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Background: Perioperative atrial fibrillation (AF) and myocardial injury after noncardiac surgery (MINS) are common complications after noncardiac surgery. Inflammation has been implicated in the pathogenesis of both disorders. The COP-AF trial tests the hypothesis that colchicine reduces the incidence of perioperative AF and MINS in patients undergoing major noncardiac thoracic surgery. Design: The 'COlchicine for the Prevention of Perioperative Atrial Fibrillation' (COP-AF) trial is an international, blinded, randomized trial that compares colchicine to placebo in patients aged at least 55 years and undergoing major noncardiac thoracic surgery with general anesthesia. Exclusion criteria include a history of AF and a contraindication to colchicine (e.g., severe renal dysfunction). Oral colchicine at a dose of 0.5 mg or matching placebo is given within 4 hours before surgery. Thereafter, patients receive colchicine 0.5 mg or placebo twice daily for a total of 10 days. The two independent co-primary outcomes are clinically important perioperative AF (including atrial flutter) and MINS during 14 days of follow-up. The main safety outcomes are sepsis or infection and non-infectious diarrhea. We aim to enroll 3,200 patients from approximately 40 sites across 11 countries to have at least 80% power for the independent evaluation of the two co-primary outcomes. Summary: COP-AF is a large randomized and blinded trial designed to determine whether colchicine reduces the risk of perioperative AF or MINS in patients who have major noncardiac thoracic surgery. Population Health Research Institute

In patients with ST-segment elevation myocardial infarction (STEMI), early initiation of high-intensity statin therapy, regardless of low-density lipoprotein (LDL) cholesterol levels, is the standard of practice worldwide. Aims: We sought to determine the effect of a similar early initiation strategy, using a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor added to the high-intensity statin, on LDL cholesterol in acute STEMI.In a randomised, double-blind trial we assigned 68 patients with STEMI undergoing primary percutaneous coronary intervention (PCI) to early treatment with alirocumab 150 mg subcutaneously or to a matching sham control. The first injection was given before primary PCI regardless of the baseline LDL level, then at 2 and 4 weeks. The primary outcome was the percent reduction in direct LDL cholesterol up to 6 weeks, analysed using a linear mixed model. Results: High-intensity statin use was 97% and 100% in the alirocumab and sham-control groups, respectively. At a median of 45 days, the primary outcome of LDL cholesterol decreased by 72.9% with alirocumab (2.97 mmol/L to 0.75 mmol/L) versus 48.1% with the sham control (2.87 mmol/L to 1.30 mmol/L), for a mean between-group difference of -22.3% (p0.001). More patients achieved the European Society of Cardiology/European Atherosclerosis Society dyslipidaemia guideline target of LDL ≤1.4 mmol/L in the alirocumab group (92.1% vs 56.7%; p0.001). Within the first 24 hours, LDL declined slightly more rapidly in the alirocumab group than in the sham-control group (-0.01 mmol/L/hour; p=0.03) with similar between-group mean values. Conclusions: In this randomised trial of routine early initiation of PCSK9 inhibitors in patients undergoing primary PCI for STEMI, alirocumab reduced LDL cholesterol by 22% compared with sham control on a background of high-intensity statin therapy. A large trial is needed to determine if this simplified approach followed by long-term therapy improves cardiovascular outcomes in patients with acute STEMI. (ClinicalTrials.gov: NCT03718286).

