Peripheral Arterial Disease Group Research Articles

Association of lower extremity peripheral arterial disease with quantitative muscle features from computed tomography angiography

ObjectivesTo explore the association between lower extremity muscle features from CTA and peripheral arterial disease (PAD) severity using digital subtraction angiography (DSA) as reference standard.MethodsInformed consent was waived for this Institutional Review Board approved retrospective study. PAD patients were recruited from July 2016 to September 2020. Two radiologists evaluated PAD severity on DSA and CTA using runoff score. The patients were divided into two groups: mild PAD (DSA score ≤ 7) vs. severe PAD (DSA score > 7). After segmenting lower extremity muscles from CTA, 95 features were extracted for univariable analysis, logistic regression model (LRM) analysis, and sub-dataset analysis (PAD prediction based on only part of the images). AUC of CTA score and LRMs for PAD prediction were calculated. Features were analyzed using Student’s t test and chi-squared test. p < 0.05 was considered statistically significant.ResultsA total of 56 patients (69 ± 11 years; 38 men) with 56 lower legs were enrolled in this study. The lower leg muscles of mild PAD group (36 patients) showed higher CT values (44.6 vs. 39.5, p < 0.001) with smaller dispersion (35.6 vs. 41.0, p < 0.001) than the severe group (20 patients). The AUC of CTA score, LRM-I (constructed with muscle features), and LRM-II (constructed with muscle features and CTA score) for PAD severity prediction were 0.81, 0.84, and 0.89, respectively. The highest predictive performance was observed in the image subset of the middle and inferior segments of lower extremity (LRM-I, 0.83; LRM-II, 0.90).ConclusionsLower extremity muscle features are associated with PAD severity and can be used for PAD prediction.Critical relevance statementQuantitative image features of lower extremity muscles are associated with the degree of lower leg arterial stenosis/occlusion and can be a beneficial supplement to the current imaging methods of vascular stenosis evaluation for the prediction of peripheral arterial disease severity.Key points• Compared with severe PAD, lower leg muscles of mild PAD showed higher CT values (39.5 vs. 44.6, p < 0.001).• Models developed with muscle CT features had AUC = 0.89 for predicting PAD.• PAD severity prediction can be realized through the middle and inferior segment of images (AUC = 0.90).Graphical

Prognostic impact of peripheral artery disease in patients with and without high bleeding risk undergoing percutaneous coronary intervention.

Peripheral artery disease (PAD) is associated with worse outcomes after percutaneous coronary intervention (PCI). The aim of this study was to assess the prognostic impact of PAD according to high bleeding risk (HBR) status. Consecutive patients undergoing PCI with drug-eluting stent implantation at a tertiary-care center (Mount Sinai Hospital) between 2012 and 2019 were stratified according to HBR and PAD status. The primary outcome was major adverse cardiac events (MACE), a composite of all-cause death, myocardial infarction (MI), and stroke 1 year after PCI. Secondary outcomes included major bleeding. Out of 16,750 patients, 43% were HBR and 57% were no-HBR. Within the two groups, PAD patients were 14% and 6%, respectively, and were more likely to have comorbidities and to undergo complex PCI than no-PAD patients. Within the HBR group, PAD was associated with an increased risk of MACE (11.4% vs. 7.3%, hazard ratio [HR]: 1.59, 95% confidence interval [CI]: 1.27-1.99, p < 0.001) and a numerical nonsignificant increase of major bleeding (8.5% vs. 6.9%, HR: 1.25, 95% CI: 0.98-1.59, p = 0.066) as compared with no-PAD. Among no-HBR patients, rates of MACE and major bleeding were numerically but not significantly higher in the PAD group. After multivariable adjustment, PAD was no longer a predictor of adverse outcomes, irrespective of HBR status. At 1-year after PCI, PAD was associated with increased 1-year risks of MACE in HBR patients. After adjustment for cardiovascular risk factors and comorbidities, the effect of PAD on adverse events was largely attenuated.

Evaluation of Cardiovascular Risk in Patients with Type 1 Diabetes: How Ankle Brachial Index Can Be Usefull?

