Risk Of Peripheral Arterial Disease Research Articles

The Promoter Polymorphism rs3918226 of the Endothelial Nitric Oxide Synthase Gene as a Novel Susceptibility Marker for Peripheral Artery Disease

This pilot study aimed to investigate the association between the single nucleotide polymorphism (SNP) rs3918226 in the promoter of the nitric oxide synthase (NOS3) gene and the risk of peripheral artery disease (PAD). DNA samples from 1263 unrelated subjects of Slavic origin, including 620 patients with PAD and 643 controls, were genotyped for the SNP rs3918226 using the MassArray-4 system. The rs3918226 polymorphism was found to be strongly associated with an increased risk of PAD regardless of coronary artery disease, hypertension, or cigarette smoking (OR=2.86, 95%CI 1.89-4.32, Pperm<0.0001). The SNP-PAD association was in almost three times stronger in females (OR=8.31 95%CI 3.07-22.48) than in males (OR=1.79 95%CI 1.10-2.93). SNP rs3918226 was correlated with ankle brachial index (ABI) and total plasma cholesterol in patients with PAD (Рperm<0.05). The NOS3 polymorphism was closely associated with SNPs rs7692387 and rs13139571 in GUCY1A3 to determine the risk of PAD, suggesting that the rs3918226 polymorphism may disrupt signaling in the nitric oxide-soluble guanylyl cyclase pathway. Diplotypes with wild-type alleles, such as NOS3 rs3918226-C/C×GUCY1A1 rs7692387G/G and NOS3 rs3918226-C/C×GUCY1A1 rs13139571C/C, showed strong protection against disease risk (FDR≤0.001). Functional SNP annotation revealed that the allele rs3918226-T was associated with decreased expression of NOS3, most strongly in the tibial arteries than in the coronary artery or aorta. The present study is the first to show that the rs3918226 polymorphism of NOS3 is a novel susceptibility marker for peripheral artery disease. Further research in independent populations is necessary to reproduce the association between polymorphism rs3918226 and disease risk.

Peripheral arterial disease in women.

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.

Aryl hydrocarbon receptor repressor (AHRR) methylation predicts risk of vascular disease: A cohort study of the general population.

Smoking is a risk factor for cardiovascular disease, but there is currently no clinically established biomarker for its cardiovascular damage. We aimed to investigate the hypothesis that aryl hydrocarbon receptor repressor (AHHR) methylation at CpG site cg05575921, a biomarker of smoking behavior, is associated with the risk of peripheral artery disease (PAD) and aortic aneurysm (AA) in the general population. In this prospective cohort study of the general population, we measured AHRR methylation in individuals from three visits of the Copenhagen City Heart Study. Information on risk factors were collected at visits with ten years intervals; visit 1 (1991-94), visit 2 (2001-03), and visit 3 (2011-15). Individuals were followed up in the Danish National Patient Register for PAD and AA until December 2018. Subhazard ratios were calculated using Fine and Gray competing risk regression. In 11,332 individuals from visit 1 (n=9,234), visit 2 (n=5,384), and visit 3 (n=4,387) there were 613 and 219 events of PAD and AA during up to 26.5 years of follow-up. AHRR hypomethylation was associated with higher risk of PAD and AA with multivariable adjusted subhazard ratios of 2.82 (1.91; 4.15) for PAD and 2.88 (1.42; 5.88) for AA in individuals within the lowest versus highest methylation quintile. We found that AHRR methylation, a strong biomarker for smoking, was associated with risk of PAD and AA. AHRR methylation could be a useful tool in more personalized risk prediction of PAD and AA.

The Identification and Evaluation of Interleukin-7 as a Myokine Biomarker for Peripheral Artery Disease Prognosis.

