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Background: The potential preventive effect of fenofibrate on lower extremity amputation (LEA) and peripheral arterial disease (PAD) in patients with type 2 diabetes (T2D) is not fully elucidated., Methods: We selected adult patients ≥ 20 years of age with T2D from the Korean National Health Insurance Service Database (2009-2012). The fenofibrate users were matched in a 1:4 ratio with non-users using propensity scores (PS). The outcome variables were a composite of LEA and PAD and the individual components. The risks of outcomes were implemented as hazard ratio (HR) with 95% confidence intervals (CI). For safety issues, the risks of acute kidney injury, rhabdomyolysis and resulting hospitalization were analyzed., Results: A total of 114,920 patients was included in the analysis with a median follow-up duration of 7.6 years (22,984 and 91,936 patients for the fenofibrate user and non-user groups, respectively). After PS matching, both groups were well balanced. The fenofibrate group was associated with significantly lower risks of composite outcome of LEA and PAD (HR 0.81; 95% CI 0.70-0.94), LEA (HR 0.76; 95% CI 0.60-0.96), and PAD (HR 0.81; 95% CI 0.68-0.96). The risk of acute kidney injury, rhabdomyolysis, or hospitalization for these events showed no significant difference between the two groups. Subgroup analyses revealed consistent benefits across age groups, genders, and baseline lipid profiles., Conclusions: This nationwide population-based retrospective observational study suggests that fenofibrate can prevent LEA and PAD in patients with T2D who are on statin therapy., (© 2024. The Author(s).)

Background: Arterial and venous cardiovascular conditions, such as coronary artery disease (CAD), peripheral artery disease (PAD), and venous thromboembolism (VTE), are genetically correlated. Interrogating underlying mechanisms may shed light on disease mechanisms. In this study, we aimed to identify (1) epidemiological and (2) causal, genetic relationships between metabolites and CAD, PAD, and VTE., Methods: We used metabolomic data from 95 402 individuals in the UK Biobank, excluding individuals with prevalent cardiovascular disease. Cox proportional-hazards models estimated the associations of 249 metabolites with incident disease. Bidirectional 2-sample Mendelian randomization (MR) estimated the causal effects between metabolites and outcomes using genome-wide association summary statistics for metabolites (n=118 466 from the UK Biobank), CAD (n=184 305 from CARDIoGRAMplusC4D 2015), PAD (n=243 060 from the Million Veterans Project), and VTE (n=650 119 from the Million Veterans Project). Multivariable MR was performed in subsequent analyses., Results: We found that 196, 115, and 74 metabolites were associated ( P <0.001) with CAD, PAD, and VTE, respectively. Further interrogation of these metabolites with MR revealed 94, 34, and 9 metabolites with potentially causal effects on CAD, PAD, and VTE, respectively. There were 21 metabolites common to CAD and PAD and 4 common to PAD and VTE. Many putatively causal metabolites included lipoprotein traits with heterogeneity across different sizes and lipid subfractions. Small VLDL (very-low-density lipoprotein) particles increased the risk for CAD while large VLDL particles decreased the risk for VTE. We identified opposing directions of CAD and PAD effects for cholesterol and triglyceride concentrations within HDLs (high-density lipoproteins). Subsequent sensitivity analyses including multivariable MR revealed several metabolites with robust, potentially causal effects of VLDL particles on CAD., Conclusions: While common vascular conditions are associated with overlapping metabolomic profiles, MR prioritized the role of specific lipoprotein species for potential pharmacological targets to maximize benefits in both arterial and venous beds., Competing Interests: P. Natarajan reports research grants from Allelica, Amgen, Apple, Boston Scientific, Genentech/Roche, and Novartis; personal fees from Allelica, Apple, AstraZeneca, Blackstone Life Sciences, Creative Education Concepts, CRISPR Therapeutics, Eli Lilly & Co, Foresite Labs, Genentech/Roche, GV, HeartFlow, Magnet Biomedicine, Merck, and Novartis; scientific advisory board membership of Esperion Therapeutics, Preciseli, and TenSixteen Bio; being a scientific cofounder of TenSixteen Bio; equity in MyOme, Preciseli, and TenSixteen Bio; and spousal employment at Vertex Pharmaceuticals, all unrelated to the present work. The other authors report no conflicts.

Background: There is a dearth of research on immunophenotyping in peripheral artery disease (PAD). This study aimed to describe the baseline characteristics, immunophenotypic profile, and quality of life (QoL) of participants with PAD in the Project Baseline Health Study (PBHS)., Methods: The PBHS study is a prospective, multicenter, longitudinal cohort study that collected clinical, molecular, and biometric data from participants recruited between 2017 and 2018. In this analysis, baseline demographic, clinical, mobility, QoL, and flow cytometry data were stratified by the presence of PAD (ankle brachial index [ABI] ≤0.90)., Results: Of 2,209 participants, 58 (2.6%) had lower-extremity PAD, and only 2 (3.4%) had pre-existing PAD diagnosed prior to enrollment. Comorbid smoking (29.3% vs 14%, P < .001), hypertension (54% vs 30%, P < .001), diabetes (25% vs 14%, P = .031), and at least moderate coronary calcifications (Agatston score >100: 32% vs 17%, P = .01) were significantly higher in participants with PAD than in those with normal ABIs, as were high-sensitivity C-reactive protein levels (5.86 vs 2.83, P < .001). After adjusting for demographic and risk factors, participants with PAD had significantly fewer circulating CD56-high natural killer cells, IgM+ memory B cells, and CD10/CD27 double-positive B cells (P < .05 for all)., Conclusions: This study reinforces existing evidence that a large proportion of PAD without claudication may be underdiagnosed, particularly in female and Black or African American participants. We describe a novel immunophenotypic profile of participants with PAD that could represent a potential future screening or diagnostic tool to facilitate earlier diagnosis of PAD., Gov Identifier: NCT03154346, https://clinicaltrials.gov/ct2/show/NCT03154346., Competing Interests: Conflict of interest JAG reports research funding from the Department of Veterans Affairs. NL reports grants from the NIH and AHA. He is a director of Bitterroot Bio and receives consulting fees unrelated to this study. FR reports consulting relationships with Healthpals, Amgen, NovoNordisk (CEC), and Novartis outside the submitted work. AH reports grants from Verily; grants and personal fees from AstraZeneca, Amgen, Bayer, Merck, and Novartis; and personal fees from Boston Scientific outside the submitted work. KM reports grants from Verily, Afferent, the American Heart Association (AHA), Cardiva Medical Inc, Gilead, Luitpold, Medtronic, Merck, Eidos, Ferring, Apple Inc, Sanifit, and St. Jude; grants and personal fees from Amgen, AstraZeneca, Bayer, CSL Behring, Johnson & Johnson, Novartis, and Sanofi; and personal fees from Anthos, Applied Therapeutics, Elsevier, Inova, Intermountain Health, Medscape, Mount Sinai, Mundi Pharma, Myokardia, Novo Nordisk, Otsuka, Portola, SmartMedics, and Theravance outside the submitted work. RVS reports advisory board fees from Philips; research support from ACIST Medical. The other authors have no conflicts of interest to disclose., (Published by Elsevier Inc.)

Background: Cardiovascular disease (CVD) and cancer are the two leading causes of death worldwide. Given their high prevalence, it is important to understand the disease burden of cancer mortality in CVD patients., Objective: We aimed to evaluate whether patients with incident CVD have a higher risk of malignancy-related mortality, compared to the general population without CVD., Methods: We performed a national population-based cohort study selecting patients with incident CVD in the Netherlands between 01 April 2000 and 31 December 2005. A reference cohort was selected from the Dutch population using age, sex and ethnicity. Mortality follow-up data were evaluated after data linkage of national registries from Statistics Netherlands until 31 December 2020., Results: A total of 2,240,879 individuals were selected with a mean follow-up of 12 years (range 0.4-21.0), of which 738,666 patients with incident CVD with a mean age of 71 ± 15 years. Malignancy mortality per 1000 person years was 84 for the reference group and 118 for patients with CVD, with the highest rate of 258 in patients with heart failure. Patients with CVD had a higher malignancy mortality risk, compared to the reference group: HR 1.35 (95%CI 1.33-1.36). Highest risks were observed in patients with venous diseases (HR 2.27, 95%CI 2.17-2.36) and peripheral artery disease (HR 1.87, 95%CI 1.84-2.01)., Conclusion: Results show that CVD predisposes to a higher cancer mortality rate. Of all CVD subtypes, HF patients have the highest cancer mortality rate and the hazards were highest in patients with venous diseases and peripheral artery disease., (© 2024 The Authors. European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.)

Background: The ankle-brachial index (ABI) is the ratio of the ankle and brachial systolic blood pressures. In the clinical setting, low ABI (< 0.9) is an indicator of peripheral atherosclerosis, while high ABI (> 1.4) is a sign of arterial stiffness and calcification. The purpose of the current study was to investigate the association between ABI and physical activity levels, measured by accelerometer., Methods: The Swedish CArdioPulmonary bioImage Study (SCAPIS) is a Swedish nationwide population-based cross-sectional cohort for the study of cardiovascular and pulmonary diseases, in which individuals aged 50-64 years were randomly invited from the general population. The study population with data on ABI, physical activity, and sedentary time based on accelerometry was 27,737. Differences between ABI categories and associations to sedentary behavior, moderate to vigorous physical activity (MVPA), and other metabolic characteristics were compared. ABI was categorized as low, ABI ≤ 0.9, borderline, ABI 0.91-0.99, normal, ABI 1.0-1.39, and high, ABI ≥ 1.4., Results: Prevalence of low ABI was higher in the most sedentary quartiles compared to the least sedentary (0.6% vs. 0.1%, p < 0.001). The most sedentary individuals also exhibited higher BMI, higher prevalence of diabetes and hypertension. The proportion of wake time spent in MVPA was lowest in those with low ABI (0.033 ± 0.004; p < 0.001) and highest in those with ABI > 1.4 (0.069 ± 0.001; p < 0.001) compared to those with normal ABI. Compared to normal ABI, the proportion of sedentary time was highest in those with low ABI (0.597 ± 0.012; p < 0.001) and lowest in those with ABI > 1.4 (0.534 ± 0.002; p = 0.004)., Conclusion: This population-based study shows that middle-aged individuals with ABI > 1.4 have the highest level of physical activity, while individuals with a lower ABI, especially those with ABI < 0.9, are less active and spend more time sedentary. Future studies are needed to understand the relationships between ABI, physical activity, and the risk of peripheral arterial and cardiovascular disease in the general population., (© 2024. The Author(s).)

