Search

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

Aims: European clinical guidelines recommend that patients with atherosclerotic cardiovascular disease (ASCVD), including ischaemic heart disease (IHD), stroke, and peripheral arterial disease (PAD), are prescribed lipid lowering treatment (LLT) and treated to target low-density lipoprotein cholesterol (LDL-C) levels. This study aimed to document trends in ASCVD, including treatment, monitoring, and achievement of target LDL-C., Methods and Results: A retrospective observational population study was performed using linked healthcare data (2010-22). Over the study period, the number of patients with ASCVD increased from 181 153 to 207 747 (8882 to 9398 per 100 000). The proportion of patients prescribed LLT decreased from 75.3% in 2010 to 67.1% in 2022; high-intensity statin therapy increased from 9.4 to 25.2%, while non-high-intensity statin therapy decreased from 59.6 to 38.2%. The prescription of high-intensity statin therapy was consistently higher amongst patients with IHD (10.9% in 2010 increasing to 28.0% in 2022) than in patients with stroke (4.7-21.6%) or PAD (3.9-10.6%).The proportion of cases with documented LDL-C decreased from 58.0% in 2010 to 49.3% in 2022. Of those with documented LDL-C in 2022, 44.0% achieved LDL-C < 1.8 mmol/L, including 45.2% of those with IHD, 42.0% of those with stroke, and only 32.8% of those with PAD., Conclusion: Prescription of LLT, including high-intensity statin therapy, documentation of LDL-C, and achievement of target LDL-C levels was relatively low, especially in PAD patients. Although target achievement in 'tested patients' increased over time, the proportion of patients undergoing lipid testing declined. More rigorous lipid management requires prioritisation, especially for PAD and stroke patients., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: A subset of individuals with major depressive disorder (MDD) have a high burden of cardiovascular risk factors and cerebral small-vessel disease, implicating vascular disease in the development of depression. Cross-sectional studies demonstrate a link between endothelial dysfunction and MDD, but the prospective association between peripheral endothelial dysfunction (PED) and an incident diagnosis of MDD is unknown., Methods and Results: Patients undergoing a baseline assessment of cardiovascular risk were evaluated for PED using reactive hyperemia-peripheral arterial tonometry (≤1.8 consistent with PED). Patient medical records were reviewed to identify those who underwent a formal clinical evaluation of MDD after the index PED evaluation. The frequency of PED was compared in those with and without MDD. Logistic regression analyses were performed to assess the association between baseline PED and incident MDD. Between January 2006 and December 2020, 1614 patients underwent testing for PED. Four hundred eighty-four (30.1%) patients underwent a formal evaluation for MDD after (0-15 years) the index procedure (mean±SD age, 52.8±13.8 years; 65.2% women). Of these, 157 (32.4%) had PED and 108 (31.0%) were diagnosed with MDD. Individuals with MDD had a higher frequency of PED (40.2% versus 30.2%; P =0.034) compared with those without MDD. In multivariable analyses, PED was significantly associated with MDD (odds ratio, 2.3 [95% CI, 1.4-3.8]; P <0.001)., Conclusions: PED is significantly associated with incident MDD. Thus, PED may be a useful marker to identify individuals at increased risk of depression who may benefit from more frequent and earlier management strategies.

Peripheral artery disease (PAD) is a progressive atherosclerotic disease that causes lower extremity arterial stenosis or occlusion. Patients with PAD are at increased risk of myocardial infarction, stroke, limitations in ambulation, and amputation. Despite the advances in medicine and technology, the outcomes from PAD, including critical limb-threatening ischemia, acute limb ischemia amputation, and mortality, remain increased among specific racial and ethnic groups that have been historically marginalized in America, including Black, Hispanic, and American Indian individuals in the United States when compared with White persons. The purpose of this review is to summarize PAD literature that incorporates racial and ethnic disparities in PAD. There are a rising number of studies focused on the interface of racial and ethnic disparities and PAD. The majority of these studies are specifically focused on Black race, whereas there are limited studies focused on other minoritized racial and ethnic groups in the United States. The application of race and ethnicity has also been shown to play a synergistic role with socioeconomic status on PAD outcomes. Effective strategies focused on implementing policies that support quality measures and focus on social determinants of health have been shown to promote health equity and reduce disparities. Current evidence suggests that biological differences are less likely to be the leading cause of disparities in PAD between racial and ethnic groups compared with White Americans and supports a renewed focus on social determinants of health to achieve health equity.

Objective: Patients with symptomatic lower extremity artery disease (LEAD) should have an optimal management in terms of lipid goal [i.e. controlled LDL-cholesterol (LDLc)] and medical treatment (triple therapy with an antiplatelet agent, a statin and an angiotensin-converting enzyme inhibitor or a angiotensin-receptor antagonist). Prevalence of LEAD patients with a LDLc < 0.55 g/l is unknown. Aims of this study were to: (i) describe the prevalence of patients with a LDLc < 0.55 g/l, (ii) describe the prevalence of patients with an optimal medical treatment; (iii) compare this management between patients with a vascular surgery history and those without a vascular surgery history; and (iv) evaluate the number of patients eligible for new lipid-lowering therapies according to FOURIER and REDUCE-IT criteria., Methods: In this single-center retrospective study, prevalence is expressed as numbers and percentages. Comparison of the number of well managed patients between LEAD patients with a vascular surgery history and those without was performed. Number of patients who would be eligible for FOURIER and REDUCE-IT studies were calculated., Results: Among the LEAD patients included in the analysis (n = 225), only 12.4% (n = 28) had a LDLc < 0.55 g/L. The prevalence of patients who received the optimal medical treatment was 50.7% (n = 114). There was no statistical difference in the prevalence of patients with and without vascular surgery history achieving the LDLc goal (n = 9 (10.6%) vs. n = 19 (13.6%); p = not significant). Ninety-three patients (46.0%) would be eligible for EVOLOCUMAB treatment according to the Fourier study design whereas 17 patients (8.4%) would be eligible for treatment with ICOSAPENT ETHYL according to the REDUCE-IT study design., Conclusion: A majority of LEAD patients did not reach the LDLc goals. LEAD patients with a vascular surgery history did not experience a better management whereas they had a more consistent follow-up., (© 2024. The Author(s).)