Background/Objectives: Myokines have been demonstrated to be associated with cardiovascular diseases; however, they have not been studied as biomarkers for peripheral artery disease (PAD). We identified interleukin-7 (IL-7) as a prognostic biomarker for PAD from a panel of myokines and developed predictive models for 2-year major adverse limb events (MALEs) using clinical features and plasma IL-7 levels. Methods: A prognostic study was conducted with a cohort of 476 patients (312 with PAD and 164 without PAD) that were recruited prospectively. Their plasma concentrations of five circulating myokines were measured at recruitment, and the patients were followed for two years. The outcome of interest was two-year MALEs (composite of major amputation, vascular intervention, or acute limb ischemia). Cox proportional hazards analysis was performed to identify IL-7 as the only myokine that was associated with 2-year MALEs. The data were randomly divided into training (70%) and test sets (30%). A random forest model was trained using clinical characteristics (demographics, comorbidities, and medications) and plasma IL-7 levels with 10-fold cross-validation. The primary model evaluation metric was the F1 score. The prognostic model was used to classify patients into low vs. high risk of developing adverse limb events based on the Youden Index. Freedom from MALEs over 2 years was compared between the risk-stratified groups using Cox proportional hazards analysis. Results: Two-year MALEs occurred in 28 (9%) of patients with PAD. IL-7 was the only myokine that was statistically significantly correlated with two-year MALE (HR 1.56 [95% CI 1.12-1.88], p = 0.007). For the prognosis of 2-year MALEs, our model achieved an F1 score of 0.829 using plasma IL-7 levels in combination with clinical features. Patients classified as high-risk by the predictive model were significantly more likely to develop MALEs over a 2-year period (HR 1.66 [95% CI 1.22-1.98], p = 0.006). Conclusions: From a panel of myokines, IL-7 was identified as a prognostic biomarker for PAD. Using a combination of clinical characteristics and plasma IL-7 levels, we propose an accurate predictive model for 2-year MALEs in patients with PAD. Our model may support PAD risk stratification, guiding clinical decisions on additional vascular evaluation, specialist referrals, and medical/surgical management, thereby improving outcomes.

Variability of flow-mediated dilation across lower and upper limb conduit arteries.

Endothelial dysfunction is an early predictor of atherosclerosis and cardiovascular disease. Flow-mediated dilation (FMD) is the goldstandard to assess endothelial function in humans. FMD reproducibility has been mainly assessed in the brachial artery (BA) with limited research in lower limb arteries. The purpose of this study was to compare FMD reproducibility in the upper limb BA and lower limb superficial femoral artery (SFA) in young healthy adults.Fifteen young healthy adults (nine males; six females) underwent FMD, resting diameter, velocity, and shear rate measurements on three occasions to determine intra-and inter-day reproducibility in both BA and SFA, assessed by coefficient of variation (CV), intraclass correlation coefficient (ICC), and Bland-Altman plots.BA FMD CVs (intra-day: 4.2%; inter-day: 8.7%) and ICCs (intra-day: 0.967; inter-day: 0.903) indicated excellent reproducibility and reliability, while for SFA FMD, both CVs (intra-day: 11.6%; inter-day: 26.7%) and ICCs (intra-day: 0.898; inter-day: 0.651) showed good/moderate reproducibility and reliability. BA FMD was significantly more reproducible than SFA FMD (p < 0.05). Diameter reproducibility was excellent and similar between arteries, while resting velocity and shear rate have lower reproducibility in the BA compared to SFA. Bland-Altman plots displayed no proportional and fixed bias between measurements.In summary, SFA FMD is less reproducible than BA FMD, with identical volume of ultrasound training. Given the increasing interest in using SFA FMD to test the efficacy of interventions targeting lower limb's vascular health and as a potential biomarker for peripheral arterial disease risk, future studies should ensure higher levels of training for adequate reproducibility.

Association between the triglyceride glucose index and atherosclerotic cardiovascular disease in the general population: analysis of the national health and nutrition examination survey 1999-2004.

The triglyceride-glucose (TyG) index, a reliable substitute indicator of insulin resistance (IR), is considered an independent risk factor for long-term outcomes in patients with cardiovascular disease. However, studies investigating the association between TyG and atherosclerotic cardiovascular disease (ASCVD) are limited and lack direct evidence. We aim to examine the relationship between the TyG index and ASCVD through a comprehensive cross-sectional study. Overall, 7212 participants from the 1999-2004 National Health and Nutrition Examination Survey were included. The baseline TyG index was calculated as ln [fasting triglyceride (mg/dL) × fasting blood glucose (mg/dL)/2]. Restricted cubic spline (RCS) regression, univariate logistic regression, and multivariate logistic regression analysis were used to evaluate the association between the TyG index and ASCVD. In the overall population, a multivariate logistic regression analysis showed that the TyG level was not only positively associated with ASCVD [OR (95%CI): 1.29 (1.01,1.64), P=0.042], coronary artery disease (CAD) [OR (95%CI): 1.82(1.33,2.48), P<0.001], and stroke [OR (95%CI): 2.68(1.54,4.69), P=0.002], but also linearly correlated with all three (P-overall<0.001; P-non-linear >0.05). Although the TyG index was not associated with peripheral arterial disease (PAD) [OR (95%CI): 1.00 (0.73,1.36), P>0.900], it showed a U-shaped correlation with PAD (P-overall <0.001; P-non-linear= 0.0085), and the risk of PAD was minimized when TyG=8.67. By incorporating the TyG index into the baseline risk model, the accuracy of ASCVD prediction was improved [AUC: baseline risk model, 0.7183 vs. baseline risk model + TyG index, 0.7203, P for comparison=0.034]. The results of the subgroup analysis were consistent with those of the main analysis. The TyG index was independently associated with ASCVD, CAD, and stroke, suggesting that it may serve as a valid indicator for predicting ASCVD in the entire population.