Introduction: Peripheral arterial disease (PAD) indicates generalised atherosclerotic disease but is often asymptomatic. The prevalence and potential risk factors of PAD were studied in ECHORN cohort study participants., Methods: Representative samples of community-dwelling people ≥40 years of age residing in Barbados, Puerto Rico, Trinidad, and the USVI were recruited. The survey included questions on diabetes, hypertension, heart disease and smoking status. Body Mass Index, HbA1c, blood glucose and lipids were determined. Ankle brachial index (ABI) was evaluated in one leg. An oscillometric device measured arm and leg systolic BP simultaneously. ABI classifications were PAD ≤0.90, borderline 0.91 to 0.99, normal 1.00 to 1.40, and non-compressible >0.40. Multivariable logistic regression tested associations of potential risk factors with PAD., Results: Of 2772 participants (mean age 57.3, 65.2% female), 35.8% were overweight, 38.1% obese, 32.4% had diabetes, 60% hypertension, and 15.4% reported heart. ABI prevalence (95% CI) by category was PAD 4.4% (3.6%, 5.1%), borderline 5.2% (4.4%, 6.1%), normal 87.0% (85.8%, 88.3%) and noncompressible 3.4% (2.7%, 4.0%). Female sex (OR 1.72, 95% CI 1.07 to 2.77), diabetes (OR 2.23, 95% CI 1.47 to 3.4), heart disease history (OR 1.74, 95% CI 1.07 to 2.83) and less than high school education vs having a university degree (OR 2.49, 95% CI 1.19 to 5.22) were independently associated with PAD., Conclusions: Testing one leg only would underestimate PAD prevalence. Increasing the ABI cutoff for identifying PAD to <1.0 when using oscillometric devices is suggested by some studies but would more than double the estimated prevalence. Guidelines need to address this issue. Female sex and lower educational attainment are important considerations when screening. While diabetes and a history of heart disease were confirmed as risk factors, the lack of association of increasing age and cigarette smoking with PAD was unexpected., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Adams et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Platelets are key mediators of atherothrombosis, yet, limited tools exist to identify individuals with a hyperreactive platelet phenotype. In this study, we investigate the association of platelet hyperreactivity and cardiovascular events, and introduce a tool, the Platelet Reactivity ExpreSsion Score (PRESS), which integrates platelet aggregation responses and RNA sequencing. Among patients with peripheral artery disease (PAD), those with a hyperreactive platelet response (>60% aggregation) to 0.4 µM epinephrine had a higher incidence of the 30 day primary cardiovascular endpoint (37.2% vs. 15.3% in those without hyperreactivity, adjusted HR 2.76, 95% CI 1.5-5.1, p = 0.002). PRESS performs well in identifying a hyperreactive phenotype in patients with PAD (AUC [cross-validation] 0.81, 95% CI 0.68 -0.94, n = 84) and in an independent cohort of healthy participants (AUC [validation] 0.77, 95% CI 0.75 -0.79, n = 35). Following multivariable adjustment, PAD individuals with a PRESS score above the median are at higher risk for a future cardiovascular event (adjusted HR 1.90, CI 1.07-3.36; p = 0.027, n = 129, NCT02106429). This study derives and validates the ability of PRESS to discriminate platelet hyperreactivity and identify those at increased cardiovascular risk. Future studies in a larger independent cohort are warranted for further validation. The development of a platelet reactivity expression score opens the possibility for a personalized approach to antithrombotic therapy for cardiovascular risk reduction., (© 2024. The Author(s).)

There is a relative scarcity of large-scale population studies investigating the relationship between the insulin resistance index of homeostasis model assessment (HOMA-IR) and vascular damage. Therefore, we assessed the association between HOMA-IR and vascular damage in adults aged 18 years and older in China. A total of 17,985 research subjects were included. Vascular damage markers and relevant laboratory tests were measured. HOMA-IR was calculated as (fasting insulin * fasting blood glucose)/22.5. Vascular damage included arteriosclerosis (ba-PWV > 1800 cm/s), peripheral artery disease (ABI < 0.9), and microalbuminuria (UACR > 30 mg/g). The relationship between HOMA-IR and vascular damage was analyzed using the RCS. The restricted cubic spline (RCS) analysis suggested that HOMA-IR was nonlinearly associated with arteriosclerosis (P for no-liner < 0.01), peripheral artery disease (P for no-liner < 0.01), and microalbuminuria (P for no-liner < 0.01). Further segmented regression analyses revealed that in study subjects with HOMA-IR < 5, we found that HOMA-IR was associated with an increased OR for arteriosclerosis (OR: 1.36, 95% CI (1.28, 1.45), P < 0.01), peripheral artery disease (OR: 1.33, 95% CI (1.10, 1.60), P < 0.01) and microalbuminuria (OR: 1.59, 95% CI (1.49, 1.70), P < 0.01). HOMA-IR is an independent risk factor for vascular damage, both macrovascular and microvascular. The phenomenon of saturation of HOMA-IR with vascular damage needs further investigation., (© 2024. The Author(s).)

Background: At present, no studies explored whether dietary fiber intake was associated with the risk of peripheral artery disease (PAD) in hypertensive patients. This study assessed the association between dietary fiber intake and PAD in hypertensive patients., Methods: This cross-sectional study collected the data of 4628 participants with the measurement of ankle-brachial pressure index in the National Health and Nutrition Examination Surveys database. Univariate logistic regression analysis was applied to identify variables associated with PAD as confounding factors. Univariate and multivariable logistic regression analyses were used to explore the association between dietary fiber intake and PAD in hypertensive patients. Subgroup analysis was stratified by age, cardiovascular disease, dyslipidemia, diabetes, smoking, and physical activity., Results: After adjusting for confounding factors, decreased risk of PAD was observed in hypertensive patients with dietary fiber intake > 21 g [odds ratio (OR) = 0.67, 95% confidence interval (CI) 0.46-0.99]. Compared with people with dietary fiber intake ≤ 21 g, those with dietary fiber intake > 21 g were associated with decreased risk of PAD in hypertensive patients < 60 years (OR = 0.23, 95%CI 0.08-0.66). In hypertensive patients without dyslipidemia, dietary fiber intake > 21 g were associated with reduced risk of PAD (OR = 0.33, 95%CI 0.12-0.95). Decreased risk of PAD was also found in hypertensive patients without diabetes in dietary fiber intake > 21 g group (OR = 0.50, 95%CI 0.31-0.78). Dietary fiber intake > 21 g was linked with reduced risk of PAD in hypertensive patients in never smoke group (OR = 0.46, 95%CI 0.24-0.86)., Conclusion: Higher dietary fiber intake was associated with reduced risk of PAD in hypertensive patients, suggesting the importance of increase the daily dietary quality especially fiber intake in hypertensive people., (© 2024. The Author(s).)

Background: Lower extremity peripheral arterial disease is a potentially lethal cardiovascular complication in patients undergoing hemodialysis. Anemia is a risk factor for cardiovascular disease among the hemodialysis population. However, whether blood hemoglobin concentration is associated with the risk of peripheral arterial disease progression in this population remains undetermined., Methods and Results: This is an extension of a 4-year multicenter, prospective, observational cohort study to 10 years. A total of 3504 Japanese patients undergoing maintenance hemodialysis were recruited between 2006 and 2007. The primary exposure was blood hemoglobin concentration at baseline. The main outcome was the first-ever incidence of major adverse limb events (MALE), composed of endovascular treatment, bypass surgery, and amputation. Multivariable-adjusted Cox proportional hazards model, Fine-Gray subdistribution hazards model, restricted cubic spline analysis, and restricted mean survival time analysis were used to determine the association of blood hemoglobin concentration with the incidence of MALE. During a median follow-up of 8.0 years, 257 patients experienced MALE. A Cox proportional hazards model showed that the risk of MALE in patients with blood hemoglobin concentrations <10.0 g/dL was significantly higher than in patients with concentrations of 11.0 to 11.9 g/dL, even after adjusting for confounding factors. In contrast, elevated hemoglobin concentration (≥12.0 g/dL) was not significantly associated with increased risk of MALE. Similar associations were observed when the Fine-Gray subdistribution regression model was used by setting all-cause mortality as the competing risk., Conclusions: A low blood hemoglobin concentration is an independent risk factor for peripheral arterial disease progression in patients undergoing maintenance hemodialysis.