Purpose of Review: To summarize evidence from recent studies of high lipoprotein(a) as a risk factor for peripheral artery disease (PAD), abdominal aortic aneurysms (AAA), and major adverse limb events (MALE). Additionally, provide clinicians with 10-year absolute risk charts enabling risk prediction of PAD and AAA by lipoprotein(a) levels and conventional risk factors., Recent Findings: Numerous studies support high lipoprotein(a) as an independent risk factor for PAD, AAA, and MALE. The strongest evidence is from the Copenhagen General Population Study (CGPS) and the UK Biobank, two large general population-based cohorts. In the CGPS, a 50 mg/dl higher genetically determined lipoprotein(a) associated with hazard ratios of 1.39 (1.24-1.56) for PAD and 1.21 (1.01-1.44) for AAA. Corresponding hazard ratio in the UK Biobank were 1.38 (1.30-1.46) and 1.42 (1.28-1.59). In CGPS participants with levels at least 99th (≥143 mg/dl) vs, less than 50th percentile (≤9 mg/dl), hazard ratios were 2.99 (2.09-4.30) for PAD and 2.22 (1.21-4.07) for AAA, with a corresponding incidence rate ratio for MALE of 3.04 (1.55-5.98) in participants with PAD., Summary: Evidence from both observational and genetic studies support high lipoprotein(a) as a causal risk factor for PAD, AAA, and MALE, and highlight the potential of future lipoprotein(a)-lowering therapy to reduce the substantial morbidity and mortality associated with these diseases., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: To evaluate the relationship between adherence to the Mediterranean diet (MD) and periphereal artery disease (PAD) in patients with type 2 diabetes mellitus (T2DM)., Methods: An observational sectional study was conducted with 174 patients diagnosed with T2DM, of which 78 patients had PAD. A patient was considered to have PAD if they obtained an ankle-brachial index (ABI) < 0.9 and/or absence of both distal pulses in one of the two feet. Data on sociodemographic and anthropometric variables, physical activity, smoking habits, biochemical blood parameters, and comorbidities were recorded. Good adherence to the MD was considered with a score ≥ 9 in MEDAS-14. Vascular factors independently associated with adherence to the MD in patients with T2DM were identified through multivariate logistic regression analysis., Results: ABI, DFU, intermittent claudication and pedal pulse absence correlated with MD adherence. DFU, intermittent claudication and posterior tibial pulse absence were associated with the final score obtained in the MEDAS-14. Nut consumption, white meat preference and sautéed dish intake were associated with PAD presence. Multivariate analysis linked MD adherence to sex (OR = 0.044, 95 % CI 0.003-0619), age (OR = 0.139, 95 % CI 0.029-0.666), duration of T2DM (OR = 7.383, 95 % CI 1.523-35.779) and age at diagnosis of T2DM (OR = 6082, 95 % IC 1.415-26.136), as well as the presence of DFU (OR = 0.000, 95 % IC 0.000-0.370) and intermittent claudication (OR = 0.004, 95 % IC 0.000-0.534)., Conclusions: Adherence to the MD is associated with a reduction in vascular complications in T2DM, highlighting its potential as a dietary intervention strategy., 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: Utilising real-world data, we quantified the burden of cardiovascular risk factors and long-term residual risk of atherothrombotic events among routine care cohorts with coronary (CAD) or peripheral (PAD) artery disease or ischemic stroke (IS) on guideline-recommended antiplatelet monotherapy (APMT)., Methods: Retrospective cohort study using data (2010-2020) from the United Kingdom Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics, including adults with CAD, PAD or IS who were first prescribed APMT (CAD/IS: aspirin; PAD: clopidogrel). Primary outcomes (recurrent events): major adverse cardiovascular events (MACE) for CAD/PAD/IS cohorts, major adverse limb events (MALE) for PAD., Results: 266,478 CAD, 13,162 PAD, and 14,788 IS patients were included (mean age: 71 years; women 37.7%-47.5 %). Risk factor burden was high and attainment of recommended goals was low. There were 73,691, 3,121 and 7,137 MACE among CAD, PAD and IS patients, respectively (median follow-up: 89.9, 42.4 and 75.9 months, respectively), and 4,767 MALE among PAD patients. MACE incidence rate per 1000 person-years was higher in IS (268.7; 95%CI 265.3-272.0) than CAD (92.9; 95%CI 92.5-93.4) or PAD cohorts (97.2; 95%CI 94.6-99.8). MALE incidence rate was 195.9 (95%CI 192.2-199.6) per 1000 person-years. IS patients presented a lower rate of hospitalisations and longer time-to-first hospitalisation, but once hospitalised, they had a longer length-of-stay. PAD patients had the highest hospitalisation rate., Conclusions: Among a contemporary cohort with cardiovascular disease on APMT, long-term residual atherothrombotic risk remains high despite being on APMT. Greater attention to risk factor control and use of appropriate evidence-based therapy is required to reduce residual risk among this very high-risk population., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: AJVV: personal fees for consulting from Bayer, during the conduct of the study; current or past participation in research grants to Imperial College London from Pfizer, Amgen, Merck Sharp & Dohme, Sanofi-Aventis, Daiichi Sankyo, and Regeneron, outside the submitted work; and personal fees for consulting from Regeneron and honoraria for lectures from Amgen, Mylan, Akcea, and Ferrer, outside the submitted work. KID: personal fees for consulting from Bayer, during the conduct of the study; grants from Pfizer, Amgen, Merck Sharp & Dohme, Sanofi-Aventis, Daiichi Sankyo, and Regeneron, outside the submitted study; and personal fees from Regeneron, outside the submitted work. NN,CCand STF:Bayer plc employees. MJF,ETand CL: none to report. KKR: personal fees for consulting from Bayer, during the conduct of the study; grants and personal fees from Aegerion, Amgen, Daiichi Sankyo, MSD, Pfizer, and Sanofi/Regeneron, and personal fees from Abbvie, Akcea, Algorithm, Astra Zeneca, Bayer, Boehringer Ingelheim, Cerenis Therapeutcics, Cipla, Dr Reddy's Laboratories, Esperion, Kowa, Lilly, Novartis, Silence Therapeutics, Takeda, and Zuellig Pharma, outside the submitted work., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Aim: Sodium-glucose co-transporter-2 inhibitors (SGLT-2is) are used to maintain glycaemic control as well as for their beneficial cardiovascular and renal effects in diabetes patients. However, increased risk of amputation and peripheral artery disease (PAD) have been observed with the use of some SGLT-2is. A meta-analysis was conducted to understand the effect of SGLT-2is on amputation and PAD events using data from randomized controlled trials (RCT)., Materials and Methods: A systematic literature review was conducted using Medline and Central databases for RCTs that involved the administration of SGLT-2is versus placebo/active comparators to diabetic patients. The primary outcome was amputation events and PAD. A random-effects model was used to calculate the pooled odds ratio, and subgroup analyses was performed., Results: A total of 51 RCTs were included in the meta-analysis with data from 97 589 patients. Meta-analysis of the data showed that there was a significant increase in PAD risk (p = 0.04) but no significant increase in amputation risk with SGLT-2i use versus placebo/active comparators (p = 0.43). Subgroup analyses demonstrated no significant difference between SGLT-2i type, duration of treatment or patient risk factors on amputation or PAD incidence. However, length of drug treatment (> 100 weeks) was associated with a significant increase in both PAD and amputation risks in the SGLT-2i treatment groups., Conclusions: The results of the meta-analysis showed no significant association between SGLT-2i use and PAD and amputation risks in diabetic patients when used for shorter treatment durations., (© 2024 John Wiley & Sons Ltd.)