Sex and age significantly modulate cardiovascular disease presentation in type 2 diabetes: a large population-based cohort study.

We aimed to describe and compare the incidence of the first cardiovascular event and its major subtypes, coronary heart disease (CHD), cerebrovascular disease, heart failure (HF), or peripheral artery disease (PAD), according to age and sex in a population-based cohort of individuals with type 2 diabetes (T2D) from a Mediterranean region. We used linked primary care electronic medical reports, pharmacy-invoicing data, and hospital admission disease registry records from the SIDIAP database, which contains linked data for 74% of the Catalonian population. We selected individuals with T2D aged 30 to 89 years free of cardiovascular disease (CVD). The primary outcome was the first presentation of CVD. The study cohort included 247,751 individuals (48.6% women, 66.8 ± 11.9 years). During a 6.99-year follow-up, the cumulative incidence of the first cardiovascular event was 23.4%. Men were at higher risk for CVD (hazard ratio [HR]: 1.47 95%CI: 1.45-1.50), CHD (HR: 1.52 95%CI: 1.47-1.57), cerebrovascular disease (HR:1.07 95%CI: 1.03-1.10) and PAD (HR: 2.30 95%CI: 2.21-2.39) than women but at a lower risk for HF (HR:0.70 95%CI: 0.68-0.73). CHD and PAD were the most frequent CVD presentations among men (28.1% and 27.5%) and HF (40.1%) in women. CHD predominated among young participants of both sexes, while HF predominated among women older than 65 and men older than 75. In individuals with T2D, the overall risk and the type of first CVD manifestation largely varied by sex and age. This epidemiological evidence should be considered in clinical practice.

A prospective observational study to evaluate a possible relationship between vitamin K antagonist therapy and risk of peripheral arterial disease in patients with type 2 diabetes.

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. 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. 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)]. 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.

Prevalence of Peripheral Arterial Disease and Principal Associated Risk Factors in Patients with Type 2 Diabetes Mellitus: The IDON-Peripheral Arterial Disease Study

The principal purpose of this study is to determine the prevalence of peripheral arterial disease (PAD), as well as the principal associated risk factors, in patients registered in the IDON-PAD database. PAD is a condition characterized by the narrowing or blockage of arteries in the body’s extremities due to plaque buildup, leading to reduced blood flow and tissue ischemia. While PAD primarily affects the lower extremities, it can lead to symptoms such as intermittent claudication and, in severe cases, ulcers and amputations. Risk factors for PAD are numerous and cumulative, including smoking, age over 50, type 2 diabetes mellitus, and hypertension. The prevalence of PAD increases with age, with rates ranging from 2.5% in those over 50 to 60% in those over 85, varying by ethnicity and study population. Diabetic patients face a higher risk of PAD-related complications and have lower success rates with revascularization procedures. The diagnosis of PAD traditionally relied on physical examination and symptoms, but the Ankle–Brachial Index is now a standard diagnostic tool due to its non-invasive nature and reliability. In Mexico, the prevalence of PAD is estimated at 10%, with significant risk factors being the duration of diabetes, hypertension, hypertriglyceridemia, and smoking. Notably, 70% of PAD cases are asymptomatic, emphasizing the importance of proactive screening. This study aimed to determine the prevalence of PAD and associated risk factors in diabetic patients aged 40 and above. The prevalence was found to be 11.2%, with high-risk waist circumference, elevated triglycerides, positive Edinburgh questionnaire, and weak pulses as significant predictors. The detection and management of PAD in diabetic patients require a comprehensive approach, including lifestyle modifications and regular screenings. Prevention strategies should focus on controlling risk factors, including obesity, hypertension, and dyslipidemia. In conclusion, PAD is a prevalent yet underdiagnosed condition in diabetic patients, necessitating proactive screening and comprehensive management to mitigate associated risks and improve patient outcomes. The principal limitation of this study is that, as it uses a cross-sectional methodology and is not an experimental study, although we can establish the prevalence of PAD as well as the associated risk factors, we cannot define causality or determine the hazard ratio for each of these factors. Special thanks to Dr. Leobardo Sauque Reyna and all participants for their contribution to this research.