Abstract: The dual pathway inhibition (DPI) with low-dose rivaroxaban and aspirin in patients with stable atherosclerotic vascular disease reduces the occurrence of cardiovascular events, with no significant increase of intracranial or other critical organ bleedings. Our observational study aimed to describe the clinical performance, adherence, and persistence of DPI therapy among a real-world setting of patients with an established diagnosis of coronary artery (CAD) and/or peripheral artery disease (PAD). We prospectively included all consecutive patients with an established diagnosis of CAD and/or PAD treated with aspirin (ASA) 100 mg once daily and rivaroxaban 2.5 mg twice daily. Clinical evaluation was performed at baseline, before starting treatment, at 1 month, and every 6 months after the study drug administration. A total of 202 consecutive patients (mean age 66 ± 10 years; male 80%) eligible to DPI therapy were included. During a mean follow-up of 664 ± 177 days, the incidence rate of major bleedings and of major adverse cardiovascular events was 0.8 and 1.1 per 100 patients/year, respectively. The adherence to pharmacological treatment was 99%. Additionally, 13.4% of patients suspended the DPI therapy during the follow-up. Minor bleedings resulted the most common cause of both temporary and permanent DPI therapy discontinuation. This observational study supports the safety of DPI with low-dose rivaroxaban and aspirin among patients with CAD and PAD in a real-world setting, showing high persistence and maximum adherence to medical treatment., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: To examine whether prior gestational diabetes mellitus (GDM) is associated with prevalent coronary heart disease (CHD), cerebrovascular disease (CeVD) and peripheral arterial disease (PAD), and all-cause mortality, in community-based women with type 2 diabetes., Methods: Baseline prevalences of CHD/CeVD/PAD/prior GDM were determined in 718 females (mean ± SD age 65.5 ± 11.9 years) from the Fremantle Diabetes Study Phase II. Deaths between baseline (2008-2011) and end-2016 were ascertained. Cox regression identified predictors of mortality with GDM as a candidate variable., Results: Compared to the 673 women without GDM, the 39 (5.4 %) with prior GDM were younger, more likely Aboriginal, smokers and obese, had longer diabetes duration and higher HbA 1c levels, and were more dyslipidemic (P ≤ 0.046). Prevalences of CHD (24.6 versus 23.1 %), CeVD (7.5 % versus 2.6 %) and PAD (27.5 % versus 23.7 %) were not significantly different in those without versus with prior GDM (P ≥ 0.35). There were 116 deaths (16.2 %) during 6.8 ± 1.6 years of follow-up. Age, Aboriginal ethnicity, marital status, current smoking, heart rate, estimated glomerular filtration rate, CHD and PAD were independently associated with all-cause mortality (P ≤ 0.023); GDM status did not add to the most parsimonious model (P = 0.62)., Conclusions: Prior GDM does not increase CVD risk or all-cause mortality in women with type 2 diabetes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Peripheral artery disease (PAD) has not only been associated with recurrent hospitalization for acute decompensated heart failure (ADHF) but is also associated with chronic kidney disease (CKD), a known risk factor for worse heart failure outcomes. The interaction of CKD with PAD in post-discharge ADHF outcomes is not well known., Methods: Since 2005, hospitalizations for ADHF were sampled from 4 US regions by the Atherosclerosis Risk in Communities (ARIC) study and classified by physician review. We examined the adjusted association of PAD with 1-year ADHF readmissions, in patients with and without CKD (defined by glomerular filtration rate [GFR] ≤60 mL/min/1.73 m 2 [stage 3a or worse])., Results: From 2005 to 2018, there were 1049 index hospitalizations for patients with ADHF (mean age 77 years, 66 % white) with creatinine data, who were discharged alive. Of these, 155 (15 %) had PAD and 66 % had CKD. In comparison to those without PAD, patients with PAD had more comorbid conditions and higher 1-year ADHF readmission rates, irrespective of CKD status. After adjustment, PAD was associated with a greater risk of 1-year ADHF readmissions, both for patients with concomitant CKD (HR, 1.70; 95 % CI: 1.29-2.24) and those without CKD (HR, 1.97; 95 % CI: 1.14-3.40); p-interaction = 0.8., Conclusion: Among patients hospitalized with ADHF, those with concurrent PAD have more prevalent cardiovascular comorbidities and higher likelihood of 1-year ADHF readmission, irrespective of CKD status. Integrating a more holistic approach in management of patients with concomitant heart failure, PAD and CKD may be an important strategy to improve the prognosis in this vulnerable population., Competing Interests: Declaration of competing interest Dr. Bhatt discloses the following relationships - Advisory Board: Angiowave, Bayer, Boehringer Ingelheim, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, Stasys; Board of Directors: American Heart Association New York City, Angiowave (stock options), Bristol Myers Squibb (stock), DRS.LINQ (stock options), High Enroll (stock); Consultant: Broadview Ventures, Hims, SFJ, Youngene; Data Monitoring Committees: Acesion Pharma, Assistance Publique-Hôpitaux de Paris, Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Boston Scientific (Chair, PEITHO trial), Cleveland Clinic, Contego Medical (Chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo; for the ABILITY-DM trial, funded by Concept Medical; for ALLAY-HF, funded by Alleviant Medical), Novartis, Population Health Research Institute; Rutgers University (for the NIH-funded MINT Trial); Honoraria: American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Chair, ACC Accreditation Oversight Committee), Arnold and Porter law firm (work related to Sanofi/Bristol-Myers Squibb clopidogrel litigation), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), CSL Behring (AHA lecture), Cowen and Company, Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (Editor in Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), K2P (Co-Chair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Oakstone CME (Course Director, Comprehensive Review of Interventional Cardiology), Piper Sandler, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national co-leader, funded by Bayer), WebMD (CME steering committees), Wiley (steering committee); Other: Clinical Cardiology (Deputy Editor); Patent: Sotagliflozin (named on a patent for sotagliflozin assigned to Brigham and Women's Hospital who assigned to Lexicon; neither I nor Brigham and Women's Hospital receive any income from this patent); Research Funding: Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Alnylam, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CinCor, Cleerly, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Otsuka, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, Youngene, 89Bio; Royalties: Elsevier (Editor, Braunwald’s Heart Disease); Site Co-Investigator: Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St. Jude Medical (now Abbott), Philips, SpectraWAVE, Svelte, Vascular Solutions; Trustee: American College of Cardiology; Unfunded Research: FlowCo.Dr. Robert J. Mentz received research support and honoraria from Abbott, American Regent, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Cytokinetics, Fast BioMedical, Gilead, Innolife, Eli Lilly, Medtronic, Medable, Merck, Novartis, Novo Nordisk, Pfizer, Pharmacosmos, Relypsa, Respicardia, Roche, Rocket Pharmaceuticals, Sanofi, Verily, Vifor, Windtree Therapeutics, and Zoll. Dr. Grodin reports consulting fees from Pfizer, Eidos/BridgeBio, Alnylam, Alexion, Intellia, and Astra-Zeneca. Dr. Matsushita received research funding from NHLBI (R01HL146132) and Resolve to Save Lives and personal fee from Fukuda Denshi, Kowa Company, and RhythmX AI outside of the submitted work. Dr. Vaduganathan has received research grant support, served on advisory boards, or had speaker engagements with American Regent, Amgen, AstraZeneca, Bayer AG, Baxter Healthcare, BMS, Boehringer Ingelheim, Chiesi, Cytokinetics, Lexicon Pharmaceuticals, Merck, Novartis, Novo Nordisk, Pharmacosmos, Relypsa, Roche Diagnostics, Sanofi, and Tricog Health, and participates on clinical trial committees for studies sponsored by AstraZeneca, Galmed, Novartis, Bayer AG, Occlutech, and Impulse Dynamics. The other authors report no disclosures., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: The objective of this study was to assess the incidence and risk factors of major adverse cardiovascular events (MACEs) in patients with systemic sclerosis (SSc)., Methods: We conducted a nationwide, population-based, cohort study using Taiwan's National Health Insurance Research Database. We performed propensity score matching (PSM) using a 1:2 ratio, resulting in inclusion of 1379 patients with SSc and 2758 non-SSc individuals in the analysis. We assessed the association between SSc and MACEs, using the multivariable Cox proportional hazard regression model with adjustment of time-dependent covariates, and investigated risk factors for MACEs in patients with SSc, shown as adjusted hazard ratios (aHRs) with 95% CIs., Results: SSc was not significantly associated with the risk of MACEs (aHR 1.04; 95% CI 0.77-1.42). Nevertheless, SSc was associated with increased risk of myocardial infarction [incidence rate ratio (IRR) 1.76; 95% CI 1.08-2.86] and peripheral arterial occlusion disease (IRR 3.67; 95% CI 2.84-4.74) but not of ischaemic stroke (IRR 0.89; 95% CI 0.61-1.29). Factors independently associated with MACEs in SSc patients included age (aHR 1.02), male gender (aHR 2.01), living in a suburban area (aHR 2.09), living in a rural area (aHR 3.00), valvular heart disease (aHR 4.26), RA (aHR 2.14), use of clopidogrel (aHR 26.65), and use of aspirin (aHR 5.31)., Conclusions: The risk of MACEs was not significantly increased in Taiwanese patients with SSc, and our investigation effectively identified the factors independently associated with MACEs in SSc patients. Additionally, patients with SSc exhibited higher risks of myocardial infarction and peripheral arterial occlusion disease but not of ischaemic stroke., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: Annual trends of lower extremity amputation due to end-stage chronic disease are on the rise in the United States. These amputations are leading to massive expenses for patients and the medical system. In Oklahoma, we have a high-risk population because access to care is low, the number of uninsured is high, cardiovascular health is poor, and our overall health care performance is ranked 50th in the country. But we know little about Oklahomans and their risk of limb loss. It is, therefore, imperative to look closely at this population to discover contemporary rates, trends, and state-specific risk factors for amputation due to diabetes and/or peripheral arterial disease (PAD). We hypothesize that state-specific groups will be identified as having the highest risk for limb loss and that contemporary trends in amputations are rising. To create implementable solutions to limb preservation, a baseline must be set., Methods: We conducted a 12-consecutive-year observational study using Oklahoma's hospital discharge data. Discharges among patients 20 years or older with a primary or secondary diagnosis of diabetes and/or PAD were included. Diagnoses and amputation procedures were identified using International Classification of Disease-9 and -10 codes. Amputation rates were calculated per 1000 discharges. Trends in amputation rates were measured by annual percentage changes (APC). Prevalence ratios evaluated the differences in amputation rates across demographic groups., Results: Over 5,000,000 discharges were identified from 2008 to 2019. Twenty-four percent had a diagnosis of diabetes and/or PAD. The overall amputation rate was 12 per 1000 discharges for those with diabetes and/or PAD. Diabetes and/or PAD-related amputation rates increased from 8.1 to 16.2 (APC, 6.0; 95% confidence interval [CI], 4.7-7.3). Most amputations were minor (59.5%), and although minor, increased at a faster rate compared with major amputations (minor amputation APC, 8.1; 95% CI, 6.7-9.6 vs major amputation APC, 3.1; 95% CI, 1.5-4.7); major amputations were notable in that they were significantly increasing. Amputation rates were the highest among males (16.7), American Indians (19.2), uninsured (21.2), non-married patients (12.7), and patients between 45 and 49 years of age (18.8), and calculated prevalence ratios for each were significant (P = .001) when compared within their respective category., Conclusions: Amputation rates in Oklahoma have nearly doubled in 12 years, with both major and minor amputations significantly increasing. This study describes a worsening trend, underscoring that amputations due to chronic disease is an urgent statewide health care problem. We also present imperative examples of amputation health care disparities. By defining these state-specific areas and populations at risk, we have identified areas to pursue and improve care. These distinctive risk factors will help to frame a statewide limb preservation intervention., Competing Interests: Disclosures None., (Published by Elsevier Inc.)