Background: Patients with type 1 diabetes (T1D) face a significantly higher mortality risk compared to the general population, primarily due to elevated rates of cardiovascular disease (CVD). Detecting cardiovascular disease at its preclinical stage is essential for effective primary prevention in this relatively young population. This study aims to assess the link between steno-risk and subclinical atherosclerotic disease, as detected by the Ankle-Brachial Index (ABI), in T1D patients and determine the prevalence of these abnormalities among them. Methods: A cohort of 312 adults with T1D (151 males and 161 females, mean age 31 ± 12 years) was examined. Patients were categorized based on their ABI values (ABI &lt; 0.9 indicating peripheral arterial disease (PAD), ABI ≥ 1.3 indicating arterial calcification (AC), and ABI between 0.9 and 1.3 indicating normal ABI). The study analyzed the relationship between ABI anomalies and cardiovascular risk factors and their association with the steno-risk category. Results: Among the patients, 138 (44.2%) had a normal ABI, 112 (35.9%) had PAD, and 62 (19.9%) had AC. AC was more prevalent in men than in women (p = 0.006). A family history of stroke was common in both the PAD and AC groups (p = 0.042 and p = 0.046, respectively). Patients with AC were often older (36 ± 13 vs. 30 ± 12; P = .012), had a longer duration of diabetes (20 ± 11 vs. 14 ± 9; P &lt; 0.001), a higher prevalence of hypertension (25.8% vs. 14.5%, P = 0.05), and a higher prevalence of smoking (19.3% vs. 9.4%, P = 0.046). A higher number of subjects with AC were found in the Steno-Risk 10–20% and Steno-Risk ≥20% categories compared to the Steno-Risk &lt; 10% (37.5 vs. 15.5; 29 vs. 15.5, p = 0.0106, respectively). Conclusion: This study demonstrates that an ABI &gt; 1.30 is more common in older patients with type 1 diabetes and is associated with a longer duration of diabetes, male gender, smoking, hypertension, and a family history of stroke. Furthermore, an ABI &gt; 1.30, indicating arterial calcification, is significantly linked to moderate and high cardiovascular risk assessed by steno-risk in patients with type 1 diabetes. The ABI may serve as a straightforward tool for screening atherosclerosis in T1D.

Near-infrared spectroscopy with a provocative maneuver to detect the presence of severe peripheral arterial disease

Current assessment standards for peripheral arterial disease (PAD), such as the ankle brachial index, are limited in their utility and portability. Near-infrared spectroscopy (NIRS) has shown some promise in diagnosing PAD when used in conjunction with a provocative maneuver. The purpose of this study was to assess the viability of NIRS in conjunction with a transient leg elevation provocative maneuver for detecting severe PAD. This retrospective observational cross-sectional study assessed 57 limbs in 34 patients receiving routine vascular screening for PAD at Madigan Army Medical Center. The patient limbs were stratified into normal (n = 17), mild (n = 9), moderate (n = 16), and severe (n = 15) PAD groups based on the clinician assessments. Additionally, the patients were assessed with NIRS measurements taken with the patient in the supine position at rest and using a provocative leg raise maneuver of transient leg elevation of 45° for 60 seconds. The resting tissue oxygen saturation (StO2) and the change in StO2 (ΔStO2) from rest to elevation were recorded and compared between the PAD severity groups via independent measures analysis of variance with the Tukey honest significant difference post hoc test. The supine resting StO2 was not different between the normal (77.5% ± 7.7%), mild (72.5% ± 7.4%), moderate (72.0% ± 10.3%), and severe (74.2% ± 5.4%) PAD groups (P = .23). However, the ΔStO2 with transient leg elevation was significantly greater in the severe PAD group (−17.2% ± 6.0%) compared with the normal (−3.9% ± 4.8%), mild (−6.9% ± 4.7%), and moderate (−9.7% ± 5.2%) PAD groups (P < .002 for all). Similar results were observed in the changes in oxyhemoglobin and deoxyhemoglobin. The leg elevation protocol was also used for two patients before and after lower limb revascularization, which demonstrated that the ΔStO2 corresponded with the clinical assessment of PAD severity. Resting supine NIRS images were unable to detect any differences among normal and limbs with different PAD severity. However, NIRS imaging with 45° leg elevation for 60 seconds showed a significant difference between severe PAD compared healthy patients and those with mild to moderate PAD in a fast, precise, and accurate manner. These preliminary data support the use of NIRS and transient leg elevation as a tool to diagnose severe PAD but do not support the use of NIRS alone as a screening test for PAD. NIRS measurements with leg elevation might be a viable noninvasive, noncontact, and portable method of assessing severe PAD for home monitoring, in rural communities, and/or in standard clinical practice.

Trainability for cardiopulmonary fitness is low in patients with peripheral artery disease.

