Search

Aims Peripheral arterial disease (PAD) is the well-known risk factor for cardiovascular events. Although low ankle-brachial index (ABI) is recognized as a risk factor in general population, low ABI without any symptoms of PAD has not been established as a prognostic marker in patients with acute myocardial infarction (AMI) yet. The purpose of this retrospective study was to examine whether asymptomatic low ABI was associated with long-term clinical outcomes in AMI patients without treatment history of PAD. Methods We included 850 AMI patients without a history of PAD and divided them into the preserved ABI (ABI ≥ 0.9) group (n=760) and the reduced ABI (ABI ＜0.9) group (n=90) on the basis of the ABI measurement during the hospitalization. The primary endpoint was the major adverse cardiovascular events (MACE) defined as the composite of all-cause death, non-fatal myocardial infarction, and hospitalization for heart failure. Results During the median follow-up duration of 497 days (Q1: 219 days to Q3: 929 days), a total of 152 MACE were observed. The Kaplan-Meier curves showed that MACE were more frequently observed in the reduced ABI group than in the preserved ABI group (p＜0.001). The multivariate COX hazard analysis revealed that reduced ABI was significantly associated with MACE (hazard ratio 2.046, 95% confidence interval 1.344-3.144, p=0.001) after controlling confounding factors. Conclusions Reduced ABI was significantly associated with long-term adverse events in AMI patients without a history of PAD. Our results suggest the usefulness of ABI as a prognostic marker in AMI patients irrespective of symptomatic PAD.

Aims Elevated serum alkaline phosphatase (ALP) levels are associated with an increased risk of cerebrocardiovascular diseases. However, the associations of ALP with peripheral arterial disease (PAD) and outcomes in patients with acute ischemic stroke (AIS) are not well-known. Methods We examined the association between ALP levels and the ankle-brachial index (ABI) in 2111 consecutive patients with AIS. A poor functional outcome was defined as a modified Rankin Scale (mRS) score of 3-6 at 3 months after stroke. A low ABI was defined as a value of ≤ 0.9. Results Of the total cohort, 482 patients (22.8%) had a low ABI. ALP levels were higher in patients with a low ABI than in those without (p＜0.001). The multivariable logistic analysis revealed that quartiles of ALP levels were significantly associated with a low ABI (odds ratio [OR]: 1.20, 95% confidence interval [CI]: 1.08-1.33). Of the 1322 patients with a premorbid mRS score of 0-2, 434 patients (32.8%) had a poor outcome. The multivariable analysis revealed that elevated serum ALP levels and a low ABI were independently associated with poor stroke outcomes after adjustment for baseline characteristics (OR: 1.21, 95% CI: 1.07-1.38, and OR: 2.00, 95% CI: 1.40-2.84, respectively). Conclusions Increased serum ALP levels are significantly associated with a low ABI. These indicators are independent prognostic factors for poor stroke outcomes at 3 months.

The objective of this study was to evaluate a measure of the responsiveness and reliability of the pulse volume recording upstroke ratio (PVRr). A database of 389 subjects undergoing lower extremity revascularization was analyzed. Subjects were included in the analysis if they had undergone pedal radiographs, had PVRs performed pre- and postlower extremity revascularization, and had regular pulsatile digital waveforms with a pressure recording on both PVRs. The responsiveness of the PVRr was assessed by means of the postoperative percent change in comparison to the digital pressures. A statistically significant negative correlation was observed (Pearson -0.421; p = .007) indicating that as digital pressures increased, the PVRr decreased. Further, measurement of the reliability of the PVRr was performed on a selection of 10 recordings by 2 residents and 3 board-certified surgeons. The observed intraclass correlation coefficient of measurements was 0.960. Results of this investigation provide evidence in support of the responsiveness and inter-rater reliability in the calculation of the pulse volume recording upstroke ratio.

Background: Hyperlipidemia is one of the major risk factors for developing a cardiovascular disease (CVD) and it is a frequent post-transplant complication, occurring in up to 60% of the renal transplant recipients (RTRs). Lipid lowering therapy with HMG-CoA reductase inhibitors (statins) is generally recommended and may reduce the overall cardiovascular risk. The aim of this study was to evaluate the lipid profile, statin administration and their relationship with arterial stiffness parameters in renal transplant recipients. Methods: Three hundred and forty-four stable RTRs (62.5% male) transplanted between 1994 and 2018 were randomly enrolled to the study. The following parameters of arterial stiffness was measured in each patient: carotid femoral pulse wave velocity (baPWV left and right, cfPWV) and pulse pressure (PP right and left). The study group was divided based on the use statins: 143 (41.6%) and 201 (58.4%). RTRs were qualified to the statin (+) and the statin (–) group, respectively. Results: In the statin (+) as compared to statin (–) group there were more patients with a CVD (32.9% vs. 14.9%) and diabetes (25.2% vs. 14.4%). In the whole study group, CVD was associated with a significant increase of both baPWV and cfPWV as well as PP (8.5 mmHg). There were significant differences in arterial stiffness parameters (baPWV, cfPWV, PP) between the statin (+) and the statin (–) group. Conclusions: Arterial stiffness was increased in RTRs with CVD and hyperlipidemia. The control of hyperlipidemia was poor in RTRs.

Peripheral arterial disease (PAD) is a phenotype of atherosclerotic disease often associated with cerebrovascular or coronary artery disease. The incidence of cardiovascular events in patients with PAD is 5.4% per year, which is higher than that of cerebrovascular or coronary artery disease. The most useful screening method for PAD is the ankle brachial pressure index (ABI). The ABI should be measured in (1) all patients with lower limb symptoms such as claudication, (2) all patients aged 65 years and over, and (3) those aged 50 to 65 years who have risk factors such as smoking and diabetes mellitus. PAD is diagnosed if the ABI is

Aim Abnormal ankle-brachial index (ABI) is regarded as peripheral artery disease and can be used to predict cardiovascular (CV) outcomes. However, the usefulness of ABI for the prediction of CV outcome in patients with normal ABI is limited. Upstroke time per cardiac cycle (UTCC) is recently reported to be associated with mortality in patients with acute myocardial infarction and the elderly. Therefore, we aimed to evaluate UTCC, left ventricular ejection fraction (LVEF), brachial-ankle pulse wave velocity (baPWV), and ABI for the prediction of mortality in patients with normal ABI. Methods Patients arranged for echocardiographic examinations were enrolled, and 1076 patients with normal ABI were included. ABI, baPWV, and UTCC were measured by an ABI-form device. Results The median follow-up to mortality was 95 months. There were 88 CV and 244 all-cause deaths. After multivariate analysis, UTCC was associated with increased CV and all-cause mortality (P ≤ 0.004). Age, diabetes, heart failure, left ventricular hypertrophy, baPWV, and LVEF were also independent predictors of CV and all-cause mortality, but ABI was not. Furthermore, UTCC had a better additive predictive value than ABI, baPWV, and LVEF for CV mortality (P ≤ 0.012). It also had a better additive predictive value than ABI and LVEF for all-cause mortality (P ≤ 0.013). Conclusions UTCC is an independent predictor for CV and all-cause mortality in patients with normal ABI. It also has a better additive predictive value of CV and all-cause mortality than ABI and LVEF. Therefore, UTCC is a simple, novel, and useful parameter for identifying high-risk patients with normal ABI.

There is currently a degree of divergence among the main clinical practice guidelines on the management of risk factors for peripheral arterial disease (PAD). This project aims to gain understanding of the management of PAD risk factors in clinical practice and to reach a multidisciplinary consensus on the strategies to be followed in order to optimize its identification, treatment, and follow-up.A multidisciplinary consensus following the Delphi methodology.Professionals (n = 130) with extensive experience in PAD participated in this consultation. The results suggest that in order to optimize the control of risk factors, efforts should be aimed at: (1) promoting the involvement and awareness of all specialists in the identification of and screening for the disease; (2) guaranteeing the possibility of evaluating the ankle-brachial index (ABI) in all the medical specialties involved; (3) promoting strategies for patients to quit smoking through the use of drugs, programs, or referrals to specialized units; (4) promoting an appropriate Mediterranean-based diet and the prescription of daily exercise; (5) raising awareness of the importance of ensuring LDL cholesterol values below 70 mg/dL, especially in symptomatic but also in asymptomatic patients (55 mg/dL following the publication of the ESC/EAS guide); (6) recommending the use of antiplatelet therapy in asymptomatic patients with diabetes mellitus (DM) and/or a pathological ABI; and (7) protocolizing the annual evaluation of ABI in high-risk patients.This document presents the 22 agreed-upon strategies which are intended to help professionals optimize multidisciplinary management of PAD risk factors.

