Incidence Of Peripheral Arterial Disease Research Articles

Temporal Trends and Mortality Patterns in Peripheral Arterial Disease: A Comprehensive Analysis of Hospitalized Patients in Kazakhstan between 2014 and 2021.

Peripheral artery disease (PAD) is a global health concern associated with arterial narrowing or blockage, leading to significant morbidity and mortality. The aim of this study is to assess the disease burden and trends in mortality utilizing nationwide administrative health data. This retrospective study utilized data from the Unified National Electronic Healthcare System (UNEHS) from 2014 to 2021. Patients meeting PAD criteria were included, with demographic and clinical data analyzed. Cox regression and Competing Risk Analysis assessed mortality risks. Between 2014 and 2021, 19,507 individuals were hospitalized due to PAD, with 8,332 (43%) being women and 11,175 (57%) men. The incidence of PAD increased markedly over the observation period, rising from 79 individuals per million population (PMP) in 2014 to 309 PMP in 2021. Concurrent heart failure (HF), acute myocardial infarction (AMI), diabetes, and essential hypertension were prevalent in 50%, 27%, 27%, and 26% of the PAD patients, respectively. Competing Risk Analysis showed a subdistribution hazard ratio (SHR) of 6.53 [95% CI: 4.65-9.19] for individuals over 80 years. Heart failure was associated with lower all-cause HR [0.80, 95% CI: 0.76-0.86, p < 0.001] but higher SHR [1.30, 95% CI: 1.18-1.44, p < 0.001]. Comorbidities such as heart failure, stroke, and acute myocardial infarction significantly increased mortality risks, while essential hypertension was associated with lower risk of death. The significant rise in the incidence rate of PAD underscores the growing burden of the disease, highlighting the urgent need for targeted preventive and management strategies in Kazakhstan.

Associations of Genetic and Lifestyle Risk Factors With Incident Peripheral Artery Disease: A Prospective Cohort Study

Associations of Genetic and Lifestyle Risk Factors With Incident Peripheral Artery Disease: A Prospective Cohort Study

Temporal Trends and Outcomes of Peripheral Artery Disease and Critical Limb Ischemia in the United States.

Peripheral arterial disease (PAD) is a progressive, systemic atherosclerotic disease that is associated with an increased risk of coronary artery disease (CAD), cerebrovascular disease (CVD), and critical limb ischemia (CLI). CLI represents the most severe stage of PAD, characterized by progressive endothelial dysfunction and arterial narrowing. We hypothesized that the incidence of CLI and PAD would increase over the study period and that the rates of in-hospital mortality and major amputations among patients admitted with CLI would rise correspondingly. We utilized the National Inpatient Sample (NIS) database from year 2016 to 2021 using the ICD-10-CM codes. Patients with a primary or secondary diagnoses of PAD were initially selected and subsequently hospitalization with CLI were appropriately identified. Cochran Armitage test was used to describe the trend of outcomes across the years. All statistical analyses were conducted using the software Stata version 17.0. From 2016-2021, there were 2,930,639 admissions for critical limb ischemia. 65% of these patients were over the age of 60 and 35.8% of these patients were women. Most of these individuals were white (64.7%), followed by African Americans (15.8%) and Hispanics (12.6%). In-hospital mortality rates varied by revascularization method, with hybrid revascularization showing the highest rate at 2.6%, followed by endovascular revascularization at 1.8%, and surgical revascularization at 1.6%. Additionally, hospitalization costs were highest for patients undergoing hybrid revascularization ($46,257 ± $36,417), compared to endovascular ($36,924 ± $27,945) and surgical revascularization ($35,672 ± $27,127). Endovascular revascularization rates seemed to increase while surgical revascularization rates decreased during this time period. PAD is a progressive, systemic atherosclerotic disease that is associated with an increased risk of CAD, CVD, and CLI. Our data showed that the rates of PAD and CLI hospitalizations has remained relatively stable from 2016-2021, but there seems to be a trend towards doing more revascularization via an endovascular approach as compared to a surgical approach.

A meta-analysis of randomized controlled studies examining the effects of sodium-glucose co-transporter-2 inhibitors on peripheral artery disease and risk of amputations.

