Baseline Ankle-brachial Index Research Articles

Patient Reported Barriers for Participation in Supervised Exercise Therapy for Symptomatic Peripheral Artery Disease

ObjectivesSupervised exercise therapy (SET) provides clinical benefit for patients suffering from intermittent claudication due to peripheral artery disease (PAD). However, enrollment in programs when offered remains low. We sought to identify patient-reported barriers to enrollment in SET as part of a prospective quality improvement program. MethodsPatients who presented to clinic and were diagnosed with claudication were offered enrollment in a prospective quality improvement protocol, offered at nine regional offices throughout our health system. Both patients who enrolled and declined enrollment were offered a 12-question questionnaire to identify potential barriers to enrollment. Additional data including gender, smoking status, ankle-brachial index (ABI), proximity to the nearest regional office, and disadvantage levels of neighborhoods (low: 1-3, medium: 4-7, and high: 8-10 area deprivation index [ADI]) was collected and compared by program participation using univariate analysis. ResultsPatients enrolled in the SET program (n=66 patients) versus those who declined (n=84 patients) were of similar age (medium age: 71.4 vs. 69.7 years, p=0.694), baseline ABI (0.6 vs. 0.6, p=0.944), smoking status (former 56.1% vs. 53.6%, p=0.668), distance away from outpatient center (8.2 mi vs. 8.4 mi, p=0.249), and had similar Connecticut state ADIs (2021 high-disadvantage: 35.4% vs 33.3%, p=0.549). Patients participating in the SET program were more likely to be male (78.8% vs. 56.0%, p=0.003). Top self-reported barriers for patients who declined participation included transportation/distance (39.3%), preference for independent walking (56.0%), inability to commit to three sessions per week (52.4%), and lack of interest (20.2%). In addition, a higher proportion of patients who declined participation identified severe barriers of preference for independent walking (39.3% vs. 1.5%, p<0.001), inability to commit to three sessions per week (26.2% vs. 3.0% p<0.001), transportation/distance issues (23.8% vs. 7.6% p=0.008), and cost (27.4% vs. 9.1%, p=0.005) as significant barriers for participation in SET. ConclusionsPatients who declined participation in SET for PAD had similar disease status and access to care than participating counterparts. Top reported barriers to enrollment include a preference for independent walking, transportation/distance, commitment to 3x/week program, and cost, which highlight areas of focus for equitable access to these limb-saving services.

Ankle-Brachial Index and Risk of Sudden Cardiac Death in the Community: The ARIC Study.

Sudden cardiac death (SCD) is a significant global public health problem accounting for 15% to 20% of all deaths. A great majority of SCD is associated with coronary heart disease, which may first be detected at autopsy. The ankle-brachial index (ABI) is a simple, noninvasive measure of subclinical atherosclerosis. The purpose of this study was to examine the relationship between ABI and SCD in a middle-aged biracial general population. Participants of the ARIC (Atherosclerosis Risk in Communities) study with an ABI measurement between 1987 and 1989 were included. ABI was categorized as low (≤0.90), borderline (0.90-1.00), normal (1.00-1.40), and noncompressible (>1.40). SCD was defined as a sudden pulseless condition presumed to be caused by a ventricular tachyarrhythmia in a previously stable individual and was adjudicated by a committee of cardiac electrophysiologists, cardiologists, and internists. Cox proportional hazards models were used to evaluate the associations between baseline ABI and incident SCD. Of the 15 081 participants followed for a median of 23.5 years, 556 (3.7%) developed SCD (1.96 cases per 1000 person-years). Low and borderline ABIs were associated with an increased risk of SCD (demographically adjusted hazard ratios [HRs], 2.27 [95% CI, 1.64-3.14] and 1.52 [95% CI, 1.17-1.96], respectively) compared with normal ABI. The association between low ABI and SCD remained significant after adjustment for traditional cardiovascular risk factors (HR, 1.63 [95% CI, 1.15-2.32]). Low ABI is independently associated with an increased risk of SCD in a middle-aged biracial general population. ABI could be incorporated into future SCD risk prediction models.