Aim: The use of vitamin K antagonists (VKAs) may increase the risk of peripheral arterial disease (PAD) because vitamin K is a strong inhibitor of medial arterial calcification. Type 2 diabetes (T2D) exposes patients to an increased risk of PAD. We examined how the use of VKAs modulates the risk of incident PAD in people with T2D., Materials and Methods: SURDIAGENE is a French cohort including 1468 patients with T2D with a prospective follow-up from 2002 to 2015. The primary outcome of the current analysis was the first occurrence of PAD, a composite of lower-limb amputation (LLA) or lower-limb revascularization. LLA and lower-limb revascularization were considered individually as secondary outcomes., Results: During a 7-year median follow-up, PAD occurred in 147 (10%) of the 1468 participants. The use of VKAs was not significantly associated with the risk of PAD [multivariable adjusted hazard ratio (HR) 1.42, 95% confidence interval (CI), 0.88-2.31]. During the study period, LLA and lower-limb revascularization occurred in 82 (6%) and 105 (7%) participants, respectively. The use of VKAs was significantly associated with increased risk of LLA [multivariable adjusted HR 1.90 (95% CI, 1.04-3.47)], but not lower-limb revascularization [multivariable adjusted HR 1.08 (95% CI, 0.59-1.97)]., Conclusions: In this prospective study, we did not observe any excess risk of PAD requiring lower-limb revascularization in people with type 2 diabetes using VKAs. However, our data suggest a high risk of LLA in VKA users. Further studies are required to confirm this observation., (© 2024 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Background: The aim of this study was to investigate the associations of blood phosphorus levels with the risk of developing medial arterial calcification (MAC) in lower-limb arteries and diabetic foot (DF) in diabetes patients. We sought to enhance the understanding of the pathophysiology of diabetic complications and develop strategies to mitigate diabetes-related risks., Methods: We conducted a retrospective analysis of 701 diabetic patients from the Department of Endocrinology at Sun Yat-Sen Memorial Hospital (2019-2023). We utilized multimodel-adjusted logistic regression to investigate the associations of serum phosphorus levels and the risk of developing MAC and DF. Restricted cubic spline plots were employed to model the relationships, and threshold analysis was used to identify inflection points. Subgroup analyses were performed to explore variations across different demographics. The diagnostic utility of phosphorus concentrations was assessed via the C index, net reclassification improvement (NRI), and integrated discrimination improvement (IDI)., Results: Of the 701 patients (mean age 63.9 years; 401 (57.20%) were male), 333 (47.50%) had MAC, and 329 (46.93%) had DF. After controlling for numerous confounding variables, each one-unit increase in phosphorus concentrations was associated with an increased risk of developing MAC (OR 2.65, 95% CI 1.97-3.57, p < 0.001) and DF (OR 1.54, 95% CI 1.09-2.18, p = 0.014). Phosphorus levels demonstrated a linear risk association, with risk not being uniform on either side of the inflection point, which was approximately 3.28 mg/dL for MAC and varied for DF (3.26 to 3.81 mg/dL). Adding the phosphorus as an independent component to the diagnostic model for MAC and DF increased the C index, NRI, and IDI to varying degrees., Conclusions: Elevated serum phosphorus levels are significantly associated with an increased risk of developing MAC and DF among diabetic people. These findings suggest that phosphorus management could be integrated into routine diagnostic processes to improve the identification and management of lower-extremity diabetic complications., (© 2024. The Author(s).)

Background: To systematically analyze differences in atherosclerotic cardiovascular disease (ASCVD) burden between young and older adults., Methods: We estimated the prevalence, mortality, and disability-adjusted life years (DALYs) of ASCVD, including ischemic heart disease (IHD), ischemic stroke (IS), and peripheral artery disease (PAD), in individuals aged 20-54 and > 55 years from 1990-2019, utilizing data from the 2019 Global Burden of Disease Study. The annual percentage changes (EAPCs) for age-specific prevalence, mortality, or DALY rates were calculated to quantify the temporal trends of ASCVD burden. We also analyzed population attribution fractions (PAF) of premature ASCVD mortality and DALYs for different risk factors and compared the burden of extremely premature, premature, and non-premature ASCVD cases based on clinical classifications., Results: From 1990-2019, the global prevalence rates of IHD, IS, and PAD in the 20-54 years age group increased by 20.55% (from 694.74 to 837.49 per 100,000 population), 11.50% (from 439.48 to 490.03 per 100,000 population), and 7.38% (from 384.24 to 412.59 per 100,000 population), respectively. Conversely, the ASCVD prevalence in > 55years age group decreased. Adverse outcome burdens, including mortality and DALYs, varied among ASCVD subtypes. The decrease in the mortality/DALY burden of IHD and IS was lower in the 20-54 years group than in the > 55 years group. For PAD, DALYs among those aged 20-54 increased but decreased among those aged > 55 years. When grouped according to socio-demographic index (SDI) values, lower SDI regions exhibited a higher proportion of young ASCVD burden. The prevalence of young IHD, IS, and PAD in low SDI regions reached 20.70%, 40.05%, and 19.31% in 2019, respectively, compared with 12.14%, 16.32%, and 9.54%, respectively, in high SDI regions. Metabolic risks were the primary contributors to the ASCVD burden in both age groups. Increased susceptibility to ambient particulate matter pollution and inadequate control of high body-mass index and high fasting plasma glucose in young individuals may partially explain the differing temporal trends between young and older individuals., Conclusions: The ASCVD burden in young individuals may become a growing global health concern, especially in areas with lower socioeconomic development levels that require more effective primary prevention strategies., (© 2024. The Author(s).)

Background: Previous cross-sectional studies have identified wide practice pattern variations in the use of peripheral vascular interventions (PVIs) for the treatment of claudication. However, there are limited data on longitudinal practice patterns. We aimed to describe the temporal trends and charges associated with PVI use for claudication over the past 12 years in the United States., Methods and Results: We conducted a retrospective analysis using 100% Medicare fee-for-service claims data to identify all patients who underwent a PVI for claudication between January 2011 and December 2022. We evaluated the trends in utilization and Medicare-allowed charges of PVI according to anatomic level, procedure type, and intervention settings using generalized linear models. Multinomial logistic regressions were used to evaluate factors associated with different levels and types of PVI. We identified 599 197 PVIs performed for claudication. The proportional use of tibial PVI increased 1.0% per year, and atherectomy increased by 1.6% per year over the study period. The proportion of PVIs performed in ambulatory surgical centers/office-based laboratories grew at 4% per year from 12.4% in 2011 to 55.7% in 2022. Total Medicare-allowed charges increased by $11 980 035 USD/year. Multinomial logistic regression identified significant associations between race and ethnicity and treatment setting with use of both atherectomy and tibial PVI., Conclusions: The use of tibial PVI and atherectomy for the treatment of claudication has increased dramatically in in ambulatory surgical center/office-based laboratory settings, non-White patients, and resulting in a significant increase in health care charges. There is a critical need to improve the delivery of value-based care for the treatment of claudication.

Background: Bilateral blood pressure (BP) measurement is important in cardiovascular prevention for identifying systolic interarm BP difference (IAD) and hypertension. We investigated sex-stratified IAD prevalence and its associations and coexistence with screen-detected peripheral atherosclerosis and hypertension. Furthermore, we determined the proportion misclassified as non-hypertensive when using the lower versus the higher reading arm., Methods: This sub-study formed part of the Viborg Screening Program (VISP), a cross-sectorial population-based cardiovascular screening programme targeting 67-year-old Danes. VISP includes screening for peripheral atherosclerosis (lower extremity arterial disease and carotid plaque), abdominal aortic aneurysm, hypertension, diabetes mellitus, and cardiac disease. Self-reported comorbidities, risk factors, and medication use were also collected. Among 4,602 attendees, 4,517 (82.1%) had eligible bilateral and repeated BP measurements. IAD was defined as a systolic BP difference ≥ 10 mmHg. IAD-associated factors (screening results and risk factors) were estimated by logistic regression; proportional coexistence was displayed by Venn diagrams (screening results)., Results: We included 2,220 women (49.2%) and 2,297 men (50.8%). IAD was more predominant in women (26.8%) than men (21.0%) (p < 0.001). This disparity persisted after adjustment [odds ratio (OR) 1.53; 95% confidence interval (CI) 1.32-1.77]. No other association was recorded with the conditions screened for, barring potential hypertension: BP 140-159/90-99 mmHg (OR 1.68, 95% CI 1.44-1.97) and BP ≥ 160/100 mmHg (OR 1.82, 95% CI 1.49-2.23). Overall, IAD and BP ≥ 160/100 mmHg coexistence was 4% in women and 5% in men; for BP ≥ 140/90 mmHg, 13% and 14%, respectively. Among those recording a mean BP ≥ 140/90 mmHg in the higher reading arm, 14.5% of women and 15.3% of men would be misclassified as non-hypertensive compared with the lowest reading arm., Conclusion: Female sex was an independent factor of IAD prevalence but not associated with other arterial lesions. Approximately 15% needed reclassification according to BP ≥ 140/90 mmHg when the lower rather than the higher reading arm was used; verifying bilateral BP measurements improved detection of potential hypertension. In future, the predictive value of sex-stratified IAD should be assessed for cardiovascular events and death to verify its potential as a screening tool in population-based cardiovascular screening., Trial Registration for Visp: NCT03395509:10/12/2018., (© 2024. The Author(s).)

Surgical site infections (SSIs) following major lower limb amputation (MLLA) in vascular patients are a major source of morbidity. The objective of this systematic review was to determine the incidence of SSI following MLLA in vascular patients. This review was prospectively registered with the International Prospective Register of Systematic Reviews (CRD42023460645). Databases were searched without date restriction using a pre-defined search strategy. The search identified 1427 articles. Four RCTs and 21 observational studies, reporting on 50 370 MLLAs, were included. Overall SSI incidence per MLLA incision was 7.2% (3628/50370). The incidence of SSI in patients undergoing through-knee amputation (12.9%) and below-knee amputation (7.5%) was higher than the incidence of SSI in patients undergoing above-knee amputation, (3.9%), p < 0.001. The incidence of SSI in studies focusing on patients with peripheral arterial disease (PAD), diabetes or including patients with both was 8.9%, 6.8% and 7.2%, respectively. SSI is a common complication following MLLA in vascular patients. There is a higher incidence of SSI associated with more distal amputation levels. The reported SSI incidence is similar between patients with underlying PAD and diabetes. Further studies are needed to understand the exact incidence of SSI in vascular patients and the factors which influence this., (© 2024 The Author(s). International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Purpose: Familial hypercholesterolemia (FH) is one of the most common inherited diseases characterized by elevated LDL-cholesterol levels, leading to early-onset atherosclerosis. While the association between FH and coronary and carotid artery disease is well-established, its association with peripheral artery disease (PAD) is less robust. This systematic review aims at exploring existing evidence on PAD prevalence and incidence in FH individuals., Methods: A comprehensive search was conducted on MEDLINE and Embase databases, for studies published between January 2013 and December 2023, evaluating prevalence and incidence of PAD in FH patients. Literature reviews, case reports, responses to editors and non-English language articles were excluded., Results: The initial research provided 53 results. After article screening, 28 articles were fully reviewed and 24 were finally included in the analysis. Among these, 19 reported PAD prevalence, while 5 PAD incidence over a mean follow-up time of 8.7 years. PAD prevalence and incidence ranged from 0.3 to 60% and from 0.5 to 4.2% respectively, probably reflecting the heterogeneity in PAD definition criteria., Conclusion: This systematic review sheds light on the limited number of studies on PAD in FH patients. Particularly, considering the potential positive effects of newly available lipid-lowering strategies on PAD outcomes, addressing this research gap is pivotal for a more comprehensive understanding of peripheral vascular manifestations in FH patients and for optimal management of this population., (© 2024. The Author(s).)

