History Of Peripheral Arterial Disease Research Articles

Improvement of peripheral microcirculation after cardioversion of atrial fibrillation.

Near-infrared spectroscopy (NIRS) is a noninvasive method to measure regional tissue oxygenation (rSO2 ). In patients with atrial fibrillation (AF), cardiac output and endothelial function are altered. Peripheral tissue oxygenation may therefore be reduced. This study aims to describe the peripheral tissue oxygenation of the feet before and after synchronized electrical cardioversion (CV) of patients with AF using NIRS. Patients with AF undergoing CV were included and screened for peripheral arterial disease (PAD), diabetes mellitus (DM), and peripheral neuropathy (PN). NIRS was performed before and after CV under continuous ECG and monitoring of peripheral oxygen saturation. NIRS was registered on the dorsoplantar and plantar area of both feet. Capillary blood gas analysis was performed and left ventricular ejection fraction (LVEF) was determined. Twelve patients (five women, seven men, age 70.8 ± 10.8 years) participated. None had history of PAD. DM was present in three (25%) patients. Two patients (16.7%) had PN. CV was successful in 11 patients. Overall, rSO2 improved significantly in all patients after CV (P=.0003). Mean improvement was 7.17%. There were no significant changes in body temperature, ankle-brachial index, sO2 , pO2 , pCO2 , pH, or lactate after CV. Heart rate was significantly lower (P<.0001) and LVEF significantly higher (P=.0123) after CV. In patients with AF, peripheral tissue oxygen saturation improves significantly after successful CV. This suggests that patients with PAD may not only benefit from interventional or surgical improvement of arterial vascularization, but also from CV in case of AF.

Clinical features and burden of new onset diabetic foot ulcers post simultaneous pancreas kidney transplantation and kidney only transplantation

BackgroundPatients with diabetes and kidney disease are at risk of diabetes-related foot ulcers (DFU). Whether this risk is modified post simultaneous pancreas-kidney (SPK) or kidney only (KO) transplant is unknown. MethodsWe evaluated the incidence of new onset DFU post SPK and KO transplant in 235 patients with diabetic kidney disease and diabetic neuropathy. In total 90 (51% male) SPK patients and 145 KO (66% male, 26% Type 1 DM) were evaluated in a single centre retrospective study. Median (range) follow up was 6 (3 to 13) years for both cohorts. ResultsWe observed that 16 (17%) of SPK and 22 (15%) KO patients respectively developed a DFU during follow up. In both cohorts a history of peripheral arterial disease [37.5% vs. 4%] and pre-transplant history of DFU were associated with post transplant DFU (p ≪ 0.05).In KO cohort, patients who developed a DFU were more likely to have T1DM than T2DM (29% vs. 10%), p ≪ 0.05. There was no impact of DFU on SPK transplant failure. In contrast patients with DFU post KO transplant had more than five fold increased hazard ratio (HR) of transplant failure as compared to those without DFU independent of other risk factors [HR 5.19 95% CI (2.05 to 13.18) p = 0.001]. ConclusionNearly 1 in 7 patients develop a new onset DFU post KO or SPK transplantation and DFU also significantly increases risk of failure of the transplanted kidney. Our results highlight the need for greater awareness of regular foot examination, DFU prevention and risk evaluation in post-transplant patients. Research in contextEvidence before this studyPatients with diabetes and kidney disease are at enhanced risk of diabetic foot ulcers (DFU). Whether this risk is modified post successful kidney only (KO) or simultaneous pancreas and kidney (SPK) transplantation is unknown. Small case series and studies with short term follow up report varied rates of incidence and are from historical cohorts before the use of modern anti-transplant medications and treatments. Short term studies also suggest that post SPK the resultant normoglycaemia may reverse some features and risk markers of DFU. There are no long term studies on the incidence and impact of diabetic foot ulcers in patients with diabetic kidney disease post SPK or KO transplantation.Added value of this studyWe report the long term follow up results on DFU incidence, clinical features and related impact on transplant viability in 235 patients with diabetic kidney disease and neuropathy post successful SPK and KO transplant at a single centre. We observed that nearly 1 in 7 patients developed a DFU during follow up and that in patients who received KO transplant onset of DFU was associated with more than 5 fold increase of transplant failure.Implications of all the available evidenceOur results highlight the need for greater awareness of regular foot examination, DFU prevention and risk evaluation in post-transplant patients. Despite normoglycaemia post SPK there is a residual burden and risk of DFU. Our work establishes a clinical rationale for further research to explore putative mechanisms that could explain the association between DFU and renal transplant dysfunction.

Impact of Low Ankle-Brachial Index on the Risk of Recurrent Vascular Events.