Outcomes of Alprostadil As an Adjuvant Therapy with Indirect Angiosomal Revascularization in Patients with Critical Limb Ischemia after Failure of Direct Revascularization

This study was carried out to assess the effectiveness of alprostadil (prostaglandin E1) when used as an adjuvant therapy with indirect revascularization in patients with critical limb ischemia (CLI) after the failure of direct revascularization (DR). At our centers, 120 patients suffering from infrainguinal peripheral arterial disease with CLI underwent a failed trial of DR procedure, all revascularization procedures were endovascular. Median follow-up was 2years and 2.5years for patients with and without diabetes mellitus (DM). In the alprostadil group, the mean age was 63.41±12.52; 36 (60%) for males and 24 (40%) for females. Post-endovascular intervention alprostadil was administrated immediately postoperatively by intravenous infusion of 40μg alprostadil diluted in 100ml of normal saline, over 2hr every 12hr for 6days. In the alprostadil group, the mean±standard deviation (SD) of the baseline ankle-brachial index (ABI) was 0.45±0.175, while the mean±SD of ABI at the end of our study was 0.65±0.216 with a difference from the baseline of 0.2±0.041 (P value=0.08, <0.05 meaning that it is significant). Our 1-month primary patency rate was 93.3%, while our 3- and 6-month patency rate was 92.9%. In the control group, the mean±SD of the baseline ABI was 0.68±0.22, while the mean±SD of ABI at the end of our study was 0.69±0.23 with a difference from the baseline of 0.01±0.01 (P value >0.05 meaning that it is nonsignificant) 1-month patency rate was 89%, while 3- and 6-month patency rate was 75%. When we compared the patient's leg vessels before and after our intervention, we found that the percentage of the no-runoff-vessels group decreased from 10 (16.7%) to 4 (6.67%). One-runoff-vessel group percentage dropped from 40 (66.7%) to 36 (60%), whereas, in the two-runoff-vessel group, the percentage increased from 10 (16.7%) to 20 (33.3%). We evaluate leg arteries; we do no pedal arch intervention in the alpostradil group. Out of the total of 60 patients, limb salvage occurred in 58 (96.7%) patients, and 2 (3.3%) patients underwent below-the-knee amputation before the study ended. Our results show the efficacy and safety of alprostadil as an adjuvant therapy with indirect angiosomal revascularization in patients with tissue loss due to CLI.

Socioeconomic factors predict successful supervised exercise therapy completion

ObjectiveSupervised exercise therapy (SET) for patients with intermittent claudication (IC) can lower the risk of progression to chronic limb-threatening ischemia and amputation, while preserving and restoring functional status. Despite supporting evidence, it remains underutilized, and among those who initiate programs, attrition rates are extremely high. We hypothesize that socioeconomic factors may represent significant barriers to SET completion. MethodsPatients with IC referred to SET at a multi-hospital, single-institution health care system (2018-2022) from a prospectively maintained database were retrospectively analyzed. Our primary endpoint was SET program completion and graduation, defined as completion of 36 sessions. Our secondary endpoints were vascular intervention within 1 year of referral and change in ankle-brachial index (ABI). Baseline demographics were assessed using standard statistical methods. Predictors of SET graduation were analyzed using multivariable logistic regression generating adjusted odds ratios (aORs) with 95% confidence intervals (CIs). Change in ABI was analyzed using t-test between subgroups. Reasons for attrition were tabulated. Patient Health Questionnaire-9 (PHQ-9), metabolic equivalent level, Vascular QOL, Duke Activity Status, and ABI were analyzed using paired t-tests across the entire cohort. ResultsFifty-two patients met inclusion criteria: mean age 67.85 ± 10.69 years, 19 females (36.54%), mean baseline ABI of 0.77 ± 0.16. The co-pays for 100% of patients were fully covered by primary and secondary insurance plans. Twenty-one patients (40.38%) completed SET. On multivariable analysis, residence in a ZIP code with median household income <$47,000 (aOR, 0.10; 95% CI, 0.01-0.76; P = .03) and higher body mass index (aOR, 0.81; 95% CI, 0.67-0.99; P = .04) were significant barriers to SET graduation. There were no differences in ABI change or vascular intervention within 1 year between graduates and non-graduates. Non-graduates reported transportation challenges (25.00%), lack of motivation (20.83%), and illness/functional limitation (20.83%) as primary reasons for SET attrition. Metabolic Equivalent Level (P ≤ .01) and Duke Activity Status scores (P = .04) were significantly greater after participating in a SET program. ConclusionsAlthough SET participation improves lower extremity and functionality outcomes, only 40% of referred patients completed therapy in our cohort. Our findings suggest that both socioeconomic and functional factors influence the odds of completing SET programs, indicating a need for holistic pre-referral assessment to facilitate enhanced program accessibility for these populations.