Objective To compare the potential healing prognosis of the different routine noninvasive techniques implemented in the International Working Group Diabetic Foot Guidelines with the novel use of hyperspectral imaging (HSI) in patients with diabetic foot ulcers (DFUs). Methods Twenty-one patients with active DFUs participated in this 1-year prospective study in a specialized diabetic foot unit between December 2018 and January 2020. HSI was performed at baseline to quantify tissue oxygenation and should be presented on an anatomical map by analyzing the following parameters: (1) oxygen saturation of the hemoglobin, (2) tissue hemoglobin index, (3) the near-infrared perfusion index, and (4) tissue water index. In addition, transcutaneous oxygen pressure (TcpO2), systolic toe and ankle pressures, ankle-brachial index, and toe-brachial index values were calculated for the ulcerated limb. The primary outcome measure was wound healing, defined as complete epithelization without any drainage confirmed for at least 10 days after closure was first documented at 24 weeks. Results During the follow-up period 14 patients (66.66 %) healed and 7 patients did not heal (33.3%) by 24 weeks. The TcpO2 optimal cut-off point as determined by a balance of sensitivity and specificity of 28.5 mm Hg that yielded a sensitivity of 91% and a specificity of 100%, and area under the curve of 0.989 (P = .005; 95% confidence interval [CI], 0.945-1.000). Followed by the oxygen saturation of the hemoglobin optimal cut-off point as determined by a balance of sensitivity and specificity of 48.5 mm Hg that yielded a sensitivity of 93% and a specificity of 0.71%, and area under the curve of 0.932 (P = .013; 95% CI, 0.787-1.000). The logistic regression analyses showed that TcpO2 was the only variable associated with wound healing at 24 weeks (P Conclusions The HSI was shown to be effective in the prognosis of DFU healing compared with other noninvasive test; only TcpO2 values resulted in better diagnosis potential in wound healing.

Purpose This study aimed to demonstrate the efficacy and safety of the SoundBite® Crossing System‒Peripheral (SCS‒P) to facilitate crossing chronic total occlusions (CTOs) of infrainguinal arteries. Failure to cross CTOs is the main cause of failed endovascular revascularization attempts. The SCS‒P is a newly developed device that uses a 0.018-inch wire to deliver acoustic shock waves and facilitate CTO crossing. Methods This clinical trial was approved by Ethics Committees of all 4 participating centers and enrolled 52 patients with symptomatic de novo infrainguinal CTOs. Technical device success, the primary efficacy endpoint, was defined as the ability to facilitate treatment of the target lesion by crossing a portion or the whole length of the CTO. Freedom from SCS‒P related major adverse events (MAEs) at 30 days post procedure was the primary safety endpoint. Results The SCS‒P met the primary efficacy and safety endpoints in 92.3% (48/52) and 100% (52/52) of subjects, respectively. Technical device success with post-procedural patency and freedom from SCS‒P related MAEs was achieved in 88.5% (46/52) of subjects. Mean CTO crossing time was 20.0 ± 30.8 minutes and the SCS‒P was able to traverse the whole CTO and enter the distal true lumen without the need of any other device in 59.6% (31/52) of subjects. Mean Rutherford category and ankle brachial index improvement at 30 days follow-up was 2.4±1.17 and 0.23±0.22, respectively. Conclusions The SCS‒P demonstrated a satisfactory safety and performance profile to cross peripheral CTOs and enter into the distal true lumen of infrainguinal CTOs.

Aims Small arteries can be visualized in the ocular fundus, and findings of retinopathy based on Scheie classification are often applied to evaluate the impact of hypertension and atherosclerosis. However, the relationship between damage in the large and small arteries has not been investigated sufficiently, especially in the early stages. The present study investigated possible associations between large artery atherosclerosis and small artery retinopathy in untreated middle-aged individuals. Methods Untreated middle-aged workers undergoing periodic health check-ups (n=7,730, 45±8 years) were enrolled in this study. The absence or presence and extent of retinopathy were characterized by ophthalmologists as hypertensive (H0-4) and atherosclerotic grades (S0-4) based on Scheie classification. Large artery atherosclerosis was examined based on functional assessment of the cardio-ankle vascular index (CAVI) and morphological assessment of the carotid intima-media thickness (IMT) by ultrasound. Results We found significant differences in CAVI and carotid IMT between individuals with and without hypertensive or atherosclerotic retinopathy. Multivariable regression analysis showed that the presence of hypertensive and atherosclerotic retinopathy was significantly associated with CAVI and carotid IMT. Logistic regression analysis with the endpoint of a hypertensive or atherosclerotic lesion revealed that CAVI and carotid IMT are independent determinants of retinopathy. Conclusions CAVI and carotid IMT were significantly associated with the presence of retinopathy based on Scheie classification in untreated middle-aged subjects, implying that atherosclerotic examination in large arteries could reveal early-stage small artery retinopathy.

Peripheral artery disease (PAD) is associated with decreased physical function and increased mortality in the general population. We previously found that PAD is common in middle-aged women with and without HIV infection, but its association with functional decline is unclear. We examine the contribution of PAD to functional decline in the Women's Interagency HIV Study, controlling for traditional cardiovascular risk factors and HIV-related factors.Analysis included 1839 participants (72% with HIV) with measured ankle-brachial index (ABI) and 4 m gait speed. ABI values categorized PAD severity. Linear models with repeated measures estimated the association of PAD severity with log-transformed gait speed after controlling for demographic, behavioral, and metabolic risk factors, and HIV/hepatitis C virus status.Median age was 50 years and more than 70% were Black. Compared with normal ABI, there was a dose-response relationship between increasing PAD severity and slower gait speed in univariable analyses: 6% slower gait speed for low-normal ABI [95% confidence interval (CI): 4-9%], 10% for borderline PAD (95% CI: 6-13%), 14% for mild PAD (95% CI: 9-18%), and 16% for moderate-severe PAD (95% CI: 5-25%). PAD severity remained associated with slower gait speed in multivariable analyses. HIV/hepatitis C virus co-infection was independently associated with 9% (95% CI: 4-14%) slower gait speed compared with those with neither infection. Among women with HIV, neither CD4+ cell count nor HIV-RNA level was associated with gait speed.In middle-aged women with and without HIV infection, greater PAD severity is associated with progressively slower gait speed. Early detection of subclinical PAD may decrease the risk of lower extremity functional impairment and its long-term health consequences.

STUDY OBJECTIVES: Whether the association between sleep-disordered breathing (SDB) and cardiovascular disease is independent of comorbid risk factors for cardiovascular disease is controversial. The objective of this study was to elucidate whether the association between SDB severity and the surrogate markers of cardiovascular disease events differs in relation to the number of comorbidities. METHODS: This cross-sectional study included 7,731 participants. Severity of SDB was determined by the oxygen desaturation index adjusted by actigraph-measured objective sleep time. Participants were stratified according to SDB severity and the number of comorbidities (hypertension, diabetes, dyslipidemia, and obesity), and the associations between the maximum value of intima-media thickness of the common carotid artery (CCA-IMT-max), brachial-ankle pulse wave velocity, and cardio-ankle vascular index were evaluated. RESULTS: Among participants with no risk factors, CCA-IMT-max increased according to SDB severity (n = 1022, P < .0001). Even after matching the background, the median CCA-IMT-max value was 14% higher in moderate-severe SDB patients than those without SDB (n = 45 in each group, P = .020). The difference was not significant for brachial-ankle pulse wave velocity and cardio-ankle vascular index. On the other hand, a significant difference in CCA-IMT-max was not found in those with multiple comorbidities. Consistently, multiple regression analysis revealed an independent association between CCA-IMT-max and moderate-severe SDB for all study participants (β: 0.0222, 95% confidence interval: 0.0039–0.0405, P = .017), but the association was not significant for stratified participants with multiple comorbidities. CONCLUSIONS: SDB severity is associated with the CCA-IMT-max level, but the independent association becomes weaker for those with multiple comorbidities. CITATION: Nakatsuka Y, Murase K, Matsumoto T, et al. Markers of cardiovascular disease risk in sleep-disordered breathing with or without comorbidities: the Nagahama Study. J Clin Sleep Med. 2021;17(12):2467–2475.

