Development and evaluation of a prediction model for peripheral artery disease-related major adverse limb events using novel biomarker data.

OBJECTIVE: Prognostic tools for individuals with peripheral artery disease (PAD) remain limited. We developed prediction models for 3-year PAD-related major adverse limb events (MALE) using demographic, clinical, and biomarker data previously validated by our group. METHODS: We performed a prognostic study using a prospectively recruited cohort of patients with PAD (n = 569). Demographic/clinical data were recorded including sex, age, comorbidities, previous procedures, and medications. Plasma concentrations of three biomarkers (N-terminal pro-B-type natriuretic peptide [NT-proBNP], fatty acid binding protein 3 [FABP3], and FABP4) were measured at baseline. The cohort was followed for 3 years. MALE was the primary outcome (composite of open/endovascular vascular intervention or major amputation). We trained three machine learning models with 10-fold cross-validation using demographic, clinical, and biomarker data (random forest, decision trees, and Extreme Gradient Boosting [XGBoost]) to predict 3-year MALE in patients. Area under the receiver operating characteristic curve (AUROC) was the primary model evaluation metric. RESULTS: Three-year MALE was observed in 162 patients (29%). XGBoost was the top-performing predictive model for 3-year MALE, achieving the following performance metrics: AUROC = 0.88 (95% confidence interval [CI], 0.84-0.94); sensitivity, 88%; specificity, 84%; positive predictive value, 83%; and negative predictive value, 91% on test set data. On an independent validation cohort of patients with PAD, XGBoost attained an AUROC of 0.87 (95% CI, 0.82-0.90). The 10 most important predictors of 3-year MALE consisted of: (1) FABP3; (2) FABP4; (3) age; (4) NT-proBNP; (5) active smoking; (6) diabetes; (7) hypertension; (8) dyslipidemia; (9) coronary artery disease; and (10) sex. CONCLUSIONS: We built robust machine learning algorithms that accurately predict 3-year MALE in patients with PAD using demographic, clinical, and novel biomarker data. Our algorithms can support risk stratification of patients with PAD for additional vascular evaluation and early aggressive medical management, thereby improving outcomes. Further validation of our models for clinical implementation is warranted.

Major Adverse Limb Events in Patients Undergoing Revascularisation for Lower Limb Peripheral Arterial Disease: A Nationwide Observational Study.

OBJECTIVE: Major adverse limb events (MALEs) are frequent in patients with lower extremity peripheral arterial disease (PAD). However, routine care MALE rate estimations after revascularisation are scarce. This study aimed to determine post-procedural MALE rates in revascularised patients with PAD and identify predictors of post-procedural MALEs. METHODS: This was a population based observational study on merged national registry data. Patients with PAD undergoing lower limb revascularisation between 2008 and 2016 were retrieved from the Swedish National Registry for Vascular Surgery. Information on comorbidities, medications, and post-procedural MALE endpoints were identified in national healthcare registries. Primary outcomes of interest were categorised as 2 - 4 point MALE composites that included limb amputation, acute lower limb ischaemia, progression to or relapse of chronic limb threatening ischaemia (CLTI), and ipsilateral re-interventions regardless of indication. Patients with intermittent claudication (IC) and CLTI were analysed separately using Kaplan-Meier estimates. Stepwise Cox proportional hazard models were used for predictor candidate analysis. RESULTS: Overall, 28 021 revascularised patients with PAD were analysed (IC, n = 10 506, 37.5%; CLTI, n = 17 515, 62.5%). During a mean follow up ± standard deviation of 3.2 ± 2.4 years, 5 226 (18.7%), 9 423 (33.6%), and 12 696 (45.3%) patients experienced a 2, 3, and 4 point MALE, respectively. The estimated one year 4 point MALE rates were 21.4% (95% confidence interval [CI] 20.6 - 22.2%) in IC and 46.9% (95% CI 46.1 - 47.7%) in CLTI. Adjusted predictors for experiencing a 4 point MALE in IC were chronic kidney disease (CKD) (hazard ratio [HR] 1.33, 95% CI 1.12 - 1.59) and previous lower limb revascularisation (HR 1.29, 95% CI 1.19 - 1.40). In CLTI, previous contralateral lower limb amputation (HR 1.60, 95% CI 1.47 - 1.73) and CKD (HR 1.25, 95% CI 1.17 - 1.34) were adjusted predictors. CONCLUSION: This study emphasises the very high MALE rates in revascularised patients with lower limb PAD, especially in CLTI. Prior lower limb revascularisation correlated with increased MALE rates in IC patients, while prior lower limb amputation was linked to subsequent MALEs in CLTI. In both IC and CLTI, CKD was associated with poorer outcomes, regardless of applied MALE definition.