Abstract 12762: Plasma Lipidomic Signature of Peripheral Artery Disease in Young and Middle-Aged American Indian Individuals: The Strong Heart Family Study

Introduction: Dyslipidemia is an independent risk factor for peripheral artery disease (PAD). Ankle-brachial index (ABI) is a sensitive and cost-effective tool for screening and predicting PAD. The association between individual lipid species and the progression in subclinical PAD, assessed by change in ABI, remains to be determined, especially in understudied populations at high risk. Hypothesis: To identify individual molecular lipid species associated with PAD progression in American Indians, independent of traditional risk factors. Methods: Using an untargeted lipidomic method by liquid chromatography-mass spectrometry, we repeatedly measured 1,542 individual lipid species in 2,830 fasting plasma samples at two time points (2001-2003 and 2006-2009, mean 5 years apart) from 1,415 unique American Indians in the Strong Heart Family Study. Participants were free of prevalent PAD at both time points. ABI was measured in the right arm and bilateral (both left and right posterior tibial artery) using a handheld Doppler and was analyzed as a continuous variable. We first identified baseline lipid species associated with change in ABI by generalized estimating equation models, adjusting for baseline age, sex, BMI, smoking, eGFR, diabetes, hypertension, lipid-lowering medication and baseline ABI. We then examined the longitudinal association between change in lipid species and change in ABI, adjusting for same covariates plus baseline lipids. Results: Participants (63% female) were aged between 18-65 (mean 38) at baseline and 22-72 (mean 43) at follow-up. Higher baseline levels of 36 lipid species were positively (ORs: 1.01 - 3.60), whereas 16 lipid species were inversely (ORs: 0.26 - 0.98), associated with change in ABI. Longitudinal changes in 77 lipid species, largely glycerolipids, glycerophospholipids, and sphingolipids, were significantly associated with change in ABI during 5-year follow-up. Conclusions: Baseline plasma lipid species and their longitudinal changes over time are significantly associated with PAD progression beyond known risk factors. These findings shed light on the role of dyslipidemia in PAD among young and middle-aged American Indians who suffer high rates of obesity, diabetes and other cardiometabolic disorders.

Optimized drug-coated balloon angioplasty of the superficial femoral and proximal popliteal arteries using the Tack Endovascular System: Tack Optimized Balloon Angioplasty (TOBA) III 24-month results in standard and long lesions.

The Tack Endovascular System is a minimal-metal dissection repair device that is purpose-built to treat post-percutaneous angioplasty (PTA) arterial dissections in patients with peripheral arterial disease (PAD). The Tack Optimized Balloon Angioplasty (TOBA) III trial evaluated the safety and effectiveness of the Tack Endovascular System in patients with superficial femoral artery (SFA) and/or proximal popliteal artery (PPA) dissection after PTA with a drug-coated balloon (DCB). The objective of this study is to report the results in the standard- (SL) and long-lesion (LL) cohorts through 24 months. The TOBA III study was a prospective, multicenter, single-arm study including patients suffering from Rutherford category 2-4 PAD. Outcomes were assessed according to pre-specified lesion length in SL ( ≥ 20 mm and ≤150 mm) and LL ( > 150 mm and ≤250 mm) cohorts. Follow-up was through 24 months. TOBA III enrolled 201 patients, 169 patients in the SL cohort and 32 in the LL cohort. At 24 months, the Kaplan-Meier estimates of freedom from major adverse events were 91.7% and 82.6% for the SL cohort and LL cohort, respectively. Kaplan-Meier estimates of freedom from clinically driven-target lesion revascularization (CD-TLR) were 92.3% in the SL cohort and 82.6% in the LL cohort. At 24 months, 78.8% of SL patients and 69.2% of LL patients experienced an improvement of >2 Rutherford categories (both cohorts p < 0.001). The baseline ankle-brachial index improved from 0.68 ± 0.18 to 0.93 ± 0.16 in the SL (p < 0.001) and from 0.62 ± 0.23 to 0.87 ± 0.15 in the LL cohort (p < 0.001) at 24 months. The 24-month results of the TOBA III trial support the safety and effectiveness of the Tack Endovascular System in patients who required post-PTA dissection repair in the SFA and PPA following DCB angioplasty for claudication and rest pain. In both the SL and LL cohorts, Tack placement was associated with sustained freedom from CD-TLR through 24 months as well as sustained improvements in Rutherford categories, ankle-brachial index, and quality of life.

Towards noninvasive early detection and classification of peripheral arterial disease stenosis severity by perfusion dynamics and artificial intelligence