Kouichi Murakami,1 Emi Inayama,1 Yukiko Itoh,1 Shoji Tuchiya,1 Masashi Iwasaki,2 Nobuko Tamura,1 Toshihiko Suzuki,3 Noriko Iwai,1 Junji Utino,4 Motoyuki Masai,4 Daiji Nagayama,5,6 Kohji Shirai4,6 1Seijinaki Mihama Narita Clinic, Narita City, Chiba, 286-0041, Japan; 2Seijinkai Mihama Katori Clinic, Katori City, Chiba, 287-0041, Japan; 3Seijinkai Mihama Sakura Clinic, Sakura City, Chiba, 285-0841, Japan; 4Seijinkai Mihama Hospital, Chiba City, Chiba, 261-0013, Japan; 5Nagayama Clinic, Oyama City, Tochigi, 323-0032, Japan; 6Sakura Hospital, School of Medicine Toho University, Sakura City, Chiba, 285-8741, JapanCorrespondence: Daiji NagayamaNagayama Clinic, 2-12-22, Tenjin-Cho, Oyama City, Tochigi, 323-0032, JapanTel/Fax +81-285-22-0219Email deverlast96071@gmail.comAim: Mortality rate of maintenance hemodialysis patients is known to be high. Cardio-ankle vascular index (CAVI) is an index reflecting the proper stiffness of the arterial tree from the origin of the aorta to the ankle. We aimed to clarify the utility of CAVI as a predictor of mortality in hemodialysis patients. The roles of age and nutritional conditions on survival were also examined.Methods: We followed 242 patients undergoing hemodialysis for 6 consecutive years. Data from 209 patients (mean age was 60 ± 11 years) excluding those with ankle-brachial index < 0.90 were then analyzed. CAVI and heart to ankle pulse wave velocity (haPWV) were measured using Vasera 1500.Results: Thirty-eight hemodialysis patients who died during the 6-year period had higher age, cardiothoracic ratio (CTR), CAVI, and haPWV, and lower diastolic blood pressure, albumin, phosphate, and calcium phosphate product. The Kaplan–Meier curves for cumulative survival among the tertile groups showed that the mortality rate was higher in the highest tertile (T3) compared to T1/T2 for both CAVI and haPWV. Receiver operating characteristic (ROC) analysis revealed that CAVI had better discriminatory power for all-cause mortality compared to haPWV. In the Cox-proportional hazards analyses, 1 SD increase in both parameters contributed independently to all-cause mortality [CAVI: HR 1.595 (95% CI 1.108– 2.297), haPWV: HR 1.695 (95% CI 1.185– 2.425)], as well as age and CTR. Both parameters above the cut-offs estimated in the ROC analysis (CAVI ≥ 9.2, haPWV ≥ 8.9) also had independent contributions to mortality.Conclusion: Through the 6 consecutive years of follow-up in 209 HD patients, increased CAVI might represent a major modifiable risk factor for all-cause mortality. Further research is needed to examine whether CAVI-lowering interventions contribute to improved prognosis.Keywords: hemodialysis patient, mortality, cardio-ankle vascular index, phosphorus

Background The relationship between obesity indices and arterial stiffness (AS) has not been fully discovered nor has it been studied in depth in large hypertensive patient populations. The aim of this study was to explore the association between body mass index (BMI) and waist-hip ratio (WHR) levels and AS based on brachial-ankle pulse wave velocity (baPWV) in Chinese rural adults with hypertension. Methods This cross-sectional study analyzed 5049 Chinese rural adults with essential hypertension. BMI was calculated as the body weight in kilograms divided by the square of the height in meters (kg/m2). Central obesity was defined as WHR ≥ 0.9 for males and ≥ 0.85 for females. Measurement of arterial stiffness was carried out via brachial-ankle pulse wave velocity (baPWV). Results The prevalence of overweight, general obesity, central obesity and increased AS were 26.88%, 3.39%, 63.85% and 44.01%, respectively. Multivariate logistic regression analysis indicated that BMI levels were negatively associated with the prevalence of increased AS (adjusted-OR per SD increase: 0.74, 95% CI 0.67–0.81, P SD increase: 1.25, 95% CI 1.14–1.36, P CI 1.28–1.81, P β per SD increase: − 0.57, 95% CI − 0.68 to − 0.46, P β per SD increase: 4.46, 95% CI 3.04–5.88, P Conclusion There was an inverse relationship between BMI levels and increased AS or baPWV levels, whereas WHR levels and central obesity were positively associated with increased AS or baPWV levels in Chinese rural adults with hypertension.

The accuracy of ankle-brachial index (ABI) and toe-brachial index (TBI) in discriminating lower extremity peripheral artery disease (PAD) has not been evaluated in patients with chronic kidney disease (CKD). We measured ABI, TBI, and Doppler ultrasound in 100 predialysis patients with CKD without revascularization or amputation. Leg-specific ABI was calculated using higher systolic blood pressure (SBP) in posterior tibial or dorsalis pedis artery divided by higher brachial SBP; alternative ABI was calculated using lower SBP in posterior tibial or dorsalis pedis artery. PAD was defined as ≥50% stenosis detected by Doppler ultrasound. PAD risk classification score was calculated using cardiovascular disease risk factors. The area under the curve (AUC, 95% confidence interval [CI]) for discriminating ultrasound-diagnosed PAD was 0.78 (0.69 to 0.87) by ABI, 0.80 (0.71 to 0.89) by alternative ABI, and 0.74 (0.63 to 0.86) by TBI. Sensitivity and specificity were 25% and 97% for ABI ≤0.9, 41% and 95% for alternative ABI ≤0.9, and 45% and 93% for TBI ≤0.7, respectively. AUC (95% CI) of PAD risk classification score was 0.86 (0.78 to 0.94) with sensitivity and specificity of 95% and 60% for risk score ≥0.10, 76% and 76% for risk score ≥0.25, and 43% and 95% for risk score ≥0.55. Combining risk score with ABI, alternative ABI, and TBI increased AUC (95% CI) to 0.89 (0.82 to 0.96), 0.89 (0.80 to 0.98), and 0.87 (0.78 to 0.96), respectively. In conclusion, current ABI and TBI diagnostic criteria have high specificity but low sensitivity for classifying PAD in patients with CKD. PAD classification risk score based on cardiovascular disease risk factors improves the accuracy of PAD classification.

Little information is available on the association between brachial-ankle pulse wave velocity (baPWV) and the risk of stroke in Chinese H-type hypertension patients. Therefore, our study aimed to assess this association between baseline baPWV and short-term risk of first stroke and to propose a cutoff value of baPWV that could predict near cerebrovascular events. A total of 9787 hypertension patients without preexisting stroke who underwent baPWV measurement were included. The primary end points were first symptomatic stroke. Secondary end points were first ischemic stroke and first hemorrhagic stroke. During a median follow-up of 20.8 months, there was a total of 138 first strokes including 123 first ischemic strokes and 15 first hemorrhagic strokes. When baPWV was categorized in quartiles, the higher risks of first stroke (HR = 1.52; 95% CI: 1.05-2.21) and first ischemic stroke (HR = 1.53; 95% CI: 1.03-2.26) were found in participants in quartile 4 (≥21.31 m/s), compared with those in quartile 1-3 (

In advanced peripheral arterial disease (PAD), medial arterial calcification is known to inflate the ankle-brachial index. An alternative method of evaluating symptomatic patients is toe-brachial indexes (TBI), where a ratio less than .7 indicates PAD and less than .4 indicates a severe form. The objective of this retrospective analysis was to investigate the association between TBIs less than .7 and angiographically verified PAD. Patients were required to have either a leg angiogram 13 months prior to or 12 months after a 6-minute walk test. Of the 174 included patients, the mean overall TBI was .450. The mean TBI by location was highest at iliac and infra-geniculate with .544 and lowest at supra-geniculate with .372. Infra-geniculate lesions were also the most frequent ( n = 46). A TBI less than .4 was found in 47.7% of patients. TBIs greater than .7 were present in 36 patients; however, only 16 had significant angiographic stenosis. In conclusion, the majority of patients with angiographic PAD had a TBI less than .7, especially less than .4. Contrary to suspicion, infra-geniculate lesions were the most common and had the highest TBI.