Prediabetes increases the risk of major limb and cardiovascular events.

BACKGROUND: Prediabetes, an intermediate stage between normal blood sugar levels and a diabetes mellitus diagnosis, is increasing in prevalence. Severe prediabetes is associated with a similar risk of complications as diabetes, but its relationship with peripheral arterial disease remains underexplored. METHODS: We conducted a retrospective cohort study involving 36,950 adult patients, utilizing electronic medical records from the National Taiwan University Hospital between 2014 and 2019. We employed multivariable Cox regression and Kaplan-Meier analysis with the log-rank test to analyze major adverse limb events (MALE) and major adverse cardiovascular events (MACE) in relation to normal glucose regulation (NGR) and prediabetes. RESULTS: During the 131,783 person-years follow-up, 17,754 cases of prediabetes and 19,196 individuals with normal glucose regulation (NGR) were identified. Kaplan-Meier analysis revealed an increased incidence of both MALE and MACE in individuals with prediabetes. (log-rank p = 0.024 and < 0.001). Prediabetes exhibited a significant association with an elevated risk of MALE (adjusted hazard ratio (aHR) 1.26 [95% CI 1.10-1.46], p = 0.001) and MACE (aHR 1.46 [1.27-1.67], p < 0.001). Furthermore, in individuals with prediabetes, the elevation in the risk of MALE commenced before HbA1c levels surpassed 5.0% (for HbA1c 5.0-5.5%: aHR 1.78 (1.04-3.04), p = 0.036; HbA1c 5.5-6.0%: aHR 1.29 [1.06-1.58], p = 0.012; aHbA1c 6.0-6.5%: aHR 1.39 [1.14-1.70], p < 0.001). Similarly, the onset of increased MACE risk was observed when HbA1c levels exceeded 5.5% (for HbA1c 5.5-6.0%: aHR 1.67 [1.39-2.01], p < 0.001; HbA1c 6.0-6.5%: HR 2.10 [1.76-2.51], p < 0.001). Factors associated with both MALE and MACE in prediabetes include advanced age, male gender, higher body mass index, and a history of heart failure or atrial fibrillation. CONCLUSION: We demonstrated higher susceptibility to MALE and MACE in prediabetes compared to normoglycemic counterparts, notwithstanding lower HbA1c levels. Complications may manifest at an earlier prediabetes trajectory. Intensive lifestyle modification may improve the prognosis of severe prediabetes.

Fatty acid binding protein 4 has prognostic value in peripheral artery disease.

OBJECTIVE: Peripheral artery disease (PAD) remains undertreated, despite its association with major amputation and mortality. This is partly due to a lack of available disease biomarkers. The intracellular protein fatty acid binding protein 4 (FABP4) is implicated in diabetes, obesity, and metabolic syndrome. Given that these risk factors are strong contributors to vascular disease, we assessed the prognostic ability of FABP4 in predicting PAD-related adverse limb events. METHODS: This was a prospective case-control study with 3 years of follow-up. Baseline serum FABP4 concentrations were measured in patients with PAD (n = 569) and without PAD (n = 279). The primary outcome was major adverse limb event (MALE; defined as a composite of vascular intervention or major amputation). The secondary outcome was worsening PAD status (drop in ankle-brachial index ≥0.15). Kaplan-Meier and Cox proportional hazards analyses adjusted for baseline characteristics were conducted to assess the ability of FABP4 to predict MALE and worsening PAD status. RESULTS: Patients with PAD were older and more likely to have cardiovascular risk factors compared with those without PAD. Over the study period, MALE and worsening PAD status occurred in 162 (19%) and 92 (11%) patients, respectively. Higher FABP4 levels were significantly associated with 3-year MALE (unadjusted hazard ratio [HR], 1.19; 95% confidence interval [CI], 1.04-1.27; adjusted HR, 1.18; 95% CI, 1.03-1.27; P = .022) and worsening PAD status (unadjusted HR, 1.18; 95% CI, 1.13-1.31; adjusted HR, 1.17; 95% CI, 1.12-1.28; P < .001). Three-year Kaplan-Meier survival analysis demonstrated that patients with high FABP4 levels had a decreased freedom from MALE (75% vs 88%; log rank = 22.6; P < .001), vascular intervention (77% vs 89%; log rank = 20.8; P < .001), and worsening PAD status (87% vs 91%; log rank = 6.16; P = .013). CONCLUSIONS: Individuals with higher serum concentrations of FABP4 are more likely to develop PAD-related adverse limb events. FABP4 has prognostic value in risk-stratifying patients for further vascular evaluation and management.

Impact of cilostazol on prevention of late failure of autologous vein grafts.