Abstract Introduction Recent guidelines suggest Ankle-Brachial Index (ABI) measurement for assessing and reducing cardiovascular risk. PAD patients suffer from generalized arterial stiffening (arteriosclerosis) and develop threatening arterial stenosis foci. ABI cannot differentiate between the two, and detecting focal stenosis is especially challenging in the elderly and diabetics suffering from severe arteriosclerosis. Thus, better diagnostic tools are required for early detection of severe arterial stenosis in order to improve patient management reduce atherosclerotic cardiovascular risk and amputation rates. Purpose We hypothesized that quantifying the peripheral perfusion dynamics would provide more sensitive indices for monitoring atherosclerotic disease severity. Thus, we compared the utility of ABI, impedance-plethysmography (IPG), and photoplethysmography (PPG) in detecting and classifying arterial-stenosis using machine learning and artificial intelligence. Methods Arterial stenosis was emulated in supine lying healthy consenting volunteers (n=31) by inflating a blood-pressure cuff around their thigh to 45 and 90 mmHg for six minutes. We quantified the perfusion dynamics by IPG and PPG signal analyses in the time-frequency domain. The induced stenosis levels were classified by artificial intelligence using novel indices. Results Hallux O2-saturation remained intact (96±3%, p=0.4) even during 90 mmHg thigh-cuff compression. The baseline ABI (1.19±0.01) remained unchanged during 45 mmHg compression, slightly declined (1.12±0.02) upon 90 mmHg compression; but, all ABI values were above the 0.9 threshold. The pulse transit time, a well-established index of arteriosclerosis, remained unchanged. Conversely, upon stenosis emulation (compression), the IPG immediately recorded a significant proportional phase delay between the compressed and contralateral legs and a significant proportional correlation decline. At baseline, the IPG phase-difference between legs over the 2–4 Hz band was 1.79±0.48° and grew to 29.5±2.4° and 71.2±1.8° upon 45 and 90 mmHg compression (p&amp;lt;0.001). The IPG inter leg correlation at the 4–6 Hz band declined from 0.962±0.005 at baseline to 0.857±0.012 and 0.676±0.015 during 45 and 90 mmHg compression (p&amp;lt;0.001). The PPG phase difference grew significantly and proportionally upon compression (p&amp;lt;0.001, n=28) but without a significant correlation decline. A neural-network classifier achieved 100% accuracy in classifying baseline and each compression level based on the IPG phase and correlation. The best classifier achieved only 81.25% accuracy, 83.33% sensitivity, and 90% Specificity based on the PPG. Conclusion Our perfusion-dynamic indices outperformed the ABI, and the IPG outperformed the PPG in detecting and classifying emulated stenosis. Differentiation between arteriosclerosis and arterial stenosis may be of immense clinical merit. Therefore, this simple, noninvasive method merits clinical evaluation. Funding Acknowledgement Type of funding sources: None.

Course of ankle-brachial-index 12 months after intravascular lithotripsy in calcified peripheral lesions

Abstract Background Intravascular lithotripsy (IVL) is a relatively novel treatment option for calcified lesions in peripheral artery disease. Little is known about the mid to long-term functional status of the patients and target lesion revascularization rate (TLR) after IVL only procedure. Purpose To evaluate the course of ankle-brachial-index (ABI) and to assess the rate of revascularization 1 year after intravascular lithotripsy performed on calcified peripheral lesions. Methods Between December 2018 and January 2021 IVL was performed on 61 limbs of 51 patients presenting with Rutherford classes 2–5. Ankle-brachial-index (ABI) was documented before the procedure as well as 1 day, 6 months and 1 year after the procedure within a single center real-life registry. Further endpoint was revascularization with PTA or peripheral bypass surgery. The vast majority of cases were done as IVL only procedure (58%) All procedures were done in upper leg/pelvic stenosis. Results ABI measurement after 12 months was done in 42 of 51 patients (82%). Three pts were missed due to media sclerosis. Due to loss of follow-up, ABI after 6 months could not be performed on 4/61 patients (7,8%) and 12-month-ABI in another 8/51 cases (15,6%). Initial baseline ABI of 0.6±0.26 before the procedure increased to 0.8±0.25 (p&amp;lt;0.0001) one day afterward. After 6 months, the ABI of 0.8±0.27 (n=49; p&amp;lt;0.0001) was still significantly improved compared to baseline. After 1 year, ABI with 0.7±0.22 was still improved, however not significantly different from baseline (Figure 1). Target lesion revascularization was needed in 7 patients (13%), 4 with subsequent IVL, 3 with PTA and 2 with peripheral bypass surgery. Conclusions In our large single center registry, IVL performed mainly as a stand-alone procedure was safe and effective even after a mid-term follow up. TLR was necessary in 13%, which is lower than in previous published IVL data (20,7% as in DISRUPT-PAD-II) [1]. ABI after 12 months improved but did maintain statistical significance, compared with other procedure like scoring balloon [2]. Funding Acknowledgement Type of funding sources: None.

Predictive Value of the Ankle-Brachial Index for All-Cause and Cardio-Cerebrovascular Mortality.

