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Peripheral arterial disease (PAD) is a major health problem in Switzerland, as myocardial infarction or stroke, all three sharing common cardiovascular (CV) risk factors and similar pathophysiological mechanisms (atherosclerosis). Unfortunately, PAD is still often overlooked, despite being fraught with significant morbidity/mortality and increasing the patient's overall CV risk. It is therefore essential to improve secondary prevention in order to decrease this burden and the overall CV risk of the patient. We will review the treatment targets for CV risk factors as secondary prevention in patients with PAD and see how the use of a vascular passport may improve management., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Peripheral arterial disease (PAD) is a widespread disease with high impact on global health. While general population screening is not currently indicated, the primary care physician has the critical role of identifying asymptomatic patients who are particularly at risk for PAD and could therefore benefit from screening. In addition, he or she must recognize the typical and atypical clinical presentations of patients with symptomatic PAD to ensure proper diagnosis and care. After an adequate medical history and clinical examination, the first diagnostic test is the « Ankle-Brachial Index » (ABI) calculation. In case of pathologic ABI (≤ 0.9, or > 1.4), or in case of normal or borderline ABI with symptoms, the patient should be referred to a vascular medicine physician for diagnostic confirmation and management., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Background Peripheral artery disease (PAD) and coronary artery disease (CAD) represent atherosclerosis in different vascular beds. We used detailed metabolic biomarker profiling to identify common and discordant biomarkers and clarify pathophysiological differences for these vascular diseases. Methods and Results We used 5 prospective cohorts from Finnish population (FINRISK 1997, 2002, 2007, and 2012, and Health 2000; n=31 657; median follow-up time of 14 years) to estimate associations between >200 metabolic biomarkers and incident PAD and CAD. Metabolic biomarkers were measured with nuclear magnetic resonance, and disease events were obtained from nationwide hospital records. During the follow-up, 498 incident PAD and 2073 incident CAD events occurred. In age- and sex-adjusted Cox models, apolipoproteins and cholesterol measures were robustly associated with incident CAD (eg, hazard ratio [HR] per SD for higher apolipoprotein B/A-1 ratio, 1.30; 95% CI, 1.25-1.36), but not with incident PAD (HR per SD for higher apolipoprotein B/A-1 ratio, 1.04; 95% CI, 0.95-1.14; P heterogeneity <0.001). In contrast, triglyceride levels in low-density lipoprotein and high-density lipoprotein were associated with both end points ( P heterogeneity >0.05). Lower proportion of polyunsaturated fatty acids relative to total fatty acids, and higher concentrations of monounsaturated fatty acids, glycolysis-related metabolites, and inflammatory protein markers were strongly associated with incident PAD, and many of these associations were stronger for PAD than for CAD ( P heterogeneity <0.001). Most differences in metabolic profiles for PAD and CAD remained when adjusting for traditional risk factors. Conclusions The metabolic biomarker profile for future PAD risk is distinct from that of CAD. This may represent pathophysiological differences.

Background Data are sparse on the prospective associations between physical activity and incidence of lower extremity peripheral artery disease (PAD). Methods and Results Linking participant data from the CCLS (Cooper Center Longitudinal Study) to Medicare claims files, we studied 19 023 participants with objectively measured midlife cardiorespiratory fitness through maximal effort on the Balke protocol who survived to receive Medicare coverage between 1999 and 2009. The study aimed to determine the association between midlife cardiorespiratory fitness and incident PAD with proportional hazards intensity models, adjusted for age, sex, body mass index, and other covariates, to PAD failure time data. During 121 288 person-years of Medicare follow-up, we observed 805 PAD-related hospitalizations/procedures among 19 023 participants (21% women, median age 50 years). Lower midlife fitness was associated with a higher rate of incident PAD in patients aged 65 years and older (low fit [quintile 1]: 11.4, moderate fit [quintile 2 to 3]: 7.8, and high fit [quintile 4 to 5]: 5.7 per 1000 person years). After multivariable adjustment for common predictors of incident PAD such as age, body mass index, hypertension, and diabetes, these findings persisted. Lower risk for PAD per greater metabolic equivalent task of fitness was observed (hazard ratio [HR], 0.93 [95% CI, 0.90-0.97]; P <0.001). Among a subset of patients with an additional fitness assessment, each 1 metabolic equivalent task increase from baseline fitness was associated with decreased risk of incident PAD (HR, 0.90 [95% CI, 0.82-0.99]; P =0.03). Conclusions Cardiorespiratory fitness in healthy, middle-aged adults is associated with lower risk of incident PAD in later life, independent of other predictors of incident PAD.

Objective: The aim of this study was to examine whether there were independent associations between abdominal aortic diameter, size index, and height index and the risk of major adverse events in patients referred for treatment of various types of aortic and peripheral occlusive and aneurysmal disease (APOAD)., Methods: In total, 1 752 participants with a variety of APOADs were prospectively recruited between 2002 and 2020 and had a maximum abdominal aortic diameter, aortic size index (aortic diameter relative to body surface area), and aortic height index (aortic diameter relative to height) measured by ultrasound at recruitment. Participants were followed for a median of 4.6 years (interquartile range 2.0 - 8.0 years) to record outcome events, including major adverse cardiovascular events (MACE), peripheral artery surgery, abdominal aortic aneurysm (AAA) events (rupture or repair), and all cause mortality. The association between aortic size and events was assessed using Cox proportional hazard analysis. The ability of aortic size to improve risk of events classification was assessed using the net reclassification index (NRI)., Results: After adjusting for other risk factors, larger aortic diameter was associated with an increased risk of MACE (hazard ratio [HR] 1.17, 95% confidence interval [CI] 1.05 - 1.31), requirement for peripheral artery surgery (HR 2.05, 95% CI 1.90 - 2.22), AAA events (HR 3.01, 95% CI 2.77 - 3.26), and all cause mortality (HR 1.20, 95% CI 1.08 - 1.32). Findings were similar for aortic size and aortic height indices. According to the NRI, all three aortic size measures significantly improved classification of risk of peripheral artery surgery and AAA events but not MACE. Aortic size index, but not aortic diameter or aortic height index, significantly improved the classification of all cause mortality risk., Conclusion: Larger abdominal aortic diameter, size index, and height index are all independently associated with an increased risk of major adverse events in patients with established vascular disease., Competing Interests: Conflicts of interest None., (Copyright © 2021 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)