In patients with peripheral arterial disease (PAD), exercise therapy is recommended to relieve leg symptoms, as noted in the 2016 AHA/ACC and 2017 ESC/ESVS guidelines. We assessed the trainability for cardiopulmonary fitness (CPF) and quality of life (QOL); three distinct patient types, namely, PAD, heart failure (HF), and stroke, were compared. This is a multicentre, retrospective analysis of prospectively collected data from three clinical studies. Data collected from 123 patients who completed 36 sessions of supervised aerobic training of moderate intensity were analysed, with 28 PAD, 55 HF, and 40 stroke patients totalling 123. Before and after training, cardiopulmonary exercise testing with non-invasive cardiac output monitoring and QOL evaluation using a 36-Item Short Form Survey (SF-36) were performed. Non-response was defined as a negative change in the post-training value compared with that in the pre-training value. The result showed an improvement in CPF in all three groups. However, cardiorespiratory fitness (CRF) increased by a lesser extent in the PAD group than in the HF and stroke groups; the physical and mental component scores (MCS) of SF-36 exhibited a similar pattern. Non-response rates of peak V˙O2, oxygen uptake efficiency slope, and MCS were higher in the PAD group. In the PAD group, non-responders regarding peak V˙O2 had a higher pulse wave velocity than responders. In patients with PAD following exercise therapy, CRF and QOL improved to a lesser extent on average; their non-response rate was also higher compared with that of HF or stroke patients. Therefore, a higher dose of exercise might be needed to elicit adaptation in PAD patients, especially those with high pulse wave velocity.

LOX-1 rs1050283 TT genotype is associated with the severity of peripheral artery disease: a cross-sectional study in Mataram, Indonesia

Background: Peripheral arterial disease (PAD) is an important consequence of atherosclerosis commonly determined based on the results of ankle-brachial index (ABI) measurements. Due to its limitations, the search for potential predictors of PAD severity is ongoing. Serum soluble Lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) levels and LOX-1 polymorphism rs1050283 are candidates for predictors of PAD severity. This study aimed to investigate the association between the LOX-1 rs1050283 TT genotype and the severity of PAD. Methods: This cross-sectional study involved PAD patients recruited consecutively. The patients were genotyped for rs1050283 (3’ UTR C&gt;T) LOX-1 single nucleotide polymorphism using the sequencing method. Serum sLOX-1 levels were measured using ELISA. Data on ABI were collected, and the patients were categorized into mild and moderate to severe PAD groups. Results: A total of 66 PAD patients with a mean age of 58.9 years participated in this study, which consisted of 45 patients with mild PAD and 21 patients with moderate to severe PAD. Multivariate logistic regression analysis showed that the TT genotype was associated with PAD severity compared to those with the CC genotype (odds ratio (OR): 15.0, 95% confidence intervals (CI): 1.1 – 209.0), while higher serum sLOX-1 levels were not. PAD severity was also associated with increasing age (OR: 5.7, 95% CI: 1.3 – 25.7) and male gender (OR: 6.0, 95% CI: 1.1 – 32.2). Conclusion: TT genotype of LOX-1 rs1050283 polymorphism was associated with PAD severity, whereas higher serum sLOX-1 levels were not. In addition, increasing age and male gender were also associated with PAD severity.

Ortalama Trombosit Hacmi/Trombosit Sayısı (MPV/PLT Oranı ile Periferik Arter Hastalığı Arasındaki İlişki

Background/Aim: In our study, we aimed to evaluate the effect of mean platelet volume/platelet count ratio on the development of peripheral artery disease (PAD) by comparing it with the control group. Material and Methods: A total of 115 patients with peripheral artery disease as a result of lower extremity color Doppler ultrasonography examination in our hospital were included in the study as the patient group and 100 individuals without peripheral artery disease as the control group. Results: History of coronary artery disease (p&amp;lt;0.001), diabetes mellitus (p=0.009), hypertension (p&amp;lt;0.001) and smoking history (p&amp;lt;0.001) were significantly higher in the PAD group than in the control group. Serum glucose (121.27±25.66 vs. 104.81±34.77; p&amp;lt;0.001), MPV levels (9.99±0.79 vs. 9.04±0.7; p&amp;lt;0.001) and MPV/PLT ratio (0.041±0.07 vs. 0.037±0.006, p&amp;lt; 0.001) were found to be significantly higher in the PAD group than in the control group. Serum HDL levels (45.03±11.5 vs. 48.67±12.52 p=0.026) were significantly lower in the PAD group than in the control group. In multivariate analysis, age, MPV and MPV/PLT ratio were determined as independent predictors for peripheral arterial disease. Conclusion: In our study, we found that MPV and MPV/PLT ratio were independent predictors of peripheral artery disease.

Maximal calf conductance is associated with 6-minute walk distance in participants with and without peripheral artery disease.