Background: The COVID-19 pandemic has led to significant disruptions in chronic disease care and forced people to stay at home. The effects of such issues on outpatients with lower extremity peripheral artery disease (PAD) remain unknown. Patients and methods: Single-centre, retrospective-prospective study conducted in a Swiss University Hospital. Patients with PAD were included between May 1 and July 31, 2020, with a follow-up visit at 12 months. Upon both visits, the Leriche-Fontaine PAD stage was recorded, and study participants underwent ankle-brachial index (ABI) calculation to assess limb perfusion. Functional capacities were assessed through the 6-minute walking and treadmill tests. Major adverse cardiovascular (MACE) and limb events (MALE) were recorded. Data collected during the pandemic were compared with the pre-pandemic period (January 1, 2019-April 30, 2020). Results: Overall, 259 patients were included. Mean age was 69 years and male sex was prevalent (69.1%). Odds of experiencing a degradation in PAD stage were lower during the pandemic than before (odds ratio [OR]: 0.43; 95% confidence interval [CI]: 0.21-0.87; p = 0.018). No significant difference was found between periods in terms of ABI trends. Both pain-free walking time at treadmill test (p = 0.003) and maximal pain intensity at 6-minute walking test (p = 0.001) significantly improved during the pandemic. Compared with the pre-pandemic period, during the pandemic patients were hospitalized less frequently (p = 0.028) and were less likely to undergo elective limb revascularization (p<0.001). No significant difference was found between periods in terms of MALE (p = 0.311), whereas non-fatal strokes were less frequently reported during the pandemic (p = 0.043). Conclusion: In a cohort of outpatients with PAD, we found no evidence of clinical deterioration during the pandemic compared with the pre-pandemic period, though rates of adverse events were nonnegligible in both periods. In case of future pandemics, patients with PAD should be encouraged to maintain an active lifestyle while being closely monitored to avoid clinical worsening.

Peripheral arterial disease (PAD) represents one of the most frequent manifestations of atherosclerosis in men and women. In both sexes, PAD is related to classical risk factors of atherosclerosis, which are similarly distributed, but some additional factors determine differences between men and women. More frequent asymptomatic disease in women than in men and less frequent screening in women may result in a false underestimation of the prevalence of PAD in women. All these factors may cause delayed diagnosis and treatment of PAD in women. Estrogen hormones have vasoprotective properties that lower the prevalence of atherosclerosis in women of younger age. However, estrogen probably does not have a protective role against the development of cardiovascular disease in women of an older age. Hormone replacement therapy (HRT) of less than one year does not appear to reduce the odds of developing PAD in postmenopausal women. It may even increase the risk of morbidity from vascular interventions. However, some studies indicated that HRT for more than one year significantly decreases the risk of PAD if administered early after the last menstruation. Also, treatment of PAD in women differs to some extent from men.

Background: Genome wide association studies (GWAS) have allowed for a rapid increase in our understanding of the underlying genetics and biology of many diseases. By capitalizing on common genetic variation between individuals, GWAS can identify DNA variants associated with diseases of interest. A variety of statistical methods can be applied to GWAS results which allows for risk factor identification, stratification, and to identify potential treatments. Peripheral artery disease (PAD) is a common vascular disease that has been shown to have a strong genetic component. This article provides a review of the modern literature and our current understanding of the role of genetics in PAD., Methods: All available GWAS studies on PAD were reviewed. A literature search involving these studies was conducted and relevant articles applying the available GWAS data were summarized to provide a comprehensive review of our current understanding of the genetic component in PAD., Results: The largest available GWAS on PAD has identified 19 genome wide significant loci, with factor V Leiden and genes responsible for circulating lipoproteins being implicated in the development of PAD. Mendelian randomization (MR) studies have identified risk factors and causal associations with smoking, diabetes, and obesity and many other traits; protein-based MR has also identified circulating lipid and clotting factor levels associated with the incidence of PAD. Polygenic risk scores may allow for improved prediction of disease incidence and allow for early identification of at-risk patients but more work needs to be done to validate this approach., Conclusions: Genetic epidemiology has allowed for an increased understanding of PAD in the past decade. Genome-wide association studies have led to improved detection of genetic contributions to PAD, and further genetic analyses have validated risk factors and may provide options for improved screening in at-risk populations. Ongoing biobank studies of chronic limb threatening ischemia patients and the increasing ancestral diversity in biobank enrollment will allow for even further exploration into the pathogenesis and progression of PAD., (Published by Elsevier Inc.)