Percutaneous coronary intervention (PCI) has demonstrated its safety and efficacy in treating left main (LM) coronary artery disease (CAD) in select patients. Polyvascular disease (PolyVD) is associated with adverse events in all-comers with CAD. However, there is little data examining the interplay between PolyVD and LM-PCI, which we sought to investigate in a retrospective single-center study. We included patients who underwent unprotected LM-PCI at a tertiary center from 2012 to 2019. The study population was stratified based on the presence or absence of PolyVD (i.e., medical history of cerebrovascular and/or peripheral artery disease in addition to LM-CAD). The primary outcome was major adverse cardiovascular events (MACE) combining all-cause mortality and spontaneous myocardial infarction within 1 year after index PCI. Overall, 869 patients were included, and 23.8% of the population had PolyVD. Subjects with PolyVD were older and had a greater burden of co-morbidities. After 1-year follow-up, PolyVD patients exhibited significantly higher rates of both MACE (22.8% vs 9.4%, p <0.001) and bleeding events compared with those without PolyVD. MACE was primarily driven by an increase in all-cause mortality (18.3% vs 7.1%, p <0.001). Results persisted after adjusting for confounders. In conclusion, in patients who underwent LM-PCI, the presence of PolyVD is linked to an increased risk of MACE and bleeding after 1 year of follow-up, which highlights the vulnerability of this population., Competing Interests: Declaration of competing interest Dr. Dangas received research grants from institutions and support for attending meetings from Daiichi Sankyo. Dr. Mehran reports institutional research payments from: Abbott, Abiomed, Affluent Medical, Alleviant Medical, Amgen, AM-Pharmacia, Arena, AstraZeneca, AtriCure Inc., Biosensors, Biotronik, Boston Scientific, Bristol-Myers Squibb, CardiaWave, CeloNova, CERC, Chiesi, Concept Medical, Cytosorbents, Daiichi Sankyo, Duke, Element Science, Essential Medical, Faraday, Idorsia Pharmaceuticals, Janssen, MedAlliance, Mediasphere, Medtelligence, Medtronic, MJH Healthcare, Novartis, OrbusNeich, Penumbra, PhaseBio, Philips, Pi-Cardia, PLx Pharma, Population Health Research Institute, Protembis, RecCor Medical Inc., RenalPro, RM Global, Sanofi, Shockwave, Vivasure, Zoll; Personal fees from: Affluent Medical, Cardiovascular Research Foundation (CRF), Cordis, Daiichi Sankyo Brasil, E.R. Squibb & Sons Science/Innovative BioPharma, Europa Group/Boston Scientific, Gaffney Events, Educational Trust, Henry Ford Health Cardiology, Ionis Pharmaceuticals, MedCon International, Novartis, NovoNordisk, PeerView Institute for Medical Education, Terumo Europe N.V., Vectura, VoxMedia, WebMD, IQVIA, Radcliffe, tarsus Cardiology; No Fees from: AMA (Scientific Advisory Board), SCAI (Women in Innovations Committee Member); Faculty CRF; Honorarium: JAMA Cardiology (Associate Editor), ACC (BOT Member, SC Member CTR Program); Equity <1% in: applied Therapeutics, Elixir Medical, Stel, ControlRad (spouse). The remaining authors have no competing interests to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Previous studies have shown an association between acute limb ischemia and higher mortality in patients with acute myocardial infarction. Although peripheral artery disease (PAD) is a well-known risk factor for development of macrovascular pathology, the effect of its severity is not well investigated in patients hospitalized for acute coronary syndrome (ACS). Using a national cohort of patients with various degrees of PAD, we investigated in-hospital outcomes in patients who were admitted for ACS. Using the 2016 to 2020 Nationwide Readmissions Database, we queried all patients who were hospitalized for ACS (unstable angina, non-ST-elevation myocardial infarction, and ST-elevation myocardial infarction). Patients were further divided into 3 groups, either no PAD (non-PAD), PAD, or critical limb ischemia (CLI). Multivariable models were designed to adjust for patient and hospital factors and examine the association between ACS and PAD severity. Of approximately 3,834,181 hospitalizations for ACS, 6.4% had PAD, 0.2% had CLI, and all others were non-PAD. After risk adjustment, in-hospital mortality was higher by 24% in PAD (adjusted odds ratio 1.24, 95% confidence interval [CI] 1.21 to 1.28) and 86% in CLI (adjusted odds ratio 1.86, 95% CI 1.62 to 2.09) compared with non-PAD. Furthermore, PAD and CLI were linked to 1.23-fold (95% CI 1.20 to 1.26) and 1.67-fold (95% CI 1.45 to 1.86) greater odds of cardiogenic shock compared with non-PAD. Additionally, PAD and CLI were linked with higher odds of mechanical circulatory support usage, cardiac arrest and acute kidney injury compared with non-PAD. Lastly, duration of hospital stay, hospitalization costs and odds of non-home discharge and 30-day readmissions were greater in patients with PAD and CLI compared with non-PAD. PAD severity was associated with worse clinical outcomes in patients with ACS, including in-hospital mortality and resource utilization., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The reported incidence of surgical site infection (SSI) after lower limb revascularization surgery varies. We conducted a systematic review and meta-analysis of population-based studies reporting the incidence of SSI in adults who underwent these surgeries in high-income countries to derive SSI quality benchmarks., Methods: We searched MEDLINE, EMBASE, CENTRAL, and Evidence-Based Medicine Reviews (inception-to-April 28th, 2022) for population-based studies estimating the cumulative incidence of SSI among adults who underwent lower limb revascularization surgery for peripheral artery disease (PAD) in high-income countries. Two investigators independently screened abstracts and full-text articles, extracted data, and assessed risks of bias. We used random-effects models to pool data and GRADE to assess certainty., Results: Among 6,258 citations, we included 53 studies (n = 757,726 patients); 8 of which (n = 435,769 patients) reported nonoverlapping data that were meta-analyzed. The pooled cumulative incidence of any SSI was 6.0 in 100 patients [95% confidence interval (CI) = 4.3-8.0 in 100 patients; n = 8 studies; n = 435,769 patients; moderate certainty]. The cumulative incidence of Szilagyi grade I (cellulitis), grade II (subcutaneous tissue), and grade III (prosthetic graft) SSI was 6.5 in 100 patients (95% CI = 4.3-8.6 in 100 patients; n = 2 studies; n = 39,645 patients; low certainty), 2.1 in 100 patients (95% CI = 2.0-2.3 in 100 patients; n = 2 studies; low certainty), and 0.4 in 100 patients (95% CI = 0.4-0.4 in 100 patients; n = 1 study; n = 333,275 patients; low certainty), respectively. The pooled cumulative incidence of any early (in-hospital/≤30-days) and late (>30-days) SSI was 6.2 in 100 patients (95% CI = 4.4-8.0 in 100 patients; n = 7 studies; n = 431,273 patients; moderate certainty) and 3.7 in 100 patients (95% CI = 2.2-5.2 in 100 patients; n = 2 studies; n = 10,565 patients; low certainty), respectively., Conclusions: This systematic review derived population-based benchmarks of the incidence of any SSI; Szilagyi I, II, and III SSI; and early and late SSI after lower limb revascularization surgery. These may be used by practicing surgeons and healthcare leaders/administrators to guide quality improvement efforts in the United States and perhaps other countries., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Frailty is common among cardiac patients; however, frailty assessment data from patients with peripheral arterial disease (PAD) are limited. The purpose of this observational study was to identify the prevalence and factors related to frailty in addition to unique frailty marker groupings in a cohort of sedentary adults with PAD. We grouped three PAD-relevant frailty characteristics using Fried's frailty phenotype -1) exhaustion, (2) weakness, and (3) slowness-and observed the prevalence of pre-frailty (1-2 characteristics) and frailty (3 characteristics) in the PAD cohort. Of the 106 participants, 34.9% were robust/non-frail, 53.8% were pre-frail, and 2.8% were frail. Exhaustion (33.3%) was the most occurring characteristic followed by weakness (20.0%) and slowness (5.0%). The grouping of weakness + slowness (10.0%) was the most prevalent followed by exhaustion + weakness (8.3%) and exhaustion + slowness (5.0%). Among pre-frail participants, ankle brachial index was correlated with a reduction in gait speed., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Lower extremity peripheral artery disease (PAD) often results from atherosclerosis, and is highly prevalent in patients with type 2 diabetes mellitus (T2DM). Individuals with T2DM exhibit a more severe manifestation and a more distal distribution of PAD compared to those without diabetes, adding complexity to the therapeutic management of PAD in this particular patient population. Indeed, the management of PAD in patients with T2DM requires a multidisciplinary and individualized approach that addresses both the systemic effects of diabetes and the specific vascular complications of PAD. Hence, cardiovascular prevention is of the utmost importance in patients with T2DM and PAD, and encompasses smoking cessation, a healthy diet, structured exercise, careful foot monitoring, and adherence to routine preventive treatments such as statins, antiplatelet agents, and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. It is also recommended to incorporate glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) in the medical management of patients with T2DM and PAD, due to their demonstrated cardiovascular benefits. However, the specific impact of these novel glucose-lowering agents for individuals with PAD remains obscured within the background of cardiovascular outcome trials (CVOTs). In this review article, we distil evidence, through a comprehensive literature search of CVOTs and clinical guidelines, to offer key directions for the optimal medical management of individuals with T2DM and lower extremity PAD in the era of GLP-1RA and SGLT2i., (© 2024. The Author(s).)