Objectives: Rheumatoid arthritis (RA), along with glucocorticoid use, is associated with cardiovascular disease. Cardiovascular safety of glucocorticoids in RA is controversial and may be related to dose and duration of use. We determined if initiating glucocorticoids in steroid-naive RA patients would increase cardiovascular event (CVE) risk in a dose and duration-dependent manner over short-term intervals., Methods: Patients enrolled in CorEvitas (formerly Corrona) RA registry. Cox proportional-hazards models estimated adjusted HRs (aHR) for incident CVE in patients who initiated glucocorticoid treatment, adjusting for RA duration, traditional cardiovascular risk factors and time-varying covariates: Clinical Disease activity Index, disease-modifying antirheumatic drugs use and prednisone-equivalent use. Glucocorticoid use assessed current daily dose, cumulative dose and duration of use over rolling intervals of preceding 6 months and 1 year., Results: 19 902 patients met criteria. 1106 CVE occurred (1.66/100 person-years). Increased aHR occurred at current doses of ≥5-9 mg 1.56 (1.18-2.06) and ≥10 mg 1.91 (1.31-2.79), without increased risk at 0-4 mg 1.04 (0.55-1.59). Cumulative dose over preceding 6 months showed increased aHR at 751-1100 mg 1.43 (1.04-1.98) and >1100 mg 2.05 (1.42-2.94), without increased risk at lower doses; duration of use over preceding 6 months exhibited increased aHR for >81 days of use 1.54 (1.08-2.32), without increased risk at shorter durations. One-year analyses were consistent., Conclusions: Over preceding 6-month and 1-year intervals, initiating glucocorticoids in steroid-naïve RA patients is associated with increased risk of CVE at daily doses ≥5 mg and increased cumulative dose and duration of use. No association with risk for CVE was found with daily prednisone of ≤4 mg or shorter cumulative doses and durations., Competing Interests: Competing interests: AJO has no financial conflicts of interest. GR and JMK are consultants for Corrona, LLC. GR is a consultant for the Corrona Research Foundation (CRF), while JMK is an officer of the CRF who serves without any form of remuneration. The CRF is a not for profit, 501(C)(3) independent charitable foundation, with no industry financial ties. DAP is an employee and shareholder of Corrona, and a consultant for Regeneron, Novartis and Roche (unrelated work), and is a member of the board of directors for CFR. JRC has research grants and/or consulting from Abbvie, Amgen, Corrona, Janssen, Lilly, Pfizer, Sanofi (for unrelated work)., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Low high-density lipoprotein (HDL)-cholesterol is frequent in patients with peripheral artery disease (PAD) and also in type 2 diabetes mellitus (T2DM), the major risk factor for PAD. The transfer of cholesterol from the other lipoproteins to HDL is an important aspect of HDL metabolism and function, and may contribute to atherogenic mechanisms that lead to PAD development., Objective: The aim of this study was to investigate the status of cholesterol transfers in patients with PAD without or with T2DM., Methods: Patients with PAD ( n = 19), with PAD and T2DM (PAD + DM, n = 19), and healthy controls ( n = 20), all paired for age, sex, and BMI were studied. Transfer of both forms of cholesterol, unesterified (UC) and esterified (EC), was performed by incubating plasma with a donor nanoemulsion containing radioactive UC and EC, followed by chemical precipitation and HDL radioactive counting., Results: Low-density lipoprotein (LDL)-cholesterol and triglycerides were similar in the three groups. Compared to controls, HDL-C was lower in PAD + DM ( p < 0.05), but not in PAD. Transfer of UC was lower in PAD + DM than in PAD and controls (4.18 ± 1.17%, 5.13 ± 1.44%, 6.59 ± 1.25%, respectively, p < 0.001). EC transfer tended to be lower in PAD + DM than in controls (2.96 ± 0.60 vs 4.12 ± 0.89%, p = 0.05). Concentrations of cholesteryl ester transfer protein (CETP) and lecithin-cholesterol acyltransferase (LCAT), both involved in HDL metabolism, were not different among the three groups., Conclusion: Deficient cholesterol transfer to HDL may play a role in PAD pathogenesis. Since UC transfer to HDL was lower in PAD + DM compared to PAD alone, it is possible that defective HDL metabolism may contribute to the higher PAD incidence in patients with T2DM.Keywords.

Peripheral artery disease (PAD) is a systemic disease associated with impaired limb function, poor quality of life, and increased cardiovascular morbidity. Its incidence has been dramatically increasing over years because of the emergence of an aging society and the increase in the number of patients with atherosclerotic risk factors. The clustering of these risk factors promotes disease development, reportedly leading to the differential location of atherosclerotic lesions in lower extremity arteries. The clinical presentations of PAD include intermittent claudication and chronic limb-threatening ischemia (CLTI). PAD is associated with a high risk of mortality and morbidity from both cardiovascular and limb events. The therapeutic goals for patients with PAD include 1) relief from PAD-related limb symptoms, 2) the prevention of new-onset and the development and recurrence of PAD, and 3) the prevention of concomitant adverse events due to coronary artery disease (CAD) and cerebrovascular disease (CVD). There are several types of antithrombotic agents, and their main role in patients with PAD is to reduce systemic events mainly including cardiovascular and lower extremity-related events. Currently, the efficacy of direct oral anticoagulant (DOAC) is also suggested by recent clinical trials. Although endovascular therapy (EVT) has been a first-line revascularization strategy for symptomatic PAD, whether clinical outcomes after EVT are comparable to those after surgical bypass therapy remains inconclusive.

Objective: To assess the association between long term risk of hospitalisation for heart failure (HHF) and lower extremity minor and major amputation (LEA) in patients initiating sodium glucose cotransporter 2 inhibitors (SGLT2i) suffering from type 2 diabetes and peripheral arterial disease (PAD). Outcomes were compared with patients without PAD and evaluated separately for the time periods before and after the official warning of the European Medicines Agency (EMA) in early 2017., Methods: This study used BARMER German health claims data including all patients suffering from type 2 diabetes initiating SGLT2i therapy between 1 January 2013 and 31 December 2019 with follow up until the end of 2020. New users of glucagon like peptide 1 receptor agonists (GLP1-RAs) were used as active comparators. Inverse probability weighting with truncated stabilised weights was used to adjust for confounding, and five year risks of HHF and LEA were estimated using Cox regression. Periods before and after the EMA warning were analysed separately and stratified by presence of concomitant PAD., Results: In total, 44 284 (13.6% PAD) and 56 878 (16.3% PAD) patients initiated SGLT2i or GLP1-RA, respectively. Before the EMA warning, initiation of SGLT2i was associated with a lower risk of HHF in patients with PAD (hazard ratio, HR, 0.85, 95% confidence interval, CI, 0.73 - 0.99) and a higher risk of LEA in patients without PAD (HR 1.79, 95% CI 1.04 - 2.92). After the EMA warning, the efficacy and safety endpoints were no longer statistically different between groups., Conclusion: The results from this large nationwide real world study highlight that PAD patients exhibit generally high amputation risks. This study refutes the idea that the presence of PAD explains the excess LEA risk associated with initiation of SGLT2i. The fact that differentials among study groups diminished after the EMA warning in early 2017 emphasises that regulatory surveillance measures worked in everyday clinical practice., (Copyright © 2021 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)

Background: The relationship between obesity indices and arterial stiffness (AS) has not been fully discovered nor has it been studied in depth in large hypertensive patient populations. The aim of this study was to explore the association between body mass index (BMI) and waist-hip ratio (WHR) levels and AS based on brachial-ankle pulse wave velocity (baPWV) in Chinese rural adults with hypertension., Methods: This cross-sectional study analyzed 5049 Chinese rural adults with essential hypertension. BMI was calculated as the body weight in kilograms divided by the square of the height in meters (kg/m 2 ). Central obesity was defined as WHR ≥ 0.9 for males and ≥ 0.85 for females. Measurement of arterial stiffness was carried out via brachial-ankle pulse wave velocity (baPWV)., Results: The prevalence of overweight, general obesity, central obesity and increased AS were 26.88%, 3.39%, 63.85% and 44.01%, respectively. Multivariate logistic regression analysis indicated that BMI levels were negatively associated with the prevalence of increased AS (adjusted-OR per SD increase: 0.74, 95% CI 0.67-0.81, P < 0.001). When BMI was instead treated as a categorical variable divided into tertiles, the same relationship was observed (P for trend < 0.001). Inversely, WHR levels were positively associated with the prevalence of increased AS (adjusted-OR per SD increase: 1.25, 95% CI 1.14-1.36, P < 0.001). Compared to subjects without central obesity, those with central obesity had a higher prevalence of increased AS (adjusted-OR: 1.52, 95% CI 1.28-1.81, P < 0.001). Linear regression models indicated similar results in the correlation between BMI or WHR levels and baPWV levels (adjusted-β per SD increase: - 0.57, 95% CI - 0.68 to - 0.46, P < 0.001; adjusted-β per SD increase: 4.46, 95% CI 3.04-5.88, P < 0.001). There were no interactions in terms of age and blood pressure on the relationship between BMI or WHR levels and the prevalence of increased AS or baPWV levels., Conclusion: There was an inverse relationship between BMI levels and increased AS or baPWV levels, whereas WHR levels and central obesity were positively associated with increased AS or baPWV levels in Chinese rural adults with hypertension., (© 2021. The Author(s).)