Background Accumulating evidences indicate that periodontitis is closely associated with endothelial dysfunction. Trimethylamine-N-oxide (TMAO), a harmful microbiota generated metabolite, has been implicated as a nontraditional risk factor for impaired endothelial function. However, whether increased circulating levels of TMAO in periodontitis patients induces endothelial dysfunction remains unknown. Methods Patients with periodontitis and periodontally healthy controls were enrolled. Periodontal inflamed surface area (PISA) was calculated to assess the inflammatory burden posed by periodontitis. The circulating TMAO was measured by high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS). Vascular endothelial function including peripheral endothelial progenitor cells (EPCs), brachial arterial flow-mediated vasodilation (FMD) and brachial-ankle pulse wave velocity (baPWV) were assessed. We also isolated and cultured EPCs from participants' peripheral blood to investigate the effect of TMAO on EPC functions in vitro. Results 122 patients with stage III-IV periodontitis and 81 healthy controls were included. Patients with periodontitis presented elevated TMAO (P = 0.002), lower EPCs (P = 0.025) and declined FMD levels (P = 0.005). The TMAO concentrations were correlated with reduced circulating EPCs and FMD levels. Moreover, TMAO can injury EPCs function in vitro, and may induce cell pyroptosis via Bax/caspase-3/GSDME pathway. Conclusions The present study demonstrates for the first time that circulating TMAO levels are increased in patients with stage III-IV periodontitis, and correlated with vascular endothelial dysfunction. These findings may provide a novel insight into the mechanism of vascular endothelial dysfunction in patient with periodontitis via TMAO-downregulated EPC functions. This article is protected by copyright. All rights reserved.

Aim To examine whether improvement in flow-mediated endothelium-dependent dilatation (FMD) of the brachial artery and brachial-ankle pulse wave velocity (baPWV) has an additive effect on achieving optimal goals of traditional risk factors to reduce cardiovascular risk in patients with coronary artery disease (CAD). Methods We assessed 323 patients with CAD and impaired vascular function, defined as an impaired FMD of the brachial artery (＜5.5%) and increased baPWV (＞1,440 cm/sec). After FMD and baPWV measurements at 24 weeks of optimal medical treatment (OMT), the study patients were followed up for ＜60 months or until a composite of cardiac death, nonfatal myocardial infarction (MI), unstable angina, or ischemic stroke occurs. Results During the median follow-up period of 35 months, cardiovascular events occurred in 72 patients. Multivariate Cox hazards analysis showed that patients with an improvement in FMD and baPWV had the lowest probability of future cardiovascular events. In addition, the improvement in FMD and baPWV had a significant incremental effect on the predictive value of the achievement of optimal goals for blood pressure (BP), low-density lipoprotein cholesterol (LDL-C), and hemoglobin A1c (HbA1c) using net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Conclusions The improvement in FMD and baPWV had additive effects on risk reduction of the achievement of the optimal goals of traditional risk factors in patients with CAD. Thus, serial measurements of FMD and baPWV may be useful for identifying CAD patients at residual risk for adverse cardiovascular events following OMT.

BACKGROUND Low ankle-brachial index (ABI) related ischemic events are common among individuals with chronic kidney disease (CKD). It is also associated with an increased risk of rapid renal function decline. The presence of peripheral artery disease (PAD) with low ABI among patients with high cardiovascular (CV) risk increases limb loss and mortality. AIMS To estimate the association between abnormal ABI and renal endpoints and all-cause mortality. METHODS A multicenter prospective cohort study was conducted among subjects with high CV risk or established CV diseases in Thailand. The subjects were divided into 3 groups based on ABI at baseline > 1.3, 0.91-1.3, and ≤ 0.9, respectively. Primary composite outcome consisted of estimated glomerular filtration rate (eGFR) decline over 40%, eGFR less than 15 mL/min/1.73 m2, doubling of serum creatinine and initiation of dialysis. The secondary outcome was all-cause mortality. Cox regression analysis and Kaplan-Meier curve were performed. RESULTS A total of 5543 subjects (3005 men and 2538 women) were included. Cox proportional hazards model showed a significant relationship of low ABI (ABI ≤ 0.9) and primary composite outcome and all-cause mortality. Compared with the normal ABI group (ABI 0.91-1.3), subjects with low ABI at baseline significantly had 1.42-fold (95% CI 1.02-1.97) and 2.03-fold (95% CI 1.32-3.13) risk for the primary composite outcome and all-cause mortality, respectively, after adjusting for variable factors. CONCLUSION Our study suggested that PAD independently predicts the incidence of renal progression and all-cause mortality among Thai patients with high CV risk.

The plasma atherogenic index (AIP) has been suggested as a useful independent predictor of cardiovascular diseases (CVDs) in high CV risk patients. We investigated the association between AIP and arterial stiffness measured by brachial–ankle pulse wave velocity (baPWV) in healthy adults. A total of 3468 healthy subjects without any metabolic or CV diseases were enrolled. Anthropometric and CV risk factors were measured. The AIP was defined as the base 10 logarithm of the ratio of the concentration of triglycerides to high-density lipoprotein-cholesterol. Subjects were classified into AIP quartiles. There were gradual deteriorations in metabolic parameters and increase in baPWV across the increasing AIP quartiles. In a fully adjusted analysis, compared with Q1 (lowest quartile) group, the odds ratio (95% confidence interval) for increased baPWV was higher in Q2 1.51, Q3 1.64, and Q4 (highest quartile) 2.77 among men, and Q2 1.09, Q3 1.55, and Q4 1.83 among women (all P trend

AIMS/INTRODUCTION In this paper, we focused on exploring the diagnostic and predictive clinical utility of ankle-brachial index (ABI) in combination with feet electrochemical skin conductance (FESC) for peripheral artery disease (PAD) in Chinese patients with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS Overall, 183 Chinese T2DM patients were enrolled in this study. The patients were classified into three groups: Group 1 comprised of uncomplicated type 2 diabetics (n = 36), Group 2 consisted of patients with diabetic peripheral neuropathy (n = 103) whereas Group 3 patients displayed peripheral artery disease (n = 44). All patients underwent Sudoscan test using a Sudoscan (Paris, France) and ABI assessment. RESULTS Multivariate logistic regression models revealed that FESC was an independent risk factor of developing PAD in patients with type 2 diabetes. The AUC for diagnostic, positive predictive and negative predictive value of ABI in combination with FESC for PAD were 0.907, 0.733 and 0.920, respectively. The specificity and sensitivity of ABI in combination with FESC for PAD were 0.914 and 0.750, respectively. CONCLUSIONS Ankle-brachial index in combination with FESC can accurately be used in early diagnosis of PAD.

A simple objective test is required to identify people with impaired physical aspects of health-related quality of life (QOL) due to intermittent claudication. This study assessed the relationship of QOL, function and physical activity to the need to stop during a six-minute walking test (6MWT) amongst people with intermittent claudication.This was a prospective case-control study conducted at two centers in Australia. 173 participants with a history of intermittent claudication and peripheral artery disease diagnosed by ankle brachial pressure index0.9, completed two 6MWTs one week apart. QOL was assessed with the short form (SF)-36. Physical activity was assessed by an accelerometer to record step count, stepping time and energy expenditure over 7 days. Physical performance was assessed by the Short Physical Performance Battery (SPPB) test. The associations of the need to stop at least once during the 6MWT with QOL, function and activity were assessed using Mann Whitney U test and analysis of covariates.Participants that had to stop at least once during the two 6MWTs (46; 26.6%) had significantly lower scores for three of the domains (physical functioning, role-physical and bodily pain) and the physical component summary (PCS) measure of the SF-36 compared to those who did not need to stop (n = 127; 73.4%). After adjusting for the risk factor co-variates (diabetes, hypertension and ankle brachial pressure index) which were significantly unequally distributed, needing to stop during the 6MWTs was significantly associated with a lower PCS score (adjusted mean 36.5, standard error 0.8 vs. 30.5, standard error 1.3; F = 14.0; P0.001; partial eta squared 0.077). Participants that had to stop at least once during the two 6MWTs had significantly lower 7-day step count, time stepping and energy expenditure, but not total SPPB score, compared to those who did not need to stop.Needing to stop during a 6MWT identified participants with intermittent claudication with poorer QOL and less physical activity compared to those that do not need to stop.

