Risk Of PAD Research Articles

The causal relationship between human blood metabolites and risk of peripheral artery disease: a Mendelian randomization study.

Peripheral Artery Disease (PAD) is a common vascular disorder typically caused by atherosclerosis, leading to impaired blood supply to the lower extremities, resulting in pain, necrosis, and even amputation. Despite extensive research into the pathogenesis of PAD, many mysteries remain, particularly regarding its association with human blood metabolites. To explore the causal relationship between 1,400 serum metabolites and PAD, a two-sample Mendelian randomization (MR) analysis was conducted. The Inverse Variance-Weighted (IVW) method was the primary technique used to estimate the causal impact of the metabolites on PAD. To enhance the analysis, several additional methods were employed: MR-Egger regression, weighted median, simple mode, and weighted mode. These methods provided a comprehensive evaluation beyond the primary IVW estimation. To ensure the validity of the MR findings, sensitivity analysis was performed. Furthermore, a bidirectional MR approach was applied to explore the possibility of a reverse causal effect between PAD and potential candidate metabolites. After rigorous selection, significant associations were found between 1-(1-enyl-stearoyl)-2-arachidonoyl-GPE (p-18:0/20:4) and X-17653 levels with PAD. 1-(1-enyl-stearoyl)-2-arachidonoyl-GPE (p-18:0/20:4) was positively associated with increased PAD risk (IVW OR = 1.13, 95% CI, 1.06-1.21; P < 0.001). X-17653 levels were associated with decreased PAD risk (IVW OR = 0.88, 95% CI, 0.83-0.94; P < 0.001). In the reverse direction, PAD was positively associated with increased 1-(1-enyl-stearoyl)-2-arachidonoyl-GPE (p-18:0/20:4) levels (IVW OR = 1.16, 95% CI, 1.01-1.34; P = 0.036). PAD was not associated with X-17653. Among 1,400 blood metabolites, 1-(1-enyl-stearoyl)-2-arachidonoyl-GPE (p-18:0/20:4) and X-17653 are significantly associated with PAD risk. Importantly, in the reverse direction, PAD was found to be positively associated with increased levels of 1-(1-enyl-stearoyl)-2-arachidonoyl-GPE (p-18:0/20:4). This highlights the bidirectional nature of the association and suggests a potential feedback mechanism between PAD and this specific lipid species. 1-(1-enyl-stearoyl)-2-arachidonoyl-GPE (p-18:0/20:4) may serve as potential biomarkers for PAD, aiding early diagnosis and providing novel avenues for personalized treatment and management. However, further validation and research are warranted despite the promising results.

, ,

Peripheral artery disease is a considered as one of the major macrovascular complications in diabetes mellitus type 2. It is chronic arteriosclerotic illness that mainly affects the lower limbs and is presented as narrowed or blocked blood vessels. The prevalence increases with the age, it affects 15-20% of persons older than 70 years age, 10-15% of the general population. Smoking and high cholesterol levels increase the risk for PAD progression in large blood vessels such as legs, while diabetes increases the risk for PAD in small blood vessels such as the feet. Critical ischemia, its most severe form can lead to limb amputation and the patient’s death, and even its asymptomatic forms are associated with a high risk of cardiovascular morbidity and mortality. Approximately more than half of all patients are asymptomatic and preventive therapy reduces the risk of complications and death, so it’s important to recognize the subclinical forms in time and to control risk factors of disease. The risk factors that can be modified are tobacco use, hypertension, hyperlipidemia, diabetes mellitus, obesity and some of them cannot be modified such as age, sex or family medical history. Diabetes mellitus type 2 is considered as the most important risk factor for development of peripheral artery disease. The experts suggest that is necessary to establish an HBA1C therapeutic target below 8% in patient with DM and PAD.

Predominantly antibody deficiency and the association with celiac disease in Sweden: A nationwide case-control study

BackgroundPredominantly antibody deficiency (PAD) is associated with noninfectious inflammatory gastrointestinal disease. Population estimates of celiac disease (CeD) risk in those with PAD are limited. ObjectiveTo estimate population risk of PAD in individuals with CeD. MethodsWe conducted a nationwide case-control study in Swedish individuals who received a diagnosis of CeD between 1997 and 2017 (n = 34,980), matched to population comparators by age, sex, calendar year, and county. The CeD was confirmed through the Epidemiology Strengthened by histopathology Reports in Sweden study, which provided information on biopsy specimens from each of Sweden's pathology departments. PAD was identified using International Classification of Diseases, 10th Revision coding and categorized according to the International Union of Immunologic Societies. Logistic regression was used to calculate adjusted odds ratios (aORs) and 95% CIs. ResultsPAD was more prevalent in CeD than in population controls (n = 105 [0.3%] vs n = 57 [0.033%], respectively). This translated to an aOR of 8.23 (95% CI 5.95-11.48). The association was strongest with common variable immunodeficiency (aOR 17.25; 95% CI 6.86-52.40), and slightly lower in other PAD (aOR 8.39; 95% CI 5.79-12.32). The risk of CeD remained increased at least 5 years after diagnosis of PAD (aOR 4.79; 95% CI 2.89-7.97, P-heterogeneity ≤ 0.001). ConclusionPAD was associated with an increased risk of CeD. A particularly strong association was seen in those with CVID, although this should be interpreted cautiously given the limited understanding of the mechanisms of histopathologic changes in these patients.