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

Association between grip strength, walking pace and incident peripheral artery disease: A prospective study of 430,886 UK biobank participants

Background and aimsPatients with peripheral artery disease (PAD) presented overall muscle weakness and reduced physical performance. Previous study focused on the impact of muscle weakness on outcomes of established PAD, however the relationship between compromised muscle function and incident PAD remained unclear. MethodsA prospective study involving 430,886 participants aged 40–69 y from UK biobank was conducted. The main outcome was incident PAD. Grip strength and walking pace were used as indicators for muscle function. Grip strength was measured using a Jamar J00105 hydraulic hand dynamometer, while walking pace was self-reported by the participants. Cox proportional hazard models were employed to investigate the relationship between grip strength, walking pace, and incident PAD. ResultsA total of 430,886 individuals were included in the final analysis. The mean age of the participants were 56.44 years, and 55.3 % were female. Over a median follow-up period of 13.81 years, 5,661 participants developed PAD. Higher grip strength, whether absolute or relative, exhibited a dose-dependent inverse association with incident PAD. Each 1 kg increment in absolute grip strength and each 0.01 kg/kg increase in relative grip strength were associated with reduced PAD risk by 2 % (HR: 0.98; 95 % CI [0.97–0.98]) and 83 % (HR: 0.17; 95 % CI [0.13–0.23]), respectively. Slow walking pace significantly correlated with increased PAD risk, while brisk walking pace was associated with decreased PAD risk. ConclusionAbsolute grip strength, relative grip strength and walking pace were inversely associated with the risk of incident PAD.

The Genetic Determinants and Genomic Consequences of Non-Leukemogenic Somatic Point Mutations.

Clonal hematopoiesis (CH) is defined by the expansion of a lineage of genetically identical cells in blood. Genetic lesions that confer a fitness advantage, such as point mutations or mosaic chromosomal alterations (mCAs) in genes associated with hematologic malignancy, are frequent mediators of CH. However, recent analyses of both single cell-derived colonies of hematopoietic cells and population sequencing cohorts have revealed CH frequently occurs in the absence of known driver genetic lesions. To characterize CH without known driver genetic lesions, we used 51,399 deeply sequenced whole genomes from the NHLBI TOPMed sequencing initiative to perform simultaneous germline and somatic mutation analyses among individuals without leukemogenic point mutations (LPM), which we term CH-LPMneg. We quantified CH by estimating the total mutation burden. Because estimating somatic mutation burden without a paired-tissue sample is challenging, we developed a novel statistical method, the Genomic and Epigenomic informed Mutation (GEM) rate, that uses external genomic and epigenomic data sources to distinguish artifactual signals from true somatic mutations. We performed a genome-wide association study of GEM to discover the germline determinants of CH-LPMneg. After fine-mapping and variant-to-gene analyses, we identified seven genes associated with CH-LPMneg (TCL1A, TERT, SMC4, NRIP1, PRDM16, MSRA, SCARB1), and one locus associated with a sex-associated mutation pathway (SRGAP2C). We performed a secondary analysis excluding individuals with mCAs, finding that the genetic architecture was largely unaffected by their inclusion. Functional analyses of SMC4 and NRIP1 implicated altered HSC self-renewal and proliferation as the primary mediator of mutation burden in blood. We then performed comprehensive multi-tissue transcriptomic analyses, finding that the expression levels of 404 genes are associated with GEM. Finally, we performed phenotypic association meta-analyses across four cohorts, finding that GEM is associated with increased white blood cell count and increased risk for incident peripheral artery disease, but is not significantly associated with incident stroke or coronary disease events. Overall, we develop GEM for quantifying mutation burden from WGS without a paired-tissue sample and use GEM to discover the genetic, genomic, and phenotypic correlates of CH-LPMneg.

Diet and exercise in relation to lower extremity artery disease.

