Incidence 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.

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.

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.

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.

Peripheral artery disease: an underdiagnosed condition in familial hypercholesterolemia? A systematic review.

Familial hypercholesterolemia (FH) is one of the most common inherited diseases characterized by elevated LDL-cholesterol levels, leading to early-onset atherosclerosis. While the association between FH and coronary and carotid artery disease is well-established, its association with peripheral artery disease (PAD) is less robust. This systematic review aims at exploring existing evidence on PAD prevalence and incidence in FH individuals. A comprehensive search was conducted on MEDLINE and Embase databases, for studies published between January 2013 and December 2023, evaluating prevalence and incidence of PAD in FH patients. Literature reviews, case reports, responses to editors and non-English language articles were excluded. The initial research provided 53 results. After article screening, 28 articles were fully reviewed and 24 were finally included in the analysis. Among these, 19 reported PAD prevalence, while 5 PAD incidence over a mean follow-up time of 8.7 years. PAD prevalence and incidence ranged from 0.3 to 60% and from 0.5 to 4.2% respectively, probably reflecting the heterogeneity in PAD definition criteria. This systematic review sheds light on the limited number of studies on PAD in FH patients. Particularly, considering the potential positive effects of newly available lipid-lowering strategies on PAD outcomes, addressing this research gap is pivotal for a more comprehensive understanding of peripheral vascular manifestations in FH patients and for optimal management of this population.

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.

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.

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.

Epidemiology of atherosclerotic cardiovascular disease in polygenic hypercholesterolemia with or without high lipoprotein(a) levels.

Epidemiology of atherosclerotic cardiovascular disease might be different in patients with polygenic hypercholesterolemia plus high levels (≥30 mg/dl) of Lp(a) (H-Lpa) than in those with polygenic hypercholesterolemia alone (H-LDL). We compared the incidence of peripheral artery disease (PAD), coronary artery disease (CAD), and cerebrovascular disease (CVD) in patients with H-Lpa and in those with H-LDL. Retrospective analysis of demographics, risk factors, vascular events, therapy, and lipid profile in outpatient clinical data. Inclusion criteria was adult age, diagnosis of polygenic hypercholesterolemia, and both indication and availability for Lp(a) measurement. Medical records of 258 patients with H-Lpa and 290 H-LDL were reviewed for occurrence of vascular events. The median duration of follow-up was 10 years (IQR 3-16). In spite of a similar reduction of LDL cholesterol, vascular events occurred more frequently, and approximately 7 years earlier (P = 0.024) in patients with H-Lpa than in H-LDL (HR 1.96 1.21-3.17, P = 0.006). The difference was around 10 years for acute events (TIA, Stroke, acute coronary events) and one year for chronic ones (P = 0.023 and 0.525, respectively). Occurrence of acute CAD was higher in H-Lpa men (HR 3.1, 95% CI 1.2-7.9, P = 0.007) while, among women, PAD was observed exclusively in H-Lpa subjects with smoking habits (P = 0.009). Patients with high Lp(a) levels suffer from a larger and earlier burden of the disease compared to those with polygenic hypercholesterolemia alone. These patients are at higher risk of CAD if they are men, and of PAD if they are women.

Modifiable Lifestyle Factors, Genetic Risk, and Incident Peripheral Artery Disease Among Individuals With Type 2 Diabetes: A Prospective Study.

To prospectively evaluate the association between modifiable lifestyle factors and peripheral artery disease (PAD) among individuals with type 2 diabetes (T2D). We included 14,543 individuals with T2D from the UK Biobank. We defined a weighted healthy lifestyle score using nonsmoking, regular physical activity, high-quality diet, moderate alcohol consumption, optimal waist-to-hip ratio, and adequate sleep duration, and categorized into unfavorable, intermediate, and favorable lifestyles. We created a genetic risk score (GRS) using 19 single nucleotide polymorphisms previously found to be associated with PAD. We modeled the association between lifestyle score and PAD, overall and stratified by PAD genetic susceptibility. After a median 13.5 years of follow-up, 628 incident cases of PAD were documented. A linear inverse association between the weighted lifestyle score and PAD was observed, with a hazard ratio (HR) (95% CI) of 0.27 (0.19, 0.38) for favorable compared with unfavorable lifestyle (Ptrend < 0.0001). An estimated 58.3% (45.0%, 69.1%) of PAD in this population could be potentially avoidable if all participants attained a favorable lifestyle. Moreover, the PAD GRS was associated with increased PAD risk (HR [95% CI] per SD increment: 1.13 [1.03, 1.23]). A favorable lifestyle was able to partially mitigate the excess risk of PAD associated with higher GRS, albeit as a nonsignificant interaction. Several biomarkers in the lipid metabolism, hepatic/renal function, and systemic inflammation pathways collectively explained 13.3% (8.5%, 20.1%) of the association between weighted lifestyle score and PAD. A favorable lifestyle was associated with lower risk of PAD among individuals with T2D, independent of genetic predisposition to PAD.

