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The incidence of metabolic syndrome (MetS), diabetes mellitus (DM), and their coexistence is increasing but whether MetS increases cardiovascular risk beyond component risk factors is controversial.We compared the risk of cardiovascular death, myocardial infarction, or stroke among patients with MetS, newly detected DM, established DM, or coexistent MetS and DM in the global REduction of Atherothrombosis for Continued Health (REACH) registry.Outpatients with or at risk for atherothrombosis were recruited between 1 December 2003 and 31 December 2004 and followed up to 4 years for cardiovascular events. Risk was compared in patients with or without MetS or DM after adjustment for age, sex, risk factors, vascular disease, fasting blood glucose, therapy, and region.Among 44,548 REACH participants, 17,887 (40%) were without MetS or DM; 6459 had MetS (15%); 12,059 had established DM (27%); 7503 had both (17%); and 640 had newly detected DM (1%). Presence of MetS was not associated with higher cardiovascular events (12.6%, adjusted HR 0.98, 95% CI 0.89-1.08). In addition, once DM was evident, patients with coexistent MetS had similar increased risk (16.1%, adjusted HR 1.33, 95% CI 1.21-1.47) as DM alone (16.7%, adjusted HR 1.36, 95% CI 1.24-1.48). Newly detected DM was associated with increased cardiovascular risk (18.5%, adjusted HR 1.26, 95% CI 1.02-1.57), similar to longstanding DM. MetS was associated with incident DM (adjusted OR 1.94).In the REACH registry, presence of newly detected DM but not metabolic syndrome was associated with an increased risk of cardiovascular events.

To describe the characteristics, treatment, and mortality in patients with ST-elevation myocardial infarction (STEMI) by use of chronic oral anticoagulant (OAC) therapy.Using data from the Global Registry of Acute Coronary Syndromes (GRACE), patient characteristics, treatment, and reperfusion strategies of STEMI patients on chronic OAC are described, and relevant variables compared with patients not on chronic OAC. Six-month post-discharge mortality rates were evaluated by Cox proportional hazard models.Of 19,094 patients with STEMI, 574 (3.0%) were on chronic OAC at admission. Compared with OAC non-users, OAC users were older (mean age 73 vs. 65 years), more likely to be female (37 vs. 29%), were more likely to have a history of atrial fibrillation, prosthetic heart valve, venous thromboembolism, or stroke/transient ischaemic attack, had a higher mean GRACE risk score (166 vs. 145), were less likely to be Killip class I (68 vs. 82%), and were less likely to undergo catheterization/percutaneous coronary intervention (52 vs. 66%, respectively). Of the patients who underwent catheterization, fewer OAC users had the procedure done within 24 h of admission (56.5 vs. 64.5% of OAC non-users). In propensity-matched analyses (n=606), rates of in-hospital major bleeding and in-hospital and 6-month post-discharge mortality were similar for OAC users and OAC non-users (2.7 and 3.7%, p=0.64; 15 and 13%, p=0.56; 15 and 12%, p=0.47, respectively), rates of in-hospital recurrent myocardial infarction (8.6 and 2.0%, p0.001) and atrial fibrillation (32 and 22%, p=0.004) were higher in OAC patients, and rates of 6-month stroke were lower (0.6 and 4.3%, p=0.038). Patients in both groups who underwent catheterization had lower mortality than those who did not undergo catheterization.This is the largest study to describe the characteristics and treatment of STEMI patients on chronic OAC. The findings suggest that patients on chronic OAC are less likely to receive guideline-indicated management, but have similar adjusted rates of in-hospital and 6-month mortality.

Obesity is frequent in type 2 diabetic patients with myocardial infarction (MI) or established cardiovascular disease. Earlier studies suggest that elevated body mass index (BMI) is associated with a favorable prognosis for persons with established vascular disease. We sought to analyse the associations between raised BMI and waist circumference with the 2-year event rate in type 2 diabetic patients with established vascular disease.Patients from the Reduction of Atherothrombosis for Continued Health (REACH) Registry, an international, prospective cohort of patients at high risk of atherothrombosis, were selected if they were diabetic and had established atherosclerotic arterial disease (n = 19,579). The main outcomes after 2-year follow-up were: all-cause death, cardiovascular death, MI, stroke, cardiovascular death/MI/stroke, and cardiovascular death/MI/stroke/rehospitalization. The rates of all-cause death, cardiovascular death, and cardiovascular death/MI/stroke decreased across increasing BMI quintile categories, whereas the same rates were stable across waist categories. The hazard ratios, adjusted for confounders, decreased significantly with increasing BMI for all-cause death (p 0.0001), cardiovascular death (p = 0.0009), cardiovascular death/MI/stroke (p = 0.0004), and all events (p = 0.002), but not for greater waist circumference.There is an apparent obesity paradox (better outcome with increasing obesity) when obesity is measured by BMI but not when measured by waist circumference in diabetic subjects.