The aims were (a) to compare the maximal calf conductance and 6-minute walk distance of participants with and without peripheral artery disease (PAD) and claudication, (b) to determine whether maximal calf conductance was more strongly associated with 6-minute walk distance in participants with PAD than in the controls, and (c) to determine whether this association was significant in participants with PAD after adjusting for ABI, as well as for demographic, anthropometric, and comorbid variables. Participants with PAD (n = 633) and without PAD (n = 327) were assessed on maximal calf conductance using venous occlusion plethysmography, and on 6-minute walk distance. Participants were further characterized on ABI, and on demographic, anthropometric, and comorbid variables. The PAD group had lower maximal calf conductance than the control group (0.136 ± 0.071 vs 0.201 ± 0.113 mL/100 mL/min/mmHg, p < 0.001). Additionally, the PAD group had a lower 6-minute walk distance (375 ± 98 m vs 480 ± 107 m, p < 0.001). Maximal calf conductance was positively associated with 6-minute walk distance in both groups (p < 0.001) and was more strongly associated in the PAD group (p < 0.001). In adjusted analyses, maximal calf conductance remained positively associated with 6-minute walk distance in the PAD group (p < 0.001) and in the control group (p < 0.001). Participants with PAD and claudication had impaired maximal calf conductance and a lower 6-minute walk distance than those without PAD, and maximal calf conductance was positively and independently associated with 6-minute walk distance within each group before and after adjusting for ABI, and for demographic, anthropometric, and comorbid variables.

Assessment of chronic limb threatening ischemia using thermal imaging

ObjectivesCurrent chronic limb threatening ischemia (CLTI) diagnostics require expensive equipment, using ionizing radiation or contrast agents, or summative surrogate methods lacking in spatial information. Our aim is to develop and improve contactless, non-ionizing and cost-effective diagnostic methods for CLTI assessment with high spatial accuracy by utilizing dynamic thermal imaging and the angiosome concept. ApproachDynamic thermal imaging test protocol was suggested and implemented with a number of computational parameters. Pilot data was measured from 3 healthy young subjects, 4 peripheral artery disease (PAD) patients and 4 CLTI patients. The protocol consists of clinical reference measurements, including ankle- and toe-brachial indices (ABI, TBI), and a modified patient bed for hydrostatic and thermal modulation tests. The data was analyzed using bivariate correlation. ResultsThe thermal recovery time constant was on average higher for the PAD (88%) and CLTI (83%) groups with respect to the healthy young subjects. The contralateral symmetry was high for the healthy young group and low for the CLTI group. The recovery time constants showed high negative correlation to TBI (ρ = -0.73) and ABI (ρ = -0.60). The relation of these clinical parameters to the hydrostatic response and absolute temperatures (|ρ|<0.3) remained unclear. ConclusionThe lack of correlation for absolute temperatures or their contralateral differences with the clinical status, ABI and TBI disputes their use in CLTI diagnostics. Thermal modulation tests tend to augment the signs of thermoregulation deficiencies and accordingly high correlations were found with all reference metrics. The method is promising for establishing the connection between impaired perfusion and thermography. The hydrostatic modulation test requires more research with stricter test conditions.

Long-Term Outcomes in Patients With Peripheral Arterial Disease Who Undergo Free Flap Reconstruction for Chronic Lower Extremity Wounds.

Free tissue transfer (FTT) is critical for limb salvage of chronic lower extremity (LE) wounds. In patients with peripheral arterial disease (PAD), FTT LE reconstruction can be challenging due to limited vessel selection for anastomosis. The study aims to evaluate our surgical and functional outcomes after FTT to LE in patients with PAD. A retrospective review identified patients who underwent LE free flap reconstruction between 2011 and 2021. All patients underwent preoperative arteriogram and subsequent FTT. Patients were classified into PAD or non-PAD cohorts, based on the presence of LE arterial stenoses or occlusions identified on arteriogram. Primary outcomes included complications, flap success, need for post-FTT vascular reintervention, limb salvage, and ambulatory status. A total of 253 patients underwent FTT to LE, with 84 patients (33.2%) in the PAD cohort. Patients with PAD had a higher prevalence of diabetes (83.3% vs 39.1%, P < 0.001) and end-stage renal disease (8.3% vs 2.4%, P = 0.028). Osteomyelitis was more common in the PAD group (73.8% vs 55.0%, P = 0.004). Free tissue transfer donor sites and flap composition were similar between cohorts. At a mean follow-up of 21.1 months, limb salvage rates were similar between non-PAD and PAD cohorts (90.5% vs 84.5%, P = 0.158), with no significant differences in ambulatory status or mortality. Higher complication rates occurred in the PAD cohort (38.1% vs 20.7%, P = 0.003), of which partial flap necrosis was more prevalent in the PAD group (6.0% vs 0.6%, P = 0.016). There was no difference in flap success rates between groups (P = 0.430). More postflap angiograms were performed in the PAD group (29.8% vs 7.1%, P < 0.001), with repeat percutaneous endovascular intervention performed in 68.0% of the PAD group versus 33.3% of the non-PAD group (P < 0.001). This is the largest study to demonstrate excellent long-term limb salvage outcomes in patients with PAD who undergo FTT to LE. Percutaneous endovascular intervention and FTT are effective methods to achieve limb salvage in vasculopathic patients with chronic LE wounds.

