183 (50.8%) with DP-ZES. Baseline characteristics were similar. For BP-SES, the 3-year TVF rate was 11.0% and for DP-ZES 17.9% [hazard ratio (HR): 0.59, 95% CI: 0.33-1.04; P=0.07]. For BP-SES, the TVR rate was lower than for DP-ZES (4.1% vs. 11.0%; HR: 0.36, 95% CI: 0.15-0.86; P=0.016), but this did not translate into between-group differences in cardiac death or MI. In small vessels (<2.75 mm), the TVR rate was also lower in BP-SES (5.6% vs. 13.9%; HR: 0.32, 95% CI: 0.11-0.91; P=0.024). Definite-or-probable stent thrombosis rates were 1.2% and 2.3% (P=0.43). In PCI patients with PADs, the 3-year TVF incidence was numerically lower in the ultrathin-strut BP-SES vs. the thin-strut DP-ZES group. Furthermore, TVR risk was significantly lower in ultrathin-strut BP-SES, mainly driven by a lower TVR rate in small vessels. BIO-RESORT trial: clinicaltrials.gov (NCT01674803); BIONYX trial: clinicaltrials.gov (NCT02508714).

Risk factor analysis for diabetic foot ulcer-related amputation including Controlling Nutritional Status score and neutrophil-to-lymphocyte ratio.

Diabetic foot ulcer often leads to amputation, and both nutritional status and immune function have been associated with this process. We aimed to investigate the risk factors of diabetic ulcer-related amputation including the Controlling Nutritional Status score and neutrophil-to-lymphocyte ratio biomarker. We evaluated data from hospital in patients with diabetic foot ulcer, performing univariate and multivariate analyses to screen for high-risk factors and Kaplan-Meier analysis to correlate high-risk factors with amputation-free survival. Overall, 389 patients underwent 247 amputations over the follow-up period. After correction to relevant variables, we identified five independent risk factors for diabetic ulcer-related amputation: ulcer severity, ulcer site, peripheral arterial disease, neutrophil-to-lymphocyte ratio and nutritional status. Amputation-free survival was lower for the moderate-to-severe versus mild cases, for the plantar forefoot versus hindfoot location, for the concomitant peripheral artery disease versus without and in the high versus low neutrophil-to-lymphocyte ratio (all p < 0.01). The results showed that ulcer severity (p < 0.01), ulcer site (p < 0.01), peripheral artery disease (p < 0.01), neutrophil-to-lymphocyte ratio (p < 0.01) and Controlling Nutritional Status score (p < 0.05) were independent risk factors for amputation in diabetic foot ulcer patients and have predictive values for diabetic foot ulcer progression to amputation.

The Challenges of Identifying Patients With Peripheral Artery Disease Utilizing Administrative Databases

Peripheral artery disease (PAD) carries a high burden of morbidity when identified in patients with coronary artery disease (CAD). However, identification of patients with concomitant CAD and PAD remains challenging. Using linked administrative databases of 207,026 individuals with CAD between 2002 and 2019 (median follow-up, 4.7 years), a model for PAD was applied to identify baseline PAD and the development of PAD during follow-up. Both baseline PAD and future PAD models demonstrated poor calibration and discrimination (c-statistic 0.618 and 0.583). In the absence of additional variables, the present models are unable to identify patients with concomitant CAD and PAD.

Trends of Concomitant Diabetes and Peripheral Artery Disease and Lower Extremity Amputation in US Medicare Patients, 2007 to 2019.