OBJECTIVES: The effectiveness of postoperative medication for the prevention of late graft failure is controversial. We conducted the present study to investigate whether cilostazol improved the mid-term outcomes after infrainguinal autologous vein bypass for chronic limb-threatening ischemia (CLTI). METHODS: From April 1994 to March 2022, we performed 590 de novo infrainguinal bypass procedures using autologous vein grafts (AVGs) in three hospitals. The bypass grafts were classified according to the postoperative prescription of cilostazol. The loss of graft patency and major adverse limb events (MALEs) were set as endpoints. Patients who died within 30 days and grafts that lost primary patency within 30 days after surgery were excluded. Data up to 3 years were analyzed. The cumulative primary patency (PP), assisted primary patency (AP), secondary patency (SP), and freedom from MALE (ffMALE) rates were calculated by the Kaplan-Meier method and compared between the cilostazol group and the non-cilostazol group. After a propensity score matching, same statistical analyses were performed. In addition, a Cox proportional hazards regression analysis that included preoperative factors, intraoperative factors, and postoperative medications was performed to identify whether cilostazol is an independent predictor for the outcomes. RESULTS: A total of 523 AVGs met inclusion criteria. Kaplan-Meier curves showed that the cilostazol group was superior to the non-cilostazol group in all outcomes, while the cilostazol group was superior to the non-cilostazol group in AP and SP after a propensity score matching. A multivariable analysis showed that non-use of cilostazol was identified as an independent predictor for loss of AP, SP, and ffMALE. CONCLUSIONS: Cilostazol improved the mid-term outcomes after infrainguinal autologous vein bypass.

Major adverse events associated with inducible cardiac ischemia during treadmill exercise testing for peripheral artery disease.

BACKGROUND: The coexistence of coronary artery disease and peripheral artery disease (PAD) is well-established. Whether myocardial ischemia by electrocardiography during treadmill testing to evaluate PAD severity is associated with adverse cardiac and limb events has not been established. The aim of the current study is to assess the risk of major adverse cardiac events (MACE), major adverse limb events (MALE), and all-cause mortality in patients with evidence of myocardial ischemia on ECG compared with those without ischemia in patients undergoing treadmill testing for PAD evaluation. METHODS: Patients undergoing treadmill exercise ankle-brachial index (ABI) evaluation (January 1, 2003, to December 31, 2006) were identified using the Mayo Clinic Gonda Vascular Laboratory database. Patients with ischemia by electrocardiogram (ECG) were age and sex matched to patients without ischemia. Outcomes were compared by ECG category. RESULTS: Of 4128 patients who underwent treadmill exercise, 170 (4.1%) had inducible myocardial ischemia by ECG. These were matched with 340 patients without ischemia. The positive ECG group had a higher percentage of diabetes mellitus (31.2% vs 21.8%; P = .02), carotid artery disease (22.4% vs 13.2%; P = .009), exercise-induced angina (14.1% vs 2.9%; P < .0001), and dyspnea (60.6% vs 35.6%; P < .0001). While the resting ABI was similar, the postexercise ABI was lower in the positive ECG group (0.5 vs 0.7; P = .04). After a median follow-up of 8 years, MACE were significantly greater in the positive ECG group (62.4% vs 46.5%; P < .001). MALE were significantly less frequent (17.1% vs 23.2%; P = .02), without an increased risk of amputation. In multivariable analysis, inducible ischemia was associated with higher incidence of MACE (hazard ratio, 1.65; 95% confidence interval, 1.25-2.16; P < .001) and lower incidence of MALE (hazard ratio, 0.51; 95% confidence interval, 0.31-0.84; P < .05). CONCLUSIONS: ECG monitoring during vascular treadmill testing identified a subset of patients with more frequent MACE but less MALE.

Feasibility and Mid-Term Outcomes of Drug-Coated Balloon Angioplasty Between Intermittent Claudication and Critical Limb Ischemia in Patients with Femoropopliteal Disease.