Background: Atherosclerosis in more than 1 vs. 1 arterial bed is associated with increased risk for major adverse cardiovascular events (MACE). This study aimed to determine whether the risk of post percutaneous coronary intervention (PCI) MACE associated with polyvascular disease (PVD) differs by sex., Methods: We analyzed 18,721 patients undergoing PCI at a tertiary-care center between 2012 and 2019. Polyvascular disease was defined as history of peripheral artery and/or cerebrovascular disease. The primary endpoint was MACE, a composite of all-cause death, myocardial infarction, or stroke at 1 year. Multivariate Cox regression was used to adjust for differences in baseline risk between patients with PVD vs. coronary artery disease (CAD) alone and interaction testing was used to assess risk modification by sex., Results: Women represented 29.2% (N = 5,467) of the cohort and were more likely to have PVD than men (21.7% vs. 16.1%; P < .001). Among both sexes, patients with PVD were older with higher prevalence of comorbidities and cardiovascular risk factors. Women with PVD had the highest MACE rate (10.0%), followed by men with PVD (7.2%), women with CAD alone (5.0%), and men with CAD alone (3.6%). Adjusted analyses revealed similar relative MACE risk associated with PVD vs. CAD alone in women and men (adjusted hazard ratio [aHR] 1.54, 95% confidence interval [CI] 1.20-1.99; P < .001 and aHR 1.31, 95% CI 1.06-1.62; P = .014, respectively; p-interaction = 0.460)., Conclusion: Women and men derive similar excess risk of MACE from PVD after PCI. The heightened risk associated with PVD needs to be addressed with maximized use of secondary prevention in both sexes., Competing Interests: Conflict of Interest Dr. Spirito received a research grant from the Swiss National Science Foundation. Dr. Dangas has received consulting fees and advisory board fees from AstraZeneca; has received consulting fees from Biosensors; and previously held stock in Medtronic. Dr. Mehran reports institutional research payments from Abbott, Abiomed, Alleviant Medical, Amgen, AM-Pharma, Applied Therapeutics, Arena, AstraZeneca, Biosensors, Biotronik, Boston Scientific, Bristol-Myers Squibb, CardiaWave, CeloNova, Chiesi, Concept Medical, CSL Behring, Cytosorbents, Daiichi Sankyo, Element Science, Faraday, Humacyte, Idorsia, I-Laser, Janssen, Magenta, Mediasphere, Medtelligence, Medtronic, Novartis, OrbusNeich, Penumbra, PhaseBio, Philips, Pi-Cardia, PLx Pharma, Protembis, RenalPro, RM Global, Shockwave, Transverse Medical, Inc., Vivasure, Zoll; personal fees from AstraZeneca, Ionis Pharmaceuticals, J-CalC, Mediasphere, Novartis, Novo Nordisk, Vectura, WebMD; Equity, (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: Peripheral arterial disease (PAD) has been associated with suboptimal treatment, high mortality, and high amputation rates. It is unclear how the COVID-19 (coronavirus disease 2019) pandemic affected this development in a long term context., Methods: This is a registry based, retrospective, nationwide cohort study including patients hospitalised with PAD as a main or secondary diagnosis and amputation surgery between 2012 - 2021 in Germany. Primary endpoints were population wide major and minor amputation rates, in hospital death, and in hospital mortality rates. Secondary endpoints were same admission revascularisations and in hospital death in the event of complications, i.e., failure to rescue (FTR). Pre-pandemic and pandemic trends, focusing on lockdown periods, were analysed., Results: A total of 365 926 patient records with PAD and amputation surgery were analysed. The median patient age was 75 years and 28.8% were female. Overall population wide amputation and in hospital mortality rates (monthly decrease -0.002/100 000, p < .001, and -0.001/100 000, p< .001, respectively) and in hospital mortality rate (8.0% for 2012 - 2014 vs. 6.5% for 2020 - 2021; p < .001) declined between 2012 and 2020. Concurrently, same admission revascularisations increased (41.0% for 2012 - 2014 vs. 47.0% for 2020 - 2021; p < .001), while FTR decreased in a subset of complications (acute ischaemia, major bleeding, compartment syndrome, and mesenterial ischaemia). In the first pandemic lockdown, there was a temporary trend change to higher major amputations rates (+0.02/100 000; p < .001) and higher in hospital mortality rates (+0.007/100 000; p < .001), which changed to a decrease as of the second lockdown (-0.03/100 000, p = .034, and -0.010/100 000, p < .001, respectively) in an interrupted time series analysis. There was no statistically significant change in observed amputation rates during lockdowns, while observed in hospital mortality rates decreased by 12.0% in the first lockdown (0.22/100 000 vs. 0.25/100 000; p = .005) compared with reference periods of the two previous years., Conclusion: Between 2012 and 2021, pre-pandemic trends toward decreasing population wide overall amputation rates, fewer major amputations, more amputation related revascularisation procedures, and lower in hospital mortality were maintained despite a temporary trend to increased major amputations and in hospital mortality during the first COVID-19 related lockdown in Germany., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: Prior studies have described risk factors associated with amputation in patients with concomitant diabetes and peripheral arterial disease (DM/PAD). However, the association between the severity and extent of tissue loss type and amputation risk remains less well-described. We aimed to quantify the role of different tissue loss types in amputation risk among patients with DM/PAD, in the context of demographic, preventive, and socioeconomic factors., Methods: Applying International Classification of Diseases (ICD)-9 and ICD-10 codes to Medicare claims data (2007-2019), we identified all patients with continuous fee-for-service Medicare coverage diagnosed with DM/PAD. Eight tissue loss categories were established using ICD-9 and ICD-10 diagnosis codes, ranging from lymphadenitis (least severe) to gangrene (most severe). We created a Cox proportional hazards model to quantify associations between tissue loss type and 1- and 5-year amputation risk, adjusting for age, race/ethnicity, sex, rurality, income, comorbidities, and preventive factors. Regional variation in DM/PAD rates and risk-adjusted amputation rates was examined at the hospital referral region level., Results: We identified 12,257,174 patients with DM/PAD (48% male, 76% White, 10% prior myocardial infarction, 30% chronic kidney disease). Although 2.2 million patients (18%) had some form of tissue loss, 10.0 million patients (82%) did not. The 1-year crude amputation rate (major and minor) was 6.4% in patients with tissue loss, and 0.4% in patients without tissue loss. Among patients with tissue loss, the 1-year any amputation rate varied from 0.89% for patients with lymphadenitis to 26% for patients with gangrene. The 1-year amputation risk varied from two-fold for patients with lymphadenitis (adjusted hazard ratio, 1.96; 95% confidence interval, 1.43-2.69) to 29-fold for patients with gangrene (adjusted hazard ratio, 28.7; 95% confidence interval, 28.1-29.3), compared with patients without tissue loss. No other demographic variable including age, sex, race, or region incurred a hazard ratio for 1- or 5-year amputation risk higher than the least severe tissue loss category. Results were similar across minor and major amputation, and 1- and 5-year amputation outcomes. At a regional level, higher DM/PAD rates were inversely correlated with risk-adjusted 5-year amputation rates (R 2  = 0.43)., Conclusions: Among 12 million patients with DM/PAD, the most significant predictor of amputation was the presence and extent of tissue loss, with an association greater in effect size than any other factor studied. Tissue loss could be used in awareness campaigns as a simple marker of high-risk patients. Patients with any type of tissue loss require expedited wound care, revascularization as appropriate, and infection management to avoid amputation. Establishing systems of care to provide these interventions in regions with high amputation rates may prove beneficial for these populations., Competing Interests: Disclosures None., (Copyright © 2024 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