Background\ud The LACE index—length of stay (L), acuity (A), Charlson co-morbidities (C), and emergent visits (E)—predicts 30-day outcomes following heart failure (HF) hospitalization but is complex to score. A simpler LE index (length of stay and emergent visits) could offer a practical advantage in point-of-care risk prediction.\ud \ud Methods and results\ud This was a sub-study of the patient-centred care transitions in HF (PACT-HF) multicentre trial. The derivation cohort comprised patients hospitalized for HF, enrolled in the trial, and followed prospectively. External validation was performed retrospectively in a cohort of patients hospitalized for HF. We used log-binomial regression models with LACE or LE as the predictor and either 30-day composite all-cause readmission or death or 30-day all-cause readmission as the outcomes, adjusting only for post-discharge services. There were 1985 patients (mean [SD] age 78.1 [12.1] years) in the derivation cohort and 378 (mean [SD] age 73.1 [13.2] years) in the validation cohort. Increments in the LACE and LE indices were associated with 17% (RR 1.17; 95% CI 1.12, 1.21; C-statistic 0.64) and 21% (RR 1.21; 95% CI 1.15, 1.26; C-statistic 0.63) increases, respectively, in 30-day composite all-cause readmission or death; and 16% (RR 1.16; 95% CI 1.11, 1.20; C-statistic 0.64) and 18% (RR 1.18; 95% CI 1.13, 1.24; C-statistic 0.62) increases, respectively, in 30-day all-cause readmission. The LE index provided better risk discrimination for the 30-day outcomes than did the LACE index in the external validation cohort.\ud \ud Conclusions\ud The LE index predicts 30-day outcomes following HF hospitalization with similar or better performance than the more complex LACE index.

Aims The LE index (Length of hospitalization plus number of Emergent visits ≤6 months) predicts 30 day all‐cause readmission or death following hospitalization for heart failure (HF). We combined N‐terminal pro‐B type natriuretic peptide (NT‐proBNP) levels with the LE index to derive and validate the LENT index for risk prediction at the point of care on the day of hospital discharge. Methods and results In this prospective cohort sub‐study of the Patient‐centred Care Transitions in HF clinical trial, we used log‐binomial regression models with LE index and either admission or discharge NT‐proBNP as the predictors and 30 day composite all‐cause readmission or death as the primary outcome. No other variables were added to the model. We used regression coefficients to derive the LENT index and bootstrapping analysis for internal validation. There were 772 patients (mean [SD] age 77.0 [12.4] years, 49.9% female). Each increment in the LE index was associated with a 25% increased risk of the primary outcome (RR 1.25, 95% CI 1.16–1.35; C‐statistic 0.63). Adjusted for the LE index, every 10‐fold increase in admission and discharge NT‐proBNP was associated with a 48% (RR 1.48; 95% CI 1.10, 1.99; C‐statistic 0.64; net reclassification index [NRI] 0.19) and 56% (RR 1.56; 95% CI 1.08, 2.25; C‐statistic 0.64; NRI 0.21) increased risk of the primary outcome, respectively. The predicted probability of the primary outcome increased to a similar extent with incremental LENT, regardless of whether admission or discharge NT‐proBNP level was used. Conclusions The point‐of‐care LENT index predicts 30 day composite all‐cause readmission or death among patients hospitalized with HF, with improved risk reclassification compared with the LE index. The performance of this simple, 3‐variable index ‐ without adjustment for comorbidities ‐ is comparable to complex risk prediction models in HF. Trial Registration: ClinicalTrials.gov Identifier: NCT02112227

Aims Data on patient characteristics, prevalence, and outcomes of atrial fibrillation (AF) patients without traditional risk factors, often labelled ‘lone AF’, are sparse. Methods and results The RE-LY AF registry included 15 400 individuals who presented to emergency departments with AF in 47 countries. This analysis focused on patients without traditional risk factors, including age ≥60 years, hypertension, coronary artery disease, heart failure, left ventricular hypertrophy, congenital heart disease, pulmonary disease, valve heart disease, hyperthyroidism, and prior cardiac surgery. Patients without traditional risk factors were compared with age- and region-matched controls with traditional risk factors (1:3 fashion). In 796 (5%) patients, no traditional risk factors were present. However, 98% (779/796) had less-established or borderline risk factors, including borderline hypertension (130–140/80–90 mmHg; 47%), chronic kidney disease (eGFR 30; 19%), diabetes (5%), excessive alcohol intake (>14 units/week; 4%), and smoking (25%). Compared with patients with traditional risk factors (n = 2388), patients without traditional risk factors were more often men (74% vs. 59%, P Conclusion Almost all patients without traditionally defined AF risk factors have less-established or borderline risk factors. These patients have a favourable 1-year prognosis, but risk of AF-related re-hospitalization remains high. Greater emphasis should be placed on recognition and management of less-established or borderline risk factors.

