Clinical Peripheral Arterial Disease Research Articles

Ankle brachial index,a non invasive tool predicts cardiovascular events after acute myocardial infarction:a 3 year follow -up study

Abstract Background / Introduction The ankle-brachial index (ABI) is a non-invasive tool that was initially used for the diagnosis of lower-extremity peripheral artery disease (PAD). It has been proven that ABI is a marker of atherosclerosis in other vascular sites and can therefore be used to predict cardiovascular events regardless the presence or not of PAD symptoms. Purpose This study aims to examine the prognostic value of ABI in the setting of acute myocardial infarction (MI), as up till now there is not enough relevant evidence. Method We followed up 441 patients [79% male;mean age 62 years;67% hypertnesive; 30% with diabetes mellitus (DM); 52% current smokers] who were hospitalized because of MI for a period of three years. All patients underwent baseline estimation of clinical and laboratory parameters during theri hospitalization.The ABI was measured according to established methodology using a certified automated device and abnormal ABI defined as a value ≤ 0.9. The primary endpoint was a composite of all-cause and cardiovascular death, as well as major cardiovascular events including decompensated heart failure, new acute coronary syndrome, cerebrovascular event, malignant arrhythmia, PAD event and new onset renal dysfunction. All events were assessed both in-hospital and within 3 years of follow-up. Results Our study population had a mean ABI of 1.1 (IQR: 1.00 to 1.18). With the use of reduced multivariate regression models ABI was proven to be a prognostic indicator for the in-hospital composite endpoint. Patients with an abnormal ABI had a threefold risk of in-hospital events [HR 2.93, 95% CI: 1.48-5.81, p=0.002]. After conducting multivariate analysis ABI maintained its predictive power of all-cause mortality [HR 2.88, 95% CI: 1.53 – 5.42, p=0.001], regardless of hypertension DM, LDL levels and smoking status of the study population in 3 years follow-up. Conclusion An impaired ABI is associated with greater risk of in-hospital events in patients with acute MI. Moreover, ABI emerges as an independent predictor of long-term all-cause mortality in those patients.The findings of this study suggest that subclinical and clinical PAD are associated with poor outcomes among patients with acute MI; thus, routine ABI tests enhance risk stratification and might carry important prognostic significance in these patients regardless of PAD symptoms.

Relationship of apolipoprotein C-III proteoform composition with ankle-brachial index and peripheral artery disease in the Multi-Ethnic Study of Atherosclerosis (MESA)

Background and aimsApolipoprotein C-III (apoC-III) proteoform composition shows distinct relationships with plasma lipids and cardiovascular risk. The present study tested whether apoC-III proteoforms are associated with risk of peripheral artery disease (PAD). MethodsApoC-III proteoforms, i.e., native (C-III0a), and glycosylated with zero (C-III0b), one (C-III1) or two (C-III2) sialic acids, were measured by mass spectrometry immunoassay on 5,734 Multi-Ethnic Study of Atherosclerosis participants who were subsequently followed for clinical PAD over 17 years. Ankle-brachial index (ABI) was also assessed at baseline and then 3 and 10 years later in 4,830 participants. ResultsHigher baseline C-III0b/C-III1 and lower baseline C-III2/C-III1 were associated with slower decline in ABI (follow-up adjusted for baseline) over time, independently of cardiometabolic risk factors, and plasma triglycerides and HDL cholesterol levels (estimated difference per 1 SD was 0.31 % for both, p < 0.01). The associations between C-III2/C-III1 and changes in ABI were stronger in men (−1.21 % vs. −0.27 % in women), and in Black and Chinese participants (−0.83 % and −0.86 % vs. 0.12 % in White). Higher C-III0b/C-III1 was associated with a trend for lower risk of PAD (HR = 0.84 [95%CI: 0.67–1.04]) that became stronger after excluding participants on lipid-lowering medications (0.73 [95%CI: 0.57–0.94]). Neither change in ABI nor clinical PAD was related to total apoC-III levels. ConclusionsWe found associations of apoC-III proteoform composition with changes in ABI that were independent of other risk factors, including plasma lipids. Our data further support unique properties of apoC-III proteoforms in modulating vascular health that go beyond total apoC-III levels.

Prevalence of and Risk Factors for Peripheral Artery Disease in Rural South Africa: A Cross-Sectional Analysis of the HAALSI Cohort.