Previous studies demonstrate geographic and racial/ethnic variation in diagnosis and complications of diabetes and peripheral artery disease (PAD). However, recent trends for patients diagnosed with both PAD and diabetes are lacking. We assessed the period prevalence of concurrent diabetes and PAD across the United States from 2007 to 2019 and regional and racial/ethnic variation in amputations among Medicare patients. Using Medicare claims from 2007 to 2019, we identified patients with both diabetes and PAD. We calculated period prevalence of concomitant diabetes and PAD and incident cases of diabetes and PAD for every year. Patients were followed to identify amputations, and results were stratified by race/ethnicity and hospital referral region. 9 410 785 patients with diabetes and PAD were identified (mean age, 72.8 [SD, 10.94] years; 58.6% women, 74.7% White, 13.2% Black, 7.3% Hispanic, 2.8% Asian/API, and 0.6% Native American). Period prevalence of diabetes and PAD was 23 per 1000 beneficiaries. We observed a 33% relative decrease in annual new diagnoses throughout the study. All racial/ethnic groups experienced a similar decline in new diagnoses. Black and Hispanic patients had on average a 50% greater rate of disease compared with White patients. One- and 5-year amputation rates remained stable at ≈1.5% and 3%, respectively. Native American, Black, and Hispanic patients were at greater risk of amputation compared with White patients at 1- and 5-year time points (5-year rate ratio range, 1.22-3.17). Across US regions, we observed differential amputation rates, with an inverse relationship between the prevalence of concomitant diabetes and PAD and overall amputation rates. Significant regional and racial/ethnic variation exists in the incidence of concomitant diabetes and PAD among Medicare patients. Black patients in areas with the lowest rates of PAD and diabetes are at disproportionally higher risk for amputation. Furthermore, areas with higher prevalence of PAD and diabetes have the lowest rates of amputation.

Gene therapy for diabetic foot ulcers: Interim analysis of a randomised, placebo-controlled phase 3 study of VM202 (ENGENSIS), a plasmid DNA expressing two isoforms of human hepatocyte growth factor.

To evaluate the status of a 7-month phase 3 study conducted to test the effect of intramuscular injections of VM202 (ENGENSIS), a plasmid DNA encoding human hepatocyte growth factor, into the calf muscles of chronic nonhealing diabetic foot ulcers with concomitant peripheral artery disease. The phase 3 study, originally aimed to recruit 300 subjects, was discontinued because of slow patient recruitment. An unprespecified interim analysis was performed for the 44 subjects enrolled to assess the status and determine the future direction. Statistical analyses were carried out for the Intent-to-Treat (ITT) population and separately for subjects with neuroischemic ulcers, using a t-test and Fisher's exact test. A logistic regression analysis was also conducted. VM202 was safe and potentially should have benefits. In the ITT population (N = 44), there was a positive trend toward closure in the VM202 group from 3 to 6 months but with no statistical significance. Levels of ulcer volume or area were found to be highly skewed between the placebo and VM202 groups. Forty subjects, excluding four outliers in both arms, showed significant wound-closing effects at month 6 (P = .0457). In 23 patients with neuroischemic ulcers, the percentage of subjects reaching complete ulcer closure was significantly higher in the VM202 group at months 3, 4, and 5 (P = .0391, .0391, and .0361). When two outliers were excluded, a significant difference was evident in months 3, 4, 5, and 6 (P = .03 for all points). A potentially clinically meaningful 0.15 increase in Ankle-Brachial Index was observed in the VM202 group at day 210 in the ITT population (P = .0776). Intramuscular injections of VM202 plasmid DNA to calf muscle may have promise in the treatment of chronic neuroischemic diabetic foot ulcers (DFUs). Given the safety profile and potential healing effects, continuing a larger DFU study is warranted with modifications of the current protocol and expansion of enrolling sites.

Depression in Patients with Peripheral Artery Disease: An Underdiagnosis with Increased Mortality