Ab. No. 181 Screening for Peripheral Arterial Disease in Asymptomatic at Risk Individuals: A Case Control Study

Introduction: Asymptomatic peripheral arterial disease can be screened by calculation of ankle brachial index (ABI) but population at risk with normal resting ABI may still have underlying atherosclerosis of the vessel wall which can be diagnosed with calculation of post exercise ABI. This study evaluated and compared postexercise ABI in normal healthy individuals without risk of peripheral arterial disease, ones at the risk of peripheral arterial disease and diagnosed patients of PAD. The study intended to identify peripheral arterial disease early in individuals who have not yet developed the disease but have more than 10% of Framingham risk score. Methods: Individuals above age of 35 years were recruited and segregated in three groups: Group A- Having diagnosed and symptomatic PAD; Group B- Individuals at risk of PAD as per Framingham risk score; Group C- Normal healthy individuals with low or no risk of PAD as per Framingham risk score. ABI was assessed at rest and after treadmill test. Absolute changes in systolic blood pressure values post exercise were also recorded. Post exercise ABI and absolute changes in systolic blood pressure were compared in all three groups. Result: Between group comparison revealed a significant difference in ABI at rest, post exercise ABI and difference in systolic ankle pressure (p value &lt;0.001). No significant difference was found between group B and group C. Conclusion: Post exercise ABI values differed between diagnosed, at risk and having low risk of PAD but were similar in at risk and low risk groups. Implications: Few individuals from group B had reduction in post exercise ABI underlining the need to periodically assess them for PAD with post exercise ABI- a non-invasive, inexpensive tool.

A cross-sectional study in type 2 diabetes patients reveals that elevated pulse wave velocity predicts asymptomatic peripheral arterial disease associated with age and diabetes duration

BackgroundPeripheral arterial disease (PAD) reduces functional capacity and raises cardiovascular risks, but underdiagnosis is common, resulting in less comprehensive care than other cardiovascular conditions. While diabetes has long been viewed as a key risk factor for PAD, recent studies indicate that its impact is influenced by the presence of concurrent cardiovascular risk factors. The aim of this study is to elucidate the intricate relationship between the prevalence of PAD, diabetic complications, and cardiovascular risk factors among asymptomatic patients with type 2 diabetes mellitus (T2DM). MethodsNinety-one patients with T2DM and no symptoms or previous diagnosis of PAD were recruited from the outpatient diabetic clinic. Clinical data were extracted from electronic medical records, and the screening for PAD was conducted using MESI mTABLET. ResultsScreening for PAD among asymptomatic individuals with T2DM revealed that 5.49 % of patients exhibit a low ankle-brachial index (ABI). Patients who had previously experienced major adverse cardiovascular events or exhibited albuminuria displayed lower ABI values. Furthermore, a striking 45.05 % of the participants displayed an abnormally high carotid-femoral pulse wave velocity (cfPWV) value, with elevated PWV values correlating with advanced age and longer diabetes duration. ConclusionsThe prevalence of elevated cfPWV is more pronounced than that of decreased ABI in T2DM patients with asymptomatic PAD and is associated with older age and longer diabetes duration, therefore measurement of both ABI and PWV is crucial for the cardiovascular risk assessment protocol for patients with T2DM and timely PAD diagnosis.

Association of statin use and outcomes in elderly with multiple risk factors: insight from the CORE registry Thailand

