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The prognostic value of growth differentiation factor-15 (GDF-15) in predicting long-term adverse outcomes in coronary heart disease (CHD) patients remains limited. Our study examines the association between GDF-15 and adverse outcomes over an extended period in CHD patients and firstly assesses the incremental prognostic effect of incorporating GDF-15 into the Framingham risk score (FRS)-based model. This single-center prospective cohort study included 3,321 patients with CHD categorized into 2,479 acute coronary syndrome (ACS) (74.6%) and 842 non-ACS (25.4%) groups. The median age was 61.0 years (range: 53.0-70.0), and 917 (27.6%) were females. Mortality and major adverse cardiovascular events (MACEs) included cardiovascular mortality, myocardial infarction (MI), stroke, and heart failure (HF) (inclusive of HF episodes requiring outpatient treatment and/or hospital admission). Cox regression models assessed the associations between GDF-15 and the incidence of all-cause mortality and MACEs. Patients were stratified into three groups based on GDF-15 levels: the first tertile group (< 1,370 ng/L), the second tertile group (1,370-2,556 ng/L), and the third tertile group (> 2,556 ng/L). The C-index, integrated discrimination improvement (IDI), net reclassification improvement (NRI), and decision curve analysis (DCA) were used to assess incremental value. Over a median 9.4-year follow-up, 759 patients (22.9%) died, and 1,291 (38.9%) experienced MACEs. The multivariate Cox model indicated that GDF-15 was significantly associated with all-cause mortality (per ln unit increase, HR = 1.49, 95% CI: 1.36-1.64) and MACEs (per ln unit increase, HR = 1.29, 95% CI: 1.20-1.38). These associations persisted when GDF-15 was analyzed as an ordinal variable (p for trend < 0.05). Subgroup analysis of ACS and non-ACS for the components of MACEs separately showed a significant association between GDF-15 and both cardiovascular mortality and HF, but no association was observed between GDF-15 and MI /stroke in both ACS and non-ACS patients. The addition of GDF-15 to the FRS-based model enhanced the discrimination for both all-cause mortality (∆ C-index = 0.009, 95% CI: 0.005-0.014; IDI = 0.030, 95% CI: 0.015-0.047; continuous NRI = 0.631, 95% CI: 0.569-0.652) and MACEs (∆ C-index = 0.009, 95% CI: 0.006-0.012; IDI = 0.026, 95% CI: 0.009-0.042; continuous NRI = 0.593, 95% CI: 0.478-0.682). DCA suggested that incorporating GDF-15 into the FRS-based model demonstrated higher net benefits compared to FRS-based models alone (All-cause mortality: FRS-based model: area under the curve of DCA (AUDC) = 0.0903, FRS-based model + GDF-15: AUDC = 0.0908; MACEs: FRS-based model: AUDC = 0.1806, FRS-based model + GDF-15: AUDC = 0.1833). GDF-15 significantly associates with the long-term prognosis of all-cause mortality and MACEs in CHD patients and significantly improves the prognostic accuracy of the FRS-based model for both outcomes., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aim: This study examines epidemiological trends of acute myocardial infarction (AMI) in Germany from 2004-2015 across different age groups, using data of the population-based KORA myocardial infarction registry., Methods: Annual age-standardised, age-group- and sex-specific mortality and event rates (incident and recurrent) per 100,000 population as well as 28-day case fatality were calculated from all registered cases of AMI and coronary heart disease deaths in 25-74-year-olds from 2004-2015 and 75-84-year-olds from 2009-2015. Average annual percentage changes (AAPC) were calculated by joinpoint regression., Results: Mortality rates declined considerably among the elderly (75-84 years), in men by -6.0% annually, due to declines of case fatality by -3.0% and incidence rate by 3.4% and in women by -10.0%, driven by declines in incidence (-9.1%) and recurrence rate (-4.9%). Significant mortality declines also occurred in males, 65-74 years of age (AAPC -3.8%). Among the age groups 25-54 years and 55-64 years, there was no substantial decline in mortality, event rates or case fatality except for a decline of incidence rate in 55-64-year-old men (AAPC -1.8%)., Conclusion: Inhomogeneous AMI trends across age-groups indicate progress in prevention and treatment for the population >64 years, while among <55-year-olds, we found no significant trend in AMI morbidity and mortality.KEY MESSAGESAge standardised AMI mortality continued to decline from 2009 to 2015 in the study region.Declines in AMI mortality were driven by declines in event rates (both incidence and recurrence rates) and case fatality.AMI trends were inconsistent across different age groups with the strongest declines in mortality and event rates among the elderly population (75-84 years of age).

Randomized controlled trials showed that soy intervention significantly improved blood lipids in people with diabetes. We sought to prospectively examine the association of soy consumption with the risk of cardiovascular death among individuals with diabetes. A total of 26,139 participants with a history of diabetes were selected from the Chinese Kadoorie Biobank study. Soy food consumption was assessed by a food frequency questionnaire. Causes of death were coded by the 10th International Classification of Diseases. The Cox proportional hazard regression was used to compute the hazard ratios. During a median follow-up of 7.8 years, a total of 1626 deaths from cardiovascular disease (CVD) were recorded. Compared with individuals who never consumed soy foods, the multivariable-adjusted risks (95% confidence intervals) of CVD mortality were 0.92 (0.78, 1.09), 0.89 (0.75, 1.05), and 0.77 (0.62, 0.96) for those who consumed soy foods monthly, 1-3 days/week, and ≥4 days/week, respectively. For cause-specific cardiovascular mortality, significant inverse associations were observed for coronary heart disease and acute myocardial infarction. Higher soy food consumption was associated with a lower risk of cardiovascular death, especially death from coronary heart disease and acute myocardial infarction, in Chinese adults with diabetes.

Objective: In patients with chronic coronary or peripheral artery disease enrolled in the Cardiovascular Outcomes for People Using Anticoagulation Strategies trial, randomised antithrombotic treatments were stopped after a median follow-up of 23 months because of benefits of the combination of rivaroxaban 2.5 mg two times per day and aspirin 100 mg once daily compared with aspirin 100 mg once daily. We assessed the effect of switching to non-study aspirin at the time of early stopping., Methods: Incident composite of myocardial infarction, stroke or cardiovascular death was estimated per 100 person-years (py) during randomised treatment (n=18 278) and after study treatment discontinuation to non-study aspirin (n=14 068)., Results: During randomised treatment, the combination compared with aspirin reduced the composite (2.2 vs 2.9/100 py, HR: 0.76, 95% CI 0.66 to 0.86), stroke (0.5 vs 0.8/100 py, HR: 0.58, 95% CI 0.44 to 0.76) and cardiovascular death (0.9 vs 1.2/100 py, HR: 0.78, 95% CI 0.64 to 0.96). During 1.02 years after early stopping, participants originally randomised to the combination compared with those randomised to aspirin had similar rates of the composite (2.1 vs 2.0/100 py, HR: 1.08, 95% CI 0.84 to 1.39) and cardiovascular death (1.0 vs 0.8/100 py, HR: 1.26, 95% CI 0.85 to 1.86) but higher stroke rate (0.7 vs 0.4/100 py, HR: 1.74, 95% CI 1.05 to 2.87) including a significant increase in ischaemic stroke during the first 6 months after switching to non-study aspirin., Conclusion: Discontinuing study rivaroxaban and aspirin to non-study aspirin was associated with the loss of cardiovascular benefits and a stroke excess., Trial Registration Number: NCT01776424., Competing Interests: Competing interests: GRD reports speaking honoraria from Bayer and Eli-Lilly. JB serves on the Advisory Board of and has received honoraria from Bayer AG. DL has received speaking honoraria from Bayer AG. VA received honoraria from Bayer, Amgen, NovoNordisk, Novartis, BMS/Pfizer alliance and Sanofi. SDB is employed by Bayer U.S., LLC, as a clinical research physician. DLB reports the following relationships advisory board: Cardax, Cereno Scientific, Elsevier Practice Update Cardiology, Medscape Cardiology, PhaseBio, PLX Pharma and Regado Biosciences; board of directors: Boston VA Research Institute, Society of Cardiovascular Patient Care and TobeSoft; chair: American Heart Association Quality Oversight Committee; Data Monitoring Committees: Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Cleveland Clinic (including for the ExCEED trial, funded by Edwards), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo), Population Health Research Institute; honoraria: American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Vice-Chair, ACC Accreditation Committee), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (editor in chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (guest editor; associate editor), Medtelligence/ReachMD (CME steering committees), Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee and USA national coleader, funded by Bayer), Slack Publications (Chief Medical Editor, Cardiology Today’s Intervention), Society of Cardiovascular Patient Care (secretary/treasurer), WebMD (CME steering committees); other: Clinical Cardiology (deputy editor), NCDR-ACTION Registry Steering Committee (chair), VA CART Research and Publications Committee (chair); research funding: Abbott, Afimmune, Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Cardax, Chiesi, CSL Behring, Eisai, Ethicon, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Idorsia, Ironwood, Ischemix, Lexicon, Lilly, Medtronic, Pfizer, PhaseBio, PLx Pharma, Regeneron, Roche, Sanofi Aventis, Synaptic and The Medicines Company; royalties: Elsevier (Editor, Cardiovascular Intervention: A Companion to Braunwald’s Heart Disease); site coinvestigator: Biotronik, Boston Scientific, CSI, St. Jude Medical (now Abbott) and Svelte; trustee: American College of Cardiology; unfunded research: Flow Co, Merck, Novo Nordisk and Takeda. SJC has received major research grants, consulting fees and speaker fees from Sanofi-Aventis, Janssen, Pfizer, Bristol-Myers Squibb, Boehringer-Ingelheim, Boston Scientific, Abbott, Bayer Pharmaceuticals Inc, Portola Pharmaceutical, Medtronic, Daiichi Sankyo and Servier. KAAF has received grants from Bayer/Janssen and AstraZeneca and has received consultancy fees from Bayer/Janssen, Sanofi/Regeneron and Verseon. EM is employed by Bayer AG, as a global clinical leader. PW has received grants and honoraria from Bayer AG, Boehringer Ingelheim, AstraZeneca and Servier. BRW has received speaking honoraria from Bayer AG. SY has received grants and honoraria from Bayer AG, Boehringer-Ingelheim, AstraZeneca, Bristol-Myers Squibb and Cadila Pharmaceuticals. JWE has received consulting fees and grant support from AstraZeneca, Bayer AG, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, Eli Lilly, GlaxoSmithKline, Pfizer, Janssen, Sanofi and Servier., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Rates for recurrent coronary heart disease (CHD) events have declined in the United States. However, few studies have assessed whether this decline has been similar among women and men., Methods: Data were used from 770 408 US women and 700 477 US men <65 years of age with commercial health insurance through MarketScan and ≥66 years of age with government health insurance through Medicare who had a myocardial infarction (MI) hospitalization between 2008 and 2017. Women and men were followed up for recurrent MI, recurrent CHD events (ie, recurrent MI or coronary revascularization), heart failure hospitalization, and all-cause mortality (Medicare only) in the 365 days after MI., Results: From 2008 to 2017, age-standardized recurrent MI rates per 1000 person-years decreased from 89.2 to 72.3 in women and from 94.2 to 81.3 in men (multivariable-adjusted P interaction by sex <0.001). Recurrent CHD event rates decreased from 166.3 to 133.3 in women and from 198.1 to 176.8 in men ( P interaction <0.001). Heart failure hospitalization rates decreased from 177.4 to 158.1 in women and from 162.9 to 156.1 in men ( P interaction=0.001). All-cause mortality rates decreased from 403.2 to 389.5 in women and from 436.1 to 417.9 in men ( P interaction=0.82). In 2017, the multivariable-adjusted rate ratios comparing women with men were 0.90 (95% CI, 0.86-0.93) for recurrent MI, 0.80 (95% CI, 0.78-0.82) for recurrent CHD events, 0.99 (95% CI, 0.96-1.01) for heart failure hospitalization, and 0.82 (95% CI, 0.80-0.83) for all-cause mortality., Conclusions: Rates of recurrent MI, recurrent CHD events, heart failure hospitalization, and mortality in the first year after an MI declined considerably between 2008 and 2017 in both men and women, with proportionally greater reductions for women than men. However, rates remain very high, and rates of recurrent MI, recurrent CHD events, and death continue to be higher among men than women.