Background and Purpose- Low ankle-brachial index (ABI) identifies a stroke subgroup with high risk of recurrent stroke, cardiovascular events, and death. However, limited data exist on the relationship between low ABI and stroke in low and middle-income countries. Therefore, we evaluated the prevalence of ABI ≤0.90 (which is diagnostic of peripheral artery disease) in nonembolic stroke patients or transient ischemic attack and assessed the correlation of low ABI with stroke risk, factors, and recurrent vascular events and death. Methods- Patients ≥45 years with acute transient ischemic attack or minor ischemic strokes were recruited consecutively from over 17 low-income and middle-income countries (Latin America [1543 patients], Middle East [1041 patients], North Africa [834 patients], and South Africa [217 patients]). The ABI measurement was performed at a single visit. Stroke recurrence and risk of new vascular events were assessed after 24 months of follow-up. Results- Among 3487 enrolled patients, abnormal ABI (<0.9) was present in 22.3 %. Patients with an ABI of ≤0.9 were more likely ( P<0.05) to be male, older, and have a history of peripheral artery disease, hypertension, and diabetes mellitus. During 2-year follow-up, the rate of major cardiovascular event was higher in patients with ABI <0.9 than those with ABI ≥0.9 (Kaplan-Meier estimates, 22.5%; 95% CI, 19.6-25.8 versus 13.7%; 21.4-15.1; P<0.001), and when ABI was categorized into 4 groups (≤0.6; 95% CI, 0.6-0.9; 0.9-1; 1-1.4), the rate of major cardiovascular event was higher in those with ABI ≤0.6 than the other groups (Kaplan-Meier estimates, 32.6%; 95% CI, 21.0-48.3 for ABI≤0.6 versus 21.7%; 95% CI, 18.8-25.0 for ABI 0.6-0.9 versus 14.3%; 95% CI, 12.4-16.6 for ABI 0.9-1 versus 13.3%; 95% CI, 11.6-15.2 for ABI 1-1.4; P<0.001). Conclusions- Among patients with nonembolic ischemic stroke or transient ischemic attack, those with low ABI had a higher rate of vascular events and death in this population. Screening for ABI in stroke patients may help identify patients at high risk of future events.

Abstract P304: Underuse of Cardiovascular Medications in Individuals With Lower Extremity Peripheral Artery Disease: the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)

Introduction: The underuse of cardiovascular therapies among individuals with lower extremity peripheral artery disease (PAD) has been reported. However, little is known about this in the Hispanic/Latinos, who may have limited access to health care and worse clinical outcomes than non-Hispanics. Methods: We studied the cross-sectional use of cardiovascular therapies including antiplatelet, lipid-lowering and antihypertensive medications among 826 HCHS/SOL participants who reported a PAD diagnosis by a physician. We studied the factors that may be associated with use of cardiovascular medications, including demographic, socioeconomic factors, acculturation, access to health care and comorbidities. Survey Poisson regression was used to generate the prevalence ratios. Factors in age-adjusted models with P≤0.10 were included in multivariate regression. Results: A total of 723 participants with medical history of PAD were free of coronary heart disease (CHD, mean age=53) while 103 patients had concurrent CHD (mean age=56). The overall age-adjusted prevalence of antiplatelet, lipid-lowering and antihypertensive medications were 31%, 26% and 34%, respectively. Individuals of Mexican background had low health insurance coverage (42%) and low use of antiplatelet (20%), statin (17%) and antihypertensive (47% among hypertensive individuals) medications. More advanced age, number of doctor visits (2+ vs 0-1) in the past year and number of cardiovascular risk factors (2+ vs 0-1) were significantly associated with using cardiovascular medications in adjusted models. Compared with those with PAD alone, individuals with PAD and concurrent CHD were more likely to use antiplatelet (PR=1.44, 95% CI 1.13-1.82) and statin (PR=1.56 [1.17-2.07]) treatment in the multivariate analysis. Conclusions: We found underuse of cardiovascular medications among Hispanic/Latino individuals with medical history of PAD. More efforts should be directed in eliminating treatment disparities in this important race-ethnic group.

Abstract TP527: Baseline Physical Activity Profiles in CREST-2 Trial Participants

Background: The importance of physical activity in preventing major vascular events has received increased attention in the past decade. Due to the inclusion of the INTERVENT lifestyle modification program, the CREST2 trial provides a unique opportunity to study physical activity profiles in patients with severe asymptomatic extracranial carotid stenosis. Hypothesis: Based on data from a trial of intracranial stenosis patients, we aimed to evaluate the hypothesis that &lt;40% of carotid stenosis subjects will have optimal physical activity levels. We also assessed key subgroups to determine patterns of physical activity. Methods: We analyzed 1087 CREST2 participants with baseline data on physical activity. The Physician-based Assessment and Counseling for Exercise (PACE) score is recorded for each patient and dichotomized as “in target” (4-8 points) or “out of target” (&lt;4 points). A PACE score of &lt;4 indicates a subject who does not engage in regular exercise. Results are analyzed for the entire trial. Chi square testing and t-tests were performed for evaluation of subgroup differences. Results: The mean age of the study population is 69.5±7.8 years (60% male). The median PACE score at baseline is 4.0 (mean 3.8±2.1; IQR 2 to 6). The Table shows baseline characteristics of patients by mean PACE score. Being male, not having diabetes mellitus, having a body mass index &lt;30kg/m2, being a non-smoker, and not having a history of peripheral arterial disease were associated with significantly higher mean PACE scores (P&lt;0.01). Conclusions: We have defined several patient groups with asymptomatic carotid stenosis that have suboptimal physical activity. These results provide opportunities for targeted efforts to improve primary stroke prevention. These baseline data will also allow investigators to determine if trial involvement and the INTERVENT program leads to improvement in the level of physical activity.