This study aims to understand the repercussions of the COVID-19 pandemic on hospitalized patients with peripheral arterial disease (PAD) in China, who did not contract SARS-CoV-2. We conducted a multicenter cross-sectional analysis comparing the characteristics and outcomes of hospitalized PAD patients across two distinct periods: Pre-pandemic (P1, from January 2018 to December 2019) and during the pandemic (P2, from January 2020 to December 2021). During P1, 762 hospitalized patients were treated, with an average age of 72.3 years, while 478 patients were treated in P2, with an average age of 65.1 years. Notably, hospitalized patients admitted during the pandemic (P2) exhibited a significantly higher incidence of chronic limb-threatening ischemia (CLTI, 70% vs 54%), diabetic foot infection (47% vs 29%), and infra-popliteal lesions (28% vs 22%). Furthermore, these patients demonstrated a marked deterioration in their Rutherford category and an increased mean score in the Wound, Ischemia, and foot Infection classification system (WIfI). Treatment during the pandemic emerged as a predictor of reduced procedural success and increased major adverse limb events. Factors such as the presence of diabetic foot infection, renal impairment, and deteriorating WIfI scores were identified as independent risk indicators for major adverse limb events. Our results demonstrate that intensive care was provided to severe cases of PAD even during the challenging circumstances of the COVID-19 pandemic. Despite the unprecedented pressures on healthcare systems, patients with severe PAD, particularly those with CLTI, continued to receive necessary in-patient care. The findings underscore the importance of timely medical interventions and extended follow-up for patients exhibiting high-risk factors., (© 2024. The Author(s).)

Among the different complications of chronic kidney diseases, peripheral arterial disease is not uncommon. Though it is an indicator of widespread atherosclerosis, sometimes it is neglected in CKD patients. Our study was done to evaluate the frequency and pattern of PAD in chronic kidney disease patients admitted in a tertiary care hospital of Bangladesh. One hundred (100) admitted patients of CKD were taken by nonrandom purposive sampling considering inclusion and exclusion criteria. After clinical evaluation and Ankle brachial index (ABI) measurement 5 cc venous blood was collected and sent to Clinical Pathology and Biochemistry department of CMCH. Data was collected in a structured proforma and analyzed. Among the 100 patients, 2.0% patient belonged to stage 3, 28.0% were in stage 4 and remaining 70.0% were in stage 5. We found the proportion of PAD in CKD were 18.0%. Among 18 PAD patients, 66.67% were in stage 5, 22.22% in stage 4 and 11.11% in stage 3. Regarding right lower limb 12 patients had some PAD, 3 patients had moderate PAD, 2 patients had borderline and 1 patient had calcified PAD. For left lower limb, 10 patients had some PAD, 4 patients had moderate PAD, 4 patients had borderline PAD. The mean AB) of the PAD patients for right limb was 0.87 and for left limb 0.84. 50.0-55.0% patients were asymptomatic. Among the PAD patients 38.9% had DM, 72.2% had HTN, 33.3% had both DM and HTN, 44.4% had other vascular events, 55.6% were smokers, 33.3% had dyslipidemia and 22.2% had family history of PAD. Renal diseases seem to have a strong association with vascular disease and PAD is not uncommon.

Background and Aims: The potential impact of peripheral artery disease (PAD) on kidney outcomes is not well understood. The aim of this study was to explore the association between PAD and end-stage kidney disease (ESKD) and chronic kidney disease (CKD)., Methods: Among 14,051 participants (mean age 54 [SD 6 years]) from the Atherosclerosis Risk in Communities study, we categorized PAD status as symptomatic PAD (intermittent claudication or leg revascularization), asymptomatic PAD (ankle-brachial index [ABI] ≤0.90 without clinical history of symptoms), and ABI 0.91-1.00, 1.01-1.10, 1.11-1.20 (reference), 1.21-1.30, and >1.30. We evaluated their associations with two kidney outcomes: ESKD (the need of renal replacement therapy or death due to kidney disease) and CKD (ESKD cases or an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m 2 with a ≥25 % decline from the baseline) using multivariable Cox proportional hazards models., Results: Over ∼30 years of follow-up, there were 598 cases of incident ESKD and 4686 cases of incident CKD. After adjusting for potential confounders, both symptomatic PAD and asymptomatic PAD conferred a significantly elevated risk of ESKD (hazard ratio 2.28 [95 % confidence interval 1.23-4.22] and 1.75 [1.19-2.57], respectively). Corresponding estimates for CKD were 1.54 (1.14-2.09) and 1.63 (1.38-1.93). Borderline low ABI 0.91-1.00 also showed elevated risk of adverse kidney outcomes after adjustment for demographic variables. Largely consistent results were observed across demographic and clinical subgroups., Conclusions: Symptomatic PAD and asymptomatic PAD were independently associated with an elevated risk of ESKD and CKD. These results highlight the importance of monitoring kidney function in persons with PAD, even when symptoms are absent., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: K.M. reports personal fees from Fukuda Denshi and Kowa Company, Ltd. Outside of the submitted work. The other authors do not have relevant conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Atherosclerotic cardiovascular diseases remain the primary cause of mortality in Italy. Individuals with a history of acute coronary syndrome, peripheral arterial disease, and ischemic stroke/transient ischemic attack face an elevated risk of recurrent major adverse cardiovascular events, including mortality. The population aging, coupled with increasing risk factors such as diabetes mellitus and obesity, exacerbates the disease's economic impact., Objectives: This study aims to comprehensively assess the economic burden of atherosclerotic cardiovascular diseases in Italy, specifically focusing on direct healthcare costs., Methods: We analyzed real-world data from administrative databases in the Marche region and Local Health Unit Umbria 2. The economic burden of patients discharged with acute coronary syndrome, peripheral arterial disease, and ischemic stroke/transient ischemic attack was evaluated, with a focus on direct costs associated with hospitalizations, drugs, and outpatient visits. Results were stratified by age, sex, comorbidities at baseline, and adherence to lipid-lowering therapy and antihypertensive agents., Results: Annually, nearly 350,000 patients were hospitalized for peripheral arterial disease, acute coronary syndrome, or ischemic stroke/transient ischemic attack. Direct health costs averaged €7190 per patient over a 2-year follow-up, with hospitalizations accounting for nearly 70% of the total. Male patients incurred significantly higher costs (€7467) than female patients (€6625). Costs correlated positively with age and with the number of baseline comorbidities, with a range from €5259 (0-1 comorbidities) to €17,095 (4+ comorbidities). Costs were significantly lower in adherent subjects (€6813) compared with non-adherent subjects (€7757)., Conclusions: This study provides valuable insights into the economic implications of atherosclerotic cardiovascular diseases in Italy, emphasizing the necessity of a comprehensive approach to preventive measures, optimal medication adherence, and lifestyle modifications to mitigate its impact., (© 2024. The Author(s).)