Adherence to the Mediterranean diet (MeD) has been associated with a reduced incidence of peripheral arterial disease (PAD)/lower extremity arterial disease (LEAD) in observational trials and in a randomized trial. In secondary prevention, a lower hazard ratio for composite major adverse cardiovascular events has been associated with better adherence to MeD in a relatively small, randomized trial. This has not been confirmed in a sub-analysis of a large interventional trial of dual antithrombotic treatment. The effects of vegetarian, vegan or low carbohydrate/ketogenic diets on the incidence and outcomes of PAD/LEAD are not known. While abdominal obesity is associated with diabetes mellitus and PAD/LEAD, the lowest incidence of PAD/LEAD has been found in subjects with a body mass index 25-29.9 kg/m2. Malnutrition is a negative prognostic factor for survival of patients with chronic limb threatening ischemia. Physical activity (PA) is an acute stressor, but habitual recreational PA results in beneficial adaptations and improved health. In observational studies, lower levels of exercise and lower physical fitness have been associated with more prevalent PAD/LEAD. In contrast to coronary artery disease, that shows a reverse J-shaped relationship between long-term endurance exercise and coronary atherosclerosis, such a relationship is not known for PAD/LEAD. A general recommendation for maintaining cardiovascular health is performing regular moderate-intensity exercise with some vigorous-intensity aerobic PA, and resistance exercise at least twice a week. Combinations of healthy behaviors are more effective in preventing PAD/LEAD than a single behavioral component. In treatment of PAD/LEAD causing intermittent claudication, supervised walking training is recommended among measures of first-line treatment, while unsupervised walking training should be considered as an alternative.

The association between fatty acids and atherosclerotic diseases: A mendelian randomization study

BackgroundThe current observational studies have disputed the relationship between various fatty acids and atherosclerotic diseases, and the causal relationship between the two is still unclear. MethodsIn this study, we utilized the available genome-wide association studies (GWAS) summary data on fatty acids and atherosclerotic diseases from the IEU OpenGWAS project. After identifying the appropriate single nucleotide polymorphisms (SNPs) as instrumental variables, we employed the MR-PRESSO outlier test to remove extreme values. Subsequently, we conducted a two-sample mendelian randomization (MR) analysis and performed sensitivity analyses to ensure the reliability of the results. ResultsThe results of MR analysis suggest that ratio of saturated fatty acids to total fatty acids is positively correlated with the incidence rate of coronary heart disease (OR = 1.341, 95% CI = 1.016 - 1.769, P value = 0.038), monounsaturated fatty acid levels is negatively correlated with the incidence of stroke (OR = 0.800, 95% CI = 0.642 - 0.996, P value = 0.046), and docosahexaenoic acid levels is negatively correlated with the incidence of peripheral artery disease (OR= 0.747, 95% CI= 0.572 - 0.976, P value= 0.033). All results showed no heterogeneity or pleiotropy, but leave-one-out tests showed that the analysis results of some fatty acids were driven by a single SNP. ConclusionsThis study highlights the existence of causal relationships between fatty acids and atherosclerotic diseases at the genetic level. These findings provide valuable insights for potential prevention measures and therapeutic targets for the three atherosclerotic diseases.

Research on the heat treatment process of intravascular nitinol stents

With the aging of China’s population and changes in dietary structure, the incidence of peripheral arterial disease (PAD) is increasing year by year, and the number of PADs requiring intervention is increasing. Atherosclerosis, inflammation, trauma or injury, structural abnormalities of ligaments or muscles, or exposure to radiation are common causes of PAD. Minimally invasive treatment is an effective method to treat PAD, and nitinol alloy vascular stent has become an effective and safe minimally invasive interventional treatment method because of its shape memory effect, super elasticity, and excellent biocompatibility. This topic mainly studies the preparation of nitinol stents through finite element analysis simulation and heat treatment shaping. The stents are analyzed by optical microscope, DSC, Tensile Testing Machine, and Radial Force Tester. The specific research results are as follows: through finite element analysis, the shaping process parameters of the stent are determined. When the diameter of the stent is expanded to 5 mm in three steps, as the heating temperature increases from 500°C to 540°C, the color of the stent surface changes from blue to yellow, the temperature of the stent Af decreases, the radial support force and the stress of the upper and lower yield plateaus of the stent increase.

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.

Infrapopliteal Bypass In Patients On Dialysis: Patency And Survival.