Aims To examine the rates of venous thromboembolism (VTE) in high-income, upper middle-income, and lower middle/low-income countries (World Bank Classification). Methods and results We examined the rates of VTE in high-income, upper middle-income, and lower middle/low-income countries (World Bank Classification) in a cohort derived from four prospective international studies (PURE, HOPE-3, ORIGIN, and COMPASS). The primary outcome was a composite of pulmonary embolism, deep vein thrombosis, and thrombophlebitis. We calculated age- and sex-standardized incidence rates (per 1000 person-years) and used a Cox frailty model adjusted for covariates to examine associations between the incidence of VTE and country income level. A total of 215 307 individuals (1.5 million person-years of follow-up) from high-income (n = 60 403), upper middle-income (n = 42 066), and lower middle/low-income (n = 112 838) countries were included. The age- and sex-standardized incidence rates of VTE per 1000 person-years in high-, upper middle-, and lower middle/low-income countries were 0.87, 0.25, and 0.06, respectively. After adjusting for age, body mass index (BMI), smoking, antiplatelet therapy, anticoagulant therapy, education level, ethnicity, and incident cancer diagnosis or hospitalization, individuals from high-income and upper middle-income countries had a significantly higher risk of VTE than those from lower middle/low-income countries [hazard ratio (HR) 3.57, 95% confidence interval (CI) 2.40–5.30 and HR 2.27, 95% CI 1.59–3.23, respectively]. The effect of country income level on VTE risk was markedly stronger in people with a lower BMI, hypertension, diabetes, non-White ethnicity, and higher education. Conclusion The rates of VTE are substantially higher in high-income than in low-income countries. The factors underlying the increased VTE risk in higher-income countries remain unknown.

The stepped-wedge (SW) cluster randomized controlled trial, in which clusters cross over in a randomized sequence from control to intervention, is ideal for the implementation and testing of complex health service interventions. In certain cases however, implementation of the intervention may pose logistical challenges, and variations in SW design may be required. We examine the logistical and statistical implications of variations in SW design using the optimization of the Patient-Centered Care Transitions in Heart Failure trial for illustration. We review the following complete SW design variations: a typical SW design; an SW design with multiple clusters crossing over per period to achieve balanced cluster sizes at each step; hierarchical randomization to account for higher-level clustering effects; nested substudies to measure outcomes requiring a smaller sample size than the primary outcomes; and hybrid SW design, which combines parallel cluster with SW design to improve efficiency. We also reviewed 3 incomplete SW design variations in which data are collected in some but not all steps to ease measurement burden. These include designs with a learning period that improve fidelity to the intervention, designs with reduced measurements to minimize collection burden, and designs with early and late blocks to accommodate cluster readiness. Variations in SW design offer pragmatic solutions to logistical challenges but have implications to statistical power. Advantages and disadvantages of each variation should be considered before finalizing the design of an SW randomized controlled trial.