Aims: Heart failure is a fatal complication of type 2 diabetes but little is known about its incidence in people with impaired glucose tolerance (IGT). We used Acarbose Cardiovascular Evaluation (ACE) trial data to identify predictors of hospitalisation for heart failure (hHF) or cardiovascular (CV) death in patients with coronary heart disease (CHD) and IGT randomised to acarbose or placebo., Methods: Independent hHF/CV death risk factors were determined using Cox proportional hazards models, with participants censored at first hHF event, CV death, or end of follow-up., Results: During median 5-year follow-up, the composite outcome of hHF/CV death occurred in 393 (6.0%) participants. Significant hHF/CV death multivariate predictors were higher age and plasma creatinine, and prior heart failure (HF), myocardial infarction (MI), atrial fibrillation (AF) and stroke. Acarbose, compared with placebo, did not reduce hHF/CV death (hazard ratio [HR] 0.89, 95% CI 0.64-1.24, P = 0.48) or hHF (HR 0.90, 95% CI 0.74-1.10, P = 0.32)., Conclusions: Patients with CHD and IGT at greater risk of hHF/CV death were older with higher plasma creatinine, prior HF, MI, AF or stroke. Addition of acarbose to optimised CV therapy to reduce post-prandial glucose excursions did not reduce the risk of hHF/CV death or hHF., Clinical Trial Registration: ClinicalTrials.gov, number NCT00829660, and the International Standard Randomised Controlled Trial Number registry, number ISRCTN91899513., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Importance: Recent European guidance supports a diminished role for exercise electrocardiography (ECG) in the assessment of suspected stable angina., Objective: To evaluate the utility of exercise ECG in contemporary practice and assess the value of combined functional and anatomical testing., Design, Setting, and Participants: This is a post hoc analysis of the Scottish Computed Tomography of the Heart (SCOT-HEART) open-label randomized clinical trial, conducted in 12 cardiology chest pain clinics across Scotland for patients with suspected angina secondary to coronary heart disease. Between November 18, 2010, and September 24, 2014, 4146 patients aged 18 to 75 years with stable angina underwent clinical evaluation and 1417 of 1651 (86%) underwent exercise ECG prior to randomization. Statistical analysis was conducted from October 10 to November 5, 2019., Interventions: Patients were randomized in a 1:1 ratio to receive standard care plus coronary computed tomography (CT) angiography or to receive standard care alone. The present analysis was limited to the 3283 patients who underwent exercise ECG alone or in combination with coronary CT angiography., Main Outcomes and Measures: The primary clinical end point was death from coronary heart disease or nonfatal myocardial infarction at 5 years., Results: Among the 3283 patients (1889 men; median age, 57.0 years [interquartile range, 50.0-64.0 years]), exercise ECG had a sensitivity of 39% and a specificity of 91% for detecting any obstructive coronary artery disease in those who underwent subsequent invasive angiography. Abnormal results of exercise ECG were associated with a 14.47-fold (95% CI, 10.00-20.41; P < .001) increase in coronary revascularization at 1 year and a 2.57-fold (95% CI, 1.38-4.63; P < .001) increase in mortality from coronary heart disease death at 5 years or in cases of nonfatal myocardial infarction at 5 years. Compared with exercise ECG alone, results of coronary CT angiography had a stronger association with 5-year coronary heart disease death or nonfatal myocardial infarction (hazard ratio, 10.63; 95% CI, 2.32-48.70; P = .002). The greatest numerical difference in outcome with CT angiography compared with exercise ECG alone was observed for those with inconclusive results of exercise ECG (5 of 285 [2%] vs 13 of 283 [5%]), although this was not statistically significant (log-rank P = .05)., Conclusions and Relevance: This study suggests that abnormal results of exercise ECG are associated with coronary revascularization and the future risk of adverse coronary events. However, coronary CT angiography more accurately detects coronary artery disease and is more strongly associated with future risk compared with exercise ECG., Trial Registration: ClinicalTrials.gov Identifier: NCT01149590.

Background: The optimal revascularization approach for patients with multivessel coronary artery disease (MVCAD) is controversial. We sought to investigate outcomes in patients undergoing coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) for non-ST elevation myocardial infarction (NSTEMI)., Methods: Adult patients with MVCAD and NSTEMI undergoing either CABG or PCI at a single institution between 2011 and 2018 were included. Multivariable analysis was utilized to determine independent predictors of death, major adverse cardiac and cerebrovascular events (MACCE), and readmissions. A subanalysis examined patients undergoing complete revascularization., Results: A total of 2001 patients were included, of whom 1480 (74.0%) underwent CABG. CABG was associated with a lower risk-adjusted hazard for death (hazard ratio, 0.59, P < .001) and with improved survival at 1 year (92.0 vs 81.8%, P < .001) and 5 years (80.7 vs 63.3%, P < .001). Additionally, freedom from MACCE (P < .001) was greater in the CABG group and cumulative readmission, rates of MI, and rates of repeat revascularization were lower with CABG (each P < .001). Among patients undergoing complete revascularization, overall survival (1 year: 92.7 vs 83.9%, P = .010; 5 years: 81.1 vs 69.4%, P < .001) and freedom from MACCE (1 year: 92.3 vs 75.2%, P < .001; 5 years: 81.7 vs 61.4%, P < .001) remained higher for the CABG group; cumulative incidence of readmission was also decreased in those undergoing CABG (P < .001)., Conclusions: In this real-world analysis of patients with MVCAD presenting with NSTEMI, revascularization with CABG resulted in improved survival with lower rates of MACCE and readmission as compared to PCI, which persisted when accounting for complete revascularization., (© 2020 Wiley Periodicals, Inc.)

This study aimed to investigate the prognostic value of high-sensitivity creatine kinase-myocardial band or fraction (hsCK-MB) in comparison with other well-established biomarkers including heart type-fatty acid binding protein (H-FABP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with stable coronary heart disease (SCHD). A total of 1,785 patients were enrolled and followed for 36 months. The primary outcome was all-cause mortality. The secondary outcomes included cardiovascular (CV) death, acute myocardial infarction (AMI), angina-related hospitalizations, and hospitalizations for heart failure. The all-cause mortality rate was significantly higher in the high hsCK-MB group compared to the low hsCK-MB group (4.64% vs. 1.88%, p = 0.0026). After adjusting for baseline covariates, there were no significant differences for the secondary outcomes. H-FABP (≥4.226 ng/mL) was the best predictor for all-cause mortality (HR = 2.68, 95% CI = 1.28-5.62, p = 0.009) and CV death (HR = 6.84, 95% CI = 1.89-22.14, p = 0.003). The high NT-proBNP group had a higher AMI-related hospitalization rate (HR = 1.91, 95% CI = 1.00-3.65, p = 0.05). Neither the addition of hsCK-MB to any other markers nor combinations of the three markers improved the prognostic significance of CV outcomes. In conclusion, hsCK-MB was an independent predictor for all-cause mortality but not CV outcomes in patients with SCHD. Combination of hsCK-MB, H-FABP and NT-proBNP failed to improve the prognostic power for all-cause mortality or CV outcomes.