Introduction: The coronavirus disease 2019 (COVID-19) pandemic's impact on vascular procedural volumes and outcomes has not been fully characterized., Methods: Volume and outcome data before (1/2019 - 2/2020), during (3/2020 - 4/2020), and following (5/2020 - 6/2020) the initial pandemic surge were obtained from the Vascular Quality Initiative (VQI). Volume changes were determined using interrupted Poisson time series regression. Adjusted mortality was estimated using multivariable logistic regression., Results: The final cohort comprised 57,181 patients from 147 US and Canadian sites. Overall procedure volumes fell 35.2% (95% CI 31.9%, 38.4%, p < 0.001) during and 19.8% (95% CI 16.8%, 22.9%, p < 0.001) following the surge, compared with presurge months. Procedure volumes fell 71.1% for claudication (95% CI 55.6%, 86.4%, p < 0.001) and 15.9% for chronic limb-threatening ischemia (CLTI) (95% CI 11.9%, 19.8%, p < 0.001) but remained unchanged for acute limb ischemia (ALI) when comparing surge to presurge months. Adjusted mortality was significantly higher among those with claudication (0.5% vs 0.1%; OR 4.38 [95% CI 1.42, 13.5], p = 0.01) and ALI (6.4% vs 4.4%; OR 2.63 [95% CI 1.39, 4.98], p = 0.003) when comparing postsurge with presurge periods., Conclusion: The first North American COVID-19 pandemic surge was associated with a significant and sustained decline in both elective and nonelective lower-extremity vascular procedural volumes. When compared with presurge patients, in-hospital mortality increased for those with claudication and ALI following the surge.

Introduction: We investigated the associations of high-sensitivity cardiac Troponin T (hs-cTnT) and N-terminal pro B-type natriuretic peptide (NT-proBNP) levels with risk of developing clinical peripheral artery disease (PAD) or a low ankle-brachial index (ABI)., Methods: Hs-cTnT and NT-proBNP were measured in 6692 and 5458 participants respectively without baseline PAD between 2000 and 2002 in the Multi-ethnic Study of Atherosclerosis. A significant number also had repeat biomarker measurement between 2004 and 2005. Incident clinical PAD was ascertained through 2017. Incident low ABI, defined as ABI <0.9 and decline of ≥0.15 from baseline, was assessed among 5920 eligible individuals who had an ABI >0.9 at baseline and at least one follow-up ABI measurement 3-10 years later. Multivariable Cox proportional hazards and logistic regression modeling were used to determine the association of these biomarkers with clinical PAD and low ABI, respectively., Results: Overall, 121 clinical PAD and 118 low ABI events occurred. Adjusting for demographic and clinical characteristics, each log unit increment in hs-cTnT and NT-proBNP was associated with a 30% (adjusted hazard ratio (HR) 1.3, 95% confidence interval (CI): 1.1, 1.6) and 50% (HR) 1.5, 95% CI: 1.2, 1.8) higher risk of clinical PAD respectively. No significant associations were observed for incident low ABI. Change in these biomarkers was not associated with either of the PAD outcomes., Conclusions: NT-proBNP and hs-cTnT are independently associated with the development of clinical PAD. Further study should determine whether these biomarkers can help to better identify those at higher risk for PAD., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background Ankle-brachial index (ABI) is used to identify lower-extremity peripheral artery disease (PAD). However, its association with severe ischemic leg outcomes (eg, amputation) has not been investigated in the general population. Methods and Results Among 13 735 ARIC (Atherosclerosis Risk in Communities) study participants without clinical manifestations of PAD (mean age, 54 [SD, 5.8] years; 44.4% men; and 73.6% White) at baseline (1987-1989), we quantified the prospective association between ABI and subsequent severe ischemic leg outcomes, critical limb ischemia (PAD with rest pain or tissue loss) and ischemic leg amputation (PAD requiring amputation) according to discharge diagnosis. Over a median follow-up of ≈28 years, there were 221 and 129 events of critical limb ischemia and ischemic leg amputation, respectively. After adjusting for demographics, ABI ≤0.90 versus 1.11 to 1.20 had a ≈4-fold higher risk of critical limb ischemia and ischemic leg amputation (hazard ratios, 3.85 [95% CI, 2.09-7.11] and 4.39 [95% CI, 2.08-9.27]). The magnitude of the association was modestly attenuated after multivariable adjustment (hazard ratios, 2.44 [95% CI, 1.29-4.61] and 2.72 [95% CI, 1.25-5.91], respectively). ABI 0.91 to 1.00 and 1.01 to 1.10 were also associated with these severe leg outcomes, with hazard ratios ranging from 1.7 to 2.0 after accounting for potential clinical and demographic confounders. The associations were largely consistent across various subgroups. Conclusions In a middle-aged community-based cohort, lower ABI was independently and robustly associated with increased risk of severe ischemic leg outcomes. Our results further support ABI ≤0.90 as a threshold diagnosing PAD and also suggest the importance of recognizing the prognostic value of ABI 0.91 to 1.10 for limb prognosis.

Aims: Peripheral artery disease (PAD) constitute a high-risk with adverse clinical outcomes. We aimed to investigate the cardiovascular outcomes following myocardial infarction (MI)., Methods and Results: This nationwide, Danish register-based follow-up study includes all patients experiencing an MI between 2000 and 2017. Patients with and without PAD were compared. Multivariable logistic regression was used to derive relative risks of 1-year major adverse cardiovascular events (MACE; all-cause mortality, reinfarction, stroke or heart failure). Individual components, cardiovascular mortality, and bleeding, standardized to age, sex and comorbidity distributions of all patients were assessed. MI patients with PAD (n = 5083, 2.9%) were older and more comorbid compared to patients without PAD (n = 174,673). After standardization, PAD was associated with higher 1-year relative risks of MACE (RR 1.21 [95% CI 1.17;1.25]), all-cause (RR 1.29 [95% CI 1.24;1.35]) and cardiovascular mortality (RR 1.3 [95% CI 1.24;1.36]), reinfarction (RR 1.17 [95% CI 1.11;1.22]), stroke (RR 1.12 [95% CI 0.92;1.32]), heart failure (RR 1.22 [95% CI 1.12;1.32]), and bleeding episodes (RR 1.25 [95% CI 1.04,1.46]). Similar results were seen in 30-day survivors after adjustment for antithrombotic post-discharge medication for MACE (RR 1.25 [95% CI 1.20,1.31]), all-cause mortality (RR 1.47 [95% CI 1.37,1.57], cardiovascular mortality (RR 1.49 [95% CI 1.37,1.61]), reinfarction (RR 1.17 [95% CI 1.08,1.12]) and heart failure (RR 1.22 [95% CI 1.12,1.32])., Conclusion: Comparing to patients without PAD, patients with PAD had increased 1-year relative risk of MACE, all-cause mortality, reinfarction, stroke, heart failure, cardiovascular mortality and bleeding following MI. The low prevalence of PAD is suggestive of considerable under-diagnosing., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: RBP4 is an adipokine with an established role in atherosclerosis, while adiponectin has unique anti-inflammatory properties. We investigated the association of RBP4 and adiponectin with the presence of symptomatic peripheral artery disease (PAD) and their possible prognostic role in major adverse cardiovascular events (MACE)., Methods: We enrolled 168 consecutive patients with symptomatic, established PAD, requiring revascularization by endovascular means of any or both of their lower limbs. 88 age- and sex-matched subjects with less than 2 classical cardiovascular risk factors served as controls. Clinical parameters, glycemic and lipid profile, RBP4 and adiponectin levels were assayed. The occurrence of MACE was recorded during the 6-month follow-up and patients were assigned to MACE and non-MACE subgroups., Results: The presence of symptomatic PAD was significantly correlated with age, diabetes, hsCRP, RBP4 and low adiponectin levels (p < 0.05). After adjustment for age, RBP4 (β = 0.498, p < 0.001), and adiponectin (β = -0.288, p < 0.001) levels remained as independent predictors of PAD presence in the whole study cohort. At baseline, MACE subgroup appeared with higher RBP-4 and hsCRP serum levels than non-MACE subgroup (p < 0.001), but no differences were detected for adiponectin (p = 0.758). Serum RBP4 levels remained independent predictor of MACE (β = 0.455, p < 0.001) after adjustment for traditional cardiovascular risk factors., Conclusions: High RBP4 and low adiponectin serum levels are independently associated with PAD presence. In addition, RBP4 is an independent predictor of MACE incidence in symptomatic PAD patients., (© 2021. The Author(s).)