BACKGROUND: The efficacy of drug-coated balloons (DCBs) in critical limb ischemia (CLI) is unclear. To investigate the clinical characteristics and outcomes of DCBs in symptomatic femoropopliteal disease between patients with intermittent claudication (IC) and CLI. METHODS: Data were retrospectively collected from three centers in Taiwan on patients who received DCBs for femoropopliteal lesions between March 2013 and June 2017. We compared the clinical characteristics and outcomes regarding binary restenosis, amputation-free survival (AFS), and major adverse limb events (MALEs) between groups. Cox proportional hazards analysis was used to identify predictors of outcome endpoints. RESULTS: We enrolled a total of 200 affected limbs in 174 patients, including 83 limbs in 71 patients with IC and 117 limbs in 103 patients with CLI. Compared to the patients with claudication, those with CLI were older and had higher proportions of medical comorbidities, tissue inflammation, poor runoff, and vessel calcification. The 3-year rates of freedom from binary restenosis (57% vs. 59%, p = 0.781), and MALEs (77% vs. 67%, p = 0.507) were similar between the two groups. However, the 3-year AFS was significantly higher in the IC group compared to the CLI group (91% vs. 73%, p = 0.001). Lesion length and severe calcification independently predicted binary restenosis, and restenotic lesion predicted MALEs. Age, congestive heart failure, and dialysis were independently associated with AFS. CONCLUSIONS: Despite advanced limb ischemia and comorbidities, the mid-term outcomes in surviving CLI patients were similar to those in the IC patients after treatment with DCBs for femoropopliteal disease.

Antithrombotic Strategies for Patients With Peripheral Artery Disease: JACC Scientific Statement.

Patients with peripheral artery disease (PAD) experience major cardiovascular and limb events. Antithrombotic strategies including antiplatelets and anticoagulants remain a cornerstone of treatment and prevention. Recent trials have shown heterogeneity in the response to antithrombotic therapies in patients presenting primarily with PAD when compared to those presenting primarily with coronary artery disease. In addition, there is observed heterogeneity with regards to the effects of antiplatelets and anticoagulants with respect to different outcomes including cardiovascular and major adverse limb events. This, coupled with risks of bleeding, requires a patient-centered and holistic assessment of benefit-risk when selecting antithrombotic strategies for patients with PAD. A global multidisciplinary work group was convened to evaluate antithrombotic strategies in PAD and to summarize the current state of the art. Common clinical scenarios around antithrombotic decision making were provided. Finally, insights with regard to implementation future investigation were described.

Lipoprotein(a) and Risks of Peripheral Artery Disease, Abdominal Aortic Aneurysm, and Major Adverse Limb Events.

BACKGROUND: Lp(a) (lipoprotein[a])-lowering therapy to reduce cardiovascular disease is under investigation in phase 3 clinical trials. High Lp(a) may be implicated in peripheral artery disease (PAD), abdominal aortic aneurysms (AAAs), and major adverse limb events (MALE). OBJECTIVES: The authors investigated the association of high Lp(a) levels and corresponding LPA genotypes with risk of PAD, AAA, and MALE. METHODS: The authors included 108,146 individuals from the Copenhagen General Population Study. During follow-up, 2,450 developed PAD, and 1,251 AAAs. Risk of MALE was assessed in individuals with PAD at baseline and replicated in the Copenhagen City Heart Study. RESULTS: Higher Lp(a) was associated with a stepwise increase in risk of PAD and AAA (P for trend <0.001). For individuals with Lp(a) levels ≥99th (≥143 mg/dL, ≥307 nmol/L) vs <50th percentile (≤9 mg/dL, ≤17 nmol/L), multivariable-adjusted HRs were 2.99 (95% CI: 2.09-4.30) for PAD and 2.22 (95% CI: 1.21-4.07) for AAA. For individuals with PAD, the corresponding incidence rate ratio for MALE was 3.04 (95% CI: 1.55-5.98). Per 50 mg/dL (105 nmol/L) genetically higher Lp(a) risk ratios were 1.39 (95% CI: 1.24-1.56) for PAD and 1.21 (95% CI: 1.01-1.44) for AAA, consistent with observational risk ratios of 1.33 (95% CI: 1.24-1.43) and 1.27 (95% CI: 1.15-1.41), respectively. In women smokers aged 70 to 79 years with Lp(a) <50th and ≥99th percentile, absolute 10-year risks of PAD were 8% and 21%, and equivalent risks in men 11% and 29%, respectively. For AAA, corresponding risks were 2% and 4% in women, and 5% and 12% in men. CONCLUSIONS: High Lp(a) levels increased risk of PAD, AAA, and MALE by 2- to 3-fold in the general population, opening opportunities for prevention given future Lp(a)-lowering therapies.

Endovascular Revascularization and Outcomes of Critical Limb-Threatening Ischemia in Trinidad and Tobago: The EVENT Pilot Study-Challenges in a Limited-Resource, Caribbean Setting.

