Risk Of Peripheral Arterial Disease Research Articles

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.

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 < 5х10 -8 and r 2 <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 > 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 >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 < 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=<0.01), ischemic stroke (OR 1.10; 95%CI 1.03-1.19; P=<0.01), PAD (OR 1.31; 95% CI 1.17-1.46; P=<0.01), and AAA (OR 1.37; 95% CI 1.21-1.55; P=<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 <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 <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 >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.

Abstract P264: HDL-C Variability and Peripheral Artery Disease

Background: Growing evidence has recognized the clinical implications of lipid variability in relation to cardiovascular disease and adverse outcomes. However, data on the association between lipid variability and the risk of incident peripheral artery disease (PAD) remain scarce compared to other manifestations like coronary artery disease and stroke. Methods: We conducted a study using data from the Chang Gung Research Database in Taiwan. A total of 93,948 patients diagnosed with hyperlipidemia between 2007 and 2013 who had at least one lipid measurement annually for four consecutive years were included in this study. Lipid levels, including total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), and triglycerides, as well as their visit-to-visit variability (average real variability, ARV), were calculated over the four-year period. Patients were followed up until December 31, 2019, for the development of incident PAD. Results: During a mean follow-up of 5.9 years, 2,735 (2.5%) of the patients had incident PAD. The mean levels of the four lipids were all significantly associated with the development of incident PAD. However, only HDL-C ARV showed a significant association with an increased risk of incident PAD, independent of traditional risk factors for atherosclerosis and lipid-lowering therapy (adjusted hazard ratio: 1.13; 95% confidence interval: 1.004-1.27 for the comparison between patients in the highest and lowest quartile of HDL-C ARV; P for trend = 0.002). A sensitivity analysis using the variability independent of the mean as the HDL-C variability index confirmed this association. The study result was consistent across all subgroups analyzed. Conclusions: In this multi-institutional database analysis, visit-to-visit variability in HDL-C was significantly associated with the risk of incident PAD, independent of traditional risk factors for atherosclerosis, mean lipid levels, and the use of lipid-lowering therapy. Absolute levels of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides were all significantly associated with the development of incident PAD. Visit-to-visit variability in HDL-C was significantly linked to the risk of incident PAD, irrespective of traditional atherosclerosis risk factors, mean lipid levels, and lipid-lowering therapy use.

Mendelian randomization study on insulin resistance and risk of hypertension and cardiovascular disease

Observational studies have suggested that insulin resistance (IR) is associated with hypertension and various cardiovascular diseases. However, the presence of a causal relationship between IR and cardiovascular disease remains unclear. Here, we applied Mendelian randomization (MR) approaches to address the causal association between genetically determined IR and the risk of cardiovascular diseases. Our primary genetic instruments comprised 53 SNPs associated with IR phenotype from a GWAS of up to 188,577 participants. Genetic association estimates for hypertension and venous thromboembolism (VTE) were extracted from UK Biobank, estimates for atrial fibrillation (AF) were extracted from the hitherto largest GWAS meta-analysis on AF, estimates for heart failure were extracted from HERMES Consortium, estimates for peripheral artery disease (PAD) and aortic aneurysm were extracted from the FinnGen Study. The main analyses were performed using the random-effects inverse-variance weighted approach, and complemented by sensitivity analyses and multivariable MR analyses. Corresponding to 55% higher fasting insulin adjusted for body mass index, 0.46 mmol/L lower high-density lipoprotein cholesterol and 0.89 mmol/L higher triglyceride, one standard deviation change in genetically predicted IR was associated with increased risk of hypertension (odds ratio (OR) 1.06, 95% CI 1.04–1.08; P = 1.91 × 10–11) and PAD (OR 1.90, 95% CI 1.43–2.54; P = 1.19 × 10–5). Suggestive evidence was obtained for an association between IR and heart failure (OR per SD change in IR: 1.19, 95% CI 1.01–1.41, P = 0.041). There was no MR evidence for an association between genetically predicted IR and atrial fibrillation, VTE, and aortic aneurysm. Results were widely consistent across all sensitivity analyses. In multivariable MR, the association between IR and PAD was attenuated after adjustment for lipids (P = 0.347) or BMI (P = 0.163). Our findings support that genetically determined IR increases the risk of hypertension and PAD.