Background: The global population is ageing rapidly and it is important to promote healthy ageing. The Healthy Ageing Index (HAI) is a comprehensive measure of health, but there is limited research on its association with other age-related outcomes. The management of an aging population necessitates considerations even among generally healthy adults, as age-related diseases often remain unaccounted for until later stages of life. This study explores the association of risk factors with HAI and its association with peripheral artery disease (PAD), muscle strength, health-related quality of life (HRQoL), and psychological distress in the Singapore Multi-Ethnic Cohort study., Methods: This cross-sectional study involved 1909 participants (median (Q1, Q3) age: 53 (48, 60) years and 59.3% females) from Singapore Multi-Ethnic Cohort study. The risk factors of HAI included age, gender, ethnicity, education level, smoking, alcohol consumption, employment, BMI and past medical histories. PAD was assessed using ankle-brachial index (ABI), handgrip strength (HGS), HRQoL with the EQ-5D-5 L questionnaire and psychological distress via the Kessler Psychological Distress Scale (K10). HAI components were assessed using relevant marker tests., Results: Older age, Malay and Indian ethnicities, unemployment, high BMI and histories of CHD, hypercholesterolaemia, tumours and TIA/stroke were associated with lower HAI scores indicative of poorer health. Higher HAI scores were associated with females and higher education levels. Lower HAI scores were significantly associated with low ABI, high K10 scores, mobility and anxiety/depression dimensions of EQ-5D-5 L., Conclusion: The most important factors associated with HAI were age, sex, ethnicity, education, unemployment, BMI and a history of health conditions. Lower HAI scores were significantly associated with PAD, lower HRQoL and psychological distress. Thus, the HAI demonstrates promise as an evaluation method for assessing PAD, overall muscle strength and HRQoL in a population-based setting., (© 2024. The Author(s).)

This article briefly discusses the risk factors for the development of lower extremity artery disease, namely smoking, diabetes mellitus, hyperlipidemia/dyslipidemia and hypertension. Each of these risk factors will be discussed in detail in forthcoming articles of the journal.

Abstract: Peripheral arterial disease (PAD) is the third leading cause of atherosclerotic morbidity after coronary heart disease and stroke yet is widely underdiagnosed and undertreated. Treatment of risk factors such as diabetes and cigarette smoking can benefit patients with PAD. Patients should have adequate blood pressure and lipid control to decrease clinical manifestations and symptoms of PAD. Use of antithrombotic medications should be individualized to the patient depending on the presence of symptoms, revascularization, and comorbidities. All patient care providers, including physicians, pharmacists, nurse practitioners, and physician assistants, should incorporate PAD screening in their at-risk patients to improve access for appropriate earlier diagnosis, initiation of guideline directed therapy, and risk factor modification to reduce both major adverse CV and limb outcomes. The purpose of this narrative review is to provide an overview of PAD and summarize clinical trial evidence and guideline recommendations for screening and treatment to increase awareness among health care providers to ultimately have a positive impact on patient care., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Non-traumatic lower limb amputation (NT-LLA) has consequences at individual and public health levels. Population based studies in sub-Saharan Africa are scarce and often related to single centre series. This study aimed to estimate the incidence of NT-LLA (minor and major) and to describe epidemiological, clinical, and prognostic aspects in Togo., Methods: This was a population based observational study conducted among all patients who underwent NT-LLA. Traumatic amputations were excluded. Sociodemographic, clinical, and work up data were collected from clinical files in any Togolese health centre from 1 January 2016 to 31 December 2021. Incidence rates were adjusted for age., Results: Over the six year period, 352 patients (59% males) underwent NT-LLA (mean ± standard deviation age 60 ± 15.7 years). The average age adjusted incidence rate of NT-LLA was 8.5 per million/year (95% confidence interval [CI] 7.6 - 9.4). Men were 1.7 times more likely to undergo a NT-LLA than women. The relative risk of NT-LLA was 48 times higher in patients with diabetes than in patients without diabetes. Around 61.0% of the NT-LLAs occurred within the 50 - 74 age group and 54.3% had diabetes mellitus. Among amputees, 54.5% had a diagnosis of peripheral artery disease (PAD) and 52.8% had diabetic ulcers, with co-existence of several factors. Less than 5% of participants had a history of smoking tobacco. Average length of hospital stay was 12 days. The in hospital mortality rate was 8.8% (9.0% for major, 6.7% for minor amputations). Only 18.2% had duplex ultrasound performed and 1.7% angiography prior to amputation. No patient underwent vascular intervention prior to amputation., Conclusion: This is the first study to report nationwide and contemporary epidemiological data on NT-LLAs in West Africa, highlighting several specificities. Large scale interventions are needed to ameliorate the care of diabetes and PAD and improve facilities for optimal management of patients at risk of amputation in Africa., (Copyright © 2024. Published by Elsevier B.V.)

Background: Diabetes can lead to micro and macro-angiopathies. The peripheral arterial disease (PAD) is a serious and an incapacitating disease. It is still under-estimated and under-treated throughout the world, particularly in sub-Saharan Africa. Doppler ultrasound, and in particular ankle brachial index (ABI), can be used to detect it. The aim was to determine the prevalence of PAD to study the clinical and ultrasonographic aspects and to identify the determining factors., Patients and Methods: This was a descriptive and analytical study over a period of 5 years, including a total of 782 diabetic patients hospitalised in the diabetology department of the CHU la Reference Nationale., Results: Among the 782 patients, 166 (21.2%) had an ABI < 0.9 reflected the PAD and 72 (9.2%) had an ABI > 1.3, suggestive of mediacalcosis. PAD of the lower limb was mild in 102 patients (61.4%), moderate in (26.3%) and severe in (12.3%). The mean age of the arteritic patients was 56.4 ± 10.2 years. Male gender predominated (59.6%) with a sex ratio of 1.6. All patients had type 2 diabetes (100%). The mean duration of diabetes was 13 ± 5.9 years. The majority of our patients with arterial disease had diabetes for at least 10 years (54.2%). The other cardiovascular in this population were obesity (45.2%), followed by hypertension and dyslipidaemia (32.5%). Diabetes was unbalanced (HbA ≥7%) in the majority of cases (75.3%). Clinically, the majority of patients had a trophic disorder (68%). Asymptomatic patients accounted for 24.6% of cases and those with intermittent claudication for 7.4%. Duplex doppler of the lower limbs showed that all patients with PAD had atheromatous lesions. The distal location was predominantly in the tibial arteries (54.8%). The determinants of PAD in this diabetic population were hypertension (p = 0.01) and obesity (p = 0.01)., Conclusion: In our series, PAD was often discovered at an advanced stage, with a non-negligible prevalence. The determining factors found were hypertension and obesity. Screening and control of major cardiovascular risk factors is a priority in the management of this disease., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Sarcopenia was recently reported to be relevant to an increased macro-and microvascular disease risk. Sarcopenia index (SI) has been identified as a surrogate marker for sarcopenia. The aim of the present study was to investigate the association between macro- and microvascular disease and SI in patients with type 2 diabetes mellitus (T2DM). A total of 783 patients with T2DM were enrolled in this cross-sectional study. The SI was calculated by (serum creatinine [mg/dL]/cystatin C [mg/L]) × 100. The subjects were divided into three groups according to SI tertiles: T1 (41.27-81.37), T2 (81.38- 99.55), and T3 (99.56-192.31). Parameters of macro- and microvascular complications, including diabetic retinopathy (DR), micro- and macroalbuminuria (MAU), diabetic peripheral neuropathy (DPN), and lower extremity peripheral artery disease (LEAD) were evaluated. Multivariate logistic regression analysis revealed that when taking the top tertile of SI as a reference, an increasing trend of the prevalence of DR, MAU, DPN, and LEAD were presented (all P for trend  < 0.05), where the OR (95% CI) for DR prevalence was 1.967 (1.252-3.090) in T2, 2.195 (1.278-3.769) in T1, for MAU was 1.805 (1.149-2.837) in T2, 2.537 (1.490-4.320) in T1, for DPN was 2.244 (1.485-3.391) in T2, 3.172 (1.884-5.341) in T1, and for LEAD was 2.017 (1.002-4.057) in T2, 2.405 (1.107-5.225) in T1 (all P  < 0.05). Patients with lower SI were more inclined to have an increased risk of macro- and microvascular damage in T2DM population, which may be related to sarcopenia., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Background: As a key treatment goal for patients with symptomatic peripheral artery disease (PAD), improving health status has also become an important end point for clinical trials and performance-based care. An understanding of patient factors associated with 1-year PAD health status is lacking in patients with PAD., Methods: The health status of 1073 consecutive patients with symptomatic PAD in the international multicenter PORTRAIT (Patient-Centered Outcomes Related to Treatment Practices in Peripheral Arterial Disease: Investigating Trajectories) registry was measured at baseline and 1 year with the Peripheral Artery Questionnaire (PAQ). The association of 47 patient characteristics with 1-year PAQ scores was assessed using a random forest algorithm. Variables of clinical significance were retained and included in a hierarchical multivariable linear regression model predicting 1-year PAQ summary scores., Results: The mean age of patients was 67.7 ± 9.3 years, and 37% were female. Variables with the highest importance ranking in predicting 1-year PAQ summary score were baseline PAQ summary score, Patient Health Questionnaire-8 depression score, Generalized Anxiety Disorder-2 anxiety score, new onset symptom presentation, insurance status, current or prior diagnosis of depression, low social support, initial invasive treatment, duration of symptoms, and race. The addition of 19 clinical variables in an extended model marginally improved the explained variance in 1-year health status (from R 2 0.312 to 0.335)., Conclusions: Patients' 1-year PAD-specific health status, as measured by the PAQ, can be predicted from 10 mostly psychosocial and socioeconomic patient characteristics including depression, anxiety, insurance status, social support, and symptoms. These characteristics should be validated and tested in other PAD cohorts so that this model can inform risk adjustment and prediction of PAD health status in comparative effectiveness research and performance-based care., Competing Interests: Disclosures J.A.S. is a consultant to Bayer, Janssen, Merck, MyoKardia, Novartis, Terumo, and United Healthcare. He receives grant support from Janssen and MyoKardia. He holds the copyright to the Peripheral Artery Questionnaire, Kansas City Cardiomyopathy Questionnaires, and the Seattle Angina Questionnaire. He also serves on the Board of Blue Cross/Blue Shield of Kansas City. E.S. is supported by NIH/National Heart, Lung, and Blood Institute (K23HL150290), Food & Drug Administration, BD, Boston Scientific, Cook, CSI, Laminate Medical, Medtronic, and Philips. He is a consultant for Abbott, Bayer, BD, Boston Scientific, Cook, CSI, Inari, Infraredx, Janssen, Medtronic, Philips, Shockwave, and VentureMed. K.G.S. reports unrestricted research grants from Cardiva Medical Inc, Cook Medical, Inc, Merck & Co, Inc, Shockwave Medical Inc, and Janssen Pharmaceutical Companies of Johnson & Johnson. She is a consultant for Optum Labs, Inc, and Abbott Laboratories. C.M-H. reports grant funding from Shockwave Medical, Inc and is a consultant for Abbott Laboratories, Cook Medical, Inc, and Optum Labs, Inc. The other authors do not have conflict of interest or financial ties to disclose., (Copyright © 2024. Published by Elsevier Inc.)