Clinical Characteristics and Adverse Events in Acute Coronary Syndrome Patients with a History of Peripheral Arterial Disease.

BackgroundIn clinical observation, patients with acute coronary syndrome complicated with peripheral artery disease have poor prognosis, so the relationship between the diseases and clinical characteristics need to be further explored.ObjectiveThis study aims to investigate clinical characteristics and independent risk factors for in-hospital adverse events in acute coronary syndrome patients with a history of peripheral arterial disease (PAD).MethodsA total of 5,682 patients with acute coronary syndrome were included into this study. These patients were divided into two groups according to the presence or absence of a history of PAD: PAD group (n = 188), and non-PAD (control) group (n = 5,494). Then, the clinical characteristics and incidence of in-hospital adverse events were analyzed; p < 0.05 was considered statistically significant.ResultsThe age of PAD patients was higher than that in the control group (65.5 ± 10.3 years vs. 58.6 ± 11 years, p < 0.001), and the proportion of PAD patients with diabetes history and stroke history was higher than that in the control group (73 [39%] vs. 1472 [26.8%], p = 0.018; 36 [19.3%] vs. 396 [7.2%], p < 0.001). The multivariate logistic regression analysis between groups based on in-hospital adverse events revealed that a history of PAD (OR = 1.791, p = 0.01), a history of diabetes (OR = 1.223, p = 0.001), and age of > 65 years old (OR = 4.670, p < 0.001) were independent risk factors for in-hospital adverse events.ConclusionA history of PAD, advanced age, and a history of diabetes are independent risk factors for in-hospital adverse events in patients with acute coronary syndrome.

Disease-specific characteristics of vascular cell adhesion molecule-1 levels in patients with peripheral artery disease

Peripheral arterial disease (PAD) is one of the most common manifestations of systemic atherosclerosis. The prevalence of unrecognized PAD is high, leading to a lack of opportunity to detect subjects at a high risk for cardiovascular events. Inflammatory processes play an important role in the disease initiation as well as in the disease progression. Vascular cell adhesion molecule 1 (VCAM-1), a biomarker of endothelial dysfunction, appears to be an important mediator in inflammatory processes. Therefore, we hypothesized that in patients with PAD, circulating VCAM-1 might be elevated due to its function in mediating adhesion of immune cells to the vascular endothelium in the process of endothelial dysfunction and inflammation, and, therefore, applicable as a diagnostic biomarker. A total of 126 non-consecutive patients were enrolled in this study, of whom 51 patients had typical clinical manifestations of PAD and as controls 75 patients with no history of PAD or cardiovascular disease. All serum samples were obtained either during hospitalization or during out-patient visits and analyzed for VCAM-1 by the ELISA. Compared with controls, median levels of VCAM-1 were significantly elevated in patients suffering from PAD (953 vs. 1352 pg/ml; p < 0.001). Furthermore, VCAM-1 appeared to be highly discriminative for the detection of PAD (AUC = 0.76; CI 0.67–0.83). We could not observe dynamics related to increasing disease stages according to Rutherford classes in patients with apparent PAD. VCAM-1 was shown to be a potential discriminator and biomarker for the severity of systemic atherosclerosis. In a logistic regression analysis, VCAM-1 was robustly associated with the diagnosis of PAD, even after correction for clinically relevant cofounders (namely age, arterial hypertension, diabetes and LDL levels). Thusly, VCAM-1 might serve as a biomarker for PAD screening and detection.