The burden of peripheral artery disease (PAD) is increasing in low- and middle-income countries. Existing literature from sub-Saharan Africa is limited and lacks population-representative estimates. We estimated the burden and risk factor profile of PAD for a rural South African population. We used data from 1883 participants from a rural, low-incomecohort of South African adults aged 40 to 69 years with available ankle-brachial index measurements. We defined clinical PAD as ankle-brachial index ≤0.90 or >1.40, and borderline PAD as ankle-brachial index >0.90 and ≤1.00. We compared the distribution of sociodemographic variables, biomarkers, and comorbidities across PAD classifications. To identify associated factors, we calculated unadjusted and age-sex-adjusted prevalence ratios (PRs) with log-binomial models. Overall, 6.6% (95% CI, 5.6-7.7) of the sample met the diagnostic criteria for clinical PAD, while 44.7% (95% CI, 42.4-47.0) met the diagnostic criteria for borderline PAD. Age (PR: 1.9 [95% CI, 1.2-3.1] for ages 50-59 years compared with 40-49 years; PR: 2.5 [95% CI, 1.5-4.0] for ages 60-69 years compared with 40-49 years); diagnosed hypertension (PR: 1.53 [95% CI, 1.08-2.17]); and C-reactive protein (PR: 1.08 [95% CI, 1.03-1.12]) were associated with increased prevalence of clinical PAD. All other examined factors were not significantly associated with clinical PAD. We found high PAD prevalence for younger age groups compared with previous research and a lack of statistical evidence for the influence of traditional risk factors for this rural, low-income population. Future research should focus on identifying the underlying risk factors for PAD in this setting. South African policymakers and clinicians should consider expanded screening for early PAD detection in rural areas.

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.

Non-esterified fatty acids and risk of peripheral artery disease in older adults: The cardiovascular health study

Background and aimsNon-esterified fatty acids have been implicated in the pathogenesis of diabetes and cardiovascular disease. No longitudinal study has assessed their effects on peripheral artery disease (PAD). We determined the relationships between NEFAs and incident clinical PAD and abnormal ankle-brachial index (ABI) in a population-based cohort of older persons. MethodsWe evaluated 4575 community living participants aged >65 years who underwent measurement of circulating NEFAs in fasting specimens and ABI in 1992–1993. Participants were assessed annually for clinical PAD until 2015 and underwent repeat ABI in 1998–1999. We used Cox proportional hazards regression to model the associations between NEFAs and risk of clinical PAD and logistic regression to model the associations of NEFAs with incident abnormal ABI. ResultsMean age was 74.8 years, 59% were female, and 17% were Black. NEFAs were associated with higher risk of clinical PAD in unadjusted and adjusted models. The adjusted hazard ratios for incident clinical PAD were 1.51 (95%CI = 1.06–2.13, p = 0.02) across extreme tertiles, and 1.14 (95%CI = 0.99–1.31, p = 0.08) per standard deviation higher NEFA. The corresponding odds ratios for abnormal ABI were 0.95 (95%CI = 0.69–1.32, p = 0.76) across extreme tertiles, and 1.03 (95%CI = 0.89–1.20, p = 0.68) per standard deviation higher NEFA. Relationships appeared similar irrespective of sex, race, or pre-existing cardiovascular disease, but were stronger later than earlier in follow-up. ConclusionsHigher serum levels of NEFAs are significantly associated with increased likelihood of clinical PAD over long-term follow-up but not with 6-year decline in ABI. NEFAs may offer a potential target for intervention against clinical PAD.

Peripheral artery disease, abnormal ankle-brachial index, and prognosis in patients with acute coronary syndrome.