Objectives We aimed to investigate the association between hypertension and asymptomatic lower extremity artery disease (LEAD) in outpatients with known history of coronary artery disease (CAD). Methods Patients with known history of CAD who have been undergone coronary angiography and have significant coronary artery stenosis (more than 60%) were included. LEAD was defined as ankle-brachial index (ABI) Results One hundred and four patients were included. 82.7% of patients were male. Mean age was 57.05 ± 7.97. The prevalence of hypertension was 35.6%, and the prevalence of LEAD was 16.3%. A higher proportion of LEAD was found in hypertensive (18.9%) compared to non-hypertensive (14.9%), although not statistically significant (OR: 1.33; 95% CI: 0.46 to 3.85; p=0.598). There was an association between ABI and systolic BP (p=0.016), but not with diastolic BP (p=0.102). Conclusions Our study showed that the prevalence of LEAD in hypertension, especially in the CAD population, is relatively high. There was no association between hypertension and LEAD, but a higher prevalence of LEAD was found in hypertensive patients. Nevertheless, LEAD screening is still recommended in hypertensive patients, especially in the CAD population, given the fact that outcomes of health and mortality are worse for those with concomitants of these diseases.

In patients with peripheral artery disease (PAD), supervised exercise at near-moderate pain improves walking ability but not ankle-brachial index (ABI) values. In a retrospective observational study, we determined vascular and functional effects of a 6-month structured pain-free exercise program in patients with claudication and compressible vessels. Four-hundred and fifty-nine consecutive patients were studied. Segmental limb pressures were measured and ABI calculated during circa-monthly hospital visits. The 6-min (6MWD) and the pain-free walking distance (PFWD) during the 6-min walking test were determined. Two daily 8-min sessions of slow–moderate in-home walking at increasing metronome-paced speed were prescribed. After excluding patients with unmeasurable ABI or incompletion of the program, 239 patients were studied. Safe and satisfactory (88%) execution of the prescribed training sessions was reported. During the visits, bilateral ABI improved (+ 0.07; p F = 46.52; p F = 5.52; p p p F = 15.91; p F = 235.93; p R2 = 0.27; p

Context Observational studies have been associated obesity with chronic kidney disease (CKD) and arterial stiffness, but the causality remains unclear. Objective We aimed to investigate the causality of obesity with CKD and arterial stiffness using mendelian randomization (MR) analysis. Methods We genotyped 14 body mass index (BMI)-associated variants validated in East Asians in 11 384 Chinese adults. A genetic risk score based on the 14 variants and the 14 individual single-nucleotide variations (SNVs, formerly single-nucleotide polymorphisms [SNPs]) were respectively used as instrumental variables (IVs). CKD was defined as estimated glomerular filtration rate less than 60 mL/min/1.73 m2. Arterial stiffness was defined as brachial-ankle pulse wave velocity greater than 1550 cm/s. Results Using the genetic risk score as the IV, we demonstrated causal relations of each 1-SD increment in BMI with CKD (odds ratio [OR]: 2.36; 95% CI, 1.11-5.00) and arterial stiffness (OR: 1.71; 95% CI, 1.22-2.39). Using the 14 SNVs individually as IVs, each 1-SD increment in BMI was casually associated with CKD (OR: 2.58; 95% CI, 1.39-4.79) and arterial stiffness (OR: 1.87; 95% CI, 1.24-2.81) in the inverse-variance weighted analysis, and MR-Egger regression revealed no evidence of horizontal pleiotropy (both P for intercept ≥ .34). The causality between obesity and CKD was validated in 2-sample MR analysis among Europeans (681 275 of Genetic Investigation of ANthropometric Traits and 133 413 of CKD Genetics). Conclusion This study provided novel insights into the causality of obesity with CKD and arterial stiffness, highlighting the importance of weight management for primary prevention and control of subclinical vascular diseases.

Objectives Indoxyl sulfate, known for its cardiovascular toxicity, is associated with vascular and coronary artery diseases and increased mortality. Peripheral arterial disease, defined by low ankle–brachial index, is associated with increased mortality in patients on hemodialysis. The present study aimed to determine the relationship between the serum indoxyl sulfate level and peripheral arterial disease in patients on maintenance hemodialysis. Methods The present cross-sectional, single-center study included 75 patients on maintenance hemodialysis. Serum indoxyl sulfate levels were determined by high-performance liquid chromatography–mass spectrometry. Ankle–brachial index values were measured using an automated oscillometric device. Patients with ankle–brachial indexes of < 0.9 were categorized into the low ankle–brachial index group. Results In the study cohort, 12 of the 75 patients (16.0%) had low ankle–brachial indexes. The rates of diabetes mellitus ( p = 0.010) as well as the serum levels of C-reactive protein ( p < 0.001) and indoxyl sulfate ( p < 0.001) were higher in the low ankle–brachial index group than the normal ankle–brachial index group. The multivariable logistic regression analysis revealed that serum levels of indoxyl sulfate (odds ratio = 1.123, 95% confidence interval 1.011–1.249, p = 0.031) and C-reactive protein (each 0.1 mg/dL increase, odds ratio = 1.169, 95% confidence interval 1.018–1.343, p = 0.027) were independently associated with peripheral arterial disease in patients on maintenance hemodialysis. Conclusions Serum indoxyl sulfate levels were associated with peripheral arterial disease in patients on maintenance hemodialysis.

This multicenter, phase 4, Prospective Randomized Open, Blinded End‐point (PROBE) study aimed to evaluate safety and efficacy of telmisartan/rosuvastatin single‐pill combination (SPC) therapy on lowering central blood pressure (BP) compared with telmisartan monotherapy in hypertensive patients with dyslipidemia in Korea. Study was terminated earlier than planned due to COVID‐19 pandemic, thus should be considered as a pilot study. Among 125 patients who met the inclusion criteria of hypertension and dyslipidemia (defined as 10‐year Atherosclerotic Cardiovascular Disease risk score over 5%), 80 patients went through 4‐week single‐group run‐in period with telmisartan 40–80 mg, then randomized to telmisartan 80 mg + rosuvastatin (10 or 20 mg) SPC group or telmisartan 80 mg monotherapy group. The central/brachial BP, brachial‐ankle pulse wave velocity (baPWV), and augmentation index (AIx) were assessed at baseline and 16 weeks later. Mean brachial SBP changed from 135.80 ± 14.22 mmHg to 130.69 ± 13.23 mmHg in telmisartan/rosuvastatin group and from 134.37 ± 12.50 mmHg to 133.75 ± 12.30 mmHg in telmisartan monotherapy group without significant difference (between‐group difference p = .149). Mean central SBP were reduced significantly in the telmisartan/rosuvastatin group with change from 126.72 ± 14.44 mmHg to 121.56 ± 14.56 mmHg while telmisartan monotherapy group showed no significant change (between‐group difference p = .028). BaPWV changed from 1672.57 ± 371.72 m/s to 1591.75 ± 272.16 m/s in telmisartan/rosuvastatin group and from 1542.85 ± 263.70 m/s to 1586.12 ± 297.45 m/s in telmisartan group with no significance (between‐group difference p = .078). Change of AIx had no significant difference (between‐group difference p = .314). Both groups showed excellent compliance rate of 96.9 ± 4.5% with no significant difference in adverse rate. Telmisartan/rosuvastatin SPC therapy was more effective in lowering central BP compared with the telmisartan monotherapy. The results of this study showed benefit of additive statin therapy in hypertensive patients combined with dyslipidemia.

Popliteal Artery Entrapment Syndrome (PAES) is an uncommon syndrome that predominantly affects young athletes. Functional PAES is a subtype of PAES without anatomic entrapment of the popliteal artery. Patients with functional PAES tend to be younger and more active than typical PAES patients. A number of differential diagnoses exist, the most common of which is chronic exertional compartment syndrome. There is no consensus regarding choice of investigation for these patients. However, exercise ankle-brachial indices and magnetic resonance imaging are less invasive alternatives to digital subtraction angiography. Patients with typical symptoms that are severe and repetitive should be considered for intervention. Surgical intervention consists of release of the popliteal artery, either via a posterior or medial approach. The Turnipseed procedure involves a medial approach with a concomitant release of the medial gastrocnemius and soleal fascia, the medial tibial attachments of the soleus and excision of the proximal third of the plantaris muscle. Injection of botulinum A toxin under electromyographic guidance has recently shown promise as a diagnostic and/or therapeutic intervention in small case series. This review provides relevant information for the clinician investigating and managing patients with functional PAES.