PS-C04-11: EFFECT OF ANKLE BRACHIAL INDEX EXAMINATION ON CENTRAL AORTIC BLOOD PRESSURE IN PATIENTS WITH PERIPHERAL ARTERY DISEASE

Background: Ankle brachial index (ABI) measurements are useful for detecting peripheral artery disease (PAD) as a screening test. In general, ABI examinations are contraindicated in patients with aortic aneurysm and history of aortic aneurysm. However, little is known whether ABI examinations elevate central aortic blood pressure (CBP). Method: From June 2018 to August 2020, we prospectively analyzed 66 patients who were performed cardiac catheterization through femoral approach and divided into peripheral artery disease complicated (PAD, N = 27) and uncomplicated (non-PAD, N = 39) groups. After insertion of pigtail catheter into both ascending (Asc), abdominal (Abd) positions, resting CBPs at Asc and Abd were measured. Subsequently, we measured each CBP during ABI, respectively. We compared resting CBP (R-CBP) and CBP during ABI (ABI-CBP) between PAD and non-PAD groups. Results: In non-PAD group, ABI-CBP at Abd was significantly higher than BL-CBP (P &lt; 0.05). On the other hand, there were no significant ABI-CBP elevation at Asc and Abd in PAD. There was no case with CBP elevation more than 20mmHg during ABI measurements in both groups. Furthermore, no clinical events were observed after ABI measurements in both groups. Conclusion: ABI was considered a safe testing in patients with suspected PAD.

Predictors of 6-Minute Walk Distance Among Aging Adults With Chronic Cardiopulmonary, Metabolic, and Renal Diseases

ABSTRACT Background The 6-minute walk test is a widely used measure of physical function in healthy people and patients with chronic conditions. Few reports have compared 6-minute walk distance (6MWD) across different conditions, and limited knowledge is available about how common covariates [age, sex, body mass index (BMI)] differentially affect 6MWD. Our purposes were to examine the 6MWD in persons with chronic conditions, compare walk distances with healthy controls, and identify predictors of 6MWD. Methods Data were aggregated from previous studies. Participants with primary diagnoses of heart failure (HF), chronic obstructive pulmonary disease (COPD), type 2 diabetes, chronic kidney disease, and peripheral artery disease (PAD) were included. Univariate and multivariate general linear models were used to estimate the impact of each condition on the 6MWD. Results The sample included 429 adults (48% female) aged 63 ± 9 years. Participants with HF, COPD, and PAD walked shorter distances than healthy controls (all P &amp;lt; 0.01). Predictors differed by group. In the HF group, age, Black race, and male sex negatively affected 6MWD. In the type 2 diabetes group, older age and high BMI were associated with shorter distances walked. In the chronic kidney disease group, higher BMI, Black race, and male sex negatively impacted 6MWD. No covariates were associated with 6MWD in the PAD, COPD, or control groups. Conclusion We found wide variation in common, nondisease-specific predictors of the 6MWD and significantly lower 6MWDs compared with healthy controls. Our findings add to our knowledge of 6MWD among aging adults with common chronic diseases.

Health status and cognitive function for risk stratification in chronic coronary and peripheral artery disease.