Relationship of apolipoprotein C-III proteoform composition with ankle-brachial index and peripheral artery disease in the Multi-Ethnic Study of Atherosclerosis (MESA)

Background and aimsApolipoprotein C-III (apoC-III) proteoform composition shows distinct relationships with plasma lipids and cardiovascular risk. The present study tested whether apoC-III proteoforms are associated with risk of peripheral artery disease (PAD). MethodsApoC-III proteoforms, i.e., native (C-III0a), and glycosylated with zero (C-III0b), one (C-III1) or two (C-III2) sialic acids, were measured by mass spectrometry immunoassay on 5,734 Multi-Ethnic Study of Atherosclerosis participants who were subsequently followed for clinical PAD over 17 years. Ankle-brachial index (ABI) was also assessed at baseline and then 3 and 10 years later in 4,830 participants. ResultsHigher baseline C-III0b/C-III1 and lower baseline C-III2/C-III1 were associated with slower decline in ABI (follow-up adjusted for baseline) over time, independently of cardiometabolic risk factors, and plasma triglycerides and HDL cholesterol levels (estimated difference per 1 SD was 0.31 % for both, p < 0.01). The associations between C-III2/C-III1 and changes in ABI were stronger in men (−1.21 % vs. −0.27 % in women), and in Black and Chinese participants (−0.83 % and −0.86 % vs. 0.12 % in White). Higher C-III0b/C-III1 was associated with a trend for lower risk of PAD (HR = 0.84 [95%CI: 0.67–1.04]) that became stronger after excluding participants on lipid-lowering medications (0.73 [95%CI: 0.57–0.94]). Neither change in ABI nor clinical PAD was related to total apoC-III levels. ConclusionsWe found associations of apoC-III proteoform composition with changes in ABI that were independent of other risk factors, including plasma lipids. Our data further support unique properties of apoC-III proteoforms in modulating vascular health that go beyond total apoC-III levels.

Abstract 3035: Associations Of Genetic And Lifestyle Risk Factors With Incident Peripheral Artery Disease: A Prospective Cohort Study

Background: The joint associations between genetic and lifestyle factors, and peripheral artery disease (PAD) remain unclear, yet understanding the connections is crucial for precise PAD prevention. Methods: Genetic susceptibility to PAD was estimated by a polygenic risk score of 50 genetic variants selected by P &lt; 5х10 -8 and r 2 &lt;0.01 from a GWAS including 31,307 cases. Tertiles categorized genetic risk into low, intermediate, and high. A healthy lifestyle score was constructed based on 4 lifestyle factors (never smoking, non-excessive alcohol consumption, high cardiometabolic healthy diet adherence, and regular physical activity) and categorized into favorable (3-4 healthy factors), intermediate (2 healthy factors), and unfavorable (0-1 healthy factors) groups. Cox regression estimated hazard ratios (HR) and 95% confidence interval (CI) with adjustment for age (time scale), sex, BMI, education, baseline cardiovascular risk factors, 20 principal components. Results: Over 11.9 years, 4299 incident PAD cases were diagnosed in 379,228 UK Biobank participants free of baseline PAD. Genetic risk and unhealthy lifestyle categories were monotonically associated with PAD. Compared with low genetic risk, the HR was 1.69 (95% CI 1.56-1.89) for high genetic risk. Compared with favorable lifestyle, the HR for unfavorable lifestyle was 2.70 (95% CI 2.50-2.94). There was no multiplicative interaction between genetic and lifestyle factors ( P = 0.461). The association between unfavorable lifestyle and higher PAD risk was consistent in genetic risk groups. Joint categorization analysis detected an HR for high genetic risk and favorable lifestyle was (1.85, 95% CI 1.54-2.22) reducing by &gt; 50%, compared with high genetic risk and unfavorable lifestyle (HR 4.76, 95% CI 4.00-5.56). Conclusions: Genetic and lifestyle factors independently associated with incident PAD. Adhering to a favorable lifestyle substantially reduced PAD risk, even in individuals at high genetic risk.