Coronary artery disease is a common co-morbidity of aortic stenosis. When needed, adding coronary artery bypass grafting (CABG) to surgical aortic valve replacement (SAVR) is the standard treatment method, but the impact of concomitant CABG on long-term outcomes is uncertain. We compared long-term outcomes of SAVR patients with and without CABG. Hospital survivors aged ≥50 years discharged after SAVR ± CABG in Finland between 2004 and 2014 (n = 6,870) were retrospectively studied using nationwide registries. Propensity score matching (1:1) was used to identify patients with comparable baseline features (n = 2,188 patient pairs, mean age 73 years). The end points were postoperative 10-year major adverse cardiovascular outcome (MACE), all-cause mortality, stroke, major bleeding, and myocardial infarction. Median follow-up was 6 years. Cumulative MACE rate (39.5% vs 35.6%; hazard ratio [HR] 1.04; p = 0.677) and mortality (32.7% vs 31.0%; HR 1.03; p = 0.729) after SAVR were comparable with or without CABG. Myocardial infarction was more common in patients with CABG (13.4% vs 6.9%; HR 1.47; p = 0.0495). Occurrence of stroke (15.1% vs 13.5%; p = 0.998) and major bleeding (20.0% vs 21.9%; p = 0.569) were comparable. There was no difference in gastrointestinal (8.1% vs 10.3%; p = 0.978) or intracranial bleeds (6.0% vs 5.5%; p = 0.794). The use of internal mammary artery in CABG did not have an impact on the results. In conclusion, matched patients with and without concomitant CABG had comparable long-term MACE, mortality, stroke, and major bleeding rates after SAVR. In conclusion, our results indicate that need for concomitant CABG has limited impact on long-term outcomes after initially successful SAVR., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition by monoclonal antibodies has been shown to reduce low density lipoprotein (LDL-C) but its effects on cardiovascular (CV) outcomes have not been fully described. The aim of this study is to assess the impact of PCSK9 inhibition on mortality and CV outcomes by pooling data from all available randomized clinical trials (RCT) of PCSK9 inhibitors. We conducted a comprehensive search of electronic databases, up to December 1, 2018, for all RCTs comparing PCSK9 inhibition to placebo or ezetimibe in patients with hypercholesterolemia or coronary artery disease receiving maximally tolerated statin for primary or secondary prevention of mortality and cardiovascular outcomes. We used random-effects meta-analyses to summarize the studies. We retained 23 RCTs having included 88,041 patients in primary and secondary prevention. The follow-up ranged from 6 to 36 months. PCSK9 inhibition was not significantly associated with reductions in total mortality (odds ratio [OR] 0.91, 95% confidence interval [CI] 078 to 1.06; p = 0.22) and CV mortality (OR 0.95, 95% CI 0.84 to 1.07; p = 0.37). In contrast, PCSK9 inhibition was associated with reductions in myocardial infarction (OR 0.80, 95% CI 0.71 to 0.91; p <0.0001), stroke (OR 0.75, 95% CI 0.65 to 0.85; p <0.0001), and coronary revascularization (OR 0.82, 95% CI 0.77 to 0.88; p <0.0001). In conclusion, PCSK9 inhibition was associated with reductions in myocardial infarction, stroke, and coronary revascularization. Future analyses may identify high-risk patients who may benefit more from these agents and longer follow-up of current or new trials may show a mortality benefit., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Within the SCOT-HEART (Scottish COmputed Tomography of the HEART Trial) trial of patients with stable chest pain, the use of coronary computed tomography angiography (CTA) reduced the rate of death from coronary heart disease or nonfatal myocardial infarction (primary endpoint)., Objectives: This study sought to assess the consistency and mechanisms of the 5-year reduction in this endpoint., Methods: In this open-label trial, 4,146 participants were randomized to standard care alone or standard care plus coronary CTA. This study explored the primary endpoint by symptoms, diagnosis, coronary revascularizations, and preventative therapies., Results: Event reductions were consistent across symptom and risk categories (p = NS for interactions). In patients who were not diagnosed with angina due to coronary heart disease, coronary CTA was associated with a lower primary endpoint incidence rate (0.23; 95% confidence interval [CI]: 0.13 to 0.35 vs. 0.59; 95% CI: 0.42 to 0.80 per 100 patient-years; p < 0.001). In those who had undergone coronary CTA, rates of coronary revascularization were higher in the first year (hazard ratio [HR]: 1.21; 95% CI: 1.01 to 1.46; p = 0.042) but lower beyond 1 year (HR: 0.59; 95% CI: 0.38 to 0.90; p = 0.015). Patients assigned to coronary CTA had higher rates of preventative therapies throughout follow-up (p < 0.001 for all), with rates highest in those with CT-defined coronary artery disease. Modeling studies demonstrated the plausibility of the observed effect size., Conclusions: The beneficial effect of coronary CTA on outcomes is consistent across subgroups with plausible underlying mechanisms. Coronary CTA improves coronary heart disease outcomes by enabling better targeting of preventative treatments to those with coronary artery disease. (Scottish COmputed Tomography of the HEART Trial [SCOT-HEART]; NCT01149590)., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Management of significant carotid stenosis in those with symptomatic coronary disease remains controversial. Staged and combined carotid endarterectomy (CEA) with coronary artery bypass grafting has been described. Yet, an understanding of the additive risks of these approaches is poor. This study sought to assess outcomes in patients with clinically relevant coronary disease undergoing either isolated CEA (ICEA) or combined CEA and coronary artery bypass (concurrent coronary artery bypass [CCAB])., Methods: All CEAs in the Vascular Quality Initiative from 2003 to 2017 were reviewed. CCABs were identified, as were ICEAs in patients with unrevascularized stable angina, unstable angina, or myocardial infarction (MI) within 6 months of operation. CCABs were compared with ICEAs as well as with a risk-matched cohort of ICEAs. Primary outcomes included perioperative stroke, all-cause death, MI, and these as composite (SDM). Univariate analysis and logistic regression were performed., Results: There were 4042 patients identified, including 2582 ICEA patients (64%) and 1460 CCAB patients (36%); 61% were male, 91% were white, and 39% had symptomatic carotid disease. Overall stroke was 3.5%, death 1.8%, and SDM 6.0%. ICEA had higher rates of postoperative MI (1.9% vs 0.9%; P = .01) but lower rates of stroke (2.8% vs 4.7%; P = .002), death (1.0% vs 3.0%; P < .001), and SDM (5.1% vs 7.5%; P = .002). After regression, predictors of SDM were congestive heart failure (odds ratio [OR], 1.7; 95% confidence interval [CI], 1.3-2.4; P < .001), urgent operation (OR, 1.6; 95% CI, 1.2-2.2; P = .001), and CCAB (OR, 1.3; 95% CI, 1.01-1.7; P = .04). After propensity matching, ICEA continued to have higher rates of perioperative MI (2.6% vs 1.0%; P = .01) and lower rates of death (1.0% vs 3.0%; P = .001). However, there were no longer differences in stroke (3.2% vs 4.6%; P = .10) or SDM (6.3% vs 7.8%; P = .18). Within the matched cohort, predictors of SDM included chronic obstructive pulmonary disease (OR, 1.6; 95% CI, 1.1-2.2; P = .01), congestive heart failure (OR, 1.7; 95% CI, 1.1-2.5; P = .01), and symptomatic carotid disease (OR, 1.5; 95% CI, 1.03-2.1; P = .03). CCAB was not significant (OR, 1.3; 95% CI, 0.9-1.8; P = .18)., Conclusions: In patients with unrevascularized, clinically relevant coronary disease, CCAB reduces operative MI but increases risk of stroke and death. After risk adjustment, MI remains higher in ICEA, but differences in 30-day stroke and SDM between ICEA and CCAB are no longer appreciated. These data suggest that CEA risk undertaken in patients with unrevascularized coronary disease is not inconsequential, and outcomes are similar to those of CCAB., (Copyright © 2019 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Purpose: Although strong associations between self-reported health and mortality exist, quality of life is not conceptualized as a cardiovascular disease (CVD) risk factor. Our objective was to assess the independent association between health-related quality of life (HRQOL) and incident CVD., Methods: This study used the REasons for Geographic And Racial Differences in Stroke data, which enrolled 30,239 adults from 2003 to 2007 and followed them over 10 years. We included 22,229 adults with no CVD history at baseline. HRQOL was measured using the SF-12 Physical Component Summary (PCS) and Mental Component Summary (MCS) scores, which range from 0 to 100, with higher scores indicating better HRQOL. Scores were normed to the general US population with mean 50 and standard deviation 10. We constructed a four-level HRQOL variable: (1) individuals with PCS & MCS < 50, (2) PCS < 50 & MCS ≥ 50, (3) MCS < 50 & PCS ≥ 50, and (4) PCS & MCS ≥ 50, which was the reference. The primary outcome was incident CVD (non-fatal myocardial infarction (MI), fatal MI or coronary heart disease (CHD) death, fatal and non-fatal stroke). Cox proportional hazards models examined associations between HRQOL and CVD., Results: Median follow-up was 8.4 (IQR 5.9-10.0) years. We observed 1766 CVD events. Compared to having PCS & MCS ≥ 50, having MCS & PCS < 50 was associated with increased CVD risk (aHR 1.46; 95% 1.24-1.70), adjusting for demographics, comorbidities, and CVD risk factors. Associations between MCS & PCS < 50 and CVD were consistent for CHD (aHR 1.54 [1.26-1.89]) and stroke (aHR 1.35 [1.05-1.72]) endpoints., Conclusions: Given strong, adjusted associations between poor HRQOL and incident CVD, self-reported health may be an excellent complement to current approaches to CVD risk identification.