It is unclear whether health status and cognitive function assessments can augment traditional coronary artery disease (CAD) and peripheral artery disease (PAD) biomedical risk prediction frameworks. We examined the association between health status and cognitive function and subsequent adverse cardiovascular and limb events in CAD and PAD. Stable CAD and PAD patients from the international, multi-centre COMPASS trial completed the visual analogue scale (VAS) of the EQ-5D-3L to assess overall health status, and the Digit Symbol Substitution test (DSST) to assess cognitive function. Main outcomes were incident development of major adverse cardiovascular events, and the combined endpoint major adverse cardiovascular or limb events. The EQ VAS (per 10 unit increase) and DSST (per 5 unit increase) were added to fully adjusted (medications, demographics, cardiovascular history and risk factors) hierarchical Cox regression models. A total of 23 433 patients were in the CAD cohort and 6899 in the PAD cohort. Among both the CAD and PAD groups, higher scores on the EQ VAS (CAD: HR = 0.89, 95%CI 0.88-0.89; PAD HR = 0.89, 95%CI 0.88-0.89) and DSST (CAD HR = 0.95, 95%CI 0.94-0.95) (PAD HR = 0.95, 95%CI 0.94-0.95) were associated with a lower risk of a major adverse cardiovascular or limb events. Population attributable risks associated with the lower two quartiles vs. upper quartiles for the EQ-5D and DSST scores were 7% and 16%, respectively in the CAD cohort; and for PAD, at 14% and 18%, respectively. Adding health status and cognitive functioning information to biomedical evaluations can augment cardiovascular risk-stratification in CAD and PAD. NCT01776424.

Positive association between urinary albumin-creatinine ratio and lower extremity peripheral arterial disease in Chinese diabetes patients: A cross-section study with propensity score matching analysis

Background and aimsElevated urinary albumin-creatinine ratio (ACR) is an established risk factor for lower extremity peripheral arterial disease (PAD) in non-diabetes individual. This study aimed to determine the relationship between urinary ACR level and PAD in diabetes population. Methods and ResultsA cross-section study with 1396 hospitalized diabetes participants from department of endocrinology and neurology were performed and the propensity score matching method was applied to reduce the effects of confounding factors between the matched PAD and Non-PAD groups. The relationship between urinary ACR and ankle–brachial index (ABI) was analyzed by linear curve fitting analyses and multiple logistic regression models. Our study showed that the prevalence of PAD (low ABI, ABI<0.9) was 7.09% in our diabetes patients. The ABI level was significantly lower in high ACR group compared with those in normal urinary ACR group (1.11 ± 0.17 vs 1.13 ± 0.15, p = 0.010). The prevalence of PAD was increased with the increased tertile's of log2-transformed ACR in total patients before and after propensity score matching (p < 0.001 and p = 0.007, respectively). The OR (95% CI) between log2-transformed ACR and PAD was 1.0 and 1.70 (1.08–2.69, p = 0.022) respectively in normal and high ACR levels in diabetes patients after adjusting for potential confounders. After propensity score matching, the OR (95% CI) between log2-transformed ACR and PAD was 1.0 and 1.85 (1.05–3.23, p = 0.031) respectively in normal and high ACR levels in diabetes patients after adjusting for potential confounders. ConclusionThe elevated urinary ACR level was associated with PAD in Chinese diabetes patients.

Plasma Gut Microbe-Derived Metabolites Associated with Peripheral Artery Disease and Major Adverse Cardiac Events.

Cardiovascular diseases are associated with gut dysbiosis, but the role of microbe-derived metabolites as biomarkers or modulators of cardiovascular disease are not well understood. This is a targeted metabolomics study to investigate the association of nine microbe-derived metabolites with lower extremity peripheral artery disease (PAD), a form of atherosclerosis, and major adverse cardiac events (MACE). The study cohort consists of individuals with intermittent claudication and ankle-brachial index (ABI) < 0.9 (N = 119) and controls without clinically-apparent atherosclerosis (N = 37). The primary endpoint was MACE, a composite endpoint of myocardial infarction, coronary revascularization, stroke, transient ischemic attack, or cardiac-related death. Plasma metabolite concentrations differed significantly between the PAD and control groups. After adjustment for traditional atherosclerosis risk factors, kynurenine, hippuric acid, indole-3-propionic acid (IPA), and indole-3-aldehyde (I3A) concentrations were negatively associated with PAD, whereas indoxyl sulfate and 3-hydroxyanthranilic acid were positively associated. Hippuric acid, IPA, and I3A correlated with ABI, a surrogate for atherosclerotic disease burden. Those in the highest I3A concentration quartile had significantly improved freedom from MACE during follow-up compared to those in the lowest quartile. This study identifies specific indole- and phenyl-derived species impacted by gut microbial metabolic pathways that could represent novel microbiome-related biomarkers of PAD.