Among patients with peripheral artery disease (PAD), depression is diagnosed in 17-25% and negatively impacts wound healing, quality of life, and survival. We hypothesized that depression is underdiagnosed in patients with PAD. Additionally, given the associations between depression and mortality in PAD patients, there is an increased need to investigate the strength of this relationship. The present analysis includes 2 studies to address the following aims: (1) Investigation of the prevalence of concomitant PAD and depression in a cohort from the Southeastern United States, and (2) Examination of the association between depression and all-cause mortality in a cohort of Canadian patients with PAD. STUDY 1: From June-August 2022, the Patient Health Questionnaire Module 9 (PHQ-9) was administered to all patients seeking PAD-related care including medical, wound/podiatric, or vascular interventional/surgical treatment, in the University of North Carolina-Chapel Hill Vascular, Wound, and Podiatry clinics. The PHQ-9 assesses symptoms over 2weeks and is scored 0-27, with higher scores indicating increasingly severe depression. Demographics, primary diagnosis, depression history, and antidepressant prescription were determined through chart review. We compared the proportion of positive depression screenings (PHQ-9≥5) to known depression. Among those treated for depression, the PHQ-9 score severity was evaluated. T-tests and χ2 tests were used to compare means and proportions. STUDY 2: From July 2015 to October 2016, the Geriatric Depression Scale Short Form was administered to adult patients with PAD undergoing revascularization. The Geriatric Depression Scale Short Form is a self-report measure of depression with a score >5 consistent with depression. The prevalence of depression was determined; primary outcome was all-cause mortality at 6months. STUDY 1: In 104 PAD patients (mean age 66.6±11.3years, 37% female), 37% of respondents scored ≥5 on the PHQ-9 survey, indicating at least mild depression. Only 18% of PAD patients had a history of depression, demonstrating a significant difference between the PHQ-9 findings and documented medical history. While depression was underdiagnosed in both men and women, men were more likely to have unrecognized depression (chi-squared statistic=35.117, df=1, P<0.001). Among those with a history of depression, 74% had a current prescription for antidepressant medication, but 57% still had an elevated PHQ-9 score indicating possible undertreatment. STUDY 2: In 148 patients (mean age 70.3±11.0years, 39% female) the prevalence of screened depression was 28.4%, but only 3.3% had a documented history of depression suggesting significant underdiagnosis. Patients with depression were significantly more likely to die within 6months of revascularization (9.5% vs. 0.9%; odds ratio 1.48, 95% confidence interval: 1.08 to 2.29). There was no association between depression and risk of length of stay, reintervention, or readmission. Depression is underdiagnosed and undertreated among patients with PAD, which has grave consequences as it is associated with 1.5 times the odds of mortality within 6months of revascularization. There is a critical need for more robust screenings and comprehensive mental health treatment for patients with concomitant depression and PAD.

History of peripheral artery disease and cardiovascular risk of real-world patients with acute coronary syndrome: Role of inflammation and comorbidities

BackgroundPatients with acute coronary syndromes (ACS) remain at risk of cardiovascular disease (CVD) recurrences. Peripheral artery disease (PAD) may identify a very high risk (VHR) group who may derive greater benefit from intensified secondary prevention. MethodsAmong ACS-patients enrolled in the prospective multi-center Special Program University Medicine (SPUM), we assessed the impact of PAD on major cardiovascular events (MACE: composite of myocardial infarction, stroke and all-cause death) and major bleeding. Multivariate analysis tested the relation of each significant variable with MACE, as well as biomarkers of inflammation and novel markers of atherogenesis. ResultsOut of 4787 ACS patients, 6.0% (n = 285) had PAD. PAD-patients were older (p < 0.001), with established CVD and signs of increased persistent inflammation (hs-CRP; 23.6 ± 46.5 vs 10.4 ± 27.2 mg/l, p < 0.001 and sFlt-1; 1399.5 ± 1501.3 vs 1047.2 ± 1378.6 ng/l, p = 0.018). In-hospital-death (3.2% vs 1.4%, p = 0.022) and -MACE (5.6% vs 3.0%, p = 0.017) were higher in PAD-patients. MACE at 1 year (18.6% vs 7.9%,p < 0.001) remained increased even after adjustment for confounders (Adj. HR 1.53, 95% CI: 1.14–2.08, p = 0.005). Major bleeding did not differ between groups (Adj. HR 1.18; 95% CI 0.71–1.97, p = 0.512). Although PAD predicted MACE, PAD-patients were prescribed less frequently for secondary prevention at discharge. ConclusionsIn this real-world ACS patient cohort, concomitant PAD is a marker of VHR and is associated with increased and persistent inflammation, higher risk for MACE without an increased risk of major bleeding. Therefore, a history of PAD may be useful to identify those ACS patients at VHR who require more aggressive secondary prevention.