The present study explored the relationship between the ankle-brachial index (ABI) (>.9) and all-cause or cardio-cerebrovascular mortality. Participant details were obtained from the National Health and Nutrition Examination Survey 1999-2004. The association between baseline ABI and the risk of mortality was evaluated by a priori defined quartile categories and on a continuous scale (per .1-unit change) with Cox regression models adjusted for demographic and traditional risk factors. A total of 7087 individuals (age: 59.6 ± 12.8years) were included; 3612 (51.0%) were male. After an average follow-up of 12.2 years, 1926 deaths occurred. Kaplan-Meier analysis showed that the lowest ABI quartile (<1.06) was associated with the highest risk of all-cause, cardio-cerebrovascular and cancer mortality (all P < .001). However, after adjusting for potential confounders, ABI ranging between 1.06 and 1.12 was associated with the lowest risk of all-cause mortality (hazard ratio .88, 95% confidence interval .78-1.00, P < .05) compared with the reference group (<1.06). Besides, splines showed the relationship was nonlinear (P < .05) and the inflection point was 1.11. In conclusion, the level of ABI associated with the lowest risk of all-cause mortality was 1.11, under which a lower ABI was independently associated with an increased risk of all-cause mortality.

487-P: Posttranslational Modifications of Apolipoproteins C-I, C-II, and C-III and Peripheral Artery Disease in Multiethnic Study of Atherosclerosis (MESA)

Apolipoproteins (apo) C-I, C-II and C-III in circulation are in several post-translational forms with distinct effects on lipoprotein metabolism. ApoC-I and apoC-II exist as dominant native and minor truncated (C-I’; C-II’) forms; apoC-III appears as unglycosylated (C-III0a) , or glycosylated with zero (C-III0b) , one (C-III1, most abundant) or two (C-III2) sialic acids. The association of these proteoforms with peripheral artery disease (PAD) in a general population is unstudied. Total apoC-I, C-II and C-III concentrations and relative amounts of their proteoforms were measured in baseline plasma of 5,681 MESA participants. The ankle-brachial index (ABI) was assessed at baseline, 3 and years. Prevalent PAD was defined as baseline ABI ≤ 0.9. Incident PAD was follow-up ABI ≤ 0.9 or a hospital-based diagnosis of PAD to include revascularization. After adjustment for baseline characteristics, lipid lowering therapy and plasma lipids, low baseline ABI was associated with low C-III0b to C-III1 ratio (C-III0b/III1, p=0.01) and high C-III2 to C-III1 ratio (C-III2/III1, p&amp;lt;0.01) . Prevalent PAD (n=226) was only associated with C-III2/III1 (OR 1.16, 95% CI: 1.01-1.33, p=0.03) . Lower ABI at follow-up was associated with lower C-III0b/III1 and higher C-III2/III1 at baseline (p&amp;lt;0.both) . Incident PAD (n=244) was associated with C-III2/III1 (HR 1.22, 1.06-1.41, p=0.01) . Total apoC-I, C-II and C-III concentrations, or apoC-I and C-II truncations were not associated with ABI at baseline and follow-up, or with cross-sectional and prospective PAD determinations. ApoC-I and apoC-II and their truncations do not appear linked with PAD. In contrast, we find different associations of apoC-III0b and apoC-III2 with prevalent and incident PAD that are independent of other risk factors, including plasma lipids. Our data provide further support that proteoforms may have unique properties not captured by “total” apolipoprotein measures. Disclosure P.Reaven: Research Support; AstraZeneca, Dexcom, Inc. J.Koska: None. S.Hansen: None. Y.Hu: None. J.Furtado: Research Support; Eli Lilly and Company, Pfizer Inc. S.Sinari: None. D.Billheimer: None. D.Nedelkov: None. M.Budoff: Research Support; Amarin Corporation, Novo Nordisk, Speaker's Bureau; Boehringer Ingelheim International GmbH, Lilly. R.Mcclelland: None. Funding National Institutes of Health (R01-HL138969)

Serum metabolomic profiles associated with subclinical and clinical cardiovascular phenotypes in people with type 2 diabetes