Abstract Introduction Statin is recommended by for lipid management in adults aged between 40 and 75 years old at risk for atherosclerotic cardiovascular disease (ASCVD). The evidence from meta-analysis suggested that the benefit of statin for primary prevention in the elderly was less robust than in the non-elderly. A dedicated randomized controlled trial of primary prevention with a statin in the elderly is currently ongoing. We aimed to study the association of statin use as a primary prevention for ASCVD on major adverse cardiac events in the elderly versus non-elderly in the Cohort Of patients with a high Risk of cardiovascular Events (CORE). Method The CORE registry was a nationwide study enrolling patients with established ASCVD or those with multiple risk factors (MRFs) between April 2011 and March 2014 in 25 hospitals. Patients with MRFs were included in the present analysis. Patients were stratified according to age and the status of statin use. The Elderly was defined as age over 75 years old. Any type and intensity of statin at baseline were counted as statin use. The primary outcome was the major adverse cardiac events (MACE), defined as the composite of all-cause death, stroke, or myocardial infarction. The association between statin use and outcomes was assessed overall and in the two groups of elderly versus non-elderly in the adjusted Cox regression models. Factors associated with both likelihood of statin use, and outcomes were used as adjusted variables. Results Of the 4,529 patients in the study, 729 patients were elderly (16.1%). The proportion of females was 57%, with a mean age of 65.6 years. The rate of statin use at baseline was similar between the elderly (84.9%) and non-elderly (83.6%) (p 0.41). The average follow-up time was 45.3 months. Statin use was associated with a significantly lower risk of MACE at five years. The incidence of MACE was highest in the elderly without statin use and lowest in non-elderly with statin use. Statin use at baseline was associated with a lower risk of MACE in both the elderly and non-elderly (p interaction 0.29). The risk of heart failure (HF) in the elderly treated with a statin was significantly lower than elderly without statin use (adjusted HR 0.37, 95%CI 0.14-0.96), while the risk of HF was similar between non-elderly with or without statin (adjusted HR 0.58, 95%CI 0.30-1.15). Statin use was associated with a lower risk of peripheral arterial disease in the elderly (adjusted HR 0.07, 95%0.01-0.73) but not in the non-elderly (adjusted HR 0.57, 95%CI 0.18-1.82). There was a trend toward lower risk of stroke, MI, or PAD in the elderly treated with statin than those without statin use (adjusted HR 0.48, 95% 0.22-1.07). Conclusion Statin use was associated with a significantly lower risk of MACE, HF, and PAD in the elderly with multiple risk factors of ASCVD in the CORE registry.MACE according to statin and age groupOutcomes according to statin and elderly

Systolic blood pressure visit-to-visit variability and outcomes in Asian patients with established or multiple risk factors for atherosclerotic cardiovascular disease: results from the CORE-Thailand

Abstract Background It is well established that high blood pressure is associated with poor outcomes in many cardiovascular conditions. However, blood pressure (BP) is dynamic and may have variation during the follow-up. We aimed to assess the association between the systolic and diastolic blood pressure visit-to-visit variability (BP-VVV) and outcomes in Asian patients with established or multiple risk factors for atherosclerotic cardiovascular disease (ASCVD) in the Cohort Of patients with a high Risk of cardiovascular Events (CORE). Methods The CORE registry was a nationwide study enrolling patients with established atherosclerotic cardiovascular disease or those with multiple risk factors (at least three atherosclerotic risk factors) between April 2011 and March 2014 in 25 hospitals. Patients in the CORE registry with blood pressure measurements in at least three visits were included in the present study. BP-VVV was defined as the standard deviation (SD) of average blood pressure. Patients were grouped into quintiles of the SD of BP. The primary outcome was major adverse cardiac events (MACE), defined as all-cause mortality, all stroke, or myocardial infarction. The associations between BP-VVV (systolic and diastolic) and outcomes were assessed in the adjusted Cox regression model. The adjusted variables included age, sex, body weight, diabetes, chronic kidney disease, current smoking, established ASCVD, and treatment with ACEI or ARB. Restrict cubic spline was used to assess the association between SBP-VVV as a continuous variable and MACE in the adjusted Cox model. Results Of the 8,886 patients in the present study, 4041 patients (45.5%) were female, with a mean age of 65.6 years. The prevalence of hypertension was 95.9%. The mean SBP at baseline was 133 mmHg. The proportion of patients with established ASCVD was 51.1%. The mean follow-up time was 45.1 months. The Kaplan-Meier rate of MACE at five years was 15.8%. Spline analysis showed a J-curve association between SBP-VVV and MACE. The group with the highest SBP-VVV (the fifth quintile) had a significantly higher risk of MACE than the group with the lowest SBP-VVV (the first quintile) (adjusted hazard ratio 1.26, 95% CI 1.05-1.51). Compared with the group with the lowest SBP-VVV (the first quintile), the fifth quintile had a significantly higher risk of stroke, all MI, heart failure, and renal function deterioration. The risk of PAD and bleeding were similar among the quintiles. Conclusion SBP-VVV significantly impacted the long-term outcomes of Asian patients with established or multiple risk factors for ASCVD. Adequate SBP control and maintaining SBP stability over time may prevent adverse events in this population.SBP-VVV and MACE

Lifetime risk of developing peripheral arterial disease: a nationwide longitudinal study

