Risk Of Peripheral Arterial Disease Research Articles

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

AimsWe 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.Material and methodsWe 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.ResultsThe 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.ConclusionsIn 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 show 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 differences per 1 SD were 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 were 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.

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

Individuals 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. We 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.). Of 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). Among 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.

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.

In Association with Other Risk Factors, Smoking Is the Main Predictor for Lower Transcutaneous Oxygen Pressure in Type 2 Diabetes.

Type 2 diabetes mellitus (T2DM) significantly increases the risk of peripheral artery disease (PAD), and diabetes is the leading cause of nontraumatic amputations. This study investigated the risk factors for transcutaneous oxygen pressure (TcPO2) in T2DM, a noninvasive method to quantify skin oxygenation and the underlying microvascular circulation. The study included 119 T2DM patients (91 male/28 female). TcPO2 measurements were conducted with the Tina TCM4 Series transcutaneous monitor (Radiometer, Copenhagen, Sweden) and skin electrodes. Patients with TcPO2 < 40 mmHg were younger (p = 0.001), had significantly higher systolic blood pressure (SBP) (p = 0.023), glycated hemoglobin (HbA1c) (p = 0.013), fasting plasma glucose (fPG) (p = 0.038), total cholesterol (p = 0.006), LDL cholesterol (p = 0.004), and had more frequent smoking habits (p = 0.001) than those with TcPO2 ≥ 40 mmHg. The main predictors for the TcPO2 value (R2 = 0.211) obtained via stepwise regression analysis were age, smoking, SBP, HbA1c, fPG, and total and LDL cholesterol. Among all the listed predictors, smoking, HbA1c, and LDL cholesterol were found to be the most significant, with negative parameter estimates of -3.051310 (p = 0.0007), -2.032018 (p = 0.0003), and -2.560353 (p = 0.0046). The results of our study suggest that in association with other risk factors, smoking is the main predictor for lower TcPO2 in T2DM.

MAXIMAL EXERCISE CAPACITY IS INVERSELY RELATED TO INCIDENT PERIPHERAL ARTERY DISEASE

BACKGROUND Maximal exercise capacity (EC) is a strong, independent predictor of incident coronary and cerebrovascular disease. However, less is known about the relationship between EC and incident peripheral artery disease (PAD). Using data from the Henry Ford Exercise Testing (FIT) Project, we evaluated the relationship between EC and incident PAD. We hypothesized that EC, measured in metabolic equivalents of task (METs), is inversely related to incident PAD. METHODS We assessed 41,268 patients (age = 55±12 yrs, 49% female, and 64% white) who completed a clinically indicated exercise stress test between January 1991 and June 2009 at a Henry Ford Health facility. Patients with established PAD at the time of testing were excluded. METs were estimated from peak treadmill speed and grade and standardized to the equivalent of a 50-year-old male to account for differences in absolute risk for a given MET level by age and sex. METs were categorized as &amp;lt;6, 6-9, 10-11, and &amp;gt;12. ICD9 codes 440.XX and 443.9 were used to identify first incidence of PAD from the test date through June 2010. Multivariable Cox regression was used to relate METs to incident PAD. Patients were censored at the date of death or last clinic visit. RESULTS During a median follow-up of 7.1 years (IQR 4.2-11.1 yrs) there were 2,596 (6%) incident diagnoses of PAD. In the adjusted analysis, each 1 MET increase in maximal EC was associated with a 7% lower risk of PAD (aHR=0.93 [0.91, 0.94]). There was a graded, inverse risk of incident PAD by MET category (see Table). A significant interaction was noted for race (overall p=.04; white [HR=0.93 (0.92, 0.95)] vs black [HR=0.91 (0.88, 0.93)], p=.02; white vs other [HR=0.97 (0.87, 1.07)], p=0.47), but not for sex (p=.79). CONCLUSION In a diverse cohort that completed a clinically indicated exercise stress test, higher EC measured in METs, is independently and inversely associated with a lower risk of incident PAD.

Association between Statin use and Incident Peripheral Artery Disease According to Race, Age, and Presence of Depression in the Multi-Ethnic Study of Atherosclerosis

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