The Academic Research Consortium (ARC) and the Standardized Data Collection for Cardiovascular Trials Initiative have recently published updated clinical and angiographic endpoint definitions for percutaneous coronary intervention trials. The aim of this document is to provide practical guidance to facilitate and harmonize the implementation of those definitions in randomized trials or registries, as well as to foster consistency among independent adjudication committees. The authors compared the ARC-2 and Standardized Data Collection for Cardiovascular Trials Initiative definitions to identify areas of consistency, complex scenarios, and definitions in need of further standardization. Furthermore, the authors compared the fourth universal definition of myocardial infarction with the ARC-2 definition of myocardial infarction. The Society for Cardiovascular Angiography and Interventions definition of periprocedural myocardial infarction was also compared with the ARC-2 definition and the fourth universal definition of myocardial infarction. An in-depth assessment was done for each individual clinical endpoint to guide clinical investigators on reporting and classifying clinical adverse events. Finally, the authors propose standard streamlined data capture templates for reporting and adjudicating death, myocardial infarction, stroke, revascularization, stent or scaffold thrombosis, and bleeding., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Clinical Endpoint Classification (CEC) in clinical trials allows FOR standardized, systematic, blinded, and unbiased adjudication of investigator-reported events. We quantified the agreement rates in the STABILITY trial on 15,828 patients with stable coronary heart disease., Methods: Investigators were instructed to report all potential events. Each reported event was reviewed independently by 2 reviewers according to prespecified processes and prespecified end point definitions. Concordance between reported and adjudicated cardiovascular (CV) events was evaluated, as well as event classification influence on final study results., Results: In total, CEC reviewed 7,096 events: 1,064 deaths (696 CV deaths), 958 myocardial infarctions (MI), 433 strokes, 182 transient ischemic attacks, 2,052 coronary revascularizations, 1,407 hospitalizations for unstable angina, and 967 hospitalizations for heart failure. In total, 71.8% events were confirmed by CEC. Concordance was high (>80%) for cause of death and nonfatal MI and lower for hospitalization for unstable angina (25%) and heart failure (50%). For the primary outcome (composite of CV death, MI, and stroke), investigators reported 2,086 events with 82.5% confirmed by CEC. The STABILITY trial treatment effect of darapladib versus placebo on the primary outcome was consistent using investigator-reported events (hazard ratio 0.96 [95% CI 0.87-1.06]) or adjudicated events (hazard ratio 0.94 [95% CI 0.85-1.03])., Conclusions: The primary outcome results of the STABILITY trial were consistent whether using investigator-reported or CEC-adjudicated events. The proportion of investigator-reported events confirmed by CEC varied by type of event. These results should help improve event identification in clinical trials to optimize ascertainment and adjudication., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Object: The purpose of this study was to fully assess the role of statins in the primary prevention of coronary heart disease (CHD)., Methods: We searched six databases (PubMed, the Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang Database, and Chinese Scientific Journal Database) to identify relevant randomized controlled trials (RCTs) from inception to 31 October 2017. Two review authors independently assessed the methodological quality and analysed the data using Rev Man 5.3 software. Risk ratios and 95% confidence intervals (95% CI) were pooled using fixed/random-effects models. Funnel plots and Begg's test were conducted to assess publication bias. The quality of the evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach., Results: Sixteen RCTs with 69159 participants were included in this review. Statins can effectively decrease the occurrence of angina (RR=0.70, 95% CI: 0.58~0.85, I 2 =0%), nonfatal myocardial infarction (MI) (RR=0.60, 95% CI: 0.51~0.69, I 2 =14%), fatal MI (RR=0.49, 95% CI: 0.24~0.98, I 2 =0%), any MI (RR=0.53, 95% CI: 0.42~0.67, I 2 =0%), any coronary heart events (RR=0.73, 95% CI: 0.68~0.78, I 2 =0%), coronary revascularization (RR=0.66, 95% CI: 0.55~0.78, I 2 = 0%), and any cardiovascular events (RR=0.77, 95% CI: 0.72~82, I 2 = 0%). However, based on the current evidence, there were no significant differences in CHD deaths (RR=0.82, 95% CI: 0.66~1.02, I 2 =0%) and all-cause mortality (RR=0.88, 95% CI: 0.76 ~1.01, I 2 =58%) between the two groups. Additionally, statins were more likely to result in diabetes (RR=1.21, 95% CI: 1.05~1.39, I 2 =0%). There was no evidence of publication biases, and the quality of the evidence was considered moderate., Conclusion: Statins seemed to be beneficial for the primary prevention of CHDs but have no effect on CHD death and all-cause mortality.

Background: Myocardial infarction with non-obstructive coronary arteries (MINOCA) is a known clinical conundrum with limited investigation. Using a large population-based cohort, we examined the incidence, demographic profile, use of evidence-based medicines (EBM) and clinical outcomes of MINOCA patients., Methods: Patients hospitalized with a primary diagnosis of MI who underwent coronary angiography between 01/04/2002 and 31/03/2014 in Alberta, Canada, were included in the study. Comparisons were made between patients with MINOCA versus obstructive coronary disease (OCD). The primary composite endpoint was 1-year all-cause death or re-MI., Results: Of 35,928 patients hospitalized with MI, 2092 (5.8%) had MINOCA. In-hospital mortality rate was 0.8% among MINOCA, and 2.7% among patients with OCD (p < 0.0001). At 6 months, cardiovascular EBM rates were significantly lower among MINOCA patients compared to OCD patients. One-year death/re-MI rate was 5.3% in MINOCA and 8.9% in patients with OCD (adjusted hazard ratio (AHR) 0.75, 95% confidence interval (CI) 0.62-0.92, p < 0.0001). Five-year mortality rates were 10.9% in MINOCA and 16.0% in patients with OCD. Upon further stratification, 770 (36.8%) of MINOCA patients had no angiographic evidence of CAD (i.e. normal angiograms). EBM rates were even lower among these patients. One-year death/re-MI rate among these patients was 3.9% as compared to 6.1% among MINOCA patients with stenosis <50% (AHR 0.68, 95% CI 0.44-1.07, p = 0.028)., Conclusions: The population-level incidence of MINOCA is approximately 5%. Despite their apparently benign anatomic findings, efforts must be made to improve secondary prevention strategies to reduce the burden of long-term adverse outcomes in this population., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Exercise and Sports in the Therapy of Chronic Diseases - Coronary Heart Disease Abstract. Despite increasingly advanced diagnostic and therapeutic methods, coronary heart disease and myocardial infarction continue to be by far the leading cause of death worldwide. This makes it all the more important in this context to make full use of known but far from optimally used therapeutic measures. Adequate physical activity in everyday life and additional targeted training lead to an evidence-based improvement in quality of life, a reduction in morbidity and above all to a significant reduction in cardiac and overall mortality. However, an accurate risk assessment of the individual patient with consistent training recommendations and monitoring is crucial in medical training advice. Today's sports recommendations for coronary heart disease have become much more liberal than before and allow patients with a relatively low risk of sudden cardiac death to do virtually any kind of exercise. This progressive posture, according to optimal risk assessment, is important, as newer data also show a dose-dependent increase in the preventive effect in coronary heart disesase patients with an increase in the extent of weekly training.

Objective: To understand the distribution and trends in 30-day coronary heart disease (CHD) case fatality rate in patients hospitalized due to acute myocardial infarction (AMI) in Beijing during 2007-2012. Methods: The clinical data of patients hospitalized due to AMI in Beijing from 1 January 2007 to 31 December 2012 were collected from "The Cardiovascular Disease Surveillance System in Beijing" . A total of 77 943 local patients aged ≥25 years were hospitalized due to AMI in Beijing during the this period. After excluding duplicate records and validation for the completeness and accuracy of the records, the clinical characteristics of the patients and 30-day CHD case fatality rate in the patients were analyzed. Trends in 30-day CHD case fatality rate in the patients were analyzed with Poisson regression models. Results: The age-standardized average 30-day CHD case fatality rate was 9.7% in the 77 943 patients. During this period, a decreasing trend was observed in 30-day CHD case fatality rate after adjusting for age and gender ( P <0.001). The age-standardized 30-day CHD case fatality rate decreased by 16.0%, from 10.8% in 2007 to 9.0% in 2012. The decreases of 30-day CHD case fatality rates were noted in both men and women, whereas 30-day CHD case fatality rate was higher in women (14.1%) than in men (7.6%) after adjusting for age. During this period, the proportion of ST-segment elevation myocardial infarction (STEMI) decreased, while the proportion of non-ST-segment elevation myocardial infarction (NSTEMI) increased with year. A significant decline (20.1%) in 30-day case fatality rate of STEMI was found, but no decline was found for 30-day mortality rate of NSTEMI. Conclusion: A decreasing trend in 30-day CHD case fatality rate was observed in the patients aged ≥25 years and hospitalized due to AMI in Beijing during 2007-2012, indicating the improvement in short-term prognosis of patients hospitalized due to AMI. Our findings highlight the urgent need to improve the treatment for woman and NSTEMI patients.

Background: In-hospital bleeding after percutaneous coronary intervention is associated with increased mortality. We studied the impact of bleeding severity, defined as magnitude of Hgb (hemoglobin) reduction from baseline (ΔHgb), on the risk of death and other adverse events., Methods and Results: We studied the association between ΔHgb, baseline characteristics, and outcomes among 7608 patients in the ADAPT-DES registry (Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents) who had information on Hgb values before and after they underwent successful percutaneous coronary intervention. Post-percutaneous coronary intervention, 5985 (78.7%) patients had a drop in Hgb, with 2684 patients (35.3%) having a ΔHgb <1.0 g/dL, 2338 (30.7%) ≥1.0 to <2.0 g/dL, 745 (9.8%) ≥2.0 to <3.0 g/dL, 145 (1.9%) ≥3.0 to <4.0 g/dL, and 73 (1.0%) ≥4.0 g/dL. The risk of dying within 2 years was 3.3% with <1.0 g/dL ΔHgb, 3.4% with ΔHgb ≥1.0 to <2.0 g/dL, 3.7% with ΔHgb ≥2.0 to <3.0 g/dL, 4.1% with ΔHgb ≥3.0 to <4.0 g/dL, and 9.8% with ΔHgb ≥4.0 g/dL ( P =0.03). The risk of major adverse cardiac events (defined as cardiac death, myocardial infarction, or stent thrombosis) was higher for patients with ΔHgb ≥4.0 g/dL (adjusted hazard ratio, 3.39; 95% confidence interval, 1.97-5.83; P <0.001) and for patients with ΔHgb ≥3.0 to <4.0 g/dL (adjusted hazard ratio, 2.17; 95% confidence interval, 1.34-3.53; P =0.002)., Conclusions: Among patients who undergo successful percutaneous coronary intervention, bleeding events that result in ΔHgb ≥4.0 g/dL are associated with a considerably increased risk of dying., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00638794., (© 2018 American Heart Association, Inc.)