Abstract Background Peripheral arterial disease (PAD) presents a substantial clinical and public health burden. It remains one of the most impactful cardiovascular conditions in terms of both number of affected individuals and its impact on the individual’s survival, functional ability, and quality of life. Nonetheless, comprehensive data on the risk of developing PAD in the general population is scant. Purpose We aimed to quantify the lifetime risk of physician-diagnosed PAD in an unselected, nationwide population. Methods We conducted analyses of the entire Danish population aged 40 years and older from 2000 through 2018 using nationwide health administrative data. All individuals free of PAD were followed for up to 19 years. The cumulative incidence and residual lifetime risk of PAD adjusted for the competing risk of death was estimated by a modified survival analysis technique. Results were stratified by age, sex, and socioeconomic status. Results The Danish population aged 40-99 years in 2000-2018 included 4,508,932 individuals, among whom 123,479 individuals were diagnosed with PAD during follow-up. The overall lifetime risk from age 40 years during the remaining lifetime was 19.9% (95% CI 19.8%-20.2%). Lifetime risk was higher in men than in women (22.7% vs. 17.8%) and among individuals living alone (22.4% among unmarried or divorced individuals vs. 19.4% among married individuals). The highest lifetime risks were observed among individuals of lower socioeconomic status, especially individuals receiving social welfare payments for whom the lifetime risk exceeded 26%. The residual risk of developing PAD fell with age; for example, a 50-year-old who had not been diagnosed with PAD would still have a 19.6% residual risk during the remaining lifetime, whereas it was 15.4% among individuals aged 70 years. Conclusions About one in five individuals are likely to be diagnosed and receive medical attention for PAD during their lifetime with substantial disparities among individual of lower socioeconomic status. This knowledge may be used in public health awareness campaigns and to promote effective strategies to prevent PAD and limit progression in those with the disease and ensure the highest life quality possible.

Elevated remnant cholesterol in atherosclerotic cardiovascular disease in diabetes: a population-based prospective cohort study

Abstract Background Elevated remnant cholesterol is observationally and causally associated with increased risk of atherosclerotic cardiovascular disease (ASCVD) in the general population; the association in individuals with diabetes is not known. Purpose We tested the hypothesis that elevated remnant cholesterol is associated with increased risk of peripheral artery disease, myocardial infarction, ischemic stroke, and any ASCVD in individuals with diabetes. Methods We studied 4,569 individuals with diabetes and 102,674 individuals without diabetes from the Copenhagen General Population Study (2003-2015). In those with diabetes, during up to 15 years of follow-up, 236 were diagnosed with peripheral artery disease, 234 with myocardial infarction, 226 with ischemic stroke, and 498 with any ASCVD in national Danish health registries. Remnant cholesterol was calculated from a standard lipid-profile as total cholesterol minus HDL cholesterol minus LDL cholesterol. Results Individuals with diabetes had higher levels of remnant cholesterol, but lower levels of LDL cholesterol, compared to individuals without diabetes (Figure 1). Statin use could explain the lower levels of LDL cholesterol but did not associate with levels of remnant cholesterol. Multivariable adjusted hazard ratios (95% confidence interval) per doubling of remnant cholesterol and LDL cholesterol were 1.8 (1.2-2.5) and 0.9 (0.6-1.2) for peripheral artery disease, 1.8 (1.3-2.6) and 1.0 (0.7-1.4) for myocardial infarction, 1.6 (1.1-2.3) and 1.1 (0.8-1.6) for ischemic stroke, and 1.7 (1.4-2.2) and 0.9 (0.7-1.1) for any ASCVD, respectively. Excess risk conferred by diabetes was 2.5-fold for peripheral artery disease, 1.6-fold for myocardial infarction, 1.4-fold for ischemic stroke, and 1.6-fold for any ASCVD. Elevated remnant cholesterol explained 14% (95% confidence interval: 6-23%) of excess risk of PAD; corresponding numbers were 26% (10-41%) for myocardial infarction, 34% (5-64%) for ischemic stroke, and 24% (12-36%) for any ASCVD (Figure 2). LDL cholesterol was lower in individuals with diabetes than in individuals without diabetes and could therefore not explain excess risk. Conclusions Elevated remnant cholesterol was associated with increased risk of ASCVD in individuals with diabetes and explained 24% of their excess risk of ASCVD. Clinical trials should determine if remnant cholesterol lowering can prevent ASCVD in individuals with diabetes.