Abstract 2124: Genetic Variation Associated With Progression And Severity Of Peripheral Artery Disease

Background: Peripheral Artery Disease (PAD) is a major source of cardiovascular morbidity and mortality, affecting &gt;230 million individuals worldwide. While PAD may initially cause exertional limb pain (claudication), progression leads to chronic limb threatening ischemia (CLTI; rest pain and/or tissue loss) and amputation, which are associated with high rates of hospitalization and death. Genetic variants associated with PAD susceptibility have been identified using genome-wide association studies (GWAS). However, the role of genetic variation in the progression of PAD and disease severity remains poorly understood. Methods: GWAS of progression to CLTI were performed among individuals with PAD in the VA Million Veteran Program (MVP) and Copenhagen Hospital Biobank (CHB), accounting for age, sex, and genetic principal components. GWAS were first performed among genetically inferred ancestry subpopulations (EUR: European; AFR: African; AMR: admixed American), and combined using fixed-effects meta-analysis. SlopeHunter was used to account for index-event bias using a GWAS of prevalent PAD. Genetic associations with PAD severity (claudication, CLTI, amputation) were evaluated using multinomial logistic regression. Results: Up to 21.1 million genetic variants were tested for association with CLTI (17,641 individuals) in comparison to PAD (75,133 individuals). A total of 3 genetic loci were associated with progression to CLTI (p &lt; 5x10 -8 ). The strongest association with CLTI was rs6025 (OR 1.25, 95% CI 1.18 to 1.34, p = 4.62x10 -12 ), a common missense variant (p.Arg534Gln) encoding Factor V Leiden, with consistent effects accounting for index-event bias. Compared to 489,538 individuals without PAD in MVP, rs6025 was associated with increased risk of non-specific PAD (OR 1.15, 95% CI 1.1 to 1.2, p = 5x10 -8 ), claudication (OR 1.14, 95% CI 1.1 to 1.2, p = 1x10 -4 ), CLTI (OR 1.42, 95% CI 1.3 to 1.6, p = 7x10 -23 ), and amputation (OR 1.54, 95% CI 1.4 to 1.8, p = 2x10 -10 ). Conclusion: Our results implicate F5 p.Arg534Gln as a risk factor for PAD progression and severe PAD manifestations including CLTI and amputation. This result provides genetic support for a potential role of anticoagulation as a treatment to prevent PAD progression and severe outcomes.

Abstract 3117: Cannabis Use Disorder And The Risk Of Atherosclerotic Cardiovascular Diseases

Introduction: With the legalization of cannabis, concerns have emerged regarding the long-term health impact of excessive use. The current literature has struggled to address questions about the adverse effects of cannabis, particularly in the context of atherosclerotic cardiovascular disease (ASCVD). Using genetic approaches to causal inference, we explored the relationship between cannabis use disorder (CUD) and ASCVD. Methods: Genetic instruments were constructed from a multi-population GWAS comprising 64,314 individuals with and 990,051 without CUD. Outcome data for coronary artery disease (CAD), ischemic stroke, peripheral artery disease (PAD), and abdominal aortic aneurysms (AAA) were derived from multi-population GWAS. Univariable Mendelian randomization (MR) was performed using the inverse-variance weighted (IVW) method to test the association of CUD with each outcome. Multivariable MR (MVMR) was performed to assess if the impact of cardiometabolic risk factors accounted for the association of CUD with ASCVD using summary statistics from publicly available GWAS of cardiometabolic risk factors. Results: CUD was associated with increased risk of CAD (OR 1.27; 95% CI 1.17-1.38; P=&lt;0.01), ischemic stroke (OR 1.10; 95%CI 1.03-1.19; P=&lt;0.01), PAD (OR 1.31; 95% CI 1.17-1.46; P=&lt;0.01), and AAA (OR 1.37; 95% CI 1.21-1.55; P=&lt;0.01). CUD also had a significant impact on cardiometabolic risk factors including triglycerides, waist-to-hip ratio, BMI, type 2 diabetes, obesity, and heart failure. The effect of CUD on ASCVD, other than stroke, remained largely independent of traditional risk factors except for lipids and tobacco smoking. Controlling for lifetime smoking index attenuated all associations between CUD and ASCVD except CAD, which remained significant (OR 1.21; 95% CI 1.11-1.31). Conclusion: Excessive cannabis use has the potential to increase ASCVD risk, independent of cardiometabolic risk factors, although this risk may in part be attributable to shared susceptibility to lipids and tobacco use. Awareness of the long-term risks of excessive cannabis use should be considered when formulating medical advice and public policy.