ObjectivesAnkle-brachial index (ABI) is an independent prognostic marker of cardiovascular events among patients with coronary artery disease (CAD). We aimed to investigate the outcome of patients hospitalized with acute coronary syndrome (ACS) and abnormal ABI.Approach and resultsABI was prospectively measured in 1,047 patients hospitalized due to ACS, who were stratified into three groups, namely, those with clinical peripheral artery disease (PAD) (N = 132), those without clinical PAD but with abnormal (< 0.9) ABI (subclinical PAD; N = 148), and those without clinical PAD with normal ABI (no PAD; N = 767). Patients were prospectively followed for 30-day major adverse cardiovascular event (MACE) and 1-year all-cause mortality. The mean age was 64 years. There was a significant gradual increase throughout the three groups in age, i.e., the incidence of prior stroke, diabetes mellitus, and hypertension (p for trend = 0.001 for all). The in-hospital course showed a gradual rise in the incidence of complications with an increase in heart failure [2.5, 6.1, and 9.2%, (p for trend = 0.001)] and acute kidney injury [2, 4.1, and 11.5%, (p for trend = 0.001)]. At day 30, there was a stepwise increase in MACE, such that patients without PAD had the lowest rate, followed by subclinical and clinical PADs (3.5, 6.8, and 8.1%, respectively, p for trend = 0.009). Similarly, there was a significant increase in 1-year mortality from 3.4% in patients without PAD, through 6.8% in those with subclinical PAD, to 15.2% in those with clinical PAD (p for trend = 0.001).ConclusionSubclinical PAD is associated with poor outcomes in patients with ACS, suggesting that routine ABI screening could carry important prognostic significance in these patients regardless of PAD symptoms.

THE SYSTOLIC RISE TIME MEASURED WIH PPG TO SCREENING PERIPHERAL ARTERY DISEASE: APPLICATION TO THE POPMETRE

Objective: Screening for Peripheral Artery Disease (PAD) remains a challenge in the prevention and care of patients with arteriosclerosis. The Ankle Brachial Index (ABI) is currently the gold standard. However, ABI is time consuming and requires some expertise to perform which is a limiting factor for global screening. The measurement of the Systolic Rise Time (SRT) of the pulse wave of the lower limb may provide an easier alternative to detect PAD. In a retrospective pilot study, we analyzed the possibility of detecting PAD using the SRT of the toe waveform using the Photo-PlethysmoGraphic signal (PPG). Design and method: We measured 79 subjects (41 patients diagnosed with different stages of PAD and 38 healthy volunteers without known PAD). In each subject, at least one lower limb was assessed with classical ABI. All subjects underwent a PPG assessment on the finger and the toe simultaneously using popmètreâ (Axelife – France). In-house software (JAVA) was used to calculate the SRT of all recorded signals. Results: 146 lower limbs were analyzed including 72 healthy and 74 subjects with PAD. The mean age of the population was 69 ± 12 years with 75% men, 28% diabetics, 47% hypertensive, 49% without clinical PAD defined as stage 0 in this study; 16% in stage 1; 32% in stage 2; 2% in stage 3 and 1% in stage 4 according to the Leriche classification. The SRT cut-off value of 160 ms identifies PAD according to Leriche starting at stage 1 with a sensitivity of 78% vs 73% for ABI &lt; 0.9 and a specificity of 86% vs 87%; a positive predictive value (PPV) of 85% vs 86% and a negative predictive value (NPV) of 79% vs 75%. In addition, the ratio between toe-SRT and finger-SRT cut-off value of 1 identifies PAD with a sensitivity of 76% and a specificity of 74%. Conclusions: SRT measured using a PPG pulse signal of the toe is promising as a facile non-invasive method to diagnose PAD (duration &lt; 14 seconds) and determine PAD stages 1 to 4 with similar specificity and sensitivity as the reference method.

Association of coronary artery calcification and thoracic aortic calcification with incident peripheral arterial disease in the Multi-Ethnic Study of Atherosclerosis (MESA).

AimsThe association of subclinical atherosclerotic disease in the coronary arteries and thoracic aorta with incident peripheral arterial disease (PAD) is unknown. We investigated the association between coronary artery calcium score (CACs) and thoracic aortic calcium score (TACs) with incident clinical and subclinical PAD.Methods and resultsThe Multi-Ethnic Study of Atherosclerosis (MESA) recruited 6814 men and women aged 45–84 from four ethnic groups who were free of clinical cardiovascular disease at enrolment. Coronary artery calcium score and thoracic aortic calcium score were measured from computed tomography scans. Participants with a baseline ankle-brachial index (ABI) ≤0.90 or >1.4 were excluded. Abnormal ABI was defined as ABI ≤0.9 or >1.4 at follow-up exam. Multivariable logistic regression and Cox proportional hazards models were used to test the associations between baseline CACs and TACs with incident abnormal ABI and clinical PAD, respectively. A total of 6409 participants (female: 52.8%) with a mean age of 61 years were analysed. Over a median follow-up of 16.7 years, 91 participants developed clinical PAD. In multivariable analysis, each unit increase in log (CACS + 1) and log (TACs + 1) were associated with 23% and 13% (P < 0.01for both) higher risk of incident clinical PAD, respectively. In 5725 (female: 52.6%) participants with an available follow-up ABI over median 9.2 years, each 1-unit increase in log (CACs + 1) and log (TACs + 1) were independently associated with 1.15-fold and 1.07-fold (P < 0.01for both) higher odds of incident abnormal ABI, respectively.ConclusionHigher baseline CACs and TACs predict abnormal ABI and clinical PAD independent of traditional cardiovascular risk factors and baseline ABI.