Association of Serum Homocysteine With Peripheral Arterial Disease in Patients Without Diabetes: A Study Based on National Health and Nutrition Examination Survey Database

This study aimed to investigate the association of serum homocysteine (Hcy) levels with peripheral arterial disease (PAD) in patients without diabetes on the basis of data from the National Health and Nutrition Examination Survey. The study used data from 3 survey cycles (1999 to 2004) in the National Health and Nutrition Examination Survey database as the research dataset. Serum Hcy levels were considered an independent variable, whereas PAD was a dependent variable. Weighted logistic regression and restricted cubic spline methods were used to explore the relation between Hcy level and PAD risk in patients without diabetes. A total of 4,819 samples were included. In the weighted logistics regression model, a significant positive association was observed between Hcy levels and the risk of PAD (odds ratio >1, p <0.05). Subgroup analysis results indicated a particularly significant association between Hcy levels and PAD risk in the older population (age ≥60 years), those with a history of smoking, and those without a history of myocardial infarction (all odds ratio >1, p <0.05) (p <0.05). Exploring the nonlinear association between Hcy levels and PAD risk through restricted cubic spline curves revealed an overall significant trend (p allover <0.05). In conclusion, elevated Hcy levels increased the risk of PAD, with a more pronounced effect observed in populations of patients without diabetes, especially in older patients (age ≥60 years), those with smoking history, and those without a history of myocardial infarction.

Association of prognostic nutritional index with peripheral artery disease in US adults: a cross-sectional study

BackgroundThe objective of this study was to investigate the relationship between the prognostic nutritional index (PNI) and peripheral artery disease (PAD).MethodsThe present study is a cross-sectional study based on the National Health and Nutrition Survey (1999–2004). The laboratory-calculated PNI was divided into four groups based on quartiles(Q1:PNI ≤ 50.00; Q2: 50.01–53.00; Q3:53.01–56.00; Q4: > 56.00). PAD was defined as an ankle brachial pressure index (ABPI) ≤ 0.9 on the left or right. The relationship between PNI and PAD was examined using multifactor weighted logistic regression analysis, as well as subgroup analysis. Subgroup analyses were conducted based on demographic and clinical variables.ResultsA total of 5,447 individuals were included in our final analysis. The age of the participants was 59.56 ± 13.10 years, and males accounted for 52.8% (n = 2820). The prevalence of PAD was 6.7% (n = 363). After adjusting for all factors, participants with Q1 still had an increased risk of PAD, with an OR value of 1.593 and a 95% CI of 1.232–1.991. Subgroup analysis showed no significant interaction among multiple factors.ConclusionsIn summary, we report that lower PNI are associated with a higher risk of PAD in US adults. It is hoped that this discovery can provide a reference for the prevention of PAD.

Association of plasma homocysteine with peripheral arterial disease in the hypertensive adults: A cross-sectional study.

Increased plasma homocysteine (Hcy) has been identified as one of the important risk factors for cardiovascular disease. However, the association between plasma Hcy and peripheral artery disease (PAD) is still controversial. This study aimed to investigate the association between plasma Hcy and PAD and the potential modifier factors in Chinese hypertensive adults. A total of 25300 hypertensive patients aged 18years or older were included in the analysis in this cross-sectional study. The outcome was PAD, which defined as an ankle-brachial index ≤0.90 in either limb. Multiple logistic regression was used to analyze the relationship between plasma Hcy and PAD. The median plasma Hcy was 14.00 (interquartile range: 11.60-17.80)μmol/L. There was a significant positive association between plasma Hcy and PAD (per SD increment; OR: 1.13; 95% CI: 1.06-1.19). Patients in the upper plasma Hcy tertile (≥16.16μmol/L) were associated with a 53% increased risk of PAD compared with patients in the lower tertile (<12.33μmol/L) after adjustment for multiple potential confounders. Subgroup analyses showed the association between Hcy and PAD was robust among various strata. Among Chinese adults with hypertension, plasma Hcy is an independent risk factor for PAD. This finding may improve the risk stratification of PAD.

Major Depressive Disorder Impacts Peripheral Artery Disease Risk Through Intermediary Risk Factors.