Portugal has one of the highest prevalence of patients on a regular dialysis program. This population has a higher incidence of peripheral arterial disease with higher rates of postoperative morbidity and mortality. Our goal was to compare outcomes between dialysis and non-dialysis patients with chronic limb threatening ischemia (CLTI) submitted to infrapopliteal bypass. A retrospective single-center study of infrapopliteal bypass for CLTI was performed between 2012 and 2019. Patients were divided in two groups based on dialysis status (group 1 incorporated patients on dialysis). Primary end point was 1-year freedom from CLTI. Secondary end points were limb-salvage, survival and primary (PP) and tertiary patency (TP) rates at 3 years of follow-up. A total of 352 infrapopliteal bypasses were performed in 310 patients with CLTI. Fourteen percent of the revascularizations were performed on dialysis patients (48/352). Median age was 73 years (interquartile range - IQR 15) and 74% (259/352) were male. Median follow-up was 26 months (IQR 42). Overall, 92% (325/352) had tissue loss and 44% (154/352) had some degree of infection. The majority of revascularization procedures were performed with vein grafts (61%, 214/352). The 30-day mortality was 4% (11/310), with no difference between groups (p = 0.627). Kaplan-Meier analysis showed no difference between groups regarding freedom from CLTI (76% vs. 79%; HR 0.96, CI 0.65-1.44, p=0.857), limb-salvage (70% vs. 82%; HR 1.40, CI 0.71-2.78, p=0.327) and survival (62% vs. 64%; HR 1.08, CI 0.60-1.94, p=0.799). PP rates were 39% in group 1 and 64% in group 2 (HR 1.71, CI 1.05-2.79, p=0.030). TP rates were not different between groups (57% and 78%; HR 1.79, CI 0.92-3.47, p=0.082). Infrapopliteal bypass for CLTI, on dialysis patients, resulted in lower PP rates. No differences were observed in freedom from CLTI, TP, limb salvage and survival.

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.

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.

Risk factors for and risk of all-cause and atherosclerotic cardiovascular disease mortality in people with type 2 diabetes and peripheral artery disease: an observational, register-based cohort study

BackgroundType 2 diabetes (T2D) and peripheral artery disease (PAD) are recognized as independent risk factors contributing to excess mortality. Contemporary observational studies exploring the associations of risk factors, and risk of all-cause and atherosclerotic cardiovascular disease mortality in persons with T2D following the onset of incident peripheral artery disease are limited. The objectives of this study were to investigate the associations of risk factors, and assess mortality risks in people with T2D compared with controls without T2D after the onset of PAD.MethodsAll persons with T2D (n = 150,215) registered in the Swedish National Diabetes Register between 2005 and 2009 were included, along with 346,423 controls without T2D matched for sex and age. Data were retrieved from several national registries, capturing information on risk factors, onset of incident peripheral artery disease, other comorbidities, socioeconomic factors, and outcomes. To compare persons with T2D and controls following the onset of peripheral artery disease regarding the risk of all-cause, and atherosclerotic cardiovascular disease mortality, Cox proportional hazard models and Kaplan-Meier curves were employed. A gradient-boosting model was utilized to estimate the relative statistical contribution of risk factors to the modeling of incident mortality risk in people with both T2D and peripheral artery disease.ResultsCrude rates of incident all-cause mortality were higher in individuals with T2D compared with controls, following the onset of PAD (600.4 (95% CI, 581.4-619.8) per 10,000 person-years versus 549.1 (95% CI, 532.1-566.5) per 10,000 person-years). Persons with T2D had an adjusted hazard ratio (HR) for all-cause mortality of 1.12 (95% CI, 1.05–1.19, P < 0.01) compared with controls after onset of incident PAD. The comparable adjusted HR for cardiovascular mortality was 1.13 (95% CI, 1.07–1.19, P < 0.01). High age and hyperglycemia at baseline played a significant role in contributing to the predictive models for incident all-cause and cardiovascular mortality among individuals with both T2D and PAD.ConclusionsThe presence of T2D with concomitant PAD is related to an increased risk of both all-cause and cardiovascular mortality compared with individuals with only PAD. This argues for implementing optimized and intensive treatment strategies for individuals with both conditions.