Abstract 2025: Evolving Burden Of Peripheral Artery Disease Attributable To Smoking In 38 Oecd Countries From 1990-2019: Global, Regional, National Variations, Age Dynamics, And Implications For Global Health

Introduction and Background: Peripheral artery disease (PAD) ranks as the 11th leading cause of mortality and disability in countries within the Organization for Economic Cooperation and Development (OECD). Smoking is recognized as a leading risk factor for PAD, and its impact on the prevalence and outcomes of PAD has significant public health implications. Method: Using Global Burden of Disease framework, Deaths, disability adjusted life years (DALYs), years lived with disability (YLDs) due to stroke attributable to Smoking were analyzed by age, sex, year and location across the 38 OECD Countries from the last 3 decades. Results: From 1990 to 2019, the total number of deaths increased from 7,226 to 10,738, and Disability-Adjusted Life Years (DALYs) rose from 191,915 to 238,577. In 2019, the United States had the highest number of deaths (3,596) and DALYs (83,073). Hungary had the highest age-standardized mortality rate in 2019 (1.7 deaths per 100,000 person-years). The 80-84 age group had the most deaths (2,233), while the 70-74 age group had the highest DALYs (45,947) in 2019. Over the past three decades, males consistently had a higher burden, with an annual percentage change in deaths of 50% compared to 45% for females, and a 32% change in DALYs for males compared to 12% for females. Conclusion: The findings highlight the urgent need for public health efforts to address the increasing burden of peripheral artery disease (PAD), particularly focusing on smoking cessation and tailored interventions for high-risk groups. Clinicians should prioritize early detection and patient counseling to mitigate PAD risk factors, especially among males with a consistently higher burden.

Risk of Adverse Cardiovascular Outcomes in Postmenopausal Women with Inflammatory Bowel Disease

BackgroundIndividuals with inflammatory bowel disease (IBD) who lack traditional cardiovascular disease (CVD) risk factors, such as young females, are observed to experience adverse CVD outcomes. Whether women with IBD have increased CVD risk after the menopause transition is unclear.MethodsWe conducted a survival analysis of Women’s Health Initiative (WHI) participants and excluded those with missing IBD diagnosis, model covariate data, follow-up data, or a baseline history of the following CVD outcomes: coronary heart disease (CHD), ischemic stroke, venous thromboembolism (VTE), peripheral arterial disease (PAD). Risk of outcomes between IBD and non-IBD women was performed using Cox proportional hazard models, stratified by WHI trial and follow-up. Models were adjusted for age, socio-demographics, comorbidities (e.g., hypertension, diabetes, hypercholesterolemia, etc.), family history, and lifestyle factors (e.g., smoking, alcohol, physical activity, body mass index, etc.).ResultsOf 134,022 WHI participants meeting inclusion criteria, 1367 (1.0%) reported IBD at baseline. Mean baseline age was 63.4 years. After adjusting for age and other confounders, no significant difference was observed between IBD and non-IBD women for the risk of CHD (HR 0.96, 95% CI 0.73–1.24), VTE (HR 1.11, 95% CI 0.81–1.52) or PAD (HR 0.64, 95% CI 0.28–1.42). After adjusting for age, risk of ischemic stroke was significantly higher (HR 1.41, 95% CI 1.06–1.88) in IBD than non-IBD women. With further adjustment, the excess risk of ischemic stroke among IBD women was attenuated and no longer statistically significant (HR 1.31, 95% CI 0.98–1.76).ConclusionsAmong postmenopausal women with IBD, risk of ischemic stroke may be higher than in non-IBD women.

Smoking as a risk factor for lower extremity peripheral artery disease in women compared to men: A systematic review and meta-analysis.