Background: Previous observational studies reported a wide variation and possible room for improvement in the treatment of patients suffering from symptomatic peripheral artery disease (PAD). Yet, systematic assessment of everyday clinical practice is lacking. A General Data Protection Regulation (GDPR) compliant registry was developed and used to collect comprehensive data on clinical treatment and outcomes regarding PAD in Germany. Here, we report baseline characteristics of patients prospectively enrolled until the end of 2020. Methods: The GermanVasc registry study is a prospective longitudinal multicentre cohort study. Between 1 st May 2018 and 31 st December 2020, invasive endovascular, open-surgical, and hybrid revascularisations of patients suffering from chronic symptomatic PAD were prospectively included after explicit informed consent (NCT03098290). For ensuring high quality of the data, we performed comprehensive risk-based and random-sample external and internal validation. Results: In total, 5608 patients from 31 study centres were included (34% females, median 69 years). On-site monitoring visits were performed at least once in all centres. The proportion of chronic limb-threatening ischaemia was 30% and 13% were emergent admissions. 55% exhibited a previous revascularisation. Endovascular techniques made 69% among all documented invasive procedures (n=6449). Thirty-five percent were classified as patients with severe systemic disease, and 3% exhibited a constant threat to life according to the American Society of Anaesthesiologists classification. The risk profile comprised of 75% former or current smokers, 36% diabetes mellitus, and in 30% a current ischemic heart disease was present. At discharge, 93% of the patients received antiplatelets and 77% received statins. Conclusions: The GermanVasc registry study provides insights into real-world practice of treatment and outcomes of 5,608 patients with symptomatic PAD in Germany. The cohort covers a broader range of disease severity and types of interventions than usually found in trials. In future studies, comparative outcomes will be analysed in more detail.

Introduction: The prevalence of type 2 diabetes mellitus (T2DM) is higher in peripheral artery disease (PAD) than in coronary artery disease (CAD) patients, and PAD overall confers higher cardiovascular risk than CAD. How cardiovascular risk compares between PAD and CAD patients when analyses are stratified by the presence of type 2 diabetes is unclear and is addressed in the present study., Research Design and Methods: We prospectively recorded major cardiovascular events (MACE; ie, cardiovascular death, myocardial infarction or stroke) over 10.0±4.7 years in 923 patients with stable CAD, of whom 26.7% had T2DM and in 292 patients with PAD, of whom 42.1% had T2DM. Four groups were analyzed: CAD patients without diabetes (CAD/T2DM-; n=677), CAD patients with T2DM (CAD/T2DM+; n=246), PAD patients without diabetes (PAD/T2DM-; n=169) and PAD patients with T2DM (PAD/T2DM+; n=123)., Results: The event rate for MACE increased over our four investigated groups: it was lowest in CAD/T2DM- patients (2.52 events per 100 person-years). It was significantly higher in CAD/T2DM+ patients (3.96 events per 100 person-years; p<0.001), in PAD/T2DM- patients (3.68 events per 100 person-years; p=0.022), and in PAD/T2DM+ patients (7.10 events per 100 person-years; p<0.001), who in turn were at a higher risk than CAD/T2DM+ or PAD/T2DM- patients (p=0.001 and p<0.001, respectively). Cox regression analysis after multivariate adjustment showed that the presence of T2DM (HR=1.44 (95% CI 1.09 to 1.92); p=0.012) and the presence of PAD versus CAD (HR=1.48 (95% CI 1.15 to 1.91); p=0.002) were mutually independent predictors of cardiovascular events., Conclusions: In conclusion, our data show that T2DM as well as the presence of PAD versus CAD are mutually independent predictors of MACE. Patients with both PAD and T2DM are at an exceedingly high risk of cardiovascular events., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The beneficial effect of multifactorial treatment of cardiovascular (CV) risk factors (RFs) in type 2 diabetes (T2D) is well established from randomized clinical trials. We prospectively evaluated the impact of such treatment in a real-world setting, on the development of subclinical arterial damage (SAD), as determined by structural/functional noninvasive biomarkers of vascular pathology (atheromatosis, carotid hypertrophy, arteriosclerosis). We prospectively studied 116 persons with T2D, treated with a multifactorial approach for CV RFs at a tertiary medical center, and 324 individuals without diabetes, for 3.2 years. The primary outcome was changes in vascular biomarkers related to SAD. At baseline, participants in the diabetes group had higher prevalence of SAD. At study end, the changes in clinical, biochemical, and lifestyle characteristics, as well as antihypertensive and lipid-lowering treatments, were comparable between the 2 groups. During follow-up, classical CV RFs (smoking, blood pressure, low-density lipoprotein-cholesterol, triglycerides) and behavioral features were significantly improved in both groups. Multivariate analysis, after adjusting for all classic CV RFs and use of antihypertensive/lipid-lowering therapies, demonstrated that all evaluated SAD biomarkers were similarly changed in the 2 groups. In conclusion, implementation of a multimodality approach of T2D treatment is feasible and efficacious in decelerating progression of SAD in routine clinical practice.

Charcot foot (CF) is a rare complication of diabetes associated with foot deformities and foot ulcers. Peripheral arterial disease (PAD) is a factor of poor prognosis in patients with diabetic foot ulcers (DFUs). However, PAD has infrequently been studied in CF. We aimed to determine the prevalence, the characteristics and the prognosis of PAD in a large group of patients with diabetic CF. We retrospectively compared 56 patients with diabetic CF to 116 patients with diabetic foot without CF. The prevalence of PAD in patients with CF was 66.1%. Compared to patients without CF, patients with CF had similar risks to have PAD (OR 0.98, 95%CI 0.50-1.94, p= .97) and neuro-ischemic DFUs (OR 1.19, 95%CI 0.57-2.49, p= .65), more risk to have lesions of distal arteries (OR 4.17, 95%CI 1.76-9.94, p= .001) and less risk to need revascularization (OR 0.14, 95%CI 0.06-0.36, p< .001). In patients with CF, PAD was strongly predicted by DFUs (OR 24.55, 95%CI 1.80-334.43, p= .016) and coronary artery disease (OR 17.11, 95%CI 1.75-167.43, p =.015). Survival rate and limb salvage rate in patients with CF were not worsened by PAD and by neuro-ischemic DFUs, respectively. In conclusion, we show that PAD should not be overlooked in patients with diabetic CF, especially in those having DFUs or coronary artery disease. PAD in patients with CF differed from that of patients without CF since it predominated in distal arteries and required less often revascularization., (Copyright © 2021 the American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.)