Safety and efficacy of second generation drug eluting stents in diabetic and non-diabetic patients

Objective: To investigate the long-term prognosis of Second generation drug-eluting stents(G2-DES) in diabetic mellitus(DM) and non-DM patients. Methods: Patients with coronary heart disease(CHD) in Fuwai Hospital from January 2013 to December 2013 who had exclusively G2-DES implantation, were consecutively included the follow-up period was 2 years. Results: A total of 6 094 patients with CHD were implanted with G2-DES, of which 1 862 patients with DM, and 4 232 patients without DM.The proportion of DM patients receiving G2-DES implantation with the following characteristics: advanced age, female, hypertension, hyperlipidemia, history of previous stroke, history of peripheral artery disease, previous history of PCI, and with triple vessel, high preoperative Syntax score, high number of target lesions, B2 or C type lesions, severe calcification lesions, and chronic occlusive disease were significantly higher than those of non-DM patients(P<0.05). The incidence of major adverse cardiac and cerebral vascular events(MACCE), target vascular revascularization(TVR) and target lesion revascularization(TLR) were higher in DM patients than in non-DM patients during 2 year's follow-up(P<0.05). The univariate COX regression analysis showed that diabetes was risk factor for MACCE in patients with CHD implanting G2-DES(HR=1.241, 95%CI: 1.053-1.463, P=0.010). However, multivariable COX analysis showed that DM was not an independent risk factor for MACCE in CHD patients with G2-DES(HR=1.125, 95%CI: 0.952-1.330, P=0.167). While age, female, preoperative Syntex score, triple vessel, B2 or C lesion were independent risk factors for poor clinical prognosis in CHD patients with G2-DES. Conclusions: (1) CHD patients with DM often accompany more clinical risk factors and complicated coronary lesions; (2) the incidence of MACCE, TVR and TLR in DM patients is significantly higher than non-DM patients with G2-DES during the 2 year's follow-up; (3) after multivariate adjustment, DM is not an independent risk factor for poor clinical prognosis in CHD patients with G2-DES, while traditional risk factors and complex coronary lesions are independent risk factors for poor clinical prognosis.

Trends in management and outcome of patients with non-ST elevation acute coronary syndromes and peripheral arterial disease

ObjectivePatients with non ST-segment elevation acute coronary syndromes (NSTE-ACS) and peripheral arterial disease (PAD) present a worse prognosis compared to those without PAD. We sought to describe contemporary trends of in-hospital management and outcome of patients admitted for NSTE-ACS with associated PAD. MethodsWe analyzed data from 6 Italian nationwide registries, conducted between 2001 and 2014, including consecutive NSTE-ACS patients. ResultsOut of 15,867 patients with NSTE-ACS enrolled in the 6 registries, 2226 (14.0%) had a history of PAD. As compared to non-PAD patients, those with PAD had significantly more risk factors and comorbidities (all p < 0.0001) that increased over time. Patients with PAD underwent less frequently coronary angiography (72.0% vs 79.2%, p < 0.0001) and percutaneous coronary intervention (PCI, 42.9% vs 51.8%, p < 0.0001), compared to patients without PAD. Over the years, a progressive and similar increase occurred in the rates of invasive procedures both in patients with and without PAD (both p for trend <0.0001). The crude in-hospital mortality rate did not significantly change over time (p for trend = 0.83). However, as compared to 2001, the risk of death was significantly lower in all other studies performed at different times, after adjustment for multiple comorbidities.. At multivariable analysis, PAD on admission was an independent predictor of in-hospital mortality [odds ratio (OR): 1.75; 95% confidence intervals (CI): 1.35–2.27; p < 0.0001]. ConclusionsOver the 14 years of observation, patients with PAD and NSTE-ACS exhibited worsening baseline characteristics and a progressive increase in invasive procedures. Whereas crude in-hospital mortality did not change over time, we observed a significant reduction in comorbidity-adjusted mortality, as compared to 2001.

Risk Score for Prediction of 10-Year Atrial Fibrillation: A Community-Based Study.

We used a large real-world data from community settings to develop and validate a 10-year risk score for new-onset atrial fibrillation (AF) and calculate its net benefit performance. Multivariable Cox proportional hazards model was used to estimate effects of risk factors in the derivation cohort (n = 96,778) and to derive a risk equation. Measures of calibration and discrimination were calculated in the validation cohort (n = 48,404). Cumulative AF incidence rates for both the derivation and validation cohorts were 5.8% at 10 years. The final models included the following variables: age, sex, body mass index, history of treated hypertension, systolic blood pressure ≥ 160 mm Hg, chronic lung disease, history of myocardial infarction, history of peripheral arterial disease, heart failure and history of an inflammatory disease. There was a 27-fold difference (1.0% vs. 27.2%) in AF risk between the lowest (-1) and the highest (9) sum score. The c-statistic was 0.743 (95% confidence interval [CI], 0.737-0.749) for the derivation cohort and 0.749 (95% CI, 0.741-0.759) in the validation cohort. The risk equation was well calibrated, with predicted risks closely matching observed risks. Decision curve analysis displayed consistent positive net benefit of using the AF risk score for decision thresholds between 1 and 25% 10-year AF risk. We provide a simple score for the prediction of 10-year risk for AF. The score can be used to select patients at highest risk for treatments of modifiable risk factors, monitoring for sub-clinical AF detection or for clinical trials of primary prevention of AF.

Clinical, biochemical and genetic risk factors for 30-day and 5-year mortality in 518 adult patients subjected to cardiopulmonary bypass during cardiac surgery - the INFLACOR study.