Importance The relative safety and patency of skeletonized vs pedicled internal mammary artery grafts in patients undergoing coronary artery bypass graft (CABG) surgery are unknown. Objective To investigate the association of skeletonized vs pedicled harvesting with internal mammary artery graft patency and clinical outcomes 1 year after CABG surgery. Design, setting, and participants This study was a post hoc analysis of the multicenter, randomized, double-blind, placebo-controlled Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) clinical trial, which enrolled 27 395 patients from 602 centers in 33 countries from March 2013 through May 2016. Eligibility criteria for the trial included CABG surgery for coronary artery disease with at least 2 grafts implanted and an estimated glomerular filtration rate of at least 30 mL/min. A total of 1002 of 1448 patients were randomized to the CABG arm of the COMPASS trial and underwent skeletonized (282 [28.1%]) or pedicled (720 [71.9%]) internal mammary artery harvesting. The patients had evaluable angiography results 1 year after surgery. Data were analyzed from October 11, 2019, to May 14, 2020. Interventions Patients underwent graft harvesting with either the pedicled technique or skeletonized technique. Main outcomes and measures The primary outcome was graft occlusion 1 year after CABG surgery, as assessed by computed tomography angiography. Results A total of 1002 patients underwent skeletonized (282 [28.1%]; mean [SD] age, 65.9 [8.1] years; 229 men [81.2%]; 194 White patients [68.8%]) or pedicled (720 [71.9%]; mean [SD] age, 64.8 [7.6] years; 603 men [83.8%]; 455 White patients [63.2%]) internal mammary artery harvesting. Rates of internal mammary artery graft occlusion 1 year after CABG surgery were higher in the skeletonized group than in the pedicled group (33 of 344 [9.6%] vs 30 of 764 [3.9%]; graft-level adjusted odds ratio, 2.41; 95% CI, 1.39-4.20; P = .002), including the left internal mammary artery to left anterior descending artery (21 of 289 [7.3%] vs 25 of 725 [3.4%]; graft-level adjusted odds ratio, 2.10; 95% CI, 1.14-3.88, P = .02). After a mean follow-up of 23 months, skeletonized graft harvesting was also associated with a higher rate of major adverse cardiovascular events (20 [7.1%] vs 15 [2.1%]; adjusted hazard ratio, 3.19; 95% CI, 1.53-6.67; P = .002) and repeated revascularization (14 [5.0%] vs 10 [1.4%]; adjusted hazard ratio, 2.75; 95% CI, 1.10-6.88; P = .03). Conclusions and relevance This post hoc analysis of the COMPASS randomized clinical trial found that harvesting of the internal mammary artery during CABG surgery using a skeletonized technique was associated with a higher rate of graft occlusion and worse clinical outcomes than the traditional pedicled technique. Future randomized clinical trials are needed to establish the safety and patency of the skeletonized technique. Trial registration ClinicalTrials.gov Identifier: NCT01776424.

Background Patients with recent coronary artery bypass graft (CABG) surgery are at risk for early graft failure, which is associated with a risk of myocardial infarction and death. In the COMPASS (Cardiovascular OutcoMes for People Using Anticoagulation StrategieS) trial, rivaroxaban 2.5 mg twice daily plus aspirin 100 mg once daily compared with aspirin 100 mg once daily reduced the primary major adverse cardiovascular events (MACE) outcome of cardiovascular death, stroke, or myocardial infarction. Rivaroxaban 5 mg twice daily alone did not significantly reduce MACE. Objectives This pre-planned substudy sought to determine whether the COMPASS treatments are more effective than aspirin alone for preventing graft failure and MACE after CABG surgery. Methods The substudy randomized 1,448 COMPASS trial patients 4 to 14 days after CABG surgery to receive the combination of rivaroxaban plus aspirin, rivaroxaban alone, or aspirin alone. The primary outcome was graft failure, diagnosed by computed tomography angiogram 1 year after surgery. Results The combination of rivaroxaban and aspirin and the regimen of rivaroxaban alone did not reduce the graft failure rates compared with aspirin alone (combination vs. aspirin: 113 [9.1%] vs. 91 [8.0%] failed grafts; odds ratio [OR]: 1.13; 95% confidence interval [CI]: 0.82 to 1.57; p = 0.45; rivaroxaban alone vs. aspirin: 92 [7.8%] vs. 92 [8.0%] failed grafts; OR: 0.95; 95% CI: 0.67 to 1.33; p = 0.75). Compared with aspirin, the combination was associated with fewer MACE (12 [2.4%] vs. 16 [3.5%]; hazard ratio [HR]: 0.69; 95% CI: 0.33 to 1.47; p = 0.34), whereas rivaroxaban alone was not (16 [3.3%] vs. 16 [3.5%]; HR: 0.99, CI: 0.50 to 1.99; p = 0.98). There was no fatal bleeding or tamponade within 30 days of randomization. Conclusions The combination of rivaroxaban 2.5 mg twice daily plus aspirin or rivaroxaban 5 mg twice daily alone compared with aspirin alone did not reduce graft failure in patients with recent CABG surgery, but the combination of rivaroxaban 2.5 mg twice daily plus aspirin was associated with similar reductions in MACE, as observed in the larger COMPASS trial. (Cardiovascular OutcoMes for People Using Anticoagulation StrategieS [COMPASS]; NCT01776424)