INTRODUCTION: This retrospective study investigated major adverse limb events (MALE) and mortality outcomes in critical limb-threatening ischemia (CLTI) patients with tissue loss after an endovascular revascularization-first (EVR-1st) strategy. METHODS: MALE and mortality were assessed in 157 consecutive patients with CLTI and tissue loss from June 2019 to June 2022 at the Eric Williams Medical Sciences Complex, Trinidad and Tobago. RESULTS: 157 patients underwent the EVR-1st strategy, of whom 20 were pivoted to immediate surgical revascularization (SR). Of the remaining 137 patients, successful EVR was achieved in 112, giving a procedural success of 82% and an all-comer overall success of 71%. The mortality and MALE rates were 2.7% and 8.9% at 2 years, respectively. Males and patients with previous major amputations were at significantly higher risk for MALE (p values of 0.016 and 0.018, respectively). There was a statistically significant difference in successful EVR for both Rutherford-Baker (RB) 5 (minor) and RB 6 (major) classifications: 63 (56%) vs. 5 (20%) and 49 (44%) vs. 20 (80%), both with a p value of 0.01. There were no differences in successful EVR amongst Wound, Ischemia, Foot Infection (WIfI) clinical stages. There were no differences in successful EVR amongst the Trans-Atlantic Inter-Society Consensus (TASC II) classifications. CONCLUSIONS: This study may prove clinically informative and applicable for an EVR-1st management strategy for high-risk patients with CLTI in a limited-resource, Caribbean setting. TRIAL REGISTRATION NUMBER: NCT05547022 (retrospectively registered).

Features of asymptomatic contralateral limb in patients with chronic limb-threatening ischemia.

BACKGROUND: The current study aimed to reveal clinical features and prognosis of asymptomatic contralateral limbs in patients undergoing revascularization for chronic limb-threatening ischemia (CLTI). METHODS: We analyzed a database of 520 CLTI patients registered in a prospective, multicenter registry in Japan. Severe ischemia in asymptomatic contralateral limbs was determined as the Wound, Ischemia, and foot Infection (WIfI) classification system Ischemia (I) grade 2/3. RESULTS: The prevalence of diabetes mellitus and dialysis-dependent renal failure was 74.2% and 53.5%, respectively. Asymptomatic limbs accounted for 65.0% [95% confidence interval (CI), 60.9-69.1%] of the overall population, and 55.0% (95% CI, 49.6-60.4%) of the asymptomatic contralateral limbs had WIfI I-2/3. The multivariate analysis identified age ≥65 years, dialysis-dependent renal failure, WIfI I-3 in the index limb, and loss of pressure sensation in the contralateral limb as independent risk factors for WIfI I-2/3 in asymptomatic contralateral limbs (all p < 0.05). The 3-year cumulative incidence rate of major adverse limb events (MALE) in asymptomatic contralateral limbs was 19.3% (95% CI, 15.1-23.7%), whereas that of all-cause mortality was 46.9% (95% CI, 41.0-52.5%). The corresponding rate including a composite of mortality and MALE was 58.8% (95% CI, 52.9-64.6%). In asymptomatic contralateral limbs, the adjusted hazard ratio of WIfI I-2/3 versus I-0/1 was 1.53 (95% CI, 1.11-2.10) for a composite of mortality and MALE, 1.96 (95% CI, 1.14-3.36) for MALE, and 1.37 (95% CI, 0.95-1.96) for mortality (p = 0.009, 0.015, and 0.091, respectively). CONCLUSIONS: Two-thirds of CLTI patients had an asymptomatic contralateral limb, and approximately half of the asymptomatic contralateral limbs were exposed to severe ischemia. Older age, dialysis-dependent renal failure, WIfI I-3 in the index limb, and loss of pressure sensation in the contralateral limb were independently associated with severe ischemia in asymptomatic contralateral limbs. In addition to mortality, MALE commonly occurred in asymptomatic contralateral limbs, especially with WIfI I-2/3.

Major Adverse Events in Patients with Peripheral Artery Disease after Endovascular Revascularization: A Retrospective Study.

OBJECTIVE: For peripheral artery disease (PAD) patients, after endovascular revascularization, it is crucial to manage associated factors that can affect the risk of major adverse events. We aimed to investigate the associated factors of major adverse events in these patients. MATERIALS AND METHODS: We conducted a retrospective longitudinal analysis using the electronic medical records from a tertiary hospital in Korea and included the data of 1263 patients. Eligible patients were categorized into four groups based on diabetes mellitus (DM) and regular exercise. The major adverse events included major adverse limb events and major adverse cardiovascular events. Major adverse events-free survival was assessed using the Kaplan-Meier method, and associated factors of major adverse events were analyzed using Cox proportional hazards analyses. RESULTS: Kaplan-Meier survival curves showed that patients with DM and non-regular exercise had a shorter major adverse events-free survival. The Cox regression analysis showed that for patients with critical limb ischemia or chronic kidney disease, the risk of major adverse events increased, while group variables were not significant. CONCLUSION: Target management of patients with DM, critical limb ischemia, and chronic kidney disease is essential to reduce major adverse events after endovascular revascularization in patients with PAD.