The term mixed leg ulcer should no longer be used today

Awound on the lower legs of patients with chronic venous insufficiency (CVI) and peripheral arterial disease (PAD) is today usually referred to as amixed leg ulcer. This does not take into account the different stages of the diseases and, thus, their pathophysiological relevance. In everyday clinical practice, this often leads, among other things, to these patients not receiving compression therapy. The multidisciplinary professional association Initiative Chronische Wunden (ICW) e. V., therefore, recommends that this undifferentiated and misleading term should no longer be used. Instead, aleg ulcer with advanced CVI and concomitant PAD in stageI-IIb according to Fontaine or Rutherford category0-3 should be classified as avenous leg ulcer, while aleg ulcer with advanced PAD in stageIII orIV according to Fontaine or Rutherford category4-6 and advanced CVI is termed an arteriovenous leg ulcer. Aleg ulcer in advanced PAD stageIV according to Fontaine or Rutherford category5 or6 without advanced CVI is called an arterial leg ulcer. Other relevant comorbidities with an influence on wound healing should also be described separately.

Abstract Number ‐ 94: An International, Multi‐Center‐Analysis Of The Safety And Feasibility Of Transradial Approach For Carotid‐Artery Stenting

Introduction Continued advancements in the treatments for neurological disease have helped interventionalists to refine approaches that offer improved surgical efficacy and patient outcomes. Carotid‐artery stenting (CAS) is a safe and effective alternative to carotid endarterectomy (CEA), that allows for revascularization of the internal carotid artery (ICA) in a minimally‐invasive manner. Traditionally, the mainstay for CAS has been through the femoral artery; however, patients with carotid‐artery disease (CAD) often have concomitant peripheral artery disease which confer increased risk of significant life‐threatening access‐site complications, such as retroperitoneal hematoma and limb ischemia. Given this, CAS via the radial artery has become increasingly popular. This study seeks to investigate the safety and feasibility of the transradial approach (TRA), in comparison to the traditional transfemoral approach (TFA), for carotid‐artery stenting. Methods The authors conducted a retrospective analysis of all adult patients (age &gt;18) who underwent carotid‐artery stenting via TRA or TFA over a 4‐year study period (2018‐2021) across 4 different international academic centers. Important variables, such as patient demographics, comorbidities, procedural details, results, and complications were collected. Statistical analysis was performed to assess the strength of association and correlation for these variables. Results A total of 313 patients were enrolled during the study period. CAS via TFA was attempted in 251 patients and via TRA in 62 patients, respectively. Overall, CAS via TRA was found to be successful in 48/62 (76%) patients, and via TFA in 246/251 (98%) patients. Baseline demographics were similar for the two groups, with a female gender predilection, median age of 69, and hypertension and hyperlipidemia serving as the most common medical comorbidities. 14/62 (22.6%) patients who underwent TRA were converted to TFA. Spasm of the radial artery, kinking of the catheter and severe tortuosity of the vessels were the primary reasons for access site conversion. A total of five major access site‐related complications, including two deaths, and seven minor complications were noted in the TFA cohort. No serious access related complications were noted in the TRA group. In the multivariate‐analysis, after adjusting for age, hyperlipidemia, chronic heart failure, combination of stent plus angioplasty and fluoroscopy times, there was no statistically significant difference observed among the 2 groups in terms of procedural (OR: 0.31; CI: 0.36‐2.69; P = 0.29) and overall access site complications (OR: 0.17, CI: 0.02‐1.98, P = 0.16). Conclusions TRA seems to be a safe alternative approach for carotid stenting. In our cohort, no serious access site‐related complications were noted with TRA in comparison to the TFA group. Continued improvements in terms of patient selection, sample size, as well as advances in technique and technology will help to further refine TRA for CAS. Further studies and analysis will need to be performed to delineate the crucial variables that contribute to improved functional outcomes for these patients.