Introduction Heart Failure (HF) is a common cause of hospitalization in older adults. The transition from hospital to home is high-risk, and gaps in transitional care can increase the risk of re-hospitalization and death. Combining health care services supported by meta-analyses, we designed the PACT-HF transitional care model. Methods Adopting an integrated Knowledge Translation (iKT) approach in which decision-makers and clinicians are partners in research, we implement and test the effectiveness of PACT-HF among patients hospitalized for HF. We use a pragmatic stepped wedge cluster randomized trial design to introduce the complex health service intervention to 10 large hospitals in a randomized sequence until all hospitals initiate the intervention. The goal is for all patients hospitalized with HF to receive self-care education, multidisciplinary care, and early follow-up with their health care providers; and in addition, for high-risk patients to receive post-discharge nurse-led home visits and outpatient care in Heart Function clinics. This requires integration of care across hospitals, home care agencies, and outpatient clinics in our publicly funded health care system. While hospitals are the unit of recruitment and analysis, patients (estimated sample size of 3200) are the unit of analysis. Primary outcomes are hierarchically ordered as time to composite all-cause readmissions / emergency department (ED) visits / death at 3 months and time to composite all-cause readmissions / ED visits at 30 days. In a nested study of 8 hospitals, we measure the patient-centered outcomes of Discharge Preparedness, Care Transitions Quality, and Quality Adjusted Life Years (QALY); and the 6-month health care resource use and costs. We obtain all clinical and cost outcomes via linkages to provincial administrative databases. Conclusions This protocol describes the implementation and testing of a transitional care model comprising health care services informed by high-level evidence. The study adopts an iKT and pragmatic approach, uses a robust study design, links clinical trial data with outcomes held in administrative databases, and includes patient-reported outcomes. Findings will have implications on clinical practice, health care policy, and Knowledge Translation (KT) research methodology.

Introduction: Fibrinolytic factors, plasminogen activator inhibitor-1, tissue plasminogen activator, tissue plasminogen activator/plasminogen activator-complex and the haemostatic factor von Willebrand factor are known markers of cardiovascular disease. Their plasma levels are adversely affected in patients with dysglycaemia, and glucose normalization with insulin glargine might improve the levels of these factors. Methods: Prespecified Swedish substudy of the Outcome Reduction with an Initial Glargine Intervention trial (ClinicalTrials.gov number, NCT00069784). Tissue plasminogen activator activity, tissue plasminogen activator antigen, plasminogen activator inhibitor-1 antigen, tissue plasminogen activator/plasminogen activator inhibitor-1 complex and von Willebrand factor were analysed at study start, after 2 years and at the end of the study (median follow-up of 6.2 years). Results: Of 129 patients (mean age of 64 ± 7 years, females: 19%), 68 (53%) and 61 (47%) were randomized to the insulin glargine and standard care group, respectively. Allocation to insulin glargine did not significantly affect the studied fibrinolytic markers or von Willebrand factor compared to standard care. Likewise, there were no significant differences in plasminogen activator inhibitor-1, tissue plasminogen activator antigen and von Willebrand factor. During the whole study period, the within-group analysis revealed a curvilinear pattern and significant changes for tissue plasminogen activator/plasminogen activator inhibitor-1 complex, tissue plasminogen activator antigen and von Willebrand factor in the insulin glargine but not in the standard care group. Conclusion: In people with dysglycaemia and other cardiovascular risk factors, basal insulin does not improve the levels of markers of fibrinolysis or von Willebrand factor compared to standard glucose-lowering treatments.