There is increasing evidence that genetic variability influences patients' early morbidity after cardiac surgery performed using cardiopulmonary bypass (CPB). The use of mortality as an outcome measure in cardiac surgical genetic association studies is rare. We publish the 30-day and 5-year survival analyses with focus on pre-, intra-, postoperative variables, biochemical parameters, and genetic variants in the INFLACOR (INFLAmmation in Cardiac OpeRations) cohort. In a prospectively recruited cohort of 518 adult Polish Caucasians, who underwent cardiac surgery in which CPB was used, the clinical data, biochemical parameters, IL-6, soluble ICAM-1, TNFα, soluble E-selectin, and 10 single nucleotide polymorphisms were evaluated for their association with 30-day and 5-year mortality. The 30-day mortality was associated with: pre-operative prothrombin international normalized ratio, intra-operative blood lactate, postoperative serum creatine phosphokinase, and acute kidney injury requiring renal replacement therapy (AKI-RRT) in logistic regression. Factors that determined the 5-year survival included: pre-operative NYHA class, history of peripheral artery disease and severe chronic obstructive pulmonary disease, intra-operative blood transfusion; and postoperative peripheral hypothermia, myocardial infarction, infection, and AKI-RRT in Cox regression. Serum levels of IL-6 and ICAM-1 measured three hours after the operation were associated with 30-day and 5-year mortality, respectively. The ICAM1 rs5498 was associated with 30-day and 5-year survival with borderline significance. Different risk factors determined the early (30-day) and late (5-year) survival after adult cardiac surgery in which cardiopulmonary bypass was used. Future genetic association studies in cardiac surgical patients should account for the identified chronic and perioperative risk factors.

Influence of micro- and macro-vascular disease and Tumor Necrosis Factor Receptor 1 on the level of lower-extremity amputation in patients with type 2 diabetes

BackgroundPatients with type 2 diabetes (T2D) face a high amputation rate. We investigated the relationship between the level of amputation and the presence of micro or macro-vascular disease and related circulating biomarkers, Tumor Necrosis Factor Receptor 1 (TNFR1) and Angiopoietin like-2 protein (ANGPTL2).MethodsWe have analyzed data from 1468 T2D participants in a single center prospective cohort (the SURDIAGENE cohort). Our outcome was the occurrence of lower limb amputation categorized in minor (below-ankle) or major (above ankle) amputation. Microvascular disease was defined as a history of albuminuria [microalbuminuria: uACR (urinary albumine-to-creatinine ratio) 30–299 mg/g or macroalbuminuria: uACR ≥ 300 mg/g] and/or severe diabetic retinopathy or macular edema. Macrovascular disease at baseline was divided into peripheral arterial disease (PAD): peripheral artery revascularization and/or major amputation and in non-peripheral macrovascular disease: coronary artery revascularization, myocardial infarction, carotid artery revascularization, stroke. We used a proportional hazard model considering survival without minor or major amputation.ResultsDuring a median follow-up period of 7 (0.5) years, 79 patients (5.5%) underwent amputation including 29 minor and 50 major amputations. History of PAD (HR 4.37 95% CI [2.11–9.07]; p < 0.001), severe diabetic retinopathy (2.69 [1.31–5.57]; p = 0.0073), male gender (10.12 [2.41–42.56]; p = 0.0016) and serum ANGPTL2 concentrations (1.25 [1.08–1.45]; p = 0.0025) were associated with minor amputation outcome. History of PAD (6.91 [3.75–12.72]; p < 0.0001), systolic blood pressure (1.02 [1.00–1.03]; p = 0.004), male gender (3.81 [1.67–8.71]; p = 0.002), and serum TNFR1 concentrations (HR 13.68 [5.57–33.59]; p < 0.0001) were associated with major amputation outcome. Urinary albumin excretion was not significantly associated with the risk of minor and major amputation.ConclusionsThis study suggests that the risk factors associated with the minor vs. major amputation including biomarkers such as TNFR1 should be considered differently in patients with T2D.

TCTAP C-027 Transbrachial Intra-aortic Balloon in Patient with Acute Coronary Syndrome and History of Peripheral Arterial Disease

TCTAP C-027 Transbrachial Intra-aortic Balloon in Patient with Acute Coronary Syndrome and History of Peripheral Arterial Disease

Incidence, timing, and type of first and recurrent ischemic events in patients with and without peripheral artery disease after an acute coronary syndrome