Temporal Trends, Practice Variation, and Associated Outcomes With IVUS Use During Peripheral Arterial Intervention.

BACKGROUND: Intravascular ultrasound (IVUS) has been shown in limited prospective studies to improve procedural outcomes for patients undergoing lower extremity peripheral arterial intervention (PVI). OBJECTIVES: The authors aimed to study temporal trends, practice variation, and associated outcomes with the use of IVUS during PVI among Medicare beneficiaries. METHODS: All PVIs performed from 2016 to 2019 among Medicare beneficiaries aged >65 years were included. Temporal trends in IVUS use were stratified by procedural location (inpatient, outpatient, or ambulatory surgery center [ASC]/office-based laboratory [OBL]) and physician specialty. The primary outcome was major adverse limb events (MALE). Inverse probability weighting was used to account for differences in baseline characteristics. Cox regression with competing risks was used to estimate weighted hazard ratios. RESULTS: During the study period, 543,488 PVIs were included, of which 63,372 (11.7%) used IVUS. A substantial growth in IVUS use was observed, which was driven by procedures performed in ASCs/OBLs (23.6% increase from quarter 1 of 2016 through quarter 4 of 2019). Among operators who used IVUS, there was also notable variation in use (median operator use 5.4% of cases; IQR: 2.2%-15.0%; range, <1%-100%). In weighted analysis, IVUS use during PVI was associated with a lower risk of MALE through a median of 514 days (adjusted hazard ratio: 0.73; 95% CI: 0.70-0.75; P < 0.0001). CONCLUSIONS: In contemporary nationwide data, IVUS use during PVI has increased since 2016, driven by growth in the ASC/OBL setting. However, there remains substantial variation in operator practice. When used during PVI, IVUS was associated with a lower risk of short- and long-term MALE.

Impact of High Lipoprotein(a) Levels on Clinical Outcomes Following Peripheral Endovascular Therapy.

BACKGROUND: Elevated lipoprotein(a) (Lp[a]) levels are an independent risk factor for the development of atherosclerotic diseases, including peripheral artery disease (PAD). However, their prognostic impact in patients with PAD remains unknown. OBJECTIVES: The aim of this study was to examine the prognostic impact of elevated Lp(a) levels in patients with PAD undergoing endovascular therapy (EVT). METHODS: In total, 1,169 patients who underwent successful EVT for symptomatic PAD between September 2016 and August 2021 were included in this study. High Lp(a) levels were defined as >30 mg/dL. The associations of high Lp(a) levels with incident major adverse cardiovascular events (MACE) (all-cause death, myocardial infarction, and stroke) and major adverse limb events (MALE) (repeat revascularization for target limb and major amputation) were analyzed. RESULTS: During a median follow-up period of 1.7 years (IQR: 0.6-3.0 years), 230 MACE (210 deaths, 15 myocardial infarctions, and 22 strokes) and 263 MALE (219 reinterventions and 36 major amputations) were observed. The cumulative incidence rate of MACE (48.1% vs 27.3%) and MALE (67.9% vs 27.2%) was significantly higher in patients with high Lp(a) levels (P < 0.001 for both). The adjusted HR were 1.93 (95% CI: 1.44-2.59; P < 0.001) for MACE and 4.15 (95% CI: 3.14-5.50; P < 0.001) for MALE. These associations were not influenced by low-density lipoprotein cholesterol levels or statin administration (P for interaction >0.05 for all). CONCLUSIONS: Elevated Lp(a) levels were independently associated with incident MACE and MALE in patients with PAD treated with revascularization irrespective of low-density lipoprotein cholesterol level and statin administration.

Principal predictors of major adverse limb events in diabetic peripheral artery disease: A narrative review.

Background and aims: The increasing prevalence of diabetes mellitus is causing a massive growth of peripheral artery disease incidences, a disabling complication of diabetic atherosclerosis, which leads often to the amputation of the affected limb. Critical limb ischemia is the terminal disease stage, which requires a prompt intervention to relieve pain and save limbs. However, patients undergoing revascularization often suffer from cardiovascular, cerebrovascular and major adverse limb events with poor outcomes. Furthermore, the same procedure performed in apparently similar patients has various outcomes and lack of an outcome predictive support causes a high lower limb arterial revascularization rate with disastrous effects for patients. We collected the main risk factors of major adverse limb events in a more readable and immediate format of the topic, to propose an overview of parameters to manage effectively peripheral artery disease patients and to propose basics of a new predictive tool to prevent from disabling vascular complications of the disease. Methods: Most recent and updated literature about the prevalence of major adverse limb events in peripheral artery disease was reviewed to identify possible main predictors. Results: In this article, we summarized major risk factors of limb revascularization failure and disabling vascular complications collecting those parameters principally responsible for major adverse limb events, which provides physio-pathological explanation of their role in peripheral artery disease. Conclusion: We evaluated and listed a panel of possible predictors of MALE (Major Adverse Limb Event) in order to contribute to the development of a predictive score, based on a summary of the main risk factors reported in scientific articles, which could improve the management of peripheral artery disease by preventing vascular accidents.