Background Risk prediction models in heart failure (HF) are typically complex, derived retrospectively from administrative databases, and modest in their ability to discriminate between high, medium, and low risk categories. The complexity of these models makes them difficult to use at the point of care. Purpose To determine if a simple risk index using Length of hospital stay (L), number of Emergency department visits in the preceding 6 months (E), and either admission or discharge N-Terminal (NT) prohormone of Brain Natriuretic Peptide (pro-BNP) at the point of care can predict 30-day readmissions in patients hospitalized for HF. Methods This is a sub-study of the Patient-Centered Care Transitions in HF (PACT-HF) stepped-wedge cluster randomized trial. We included 772 patients hospitalized for HF at 10 Canadian hospitals. We used log-binomial regression models with Length of stay, Emergency department visits in the preceding 6 months, and either admission or discharge N-Terminal prohormone of Brain Natriuretic Peptide (NT-pro-BNP) as the predictor variables and 30-day all-cause readmission as the outcome. We derived the LENT risk score from the β-coefficients of the regression model (Fig. 1). All the models were adjusted for post-discharge services. We assessed model discrimination with C-statistics and model calibration with the net reclassification index (NRI). We used the bootstrapping approach with 100 runs for internal validation. Results The LENT index had a possible score ranging from 1 to 13 (Fig 1). Increments in the LENT risk score were associated with an increased risk of 30-day readmission; a 1-point increase in the LENT index using the admission and discharge NT-pro-BNP predicted a 23% and 19% increase in 30-day readmission risk, respectively. The internal validation produced similar results. Compared to a null model, the LE index had an NRI of 0.35 [95% CI 0.18, 0.53], and admission and discharge NT-pro-BNP further improved calibration of the LE index (NRI 0.15 [95% CI 0, 0.32] and 0.20 [95% CI 0.03, 0.37], respectively). The LENT index offered modest discrimination for 30-day readmission (C-statistic 0.64 [95% CI 0.59, 0.69]), similar to more complex risk models. Figure 1. The LENT index scoring system Conclusion A simple risk index based on Length of stay, Emergent visits, and NT-pro-BNP at the point of care can reliably predict 30-day readmissions. The LENT index offers ease of use over traditional risk prediction models. Acknowledgement/Funding Canadian Institutes of Health Research, Ontario MOHLTC, Roche Diagnostics

Aims\ud Heart failure (HF) guidelines place patients into 3 discrete groups according to left ventricular ejection fraction (LVEF): reduced (

Aims: Total and free testosterone and sex hormone-binding globulin may affect cardiovascular prognosis in women. The objective was to study the association between sex hormones and prognosis in women with dysglycemia and high cardiovascular risk. Methods: This epidemiological report included dysglycemic women from the Outcome Reduction with an Initial Glargine Intervention trial ( n = 2848) with baseline total testosterone and sex hormone-binding globulin. Free testosterone was calculated with the Vermeulen formula. Cox regression analyses adjusted for variables including age, previous diseases and pharmacological treatments were used to estimate the association between these levels and the composite cardiovascular outcome (death from cardiovascular causes, nonfatal myocardial infarction or nonfatal stroke) and all-cause mortality per one standard deviation. Results: Patients (73% post-menopausal) were followed for a median of 6.1 years during which 377 cardiovascular events and 389 deaths occurred. In Cox analyses, total and free testosterone were not associated with any outcomes, but sex hormone-binding globulin was related to all-cause mortality in age adjusted (HR 1.15; 95% CI 1.06–1.24; p Conclusions: Increasing levels of baseline sex hormone-binding globulin were associated with an increased risk of all-cause mortality in dysglycemic women at high cardiovascular risk. Trial registration ClinicalTrials.gov no. NCT00069784.