BackgroundAtherosclerotic cardiovascular diseases (CVD) is the leading cause of death in diabetes, but the full range of biomarkers reflecting atherosclerotic burden and CVD risk in people with diabetes is unknown. Metabolomics may help identify novel biomarkers potentially involved in development of atherosclerosis. We investigated the serum metabolomic profile of subclinical atherosclerosis, measured using ankle brachial index (ABI), in people with type 2 diabetes, compared with the profile for symptomatic CVD in the same population.MethodsThe Edinburgh Type 2 Diabetes Study is a cohort of 1,066 individuals with type 2 diabetes. ABI was measured at baseline, years 4 and 10, with cardiovascular events assessed at baseline and during 10 years of follow-up. A panel of 228 metabolites was measured at baseline using nuclear magnetic resonance spectrometry, and their association with both ABI and prevalent CVD was explored using univariate regression models and least absolute shrinkage and selection operator (LASSO). Metabolites associated with baseline ABI were further explored for association with follow-up ABI and incident CVD.ResultsMean (standard deviation, SD) ABI at baseline was 0.97 (0.18, N = 1025), and prevalence of CVD was 35.0%. During 10-year follow-up, mean (SD) change in ABI was + 0.006 (0.178, n = 436), and 257 CVD events occurred. Lactate, glycerol, creatinine and glycoprotein acetyls levels were associated with baseline ABI in both univariate regression [βs (95% confidence interval, CI) ranged from − 0.025 (− 0.036, − 0.015) to − 0.023 (− 0.034, − 0.013), all p < 0.0002] and LASSO analysis. The associations remained nominally significant after adjustment for major vascular risk factors. In prospective analyses, lactate was nominally associated with ABI measured at years 4 and 10 after adjustment for baseline ABI. The four ABI-associated metabolites were all positively associated with prevalent CVD [odds ratios (ORs) ranged from 1.29 (1.13, 1.47) to 1.49 (1.29, 1.74), all p < 0.0002], and they were also positively associated with incident CVD [ORs (95% CI) ranged from 1.19 (1.02, 1.39) to 1.35 (1.17, 1.56), all p < 0.05].ConclusionsSerum metabolites relating to glycolysis, fluid balance and inflammation were independently associated with both a marker of subclinical atherosclerosis and with symptomatic CVD in people with type 2 diabetes. Additional investigation is warranted to determine their roles as possible etiological and/or predictive biomarkers for atherosclerotic CVD.

Ankle-Brachial Index and Energy Production in People Without Peripheral Artery Disease: The BLSA.

BackgroundLower ankle‐brachial index (ABI) values within the 0.90 to 1.40 range are associated with poorer mitochondrial oxidative capacity of thigh muscles in cross‐sectional analyses. Whether ABI decline is associated with greater declines in thigh muscle oxidative capacity with aging is unknown.Method and ResultsWe analyzed data from 228 participants (100 men) of the BLSA (Baltimore Longitudinal Study of Aging), aged 39 to 97 years, with an ABI between 0.9 and 1.40 at baseline and at follow‐up (mean follow‐up period of 2.8 years). We examined mitochondrial oxidative capacity of the left thigh muscle, by measuring the postexercise phosphocreatine recovery rate constant (kPCr) from phosphorus‐31 magnetic resonance spectroscopy. Greater kPCr indicated higher mitochondrial oxidative capacity. Although kPCr was available on the left leg only, ABI was measured in both legs. Longitudinal rates of change (Change) of left and right ABI and kPCr of the left thigh muscle were estimated using linear mixed effects models, and their association was analyzed by standardized multiple linear regressions. In multivariate analysis including sex, age, baseline kPCr, both left and right baseline ABI, and ABI change in both legs, (kPCr)Change was directly associated with ipsilateral (left) (ABI)Change (standardized [STD]‐β=0.14; P=0.0168) but not with contralateral (right) (ABI)Change (P=0.22). Adjusting for traditional cardiovascular risk factors, this association remained significant (STD‐β=0.18; P=0.0051). (kPCr)Change was steeper in White race participants (STD‐β=0.16; P=0.0122) and body mass index (STD‐β=0.13; P=0.0479). There was no significant association with current smoking status (P=0.63), fasting glucose (P=0.28), heart rate (P=0.67), mean blood pressure (P=0.78), and low‐density lipoprotein (P=0.75), high‐density lipoprotein (P=0.82), or triglycerides (P=0.15).ConclusionsIn people without peripheral arterial disease, greater decline in ABI over time, but not baseline ABI, was associated with faster decline in thigh mitochondrial oxidative capacity in the ipsilateral leg. Further studies are needed to examine whether early interventions that improve lower extremity muscle perfusion can improve and prevent the decline of muscle energetics.

Ankle brachial indices and anaerobes: is peripheral arterial disease associated with anaerobic bacteria in diabetic foot ulcers?