Aim: The aim of the current study was to describe the clinical profile, frequency of in-hospital complications, and predictors of adverse events in patients undergoing endovascular therapy (EVT) for acute limb ischemia (ALI), and to compare them with those of patients undergoing EVT for chronic symptomatic peripheral artery disease (PAD)., Methods: The current study compared 2,398 cases of EVT for ALI with 74,171 cases of EVT for chronic symptomatic PAD performed between January 2015 and December 2018 in Japan. We first compared the clinical profiles of ALI patients with those of PAD patients. We then evaluated the proportion of in-hospital complications and investigated their risk factors in the ALI patients. The association of clinical characteristics with the risk of in-hospital complications was analyzed via logistic regression modeling., Results: Patients with ALI were older and had a higher prevalence of female sex, impaired mobility, and history of cerebrovascular disease, but a lower prevalence of cardiovascular risk factors and history of coronary artery disease. The proportion of in-hospital EVT-related complications in ALI was 6.1% and was significantly higher compared with those in chronic symptomatic PAD patients (2.0%, P＜0.001). Bedridden status (adjusted odds ratio [aOR], 1.74 [1.14 to 2.66]; P=0.010), history of coronary artery disease (aOR, 1.80 [1.21 to 2.68]; P=0.004), and a suprapopliteal lesion (aOR, 1.70 [1.05 to 2.74]; P=0.030) were identified as independent risk factors for in-hospital complications., Conclusion: The current study demonstrated that ALI patients with significant comorbidities show a higher proportion of in-hospital complications after EVT.

Chronic limb-threatening ischemia requires aggressive risk factor management and a thoughtful approach to the complex decision of best strategy for revascularization. Patients often have multilevel disease amenable to endovascular, open surgical, or hybrid approaches. Limited high-quality evidence is available to support a specific strategy; randomized trials are ongoing. Acute limb ischemia is associated with a high risk of limb loss and mortality. Catheter-directed thrombolysis is mainstay of therapy in patients with marginally threatened limbs, whereas those immediately threatened with motor deficits require more rapid restoration of flow with open or endovascular techniques that can establish flow in single setting., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Previous studies reported that the aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio (AST/ALT) was a risk factor in cardiovascular disease. Peripheral artery disease (PAD) is an important risk factor for cardiovascular death. However, only a few studies investigated the correlations between the AST/ALT ratio and PAD. We analyzed data from 10 900 patients with hypertension from the Chinese Hypertension Registry Study; 350 patients had PAD (prevalence 3.2%). After adjusting for potential confounders, the AST/ALT ratio was independently and positively associated with risk of PAD (OR: 1.31, 95% CI, 1.13-1.59), and a significant increased risk of PAD for the third AST/ALT ratio tertile (T3) compared with the first tertile (T1; OR: 1.49, 95% CI, 1.09-2.04, P trend = .005) was found. Moreover, when we combined T1 and T2 into one group and used it as a reference group, the risk of PAD increased with the increase in AST/ALT; the risk ratio was 1.52 (95% CI, 1.20-1.95). A higher AST/ALT ratio (≥1.65) was associated with PAD risk in Chinese adults with hypertension. Our results suggest that the AST/ALT ratio may help identify patients at high risk of vascular end points and might be a convenient, economical, and effective tool for evaluating the risk of atherosclerosis.

Peripheral artery disease is a highly morbid yet undertreated atherosclerotic disease. The cornerstones of peripheral artery disease therapy consist of smoking cessation, lipid-lowering therapy, and hypertension treatment. More recently, clinical trials have demonstrated that novel antiplatelet and antithrombotic therapies reduce the risk of both cardiovascular and limb events in this patient population. In this review, we highlight the components of optimal medical therapy of peripheral artery disease and the evidence base for these therapies., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background and Aims: The ankle-brachial index (ABI) is a diagnostic test for screening and detecting peripheral artery disease (PAD), as well as a risk enhancer in the AHA/ACC guidelines on the primary prevention of atherosclerotic cardiovascular disease (ASCVD). However, our understanding of the association between ABI and cardiovascular risk in contemporary older populations is limited. Additionally, the prognostic value of ABI among individuals with prior ASCVD is not well understood., Methods: Among 5,003 older adults at ARIC visit 5 (2011-2013) (4,160 without prior ASCVD [median age 74 years, 38% male], and 843 with ASCVD [median age 76 years, 65% male]), we quantified the association between ABI and the risk of heart failure (HF), and composite coronary heart disease and stroke (CHD/stroke) using multivariable Cox regression models., Results: Over a median follow-up of 5.5 years, we observed 400 CHD/stroke events and 338 HF cases (242 and 199 cases in those without prior ASCVD, respectively). In participants without a history of ASCVD, a low ABI ≤0.9 (relative to ABI 1.11-1.20) was associated with both CHD/stroke and HF (adjusted hazard ratios 2.40 [95% CI: 1.55-3.71] and 2.23 [1.40-3.56], respectively). In those with prior ASCVD, low ABI was not significantly associated with CHD/stroke, but was with HF (7.12 [2.47-20.50]). The ABI categories of 0.9-1.2 and > 1.3 were also independently associated with increased HF risk. Beyond traditional risk factors, ABI significantly improved the risk discrimination of CHD/stroke in those without ASCVD and HF, regardless of baseline ASCVD., Conclusions: Low ABI was associated with CHD/stroke in those without prior ASCVD and higher risk of HF regardless of baseline ASCVD status. These results support ABI as a risk enhancer for guiding primary cardiovascular prevention and suggest its potential value in HF risk assessment for older adults., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: The COVID-19 pandemic has led to widespread postponement and cancelation of elective vascular surgeries in Switzerland. The consequences of these decisions are poorly understood., Patients and Methods: In this observational, retrospective, single-center cohort study, we describe the impact of COVID-19 pandemic containment strategies on patients with lower extremity peripheral arterial disease (PAD) referred during the period March 11, to May 11, 2020, compared to the same time frames in 2018 to 2019. Patients admitted for acute limb ischemia (ALI) or chronic PAD and undergoing urgent or elective vascular surgery or primary amputation were included. Patients' characteristics, indications for admission, and surgical features were analyzed. The occurrence of 30 day outcomes was assessed, including length of stay, rates of major adverse cardiovascular events (MACE) and major adverse limb events (MALE), and procedural and hemodynamic success., Results: Overall, 166 patients were included. Fewer subjects per 10 day period were operated in 2020 compared to, 2018 to 2019 (6.7 vs. 10.5, respectively; P < 0.001). The former had higher rates of chronic obstructive pulmonary disease (COPD) (25% vs. 11.1%; P = 0.029), and ASA score (3.13 vs. 2.90; P = 0.015). The percentage of patients with ALI in 2020 was about double that of the same period in 2018 to 2019 (47.5% vs. 24.6%; P = 0.006). Overall, the types of surgery were similar between 2020 and 2018 to 2019, while palliative care and primary amputations occurred only in 2020 (5 out 40 cases). The rate of post-operative MACE was significantly higher in 2020 (10% vs. 2.4%; P = 0.037)., Conclusions: During the first state of emergency for COVID-19 pandemic in 2020, less regular medical follow-up and hindered hospital access could have resulted in more acute and advanced clinical presentations of patients with PAD undergoing surgery. Guidelines are needed to provide appropriate care to this vulnerable population and avoid a large-scale disaster., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Vitamin D (VD) deficiency is considered an important risk factor for the development of atherosclerosis and aortic aneurysms. The deficiency is claimed to enhance degeneration and remodeling of collagen and elastin fibers in the artery wall, leading to its weakening and progressive dilatation. This study aimed to assess vitamin D status, in outpatients with abdominal aneurysms (AAA) and peripheral artery disease (PAD) not treated with VD, and factors affecting serum 25-OH-D levels., Methods and Results: This cross-sectional study involved 59 outpatients with AAA and 150 with PAD. AAA was defined as local dilation of the aorta diameter >30 mm in imaging. None of the patients was prescribed VD containing medicines. Serum 25-OH, iPTH, phosphorus and calcium levels were assessed in all study participants. VD status was categorized according to commonly used cut-offs for serum 25-OH-D (<20 ng/mL - deficiency, <30 ng/mL -insufficiency). Serum 25-OH-D levels were similar in patient with AAA and PAD [1-3Q: 26.2 (18.8-37.6) vs 21.8 (15.9-31.4) ng/mL; p = 0.30], with deficiency noted in 25.4% with AAA and 41.8% with PAD (p < 0.05). Multiple regression analysis revealed that VD deficiency was explained by past stroke episodes [OR = 2.80 (95%CI: 1.22-6.41)]. Secondary hyperparathyroidism was diagnosed in 1.7% of patients with AAA and 1.9% with PAD., Conclusions: The frequency of VD deficiency in outpatient with AAA is not greater than in those with PAD. Past stroke episode is associated with an increased occurrence of VD deficiency in both outpatients with AAA and PAD other than sun exposure and diet., Competing Interests: Declaration of competing interest We have no conflicts of interest to disclose., (Copyright © 2021 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background: Differences in comorbidity, pharmacotherapy, cardiovascular (CV) outcome, and mortality between myocardial infarction (MI) patients and peripheral arterial disease (PAD) patients are not well documented., Aim: The aim of this study was to compare comorbidity, treatment patterns, CV outcome, and mortality in MI and PAD patients, focusing on sex differences., Methods: This observational, population-based study used data retrieved from mandatory Swedish national registries. The risks of MI and death were assessed by Kaplan-Meier analysis. Secondary preventive drug use was characterized. Cox proportional risk hazard modelling was used to determine the risk of specific events., Results: Overall, 91,808 incident MI patients and 52,408 PAD patients were included. CV mortality for MI patients at 12, 24, and 36 months after index was 12.3%, 19.3%, and 25.4%, and for PAD patients it was 15.5%, 23.4%, and 31.0%. At index, 89% of MI patients and 65% of PAD patients used aspirin and 74% and 53%, respectively, used statins. Unlike MI women, women with PAD had a lower rate of other CV-related comorbidities and a lower risk of CV events (age-adjusted hazard ratio 0.81, 95% confidence interval 0.79‒0.84), CV death (0.78, 0.75‒0.82), and all-cause death (0.78, 0.76‒0.80) than their PAD male counterparts., Conclusion: PAD patients were less intensively treated and had a higher CV mortality than MI patients. Women with PAD were less likely than men to present with established polyvascular disease, whereas the opposite was true of women with MI. This result indicates that the lower-limb vasculature may more often be the index site for atherosclerosis in women., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Peripheral artery disease (PAD) is a progressive atherosclerotic disease that negatively affects individuals' functional status and health-related quality of life (HRQOL). This study aimed to investigate the HRQOL and associated factors in patients with PAD in Korea. We conducted a cross-sectional study using self-administered questionnaires in a tertiary hospital in Seoul. We measured HRQOL using the EuroQol-5 dimensions-5 levels (EQ-5D-5L) questionnaire and the functional status using a PAD-specific walking impairment questionnaire. We also measured health behavior, social support, walking impairment, general health perceptions, and clinical characteristics; lastly, we performed a descriptive analysis and multiple linear regression analysis. Participants of this study comprised 138 patients (mean age 69.04 ± 10.94 years; men 91.3%). The mean EQ-5D-5L utility score was 0.81 ± 0.17. The patients' HRQOL was significantly associated with claudication pain (β = -0.188, p = 0.012), walking distance (β = 0.371, p < 0.001), and stair climbing (β = 0.315, p = 0.001). The regression model predicted 60.4% of patients' HRQOL (F = 15.92, p < 0.001). Our study showed that less severe claudication pain and a low degree of difficulty in walking distance and stair climbing were significantly related to better HRQOL. To enhance patients' HRQOL, health professionals should focus on managing symptoms and improving functional status.