Background The Length of stay, Acuity, Comorbidities, Emergency department visits in prior 6 months (LACE) index threshold of 10 predicts readmission or death in general medical patients in administrative databases. We assessed whether the unadjusted LACE index, computed at the bedside, can predict 30-day outcomes in patients hospitalized for heart failure. Methods We used logistic regression with LACE as the continuous predictor and 30-day readmissions and 30-day readmission or death as outcomes. We determined a suitable LACE threshold using logistic regression and the closest-to-(0,1) criterion for dichotomized LACE scores. We assessed model discrimination with C statistics and 95% CI. Results Of 378 patients, a majority (91%) had LACE scores ≥10. Incremental LACE scores increased the odds of 30-day readmissions (odds ratio [OR] 1.13, 95% CI 1.02-1.24) and 30-day readmissions or death (OR 1.11, 95% CI 1.01-1.22). C statistics for 30-day readmissions (0.59, 95% CI 0.52-0.65) and 30-day readmission or death (0.57, 95% CI 0.51-0.64) were nonsignificantly lower than the Centers for Medicare/Medicaid Services–endorsed readmission risk score (0.61, 95% CI 0.55-0.67 and 0.62, 95% CI 0.55-0.68, respectively). LACE ≥13 predicted 30-day readmissions (OR 1.91, 95% CI 1.17-3.09) and 30-day readmission or death (OR 1.59, 95% CI 1.00-2.54), and met the closest-to-(0,1) criterion for optimal threshold. Conclusions LACE calculated at the bedside predicts 30-day clinical outcomes in hospitalized heart failure patients. While there is a continuum of risk, a threshold of ≥13 is more suitable than ≥10 to identify high-risk patients. Given its modest discrimination, however, we do not recommend its preferential use over validated risk prediction tools such as readmission risk score.

Well-designed randomized controlled trials (RCTs) are the gold standard for informing clinical practice. However, RCTs often do not enroll participants representative of the patient population for whom the tested interventions will be applied. The aim of this study was to estimate the enrolment of

Aims: Testosterone and its binding protein sex hormone-binding globulin have been associated with cardiovascular disease and dysglycaemia. However, information on the prognostic implication in patients at high cardiovascular risk with dysglycaemia is inconsistent. The study objective was to determine whether testosterone and/or sex hormone-binding globulin predict cardiovascular events or death in dysglycaemic patients. Methods: Dysglycaemic males at high cardiovascular risk ( n = 5553) who participated in the Outcome Reduction with an Initial Glargine Intervention (ORIGIN) trial and provided baseline blood samples were studied. Testosterone and sex hormone-binding globulin were measured at baseline and used to estimate free testosterone. Low levels of total and free testosterone were defined as ≤300 ng/dl and ≤7 ng/dl, respectively. Patients were followed for six years for cardiovascular events (defined as the composite of cardiovascular death, non-fatal myocardial infarction or stroke) and all-cause mortality. Results: The mean total and free testosterone levels were 416.6 ng/dl and 8.4 ng/dl, and low levels were present in 13% and 37% of the patients. The median sex hormone-binding globulin level was 35 nmol/l. In Cox regression models adjusted for age, previous diseases and pharmacological treatment, neither total nor free testosterone predicted cardiovascular events. However, a one-standard-deviation increase in sex hormone-binding globulin predicted both cardiovascular events (hazard ratio 1.07; 95% confidence interval 1.00–1.14; p = 0.03) and all-cause mortality (hazard ratio 1.13; 95% confidence interval 1.06–1.21; p Conclusion: Sex hormone-binding globulin, but not total testosterone, predicts cardiovascular disease and all-cause mortality in dysglycaemic males at high cardiovascular risk.

7 p., Objective To evaluate the performance of the non-laboratory INTERHEART risk score (NL-IHRS) to predict incident cardiovascular disease (CVD) across seven major geographic regions of the world. The secondary objective was to evaluate the performance of the fasting cholesterol-based IHRS (FC-IHRS). Methods Using measures of discrimination and calibration, we tested the performance of the NL-IHRS (n=100 475) and FC-IHRS (n=107 863) for predicting incident CVD in a community-based, prospective study across seven geographic regions: South Asia, China, Southeast Asia, Middle East, Europe/North America, South America and Africa. CVD was defined as the composite of cardiovascular death, myocardial infarction, stroke, heart failure or coronary revascularisation. Results Mean age of the study population was 50.53 (SD 9.79) years and mean follow-up was 4.89 (SD 2.24) years. The NL-IHRS had moderate to good discrimination for incident CVD across geographic regions (concordance statistic (C-statistic) ranging from 0.64 to 0.74), although recalibration was necessary in all regions, which improved its performance in the overall cohort (increase in C-statistic from 0.69 to 0.72, p

The role of testosterone and sex hormone-binding globulin (SHBG) in female cardiovascular disease and dysglycemia is debated. The present objective was to investigate the prognostic impact of total (TT) and free testosterone (FT) and SHBG in women at high cardiovascular risk and dysglycemia.