Analyses of serum and urinary metabolites in individuals with peripheral artery disease (PAD) consuming a bean-rich diet: relationships with drug metabolites.

Peripheral artery disease (PAD) has high morbidity and mortality rates. A metabolomics approach was employed to determine whether consumption of bean-rich diets for 8weeks would impact the metabolomic profile of individuals with PAD. Serum and urine, collected from 54 participants with clinical PAD at baseline and after 8weeks on 0.3 cups beans/day (n= 19), 0.6 cups beans/day (n= 20), or control (n= 23) diet, and the beans were extracted and analyzed using LC-QTOF-MS. As a result, PGE2 p-acetamidophenyl ester, PGF2α diethyl amide and 5-l-glutamyl-l-alanine were significantly changed in the serum or urine of bean groups compared with control. Significant changes (P< 0.05) in the profile and/or levels of 22 flavonoids present in bean extracts showed the potential importance of the mixture of beans used in this study. In a subset of participants taking metoprolol, after 8weeks the bean-rich diets significantly elevated metoprolol in the serum while reducing it in urine compared with baseline. In addition, the diets significantly enhanced the urinary excretion of metformin. In conclusion, several biochemical pathways including prostaglandins and glutathione were affected by bean consumption. Significant changes in the metabolism of metoprolol and metformin with bean consumption suggested the presence of diet-drug interactions that may require adjustment of the prescribed dose. ClinicalTrials.gov Identifier: NCT01382056. Novelty: Bean consumption by people with PAD alters the levels of certain metabolites in serum and urine. Different bean types (black, red kidney, pinto, navy) have unique flavonoid profiles. Metabolomics revealed potential diet-drug interactions as serum and/or urinary levels of metoprolol and metformin are modified by bean consumption.

A new invasive method to assess pulse wave velocity during cardiac catheterization

Abstract Pulse wave velocity (PWV) is an independent cardiovascular risk factor (CVRF), and there are multiple ways to measure it with more or less accuracy. We sought to easily develop an invasive gold standard axial PWV during cardiac catheterization between ascending aorta (AAo) and tibial artery (TIB) or humeral artery (HUM). Aorto-humeral PWV is not a usual measurement site because of its difficulty to estimate it non-invasively. Axial PWV demonstrates a greater correlation with CVRF, with carotid-femoral PWV the common way to estimate it non-invasively in hypertensive patients and others. Methods 26 patients were enrolled for AAo-TIB PWV measurements and 50 for AAo-HUM. A cuff connected to the hemodynamic Phillips workstation of the cathlab was placed around the right leg, at mid-calf, and was inflated to superimpose TIB pulsatile blood pressure waves on AAo blood pressure recorded with a fluid filled diagnostic 5 Fr or interventional 6 Fr catheter left at the end of the diagnostic coronary angiography in the ascending aorta. The distance between AAo and TIB was estimated by the distance between axillary and iliac crest, added with the distance between iliac crest and mid-calf. PWV was then calculated from the length estimated between AAo and mid-calf, and the time delay between AAo and TIB pulses (see figure) by gating to the R-wave of the ECG (upper trace) for both measurements, using a dedicated software written in MatLab®. For AAo=HUM PWV, in 50 patients the pressure of the catheter was sequencially recorded in the AoAsc then pulled back in the humeral artery. Both recordings were matched off-line based on the R top of the ECG recorded and the delay between the rise of the 2 pressure curves in the same MatLab® software. Results Mean age of our patients is 62,7±9,2 years. 82% had chronic hypertension and 33% had diabetes mellitus. 4 patients (15%) had clinical peripheral artery disease and only one had a stenting on femoral artery. No patients had previous vascular bypass. Aorto-tibial PWV showed an average PWV at 8.4±1.4 m/s. Aorto-humeral PWV showed an average PWV at 7.2±1.8 m/s. The PWV tended to be 0,6 m/s lower in patients with ≤2 cardiovascular risk factors versus &amp;gt;3. Conclusion We describe a simple and accurate PWV gold standard that can be recorded in any patient admitted for a coronary angiography. Aorto-tibial PWV is easier to obtain. Adding this parameter in the global assessment of patients with hypertension or other CVD will refine their CVRF profile. Funding Acknowledgement Type of funding sources: None.