The ankle-brachial index is a commonly used tool for identifying peripheral artery disease for cardiovascular risk stratification. An abnormal ankle-brachial index occurs only following extensive peripheral atherosclerosis occlusion, and thus has poor sensitivity for coronary atherosclerosis. There is a critical need for the development of tools that can detect risk prior to advanced stages of atherosclerosis. We sought to determine the sensitivity of femoral ultrasound for coronary artery disease. In this prospective, cross-sectional study, participants (n = 124) underwent ankle-brachial index measurement and femoral ultrasound for assessment of intima-media thickness, maximal plaque height, and total plaque area following coronary angiography. Receiver operating characteristic areas under the curve were plotted for identifying significant coronary artery disease (≥ 50% stenosis). Logistic regression was utilized to evaluate associations. 64% of participants had significant, angiography-confirmed coronary artery disease. Femoral ultrasound plaque area yielded the highest area under the curve for detecting significant coronary disease (area under the curve = 0.731). In contrast, an abnormal ankle-brachial index (≤ 0.90) produced an area under the curve of 0.568. Femoral ultrasound had a higher sensitivity (85%) than the ankle-brachial index (25%) for ruling out significant coronary artery disease. Both ankle-brachial index and femoral ultrasound have similar capacity to detect peripheral artery disease. Femoral ultrasound has a significantly greater discriminatory power than ankle-brachial index to detect clinically significant coronary artery disease. Ultrasound-captured femoral plaque burden directly delineates the extent of peripheral arterial disease and is better at ruling out significant coronary atherosclerosis than the ankle-brachial index.

Background Triglyceride–glucose (TyG) index, a simple surrogate marker of insulin resistance, has been reported to be associated with arterial stiffness. However, previous studies were limited by the cross-sectional design. The purpose of this study was to explore the longitudinal association between TyG index and progression of arterial stiffness. Methods A total of 6028 participants were derived from the Kailuan study. TyG index was calculated as ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2]. Arterial stiffness was measured using brachial-ankle pulse wave velocity (baPWV). Arterial stiffness progression was assessed by the annual growth rate of repeatedly measured baPWV. Multivariate linear regression models were used to estimate the cross-sectional association of TyG index with baPWV, and Cox proportional hazard models were used to investigate the longitudinal association between TyG index and the risk of arterial stiffness. Results Multivariate linear regression analyses showed that each one unit increase in the TyG index was associated with a 39 cm/s increment (95%CI, 29–48 cm/s, P P P P non-linearity = 0.005). Conclusion Participants with a higher TyG index were more likely to have a higher risk of arterial stiffness. Subjects with a higher TyG index should be aware of the following risk of arterial stiffness progression, so as to establish lifestyle changes at an early stage.

Left ventricular hypertrophy (LVH) is the most common target organs damage in the hypertension patients. Abnormal low (≤0.9) or high (≥1.40) ankle brachial index (ABI) are associated with an increased risk of cardiovascular events. However, the relationships between a high ABI in the normal range (0.9–1.4) and LVH in Han Chinese hypertension are not entirely elucidated. This study included 3953 hypertension patients aged 40–75 years among Han Chinese. Hypertension was defined as systolic blood pressure≥140 mm Hg, diastolic blood pressure≥90 mm Hg, or history of antihypertensive drug use. Left ventricular mass (LVM) was measured by transthoracic echocardiography. LVH was diagnosed by using the criteria of LVM ≥49.2 g/m2.7 for men and 46.7 g/m2.7 for women. Our study suggested that the ABI was higher in patients with LVH than in those without (1.13±0.11, 1.11±0.11, p

Increased left ventricular (LV) afterload in patients with aortic stenosis consists of valvular and vascular loads; however, the effects of vascular load induced by arterial stiffness on clinical outcomes after transcatheter aortic valve replacement (TAVR) remain unclear. This study evaluated the prognostic value of brachial-ankle pulse wave velocity (baPWV) after TAVR.A retrospective study including 161 consecutive patients who underwent TAVR with a pre-procedural baPWV assessment was conducted. We investigated the association between baPWV and the 1-year composite outcome comprising all-cause death and rehospitalization related to heart failure. Echocardiographic measurements including the LV mass index (LVMi) and LV diastolic function at 1, 6, and 12 months after TAVR were assessed.Of the 161 patients, 31 patients experienced composite outcome within 1 year after TAVR. The receiver operating characteristic curve analysis revealed that the discriminating baPWV level to discern 1-year composite outcome was 1,639 cm/s, and all subjects were allocated to two groups based on the result. Baseline characteristics were comparable between the high baPWV (n = 72) and low baPWV groups (n = 89). The Kaplan-Meier curve revealed a significantly higher cumulative 1-year composite outcome in the high baPWV group than in the low baPWV group (31% vs. 10%; log-rank test, p0.001). High baPWV was an independent predictor of the 1-year composite outcome (adjusted hazard ratio, 3.42; 95% confidence interval, 1.62-7.85; p = 0.002). Furthermore, post-procedural echocardiography revealed that the high baPWV group had less LVMi regression and higher E/e' after TAVR compared to the low baPWV group. The delayed reversal in LVMi and diastolic function attributable to arterial stiffness might be linked to impaired clinical outcomes after TAVR.Higher baPWV could be associated with adverse clinical outcomes and delayed reverse LV remodeling after TAVR.

Cold stimuli increase arterial stiffness, but it has not been explored whether arterial stiffness increases after swimming in cooler water. To investigate the effects of water temperature on changes in arterial stiffness after swimming, 13 men participated in three trials of 20-min swimming in 25 and 30°C water (S25 and S30, respectively) and sitting at poolside (CON) in random order. There were no significant differences between the S25 and S30 trials in mean swimming distance (719 vs. 722 m) and heart rate reserve during swimming (63% vs. 63%). Sublingual temperature was lower after swimming in 25°C water versus before swimming. Aortic pulse wave velocity (aortic PWV, an index of central arterial stiffness based on applanation tonometry) and brachial-ankle pulse wave velocity (baPWV, an index of systemic arterial stiffness based on air plethysmography) were higher 30 min after versus before swimming in 25°C water. Aortic PWV recovered to pre-swimming levels by 60 min after swimming in 25°C water, but baPWV was higher even at 60 min after swimming. PWVs did not change in the CON and S30 trials. Systemic vascular resistance based on Doppler ultrasonography did not change, but forearm vascular resistance based on strain-gauge plethysmography was higher 30 and 60 min after swimming in 25°C water. Heart rate was higher, but stroke volume was lower 30 min after swimming in 25°C water, resulting in no detectable change in cardiac output. In conclusion, arterial stiffness increases acutely after moderate-intensity swimming in cooler water.