Background—Serum biomarkers may identify people at risk for cardiovascular (CV) outcomes. Biobanked serum samples from 8494 participants with dysglycemia in the completed Outcome Reduction With Initial Glargine Intervention trial were assayed for 284 biomarkers to identify those that could identify people at risk for a CV outcome or death when added to clinical measurements.Methods and Results—A multiplex analysis measured a panel of cardiometabolic biomarkers in 1 mL of stored frozen serum from every participant who provided biobanked blood. After eliminating undetectable or unanalyzable biomarkers, 8401 participants who each had a set of 237 biomarkers were analyzed. Forward-selection Cox regression models were used to identify biomarkers that were each independent determinants of 3 different incident outcomes: (1) the composite of myocardial infarction, stroke, or CV death; (2) these plus heart failure hospitalization or revascularization; and (3) all-cause death. When added to clinical variables, 10 biomarkers were independent determinants of the 1405 CV composite outcomes observed during follow-up; 9 biomarkers (including 8 of these 10) were independent determinants of the 2435 expanded composite outcomes; and 15 (including the 10 CV composite biomarkers) were independent determinants of the 1340 deaths. Adjusted C statistics increased from 0.64 for the clinical variables to 0.71 and 0.68 for the 2 CV composite outcomes, respectively, with the greatest increase to 0.75 for death (PConclusions—A systematic hypothesis-free approach identified combinations of up to 15 cardiometabolic biomarkers as independent determinants of CV outcomes or death in people with dysglycemia.Clinical Trial Registration—URL:http://www.clinicaltrials.gov. Unique identifier: NCT00069784.

Background— Interventional cardiologists receive one of the highest levels of annual occupational radiation exposure. Further measures to protect healthcare workers are needed. Methods and Results— We evaluated the efficacy of a pelvic lead shield and a novel surgical cap in reducing operators’ radiation exposure. Patients undergoing coronary angiography or percutaneous coronary intervention (n=230) were randomized to have their procedure with or without a lead shield (Ultraray Medical, Oakville, Canada) placed over the patient. During all procedures, operators wore the No Brainer surgical cap (Worldwide Innovations and Technology, Kansas City, KS) designed to protect the head from radiation exposure. The coprimary outcomes for the lead shield comparison were (1) operator dose (µSv) and (2) operator dose indexed for air kerma (µSv/mGy). For the cap comparison, the primary outcome was the difference between total radiation dose (µSv; internal and external to cap). The lead shield use resulted in a 76% reduction in operator dose (mean dose, 3.07; 95% confidence interval [CI], 2.00–4.71 µSv lead shield group versus 12.57; 95% CI, 8.14–19.40 µSv control group; P P P Conclusions— The use of a pelvic lead shield and the cap reduced significantly the operator radiation exposure and can be easily incorporated into clinical practice. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT02128035.

Introduction: In most regions of the world, cardiovascular disease (CVD) risk scores have undergone limited evaluation in prospective cohort studies to determine their accuracy for estimating CVD risk. Objectives: We evaluated the performance of the Non-laboratory INTERHEART Risk Score (NL-IHRS) and fasting-cholesterol based IHRS (FC-IHRS) across seven distinct geographic regions in the Prospective Urban Rural Epidemiology (PURE) study. Methods: We tested the performance of the NL-IHRS (N1⁄498,775) and FC-IHRS (N1⁄4108,516) for predicting incident CVD in a community-based, prospective study across 7 geographic regions: South Asia, China, Southeast Asia, Middle East, Europe/ North America, South America and Africa. CVD was defined as the composite outcome of cardiovascular death, myocardial infarction, stroke, heart failure or coronary revascularization. The performance of the score was evaluated using measures of discrimination (e.g. concordance-statistic [C-statistic]) and calibration (e.g. intercept and calibration slope). Results: The NL-IHRS had satisfactory discrimination for incident CVD, although recalibration was necessary in all regions, which improved its overall performance (C-statistic (0.67 to 0.71, p