Background and Aims: Whether gamma-glutamyl transferase (GGT) or alkaline phosphatase (ALP) is a better prognostic marker in patients with coronary heart disease (CHD) remains unknown. The aim of this study was to compare the prognostic value of GGT and ALP in patients with CHD., Methods and Results: This study included 3768 patients with CHD. The main study outcome was 3-year all-cause mortality. The median values of GGT and ALP were 36.2 U/L and 69.3 U/L. Patients were divided into subgroups according to GGT or ALP activity > or ≤median. Overall, there were 304 deaths: 195 deaths occurred in patients with GGT >median (n = 1882) and 109 deaths occurred in patients with GGT ≤median (n = 1886); Kaplan-Meier [KM] estimates of all-cause mortality were 11.9% and 6.4% (unadjusted hazard ratio [HR] = 1.85, 95% confidence interval [CI], 1.46 to 2.34]; P < 0.001). According to ALP activity, 186 deaths occurred in patients with ALP >median (n = 1883) and 118 deaths occurred in patients with ALP ≤median (n = 1885); KM estimates of all-cause mortality were 11.4% and 7.1% (unadjusted HR = 1.64 [1.30-2.06]; P < 0.001). After adjustment, GGT (adjusted HR = 1.32 [1.11-1.58]; P = 0.002) but not ALP (adjusted HR = 1.20 [1.00-1.43]; P = 0.051, with both HR calculated per 1 unit increment in logarithmic GGT or ALP scale) remained significantly associated with the risk for mortality. The C statistic of the mortality model with GGT was greater than the C statistic of the model with ALP (0.831 [0.802-0.859] vs. 0.826 [0.793-0.855]; P < 0.001)., Conclusions: In patients with CHD, GGT was a stronger correlate of all-cause mortality than ALP., (Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Chronic obstructive pulmonary disease (COPD) has been associated with coronary mortality. Yet, data about the association between COPD and acute myocardial infarction (MI) remain scarce. We aimed to study airway obstruction as a predictor of MI and coronary mortality among 5576 Finnish adults who participated in a national health examination survey between 1978 and 1980. Subjects underwent spirometry, had all necessary data, showed no indications of cardiovascular disease at baseline, and were followed up through record linkage with national registers through 2011. The primary outcome consisted of a major coronary event-that is, hospitalization for MI or coronary death, whichever occurred first. We specified obstruction using the lower limit of normal categorization. Through multivariate analysis adjusted for potential confounding factors for coronary heart disease, hazard ratios (HRs) (with the 95% confidence intervals in parentheses) of a major coronary event, MI, and coronary death reached 1.06 (0.79-1.42), 0.84 (0.54-1.31), and 1.40 (1.04-1.88), respectively, in those with obstruction compared to others. However, in women aged 30-49 obstruction appeared to predict a major coronary event, where the adjusted HR reached 4.21 (1.73-10.28). In conclusion, obstruction appears to predict a major coronary event in younger women only, whereas obstruction closely associates with the risk of coronary death independent of sex and age.

Aims: To study the relation between visit-to-visit variability of blood pressure (BP) and cardiovascular risk in patients with stable coronary heart disease., Methods and Results: In 15 828 patients from the STABILITY trial (darapladib vs. placebo in patients with established coronary heart disease), BP variability was assessed by the standard deviation (SD) of systolic BP, the SD of diastolic BP, maximum BP, and minimum BP, from 5 measurements (baseline and months 1, 3, 6, and 12) during the first year after randomisation. Mean (SD) average BP during the first year of study was 131.0 (13.7) mmHg over 78.3 (8.3) mmHg. Mean (SD) of the visit-to-visit SD was 9.8 (4.8) mmHg for systolic and 6.3 (3.0) mmHg for diastolic BP. During the subsequent median follow-up of 2.6 years, 1010 patients met the primary endpoint, a composite of time to cardiovascular death, myocardial infarction, or stroke. In Cox regression models adjusted for average BP during first year of study, baseline vascular disease, treatment, renal function and cardiovascular risk factors, the primary endpoint was associated with SD of systolic BP (hazard ratio for highest vs. lowest tertile, 1.30, 95% CI 1.10-1.53, P = 0.007), and with SD of diastolic BP (hazard ratio for highest vs. lowest tertile, 1.38, 95% CI 1.18-1.62, P < 0.001). Peaks and troughs in BP were also independently associated with adverse events., Conclusion: In patients with stable coronary heart disease, higher visit-to-visit variabilities of both systolic and diastolic BP are strong predictors of increased risk of cardiovascular events, independently of mean BP., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.)

Background: Elderly women are at high risk of coronary heart disease (CHD) and heart failure. High-sensitivity assays allow detection of cardiac troponin I (hsTnI) well below diagnostic cutoffs for acute coronary syndrome. We investigated the association between these levels with future cardiac events in community-based ambulant white women aged over 70 years initially recruited for a 5-year randomized, controlled trial of calcium supplements., Methods and Results: This was a prospective study of 1081 elderly women without clinical CHD at baseline (1998) or hsTnI above the diagnostic cutoffs for acute coronary syndrome with 14.5-year follow-up hospitalization and mortality (events). Two hundred forty-three (22%) women had CHD events, 163 (15%) myocardial infarction or CHD death (hard CHD), and 109 (10%) heart failure. In 99.6% of available serum samples, hsTnI was above the level of detection (median, 4.5 ng/L; interquartile range, 3.6-5.8). After adjusting for Framingham risk factors, each SD natural log-transformed hsTnI increase was associated with an increased hazard for CHD (hazard ratio, 1.34; 95% CI, 1.18-1.53; P <0.001) hard CHD (hazard ratio, 1.51; 95% CI, 1.29-1.76; P <0.001), and heart failure (hazard ratio, 1.65; 95% CI, 1.36-1.99; P <0.001). Step-wise increases in relative hazards were observed with increasing quartiles of hsTnI ( P for trend, <0.001), whereas the addition of hsTnI to conventional risk factors modestly improved discrimination indices: Harrell's c-statistic, net reclassification, and integrated discrimination ( P <0.05)., Conclusions: Cardiac troponin I is independently associated with future cardiac events in elderly women without apparent clinical manifestations. The addition of cardiac troponin I to conventional risk factors may modestly improve risk prediction in this setting., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Background: Coronary heart disease (CHD) is the single most common cause of death globally. However, with falling CHD mortality rates, an increasing number of people live with CHD and may need support to manage their symptoms and improve prognosis. Cardiac rehabilitation is a complex multifaceted intervention which aims to improve the health outcomes of people with CHD. Cardiac rehabilitation consists of three core modalities: education, exercise training and psychological support. This is an update of a Cochrane systematic review previously published in 2011, which aims to investigate the specific impact of the educational component of cardiac rehabilitation., Objectives: 1. To assess the effects of patient education delivered as part of cardiac rehabilitation, compared with usual care on mortality, morbidity, health-related quality of life (HRQoL) and healthcare costs in patients with CHD.2. To explore the potential study level predictors of the effects of patient education in patients with CHD (e.g. individual versus group intervention, timing with respect to index cardiac event)., Search Methods: We updated searches from the previous Cochrane review, by searching the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library, Issue 6, 2016), MEDLINE (Ovid), Embase (Ovid), PsycINFO (Ovid) and CINAHL (EBSCO) in June 2016. Three trials registries, previous systematic reviews and reference lists of included studies were also searched. No language restrictions were applied., Selection Criteria: 1. Randomised controlled trials (RCTs) where the primary interventional intent was education delivered as part of cardiac rehabilitation.2. Studies with a minimum of six-months follow-up and published in 1990 or later.3. Adults with a diagnosis of CHD., Data Collection and Analysis: Two review authors independently screened all identified references for inclusion based on the above inclusion criteria. One author extracted study characteristics from the included trials and assessed their risk of bias; a second review author checked data. Two independent reviewers extracted outcome data onto a standardised collection form. For dichotomous variables, risk ratios and 95% confidence intervals (CI) were derived for each outcome. Heterogeneity amongst included studies was explored qualitatively and quantitatively. Where appropriate and possible, results from included studies were combined for each outcome to give an overall estimate of treatment effect. Given the degree of clinical heterogeneity seen in participant selection, interventions and comparators across studies, we decided it was appropriate to pool studies using random-effects modelling. We planned to undertake subgroup analysis and stratified meta-analysis, sensitivity analysis and meta-regression to examine potential treatment effect modifiers. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to evaluate the quality of the evidence and the GRADE profiler (GRADEpro GDT) to create summary of findings tables., Main Results: This updated review included a total of 22 trials which randomised 76,864 people with CHD to an education intervention or a 'no education' comparator. Nine new trials (8215 people) were included for this update. We judged most included studies as low risk of bias across most domains. Educational 'dose' ranged from one 40 minute face-to-face session plus a 15 minute follow-up call, to a four-week residential stay with 11 months of follow-up sessions. Control groups received usual medical care, typically consisting of referral to an outpatient cardiologist, primary care physician, or both.We found evidence of no difference in effect of education-based interventions on total mortality (13 studies, 10,075 participants; 189/5187 (3.6%) versus 222/4888 (4.6%); random effects risk ratio (RR) 0.80, 95% CI 0.60 to 1.05; moderate quality evidence). Individual causes of mortality were reported rarely, and we were unable to report separate results for cardiovascular mortality or non-cardiovascular mortality. There was evidence of no difference in effect of education-based interventions on fatal and/or non fatal myocardial infarction (MI) (2 studies, 209 participants; 7/107 (6.5%) versus 12/102 (11.8%); random effects RR 0.63, 95% CI 0.26 to 1.48; very low quality of evidence). However, there was some evidence of a reduction with education in fatal and/or non-fatal cardiovascular events (2 studies, 310 studies; 21/152 (13.8%) versus 61/158 (38.6%); random effects RR 0.36, 95% CI 0.23 to 0.56; low quality evidence). There was evidence of no difference in effect of education on the rate of total revascularisations (3 studies, 456 participants; 5/228 (2.2%) versus 8/228 (3.5%); random effects RR 0.58, 95% CI 0.19 to 1.71; very low quality evidence) or hospitalisations (5 studies, 14,849 participants; 656/10048 (6.5%) versus 381/4801 (7.9%); random effects RR 0.93, 95% CI 0.71 to 1.21; very low quality evidence). There was evidence of no difference between groups for all cause withdrawal (17 studies, 10,972 participants; 525/5632 (9.3%) versus 493/5340 (9.2%); random effects RR 1.04, 95% CI 0.88 to 1.22; low quality evidence). Although some health-related quality of life (HRQoL) domain scores were higher with education, there was no consistent evidence of superiority across all domains., Authors' Conclusions: We found no reduction in total mortality, in people who received education delivered as part of cardiac rehabilitation, compared to people in control groups (moderate quality evidence). There were no improvements in fatal or non fatal MI, total revascularisations or hospitalisations, with education. There was some evidence of a reduction in fatal and/or non-fatal cardiovascular events with education, but this was based on only two studies. There was also some evidence to suggest that education-based interventions may improve HRQoL. Our findings are supportive of current national and international clinical guidelines that cardiac rehabilitation for people with CHD should be comprehensive and include educational interventions together with exercise and psychological therapy. Further definitive research into education interventions for people with CHD is needed.