Objective: Adherence to antiplatelet therapy is recommended but unexplored in patients with symptomatic lower extremity peripheral arterial disease (PAD). Therefore, this study aimed to determine adherence and persistence to antiplatelet therapy in patients with PAD, defined as intermittent claudication and chronic limb threatening ischaemia., Design: Population based nationwide cohort study., Methods: This study included all Danish citizens aged ≥ 40 years with a first inpatient or outpatient diagnosis of symptomatic PAD between 2010 - 2017, and who had at least one prescription claim for aspirin and/or clopidogrel within 90 days after diagnosis. Adherence was determined by the proportion of days covered (PDC) during the first year after diagnosis. Persistence was defined as no treatment gap ≥ 30 days between prescription renewals over three year follow up., Results: A total of 39 687 patients were eligible for inclusion, of whom 23 279 (58.7%) claimed a prescription for aspirin and/or clopidogrel within 90 days of diagnosis. Among these, 12 898 (55.4%) were prevalent users, while the remainder comprised new users who initiated the therapy after the index PAD diagnosis. The mean PDC was 74.5% (SD 35.0%) for prevalent users and 60.5% (SD 30.5%) for new users. Adherence increased with age and number of concomitant drugs. The overall one year cumulative incidence treatment discontinuation was 13.0% (95% CI 12.5 - 13.4%) overall, 17.2% (CI 16.6 - 17.9%) for prevalent users, and 7.9% (CI 7.4 - 8.4%) for new users. At three year follow up, the cumulative incidence of discontinuation was 31.5% (CI 30.9 - 32.2%) overall, 44.6% (CI 43.7 - 45.4%) for prevalent users, and 14.6% (CI 13.9 - 15.3) for new users., Conclusion: Less than 60% of patients with newly diagnosed symptomatic PAD claimed a prescription for antiplatelet therapy within 90 days of diagnosis, and both adherence and persistence were moderate during the first year after diagnosis. These findings underscore the importance of efforts to improve the initiation and continuation of antiplatelet therapy in patients with PAD., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Peripheral artery disease (PAD) is the lower limb manifestation of systemic atherosclerotic disease. PAD may initially present with symptoms of intermittent claudication, whilst chronic limb-threatening ischaemia (CLTI), the end stage of PAD, presents with rest pain and/or tissue loss. PAD is an age-related condition present in over 10% of those aged ≥65 in high-income countries. Guidelines regarding definition, diagnosis and staging of PAD and CLTI have been updated to reflect the changing patterns and presentations of disease given the increasing prevalence of diabetes. Recent research has changed guidelines on optimal medical therapy, with low-dose anticoagulant plus aspirin recommended in some patients. Recently published randomised trials highlight where bypass-first or endovascular-first approaches may be optimal in infra-inguinal disease. New techniques in endovascular surgery have increased minimally invasive options for ever more complex disease. Increasing recognition has been given to the complexity of patients with CLTI where a high prevalence of both frailty and cognitive impairment are present and a significant burden of multi-morbidity and polypharmacy. Despite advances in minimally invasive revascularisation techniques and reduction in amputation incidence, survival remains poor for many with CLTI. Shared decision-making is essential, and conservative management is often appropriate for older patients. There is emerging evidence of the benefit of specialist geriatric team input in the perioperative management of older patients undergoing surgery for CLTI. Recent UK guidelines now recommend screening for frailty, cognitive impairment and delirium in older vascular surgery patients as well as recommending all vascular surgery services have support and input from specialist geriatrics teams., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Geriatrics Society.)

Background: This post hoc subanalysis aimed to investigate the impact of polyvascular disease (PolyVD) in patients with acute myocardial infarction (AMI) in the contemporary era of percutaneous coronary intervention (PCI)., Methods and results: The Japan Acute Myocardial Infarction Registry (JAMIR), a multicenter prospective registry, enrolled 3,411 patients with AMI between December 2015 and May 2017. Patients were classified according to complications of a prior stroke and/or peripheral artery disease into an AMI-only group (involvement of 1 vascular bed [1-bed group]; n=2,980), PolyVD with one of the complications (2-bed group; n=383), and PolyVD with both complications (3-bed group; n=48). The primary endpoint was all-cause death. Secondary endpoints were major adverse cardiovascular events (MACE), including cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and major bleeding. In the 1-, 2-, and 3-bed groups, the cumulative incidence of all-cause death was 6.8%, 17.5%, and 23.7%, respectively (P<0.001); that of MACE was 7.4%, 16.4%, and 33.8% (P<0.001), respectively; and that of major bleeding was 4.8%, 10.0%, and 13.9% (P<0.001), respectively. PolyVD was independently associated with all-cause death (hazard ratio [HR] 2.21; 95% confidence interval [CI], 1.48-3.29), MACE (HR 2.07; 95% CI 1.40-3.07), and major bleeding (HR 1.68; 95% CI 1.04-2.71)., Conclusions: PolyVD was significantly associated with worse outcomes, including thrombotic and bleeding events, in the contemporary era of PCI in AMI patients.

Competing Interests: Conflict of interest: none declared.

Aims: The epidemiology of lower extremity artery disease (LEAD) is evolving. This meta-analysis of aggregate data aimed to (i) determine the global prevalence of LEAD and by regions in the 21st century and (ii) update the associated risk factors in this period., Methods and Results: A systematic literature review was performed through PubMed, Cochrane, Scopus, Science Direct, and Google Scholar databases, restricted to general population studies between January 2000 and September 2021, with LEAD defined by a low (

Background: Peripheral artery disease (PAD) is associated with high morbidity and mortality and has been commonly described as a coronary heart disease equivalent. Statin medications are recommended for primary prevention of atherosclerotic cardiovascular disease (CVD) among other indications. Therefore, understanding the longitudinal relationship of incident PAD is necessary to inform future research on how to prevent the disease. Depression complicates CVD patients' ability to properly adhere to their medications, yet the effect of depression on the relationship between statin use and incident PAD is understudied. People with PAD have a higher incidence of depressive symptoms than people without PAD. Black American and Hispanic populations are disproportionately affected by both PAD and depression yet research on the modifying effect of either race or depression on the relationship between statin use and onset of PAD is minimal. While statin utilization is highest for ages 75-84 years, there is minimal evidence of favorable risk-benefit balance. Consequently, in this project, we examined the relationship between statin use and incident PAD and whether this relationship is modified by race/ethnicity, depressive symptoms, or age., Methods: We used data on participants from the Multi-Ethnic Study of Atherosclerosis from visit 1 (2000) through study visit 6 (2020) who had three separate measurements of the ankle-brachial index (ABI) taken at visit 1, visit 3, and visit 5. Incident PAD was defined as 1) incident lower extremity amputation or revascularization or 2) ABI less than 0.90 coupled with ABI decrease greater than 0.15 over the follow-up period. Statin use was noted on the study visit prior to incident PAD diagnosis while depressive symptoms were measured at exam 1, visit 3, and visit 5. Propensity score matching was implemented to create balance between the participants in the two treatment groups, that is, statin-treated and statin-untreated groups, to reduce the problem of confounding by indication. Propensity scores were calculated using multivariate logistic regression model to estimate the probability of receiving statin treatment. We used Cox proportional hazards regression to investigate the relationship between time-dependent statin use as well as other risk factors with incident PAD, overall and stratified by 1) race, 2) depression status, and 3) age., Results: A total of 4,210 participants were included in the final matched analytic cohort. There were 810 incident cases (19.3%) of PAD that occurred over an average (mean) of 11.3 years (SD = 5.7) of follow-up time. In the statin-treated group, and with an average follow-up time of 12.5 years (SD = 5.6), there were 281 cases (13.4%) of incident PAD with the average follow-up time of 10.1 years (SD = 5.5), whereas in the statin-untreated group, there were 531 cases (25.2%) (P < 0.001). Results demonstrate a lower risk of PAD event in the statin-treated group compared to the untreated group (hazard ratio [HR] = 0.45, 95% confidence interval [CI]: 0.33-0.62) over the span of 18.5 years. The interactions between 1) depression and 2) race with statin use for incident PAD were not significant. However, other risk factors which were significant included Black American race that had approximately 30% lower hazard of PAD compared to non-Hispanic White (HR = 0.70, 95% CI: 0.58-0.84); age-stratified models were also fitted, and stain use was still a significant treatment factor for ages 45-54 (HR = 0.45, 95% CI: 0.33-0.63), 55-64 (HR = 0.61, 95% CI: 0.46-0.79), and 65-74 years (HR = 0.61, 95% CI: 0.48-0.78) but not for ages 75-84 years., Conclusions: Statin use was associated with a decreased risk of incident PAD for those under the age of 75 years. Neither race nor depression significantly modified the relationship between statin use and incident PAD; however, the risk of incident PAD was lower among Black Americans. These findings highlight that the benefit of statin may wane for those over the age of 75 years. Findings also suggest that statin use may not be compromised in those living with depression., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aims: Type 2 diabetes (T2D) is a risk factor for cardiovascular and non-cardiovascular mortality. However, global distribution of cause-specific deaths in T2D is poorly understood. We characterized cause-specific deaths by geographic region among individuals with T2D at risk for cardiovascular disease (CVD)., Methods and Results: The international EXSCEL trial included 14,752 participants with T2D (73% with established CVD). We identified the proportion of deaths over 5-year follow-up attributed to cardiovascular and non-cardiovascular causes, and associated risk factors. During median 3.2-year follow-up, 1,091 (7.4%) participants died. Adjudicated causes of death were 723 cardiovascular (66.3% of deaths), including 252 unknown, and 368 non-cardiovascular (33.7%). Most deaths occurred in North America (N = 356/9.6% across region) and Eastern Europe (N = 326/8.1%), with fewest in Asia/Pacific (N = 68/4.4%). The highest proportional cause-specific deaths by region were sudden cardiac in Asia/Pacific (23/34% of regional deaths) and North America (86/24%); unknown in Eastern Europe (90/28%) and Western Europe (39/21%); and non-malignant non-cardiovascular in Latin America (48/31%). Cox proportional hazards model for adjudicated causes of death showed prognostic risk factors (hazard ratio [95% CI]) for cardiovascular and non-cardiovascular deaths, respectively: heart failure 2.04 (1.72-2.42) and 1.86 (1.46-2.39); peripheral artery disease 1.83 (1.54-2.18) and 1.78 (1.40-2.26); and current smoking status 1.61 (1.29-2.01) and 1.77 (1.31-2.40)., Conclusions: In a contemporary T2D trial population, with and without established CVD, leading causes of death varied by geographic region. Underlying mechanisms leading to variability in cause of death across geographic regions and its impact on clinical trial endpoints warrant future research., (Copyright © 2024. Published by Elsevier Inc.)