Outcomes of vascular allograft transplants in the autonomous community of Catalonia, Spain.

BACKGROUND: The transplantation of tissues is a developing practice. Improving cryopreservation techniques and emerging of new immunobiology concepts have let to establish the transplant of vascular allografts as a suitable alternative. This study aims to expose the Catalan experience in vascular allograft transplantation by disclosing basic data about clinical outcomes. MATERIALS AND METHODS: Data about vascular allografts transplants was gathered from the Registry of Vascular and Valvular Transplantation of Catalonia, Spain. Basic data regards to clinical outcomes are presented. Kaplan-Meier and statistical analysis were performed using SPSS Ver. 20 for Mac (Chicago USA). RESULTS: One hundred and seventy-one adults were transplanted. The overall 5-year SR was 51.5%. Survival (SR) differs with the territory revascularized, ranging from 37.5% to 55.6% at five years. Major adverse limb event-free rate ranges from 13.3% to 50.1% according to the area treated. The Primary patency rate is higher in the supra-inguinal revascularization and lowers when a distal vessel target is treated. CONCLUSION: Only one guideline-supported indication is currently done for allografts, and our results match with this indication. Our results are extensive and susceptible to analysis to address future projects, which are required to reconsider new or specific indications. More studies are needed to clarify the outcomes of arterial allografts.

ANTECEDENTES: El trasplante de tejido es una practica clínica en crecimiento. Las mejoras en técnicas de criopreservación y los nuevos conceptos sobre inmunobiología ha permitido que el trasplante vascular sea una alternativa a considerar. Este estudio expone la experiencia catalana en trasplante de tejido vascular mediante la exposición de datos clínicos. MATERIALES AND MÉTODOS: Los datos sobre trasplantes de aloinjertos vasculares se obtuvieron del Registro de trasplantes vasculares y valvulares de Cataluña, España (ReVAC). Se presentan datos básicos relacionados con los resultados clínicos. Kaplan Meier y el análisis estadístico se realizó con SPSS Ver. 20 para Mac (Chicago EE. UU.). RESULTADOS: 171 adultos fueron trasplantados. La supervivencia a 5 años fue del 51,5%. La supervivencia (SR) difiere con el territorio revascularizado, oscilando entre el 37,5% y el 55,6% a los cinco años. La tasa de sujetos libres de evento mayor en la extremidad (MALE-Free Rate) oscila entre el 13,3% y el 50,1% según la zona tratada. La tasa de permeabilidad primaria es mayor en la revascularización supra-inguinal y menor cuando se trata un vaso diana distal. CONCLUSIÓN: En la actualidad, solo hay una indicación de trasplante de aloinjertos respaldada por las guías clínicas y nuestros resultados coinciden con esta indicación. Nuestros resultados son amplios y susceptibles de análisis para abordar proyectos futuros que se requieren para reconsiderar indicaciones nuevas o específicas. Se necesitan más estudios para aclarar los resultados de los aloinjertos arteriales.

Impact of sarcopenia in aortoiliac occlusive disease in Mediterranean population.

BACKGROUND: This study aims to validate the psoas muscle area and psoas muscle density as morphometric predictors in cardiovascular and cerebrovascular endpoints in patients with extensive aortoiliac peripheral arterial disease. METHODS: A total of 57 patients (55 males, 2 females; mean age 60±8.2 years; range, 35 to 83 years) with Trans-Atlantic Inter-Society Consensus type D lesions who underwent revascularization at two Portuguese tertiary hospitals between January 2013 and July 2019 were retrospectively analyzed. The patients with a recent (<6 months) computed tomography scan prior to the revascularization procedure were included in the study. Both centers offered to their patients open and endovascular repair of aortoiliac peripheral arterial disease. Major adverse cardiovascular and cerebrovascular events and major adverse limb events were evaluated. RESULTS: The median follow-up was 20 months. The mean survival rate was 93±3.4% at 30 days and 62.7±8.6% at 48 months. The discriminative thresholds found in this population were 2,175.8 mm2 for total psoas area and 51.75 Hounsfield unit for psoas muscle density. There was a statistically significant difference in the one-year survival rate (p=0.003 and p=0.291, respectively) and major adverse cardiovascular and cerebrovascular events (p=0.005 and p=0.206, respectively) for total psoas area compared to psoas muscle density. CONCLUSION: Total psoas area shows a prognostic value for survival and major adverse cardiovascular and cerebrovascular events in this patient population.