Background:Lower extremity amputations from diabetic foot ulcers (DFUs) are rebounding, and new biomarkers that predict wound healing are urgently needed. Anaerobic bacteria have been associated with persistent ulcers and may be a promising biomarker beyond currently recommended vascular assessments. It is unknown whether anaerobic markers are simply a downstream outcome of peripheral arterial disease (PAD) and ischemia, however. Here, we evaluate associations between two measures of anaerobic bacteria—abundance and metabolic activity—and PAD.Methods:We built a prospective cohort of 37 patients with baseline ankle brachial index (ABI) results. Anaerobic bacteria were measured in two ways: DNA-based total anaerobic abundance using 16S rRNA gene amplicon sequencing and resulting summed relative abundance, and RNA-based metabolic activity based on bacterial read annotation of metatranscriptomic sequencing. PAD was defined three ways: PAD diagnosis, ABI results, and a dichotomous definition of mild ischemia (versus normal) based on ABI values. Statistical associations between anaerobes and PAD were evaluated using univariate odds ratios (ORs) or Spearman’s correlations.Results:Total anaerobe abundance was not significantly associated with PAD diagnosis, ABI results, or mild ischemia (ORPAD = 0.47, 95% CI = 0.023–7.23, p = 0.60; Spearman’s correlation coefficientABI = 0.24, p = 0.17; ORmild ischemia = 0.25, 95% CI = 0.005–5.86, p = 0.42). Anaerobic metabolic activity was not significantly associated with PAD diagnosis, ABI results, or mild ischemia (ORPAD = 1.99, 95% CI = 0.17–21.44, p = 0.57; Spearman’s correlation coefficientABI = 0.12, p = 0.52; ORmild ischemia = 0.90, 95% CI = 0.03–15.16, p = 0.94).Conclusion:Neither anaerobic abundance nor metabolic activity was strongly associated with our three definitions of PAD. Therefore, anaerobic bacteria may offer additional prognostic value when assessing wound healing potential and should be investigated as potential molecular biomarkers for DFU outcomes.

Effects of a 16-week physical training on clinical outcomes in patients with hypertension and chronic kidney disease: NEPHROS post-trial follow-up.

The NEPHROS is a randomized controlled trial which applied a 16-week aerobic and resistance training to patients with chronic kidney disease (CKD) and high blood pressure. This report describes a long-term post-trial follow-up, comparing survival, health-related quality of life (HRQoL), and estimated glomerular filtration rate (GFR) change between the intervention and control groups according to in-trial cardiovascular risk factors. Three years after the original trial, NEPHROS participants were re-evaluated. Cox proportional hazards model was used to compare survival time and linear regression for changes in GFR and physical and mental HRQoL summary scores between intervention and control groups according to age, sex, and in-trial GFR, C-reactive protein, glucose, lipids, ankle-brachial index (ABI), functional capacity, and blood pressure. Of the 150 participants of NEPHROS, 128 were included in the long-term analysis. The previous exercise training had no effects on survival, GFR, or HRQoL. Baseline in-trial GFR (HR = 0.95, 95%CI: 0.92; 0.98) and ABI (HR = 0.03, 95%CI: 0.002; 0.43) were positive independent predictors for survival. Lower ABI (coefficient = 9.00, 95%CI: 0.43; 17.5) and higher systolic blood pressure (coefficient = -0.13, 95%CI: -0.24; -0.03) were independent predictors for GFR decline. A 16-week exercise program had no long-term effect on survival, quality of life, or glomerular filtration in patients with CKD stages 2 to 4. Lower GFR and ABI and higher systolic blood pressure were associated with poorer prognosis among CKD patients.

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.

Reduction in Acute Limb Ischemia With Rivaroxaban Versus Placebo in Peripheral Artery Disease After Lower Extremity Revascularization: Insights From VOYAGER PAD.

Patients with peripheral artery disease (PAD) are at heightened risk of acute limb ischemia (ALI), a thrombotic event associated with amputation, disability, and mortality. Previous lower extremity revascularization (LER) is associated with increased ALI risk in chronic PAD. However, the pattern of risk, clinical correlates, and outcomes after ALI early after LER are not well-studied, and effective therapies to reduce ALI post-LER are lacking. The VOYAGER PAD trial (Vascular Outcomes Study of ASA [Acetylsalicylic Acid] Along With Rivaroxaban in Endovascular or Surgical Limb Revascularization for PAD; rNCT02504216) randomized patients with PAD undergoing LER to rivaroxaban 2.5 mg twice daily or placebo on a background of low-dose aspirin. The primary outcome was a composite of ALI, major amputation of vascular cause, myocardial infarction, ischemic stroke, or cardiovascular death. ALI was prospectively ascertained and adjudicated by a blinded committee. The cumulative incidence of ALI was calculated using Kaplan-Meier estimates, and Cox proportional hazards models were used to generate hazard ratios and associated CIs. Analyses were performed as intention-to-treat. Among 6564 patients followed for a median of 2.3 years, 382 (5.8%) had a total of 508 ALI events. In placebo patients, the 3-year cumulative incidence of ALI was 7.8%. After multivariable modeling, previous LER, baseline ankle-brachial index <0.50, surgical LER, and longer target lesion length were associated with increased risk of ALI. Incident ALI was associated with subsequent all-cause mortality (hazard ratio [HR], 2.59 [95% CI, 1.98-3.39]) and major amputation (HR, 24.87 [95% CI, 18.68-33.12]). Rivaroxaban reduced ALI relative to placebo by 33% (absolute risk reduction, 2.6% at 3 years; HR, 0.67 [95% CI, 0.55-0.82]; P=0.0001), with benefit starting early (HR, 0.45 [95% CI, 0.24-0.85]; P=0.0068 at 30 days). Benefit was present for severe ALI (associated with death, amputation, or prolonged hospitalization and intensive care unit stay, HR, 0.58 [95% CI, 0.40-0.83]; P=0.003) and regardless of LER type (surgical versus endovascular revascularization, P interaction=0.42) or clopidogrel use (P interaction=0.59). After LER for symptomatic PAD, ALI is frequent, particularly early after LER, and is associated with poor prognosis. Low-dose rivaroxaban plus aspirin reduces ALI after LER, including ALI events associated with the most severe outcomes. The benefit of rivaroxaban for ALI appears early, continues over time, and is consistent regardless of revascularization approach or clopidogrel use.