Diabetes mellitus (DM) and also anemia are common in the elderly and have a negative impact on the clinical outcomes of patients. The coexistence of anemia and DM seems to be insufficiently recognized; therefore, the aim of our study is to analyze the incidence and clinical consequences of this coexistence, including mortality, in the population of people aged ≥60. A retrospective study was conducted on 981 primary care clinic patients aged ≥60 during 2013-2014. The prevalence of coexistence of DM and anemia (defined in accordance with WHO) and data on the incidence of comorbidities, hospitalization, medical procedures, and all-cause mortality were analyzed. In the study population, 25% had DM, while 5.4% had both DM and anemia. Peripheral artery disease (PAD) was found in 48 patients (4.89%) of the entire study population, more often in men ( p < 0.001). Diabetic patients with anemia compared to nonanemic diabetics had more comorbidities (median 4 (4, 5) vs. 3 (2-4); p < 0.001)-PAD more often ( p = 0.004), more hospitalization (median 2 (0-11) vs. 0 (0-11); p < 0.001), and more frequent medical procedures (e.g., percutaneous coronary intervention ( p < 0.001), coronary artery bypass surgery ( p = 0.027), arteriography ( p < 0.001), and bypass surgery or endovascular treatments of lower limb ischemia ( p < 0.001)). The cumulative survival of patients with both DM and anemia vs. nonanemic diabetics at 36 months was 86.4% vs. 99.3% ( p < 0.001). A multivariate logistic regression model showed anemia to be a significant risk factor for death in diabetic patients ( p = 0.013). Patients with both DM and anemia have more comorbidities than nonanemic diabetic patients; they are more often hospitalized, require medical procedures more frequently, and are at a higher risk of death. Effective treatment of anemia in patients with DM is advisable and may well improve the prognosis of patients., Competing Interests: All authors declare that they have no conflict of interest., (Copyright © 2021 S. S. Michalak et al.)

The forthcoming increase in the number of people with diabetes mellitus (DM) is likely to lead to an absolute and relative increase in the number of people with a combination of DM and peripheral artery disease (PAD). Due to different pathophysiological processes and presentation, diagnosis and treatment in these patients are more complicated compared to non-DM related PAD. Understanding the differences, pitfalls and concerns in patients with combined DM-PAD would result in better care for these patients, who are at high risk of cardiovascular comorbidities, mortality and amputation. Introduced by two case reports, we provide an overview of current guidelines, recent literature and innovations to address these critical issues.

Introduction: Mixed arterial-venous lower extremity disease (AVLED) poses a unique challenge for clinicians. This review will outline the impact mixed AVLED has on patients and the healthcare system, by reviewing its epidemiology, diagnosis, current treatment, and the challenges encountered implementing therapies., Evidence Acquisition: An extensive search of current literature from online sources, journals and book chapters identified the current challenges facing the treatment of mixed arterial venous ulcers of the lower extremities and potential solutions to these challenges., Evidence Synthesis: The challenges that are identified in the search are the time to heal AVLED, patient education and motivation, early detection of AVLED, wound care center development, treatment consensus from multidisciplinary team members, and cost of treatment., Conclusions: AVLED ulcers are a challenging problem, but over time we have continued and will continue to improve patient care and tackle these difficult challenges as we have throughout the last century. A diagnostic algorithm to address how we approach these patients in terms of conservative care with wound care and compression and treat arterial and venous insufficiency is crucial. In looking to the future, continued standardization of wound care centers will overcome the social and financial challenges faced by patients and continued clinical research will improve targeted therapies and treatment challenges faced by physicians.