Aims: To assess whether the use of beta-blockers influences mortality and the incidence of major cardiovascular events in patients with diabetes and coronary heart disease (CHD)., Materials and Methods: Using data from the Bypass Angioplasty Revascularization Investigation 2 Diabetes trial, we performed Cox proportional hazards analysis to assess the effects of β-blockers on all-cause mortality in 2244 patients with type 2 diabetes who had stable CHD with and without a history of myocardial infarction (MI)/heart failure with reduced left ventricular ejection fraction (HFrEF)., Results: All-cause mortality in patients with MI/HFrEF was significantly lower in those receiving β-blockers than in those not receiving β-blockers (adjusted hazard ratio [HR] 0.60, 95% confidence interval [CI] 0.37-0.98; P  = .04), whereas that in patients without MI/HFrEF did not significantly differ (adjusted HR 0.91, 95% CI 0.76-1.32; P  = .64). Among patients with MI/HFrEF, all-cause mortality in those who received intensive medical therapy alone for CHD was significantly lower in those on β-blockers than in those not on β-blockers (adjusted HR 0.45, 95% CI 0.23-0.88; P  = .02); however, mortality in patients who received early revascularization for CHD was not significantly lower in those on β-blockers (adjusted HR 0.81, 95% CI 0.40-1.65; P  = .57). The risk of major cardiovascular events in patients without MI/HFrEF was not significantly different between those on and those not on β-blocker treatment., Conclusions: In patients with diabetes and CHD, the use of β-blockers was effective in reducing all-cause mortality in those with MI/HFrEF but not in those without MI/HFrEF., (© 2017 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Background: Despite the proven advantages of total arterial grafting in patients undergoing coronary artery bypass operation, its benefits in the elderly population at long-term follow-up have been widely debated to date., Methods: Among 988 consecutive patients scheduled to undergo coronary artery bypass grafting operation, we performed a propensity-matched analysis in a population with double and triple vessel disease and older than 70 years and compared patients receiving total arterial grafting (G1; n = 315 patients) with conventional myocardial revascularization (left internal mammary artery on left anterior descending coronary artery plus saphenous vein grafts; G2; n = 201 patients). Two groups of 175 patients were obtained after matching. Primary end points were overall survival and survival free from cardiac-related mortality, whereas secondary end point was the occurrence of major adverse cardiovascular and cerebrovascular events (MACCEs; cardiac death, myocardial infarction, repeated revascularization on grafted vessels, stroke)., Results: Preoperative and intraoperative patients' characteristics were similar among the groups, as well the incidence of hospital mortality (none in both groups). At a median follow-up time of 89 months, total arterial grafting was associated with significantly improved actuarial overall survival (G1: 67.5% ± 4.6%, G2: 57.0% ± 4.4%, p = 0.029), survival free from cardiac-related mortality (G1: 86.9% ± 3.4%, G2: 75.9 ± 4.0%, p = 0.02), and occurrence of MACCEs (G1: 78.8 ± 3.9%, G2: 65.5% ± 4.4%, p = 0.017). Multivariate Cox regression analysis depicted conventional myocardial revascularization as an independent predictor of cardiac-related mortality (hazard ratio [HR] 2.5, 95% confidence interval [CI]: 1.3 to 4.8, p = 0.005) and MACCEs (HR 2.1, 95% CI: 1.2 to 3.4, p = 0.005)., Conclusions: Total arterial myocardial revascularization in elderly patients is associated with a reduced late incidence of cardiac-related mortality and major cerebral and cardiovascular events compared with the use of saphenous grafts, thereby providing improved long-term benefits also in this specific subset of patients., (Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: A 1-year follow-up, polymer-free metallic stent coated with biolimus-A9 followed by 1-month dual antiplatelet therapy is safer and more effective than a bare-metal stent (BMS) for patients with high risk of bleeding., Objectives: This study analyzed 2-year outcomes to determine whether these benefits are maintained., Methods: In a prospective, multicenter, double-blind trial, we randomized 2,466 high bleeding risk patients to receive a drug-coated stent (DCS) or a BMS followed by 1-month dual antiplatelet therapy. The primary safety endpoint was a composite of cardiac death, myocardial infarction, or stent thrombosis. The primary efficacy endpoint was clinically driven target lesion revascularization., Results: At 2 years, the primary safety endpoint had occurred in 147 DCS and 180 BMS patients (15.3%) (hazard ratio: 0.80; 95% confidence interval: 0.64 to 0.99; p = 0.039). Clinically driven target lesion revascularization occurred for 77 DCS and 136 BMS patients (12.0%) (hazard ratio: 0.54; 95% confidence interval: 0.41 to 0.72; p < 0.0001). Major bleeding occurred in 8.9% of DCS and 9.2% of BMS patients (p = 0.95), and a coronary thrombotic event (myocardial infarction and/or stent thrombosis) occurred in 8.2% of DCS and 10.6% of BMS patients (p = 0.045). One-year mortality was 27.1% for a major bleed and 26.3% for a thrombotic event. At 2 years, multivariate correlates of major bleeding were age >75 years, anemia, raised plasma creatinine, and planned long-term anticoagulation. Correlates of the primary safety endpoint were age, anemia, congestive heart failure, multivessel disease, number of stents implanted, and use of a BMS rather than a DCS., Conclusions: Safety and efficacy benefits of DCS over BMS were maintained for 2 years in high bleeding risk patients. Rates of major bleeding and coronary thrombotic events were no different and were associated with a substantial and comparable mortality risk. (A Prospective Randomized Comparison of the BioFreedom Biolimus A9 Drug Coated Stent Versus the Gazelle Bare Metal Stent in Patients With High Risk of Bleeding [LEADERS FREE]; NCT01623180)., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Aim: To comparatively analyze the registered mortality rates from coronary heart disease (CHD) as a whole, as well as myocardial infarction (MI) and other acute forms of CHD during a 15-year period in the Russian Federation (RF, 2000-2014) and the United States of America (USA, 1999-2013)., Material and Methods: Primary data were obtained from the database of the RF State Statistics Service, the World Health Organization Mortality Database, Human Mortality Database, then converted into standardized mortality rates and are presented in three age groups (30+, 30-49, and 50+ years old) in men and women separately., Results: The analysis revealed a substantial excess of the registered mortality rates from CHD in the RF versus in the USA, as well as a lower incidence of MI and a higher incidence of other acute CHD forms registered as the cause of death. It also showed considerable differences in the structure of registered types of MI as the cause of mortality., Conclusion: The differences found in the mortality rates from CHD, MI, and other acute forms of CHD in the RF and the USA can be explained by objective (the higher prevalence of cardiovascular risk factors, the higher and earlier incidence of CHD in the RF, as well as differences in the organization of medical care and, as a result, actually higher mortality rates from CHD in Russia) and subjective (differences in approaches to statistically developing a population-based mortality rate, as well as defects in filling out the medical documents and coding the causes of death) factors.

Significant associations between clinical history factors, lipid metabolism parameters, and type of atherosclerotic process (area of vascular lesions and severity of clinical manifestations) were detected. The predominance of generalized atherosclerosis in chronic coronary heart disease group was associated with patients' age, more incident excessive body weight and type 2 diabetes mellitus, and more severe course of arterial hypertension. Increased lipid spectrum atherogenicity was significantly more often observed in generalized atherosclerosis in the myocardial infarction group. Angiography and postmortem examination of coronary arteries detected two trends of atherogenic remodeling of the coronary vessels: more pronounced stenosis of the main vessels in autopsy specimens from myocardial infarction patients with mainly coronary atherosclerosis and more extensive coronary bed involvement in chronic coronary heart disease patients with generalized atherosclerosis.

Chronic kidney disease (CKD) status might modify the predictive effect of peripheral endothelial dysfunction on cardiovascular events after percutaneous coronary intervention (PCI). The aim of this study was to examine the differential effect of peripheral endothelial dysfunction on clinical outcome after PCI between CKD and non-CKD patients. We conducted a cohort study of 435 patients following PCI. CKD was defined as estimated glomerular filtration rate <60 mL/min/1.73 m(2). Peripheral endothelial dysfunction was examined using reactive hyperemia-peripheral arterial tonometry index (RHI), and we divided patients into low- and high-natural logarithmic RHI (Ln-RHI) group. The endpoint was a composite of cardiovascular death, nonfatal myocardial infarction, ischemic stroke, hospitalization due to unstable angina pectoris, and coronary revascularization. A total of 56 patients had a cardiovascular event. Patients who suffered a cardiovascular event had significantly lower Ln-RHI than other patients in the non-CKD group (0.46 ± 0.18 versus 0.60 ± 0.25; P = 0.002). Kaplan-Meier analysis demonstrated a significantly higher probability of cardiovascular events in low Ln-RHI patients in the non-CKD group (log-rank test: P = 0.003). Multivariate Cox proportional hazards analysis identified Ln-RHI as an independent and significant predictor of future cardiovascular events in the non-CKD group (HR: 0.096; 95 % CI 0.02-0.47; P = 0.004) but not in the CKD group. There was a differential effect of peripheral endothelial dysfunction on clinical outcome after PCI between CKD and non-CKD patients, and peripheral endothelial dysfunction significantly correlates with subsequent cardiovascular events after PCI in non-CKD patients.