Clinical characteristics and outcomes of atrial fibrillation patients with peripheral artery disease: the Fushimi AF Registry

Abstract Background Atrial fibrillation (AF) represents the common arrhythmia and increases the risk of thromboembolism. Risk assessment for thromboembolism is important for the management of AF patients. Peripheral artery disease (PAD) is identified as a risk factor for thromboembolism in CHA2DS2-VASc score. However, there are little data on clinical characteristics and cardiovascular events of AF patients with PAD. Purpose In this study, we investigated the clinical characteristics and outcomes of AF patients with PAD. Methods The Fushimi AF Registry, a community-based prospective survey, was designed to enroll all of the AF patients who visited the participating medical institutions in Fushimi-ku, Kyoto, Japan. The inclusion criterion of the registry is the documentation of AF at 12-lead electrocardiogram or Holter monitoring at any time, and there are no exclusion criteria. We started to enroll patients from March 2011 and follow up data including prescription status were available in 4,464 patients from March 2011 to August 2021. Median follow-up period was 1,848 days. Results Of 4,464 patients, 183 patients had PAD (4.1%; PAD group). The mean age was higher in PAD group than no-PAD group (PAD group vs. no-PAD group: 76.7 vs. 73.5; p&amp;lt;0.01). Patients with PAD had more co-morbidities such as stroke, systemic embolism, congestive heart failure, hypertension, diabetes mellitus, dyslipidemia coronary artery disease and chronic kidney disease than those without PAD. Thus, CHADS2 score, CHA2DS2-VASc score and HAS-BLED score were higher in PAD group than no-PAD group (2.81 vs. 2.00; p&amp;lt;0.01, 5.17 vs. 3.30; p&amp;lt;0.01, 2.42 vs. 1.71; p&amp;lt;0.01, respectively). The proportion of patients with oral anticoagulant was similar between the two groups and the proportion of patients with antiplatelet drug was higher in PAD group than no-PAD group (59.0% vs. 55.6%; p=0.36, 62.9% vs. 24.7%; p&amp;lt;0.01, respectively). The incidences of all-cause death, cardiac death and myocardial infarction were higher in PAD group than no-PAD group (11.4 vs. 4.6 per 100 person-years; log-rank p&amp;lt;0.01, 1.7 vs. 0.8 per 100 person-years; log-rank p&amp;lt;0.01, 1.2 vs. 0.2 per 100 person-years; log-rank p&amp;lt;0.01). However, the incidence of stroke or systemic embolism was similar between the two groups (2.9 vs. 2.2 per 100 person-years, log-rank p=0.19). Finally, the incidence of composite of cardiac death, stroke, systemic embolism or myocardial infarction was higher in PAD group than no-PAD group (6.0 vs. 3.0 per 100 person-years; log-rank p&amp;lt;0.01). Conclusion AF patients with PAD had significantly higher risk for death and cardiac events, whereas the incidence of thromboembolism was similar between AF patients with and without PAD. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Japan Agency for Medical Research and Development

Maximal Calf Vasodilation Influences 6-Minute Walk Distance In PAD And Non-PAD Groups

PURPOSE: To (1) compare the maximal calf vascular conductance and 6-minute walk distance (6MWD) of participants with and without symptomatic peripheral artery disease (PAD), and (2) determine whether maximal calf vascular conductance was associated with 6MWD in both groups before and after adjusting for ankle-brachial index (ABI), and for demographic, anthropometric, and co-morbid characteristics. METHODS: Participants with (n = 633, 67.7 + 8.4 yr) and without (n = 327, 63.9 ± 10.4 yr) PAD underwent ambulatory function testing including 6MWD, resting ABI, and plethysmographic measurements of calf blood flow and vascular conductance at rest and during maximal hyperemia (ischemic toe raises to fatigue). Participants were further characterized on demographic, anthropometric, and co-morbid (age, hypertension, diabetes, smoking, etc) variables. RESULTS: The PAD group had lower maximal calf conductance (135.8 ± 71.4 vs. 200.7 ± 112.7 % reperfusion/min/mmHg, p < 0.001) and shorter 6MWD (375 ± 98 vs. 480 ± 107 meters, p < 0.001) than the non-PAD group (means+SD). Maximal calf conductance was positively associated with 6MWD in the PAD group (p < 0.001) and in the non-PAD group (p < 0.001). These positive associations remained significant after adjusting for disease severity (ABI) and co-morbid conditions in the PAD group (p < 0.001), and after adjusting for age and co-morbid conditions in the non-PAD group (p < 0.001). Calf circumference was also a significant independent predictor of 6MWD in both groups (p < 0.001) CONCLUSIONS: Maximal calf vascular conductance, an index of microvascular function, is important in explaining variance in 6MWD in PAD and non-PAD groups, even after controlling for ABI and the influences of co-morbid conditions.