BACKGROUND Limb ischemia is a major complication of femoral venoarterial extracorporeal membrane oxygenation (VA-ECMO). Use of ankle-brachial index (ABI) to monitor limb perfusion in VA-ECMO has not been described. We report our experience monitoring femoral VA-ECMO patients with serial ABI and the relationships between ABI and near infrared spectroscopy (NIRS). METHODS This is a retrospective single-center review of consecutive adult patients placed on femoral VA-ECMO between January 2019 and October 2019. Data were collected on patients with paired ABI and NIRS values. Relationships between NIRS and ABI of the cannulated (E-NIRS and E-ABI) and non-cannulated legs (N-NIRS and N-ABI) along with the difference between legs (d-NIRS and d-ABI) were determined using Pearson correlation. RESULTS Overall, 22 patients (mean age 56.5 ± 14.0 years, 72.7% male) were assessed with 295 E-ABI and E-NIRS measurements, and 273 N-ABI and N-NIRS measurements. Mean duration of ECMO support was 129.8 ± 78.3 h. ECMO-mortality was 13.6% and in-hospital mortality was 45.5%. N-ABI and N-NIRS were significantly higher than their ECMO counterparts (ABI mean difference 0.16, 95% confidence interval [CI]: 0.13-0.19, p

Background Peripheral arterial disease is a stenosis or occlusion of peripheral arteries that results in compromised blood flow and muscle ischemia. The available diagnostic methods are mostly used to measure and visualize blood flow and are not useful in the evaluation of perfusion, especially in diabetic patients, which is now considered to be a research priority by most of the vascular societies around the world as this is still a relatively poorly studied phenomenon. Objective The aim of this review is to explore the clinical significance of muscle tissue oxygenation monitoring in lower-extremity peripheral artery disease diagnosis using the near-infrared spectroscopy method. Methods A systematic search in PubMed, CINAHL, and Cochrane databases was performed to identify clinical near-infrared spectroscopy (NIRS) studies in English and Russian, published until September 2019, involving muscle tissue oxygenation in peripheral arterial disease (PAD). The manuscripts were reviewed by two researchers independently and scored on the quality of the research using MINORS criteria. Results After screening 443 manuscripts, 23 studies ( n = 1580) were included. NIRS-evaluated recovery time seems to be more accurate than ankle-brachial index in diabetic patients to differentiate between moderate and severe claudication. Consistent findings across all the included studies showed that both the oxygenation and deoxygenation rates as well as the recovery times varied from patient to patient and therefore were not suitable for standardization. Conclusions The clinical relevance of routine use of NIRS to diagnose PAD is unproven; therefore, its use is not currently part of standard-of-care for patients with PAD since the absolute values seem to vary significantly, depending on the outside conditions. More data need to be provided on the possible use of NIRS monitoring intraoperatively where the conditions can be more controlled.

Objective: Arterial stiffness (ArSt) describes a loss of arterial wall elasticity and is an independent predictor of cardiovascular events. A cardiometabolic-based chronic disease model integrates concepts of adiposity-based chronic disease (ABCD), dysglycemia-based chronic disease (DBCD), and cardiovascular disease. We assessed if ABCD and DBCD models detect more people with high ArSt compared with traditional adiposity and dysglycemia classifiers using the cardio-ankle vascular index (CAVI). Methods: We evaluated 2070 subjects aged 25 to 64 years from a random population-based sample. Those with type 1 diabetes were excluded. ABCD and DBCD were defined, and ArSt risk was stratified based on the American Association of Clinical Endocrinologists criteria. Results: The highest prevalence of a high CAVI was in stage 2 ABCD (18.5%) and stage 4 DBCD (31.8%), and the lowest prevalence was in stage 0 ABCD (2.2%). In univariate analysis, stage 2 ABCD and all DBCD stages increased the risk of having a high CAVI compared with traditional classifiers. After adjusting for age and gender, only an inverse association between obesity (body mass index >= 30 kg/m(2)) and CAVI remained significant. Nevertheless, body mass index was responsible for only 0.3% of CAVI variability. Conclusion: The ABCD and DBCD models showed better performance than traditional classifiers to detect subjects with ArSt; however, the variables were not independently associated with age and gender, which might be explained by the complexity and multifactoriality of the relationship of CAVI with the ABCD and DBCD models, mediated by insulin resistance. (C) 2021 AACE. Published by Elsevier Inc. All rights reserved.

Background While often thought of as a diagnostic tool, ultrasound (US) can also potentially be used as a therapeutic modality. US applies mechanical stress on endothelial cells and induces nitric oxide synthase, which regulates the secretion of nitric oxide, a potent vasodilator. In animal ischemic models, US has been shown to improve hindlimb, myocardial, and cerebral perfusion. We performed a pilot trial of US therapy in the lower extremities of human subjects with intermittent claudication. Methods 10 subjects (5 male, 5 female, mean age 69.7 ± 10.3) with intermittent claudication were recruited. Both legs were placed in a specially designed boot with a water interface between US transducers and the legs. Subjects underwent pulsed US therapy at 250 kHz frequency for 30 min for three treatments a week for six weeks. Pre and post treatment ankle:brachial index (ABI), 6-min walk (6 MW), Walking Impairment Questionnaire (WIQ), and Short Form 36 (SF36) were performed. Pre and post-treatment results were compared with paired t-test. Results Six minute walking distance at baseline was 352 ± 70 m, after one treatment session 353 ± 70 m (p = 0.99), and at completion 372 ± 71 m (p = 0.015). There was a trend toward improved ABI after 6 weeks of treatment (0.53 ± 0.17 vs 0.64 ± 0.12, p = 0.083). After six weeks, significant improvements were noted in overall WIQ score (2.00 ± 1.48 vs 2.63 ± 1.38, p = 0.0001), WIQ (distance) 2.07 ± 1.54 vs 2.73 ± 1.42 (p = 0.036), and WIQ (stair) 2.00 ± 1.67 vs 2.62 ± 1.24, p = 0.034, with a trend in WIQ (speed), 1.89 ± 1.26 vs 2.46 ± 1.43, p = 0.069. In the SF-36, significant improvements were noted in the domains of physical functioning (44.0 ± 41.6 vs 50.5 ± 41.1, p = 0.009) and role limitations – physical (35.0 ± 48.3 vs 60.0 ± 49.6, p = 0.006) after six weeks. Conclusions Therapeutic US is a potential noninvasive treatment for intermittent claudication. Pilot study patients noted significant improvements in 6 MW and WIQ results after 6 weeks of treatment. A nonsignificant improvement in ABI was noted. Further research will be needed to clarify optimal treatment frequency and duration.

Faster pulse wave velocity (PWV) is known to be associated with the incidence of cardiovascular diseases (CVD). The aim of this study was to clarify the hypothesis that PWV may be associated with future CVD events even when its time‐dependent changes were adjusted. We also investigated a prognostic significance of cardio‐ankle vascular index, another index of arterial stiffness. Study participants included 8850 community residents. The repeated measures of the clinical parameters at 5.0 years after the baseline were available for 7249 of the participants. PWV was calculated using the arterial waveforms measured at the brachia and ankles (baPWV). The cardio‐ankle vascular index was calculated by estimated pulse transit time from aortic valve to tibial artery. During the 8.53 years follow‐up period, we observed 215 cases of CVD. The incidence rate increased linearly with baPWV quartiles (per 10 000 person‐years: Q1, 2.7; Q2, 12.6; Q3, 22.5; Q4, 76.2), and the highest quartile was identified as an independent determinant of incident CVD by conventional Cox proportional hazard analysis adjusted for known risk factors [hazard ratio (HR), 4.00; p = .007]. Per unit HR of baPWV (HR, 1.15; p

Aims A diabetic foot ulcer (DFU) is associated with increased cardiovascular risk and mortality, independently of ulcer etiology (ischemic, neuro-ischemic or neuropathic). Ankle–brachial index (ABI) is the most commonly used test when diagnosing peripheral macrovascular disease and is a well-known marker for increased cardiovascular risk. Transcutaneous oxygen pressure (TcPO2) is considered to better evaluate microvascular function and has in previous studies shown correlations with both wound healing and survival. The aim of this study was to evaluate the combined impact of a low TcPO2 ( Methods Type 2 diabetes patients aged 2 were screened for participation. The primary endpoint was mortality after three years, assessed from the National Death Registry in Sweden. Results The study enrolled 235 participants with a median age of 76 years. Individuals with either an abnormally high or low ABI in combination with a low TcPO2 had the worst survival rates, with three-year mortality of 54%, compared to 42% in those with one abnormal variable (either ABI or TcPO2), and 21% in those with normal ABI and TcPO2. Conclusions Combining ABI and TcPO2 when risk stratifying DFU patients seems to provide additional predictive information, not only concerning ulcer healing and limb salvage, but also on survival.