BackgroundPatients with peripheral artery disease (PAD) are known to have an increased risk of ischemic cardiovascular events. However, the influence of concomitant PAD on first and subsequent recurrent ischemic events after an acute coronary syndrome (ACS) remains poorly characterized. MethodsWe analyzed the combined data set from 4 randomized trials (PLATO, APPRAISE-2, TRA-CER, and TRILOGY ACS) in ACS for a follow-up length of 1 year. Using multivariable regression, we examined the association between PAD and major adverse cardiovascular events, a composite of cardiovascular death, myocardial infarction, and stroke. Among patients with a nonfatal first event, we evaluated the incidence and type of a second recurrent event. ResultsA total of 4,098 of 48,094 (8.5%) post-ACS patients had a history of PAD. The unadjusted frequency of major adverse cardiovascular events was 2-fold higher in patients with PAD (14.3% vs 7.5%) over a median (25th-75th) follow-up of 353 (223-365) days with an adjusted hazard ratio of 1.63 (95% CI: 1.48-1.78; P < .001). The frequency of recurrent ischemic events among those patients with a first, nonfatal event was higher among those with PAD (40.0% vs 27.7%). The relative frequency of each event type (cardiovascular death, noncardiovascular death, myocardial infarction, or stroke) within first and subsequent ischemic events was similar regardless of PAD status at baseline. ConclusionsPatients with PAD have a significantly higher risk of first and recurrent ischemic events in the post-ACS setting. These findings highlight the opportunity for improved treatments in patients with PAD who experience an ACS.

Abstract MP17: Galectin-3 and Subsequent Risk of Lower-extremity Peripheral Artery Disease: The Atherosclerosis Risk in Communities (ARIC) Study

Background: Galectin-3 is involved in the regulation of inflammation and the formation of fibrosis and has been liked to atherosclerosis. However, there are no studies investigating prospective associations of galectin-3 with incidence of lower-extremity peripheral artery disease (PAD). Methods: Among 9,827 ARIC participants without a history of PAD, we investigated whether galectin-3 (measured at visit 4 [1996-98]) was associated with incident clinical PAD through 2013, defined as hospitalizations with PAD diagnosis or leg revascularization. We defined PAD cases with rest pain or tissue loss as critical limb ischemia (CLI). We constructed Cox models with galectin-3 modeled categorically (quartiles) and continuously (log transformed). Results: During a median follow-up of 15.8 years, 287 participants developed PAD (105 incident CLI cases). In demographically adjusted models, galectin-3 demonstrated a dose-response association with incident PAD: hazard ratios (HRs) 2.55 (95% CI 1.80-3.61) and 1.69 (1.18-2.41) for the highest and second highest quartiles, as compared to the lowest quartile (Table; Model 1). Additional adjustment for traditional cardiovascular risk factors attenuated the associations, although the highest quartile remained borderline significant (HR 1.44 [0.99-2.07], p=0.051, Table: Model 2) and galectin-3 as a continuous variable remained significant (1.15 [1.02-1.29]). Similar results were observed for the association of galectin-3 with CLI. Conclusions: Galectin-3 was modestly associated with future risk of clinical PAD events in a community-based cohort, supporting the involvement of inflammation and fibrosis in the development of clinical PAD.

Design of a Randomized Placebo-Controlled Trial to Assess Dabigatran and Omeprazole in Patients with Myocardial Injury after Noncardiac Surgery (MANAGE)

BackgroundWorldwide approximately 200 million adults undergo major surgery annually, of whom 8 million are estimated to suffer a myocardial injury after noncardiac surgery (MINS). There is currently no trial data informing the management of MINS. Antithrombotic agents such as direct oral anticoagulants might prevent major vascular complications in patients with MINS. MethodsThe Management of Myocardial Injury After Noncardiac Surgery (MANAGE) trial is a large international blinded randomized controlled trial of dabigatran vs placebo in patients who suffered MINS. We used a partial factorial design to also determine the effect of omeprazole vs placebo in reducing upper gastrointestinal bleeding and complications. Both study drugs were initiated in eligible patients within 35 days of suffering MINS and continued for a maximum of 2 years. The primary outcome is a composite of major vascular complications for the dabigatran trial and a composite of upper gastrointestinal complications for the omeprazole trial. We present the rationale and design of the trial and baseline characteristics of enrolled patients. ResultsThe trial randomized 1754 patients between January 2013 and July 2017. Patients' mean age was 69.9 years, 51.1% were male, 14.3% had a history of peripheral artery disease, 6.6% had a history of stroke or transient ischemic attack, 12.9% had a previous myocardial infarction, and 26.0% had diabetes. The diagnosis of MINS was on the basis of an isolated ischemic troponin elevation in 80.4% of participants. ConclusionMANAGE is the first randomized controlled trial to evaluate a potential treatment of patients who suffered MINS.