Associations of cardiac injury biomarkers with risk of peripheral artery disease: The Multi-Ethnic Study of Atherosclerosis

IntroductionWe investigated the associations of high-sensitivity cardiac Troponin T (hs-cTnT) and N-terminal pro B-type natriuretic peptide (NT-proBNP) levels with risk of developing clinical peripheral artery disease (PAD) or a low ankle–brachial index (ABI). MethodsHs-cTnT and NT-proBNP were measured in 6692 and 5458 participants respectively without baseline PAD between 2000 and 2002 in the Multi-ethnic Study of Atherosclerosis. A significant number also had repeat biomarker measurement between 2004 and 2005. Incident clinical PAD was ascertained through 2017. Incident low ABI, defined as ABI <0.9 and decline of ≥0.15 from baseline, was assessed among 5920 eligible individuals who had an ABI >0.9 at baseline and at least one follow-up ABI measurement 3–10 years later. Multivariable Cox proportional hazards and logistic regression modeling were used to determine the association of these biomarkers with clinical PAD and low ABI, respectively. ResultsOverall, 121 clinical PAD and 118 low ABI events occurred. Adjusting for demographic and clinical characteristics, each log unit increment in hs-cTnT and NT-proBNP was associated with a 30% (adjusted hazard ratio (HR) 1.3, 95% confidence interval (CI): 1.1, 1.6) and 50% (HR) 1.5, 95% CI: 1.2, 1.8) higher risk of clinical PAD respectively. No significant associations were observed for incident low ABI. Change in these biomarkers was not associated with either of the PAD outcomes. ConclusionsNT-proBNP and hs-cTnT are independently associated with the development of clinical PAD. Further study should determine whether these biomarkers can help to better identify those at higher risk for PAD.

Relationship between Retinal Nerve Fiber Layer Thickness and Aortic Distensibility in Peripheral Arterial Disease Patients.

Aim and objectiveTo evaluate the relationship between aortic distensibility (AD) and aortic stiffness B index (ASBI) with retinal nerve fiber layer (RNFL) thickness measured with HD-OCT in peripheral arterial disease (PAD) patients.Materials and methodsTwenty-six PAD patients and 22 age-matched healthy control were enrolled. Subjects with PAD were classified into two groups. Patients with diabetes (DM) or hypertension (HT) comprised group I (n = 18) and without DM or HT comprised group II (n = 8). Color Doppler imaging was performed on all patients and PAD was diagnosed by using the ankle-brachial index (ABI). Retinal nerve fiber layer thickness values between control and PAD patients and correlations between RNFL thickness and aortic stiffness parameters (AD and ASBI) were evaluated.ResultsThe inferior-nasal and inferior-temporal quadrant were the thickest in healthy subjects and the PAD group. Retinal nerve fiber layer thickness significantly decreased in superior-nasal, temporal, inferior-nasal quadrants in group I than healthy subjects (p < 0.001, p = 0.005, p < 0.001). Temporal and inferior-nasal quadrant thicknesses were statistically significantly thinner in group II than controls (p = 0.02, p < 0.001). The nasal RNFL quadrant was significantly thinner in group I than group II (p = 0.014). The correlation between RNFL thickness and aortic elasticity parameters in each group was not found to be significant.Conclusion and clinical significanceIsolated PAD without DM or HT may lead to localized RNFL loss in temporal and inferior-nasal quadrants. Aortic elasticity parameters did not seem to be correlated with RNFL thickness in PAD.How to cite this articleKumova D, Aktas Z, Eyiol A, et al. Relationship between Retinal Nerve Fiber Layer Thickness and Aortic Distensibility in Peripheral Arterial Disease Patients. J Curr Glaucoma Pract 2021;15(2):86–90.