TO STUDY OCCURRENCE OF PERIPHERAL ARTERIAL DISEASE IN YOUNG PATIENTS WITH CORONARY ARTERY DISEASE USING ANKLE BRACHIAL INDEX -A SMS HOSPITAL BASED OBSERVATIONAL STUDY

Background: Coronary artery disease (CAD) and peripheral arterial disease (PAD) both are manifestations of systemic atherosclerosis. Many patients with CAD have associated PAD however, many patients are asymptomatic and thus remain underdiagnosed. Currently, little is known about the actual incidence and clinical implications of asymptomatic PAD in young patients less than 50-year-old undergoing coronary angiography in Indian population, so we will conduct this study to assess the prevalence of previously unrecognized PAD among patients with suspected ischemic heart disease undergoing coronary angiography, and to determine the relationship among PAD, severity of coronary angiographic stenosis, and major cardiovascular risk factors, in western Indian population. Method: This is an observational study conducted at a tertiary referral hospital. A total of 395 patients referred for coronary angiography without a prior diagnosis of PAD, between January 2023 to June 23 who fulfilling eligibility criteria of study, were included. Patients were evaluated through detailed medical history taking, a questionnaire survey to assess symptoms and functional status, ankle-brachial index (ABI) measurement, and coronary angiography. PAD was considered present if the ABI was&lt; 0.90 in either leg. Result: In all patients, the prevalence of previously unrecognized PAD was 5.8%. There was significant difference between men and women (7.2% vs 1.1%, P=0.027). Abnormal angiographic results were seen in 63% (249 of 395). The prevalence of PAD was 7.2% in patients with abnormal coronary angiographic result, higher than that in patients with normal results but not statistically significant (3.2%, P=0.119). Patients with PAD were significantly older, and had higher rates of hypertension, dyslipidaemia, diabetes mellitus, current smoking, history of CAD than patients without PAD demonstrating high occurrence of PAD strongly associated with conventional risk factor for CAD. The occurrence of asymptomatic PAD was more among stable ischemic heart disease group(p=0.04). In our analysis, patients with PAD had a more severe form of CAD manifested by a higher frequency of multivessel coronary disease(p=0.002). Conclusion: The high occurrence of asymptomatic PAD in young patients with CAD confirms the importance of active screening for PAD by using ABI even in young patients. Routine determination of ABI in the clinical evaluation of all patients with CAD may helpful inidentifyhigh-risk patients.

Hubungan Kadar Hba1c dan Kolesterol Total dengan Kejadian Peripheral Arterial Disease pada Pasien Diabetes Mellitus Tipe 2

Type 2 diabetes mellitus (DMT2) is caused by the inability of pancreatic beta cells to produce insulin and tissue resistance to insulin. T2DM requires ongoing treatment to control blood sugar and prevent complications such as Peripheral Arterial Disease (PAD) and high cholesterol problems. HbA1c measurement and total cholesterol monitoring are important in diabetes management and prevention of serious complications. An observational analytical study, cross-sectional approach was conducted in September 2022 at Gatak Health Center, Sukoharjo on 65 patients with T2DM. The data were analyzed with a 2x2 chi square test table. The results of the study found that 21 (32.3%) research subjects experienced PAD. Bivariate test between total cholesterol and Hba1c with consecutive PAD incidence p = 0.377; p = 0.416. It can be concluded that there is no significant relationship between the variables total cholesterol and Hba1c with the incidence of PAD. This can be caused by lack of control over other risk factors for PAD events such as smoking, hypertension, duration of diabetes, age, and gender.&#x0D; &#x0D;