Identifying Patients With Peripheral Artery Disease Using the Electronic Health Record: A Pragmatic Approach

BackgroundPeripheral artery disease (PAD) is underdiagnosed due to poor patient and clinician awareness. Despite this, no widely accepted PAD screening is recommended. ObjectivesThe authors used machine learning to develop an automated risk stratification tool for identifying patients with a high likelihood of PAD. MethodsUsing data from the electronic health record (EHR), ankle-brachial indices (ABIs) were extracted for 3,298 patients. In addition to ABI, we extracted 60 other patient characteristics and used a random forest model to rank the features by association with ABI. The model identified several features independently correlated with PAD. We then built a logistic regression model to predict PAD status on a validation set of patients (n = 1,089), an external cohort of patients (n = 2,922), and a national database (n = 2,488). The model was compared to an age-based and random forest model. ResultsThe model had an area under the curve (AUC) of 0.68 in the validation set. When evaluated on an external population using EHR data, it performed similarly with an AUC of 0.68. When evaluated on a national database, it had an AUC of 0.72. The model outperformed an age-based model (AUC: 0.62; P < 0.001). A random forest model with inclusion of all 60 features did not perform significantly better (AUC: 0.71; P = 0.31). ConclusionsStatistical techniques can be used to build models which identify individuals at high risk for PAD using information accessible from the EHR. Models such as this may allow large health care systems to efficiently identify patients that would benefit from aggressive preventive strategies or targeted-ABI screening.

Abstract 560: Genetics Of Physical Activity And Risk Of Cardiovascular Disease

Objective: Sedentary lifestyle with minimal physical activity is a well-established risk factor for poor metabolic health outcomes. Atherosclerotic cardiovascular diseases (ASCVD) are often thought to be associated with physical inactivity, although observational studies may be limited by residual confounding which makes causal inference challenging. Mendelian Randomization (MR) is a method which leverages the naturally random allocation of genetic variants as a natural experiment, permitting causal inference. To better characterize sedentary lifestyle behaviors, we performed a genome-wide association study (GWAS) of sedentary behaviors using genomic structural equation modeling (SEM) and conducted a MR study using this phenotype to characterize the relationship of physical inactivity to ASCVD. Methods: Genomic SEM was performed to integrate three separate GWAS of physical activity and sedentary behavior into a common factor model. Following this, two-sample univariate and multivariable MR testing the effect of sedentary behavior on ASCVD traits was performed. Outcome data was taken from the Million Veteran Program (MVP) for PAD and CAD, and the GIGASTROKE consortium for stroke. Results: The common factor GWAS of sedentary behavior identified 44 genomic risk loci. 32 of the 44 lead variants were not significantly associated with the original sedentary traits, pointing toward possible new genetic mechanisms. On gene-based testing, the CADM2 gene was implicated as the strongest risk locus of 156 mapped genes; this gene has been associated with impulsivity, substance use and obesity in prior studies. MR experiments revealed sedentary behaviors were associated with a significantly increased risk of CAD, PAD, and ischemic stroke; these effects were no longer significant when controlling for smoking, BMI, and diabetes as confounders. Conclusions: This study takes the largest available GWASs of PAD, CAD, and Stroke, and compares them against a novel GWAS of sedentary behavior traits. The findings suggest that the effects of sedentary behavior on ASCVD traits are likely not independent from other contributing factors (smoking; BMI), but that there is a shared causal pathway between these traits that has implications on the development of ASCVD.

ANKLE BRACHIAL INDEX (ABI) AND ACCELEROMETER PATTERNS OF DAILY PHYSICAL ACTIVITY IN HCHS/SOL

Abstract The benefits of routine engagement in physical activity (PA) on vascular health are well established; lesser known is whether vascular health associates with accelerometry-based daily patterns of PA in mid-to-late life. Using linear regression models adjusted for demographics and comorbidities, we modeled the cross-sectional associations between ankle brachial index (ABI) and PA patterns (diurnal activity and activity fragmentation) in 7,848 HCHS/SOL participants (45.5% men, 56.4±0.2 years). Compared to those with normal ABI (1.0-1.4), those with low ABI (≤0.9) had more fragmented daily activity (B=1.0%, SE=0.4, p=.04); primarily between 12 and 8 PM (B=1.66%, SE=0.55, p&amp;lt;.01). Similarly, those with low ABI had lower daily activity throughout the day (B=-0.09 log-counts, SE=0.05, p&amp;lt;.05) also mainly between 12 and 8 PM (B=-0.16 log-counts, SE=0.55, p&amp;lt;.01). Results suggest a diminished, less favorable PA profile patterns in those with low ABI. Future longitudinal studies should consider whether patterns of PA assist in determining PAD risk.

Impact of direct-acting antiviral treatment for hepatitis C on cardiovascular diseases and extrahepatic cancers.