Considerations for Patients With Peripheral Artery Disease During the COVID-19 Pandemic

New York City was one of the epicenters of the COVID-19 pandemic. The management of peripheral artery disease (PAD) during this time has been a major challenge for health care systems and medical personnel. This document is based on the experiences of experts from various medical fields involved in the treatment of patients with PAD practicing in hospitals across New York City during the outbreak. The recommendations are based on certain aspects including the COVID-19 infection status as well as the clinical PAD presentation of the patient. Our case-based algorithm aims at guiding the treatment of patients with PAD during the pandemic in a safe and efficient way.

Abstract 14158: Ankle-brachial Index and Risk of Severe Ischemic Leg Outcomes in a Community-based Population: The Atherosclerosis Risk in Communities (ARIC) Study

Introduction: Ankle-brachial index (ABI) ≤ 0.9 is used to define lower-extremity peripheral artery disease (PAD). However, the association between ABI and severe ischemic leg outcomes in the general population has not been investigated. Hypothesis: Lower ABI is independently associated with risk of severe ischemic leg outcomes. Methods: We studied 13,742 ARIC participants (median age 54 [SD 5.75] years, 45% males) without intermittent claudication or a history of revascularization for PAD at baseline (1987-89). We quantified the association of ABI with risk of severe ischemic leg outcomes using Cox regression. ABI was modeled as a restricted cubic spline allowing for potentially non-linear associations. Severe ischemic leg outcomes were ascertained through ICD codes and included critical limb ischemia (CLI) (defined as PAD with rest pain or tissue loss) and ischemic leg amputation (amputations with PAD diagnosis). Results: Over a median of 28 years of follow-up, there were 221 and 129 events of CLI and ischemic leg amputation, respectively. Lower ABI was linearly associated with both CLI and ischemic leg amputation (Figure). With ABI 1.25 as the reference, adjusted hazard ratios of CLI were 2.48 (95% CI 1.15-5.36) at ABI 0.7, 1.97 (1.30-2.99) at ABI 0.9, and 1.73 (1.18-2.54) at ABI 1.0. The corresponding hazard ratios of ischemic leg amputation were 3.57 (1.44-8.81), 2.63 (1.54-4.48), and 2.23 (1.34-3.70), respectively. The association was largely consistent in demographic and clinical subgroups, although the results were less evident in younger and female participants compared to their counterparts. Conclusions: In middle-aged adults without clinical PAD, lower ABI was independently and linearly associated with higher risk of severe ischemic leg outcomes. Our results support the value of ABI as an indicator for leg vascular condition and also indicate that ABI 0.9-1.1 should not be considered normal for ischemic leg prognosis.

Association of Circulating Hepatocyte Growth Factor and Risk of Incident Peripheral Artery Disease: The Multi-Ethnic Study of Atherosclerosis.

Higher levels of hepatocyte growth factor (HGF) have been associated with the presence of peripheral arterial disease (PAD), but prospective associations are unknown. We examined the association of circulating HGF levels with incident PAD. Between 2000 and 2002, HGF was measured in 6742 Multi-Ethnic Study of Atherosclerosis participants without PAD. Incident clinical PAD, adjudicated on the basis of a positive history for the presence of disease-related symptoms or treatment, was ascertained through 2015. Incident low ankle-brachial index (ABI), defined as an ABI < 0.9 and a decline of ≥ 0.15, was assessed among 5736 individuals who had an ABI > 0.9 at baseline and ≥1 follow-up ABI measurement 3 to 10 years later. There were 116 clinical PAD and 197 low ABI events that occurred over a median follow-up of 14 and 9 years, respectively. After adjustment for demographic and clinical variables, a standard deviation increment of HGF (303 ng/L) was associated with an increased risk of clinical PAD (hazard ratio: 1.21; 95% confidence interval [CI]: 1.05-1.39) but not a low ABI (rate ratio: 1.03; 95% CI: 0.85-1.25). In conclusion, higher HGF levels were modestly associated with an increased risk of developing clinical PAD.