227 Depressive Symptoms and Incident Peripheral Arterial Disease among adults in the Chronic Renal Insufficiency Cohort (CRIC) Study

227 Depressive Symptoms and Incident Peripheral Arterial Disease among adults in the Chronic Renal Insufficiency Cohort (CRIC) Study

Abstract P413: Epigenetic Age Acceleration Measures Predict Cardiovascular Outcomes in Diabetic Kidney Disease

Introduction: Cardiovascular disease (CVD) remains the leading cause of mortality in the US, highlighting the need for novel approaches to its prediction, prevention, and management. Epigenetic age acceleration (EAA), or increased DNA methylation-based age relative to chronological age, is a promising biomarker of disease risk. While previous studies have prospectively linked EAA to CVD, recent work in patients with end-stage kidney disease showed no association between EAA and mortality from CVD, underscoring a need for more research across patient populations. Hypothesis: EAA measures, specifically intrinsic epigenetic age acceleration (IEAA), extrinsic epigenetic age acceleration (EEAA), phenotypic epigenetic age acceleration (PhenoAA), and Grim epigenetic age acceleration (GrimAA), are associated with incident CVD in diabetic kidney disease (DKD). Methods: In a subset of 496 participants from the Chronic Renal Insufficiency Cohort with DKD, selected based on kidney function decline over follow-up (large versus small), we examined four EAA measures: IEAA, EEAA, PhenoAA, and GrimAA. GrimAA is comprised of eight DNA methylation-based biomarkers, including plasminogen activator inhibitor-1 age acceleration (PAI-1 AA ) and tissue inhibitor of matrix metalloproteinase (TIMP-1 AA ), which were also assessed. Primary outcomes were incident CVD, atherosclerotic CVD, and CVD mortality; secondary outcomes included myocardial infarction, congestive heart failure (CHF), cerebrovascular accident, and peripheral artery disease (PAD). Cox proportional models tested associations between the EAA measures and CVD endpoints after adjusting for baseline demographics, clinical center, kidney function decline as a study design feature, lifestyle, and clinical risk factors. Results: Participants were predominantly male (63%), with a median age of 57 years, median eGFR of 44 mL/min/1.73m 2 , and mean hemoglobin A1c of 8.0%. After adjusting for multiple testing, each standard deviation increase in GrimAA was associated with incident CVD (HR=1.27; 95% confidence interval [CI], 1.08-1.50; p=0.012) and PAD (HR=1.65; 95% CI, 1.15-2.37; p=0.006). Likewise, PAI-1 AA was significantly associated with incident CVD (HR=1.24; 95% CI, 1.06-1.44; p=0.006) and PAD (HR=1.46; 95% CI, 1.17-1.81; p=0.001), while TIMP-1 AA was associated with CHF (HR=1.32; 95% CI, 1.09-1.60; p=0.005). Nominally significant associations between IEAA and atherosclerotic CVD were also identified (HR=1.24; 95% CI, 1.00-1.53; p=0.049). Similarly, EEAA was nominally associated with incident CVD (HR 1.22; 95% CI, 1.01-1.47, p=0.039). Conclusion: EAA measures, notably GrimAA, are promising CVD biomarkers in DKD patients. Associations of GrimAA components PAI-1 AA and TIMP-1 AA with incident CVD add to the accumulating evidence of their predictive and therapeutic potential.

Abstract P267: Associations of Urinary Zinc With Incident Peripheral Arterial Disease and Amputation in the Strong Heart Study

Background: Urinary zinc has been associated with cardiometabolic endpoints including diabetes and peripheral artery disease (PAD), but evidence from prospective studies is limited. Objective: Our goal was to evaluate the prospective association between urinary zinc levels and incident PAD and amputation events in a large population-based cohort of American Indian adults in the US, the Strong Heart Study (SHS) cohort. Methods: A total of 2,049 PAD-free and 2,184 amputation-free participants at the baseline examination (1989-91) were included (mean 56 years, 61% female). The median (IQR) urinary zinc levels were 538 (388, 765) μg/g creatinine among PAD-free participants and 547 (396, 784) μg/g creatinine among amputation-free participants. PAD (defined as ankle brachial index &lt;0.9 or &gt;1.4) and amputation events were collected through the second (1993-1995) and third (1997-1999) SHS examination visits. We used logistic regression models to evaluate the progressively adjusted odds ratios (ORs) of PAD and amputation by increasing quantile of urinary zinc. Results: Over the two prospective study visits, 345 participants developed PAD and 23 underwent amputation. After adjustment for CVD risk factors including age, sex, location, body mass index, smoking and alcohol use status, cholesterol levels, estimated glomerular filtration rate, hypertension and diabetes, the ORs per IQR change in urine zinc levels were 1.16 (95% CI: 0.98, 1.38) for PAD, and 1.74 (95% CI: 1.04, 2.92) for amputation. Further adjusting the models for plasma fasting glucose reduced the magnitude of the association between high urinary zinc levels on PAD (OR: 1.09, 95% CI: 0.91, 1.31) and amputation (OR: 1.32, 95% CI: 0.72, 2.44). Conclusions: High urinary zinc levels were prospectively associated with PAD and amputation events, an association that appears to be partly related to lack of glycemic control. Further research is needed to better understand the complex relationship between urinary zinc, glycemic control and CVD.