To investigate whether the relationship between smoking and peripheral artery disease (PAD) differs by sex (PROSPERO CRD42022352318). PubMed, EMBASE, and CINAHL were searched (3 March 2024) for studies reporting associations between smoking and PAD in both sexes, at least adjusted for age. Data were pooled using random effects. Between-study heterogeneity was examined using I2 statistic and Cochran's Q test. Newcastle-Ottowa Scale was adopted for quality assessment. Four cohort studies (n = 2,117,860, 54.4% women) and thirteen cross-sectional studies (n = 230,436, 59.9% women) were included. In cohort studies, former and current smokers had higher risk of PAD than never smokers. Compared to those who never or previously smoked, women current smokers (relative risk (RR) 5.30 (95% confidence interval 3.17, 8.87)) had higher excess risk of PAD than men (RR 3.30 (2.46, 4.42)), women-to-men ratio of RR 1.45 (1.30, 1.62)(I2 = 0%, p = 0.328). In cross-sectional studies, risk of PAD was higher among former and current compared to never smokers, more so in men, women-to-men ratios of odds ratio: 0.64 (0.46, 0.90)(I2 = 30%, p = 0.192), 0.63 (0.50, 0.79)(I2 = 0%, p = 0.594), respectively. For both sexes, risk of PAD was higher among current smokers compared to those who were not currently smoking. Cohort studies and five cross-sectional studies were of good quality, scoring 6 to 8 of a possible maximum 9 points. Eight cross-sectional studies scored 2 to 5. Further research is required to elucidate sex differences in the relationships between smoking and PAD, as the current evidence is limited and mixed. Tobacco-control programs should consider both sexes.

Association between alcohol consumption and peripheral artery disease: two de novo prospective cohorts and a systematic review with meta-analysis

Abstract Aims The association between alcohol consumption and risk of peripheral artery disease (PAD) is inconclusive. We conducted this study to examine the association between alcohol consumption and PAD risk in two de novo cohort studies and a meta-analysis of observational studies. Methods and results A systematic review was conducted to identify studies on alcohol consumption in relation to PAD risk. We further used data from two cohorts of 70 116 Swedish and 405 406 British adults and performed a meta-analysis of results from previously published studies and current cohort studies. There was a U-shaped association between alcohol consumption and incident PAD risk in the Swedish and British cohorts. The meta-analysis of results of these two cohorts and previously published studies found that compared with non- or never-drinkers, the relative risk of PAD was 0.83 [95% confidence interval (CI) 0.77–0.89], 0.81 (95% CI 0.74–0.90), and 0.94 (95% CI 0.83–1.07) for light, moderate, and high-to-heavy alcohol drinkers, respectively. The nonlinear meta-analysis revealed a possibly U-shaped association between alcohol consumption and PAD risk (P nonlinearity &amp;lt;0.001). The risk of PAD was observed to be the lowest for 2 drinks/week and to be pronounced for ≥10 drinks/week. All these associations persisted in a sensitivity meta-analysis including cohort and other types of observational studies. Conclusion Alcohol intake ≤2 drinks/week was associated with a reduced risk of PAD, and the risk of PAD became pronounced with intake ≥10 drinkers/week.

Comparison of Postexercise Ankle Brachial Index in at Risk versus Diagnosed Peripheral Arterial Disease Population

Abstract Background: Peripheral arterial disease (PAD) is characterized by stenosis or occlusion in the arteries of the limb causing limitation in the distal blood flow. Out of the various risk factors identified, diabetes and cigarette smoking are the strongest predictors of PAD. PAD results from atherosclerosis of the vessel wall. Patients with lower extremity PAD have clinical presentation of intermittent claudication and atypical leg pain. In patients with arterial stenosis, there is a drop in pressure and flow across stenosis. Asymptomatic PAD approximately 20%–50% of total patients diagnosed with PAD. Ankle brachial index (ABI) is clinically widely used modality which helps to identify the disease. ABI test is the ratio of systolic ankle blood pressure and highest systolic brachial blood pressure. Population at risk with normal resting ABI may still have PAD. For such population, postexercise ABI is recommended. This study evaluated and compared ABI postexercise in normal healthy individuals without risk of PAD, at risk of PAD. Materials and Methods: This study is an observational study. Population with age more than 35 years were selected. Framingham Risk Score was taken for normal and at-risk population. Subjects were recruited in three groups: A, B, and C. ABI at rest was assessed. Individuals performed exercise treadmill test. Immediately, after completing the exercise, postexercise ABI was taken. Absolute systolic blood pressure values and postexercise ABI values were obtained in all three groups and then were compared. Data were analyzed using the SPSS software version 26. Results: The results of this study showed that for all the three groups, there was a significant difference in ABI at rest, postexercise ABI, and difference in systolic ankle pressure as P value was &lt;0.001. When the Chi-squared test was done for postexercise ABI and postsystolic ankle pressure in between Group B and Group C, there was no significant difference found as the P value was &gt;0.05. Conclusion: On comparison with at risk and normal individuals, no significant difference was found in terms of postexercise ABI and change in systolic ankle pressure.