Cholesterol mass efflux capacity and risk of peripheral artery disease: The Multi-Ethnic Study of Atherosclerosis

Background and aimsWe aimed to assess the relationship of HDL (high-density lipoprotein)-mediated cholesterol mass efflux capacity (CMEC) with risk of incident peripheral artery disease (PAD). MethodsCMEC was measured in 1458 Multi-Ethnic Study of Atherosclerosis participants between 2000 and 2002 as part of a case-control study matched for incident cardiovascular disease and progression of carotid plaque by ultrasound. Incident clinical PAD, adjudicated on the basis of a positive history for the presence of disease-related symptoms or treatment, was ascertained through 2015 in 1419 individuals without clinical PAD at baseline. Subclinical PAD, defined as an ankle-brachial index (ABI) ≤1.0, was assessed among 1255 individuals with a baseline ABI >1.0 and at least one follow-up ABI measurement 3–10 years later. Cox proportional hazards and relative risk regression modeling per SD increment of CMEC were used to determine the association of CMEC with clinical and subclinical PAD, respectively. ResultsThere were 38 clinical PAD and 213 subclinical PAD events that occurred over a mean follow-up of 6.0 and 6.5 years respectively. After adjustment for age, gender, and race, higher CMEC levels were not associated with clinical PAD (hazard ratio 1.25; 95% CI 0.89, 1.75) or subclinical PAD (risk ratio 1.02; 95% CI, 0.94, 1.11). ConclusionsThese findings suggest that HDL-mediated cholesterol efflux is not significantly associated with incident clinical and subclinical PAD.

Valvular calcification and risk of peripheral artery disease: the Multi-Ethnic Study of Atherosclerosis (MESA).

The detection of cardiac valvular calcification on routine imaging may provide an opportunity to identify individuals at increased risk for peripheral artery disease (PAD). We investigated the associations of aortic valvular calcification (AVC) and mitral annular calcification (MAC) with risk of developing clinical PAD or a low ankle-brachial index (ABI). AVC and MAC were measured on cardiac computed tomography in 6778 Multi-Ethnic Study of Atherosclerosis participants without baseline PAD between 2000 and 2002. Clinical PAD was ascertained through 2015. Incident low ABI, defined as ABI <0.9 and decline of ≥0.15, was assessed among 5762 individuals who had an ABI >0.9 at baseline and at least one follow-up ABI measurement 3-10 years later. Adjusted Cox proportional hazards and Poisson regression modelling were used to determine the association of valvular calcification with clinical PAD and low ABI, respectively. There were 117 clinical PAD and 198 low ABI events that occurred over a median follow-up of 14 years and 9.2 years, respectively. The presence of MAC was associated with an increased risk of clinical PAD [hazard ratio 1.79; 95% confidence interval (CI) 1.04-3.05] but not a low ABI (rate ratio 1.28; 95% CI 0.75-2.19). No significant associations were noted for the presence of AVC and risk of either clinical PAD. MAC is associated with an increased risk of developing clinical PAD. Future studies are needed to corroborate our findings and better understand whether MAC holds any predictive value as a risk marker for PAD.

GlycA, a Novel Inflammatory Marker and Its Association With Peripheral Arterial Disease and Carotid Plaque: The Multi-Ethnic Study of Atherosclerosis.

GlycA, a composite biomarker of systemic inflammation, is associated with cardiovascular disease (CVD) and mortality, but its relationship with peripheral artery disease (PAD) is unknown. We assessed whether plasma GlycA is associated with ankle-brachial index (ABI), carotid plaque (CP), and incident clinical PAD among 6466 Multi-Ethnic Study of Atherosclerosis participants without CVD at baseline. GlycA, ABI, and CP were measured at baseline. Both ABI and CP were remeasured at 10 years. Incident clinical PAD was ascertained from hospital records. We used logistic, Cox, and linear mixed regression models adjusted for demographic and lifestyle factors. Mean (standard deviation, SD) was 62 (10) years for age and 381 (61) µmol/L for GlycA; 53% were women. GlycA was associated with both prevalent low ABI ≤0.8 (prevalence odds ratio [95% confidence interval, CI] per SD increment in GlycA, 1.65 [1.39-1.97]) and CP (1.19 [1.11-1.27]) at baseline. There were no significant associations of GlycA with incident low ABI, incident CP, or 10-year change in ABI or CP score. We identified 110 incident cases of PAD after 79 590 person-years. The hazard ratio (95% CI) of incident PAD per SD increment in GlycA was 1.38 (1.14-1.66). In conclusion, GlycA was associated with prevalent low ABI, prevalent CP, and incident PAD after a median of 14 years.