There is a well-established and strong link between high lipoprotein(a) concentration and coronary heart disease, but the evidence regarding peripheral artery disease and carotid atherosclerosis is not as conclusive. This review aims to summarize the relationships between lipoprotein(a), peripheral artery disease and carotid atherosclerosis, in order to try to understand the weight of lipoprotein(a) in determining the development, progression and any complications of atherosclerotic plaque at the carotid and peripheral artery level. There is currently no effective therapy to reduce lipoprotein(a) concentration, but understanding its significance as a vascular risk factor is the starting point to then explore (when effective therapies become available) if there is the possibility, even in patients with peripheral artery disease and carotid atherosclerosis, to achieve better control of the residual vascular risk that is ultimately induced by lipoprotein(a)., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Background: Patients with peripheral artery disease face high amputation and mortality risk. When assessing vascular outcomes, consideration of mortality as a competing risk is not routine. We hypothesize standard time-to-event methods will overestimate major amputation risk in chronic limb-threatening ischemia (CLTI) and non-CLTI. Methods : Patients undergoing peripheral vascular intervention from 2017 to 2018 were abstracted from the Vascular Quality Initiative registry and stratified by mean age (⩾ 75 vs < 75 years). Mortality and amputation data were obtained from Medicare claims. The 2-year cumulative incidence function (CIF) and risk of major amputation from standard time-to-event analysis (1 - Kaplan-Meier and Cox regression) were compared with competing risk analysis (Aalen-Johansen and Fine-Gray model) in CLTI and non-CLTI. Results : A total of 7273 patients with CLTI and 5095 with non-CLTI were included. At 2-year follow up, 13.1% of patients underwent major amputation and 33.4% died without major amputation in the CLTI cohort; 1.3% and 10.7%, respectively, in the non-CLTI cohort. In CLTI, standard time-to-event analysis overestimated the 2-year CIF of major amputation by 20.5% and 13.7%, respectively, in patients ⩾ 75 and < 75 years old compared with competing risk analysis. The standard Cox regression overestimated adjusted 2-year major amputation risk in patients ⩾ 75 versus < 75 years old by 7.0%. In non-CLTI, the CIF was overestimated by 7.1% in patients ⩾ 75 years, and the adjusted risk was overestimated by 5.1% compared with competing risk analysis. Conclusions : Standard time-to-event analysis overestimates the incidence and risk of major amputation, especially in CLTI. Competing risk analyses are alternative approaches to estimate accurately amputation risk in vascular outcomes research., Competing Interests: Declaration of conflicting interestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr Mena-Hurtado reports unrestricted research grants from Abbott, Merck, and Shockwave and is a consultant for Cook, Novo Nordisk, and Terumo. Dr Smolderen reports unrestricted research grants from Abbott, Shockwave, and Johnson & Johnson; she is a consultant for Cook, Terumo, Novo Nordisk, and Happify. The other authors report no competing interests.

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.

Background: Mixed Arterial and Venous Leg Ulcers (MAVLU) are challenging. Clinical evidence specific to MAVLU management is scarce. We evaluated our recent experience with MAVLU patients and reviewed current data regarding MAVLU epidemiology, aetiology, diagnostic assessment and management options., Methods: A prospective leg ulcer database was retrospectively interrogated to determine the prevalence and clinical outcome of MAVLU over 2-year period (2021-2022). The literature was reviewed to determine if optimal treatment strategies., Results: 307 patients attended the ulcer clinic over a 2-year period. Most were venous leg ulcers (71%), 24% were arterial and 5% were MAVLU. The highest healing rate was in MAVLU (93%), followed by (74%) and (41%), in arterial and venous leg ulcer groups, respectively., Conclusion: Evidence-based guidelines for MAVLU remain lacking. Well-developed randomised controlled trials are warranted to guide current clinical practice., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Peripheral artery disease (PAD) is a common disease associated with atherosclerosis, leading to significant mortality and morbidity worldwide. Our study focuses on the association between insulin resistance (IR) and PAD, specifically investigating the triglyceride-glucose index (TyG) as a potential surrogate marker of IR in the context of PAD by pooling the existing studies on this topic., Methods: Online databases, including PubMed, Embase, Scopus, and the Web of Science, were searched to find the studies comparing the TyG index in PAD vs. control, reporting the TyG index among PAD severities, and assessing the association of increase in TyG with PAD prevalence. Random-effect meta-analysis was performed to calculate the standardized mean difference (SMD) and 95% confidence interval (CI) for TyG level comparison and to calculate pooled odds ratio (ORs) for a 1-unit increase in TyG and higher vs. lower quartile/tertile of TyG association with PAD., Results: In the final review, 22 studies comprising 73,168 cases were included. Random-effect meta-analysis showed that patients with PAD had significantly higher levels of the TyG index compared with controls (SMD 0.76, 95%CI 0.65-0.88, P < 0.001). Also, higher severities of PAD were associated with higher TyG levels (SMD 0.48, 95%CI 0.22-0.74, P = 0.0003). Additionally, a 1-unit increase in TyG was associated with a 60% increase in odds of PAD (OR 1.60, 95%CI 1.41-1.80, P < 0.001). Finally, the highest quartile (Q4) of TyG had significantly higher odds of PAD compared to Q1 (OR 1.94, 95%CI 1.49-2.54, P < 0.001)., Conclusion: Our meta-analysis has identified a significant association between TyG levels and PAD and its severity. These findings not only contribute to our understanding of the role of IR in PAD pathology but also offer clinicians an exact index for evaluating PAD risk and its complications. This could potentially lead to more effective prevention and management strategies in the future., (© 2024. The Author(s).)