Objective: Peripheral artery disease (PAD) affects more than 200 million people worldwide, among whom more than two-thirds reside in low- and middle-income countries. China, as the largest low- and middle-income country, faces a challenge from the burden of PAD as the country undergoes economic expansion. We compared the patterns of PAD between China and Western countries to determine if there are differences in risk factors, awareness, or treatment of PAD., Methods: Literature searches were performed both in English databases and Chinese databases covering January 1, 1995, to March 1, 2020. Both landmark and high-quality articles were evaluated., Results: The prevalence of PAD in high-income countries increases linearly with age, whereas PAD increases slowly until the middle 60s and exponentially thereafter in China. In contrast with Western countries, the prevalence of PAD in China is reported to be higher in women than in men. There is a higher prevalence of risk factors in China, but the rates of awareness and treatment of these risk factors are low., Conclusions: The lack of awareness and lower rates of treatment and control of PAD and its risk factors in China may be underlying the higher prevalence of PAD in women than in men as well as the steep increase in PAD after the middle 60s. In all countries, more attention should be paid to the planning and implementation of preventative strategies and clinical services. The societal and economic effects of PAD are considerable and ongoing studies are needed to help curtail the burden of this disease., (Published by Elsevier Inc.)

Introduction and Objectives: The ankle-brachial index (ABI) is an indicator of peripheral artery disease (PAD). The aim of this study was to assess the association between PAD, measured with the ABI, and cognitive function in persons with overweight or obesity and metabolic syndrome., Methods: Cross-sectional study conducted with baseline data from the PREDIMED-Plus study, which included 4898 participants (after exclusion of those without ABI measurements) aged between 55 and 75 years, and with overweight or obesity and metabolic syndrome. At the baseline assessment, we measured the ABI with a standardized protocol and assessed the presence of other cardiovascular risk factors (eg, diabetes, dyslipidemia, hypertension). Cognitive function was evaluated using several tests validated for the Spanish population (mini-mental state examination [MMSE], phonological and semantic verbal fluency test, WAIS-III working memory index [WMI], parts A and B of the trail making test (TMT), and clock drawing test). Generalized linear models were used to assess the association between the ABI and cognitive function., Results: Among the participants, 3.4% had PAD defined as ABI ≤ 0.9, and 3.3% had arterial calcification defined as ABI ≥ 1.4. PAD was associated with age, systolic blood pressure and obesity indicators, while arterial calcification was also associated with obesity and diabetes. No significant associations were observed between cognitive function and ABI or PAD., Conclusions: In our sample, the presence of PAD increased with age, blood pressure, and obesity. No significant association was observed between ABI, PAD, or cognitive function., (Copyright © 2020 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

There is a lack of clarity and guidance for screening peripheral artery disease (PAD) in persons with chronic kidney disease (CKD) and end stage kidney disease (ESKD) despite this group being at excess risk of cardiovascular disease (CVD). In this current study, we performed a systematic review and meta-analysis to examine the prevalence and risk factors for PAD in persons with CKD in Australian cohorts. We used the inverse variance heterogeneity meta-analysis with double arcsine transformation to summarize the prevalence of PAD (with 95% CIs). Nine studies and 18 reports from the Australia and New Zealand dialysis and transplant registry with 36 cohorts were included in the review. We found a substantially higher PAD prevalence in cohorts based on an ankle-brachial index (ABI) or toe systolic pressure (TBI) than cohorts based on self-reported history. Higher PAD prevalence was observed in ESKD persons than CKD persons without dialysis (PAD diagnosis based on ABI or TBI: 31% in ESKD persons and 23% in CKD persons, PAD diagnosis based on self-reported history: 17% in ESKD persons and 10% in CKD persons). Older age, Caucasian race, cerebrovascular disease and haemodialysis were associated with the presence of PAD in ESKD persons. Our findings indicated a considerable proportion of PAD in CKD and ESKD persons particularly in those with ESKD. To develop and provide an adequate plan to clinically manage CKD patients with PAD, evidence of cost-effectiveness and clinical benefit of early detection of PAD in persons with CKD in Australia is recommended for future studies., (© 2021 Asian Pacific Society of Nephrology.)

Background: A high intake of marine n-3 polyunsaturated fatty acids (PUFAs) may lower the risk of coronary heart disease and ischemic stroke. The association between intake of marine n-3 PUFAs and development of peripheral artery disease (PAD), however, remains unexplored. We hypothesised that intake of marine n-3 PUFAs, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and the sum of EPA + DHA was associated with a lower risk of incident PAD., Methods: We used data from the Danish Diet, Cancer and Health cohort and investigated the associations between intake of EPA, DHA and EPA + DHA and development of PAD. Information on intake of n-3 PUFAs was obtained through a validated food frequency questionnaire. Potential PAD cases were identified through linkage to the Danish National Patient Register and subsequently, all cases were validated., Results: Data were available from 55,248 participants and during a median of 13.6 years of follow-up, 950 cases of PAD were identified. Multivariate Cox regression analyses with adjustments for established risk factors showed no statistically significant associations between intake of EPA (p = 0.255), DHA (p = 0.071) or EPA + DHA (p = 0.168) and the rate of incident PAD., Conclusions: We did not confirm our hypothesis that intake of EPA, DHA or EPA + DHA was associated with a lower risk of incident PAD., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited part of Springer Nature.)

We sought to assess temporal trends in peripheral artery disease (PAD)-related hospitalization rates in Ontario. Trends in quarterly rates of PAD hospitalization per 100,000 Ontarians between 2006 and 2019 were assessed using autocorrelated linear regression. Stratified analyses according to age, sex, and most responsible diagnosis code type (with vs without diabetes-specific PAD codes) were performed. From 2006 to 2019, overall PAD hospitalizations did not decrease significantly when diabetes-specific codes were included. A significant decrease was observed among women and those older than 65 years old. Future studies of PAD epidemiology and outcomes using administrative data should include diabetic angiopathy., (Copyright © 2021 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Aims: This review aims to explore the current guidance and issues surrounding lipid optimisation of patients with peripheral arterial disease (PAD)., Methods: A narrative review of the global PAD guidance, specifically focusing on low density lipoprotein cholesterol (LDL-C) reduction methods including; 'treating to target', 'fire and forget' and LDL-C percentage reduction. Advanced literature searches were carried out in Pubmed and Google Scholar databases comparing most recent PAD lipid guidance., Results: PAD lipid guidance could be improved internationally to help clinicians implement the best lipid-reduction strategies for their patients and challenge the arbitrary 1.4 mmol/L LDL-C target in line with novel proprotein convertase subtilisin/kexin type 9 inhibitors trials. By educating primary and secondary care staff on the benefits of maximal lipid-reduction therapies, we can reduce major adverse cardiovascular events and major adverse limb events. Championing PAD community clinics may lead to earlier prevention. Research comparing lipid-reduction strategies in practice is needed to improve outcomes internationally, and ongoing practice audited to understand the extent of under-prescribing in PAD., Conclusions: This review highlights the current PAD lipid-reduction treatments and the clarity issues of global guidance. Further research is needed to tackle ongoing mortality and morbidity rates in PAD patients against their better off cardiovascular disease (CVD) peers. MESH KEY TERMS: "Cholesterol", "Hydroxymethylglutaryl-CoA Reductase Inhibitors", "Ezetimibe", "Evolocumab", "Alirocumab", "Peripheral Arterial Disease", "Vascular Disease", "Atherosclerosis", "Secondary Prevention", "Lipoprotein, LDL"., (Copyright © 2021. Published by Elsevier Inc.)