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.

Abstract P210: Incident Venous Thromboembolism and Subsequent Risk of Cardiovascular Outcomes: The Atherosclerosis Risk in Communities (ARIC) Study

Background: Venous thromboembolism (VTE) and atherothrombosis have different mechanisms of thrombosis formation. A few previous studies reported those having a VTE have greater risk of incident atherothrombotic disease. These studies have several limitations, such as inadequate adjustment for key confounders (e.g., obesity), selected study populations in clinical trials, and small sample size. Moreover, the links of VTE to heart failure (HF) and peripheral artery disease (PAD) are not well understood. Hypothesis: VTE is independently associated with a range of incident cardiovascular outcomes. Methods: In 12,988 ARIC participants without history of VTE or cardiovascular disease at baseline (1987-89), we quantified the association of VTE, as a time-varying exposure, with incident myocardial infarction (MI), stroke, HF, PAD (overall and its severe form, critical limb ischemia [CLI]) using multivariable Cox regression. We also considered unprovoked and provoked VTE separately. Results: Over a median follow-up of 25 years, 901 participants experienced incident VTE. In the same timeframe, there were 1,950 MI events, 1,247 stroke events, 2,981 HF events, and 516 PAD cases (including 207 CLI cases). Participants with VTE, compared to those without, had a higher risk of all cardiovascular outcomes ( Table ). The associations were particularly evident for incident PAD and CLI (adjusted HR 2.32 [95% CI 1.53, 3.52] and 3.44 [2.01, 5.88], respectively). Provoked VTE showed similar associations with all cardiovascular outcomes, whereas unprovoked VTE was significantly associated with MI, HF, and CLI only ( Table ). Conclusions: In this large community-based study, VTE was robustly associated with subsequent risk of different cardiovascular outcomes, independent of potential confounders. Patients with VTE should be considered at high risk of other cardiovascular outcomes and receive optimal preventive therapy for cardiovascular diseases, including atherosclerotic disease and HF.

Arm and ankle blood pressure indices, and peripheral artery disease, and mortality: a cohort study.

Few studies have compared arm and ankle blood pressures (BPs) with regard to peripheral artery disease (PAD) and mortality. These relationships were assessed using data from three large prospective clinical trials. Baseline BP indices included arm systolic BP (SBP), diastolic BP (DBP), pulse pressure (arm SBP minus DBP), ankle SBP, ankle-brachial index (ABI, ankle SBP divided by arm SBP), and ankle-pulse pressure difference (APPD, ankle SBP minus arm pulse pressure). These measurements were categorized into four groups using quartiles. The outcomes were PAD (the first occurrence of either peripheral revascularization or lower-limb amputation for vascular disease), the composite of PAD or death, and all-cause death. Among 40 747 participants without baseline PAD (age 65.6 years, men 68.3%, diabetes 50.2%) from 53 countries, 1071 (2.6%) developed PAD, and 4955 (12.2%) died during 5 years of follow-up. Incident PAD progressively rose with higher arm BP indices and fell with ankle BP indices. The strongest relationships were noted for ankle BP indices. Compared with people whose ankle BP indices were in the highest fourth, adjusted hazard ratios (95% confidence interval) for each lower fourth were 1.64 (1.31-2.04), 2.59 (2.10-3.20), and 4.23 (3.44-5.21) for ankle SBP; 1.19 (0.95-1.50), 1.66 (1.34-2.05), and 3.34 (2.75-4.06) for ABI; and 1.41 (1.11-1.78), 2.04 (1.64-2.54), and 3.63 (2.96-4.45) for APPD. Similar patterns were observed for mortality. Ankle BP indices provided the highest c-statistics and classification indices in predicting future PAD beyond established risk factors. Ankle BP indices including the ankle SBP and the APPD best predicted PAD and mortality.