Background: Although red meat consumption has been associated with risk of atherosclerotic coronary artery disease and stroke, no prospective study has examined this with the risk of chronic limb-threatening ischemia (CLTI)., Methods: In a prospective study of 63,257 Chinese in Singapore, who were aged 45-74 years old at recruitment, diet was assessed via a validated semi-quantitative food frequency questionnaire. Incident CLTI cases were ascertained via linkage with nationwide hospital records for lower extremity amputation or angioplasty for peripheral arterial disease. Multivariable Cox models were used to examine associations between quartiles of meat intake and CLTI risk., Results: After a mean follow-up of 18.8 years, there were 1069 cases of CLTI. Higher intake of red meat intake was associated with increased risk of CLTI in a stepwise manner. Comparing extreme quartiles of red meat intake, the hazard ratio (HR) for the association with CLTI risk was 1.24 [95% confidence interval (CI) = 1.03-1.49; P-trend = 0.02]. In stratified analysis, red meat intake had a stronger association with CLTI risk among those without diabetes [HR (95% CI) comparing extreme quartiles = 1.41 (1.10-1.80); P-trend = 0.03] than among those with diabetes at baseline [HR (95% CI) comparing extreme quartiles = 1.04 (0.79-1.38); P-trend = 0.05] (P-interaction = 0.03). Otherwise, the associations were not different by sex, BMI, smoking status, hypertension, alcohol consumption, or history of cardiovascular diseases. Using a theoretical model in substitution analysis that substituted three servings per week of red meat with poultry or fish/shellfish, the relative risk of CLTI was reduced by 13-14%., Conclusions: Consumption of red meat was associated with higher CLTI risk in this Asian cohort. Substituting red meat with poultry or fish/shellfish may reduce this risk., (© 2024. The Author(s).)

Background: A national guideline on peripheral arterial disease management in England was issued in August 2012. The impact on revascularization rates was examined and variation with socioeconomic deprivation assessed., Methods: Annual hospital admissions for England over 10 years (2008-2009 to 2017-2018) were examined using interrupted time series analysis. A pragmatic approach was used to classify admissions for revascularization into moderate and severe categories., Results: There were 309 839 admissions (56% for moderate peripheral arterial disease), with an overall annual admission rate for revascularization of 86 per 100 000 population aged 25+ years. The rate for moderate peripheral arterial disease marginally increased by 0.29 per 100 000 per year (95% c.i. -0.22 to 0.80) from 2008-2009 to 2012-2013. Following guideline introduction, this rate decreased. The equivalent for severe peripheral arterial disease increased by 1.33 per 100 000 (0.78 to 1.88). Following guideline introduction, this rate plateaued. The change in rate (slope) for moderate peripheral arterial disease of -2.81 per 100 000 per year (-3.52 to -2.10) after guideline introduction was greater than the change in rate for severe peripheral arterial disease of -1.95 per 100 000 per year (-2.73 to -1.17). For moderate peripheral arterial disease, the annual rate in the most socioeconomically deprived category was 15.6 per 100 000 lower in 2017-2018 compared with 2012-2013 (24.3% decrease). The impact progressively diminished with decreasing deprivation. In the least deprived category, the reduction was 5.2 per 100 000 (12.9% decrease). For severe peripheral arterial disease, the decrease was 1.2 per 100 000 (3.1% reduction) with no consistent variation in relation to deprivation., Conclusion: Introduction of the national peripheral arterial disease management guideline in England was associated with a reduction in admission rates for revascularization, especially for moderate peripheral arterial disease, with greater reduction in rates for moderate peripheral arterial disease in more socioeconomically deprived areas. Association, however, does not necessarily imply causation and alternative explanations cannot be ruled out., (© The Author(s) 2024. Published by Oxford University Press on behalf of BJS Foundation Ltd.)

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).)

Introduction: It is well known that peripheral artery disease (PAD) and coronary artery disease (CAD) coexist and therefore, patients diagnosed with PAD have an increased chance of developing concomitant CAD. CAD-related complications could be a leading cause of postoperative mortality in individuals with PAD undergoing vascular surgery. We present a case series of 48 patients who underwent coronary angiography before vascular surgery and an updated review of previous reports to determine the prevalence of concomitant CAD in a convenience sample of Iranian patients., Methods: This cross-sectional study was performed on 48 patients with confirmed PAD admitted to Imam Ali Hospital, affiliated with the Kermanshah University of Medical Sciences (KUMS), Kermanshah Province, Iran. A vascular surgeon diagnosed PAD based on the patient's symptoms, Doppler ultrasound, and CT angiography (CTA). All patients underwent coronary angiography to determine if they also had CAD. We defined significant CAD as a ≥70% luminal diameter narrowing of a major epicardial artery or a ≥50% narrowing of the left main coronary artery., Results: Of 48 patients, 35 (72.9%) were male, 13 (27.1%) were female, and the mean age was 64.18±12.11 years (range, 30 to 100 years). The incidence of CAD in patients with PVD was 85.42% (41/48). The patients with CAD were more likely to be hypertensive than those without CAD (80.5 vs. 14.3, p-value<0.001). Of 41 patients with CAD, 9 (22.0%) had one-vessel disease, 10 (24.3%) had two-vessel disease, and 22 (53.7%) had three-vessel disease., Conclusion: Hypertension was a significant risk factor for CAD. Patients with hypertension and multiple major coronary risk factors scheduled for PVD surgery should be carefully evaluated for concomitant CAD., Competing Interests: Declaration of competing interest The authors declare there is no actual or potential conflict of interest., (Copyright © 2024. 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: 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.)