Comparison of arterial stiffness in non-hypertensive and hypertensive population of various age groups

Objective: To investigate the impact of blood pressure and age on arterial stiffness in general population. Methods: Participants who took part in 2010, 2012 and 2014 Kailuan health examination were included. Data of brachial ankle pulse wave velocity (baPWV) examination were analyzed. According to the WHO criteria of age, participants were divided into 3 age groups: 18-44 years group (n=11 608), 45-59 years group (n=12 757), above 60 years group (n=5 002). Participants were further divided into hypertension group and non-hypertension group according to the diagnostic criteria for hypertension (2010 Chinese guidelines for the managemengt of hypertension). Multiple linear regression analysis was used to analyze the association between systolic blood pressure (SBP) with baPWV in the total participants and then stratified by age groups. Multivariate logistic regression model was used to analyze the influence of blood pressure on arterial stiffness (baPWV≥1 400 cm/s) of various groups. Results: (1)The baseline characteristics of all participants: 35 350 participants completed 2010, 2012 and 2014 Kailuan examinations and took part in baPWV examination. 2 237 participants without blood pressure measurement values were excluded, 1 569 participants with history of peripheral artery disease were excluded, we also excluded 1 016 participants with history of cardiac-cerebral vascular disease. Data from 29 367 participants were analyzed. The age was (48.0±12.4) years old, 21 305 were males (72.5%). (2) Distribution of baPWV in various age groups: baPWV increased with aging. In non-hypertension population, baPWV in 18-44 years group, 45-59 years group, above 60 years group were as follows: 1 299.3, 1 428.7 and 1 704.6 cm/s, respectively. For hypertension participants, the respective values of baPWV were: 1 498.4, 1 640.7 and 1 921.4 cm/s. BaPWV was significantly higher in hypertension group than non-hypertension group of respective age groups (P<0.05). (3) Multiple linear regression analysis defined risk factors of baPWV: Multivariate linear regression analysis showed that baPWV was positively correlated with SBP(t=39.30, P<0.001), and same results were found in the sub-age groups (t-value was 37.72, 27.30, 9.15, all P<0.001, respectively) after adjustment for other confounding factors, including age, sex, pulse pressure(PP), body mass index (BMI), fasting blood glucose (FBG), total cholesterol (TC), smoking, drinking, physical exercise, antihypertensive medications, lipid-lowering medication. (4) Multivariate logistic regression analysis of baPWV-related factors: After adjustment for other confounding factors, including age, sex, PP, BMI, FBG, TC, smoking, drinking, physical exercise, antihypertensive medication, lipid-lowering medication, multivariate logistic regression analysis showed that risks for increased arterial stiffness in hypertension group were higher than those in non-hypertension group, the OR in participants with hypertension was 2.54 (2.35-2.74) in the total participants, and same results were also found in sub-age groups, the ORs were 3.22(2.86-3.63), 2.48(2.23-2.76), and 1.91(1.42-2.56), respectively, in each sub-age group. Conclusion: SBP is positively related to arterial stiffness in different age groups, and hypertension is a risk factor for increased arterial stiffness in different age groups. Clinical Trial Registry Chinese Clinical Trial Registry, ChiCTR-TNC-11001489.

Peripheral arterial disease is associated with higher mortality in patients with incident acute myocardial infarction

BackgroundLittle data is available on short- and long-term survival in patients with peripheral arterial disease (PAD) after acute myocardial infarction (AMI). We aimed to examine the association of PAD and 28-day case fatality as well as long-term mortality in a population-based sample of patients with incident AMI. MethodsIn this secondary analysis of data from the German MONICA/KORA Myocardial Infarction Registry 4307 patients aged 28–74years with incident AMI with and without history of PAD (information derived from medical chart) were included. Data were collected between 2000 and 2008. Patients were followed-up until December 2011. Associations between PAD and 28-day case fatality were examined via multivariable logistic regression models, between PAD and long-term mortality with Cox proportional hazards regression models, respectively. ResultsFrom 303 (8.9%) patients with PAD, 22 (7.3%) died within 28-days post-AMI in contrast to 96 (2.9%) of patients without PAD. However, the fully adjusted model (OR 1.55, 95% CI 0.89–2.70) revealed no significant association. Long-term follow-up (median 5.7years) yielded 100 (32.4%) versus 483 (14.4%) cases of deaths among patients with and without PAD, respectively. This association was significant (fully adjusted model: HR 1.70, 95% CI 1.35–2.13), persisted up to 11years after AMI and was present in all subgroups according to age, sex and history of diabetes. The highest long-term mortality risk was found for patients younger than 63years with PAD (HR 2.19; 95% CI 1.41–3.39). ConclusionAMI patients with PAD differ considerably from their counterparts without PAD in terms of long-term survival.