Background There is currently no data showing the prevalence of peripheral arterial disease in Nepal, although they have a high incidence of risk factors in their population such as diabetes, hypertension, and high volume of smoke inhalation. Objective To quantify a gap in medical education curriculum in Nepal as it pertains to medical trainees that have a lack of exposure to peripheral arterial disease (PAD) in a clinical setting as well as improve lecture quality on peripheral arterial disease. Method A survey was sent out to 615 medical trainees in Nepal with a survey completion rate of 44%. The results indicate that both medical students and intern doctors feel most confident in their ability to diagnose peripheral arterial disease and comfortable ordering a workup for peripheral arterial disease when their education includes both a dedicated lecture and care of a patient. Result The self-reported ability to diagnose peripheral arterial disease increased in medical students from 21.9% in the lecture only group to 44.4% in the group who had both lecture and cared for a patient. The current curriculum at the Kathmandu University School of Medical Sciences only allows two hours in the medical school to cover all vascular topics and is taught with a traditional PowerPoint method. Conclusion To improve this area of curriculum, we recommend increasing the allotted time for lectures as well as demonstrate on live patients the evaluation for peripheral arterial disease.

Peripheral artery disease (PAD) is highly prevalent, affecting up to 20% of people over 70 years of age. To test the hypothesis that PAD promotes the pathogenesis of vascular cognitive impairment (VCI), we compared cognitive function in older adults with symptomatic PAD and in participants without PAD who had a burden of comorbid conditions. Furthermore, we compared the cognitive function of these groups after adjusting for demographic and clinical characteristics, comorbid conditions, and cardiovascular risk factors. Participants with PAD (age: 69 ± 8 years; n = 58) and those without PAD (age: 62 ± 8 years; n = 30) were assessed on a battery of eight neuropsychological tests. The tests assessed attention and working memory, verbal memory, non-verbal memory, perceptuo-motor speed, and executive function. Participants were further characterized on demographic and clinical characteristics, comorbid conditions, cardiovascular risk factors, and ankle-brachial index. The PAD group had significantly lower neuropsychological scores than the non-PAD control group on all eight tests (P < .01). After adjusting for covariates, significantly worse scores in the PAD group persisted for verbal memory, measured by tests on logical memory-immediate recall (P = .022), and logical memory-delayed recall (P < .001), and for attention and working memory, measured by tests on digits forward (P < .001), and digits backward (P = .003). Participants with symptomatic PAD have substantially lower levels of performance on tests of attention, working memory, and verbal memory than participants without PAD independent of demographic characteristics and comorbid health burdens. These findings provide additional evidence in support of the concept that generalized accelerated vascular aging manifesting as symptomatic PAD in the peripheral circulation also affects the brain promoting the pathogenesis of VCI. These cognitive difficulties may also negatively impact symptomatic patient's ability to understand and adhere to behavioral and medical therapies, creating a vicious cycle. We speculate that more intensive follow-up may be needed to promote adherence to therapies and monitor cognitive decline that may affect care., (© 2021. American Aging Association.)

Background: Peripheral artery disease (PAD) affects >200 million people worldwide and is associated with high mortality and morbidity. We sought to identify genomic variants associated with PAD overall and in the contexts of diabetes and smoking status., Methods: We identified genetic variants associated with PAD and then meta-analyzed with published summary statistics from the Million Veterans Program and UK Biobank to replicate their findings. Next, we ran stratified genome-wide association analysis in ever smokers, never smokers, individuals with diabetes, and individuals with no history of diabetes and corresponding interaction analyses, to identify variants that modify the risk of PAD by diabetic or smoking status., Results: We identified 5 genome-wide significant ( P association ≤5×10 -8 ) associations with PAD in 449 548 (N cases =12 086) individuals of European ancestry near LPA (lipoprotein [a]), CDKN2BAS1 (CDKN2B antisense RNA 1), SH2B3 (SH2B adaptor protein 3) - PTPN11 (protein tyrosine phosphatase non-receptor type 11), HDAC9 (histone deacetylase 9), and CHRNA3 (cholinergic receptor nicotinic alpha 3 subunit ) loci (which overlapped previously reported associations). Meta-analysis with variants previously associated with PAD showed that 18 of 19 published variants remained genome-wide significant. In individuals with diabetes, rs116405693 at the CCSER1 (coiled-coil serine rich protein 1 ) locus was associated with PAD (odds ratio [95% CI], 1.51 [1.32-1.74], P diabetes =2.5×10 -9 , P interactionwithdiabetes =5.3×10 -7 ). Furthermore, in smokers, rs12910984 at the CHRNA3 locus was associated with PAD (odds ratio [95% CI], 1.15 [1.11-1.19], P smokers =9.3×10 -10 , P interactionwithsmoking =3.9×10 -5 )., Conclusions: Our analyses confirm the published genetic associations with PAD and identify novel variants that may influence susceptibility to PAD in the context of diabetes or smoking status.

Objectives: Recent studies have proposed associations between systemic sclerosis (SSc) and atherosclerosis and between SSc and cardiovascular disease. However, in Asia, no large-scale studies have focused on the association between peripheral arterial disease (PAD) and SSc., Setting: A nationwide observation retrospective cohort study., Participants: The National Health Insurance Research Database was used for selecting patients diagnosed with SSc from 2000 to 2011. Patients diagnosed with PAD before the index date were excluded., Primary and Secondary Outcome Measures: The SSc cohort comprised 1106 patients with SSc, and the non-SSc cohort comprised 4424 matched controls. The Cox proportional hazards regression model was used for analysing the adjusted risk of PAD between the case and control patients., Results: The SSc cohort exhibited a significantly higher risk (HR=2.15, 95% CI=1.47 to 3.14) of PAD than did the non-SSc cohort. Patients with heart failure exhibited the highest risk of PAD (adjusted HR=2.10, 95% CI=1.20 to 3.70). Moreover, even without any comorbidities, the SSc cohort exhibited a significantly higher risk (adjusted HR=4.17 fold, 95% CI=1.98 to 8.77) of PAD than did the non-SSc cohort., Conclusion: SSc is associated with a significantly high risk of PAD. Further studies are required to reduce the PAD risk among patients with SSc., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: The aim was to assess trends in peripheral arterial disease (PAD) incidence and mortality rates in European Union(15+) countries between 1990 and 2017., Methods and Results: This observational study used data obtained from the 2017 Global Burden of Disease study. Age-standardised mortality and incidence rates from PAD were extracted from the Global Health Data Exchange for EU15+ countries for the years 1990-2017. Trends were analysed using Joinpoint regression analysis.Between 1990 and 2017, the incidence of PAD decreased in all 19 EU15+ countries for females, and in 18 of 19 countries for males. Increasing PAD incidence was observed only for males in the United States (+1.4%). In 2017, the highest incidence rates were observed in Denmark and the United States for males (213.6 and 202.3 per 100,000, respectively) and in the United States and Canada for females (194.8 and 171.1 per 100,000, respectively). There was a concomitant overall trend for increasing age-standardised mortality rates in all EU15+ countries for females, and in 16 of 19 EU15+ countries for males between 1990 and 2017. Italy (-25.1%), Portugal (-1.9%) and Sweden (-0.6%) were the only countries with reducing PAD mortality rates in males. The largest increases in mortality rates were observed in the United Kingdom (males +140.4%, females +158.0%) and the United States (males +125.7%, females +131.2%)., Conclusions: We identify shifting burden of PAD in EU15+ countries, with increasing mortality rates despite reducing incidence. Strong evidence supports goal-directed medical therapy in reducing PAD mortality - population-wide strategies to improve compliance to optimal goal-directed medical therapy are warranted., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)