Ankle-Brachial Index for Risk Stratification in Patients With Symptomatic Peripheral Artery Disease With and Without Prior Lower Extremity Revascularization: Observations From the EUCLID Trial.

[Figure: see text].

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.

Isolated low toe-brachial index is associated with increased mortality and morbidity: a retrospective cohort study.

The aim was to assess the prognostic impact of perfusion assessments including ankle-brachial Index (ABI) and toe-brachial Index (TBI) on survival of patients who present with diabetic foot ulceration and to analyse clinical outcomes when patients are categorised into three levels of limb ischaemia. This was a retrospective cohort analysis of consecutive patients presenting with foot ulceration. Patients continued with their standard of care, after having baseline assessments of limb perfusion. Patients were retrospectively categorised into three groups according to baseline ABI and TBI: Group 1 (n=31) non-ischaemic (TBI≥0.75, ABI≥0.9), Group 2 (n=67) isolated low TBI with foot ischaemia (TBI<0.75, ABI≥0.90) and Group 3 (n=30) foot-leg ischaemia (TBI<0.75, ABI<0.90). A total of 128 patients took part in the study. Low TBI was associated with a significant decrease in patient survival (42±20 versus 51±16 months, p=0.011). There was a progressive and significant decline in mean patient survival time (51±16 versus 44±20 versus 39±22 months, respectively, for ANOVA across the three groups, p=0.04). Patients with isolated low TBI had angioplasty and bypass at a rate similar to that of patients in Group 3 (low ABI and low TBI). The proportion of angioplasties was significantly higher in the isolated low TBI (19.4% (13/67) versus the non-ischaemic 3.2% (1/31), p=0.033). Such revascularisation resulted in ulcer healing within the foot ischaemic group that was similar to the non-ischaemic group (68% versus 60% over 12 months, p=0.454). Regardless of ABI level, measurement of TBI identifies patients with isolated low TBI who require specialised care pathways and revascularisation to achieve ulcer healing that is similar to non-ischaemic patients.

Change in ankle–brachial index and mortality among individuals with chronic kidney disease: findings from the Chronic Renal Insufficiency Cohort Study

Patients with chronic kidney disease (CKD) have an increased risk of peripheral arterial disease (PAD). The ankle-brachial index (ABI), a noninvasive measure of PAD, is a predictor of adverse events among individuals with CKD. In general populations, changes in ABI have been associated with mortality, but this association is not well understood among patients with CKD. We conducted a prospective study of 2920 participants in the Chronic Renal Insufficiency Cohort Study without lower extremity revascularization or amputation at baseline and with at least one follow-up ABI measurement (taken at annual visits) during the first 4 years of follow-up. The ABI was obtained by the standard protocol. In Cox proportional hazard regression analyses, we found a U-shaped association of average annual change in ABI with all-cause mortality. After adjusting for baseline ABI and other covariates, compared with participants with an average annual change in ABI of 0-<0.02, individuals with an average annual change in ABI <-0.04 or ≥0.04 had multivariable-adjusted hazard ratios (HRs) of 1.81 [95% confidence interval (CI) 1.34-2.44) and 1.42 (95% CI 1.12-1.82) for all-cause mortality, respectively. Compared with the cumulative average ABI of 1.0-<1.4, multivariable-adjusted HRs for those with a cumulative average ABI of <0.9, 0.9-<1.0 and ≥1.4 were 1.93 (95% CI 1.42-2.61), 1.20 (0.90-1.62) and 1.31 (0.94-1.82), respectively. This study indicates both larger decreases and increases in average annual changes in ABI (>0.04/year) were associated with higher mortality risk. Monitoring changes in ABI over time may facilitate risk stratification for mortality among individuals with CKD.