Although guidelines recommend similar evaluation and treatment for both sexes, differences in approach and outcomes have been reported.Prospective, observational registry.Consecutive patients at high cardiovascular risk were assessed for risk factors and management at baseline,and followed-up for 2 years.Twenty-two thousand and twenty-eight patients with documented arterial disease (symptomatic) or three or more atherothrombotic risk factors (asymptomatic) completed the 2-year follow-up of the REduction of Atherothrombosis for Continued Health Registry in Europe (women, 31.5%; men, 68.4%). Women patients were 3.3 years (mean) older than men. Few differences were observed between asymptomatic men and women in risk factor profile or management at baseline. Higher proportions of symptomatic women than men had diabetes (P0.001), hypertension (P0.0001), elevated total cholesterol levels (P0.0001) or elevated triglycerides (P0.01). A much lower proportion of women than men were current smokers (asymptomatic, 14.6 vs. 29.3%; symptomatic, 11.9 vs.19.5%, both P0.0001). Within the symptomatic population, women received antithrombotic agents (91.8 vs. 94.9%,P0.0001) and lipid-lowering agents (68.2 vs. 73.1%, P0.0001) less frequently than men. After multivariate adjustment,fewer symptomatic women than men had undergone coronary revascularizations at 2 years (odds ratio, 0.72; 95% confidence interval, 0.61-0.85). There were no differences in primary outcomes, including cardiovascular death/myocardial infarction/stroke (odds ratio, 1.01, 95% confidence interval, 0.93-1.11, P=0.78), between the sexes.Although no differences were found in cardiovascular event rates at 2-year follow-up, secondary prevention could be improved in women, which might further reduce event rates.

Aims To evaluate the influence of achieving secondary prevention target treatment goals for cardiovascular (CV) risk factors on clinical outcomes in patients with prior coronary artery bypass surgery (CABG). Methods and results Accordingly, we analysed treatment to target goals in patients with prior CABG and atherothrombotic disease or known risk factors (diabetes, hypertension, hypercholesterolaemia, smoking, obesity) enrolled in the global REduction in Atherothrombosis for Continued Health (REACH) Registry, and their association with 1 year outcomes. A total of 13 907 of 68 236 patients (20.4%) in REACH had a history of prior CABG, and 1 year outcomes data were available for 13 207 of these. At baseline 75% risk factors at goal, respectively; P for trend 0.059). Conclusion Risk-factor control varied greatly in CABG patients. Although CABG patients are frequently treated with appropriate therapies, these treatments fail to achieve an adequate level of prevention in many. This failure was associated with a trend for worse age-, gender-, and region-adjusted clinical outcomes. Thus, perhaps secondary prevention after CABG needs to focus on more comprehensive modification of risk factors to target goals in the hope of preventing subsequent CV events, and represents an opportunity to improve CV health.

To determine the relationship between anticoagulation levels during percutaneous coronary intervention, and ischaemic events and bleeding.A sub-analysis from the STEEPLE trial was conducted. Pre-defined target anticoagulation levels were achieved in 86% of patients receiving enoxaparin, compared with 20% receiving unfractionated heparin (UFH) (P0.001). A significant relationship was observed between anti-Xa levels0.9 IU/mL and covariate-adjusted rate of non-coronary artery bypass graft-related major and minor bleeding [odds ratio (OR) 1.6, 95% CI 1.0-2.5 for each unit of anti-Xa; P = 0.03]; anti-Xa levels and covariate-adjusted incidence of death, myocardial infarction, or revascularization showed no significance (P = 0.47). Major bleeding increased significantly with an activated clotting time (ACT)325 s (OR 1.6, 95% CI 1.1-2.2 per 100 s; P = 0.04). A significant relationship with increasing ischaemic events was observed when ACT was325 s (OR 0.7, 95% CI 0.2-0.8 per 100 s; P = 0.006) indicating a narrow therapeutic window.Target anticoagulation levels were achieved more readily in patients receiving enoxaparin. An anti-Xa level of up to 0.9 IU/mL has a good safety and efficacy profile; poor achievement of target ACT with UFH makes assessing the optimal range difficult.