Background: Elevated apoB-containing lipoproteins (=remnants+LDLs [low-density lipoproteins]) are a major risk factor for atherosclerotic cardiovascular disease, including peripheral artery disease (PAD) and myocardial infarction. We tested the hypothesis that remnants and LDL both explain part of the increased risk of PAD conferred by elevated apoB-containing lipoproteins. For comparison, we also studied the risk of chronic limb-threatening ischemia and myocardial infarction., Methods: apoB, remnant cholesterol, and LDL cholesterol were measured in 93 461 individuals without statin use at baseline from the Copenhagen General Population Study (2003-2015). During up to 15 years of follow-up, 1207 had PAD, 552 had chronic limb-threatening ischemia, and 2022 had myocardial infarction in the Danish National Patient Registry. Remnant and LDL cholesterol were calculated from a standard lipid profile. Remnant and LDL particle counts were additionally measured with nuclear magnetic resonance spectroscopy in 25 347 of the individuals. Results were replicated in 302 167 individuals without statin use from the UK Biobank (2004-2010)., Results: In the Copenhagen General Population Study, multivariable adjusted hazard ratios for risk of PAD per 1 mmol/L (39 mg/dL) increment in remnant and LDL cholesterol were 1.9 (95% CI, 1.5-2.4) and 1.1 (95% CI, 1.0-1.2), respectively; corresponding results in the UK Biobank were 1.7 (95% CI, 1.4-2.1) and 0.9 (95% CI, 0.9-1.0), respectively. In the association from elevated apoB to increased risk of PAD, remnant and LDL cholesterol explained 73% (32%-100%) and 8% (0%-46%), respectively; corresponding results were 63% (30%-100%) and 0% (0%-33%) for risk of chronic limb-threatening ischemia and 41% (27%-55%) and 54% (38%-70%) for risk of myocardial infarction; results for remnant and LDL particle counts corroborated these findings., Conclusions: PAD risk conferred by elevated apoB-containing lipoproteins was explained mainly by elevated remnants, while myocardial infarction risk was explained by both elevated remnants and LDL., Competing Interests: Disclosures B.G. Nordestgaard reports consultancies and talks sponsored by AstraZeneca, Sanofi, Regeneron, Akcea, Amgen, Kowa, Denka, Amarin, Novartis, Novo Nordisk, Esperion, Abbott, Silence Therapeutics, USV, Mankind, Lilly, Arrowhead, and Marea. The other authors report no conflicts.

Background: In the latest American Heart Association guidelines, influenza vaccination is recommended for patients with peripheral arterial disease (PAD). The vaccination coverage in this specific population is currently unknown. This study aims to determine the adherence to influenza vaccination in a PAD population and identify associated determinants. Patients and methods. Hospitalized patients and outpatients with PAD from two university departments of vascular medicine were prospectively included. A questionnaire was administered to collect sociodemographic data, cardiovascular risk factors, influenza vaccination status, history of cardiovascular disease, and perception and knowledge about vaccination. Logistic regression was conducted to assess vaccination determinants. Results: Over a six-month period, 494 patients were included (median age 69.5, IQR [63-77], 78% male). Overall, 60.1% were either vaccinated or intended to be (Group 1). Vaccination was associated with age (odds-ratio [OR]=1.055, 95% confidence intervals [95%CI]: 1.035-1.075, p<0.0001), abdominal aorta aneurysm (OR=0.390, 95%CI: 0.229-0.664, p=0.001), chronic obstructive pulmonary disease (OR=0.545, 95%CI: 0.367-0.810, p=0.003), chronic renal disease (OR=0.630, 95%CI: 0.400-0.993, p=0.046), and valvulopathy (OR=2.444, 95%CI: 1.122-5.326, p=0.025). Only 25.3% received vaccination information mainly from their general practitioners. Among patients against vaccination, 59.9% considered themselves not concerned about potential influenza consequences on their PAD, and 37.6% did not intend to change their decision. Conclusions: This study highlights the low adherence to influenza vaccination in the PAD population of 2 university hospital centers. Vaccination is often related to age, and there is a need for adapted information regarding influenza consequences on cardiovascular disease overall, particularly on PAD. Addressing common information and advice about vaccination will be a challenge.

Background: To investigate whether the relationship between smoking and peripheral artery disease (PAD) differs by sex (PROSPERO CRD42022352318)., Methods: PubMed, EMBASE, and CINAHL were searched (3 March 2024) for studies reporting associations between smoking and PAD in both sexes, at least adjusted for age. Data were pooled using random effects. Between-study heterogeneity was examined using I2 statistic and Cochran's Q test. Newcastle-Ottowa Scale was adopted for quality assessment., Results: Four cohort studies (n = 2,117,860, 54.4% women) and thirteen cross-sectional studies (n = 230,436, 59.9% women) were included. In cohort studies, former and current smokers had higher risk of PAD than never smokers. Compared to those who never or previously smoked, women current smokers (relative risk (RR) 5.30 (95% confidence interval 3.17, 8.87)) had higher excess risk of PAD than men (RR 3.30 (2.46, 4.42)), women-to-men ratio of RR 1.45 (1.30, 1.62)(I2 = 0%, p = 0.328). In cross-sectional studies, risk of PAD was higher among former and current compared to never smokers, more so in men, women-to-men ratios of odds ratio: 0.64 (0.46, 0.90)(I2 = 30%, p = 0.192), 0.63 (0.50, 0.79)(I2 = 0%, p = 0.594), respectively. For both sexes, risk of PAD was higher among current smokers compared to those who were not currently smoking. Cohort studies and five cross-sectional studies were of good quality, scoring 6 to 8 of a possible maximum 9 points. Eight cross-sectional studies scored 2 to 5., Discussions: Further research is required to elucidate sex differences in the relationships between smoking and PAD, as the current evidence is limited and mixed. Tobacco-control programs should consider both sexes., Competing Interests: MW has done recent consultancy for Amgen and Freeline outside the submitted work, no support from any organization, for the submitted work, no other relationships or activities that could appear to have influenced the submitted work. All other authors have nothing to declare., (Copyright: © 2024 Xu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Aim: Patients with peripheral artery disease (PAD) represent a high-risk population with increased morbidity and mortality. We aimed to examine trends in myocardial infarction (MI), PAD and adverse clinical outcomes from years 2000 to 2019., Methods: This nationwide Danish-based registry study included all patients with MI from years 2000-2019. Patients with PAD were compared to patients without PAD. Temporal changes in PAD prevalence over time was examined using the Cochrane-Armitage trend test, and Cox regression was used to test for between-group significance in all care and outcome measures., Results: A total of 196,635 patients experienced an MI within the study time frame; the prevalence of PAD over time showed a slight increase (p < 0.01). Patients with MI and a concurrent PAD diagnosis elicited a heavier burden of comorbidities. The primary MACE endpoint showed significant decreases in both patients with and without PAD (p < 0.01); the decrease was more marked in patients without a concurrent PAD diagnosis (p < 0.01) alongside with 1-year all-cause mortality (p < 0.01). There was a slight increase in initiation of preventive pharmacotherapy with a prominent increase in initiation of P2Y12-inhibitors post discharge in patients without PAD in comparison to patients with PAD, and the same pattern applied for lipid lowering agents (p < 0.01). Also, there was an increase in revascularization in patients with MI but more markedly in patients without coexisting PAD., Conclusions: Despite significant decreases in MACE and mortality and significant increases in guideline-recommended care and revascularization over time for MI patients both with and without PAD, improvement in all these measures was less prominent in patients with MI and concomitant PAD., Competing Interests: Declaration of competing interest The authors report no relationships that could be construed as a conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The aim of our study was to explore the characteristics of the arterial risk factors and ankle-brachial index (ABI) in patients with lower extremity chronic venous disease (LECVD)., Methods: A total of 2642 subjects were employed in our study. The lifestyle and clinical data were collected. The history of vascular diseases contained coronary artery disease, stroke, hypertension, and diabetes. ABI low than 0.9 was considered as lower extremity artery disease (LEAD). A series of blood indicators were measured., Results: Patients with ABI low than 0.9 belonged to the group of LEAD. Age, smoking, drinking, hypertension, diabetes mellitus, lipid-lowering drug, antidiabetic, total protein, total protein, triglyceride, low-density lipoprotein cholesterol, glycosylated hemoglobin and homocysteine were the common risk factors shared by LEAD and LECVD (P<0.05). The prevalence of LEAD in patients with LECVD was higher than those without LECVD (P<0.05). In Pearson correlation analysis, LECVD was related to LEAD (P<0.05). Before and after adjusted shared factors, as the performance of the logistic regression models, LEAD was an independent risk factor for the prevalence of LECVD (OR=2.937, 95% CI: [1.956, 4.411], P<0.001)., Conclusions: Our study demonstrated that an ABI lower than 0.9 is an independent risk factor for LECVD.

Background: Smoking represents the well-known enemy of vascular well-being. Numerous previous studies emphasised the important role of smoking on the development and progression of atherosclerotic cardiovascular disease. The current study aimed to identify hurdles and barriers for an insufficient implementation of secondary prevention in the treatment of lower extremity peripheral arterial disease (PAD). Methods: All members of the German Society for Vascular Surgery and Vascular Medicine (DGG) with valid email addresses were invited to participate in an electronic survey on smoking. Results are descriptively presented. Results: Amongst 2716 invited participants, 327 (12%) submitted complete responses, thereof 33% women and 80% between 30 and 59 years old (87% board certified specialists). 83% were employed by hospitals (56% teaching hospital, 14% university, 13% non-academic) and 16% by outpatient facilities. 6% are active smokers (63% never) while a mean of five medical education activities on smoking cessation were completed during the past five years of practice. Only 27% of the institutions offered smoking cessation programs and 28% of the respondents were aware of local programs while a mean of 46% of their patients were deemed eligible for participation. 63% of the respondents deemed outpatient physicians primarily responsible for smoking cessation, followed by medical insurance (26%). Conclusions: The current nationwide survey of one scientific medical society involved in the care of patients with vascular disease revealed that smoking cessation, although being commonly accepted as important pillar of comprehensive holistic care, is not sufficiently implemented in everyday clinical practice.