Association of serum levels of osteopontin and osteoprotegerin with adverse outcomes after endovascular revascularisation in peripheral artery disease

BackgroundOsteoprotegerin (OPG) and osteopontin (OPN) are vascular calcification inhibitors with a known role in the atherosclerotic and inflammatory process. We investigated their relationship with adverse outcomes (restenosis/adverse cardiovascular events) after endovascular revascularisation of patients with peripheral arterial disease (PAD).Methods203 consecutive patients were enrolled in the PAD group (PADG) and 78 age and sex-matched subjects with less than two cardiovascular risk factors served as control group (COG). PADG underwent standard medical assessment at baseline and 12 months after the procedure. During follow up major adverse cardiovascular events (MACEs) including arterial restenosis with need for reintervention were documented and the PADG was divided accordingly into two subgroups.ResultsDuring 12-month follow-up, 82 MACE were recorded (MACE subgroup). The rest of 124 PAD patients remained free of MACE (non-MACE subgroup). At baseline, OPG (9.89 ± 2.85 ng/ml vs 3.47 ± 1.95 ng/ml, p < 0.001) and OPN (79.99 ± 38.29 ng/ml vs 35.21 ± 14.84 ng/ml, p < 0.001) levels were significantly higher in PADG compared to COG, as well as in MACE subgroup compared to non-MACE subgroup (13.29 ± 3.23 ng/ml vs 10.86 ± 3 ng/ml and 96.45 ± 40.12 ng/ml vs 78.1 ± 38.29 ng/ml, respectively). An independent association of PAD with OPG and OPN was found in the whole patient cohort. Although OPG and OPN were significantly related to MACE incidence in the univariate analysis, multiple logistic regression analysis failed to detect any independent predictor of MACE within the PADG.ConclusionBaseline high OPG and OPN levels were independently associated with PAD presence. Even higher levels of those biomarkers were detected among PAD patients with MACE, however, their prognostic role should be further clarified.

Peripheral artery disease affects the function of the legs of claudicating patients in a diffuse manner irrespective of the segment of the arterial tree primarily involved.

Different levels of arterial occlusive disease (aortoiliac, femoropopliteal, multi-level disease) can produce claudication symptoms in different leg muscle groups (buttocks, thighs, calves) in patients with peripheral artery disease (PAD). We tested the hypothesis that different locations of occlusive disease uniquely affect the muscles of PAD legs and produce distinctive patterns in the way claudicating patients walk. Ninety-seven PAD patients and 35 healthy controls were recruited. PAD patients were categorized to aortoiliac, femoropopliteal and multi-level disease groups using computerized tomographic angiography. Subjects performed walking trials both pain-free and during claudication pain and joint kinematics, kinetics, and spatiotemporal parameters were calculated to evaluate the net contribution of the calf, thigh and buttock muscles. PAD patients with occlusive disease affecting different segments of the arterial tree (aortoiliac, femoropopliteal, multi-level disease) presented with symptoms affecting different muscle groups of the lower extremity (calves, thighs and buttocks alone or in combination). However, no significant biomechanical differences were found between PAD groups during the pain-free conditions with minimal differences between PAD groups in the claudicating state. All statistical differences in the pain-free condition occurred between healthy controls and one or more PAD groups. A discriminant analysis function was able to adequately predict if a subject was a control with over 70% accuracy, but the function was unable to differentiate between PAD groups. In-depth gait analyses of claudicating PAD patients indicate that different locations of arterial disease produce claudication symptoms that affect different muscle groups across the lower extremity but impact the function of the leg muscles in a diffuse manner generating similar walking impairments.

Impact of cardiac surgery with cardiopulmonary bypass on symptom progression in the early postoperative period in patients with peripheral arterial disease.

This study aims to examine whether cardiac surgery with cardiopulmonary bypass (CPB) leads to symptom progression in the early postoperative period in patients with the peripheral arterial disease (PAD) undergoing coronary artery bypass grafting surgery (CABG). This retrospective study included one hundred fifty consecutive adult patients with PAD at Fontaine stage 2b (pain-free walking distance less than 100 m) undergoing CABG. The control group comprised 150 consecutive adult patients undergoing CABG with a normal ankle-brachial index (ABI). Symptom progression was defined as the development of ischemic rest pain (Fontaine stage 3). In the first week after surgery, 91 of 150 patients (60.6%) had symptom progression in the PAD group. Rest pain resolved in most of these patients on the 15th postoperative day. At the end of the second month, rest pain resolved in all patients. Logistic regression analysis revealed that ABI (<0.5), CPB time (≥100 mins), nadir hct levels (≤25 %) on CPB, and postoperative nadir hct levels (<25%) were independently associated with postoperative symptom progression. Our results suggest that cardiac surgery with CPB may lead to symptom progression in patients with severe claudication in the early postoperative period.