Aims To assess whether the use of the femoral or radial approach for percutaneous coronary intervention (PCI) interacted with the efficacy and safety of cangrelor, an intravenous P2Y12 inhibitor, in CHAMPION PHOENIX. Methods and results A total of 11 145 patients were randomly assigned in a double-dummy, double-blind manner either to a cangrelor bolus and 2-h infusion or to clopidogrel at the time of PCI. The primary endpoint, a composite of death, myocardial infarction, ischaemia-driven revascularization, or stent thrombosis, and the primary safety endpoint, Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) defined severe bleeding, were evaluated at 48 h. Of the patients undergoing PCI and receiving study drug treatment, a total of 8064 (74%) and 2855 (26%) patients underwent femoral or radial PCI, respectively. Among the femoral cohort, the primary endpoint rate was 4.8% with cangrelor vs. 6.0% with clopidogrel (odds ratio, OR [95% confidence interval, CI] = 0.79 [0.65–0.96]); among the radial cohort, the primary endpoint was 4.4% with cangrelor vs. 5.7% with clopidogrel (OR [95% CI] = 0.76 [0.54–1.06]), P -interaction 0.83. The rate of GUSTO severe bleeding in the femoral cohort was 0.2% with cangrelor vs. 0.1% with clopidogrel (OR [95% CI] = 1.73 [0.51–5.93]). Among the radial cohort, the rate of GUSTO severe bleeding was 0.1% with cangrelor vs. 0.1% with clopidogrel (OR [95% CI] = 1.02 [0.14–7.28]), P -interaction 0.65. The evaluation of safety endpoints with the more sensitive ACUITY-defined bleeding found major bleeding in the femoral cohort to be 5.2% with cangrelor vs. 3.1% with clopidogrel (OR [95% CI] = 1.69 [1.35–2.12]); among the radial cohort the rate of ACUITY major bleeding was 1.5% with cangrelor vs. 0.7% with clopidogrel (OR [95% CI] = 2.17 [1.02–4.62], P -interaction 0.54). Conclusion In CHAMPION PHOENIX, cangrelor reduced ischaemic events with no significant increase in GUSTO-defined severe bleeding. The absolute rates of bleeding, regardless of the definition, tended to be lower when PCI was performed via the radial artery. Clinical trial registration identifier: [NCT01156571][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01156571&atom=%2Fehj%2F37%2F14%2F1122.atom

Objective: Most currently available percutaneous delivery methods for arterial gene therapy are limited by the need for a long incubation period, which may lead to unacceptable tissue ischemia, especially in the coronary vasculature. Conversely, shorter incubation times may result in inefficient gene transfer, especially in atheromatous arteries. A new local delivery autoperfusion multichamber catheter is now available which permits local delivery in the coronary arterial system without inducing myocardial ischemia. The present study aimed at evaluating the performance of this catheter for achieving arterial gene transfer using replication-defective adenoviral vectors in normal and atheromatous arteries. Methods: A replication-defective adenoviral vector carrying a nuclear-targeted β-galactosidase reporter gene (Ad-RSVβgal, 5.10[[9]][1] plaque-forming units [pfu]) was delivered to the iliac arteries of normal ( n = 7) and atheromatous (1% cholesterol diet + arterial abrasion) ( n = 6) rabbits, via a multichamber autoperfusion balloon catheter (DispatchTM, SciMed). Duration of gene delivery was 60 min. Results: Three days later, marked expression of the reporter gene was detected by histochemistry in the endothelium at the delivery site (percentage of transfected cells: 16 ± 8% /artery (range 11–25%). There was a low transduction rate in medial smooth muscle cells 0.7 ± 0.4% /artery (range 0.3–1.1%). In atheromatous arteries, transduction was consistently achieved in the superficial layers of the neointima but was lower (1.1 ± 0.5% /artery, range 0.3–1.7%). Transgene expression was detected by histochemistry in the liver of 3/13 animals, suggesting that there is a substantial risk of systemic dissemination of the viral vectors. Conclusion: Efficient arterial gene delivery to endothelial and superficial smooth muscle cells is feasible using local delivery of adenoviral vectors via the DispatchTM autoperfusion catheter, in both normal and atheromatous arteries. This perfusion catheter may be a useful tool for coronary artery gene transfer. [1]: #ref-9