Abstract P308: The Association of Height With Incident Peripheral Arterial Disease in the Atherosclerosis Risk in Communities (ARIC) Study

Background: A number of cross-sectional studies have reported shorter height as a risk factor for peripheral artery disease (PAD) defined by low ABI. People of shorter stature may have a naturally lower ABI stemming from a relatively lower ankle blood pressure, as function of the shorter distance from the heart to the distal leg arteries. If shorter height is related to PAD, height should also be associated with clinical PAD. We aimed to investigate the association of height with clinical PAD and critical limb ischemia (CLI) in a prospective cohort analysis. Methods: Using data from the ARIC Study, we investigated the association of height with development of PAD and CLI, defined based on ICD-9 codes, for the 14,668 participants at Visit 1 without prevalent PAD/CLI over a median follow-up time of 25.9 years. We modeled risk for PAD and CLI over time using Cox proportional hazards regression. Results: 6,652 (45.4%) participants were men, with a mean age of 55 (SD 6) years old, compared to 54 (SD 6) years old in women. 1,460 (22%) men and 2,321 (29%) women were African American. Men tended to be taller and have a higher weight compared to women. Within each sex, there were no significant differences by quartile of height in terms of demographic factors or clinical comorbidities. For men in height quartile 2 compared to quartile 1, there was a decreased risk of PAD in unadjusted analysis (HR=0.69; 95% CI 0.51-0.94). However, this HR was no longer significant after full adjustment (Table 1). In women, the risk of CLI was higher in the fourth quartile of height compared to quartile 1 after adjustment for demographic factors (HR=1.69; 95% CI: 1.00-2.84). However this HR also became non-significant after full adjustment. For both genders, the HR of either PAD or CLI per one SD increase in height was not significant. Conclusions: In contrast to previous cross-sectional studies which showed and association between shorter height and PAD based on ABI, our prospective study showed null associations between height and clinical PAD.

Korelasi antara Ankle-Brachial Index, Pulse Oximetry, dan Ankle Peak Systolic Velocity Penderita Diabetes Melitus tanpa Obesitas Abdominal

Background: Diabetes Mellitus is the most common complication of vascular complications, one of which is peripheral arterial disease (PAD), which can increase morbidity and mortality in diabetic patient.Early screening parameter and diagnosis of PAD that currently still largely accepted are Ankle-Brachial Index (ABI) and pulse oximetry. ABI and pulse oximetry each has advantages and disadvantages. Patients with diabetes, especially if accompanied by abdominal obesity often have arterial sti?ness so that the value of ABI actually increased, in this case pulse oximetry has a higher sensitivity. Ankle Peak Systolic Velocity (APSV) which is the average of Peak Systolic Velocity (PSV) of anterior and posterior tibial artery at ankle joint level is a new parameter for assessing ischemia of the lower limb and is not in?uenced by arterial sti?ness. The purpose of this study was to determine and analyze the correlation between ankle-brachial index, pulse oximetry and ankle peak systolic velocity in DM patients without abdominal obesity.Materials and methods: This study was observational analytic with cross-sectional design study in subjects with DM without abdominal obesity who meet the inclusion and exclusion criteria.Results: The subjects consisted of 38 limbs from 19 people, 11 (57.9%) males and 8 (42.1%) women aged 47-68 years. Spearman test showed a positive correlation was signifcant between ABI with APSV (r = 0.549, p &lt;0.001). Correlation between ABI and pulse oximetry; pulse oximetry and APSV showed weak signifcant negative correlation (r = -0.347, p &lt;0.05 and r = -0.369, p &lt;0.05). Only APSV which has a strong positive correlation with clinical PAD signifcantly (r = 0.743, p &lt;0.001).Conclusions: There is no strong correlation between ABI, pulse oximetry and APSV in DM patients without abdominal obesity. APSV can replace ABI and pulse oximetry as a non-invasive examination of diabetic patients for screening and follow-up PAD