23 AHA’s Essential Eight: Opportunities for Preventive Care among Adults with Peripheral Arterial Disease

OBJECTIVES/GOALS: The objective was to examine the American Heart Association’s (AHA) Essential Eight metrics of cardiovascular (CV) health among Black and White adults with peripheral arterial disease (PAD) collected via validated surveys and medical records. Each metric was examined in association with available social determinants of health (SDoH) factors. METHODS/STUDY POPULATION: This observational study completed data collection through surveys and medical record review. Validated surveys were used to collect Essential Eight metrics of diet, physical activity, sleep, and smoking status. Medical records were used to collect data on body mass index, blood lipids, blood glucose, and blood pressure. Participants with a diagnosis of lower extremity PAD, ability to complete surveys, and provided informed written consent were eligible. Equal numbers of Black and White participants were enrolled. Essential Eight metrics were used to calculate CV health scores for each participant. Scores were examined for association with SDoH factors and by race using Student’s T-test or ANOVA for continuous variables or Chi-Square tests for categorical variables. RESULTS/ANTICIPATED RESULTS: A total of 50 participants will be enrolled, with the expected majority being men and half self-reporting as Black individuals. Worse SDoH is expected to be associated with lower CV health metrics, including lower levels of physical activity and higher levels of saturated fatty food consumption. Higher levels of blood lipids, blood glucose, and blood pressure are expected to be associated with worse SDoH factors. We expect this association to be attenuated by rates of CV medications, such as statin therapy, antiglycemic medications, and antihypertensive medications. No effect modification by rurality is expected, although our projected sample size is small and may impact the ability to examine this interaction. DISCUSSION/SIGNIFICANCE: Black Americans, particularly in the Deep South, are at elevated risk for PAD and critical limb ischemic events, such as amputation. Understanding CV health metrics and SDoH characteristics among adults with PAD is essential to reduce disparities in care and provide valuable information for those at highest risk for complications.

Remnant Cholesterol, Not LDL Cholesterol, Explains Peripheral Artery Disease Risk Conferred by apoB: A Cohort Study.

Elevated apoB-containing lipoproteins (=remnants+LDLs [low-density lipoproteins]) are a major risk factor for atherosclerotic cardiovascular disease, including peripheral artery disease (PAD) and myocardial infarction. We tested the hypothesis that remnants and LDL both explain part of the increased risk of PAD conferred by elevated apoB-containing lipoproteins. For comparison, we also studied the risk of chronic limb-threatening ischemia and myocardial infarction. apoB, remnant cholesterol, and LDL cholesterol were measured in 93 461 individuals without statin use at baseline from the Copenhagen General Population Study (2003-2015). During up to 15 years of follow-up, 1207 had PAD, 552 had chronic limb-threatening ischemia, and 2022 had myocardial infarction in the Danish National Patient Registry. Remnant and LDL cholesterol were calculated from a standard lipid profile. Remnant and LDL particle counts were additionally measured with nuclear magnetic resonance spectroscopy in 25 347 of the individuals. Results were replicated in 302 167 individuals without statin use from the UK Biobank (2004-2010). In the Copenhagen General Population Study, multivariable adjusted hazard ratios for risk of PAD per 1 mmol/L (39 mg/dL) increment in remnant and LDL cholesterol were 1.9 (95% CI, 1.5-2.4) and 1.1 (95% CI, 1.0-1.2), respectively; corresponding results in the UK Biobank were 1.7 (95% CI, 1.4-2.1) and 0.9 (95% CI, 0.9-1.0), respectively. In the association from elevated apoB to increased risk of PAD, remnant and LDL cholesterol explained 73% (32%-100%) and 8% (0%-46%), respectively; corresponding results were 63% (30%-100%) and 0% (0%-33%) for risk of chronic limb-threatening ischemia and 41% (27%-55%) and 54% (38%-70%) for risk of myocardial infarction; results for remnant and LDL particle counts corroborated these findings. PAD risk conferred by elevated apoB-containing lipoproteins was explained mainly by elevated remnants, while myocardial infarction risk was explained by both elevated remnants and LDL.