The impact of direct-acting antivirals (DAAs) on extrahepatic complications in chronic hepatitis C (CHC) patients remains poorly described. We estimated the association of DAAs with cardiovascular events and extrahepatic cancers. The prospective ANRS CO22 HEPATHER cohort was enriched with individual data until December 2018 from the French Health Insurance Database (SNDS). CHC patients were enrolled between August 2012 and December 2015 in 32 French hepatology centers. A total of 8148 CHC adults were selected. Cardiovascular events (stroke, acute coronary syndrome, pulmonary embolism, heart failure, arrhythmias and conduction disorders [ACD], peripheral arterial disease [PAD]) and extrahepatic solid cancers were derived from the SNDS. Associations between DAAs and extrahepatic events were estimated using marginal structural models, with adjustments for clinical confounders. Analyses of 12 905 person-years of no DAA exposure and 22 326 person-years following DAA exposure showed a decreased risk of PAD after DAA exposure (hazard ratio [HR], 0.54; 95% CI, 0.33-0.89), a beneficial effect of DAAs on overall cardiovascular outcomes in patients with advanced fibrosis (aHR, 0.58; 95% CI, 0.42-0.79), and an increased risk of ACD (hazard ratio [HR], 1.46; 95% CI, 1.04-2.04), predominant after the first year following DAA initiation. There was no association between DAAs and extrahepatic cancer risk (HR, 1.23; 95% CI, 0.50-3.03). DAAs were not associated with extrahepatic cancer development or reduction. They were associated with a decreased risk of PAD and an increased risk of ACD, supporting long-term cardiac monitoring after DAA therapy.

Peripheral Arterial Diseases and Diabetes Mellitus: Associations With Quality of Health Measures in Patients Undergoing Percutaneous Vascular Interventions

BackgroundPeripheral arterial disease (PAD) is more prevalent and severe in patients with diabetes mellitus (DM) compared with those without DM. Peripheral vascular intervention (PVI) is often used in patients failing conservative management. The association of PVI with health status in diabetic patients has yet to be determined. MethodsWe analyzed the clinical response to PVI in DM (n = 203, 52 %) compared with non-DM patients (n = 183, 48 %), using the Peripheral Arterial Questionnaire (PAQ) for patients during baseline and a maximum 6 months after PVI. We used the PAQ summary score, which summarized the patients' level of physical and social function, patient symptoms, and overall quality of life. This represented the PAD-related Quality of Health (QOH). Our score range is between 0 (lowest health quality) and 100 (highest health quality). ResultsCompared with non-DM patients, those with DM were more likely to have a history of prior PVI, an increased prevalence of PAD risk factors, and significantly lower QOH scores at baseline (32.7 ± 20 vs 37.5 ± 20.6, p = 0.02). After adjustment for baseline confounding, neither the baseline, the change, nor the final summary scores were significantly different between groups, suggesting similar symptomatic and functional improvement in non-DM and DM patients post-PVI.CONCLUSIONS: Following PVI, PAD-specific health status showed a similar improvement in patients with and without DM, illustrating that use of this strategy among patients with multiple comorbidities or diffuse PAD as useful.

Abstract 15085: Modest Reduction in Ankle-Brachial Index Measurements and Risk of Major Adverse Limb Events Among 133,373 Veterans

Introduction: Low resting ankle-brachial index (ABI) serves as a non-invasive biomarker of poor limb outcomes. Whether modest decrements in ABI translate into higher risks of major adverse limb events (MALE) are unclear, particularly among women and minorities, because prior studies are small or lack racial diversity and incident outcomes. Methods: We analyzed data from participants in the Veterans Affairs Birth Cohort, a prospective, longitudinal cohort of veterans born between 1945-1965 with no clinical history of PAD prior to ABI testing. Participants were enrolled on or after 1/1/2000 and followed through 12/31/2016. The exposure was resting ABI and the outcome was MALE defined as limb revascularization or amputation based on VA and Medicare ICD-9/10 and CPT codes. Cox proportional hazards models assessed the association between ABI and MALE among black and white men and women. Models were adjusted for demographics and PAD risk factors ( Figure Legend ). Results: The analysis included 23,733 black men, 1,257 black women, 96,220 white men, and 2,813 white women. There were 14,431 MALE events. Risk for MALE across the ABI spectrum followed a j-shaped distribution ( Figure ). Both low and high ABIs were associated with an increased risk of MALE for black and white men and women ( Figure ). When we analyzed each sex/race group separately, as compared to a normal ABI measurement (1.11-1.20), a modestly reduced ABI (0.81-0.90) was associated with a significantly increased risk of MALE: black men HR adj , 2.17; 95% CI, 1.67-2.80; black women HR adj , 3,24; 95% CI, 1.21-8.69; white men HR adj , 3.04; 95% CI, 2.68-3.46; white women HR adj , 4.56; 95% CI, 1.73-11.99. Conclusions: In a large, diverse cohort of people free of prior PAD, a modest reduction in ABI was associated with a greater than two-fold increased risk of MALE for all sex/race groups. Further studies are needed to better understand why MALE occurs in this patient population despite only mildly reduced limb perfusion.