Major depressive disorder (MDD) has been identified as a causal risk factor for multiple forms of cardiovascular disease. Although observational evidence has linked MDD to peripheral artery disease (PAD), causal evidence of this relationship is lacking. Inverse variance weighted 2-sample Mendelian randomization was used to test the association the between genetic liability for MDD and genetic liability for PAD. Genetic liability for MDD was associated with increased genetic liability for PAD (odds ratio [OR], 1.17 [95% CI, 1.06-1.29]; P=2.6×10-3). Genetic liability for MDD was also associated with increased genetically determined lifetime smoking (β=0.11 [95% CI, 0.078-0.14]; P=1.2×10-12), decreased alcohol intake (β=-0.078 [95% CI, -0.15 to 0]; P=0.043), and increased body mass index (β=0.10 [95% CI, 0.02-0.19]; P=1.8×10-2), which in turn were associated with genetic liability for PAD (smoking: OR, 2.81 [95% CI, 2.28-3.47], P=9.8×10-22; alcohol: OR, 0.77 [95% CI, 0.66-0.88]; P=1.8×10-4; body mass index: OR, 1.61 [95% CI, 1.52-1.7]; P=1.3×10-57). Controlling for lifetime smoking index, alcohol intake, and body mass index with multivariable Mendelian randomization completely attenuated the association between genetic liability for MDD with genetic liability for PAD. This work provides evidence for a possible causal association between MDD and PAD that is dependent on intermediate risk factors, adding to the growing body of evidence suggesting that effective management and treatment of cardiovascular diseases may require a composite of physical and mental health interventions.

Peripheral artery disease mediating the effect of metabolic syndrome related diseases on lower limb ulcers: Mendelian randomization analysis.

Previous observational studies have demonstrated a correlation between metabolic syndrome related diseases and an elevated susceptibility to ulcers of lower limb. It has been suggested that this causal relationship may be influenced by the presence of peripheral artery disease (PAD). Nevertheless, the precise contribution of these factors as determinants of ulcers of lower limb remains largely unexplored. This research incorporated information on hypertension, BMI, hyperuricemia, type 2 diabetes, PAD, and ulcers of lower limb sourced from the GWAS database. Univariate Mendelian randomization (SVMR) and multivariate Mendelian randomization (MVMR) methods were employed to assess the association between metabolic syndrome related diseases, including hypertension, obesity, hyperuricemia, and type 2 diabetes, as well as to investigate whether this association was influenced by PAD. Univariate Mendelian randomization analysis showed that genetically predicted hypertension, BMI, and type 2 diabetes were associated with an increased risk of PAD and ulcers of lower limb, and PAD was associated with an increased risk of ulcers of lower limb, but there is no causal relationship between hyperuricemia and ulcers of lower limb. The results of multivariate Mendelian randomization showed that PAD mediated the causal relationship between hypertension, obesity and ulcers of lower limb, but the relationship between type 2 diabetes and ulcers of lower limb was not mediated by PAD. Hypertension, BMI and type 2 diabetes can increase the risk of ulcers of lower limb, and PAD can be used as a mediator of hypertension and obesity leading to ulcers of lower limb, These findings may inform prevention and intervention strategies directed toward metabolic syndrome and ulcers of lower limb.

Association between red cell distribution width-and-albumin ratio and the risk of peripheral artery disease in patients with diabetes.

The aim of this study is to explore the association between red blood cell distribution width-to-albumin ratio (RAR) and the risk of peripheral artery disease (PAD) in patients with diabetes. This cross-sectional study extracted the data of 1,125 participants with diabetes from the National Health and Nutrition Examination Survey database. A weighted univariable logistic regression model was used to explore variables associated with PAD. With PAD as the outcome variable, a weighted logistic regression model was established. The odds ratio (OR) and 95% confidence interval (CI) were effect size. After adjusting for covariates, the risk of PAD in patients with diabetes was observed in those with higher RAR (OR = 1.83; 95% CI: 1.06-3.15). In addition, RAR ≥3.25 was related to increased risk of PAD in patients with diabetes (OR = 2.04; 95% CI: 1.05-3.95). In people with diabetes aged ≥65, RAR was a risk factor for PAD with an OR value of 2.67 (95% CI: 1.30-5.46). RAR≥3.25 was associated with increased risk of PAD (OR = 3.06; 95% CI: 1.15-8.11) relative to RAR <2.80. In people with diabetes who smoked, the risk of PAD was elevated in those with RAR ≥3.25 (OR = 2.85; 95% CI: 1.28-6.32). As for patients with cardiovascular disease, the risk of PAD was elevated as the increase of RAR (OR = 2.31; 95% CI: 1.05-5.10). RAR ≥3.25 was correlated with increased risk of PAD (OR = 3.75; 95% CI: 1.42-9.87). The area under the curve of RAR for the risk of PAD in patients with diabetes was 0.631 (95% CI: 0.588-0.675). A higher RAR was related to increased risk of PAD in patients with diabetes. The findings might offer a reference for the management of PAD in patients with diabetes.