Peripheral Revascularization in Patients With Peripheral Artery Disease With Vorapaxar: Insights From the TRA 2°P-TIMI 50 Trial.

OBJECTIVES: The aim of this study was to determine whether the reduction in peripheral revascularization with vorapaxar in patients with peripheral artery disease (PAD) is directionally consistent across indications, including acute limb ischemia, progressively disabling symptoms, or both. BACKGROUND: The protease-activated receptor-1 antagonist vorapaxar reduces peripheral revascularization in patients with PAD. METHODS: The TRA 2°P-TIMI 50 (Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events-Thrombolysis in Myocardial Infarction 50) trial randomized 26,449 patients with histories of myocardial infarction, stroke, or symptomatic PAD to vorapaxar or placebo on a background of standard therapy. A total of 5,845 patients had a known history of PAD at randomization. Peripheral revascularization procedures reported by the site were a pre-specified outcome. We explored whether the benefit of vorapaxar was consistent across indication and type of procedure. RESULTS: Of the 5,845 patients with known PAD, a total of 934 (16%) underwent at least 1 peripheral revascularization over 2.5 years (median). More than one-half (55%) were for worsening claudication, followed by critical limb ischemia (24%), acute limb ischemia (16%), and asymptomatic severe stenosis (4%). Vorapaxar significantly reduced peripheral revascularization (19.3% for placebo, 15.4% for vorapaxar; hazard ratio: 0.82; 95% confidence interval: 0.72 to 0.93; p = 0.003), with a consistent pattern of efficacy across indication. CONCLUSIONS: Vorapaxar reduces peripheral revascularization in patients with PAD. This benefit of vorapaxar is directionally consistent across type of procedure and indication. (Trial to Assess the Effects of Vorapaxar [SCH 530348; MK-5348] in Preventing Heart Attack and Stroke in Patients With Atherosclerosis [TRA 2°P - TIMI 50] [P04737]; NCT00526474).

3-Year Outcomes of the OLIVE Registry, a Prospective Multicenter Study of Patients With Critical Limb Ischemia: A Prospective, Multi-Center, Three-Year Follow-Up Study on Endovascular Treatment for Infra-Inguinal Vessel in Patients With Critical Limb Ischemia.

OBJECTIVES: This study sought to investigate the 3-year follow-up results of OLIVE registry patients. BACKGROUND: Although favorable 12-month clinical outcomes after endovascular therapy (EVT) in OLIVE registry patients with critical limb ischemia (CLI) from infrainguinal disease have been reported, long-term results after EVT remain unknown. METHODS: This was a prospective multicenter registry study that consecutively enrolled patients who received infrainguinal EVT for CLI. The primary outcome was 3-year amputation-free survival (AFS), whereas secondary outcome measures were 3-year freedom from major adverse limb events (MALE), wound-free survival, and wound recurrence rate. Prognostic predictors for each outcome were also elucidated by Cox proportional hazard regression analysis or the log-rank test. RESULTS: The completion rate of 3-year follow-up was 95%. Three-year AFS, freedom from MALE, and wound-free survival rates were 55.2%, 84.0%, and 49.6%, respectively. Wound recurrence out to 3 years was 43.9%. After multivariable analysis, age (hazard ratio [HR]: 1.43, p = 0.001), body mass index ≤18.5 (HR: 2.17, p = 0.001), dialysis (HR: 2.91, p < 0.001), and Rutherford 6 (HR: 1.64, p = 0.047) were identified as predictors of 3-year major amputation or death. Statin use (HR: 0.28, p = 0.02), Rutherford 6 (HR: 2.40, p = 0.02), straight-line flow to the foot (HR: 0.27, p = 0.001), and heart failure (HR: 1.96, p = 0.04) were identified as 3-year MALE predictors. Finally, CLI due to isolated below-the-knee lesion was a wound recurrence predictor (HR: 4.28, p ≤ 0.001). Three-year survival, freedom from major amputation, and reintervention rates were 63.0%, 87.9%, and 43.2%. CONCLUSIONS: In CLI patients with infrainguinal lesions, 3-year clinical results of EVT were reasonable despite high reintervention and moderate ulcer recurrence rate. (A Prospective, Multi-Center, Three-Year Follow-Up Study on Endovascular Treatment for Infra-Inguinal Vessel in Patients With Critical Limb Ischemia [OLIVE 3-Year Follow-Up Study]; UMIN000014759).