Evaluating the impact of glucokinase activation on risk of cardiovascular disease: a Mendelian randomisation analysis

BackgroundGlucokinase activators (GKAs) are an emerging class of glucose lowering drugs that activate the glucose-sensing enzyme glucokinase (GK). Pending formal cardiovascular outcome trials, we applied two-sample Mendelian randomisation (MR) to investigate the impact of GK activation on risk of cardiovascular diseases.MethodsWe used independent genetic variants in or around the glucokinase gene meanwhile associated with HbA1c at genome-wide significance (P < 5 × 10−8) in the Meta-Analyses of Glucose and Insulin-related traits Consortium study (N = 146,806; European ancestry) as instrumental variables (IVs) to mimic the effects of GK activation. We assessed the association between genetically proxied GK activation and the risk of coronary artery disease (CAD; 122,733 cases and 424,528 controls), peripheral arterial disease (PAD; 7098 cases and 206,541 controls), stroke (40,585 cases and 406,111 controls) and heart failure (HF; 47,309 cases and 930,014 controls), using genome-wide association study summary statistics of these outcomes in Europeans. We compared the effect estimates of genetically proxied GK activation with estimates of genetically proxied lower HbA1c on the same outcomes. We repeated our MR analyses in East Asians as validation.ResultsGenetically proxied GK activation was associated with reduced risk of CAD (OR 0.38 per 1% lower HbA1c, 95% CI 0.29–0.51, P = 8.77 × 10−11) and HF (OR 0.54 per 1% lower HbA1c, 95% CI 0.41–0.73, P = 3.55 × 10−5). The genetically proxied protective effects of GKA on CAD and HF exceeded those due to non-targeted HbA1c lowering. There was no causal relationship between genetically proxied GK activation and risk of PAD or stroke. The estimates in sensitivity analyses and in East Asians were generally consistent.ConclusionsGKAs may protect against CAD and HF which needs confirmation by long-term clinical trials.

Frailty and outcomes following revascularization of lower-extremity peripheral artery disease: Insights from the Vascular Quality Initiative (VQI).

Multiple frailty screening tools are implemented; however, it is unclear whether they perform in a comparable way for both frailty detection and prediction of perioperative outcomes in patients undergoing lower-extremity revascularization. Patients undergoing lower-extremity revascularization were identified from the Vascular Quality Initiative (VQI) national database. Two cohorts were established based on the revascularization type (percutaneous vascular interventions (PVI) or lower-extremity bypass). Frailty was assessed by the 5-item modified frailty index (mFI-5) and the VQI-derived risk analysis index (RAI). Out of 134,081 patients undergoing PVI, frailty was identified in 67% by mFI-5 and 28% by RAI. Similarly, out of 41,316 patients in the bypass cohort, frailty was identified in 69% by mFI-5 and 16% by RAI. There was little agreement between the two frailty tools for both vascular cohorts (PVI: kappa: 0.17; bypass: kappa: 0.13). In an adjusted analysis, frailty as assessed by mFI-5 and RAI was associated with higher odds of mortality in both cohorts (p < 0.001). A significant association between frailty and unplanned amputations was only noted in the bypass cohort when RAI was applied (OR: 1.50, p < 0.01). The addition of frailty to traditional PAD risk factors marginally improved model performance to predict mortality and unplanned major amputations. There was significant variation in frailty detection by mFI-5 and RAI. Although frailty was associated with mortality, the predictive value of these tools in predicting outcomes in PAD was limited. Future research should focus on designing new frailty screening tools specific to the PAD population.

Metabolic Biomarker Discovery for Risk of Peripheral Artery Disease Compared With Coronary Artery Disease: Lipoprotein and Metabolite Profiling of 31 657 Individuals From 5 Prospective Cohorts.