Impact of Body Mass Index on Outcomes after Mesenteric Revascularization for Chronic Mesenteric Ischemia

Historically, patients with chronic mesenteric ischemia (CMI) are underweight with a low body mass index (BMI). However, with the recent obesity epidemic many of these patients now are overweight with a high BMI. We evaluated the impact of BMI on outcomes after mesenteric revascularization for CMI. A retrospective chart review of patients undergoing open or endovascular mesenteric revascularization for CMI between January 2000 and June 2015 was performed. Demographics, comorbidities, BMI, Society for Vascular Surgery-combined comorbidity score, treatment modality, postoperative complications, reintervention, and all-cause mortality were analyzed. The primary end point for the study was all-cause mortality at 5years. Patients were stratified using the World Health Organization BMI criteria. Univariate, Kaplan-Meier survival, and multivariate analyses were performed. In the study period, 104 unique patients underwent mesenteric revascularization for CMI, for 77 of whom BMI information was available. Of these 77, 30 patients were treated by endovascular revascularization, and 47 patients were treated by open revascularization. Overall, 27 (35.1%) were overweight or obese with a BMI ≥25. Median follow-up time was 41months. High BMI patients were less likely to have weight loss at the time of surgery (P=0.004). Stratified by BMI <25 versus BMI ≥25, 5-year survival for patients treated by open revascularization was 90% versus 50% (P=0.02); survival for patients treated by endovascular revascularization was 27% vs. 53% (P=0.37). Multivariate survival analysis identified active smoking, hypertensive chronic kidney disease, open repair with the use of venous conduit instead of prosthetic conduit (P<0.001), and history of peripheral arterial disease (PAD) (P=0.002), as independent predictors of increased all-cause mortality. BMI needs to be considered in assessing and counseling patients on outcomes of mesenteric revascularization for CMI, as a BMI over 25 is associated with poorer long-term survival after open revascularization. Smoking, hypertensive chronic kidney disease, PAD, and open repair with the use of venous conduit are independent predictors of long-term mortality after mesenteric revascularization independent of BMI.

Rivaroxaban with or without aspirin in patients with stable peripheral or carotid artery disease: an international, randomised, double-blind, placebo-controlled trial

Patients with peripheral artery disease have an increased risk of cardiovascular morbidity and mortality. Antiplatelet agents are widely used to reduce these complications. This was a multicentre, double-blind, randomised placebo-controlled trial for which patients were recruited at 602 hospitals, clinics, or community practices from 33 countries across six continents. Eligible patients had a history of peripheral artery disease of the lower extremities (previous peripheral bypass surgery or angioplasty, limb or foot amputation, intermittent claudication with objective evidence of peripheral artery disease), of the carotid arteries (previous carotid artery revascularisation or asymptomatic carotid artery stenosis of at least 50%), or coronary artery disease with an ankle-brachial index of less than 0·90. After a 30-day run-in period, patients were randomly assigned (1:1:1) to receive oral rivaroxaban (2·5 mg twice a day) plus aspirin (100 mg once a day), rivaroxaban twice a day (5 mg with aspirin placebo once a day), or to aspirin once a day (100 mg and rivaroxaban placebo twice a day). Randomisation was computer generated. Each treatment group was double dummy, and the patient, investigators, and central study staff were masked to treatment allocation. The primary outcome was cardiovascular death, myocardial infarction or stroke; the primary peripheral artery disease outcome was major adverse limb events including major amputation. This trial is registered with ClinicalTrials.gov, number NCT01776424, and is closed to new participants. Between March 12, 2013, and May 10, 2016, we enrolled 7470 patients with peripheral artery disease from 558 centres. The combination of rivaroxaban plus aspirin compared with aspirin alone reduced the composite endpoint of cardiovascular death, myocardial infarction, or stroke (126 [5%] of 2492 vs 174 [7%] of 2504; hazard ratio [HR] 0·72, 95% CI 0·57-0·90, p=0·0047), and major adverse limb events including major amputation (32 [1%] vs 60 [2%]; HR 0·54 95% CI 0·35-0·82, p=0·0037). Rivaroxaban 5 mg twice a day compared with aspirin alone did not significantly reduce the composite endpoint (149 [6%] of 2474 vs 174 [7%] of 2504; HR 0·86, 95% CI 0·69-1·08, p=0·19), but reduced major adverse limb events including major amputation (40 [2%] vs 60 [2%]; HR 0·67, 95% CI 0·45-1·00, p=0·05). The median duration of treatment was 21 months. The use of the rivaroxaban plus aspirin combination increased major bleeding compared with the aspirin alone group (77 [3%] of 2492 vs 48 [2%] of 2504; HR 1·61, 95% CI 1·12-2·31, p=0·0089), which was mainly gastrointestinal. Similarly, major bleeding occurred in 79 (3%) of 2474 patients with rivaroxaban 5 mg, and in 48 (2%) of 2504 in the aspirin alone group (HR 1·68, 95% CI 1·17-2·40; p=0·0043). Low-dose rivaroxaban taken twice a day plus aspirin once a day reduced major adverse cardiovascular and limb events when compared with aspirin alone. Although major bleeding was increased, fatal or critical organ bleeding was not. This combination therapy represents an important advance in the management of patients with peripheral artery disease. Rivaroxaban alone did not significantly reduce major adverse cardiovascular events compared with asprin alone, but reduced major adverse limb events and increased major bleeding. Bayer AG.