Background: We evaluated lipoprotein-associated phospholipase A2 (Lp-PLA2) activity in patients with stable coronary heart disease before and during treatment with darapladib, a selective Lp-PLA2 inhibitor, in relation to outcomes and the effects of darapladib in the STABILITY trial., Methods and Results: Plasma Lp-PLA2 activity was determined at baseline (n=14 500); at 1 month (n=13 709); serially (n=100) at 3, 6, and 18 months; and at the end of treatment. Adjusted Cox regression models evaluated associations between Lp-PLA2 activity levels and outcomes. At baseline, the median Lp-PLA2 level was 172.4 μmol/min per liter (interquartile range 143.1-204.2 μmol/min per liter). Comparing the highest and lowest Lp-PLA2 quartile groups, the hazard ratios were 1.50 (95% CI 1.23-1.82) for the primary composite end point (cardiovascular death, myocardial infarction, or stroke), 1.95 (95% CI 1.29-2.93) for hospitalization for heart failure, 1.42 (1.07-1.89) for cardiovascular death, and 1.37 (1.03-1.81) for myocardial infarction after adjustment for baseline characteristics, standard laboratory variables, and other prognostic biomarkers. Treatment with darapladib led to a ≈65% persistent reduction in median Lp-PLA2 activity. There were no associations between on-treatment Lp-PLA2 activity or changes of Lp-PLA2 activity and outcomes, and there were no significant interactions between baseline and on-treatment Lp-PLA2 activity or changes in Lp-PLA2 activity levels and the effects of darapladib on outcomes., Conclusions: Although high Lp-PLA2 activity was associated with increased risk of cardiovascular events, pharmacological lowering of Lp-PLA2 activity by ≈65% did not significantly reduce cardiovascular events in patients with stable coronary heart disease, regardless of the baseline level or the magnitude of change of Lp-PLA2 activity., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00799903., (© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Objective: To examine the traditional diet-heart hypothesis through recovery and analysis of previously unpublished data from the Minnesota Coronary Experiment (MCE) and to put findings in the context of existing diet-heart randomized controlled trials through a systematic review and meta-analysis., Design: The MCE (1968-73) is a double blind randomized controlled trial designed to test whether replacement of saturated fat with vegetable oil rich in linoleic acid reduces coronary heart disease and death by lowering serum cholesterol. Recovered MCE unpublished documents and raw data were analyzed according to hypotheses prespecified by original investigators. Further, a systematic review and meta-analyses of randomized controlled trials that lowered serum cholesterol by providing vegetable oil rich in linoleic acid in place of saturated fat without confounding by concomitant interventions was conducted., Setting: One nursing home and six state mental hospitals in Minnesota, United States., Participants: Unpublished documents with completed analyses for the randomized cohort of 9423 women and men aged 20-97; longitudinal data on serum cholesterol for the 2355 participants exposed to the study diets for a year or more; 149 completed autopsy files., Interventions: Serum cholesterol lowering diet that replaced saturated fat with linoleic acid (from corn oil and corn oil polyunsaturated margarine). Control diet was high in saturated fat from animal fats, common margarines, and shortenings., Main Outcome Measures: Death from all causes; association between changes in serum cholesterol and death; and coronary atherosclerosis and myocardial infarcts detected at autopsy., Results: The intervention group had significant reduction in serum cholesterol compared with controls (mean change from baseline -13.8%v-1.0%; P<0.001). Kaplan Meier graphs showed no mortality benefit for the intervention group in the full randomized cohort or for any prespecified subgroup. There was a 22% higher risk of death for each 30 mg/dL (0.78 mmol/L) reduction in serum cholesterol in covariate adjusted Cox regression models (hazard ratio 1.22, 95% confidence interval 1.14 to 1.32; P<0.001). There was no evidence of benefit in the intervention group for coronary atherosclerosis or myocardial infarcts. Systematic review identified five randomized controlled trials for inclusion (n=10,808). In meta-analyses, these cholesterol lowering interventions showed no evidence of benefit on mortality from coronary heart disease (1.13, 0.83 to 1.54) or all cause mortality (1.07, 0.90 to 1.27)., Conclusions: Available evidence from randomized controlled trials shows that replacement of saturated fat in the diet with linoleic acid effectively lowers serum cholesterol but does not support the hypothesis that this translates to a lower risk of death from coronary heart disease or all causes. Findings from the Minnesota Coronary Experiment add to growing evidence that incomplete publication has contributed to overestimation of the benefits of replacing saturated fat with vegetable oils rich in linoleic acid., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

The purpose of this study was to compare the outcomes of patients undergoing cardiac transplantation stratified by body mass index (BMI, kg m(-)(2)). The Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease registry captured 220 cardiac transplantations in Alberta, Canada from January 2004 to April 2013. All recipients were stratified by BMI into five groups (BMI: <20, 20-24.9, 25-29.9, 30-<34.9 and ⩾35). Patient characteristics were analyzed by analysis of variance and χ(2) analyses. Kaplan-Meier was used to examine survival differences. Preoperative characteristics demonstrated significant increases in metabolic syndrome, prior myocardial infarction and prior coronary artery bypass graft in patients with morbid obesity. Intra-operatively, there was an increase in cardiopulmonary bypass time in patients with morbid obesity (P<0.01). Postoperative analysis revealed increased rates of early complications (<30 days), associated with a BMI >35. Long-term survival was also significantly decreased in patients with morbid obesity. Of interest, obesity (BMI, 30-34.9) was not associated with decreased survival. These findings suggest that, post-cardiac transplantation, patients who have a BMI ⩾35 have lower long-term survival compared with all other BMI groups. However, patients with BMI 30-34.9 did not have significantly worse outcomes and should not be excluded for heart transplantation based on BMI.

Background: Coronary heart disease (CHD) is the single most common cause of death globally. However, with falling CHD mortality rates, an increasing number of people live with CHD and may need support to manage their symptoms and prognosis. Exercise-based cardiac rehabilitation (CR) aims to improve the health and outcomes of people with CHD. This is an update of a Cochrane systematic review previously published in 2011., Objectives: To assess the effectiveness and cost-effectiveness of exercise-based CR (exercise training alone or in combination with psychosocial or educational interventions) compared with usual care on mortality, morbidity and HRQL in patients with CHD.To explore the potential study level predictors of the effectiveness of exercise-based CR in patients with CHD., Search Methods: We updated searches from the previous Cochrane review, by searching Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 6, 2014) from December 2009 to July 2014. We also searched MEDLINE (Ovid), EMBASE (Ovid), CINAHL (EBSCO) and Science Citation Index Expanded (December 2009 to July 2014)., Selection Criteria: We included randomised controlled trials (RCTs) of exercise-based interventions with at least six months' follow-up, compared with a no exercise control. The study population comprised men and women of all ages who have had a myocardial infarction (MI), coronary artery bypass graft (CABG) or percutaneous coronary intervention (PCI), or who have angina pectoris, or coronary artery disease. We included RCTs that reported at least one of the following outcomes: mortality, MI, revascularisations, hospitalisations, health-related quality of life (HRQL), or costs., Data Collection and Analysis: Two review authors independently screened all identified references for inclusion based on the above inclusion and exclusion criteria. One author extracted data from the included trials and assessed their risk of bias; a second review author checked data. We stratified meta-analysis by the duration of follow up of trials, i.e. short-term: 6 to 12 months, medium-term: 13 to 36 months, and long-term: > 3 years., Main Results: This review included 63 trials which randomised 14,486 people with CHD. This latest update identified 16 new trials (3872 participants). The population included predominantly post-MI and post-revascularisation patients and the mean age of patients within the trials ranged from 47.5 to 71.0 years. Women accounted for fewer than 15% of the patients recruited. Overall trial reporting was poor, although there was evidence of an improvement in quality of reporting in more recent trials.As we found no significant difference in the impact of exercise-based CR on clinical outcomes across follow-up, we focused on reporting findings pooled across all trials at their longest follow-up (median 12 months). Exercise-based CR reduced cardiovascular mortality compared with no exercise control (27 trials; risk ratio (RR) 0.74, 95% CI 0.64 to 0.86). There was no reduction in total mortality with CR (47 trials, RR 0.96, 95% CI 0.88 to 1.04). The overall risk of hospital admissions was reduced with CR (15 trials; RR 0.82, 95% CI 0.70 to 0.96) but there was no significant impact on the risk of MI (36 trials; RR 0.90, 95% CI 0.79 to 1.04), CABG (29 trials; RR 0.96, 95% CI 0.80 to 1.16) or PCI (18 trials; RR 0.85, 95% CI 0.70 to 1.04).There was little evidence of statistical heterogeneity across trials for all event outcomes, and there was evidence of small study bias for MI and hospitalisation, but no other outcome. Predictors of clinical outcomes were examined across the longest follow-up of studies using univariate meta-regression. Results show that benefits in outcomes were independent of participants' CHD case mix (proportion of patients with MI), type of CR (exercise only vs comprehensive rehabilitation) dose of exercise, length of follow-up, trial publication date, setting (centre vs home-based), study location (continent), sample size or risk of bias.Given the heterogeneity in outcome measures and reporting methods, meta-analysis was not undertaken for HRQL. In five out of 20 trials reporting HRQL using validated measures, there was evidence of significant improvement in most or all of the sub-scales with exercise-based CR compared to control at follow-up. Four trial-based economic evaluation studies indicated exercise-based CR to be a potentially cost-effective use of resources in terms of gain in quality-adjusted life years.The quality of the evidence for outcomes reported in the review was rated using the GRADE method. The quality of the evidence varied widely by outcome and ranged from low to moderate., Authors' Conclusions: This updated Cochrane review supports the conclusions of the previous version of this review that, compared with no exercise control, exercise-based CR reduces the risk of cardiovascular mortality but not total mortality. We saw a significant reduction in the risk of hospitalisation with CR but not in the risk of MI or revascularisation. We identified further evidence supporting improved HRQL with exercise-based CR. More recent trials were more likely to be well reported and include older and female patients. However, the population studied in this review still consists predominantly of lower risk individuals following MI or revascularisation. Further well conducted RCTs are needed to assess the impact of exercise-based CR in higher risk CHD groups and also those presenting with stable angina. These trials should include validated HRQL outcome measures, explicitly report clinical event outcomes including mortality and hospital admissions, and assess costs and cost-effectiveness.