BackgroundPeripheral artery disease (PAD) and coronary artery disease (CAD) represent atherosclerosis in different vascular beds. We used detailed metabolic biomarker profiling to identify common and discordant biomarkers and clarify pathophysiological differences for these vascular diseases.Methods and ResultsWe used 5 prospective cohorts from Finnish population (FINRISK 1997, 2002, 2007, and 2012, and Health 2000; n=31 657; median follow‐up time of 14 years) to estimate associations between >200 metabolic biomarkers and incident PAD and CAD. Metabolic biomarkers were measured with nuclear magnetic resonance, and disease events were obtained from nationwide hospital records. During the follow‐up, 498 incident PAD and 2073 incident CAD events occurred. In age‐ and sex‐adjusted Cox models, apolipoproteins and cholesterol measures were robustly associated with incident CAD (eg, hazard ratio [HR] per SD for higher apolipoprotein B/A‐1 ratio, 1.30; 95% CI, 1.25–1.36), but not with incident PAD (HR per SD for higher apolipoprotein B/A‐1 ratio, 1.04; 95% CI, 0.95–1.14; P heterogeneity<0.001). In contrast, triglyceride levels in low‐density lipoprotein and high‐density lipoprotein were associated with both end points (P heterogeneity>0.05). Lower proportion of polyunsaturated fatty acids relative to total fatty acids, and higher concentrations of monounsaturated fatty acids, glycolysis‐related metabolites, and inflammatory protein markers were strongly associated with incident PAD, and many of these associations were stronger for PAD than for CAD (P heterogeneity<0.001). Most differences in metabolic profiles for PAD and CAD remained when adjusting for traditional risk factors.ConclusionsThe metabolic biomarker profile for future PAD risk is distinct from that of CAD. This may represent pathophysiological differences.

O72: SECONDARY PREVENTION OF CARDIOVASCULAR DISEASE IN PERIPHERAL ARTERY DISEASE PATIENTS

Abstract Introduction Peripheral artery disease (PAD) is associated with significant cardiovascular morbidity and mortality which can be reduced by the treatment of atherosclerotic risk factors. Recent research demonstrates that novel drugs can significantly enhance PAD outcomes. However, the uptake of these drugs is uncertain. We wished to audit current atherosclerotic management in PAD patients as well as their eligibility for newer drugs - PCSK 9 inhibitors, SGLT2 inhibitors, and DOAC drugs – in accordance with relevant guidelines and trials. Method 100 PAD inpatients and outpatients seen at a teaching hospital in the UK within the month of March 2019 were assessed. Medications from PAD patients were recorded from hospital records and patient histories were assessed for secondary prevention of cardiovascular disease - lipids, blood pressure, diabetic control, and atherothrombotic prevention. Result showed that compliance with NICE guidelines had a wide range – from 19% of outpatients on correct lipid control to 89% of inpatients on optimal atherothrombotic management. Based on the best evidence of eligibility: 0 of 41 eligible patients were taking PCSK9 Inhibitors, 1 out of the 71 was on an SGLT 2 inhibitor and 6 of 98 patients were on Rivaroxaban. Conclusion This audit shows adherence to NICE guidelines is variable for secondary prevention of atherosclerosis in PAD patients. Furthermore, very few novel treatments had been prescribed for suitable patients. Overall, prescribing for PAD risk factor management can be significantly improved. A solution could be dedicating risk factor clinics led by nurses, pharmacists or physicians. Take-home message Steps need to be taken to prevent cardiovascular disease in peripheral arterial disease patients. Steps include improvements in the following of guidelines, exploration of novel treatments, and the introduction of special risk factor clinics focused on improving the prognosis of the patients.

Heart Rate Predicts the Risk of New-Onset Peripheral Arterial Disease in a Community-Based Population in China.

IntroductionElevated heart rate is linked with poor prognosis and has been shown to accelerate the progress of atherosclerosis. However, the association between heart rate and new-onset PAD is unknown.MethodsA total of 3463 participants without PAD at baseline from a community-based cohort in Beijing were included and followed up for 2.3 years. PAD was defined as ankle–brachial index (ABI) ≤0.9. We used multivariate logistic regression models to investigate the association of heart rate and the risk of new-onset PAD.ResultsParticipants were 56.67 ± 8.54 years old, and 36.12% were men. The baseline ABI was 1.11 ± 0.08, and the incidence of new-onset PAD was 2.97%. Multivariate regression models, adjusted for sex, age, risk factor of atherosclerosis, medications, and baseline ABI, showed that heart rate was significantly associated with incidence of PAD (odds ratio [OR] = 1.22, 95% confidence interval [CI]: 1.03–1.43, P = 0.020); every increase of 10 heart beats per minute (bpm) was associated with a 22% increase in the odds of developing new-onset PAD. Respondents in the higher-heart rate group (≥80 bpm) had an increased risk of new-onset PAD, compared with those in the lower-heart rate group (<80 bpm) (OR = 1.73, 95% CI: 1.14–2.63, P = 0.010). Subgroup analyses revealed no significant heterogeneity among the analyzed subgroups.ConclusionElevated heart rate was independently associated with the risk of new-onset PAD in a community-based population in Beijing. Heart rate management should be considered for the purpose of PAD prevention.