Objective: To assess the effects of colchicine, which has been shown to reduce the risks of coronary artery disease but scarcely studied in peripheral artery disease (PAD), on major adverse limb events (MALE) in patients with PAD., Methods: This is a retrospective study based on a nationwide database. Patients who were diagnosed with PAD between 2010 and 2020 and prescribed with colchicine after the diagnosis of PAD were identified. Patients were then categorized into the colchicine or the control group according to drug use. Propensity score matching was performed to mitigate selection bias. Risks of MALE (including lower limb revascularization and nontraumatic amputation) and major adverse cardiovascular events were compared between the two groups., Results: After patient selection and propensity score matching, there were 60,219 patients in both colchicine and control groups. After a mean follow-up of 4.5 years, the risk of MALE was significantly lower in the colchicine group compared with control (subdistribution HR, 0.75; 95% CI, 0.71 to 0.80), as were the incidence of both components of MALE, lower limb revascularization and major amputations. Colchicine treatment was also associated with lower risk of cardiovascular death. The lower risk of MALE observed with colchicine therapy was accentuated in the subgroup of patients receiving concomitant urate-lowering medications., Conclusion: In patients diagnosed with PAD, the use of colchicine is associated with lower risks of MALE and cardiovascular death. Anti-inflammatory therapy with colchicine may provide benefits in vascular beds beyond the coronary arteries., (Copyright © 2024 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

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: Preventing lower-extremity amputations (LEAs) is pivotal. In the present study, we aimed to examine the recent trends in nontraumatic LEAs seen in the Northern Danish Region., Methods: Using data from the regional Business Intelligence unit, we identified all nontraumatic LEAs (n = 689) performed in people above 50 years of age in the Northern Danish Region between January 2016 and December 2021 (approximately 600,000 inhabitants). Persons with diabetes (n = 26,025) were identified based on International Classification of Diseases-10 codes and data from the National Health Insurance Service Registry, while preventive vascular procedures (n = 1,097) were identified using surgical codes. Major LEA was defined as any amputation above the ankle. Incidence rates were expressed as events per 1,000 person-years. Trends were described as differences between the periods 2016-2018 and 2019-2021., Results: A total of 249 (36%) major LEAs were performed in people with diabetes. People with diabetes were younger (71 vs 77 years, P < 0.001) and more frequently male (70% versus 54%, P < 0.001). Between 2016-2018 and 2019-2021, the incidence of major LEA declined from 1.76 (95% CI: 1.75-1.76) to 1.39 (1.39-1.39) in people with diabetes and from 0.47 (0.47-0.47) to 0.20 (0.20-0.20) in people without diabetes (all P < 0.001). Simultaneously, the incidence of preventive vascular surgery increased from 2.26 (2.26-2.26) to 3.48 (3.48-3.48) in people with diabetes and declined slightly in people without 0.49 (0.49-0.49) to 0.47 (0.47-0.47) (all P < 0.001)., Conclusions: Despite significant declines in major LEA in both people with and without diabetes, most of the decline was driven by a large reduction in major LEAs in people without diabetes., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: This study explored the utility of NLR (neutrophil-to-lymphocyte ratio) as a marker to predict Lower Extremity Peripheral Artery Disease (PAD) in the Chinese population, as well as to assess its consistency and diagnostic value with digital subtraction angiography., Methods: Patients were distributed into three groups according to the angiography in lower limb arterial: group L1, plaque with no stenosis; group L2, plaque with luminal stenosis and group L3, total vascular occlusion. Changes in the neutrophil-to-lymphocyte ratio were documented and compared among groups., Results: Compared to group L1, NLR was significantly increased in L2 (1.76 vs 2.35, p =0.037) and L3 (1.76 vs 3.60, p< 0.001), with a gradual decrease in ABI (Ankle-Brachial Index, 1.11 vs 1.02 vs 0.94, p< 0.001). Those older patients with higher prevalence of hypertension ( p =0.002), obesity ( p =0.032), or reduced high-density lipoprotein cholesterol ( p =0.020) were more likely to develop PAD; higher glycosylated hemoglobin ( p =0.045), low-density lipoprotein cholesterol ( p =0.006), and systolic blood pressure ( p< 0.001) levels led to a greater tendency to suffer stenosis or even occlusion; the probability of severe stenosis (>70%) increased to 2.075 times for every 1 increase in NLR, while it was 46.8% for every 0.1 increase in ABI. The optimal NLR cut-off value to predict severe stenosis in PAD was 2.73. Receiver operating characteristic curve analysis of the inflammatory biomarkers and severe stenosis prediction displayed an area under the curve of 0.81., Conclusion: NLR could serve as a new noninvasive and accurate marker in predicting PAD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Wang, Jia, Jiang, Yang, Wang and Zhang.)

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).)

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).)

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: 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.

Introduction: Dyslipidemia is an established risk factor for cardiovascular diseases. We aimed to review its role in the pathogenesis of lower extremity arterial disease (LEAD), as well as the effect of lipid-lowering treatment on the progression of LEAD., Evidence Acquisition: PubMed/MedLine, EMBASE and Scopus were searched between January 1990 and January 2024 for articles investigating the role of dyslipidemias and hyperlipidemias in the pathogenesis of LEAD. A separate search focused on the effects of lipid-lowering therapy on patients with LEAD., Evidence Synthesis: There is evidence that dyslipidemias play a major role in the development of LEAD. All patients with LEAD should receive intensive lipid-lowering therapy for the reduction not only of claudication symptoms and amputation rates, but also of myocardial infarction and cardiovascular event rates., Conclusions: Vascular specialists should keep in mind the pivotal role of dyslipidemia in the pathogenesis and progression of LEAD.

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.)

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.)

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.)

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: 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.)

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).)