Objective No agreement has been reached regarding which bedside test is the most useful for the diagnosis of peripheral arterial disease (PAD) in patients with diabetes. The aim of the present systematic review and meta-analysis was to evaluate the performance of bedside tests for the detection of PAD in individuals with diabetes. Methods MEDLINE and EMBASE databases were systematically searched for studies providing data on the diagnostic performance of bedside tests used for the detection of PAD in those with diabetes. A meta-analysis was performed to obtain pooled estimates of sensitivity and specificity for the diagnosis of PAD. Results A total of 18 studies, reporting on a total of 3016 limbs of diabetic patients, were included in our qualitative review. Of these, 11 studies (1543 limbs) were included in the meta-analysis of diagnostic accuracy: ankle-brachial pressure index (9 studies and 1368 limbs; sensitivity, 63.5% [95% confidence interval (CI), 51.7%-73.9%]; specificity, 89.3% [95% CI, 81.1%-94.2%]); toe-brachial pressure index (3 studies and 221 limbs; sensitivity, 83.0% [95% CI, 59.1-94.3%]; specificity, 66.3% [95% CI, 41.3%-84.6%]); and tibial waveform assessment (4 studies and 397 limbs; sensitivity, 82.8% [95% CI, 73.3%-89.4%], specificity, 86.8% [95% CI, 75.5%-93.3%]). Overall, we found a high risk of bias across the studies, most frequently relating to patient selection and the lack of blinding. Conclusions The toe-brachial pressure index, pulse oximetry, and tibial arterial waveform assessment demonstrated some promise, warranting further investigation.

Aim: Fatty liver and the liver fibrosis are known risk factors for cardiovascular disease (CVD). The severity of fatty liver can be assessed by determining the fatty liver index (FLI), and the severity of liver fibrosis can be assessed by determining the fibrosis-4 (FIB-4) score. We examined the differences in the associations of these two liver scoring systems with the pathophysiological abnormalities associated with the risk of development of CVD. Methods: The FLI and FIB-4 score were calculated in 2,437 Japanese men without any history of CVD. The serum NT-pro-BNP levels and brachial-ankle pulse wave velocity (baPWV) were also measured at the start of the study and the end of three years’ follow-up. Results: The FLI was significantly correlated with the baPWV ( p ＜0.01) and the FIB-4 score was significantly correlated with the serum NT-pro-BNP level ( p ＜0.01). Furthermore, the delta change of the FLI was significantly correlated with the delta change of the baPWV during the study period ( p =0.01), and the delta change of the FIB-4 score was significantly correlated with the delta change of the serum NT-pro-BNP level during the study period ( p ＜0.01). Conclusions: While the FIB-4 score may serve as a marker of the risk of development of heart failure, the FLI may be a marker of arterial stiffness in Japanese men without any history of CVD.

Many studies have reported that adults with congenital heart disease suffer from hypertension and cardiovascular disease even at younger ages. Therefore, we analyzed early vascular aging, which is defined as pulse wave velocity values higher than the 95th percentile for age and sex, and clarified the relationship between early vascular aging and many parameters related to cardiovascular disorders in adults with congenital heart disease. We enrolled 72 adult patients with congenital heart disease and measured their brachial-ankle pulse wave velocity. Comparing the data between age- and sex-matched controls, patients with a pulse wave velocity higher than the 95th percentile for age and sex were defined as exhibiting early vascular aging. The parameters of patients with and without early vascular aging were compared. Early vascular aging was observed in 15.6% of the patients. Age, systolic blood pressure, diastolic blood pressure, pulse pressure, blood sugar, hemoglobin A1c, uric acid, low-density lipoprotein cholesterol, and triglyceride levels were positive determinants of early vascular aging. Logistic regression analysis proved that systolic blood pressure was a significant determinant of early vascular aging (odds ratio, 1.128, 95% confidence interval, 1.049-1.214; p = 0.001). The prevalence of early vascular aging is high in adult patients with congenital heart disease. Because early vascular aging can damage a patient's vulnerable heart, careful follow-up of blood pressure and pulse wave velocity is essential.

Approximately one in five professional cycling athletes will eventually develop a sport-related vascular problem. However, detecting such flow limitation is a diagnostic challenge as the sensitivity of the currently available standard diagnostic tools is limited.Here we present an athlete with exercise-induced pain and weakness of the left leg. During the physical examination, pulsations of the femoral artery were palpable but less prominent. He was analyzed in an ongoing research project aimed at improving methods detecting sport-related leg flow limitations.During functional testing, the ankle-brachial index of the left leg was moderately lowered. However, results of near-infrared spectroscopy and pedal power measurements were largely abnormal suggesting a severe flow limitation.Combining post-exercise ankle-brachial index, near-infrared spectroscopy, and pedal power measurements as routine diagnostic functional testing suggested a severe arterial flow inflow limitation. Conventional diagnostics encompassing duplex-Doppler echography and magnetic resonance angiography confirmed a femoral artery occlusion.https://www.trialregister.nl/ identifier is Trial NL8557.

SUMMARY OBJECTIVE: To assess the prevalence of altered ankle-brachial index (1.3) in patients with type 1 diabetes and to compare it with the presence of subclinical atherosclerosis by carotid ultrasound. METHODS: Prospective, cross-sectional study in which 45 adults with type 1 diabetes were evaluated (age 34±10 years, 46.7% men). The data collected included anamnesis, clinical evaluation, calculation of the ankle-brachial index (relationship between systolic blood pressure in the ankle and brachial artery), and performance of carotid ultrasound. RESULTS: Thirty-two patients had ankle-brachial index >1.3 (66.7%) and no patient had ankle-brachial index 35 years and ankle-brachial index >1.4 showed a good correlation with atherosclerosis (r=0.49, p=0.021; r=0.56, p=0.008, respectively). A model associating age >35 years and ankle-brachial index >1.4 showed an excellent relationship with atherosclerosis (r=0.59, p=0.004). CONCLUSIONS: Our study showed that vascular calcification (ankle-brachial index >1.4) was frequent in this population with type 1 diabetes and associated with subclinical atherosclerosis. A model combining ankle-brachial index >1.4 and age >35 years showed an excellent correlation with atherosclerosis and can assist in clinical suspicion and optimize the request for additional tests.

Chronic disease of people living with human immunodeficiency virus (HIV) infection are now approaching those of the general population. Previous, in vitro studies shown that HIV causes arterial injuries resulting in inflammation and atherosclerosis but direct relationship between HIV infection clinical stages and lower extremity arterial disease (LEAD) remain controversial. No study assessed, with an accurate method, both the prevalence of LEAD and the influence of HIV severity on LEAD in HIV outpatients in Central Africa. A cross-sectional study was conducted among 300 HIV-infected outpatients, aged ≥ 40 years in Bujumbura, Burundi. All patients underwent ankle-brachial index (ABI) measurement and LEAD was diagnosed by ABI ≤ 0.9. The prevalence of LEAD was 17.3% (CI 95% 13.2–22.1). The mean age was 49.6 ± 7.1 years. On multivariable analysis, factors associated with LEAD were hypertension (OR = 2.42; 95% CI 1.10–5.80), and stage IV HIV clinical infection (OR = 4.92, 95% CI 1.19–20.36). This is the first study performed on a large HIV population in Central Africa, reporting high LEAD prevalence. It underlines the influence of HIV infection on peripheral atherosclerosis at latest clinical stages and the need for LEAD screening in HIV-infected patients.

Casein hydrolysate has been shown to improve arterial stiffness as estimated by brachial-ankle pulse wave velocity (baPWV) in untreated hypertensive patients. Facial pigmentation is associated with atherosclerosis, both of which are supposed to be modulated by tissue accumulation of advanced glycation end products (AGEs). However, effects of casein hydrolysate on facial pigmentation and AGEs remain largely unknown. This randomized double-blind placebo-controlled trial evaluated whether and how casein hydrolysate improves facial pigmentation in 80 nonhypertensive Japanese patients. Study participants were randomly assigned to receive either active tablets containing casein hydrolysate or placebo for 48 weeks. Facial pigmentation area, baPWV, and skin accumulation levels of AGEs were evaluated by Robo Skin Analyzer RSA50S II, volume-plethysmographic apparatus, and AGE Reader, respectively, at baseline and at the end of the intervention. Treatment with casein hydrolysate, but not placebo significantly reduced triglycerides and facial pigmentation area. There were significant differences of changes in triglycerides, facial pigmentation area, skin accumulation levels of AGEs, and baPWV between the two groups. Furthermore, changes in triglycerides and skin accumulation levels of AGEs were positively and independently associated with those in facial pigmentation area, whereas changes in baPWV were not. This study suggests that casein hydrolysate reduces facial pigmentation area in nonhypertensive participants partly by decreasing skin accumulation levels of AGEs. Clinical-Trials.gov ID: UMIN000027675.

International audience