Omega-3 Polyunsaturated Fatty Acids are not associated with Peripheral Artery Disease in a Meta-Analysis from the Multi-Ethnic Study of Atherosclerosis and Atherosclerosis Risk in Communities Study Cohorts

BackgroundResearch suggests omega-3 polyunsaturated fatty acids (PUFAs) exert favorable effects on several biological processes involved in the development and progression of atherosclerotic cardiovascular disease (ASCVD). However, studies examining the relationship between omega-3 PUFAs and peripheral artery disease (PAD) are scarce. ObjectivesWe evaluated the associations between omega-3 PUFAs and incident PAD in a meta-analysis of the Multi-Ethnic Study of Atherosclerosis (MESA) and Atherosclerosis Risk in Communities (ARIC) study cohorts. MethodsOmega-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were measured at baseline for all MESA (n = 6495) and Minnesota ARIC participants (n = 3612). Incident clinical PAD events (MESA n = 106; ARIC n = 149) identified primarily through ICD discharge codes were assessed through follow-up of each cohort. Associations between omega-3 PUFAs (EPA, DHA, and EPA+DHA) and incident PAD were modeled in MESA and ARIC as quartiles and continuously using Cox proportional hazards regression, respectively. A fixed-effects meta-analysis was conducted to evaluate associations in the 2 cohorts combined. ResultsIn the fully adjusted model, in 10,107 participants, no significant associations were observed between EPA, DHA, or EPA+DHA, and incident PAD modeled as quartiles or continuously for either MESA or ARIC cohorts separately or in the meta-analysis after a follow-up of approximately 15 y. ConclusionThis study is consistent with previous literature indicating that the beneficial effects of omega-3 PUFAs on the markers of ASCVD may not translate to a clinically meaningful decrease in PAD risk.

Abstract 12532: Maximal Exercise Capacity is Inversely Related to Incident Peripheral Artery Disease: Data From the Henry Ford Exercise Testing (FIT) Project

Introduction: 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. Hypothesis: 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 &lt;6, 6-9, 10-11, and &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.

Abstract 18709: Disparities in Socioeconomic Metrics Associated With Adverse Outcomes Among Medicare Beneficiaries Undergoing Peripheral Endovascular Intervention

Background Low socioeconomic status (SES) is associated with an increased incidence of peripheral artery disease, however there is a lack of granularity in the specific metrics that contribute to this discrepancy. We examine the association of community-level economic distress with adverse outcomes in patients undergoing peripheral endovascular intervention (PVI). Hypothesis: Socioeconomically distressed communities have non-healthcare-related, structural disparities that contribute to incident PVI and adverse outcomes. Methods: Medicare beneficiaries ≥66 years of age from 2016 to 2018 were evaluated to determine the incidence of femoropopliteal PVI. The Distressed Community Index (DCI) was used to categorize adults as distressed (DCI ≥80) or not distressed (DCI &lt;80). Composite outcome of death and major amputation within 1 year of PVI were examined by level of distress using individual community-level metrics. Results: Socioeconomically distressed adults underwent 158 PVIs per 100000 distressed beneficiaries compared with 109 PVIs per 100000 non-distressed beneficiaries (risk ratio, 1.45 [95% CI, 1.42-1.48]; P&lt;0.001). Distressed adults who underwent PVI were more likely to be female (45.5% versus 43.1%; P&lt;0.001) and Black race (21.9% versus 10.1%; P&lt;0.001) (Table I). There was a strong association between distress and the composite outcome at 1 year (incidence rate ratio, 1.11 [95% CI 1.07-1.16; P=0.0001]). Distressed adults lacked high school diplomas (11.88% versus 11.15%; P&lt;0.001), had higher rates of unemployment (24.11% versus 22.76%; P&lt;0.001), and greater housing vacancy rates (9.74% versus 9.31%; P&lt;0.001). Conclusion: Socioeconomic distress is associated with higher rates of PVI-incidence and post-PVI adverse outcomes. This may be driven by structural inadequacies inherent to low SES communities that need to be addressed in order to narrow the gap in care among distressed adults undergoing PVI.