Objective: To compare population-level trends in 30-day case fatality following incident myocardial infarction (MI) in people with diabetes and those without diabetes., Methods: We identified all hospitalised incident MIs in 35-84 year olds from the Western Australian Data Linkage System for 1998-2010, stratified by diabetes status. Crude and age- and sex-standardised 30-day case fatality were estimated, and age- and sex-adjusted trends were calculated from logistic regression. We calculated the trend in risk of 30-day death associated with diabetes from multivariable logistic regression, adjusting for demographics, comorbidities and MI type., Results: 26 610 hospitalised incident MI cases were identified, 24.8% of whom had diabetes. The prevalence of heart failure fell in people with diabetes, concurrent with increasing chronic kidney disease and prior coronary heart disease and increasing levels of evidence-based therapies. Case fatality in people with diabetes fell from 11.65%, in 1998-2001, to 3.96% by 2008-2010. Age- and sex-standardised case fatality declined at a greater rate in those with diabetes (-10.6%/year, 95% CI -12.8% to -8.2%) compared to non-diabetics (-6.9%/year, 95% CI -8.3% to -5.3%; interaction p=0.005). The adjusted risk of 30-day death after incident MI was 1.23 times higher in diabetics than non-diabetics in 1998-2001 (95% CI 1.01 to 1.50), but was lower by 2008-2010 (OR 0.64, 95% CI 0.46 to 0.88)., Conclusions: Greater improvements in 30-day case fatality following incident MI in people with diabetes during the 13-year study period has led to diabetes no longer being an independent predictor of early death following incident MI by 2008-2010., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: Few contemporary studies examine trends in recurrent coronary heart disease (CHD) events and mortality after acute myocardial infarction (AMI) and whether these trends vary by race or sex., Methods: We used data from the national 5% random sample of Medicare fee-for-service beneficiaries for 1999 to 2010. We included beneficiaries who experienced an AMI (International Classification of Disease [ICD] 9 410.xx, except 410.x2) between January 1, 2001, and December 31, 2009. Each beneficiary's first AMI was included as their index event. Outcomes included all-cause mortality, recurrent AMI, and recurrent CHD events during the 365days after discharge for the index AMI. To examine secular trends, we pooled calendar years into 3 periods (2001-2003, 2004-2006, and 2007-2009)., Results: Among 48,688 beneficiaries with index AMIs from 2001 to 2009, we observed decreases in the age-adjusted rates for mortality (-3.8% for each 3-year period, 95% CI -6.1% to -1.6%, P trend = .001), recurrent AMI (-15.0%, 95% CI -18.6% to -11.2%, P trend < .001), and recurrent CHD events (-11.1%, 95% CI -14.0% to -8.0%, P trend < .001) in the 365days after the index AMI. In 2007 to 2009, blacks had excess risk relative to whites for mortality and recurrent AMI (black/white incidence rate ratio of 1.38 for mortality [95% CI 1.21-1.57] and 1.38 for recurrent AMI [95% CI 1.07-1.79])., Conclusions: Despite overall favorable trends in lower mortality and recurrent events after AMI, efforts are needed to reduce racial disparities., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Patients with stable coronary heart disease (CHD) have widely varying prognoses and treatment options. Validated models for risk stratification of patients with CHD are needed. We sought to evaluate traditional and novel risk factors as predictors of secondary cardiovascular (CV) events, and to develop a prediction model that could be used to risk stratify patients with stable CHD., Methods and Results: We used independent derivation (912 participants in the Heart and Soul Study) and validation (2876 participants in the PEACE trial) cohorts of patients with stable CHD to develop a risk prediction model using Cox proportional hazards models. The outcome was CV events, defined as myocardial infarction, stroke, or CV death. The annual rate of CV events was 3.4% in the derivation cohort and 2.2% in the validation cohort. With the exception of smoking, traditional risk factors (including age, sex, body mass index, hypertension, dyslipidemia, and diabetes) did not emerge as the top predictors of secondary CV events. The top 4 predictors of secondary events were the following: N-terminal pro-type brain natriuretic peptide, high-sensitivity cardiac troponin T, urinary albumin:creatinine ratio, and current smoking. The 5-year C-index for this 4-predictor model was 0.73 in the derivation cohort and 0.65 in the validation cohort. As compared with variables in the Framingham secondary events model, the Heart and Soul risk model resulted in net reclassification improvement of 0.47 (95% CI 0.25 to 0.73) in the derivation cohort and 0.18 (95% CI 0.01 to 0.40) in the validation cohort., Conclusions: Novel risk factors are superior to traditional risk factors for predicting 5-year risk of secondary events in patients with stable CHD., (© 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Background: We examined whether type of menopause affects sex differences in coronary heart disease (CHD) events and whether the impact is similar in blacks and whites., Methods and Results: Participants were enrolled in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort between 2003 and 2007 without CHD at baseline (n=23 086). Cox regression models were used to calculate the hazard of incident nonfatal CHD (definite or probable myocardial infarction) and acute CHD death, adjusting for age, age at last menstrual period <45 years, region, education level, income, diabetes, smoking, systolic blood pressure, lipid levels, albumin-creatinine ratio, physical activity, C-reactive protein, body mass index, waist circumference, and medication use. White women in natural menopause (hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.31, 0.66) and surgical menopause (HR, 0.65; 95% CI, 0.42, 0.99) had a reduced hazard of nonfatal events, compared to white men. Black women in natural menopause (HR, 0.69; 95% CI, 0.47, 1.03), but not surgical menopause (HR, 0.81; 95% CI, 0.51, 1.29), had a marginally reduced hazard of nonfatal events, compared to black men. Women had lower risk of acute CHD death than men regardless of their menopause type and race., Conclusions: Sex differences in the risk of incident CHD events were larger among whites than blacks and varied by type of menopause. Women consistently had a lower risk of incident CHD death than men, but the magnitude of sex differences was greater in whites than blacks for nonfatal events, regardless of menopause type., (© 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Study Objectives: The aim of the study was to determine the association of objectively measured sleep disordered breathing (SDB) with incident coronary heart disease (CHD) or heart failure (HF) in a nonclinical population., Design: Longitudinal analysis of a community-dwelling cohort followed up to 24 y., Setting: Sleep laboratory at the Clinical Research Unit of the University of Wisconsin Hospital and Clinics., Participants: There were 1,131 adults who completed one or more overnight polysomnography studies, were free of CHD or HF at baseline, were not treated by continuous positive airway pressure (CPAP), and followed over 24 y., Interventions: None., Measurements and Results: In-laboratory overnight polysomnography was used to assess SDB, defined by the apnea-hypopnea index (AHI) using apnea and hypopnea events per hour of sleep. Incident CHD or HF was defined by new reports of myocardial infarction, coronary revascularization procedures, congestive heart failure, and cardiovascular deaths. We used baseline AHI as the predictor variable in survival analysis models predicting CHD or HF incidence adjusted for traditional confounders. The incidence of CHD or HF was 10.9/1,000 person-years. The mean time to event was 11.2 ± 5.8 y. After adjusting for age, sex, body mass index, and smoking, estimated hazard ratios (95% confidence interval) of incident CHD or HF were 1.5 (0.9-2.6) for AHI > 0-5, 1.9 (1.05-3.5) for AHI 5 ≤ 15, 1.8 (0.85-4.0) for AHI 15 ≤ 30, and 2.6 (1.1-6.1) for AHI > 30 compared to AHI = 0 (P trend = 0.02)., Conclusions: Participants with untreated severe sleep disordered breathing (AHI > 30) were 2.6 times more likely to have an incident coronary heart disease or heart failure compared to those without sleep disordered breathing. Our findings support the postulated adverse effects of sleep disordered breathing on coronary heart disease and heart failure., (© 2015 Associated Professional Sleep Societies, LLC.)

Background: Eptifibatide, a small-molecule glycoprotein IIb/IIIa inhibitor, is conventionally administered as a bolus plus infusion. A growing number of clinicians are using a strategy of catheterization laboratory-only eptifibatide (an off-label use) as procedural pharmacotherapy for patients undergoing percutaneous coronary intervention although the comparative effectiveness of this approach is unknown., Methods and Results: We compared the in-hospital outcome of patients undergoing percutaneous coronary intervention across 47 hospitals and treated with eptifibatide bolus plus infusion with those treated with a catheterization laboratory-only regimen. We used optimal matching to link the use of catheterization laboratory-only eptifibatide with clinical outcomes, including mortality, myocardial infarction, bleeding, and need for transfusion. Of the 84 678 percutaneous coronary interventions performed during 2010 to 2011, and meeting our inclusion criteria, eptifibatide was administered to 21 296 patients. Of these, a catheterization laboratory-only regimen was used in 4511 patients, whereas 16 785 patients were treated with bolus plus infusion. In the optimally matched analysis, compared with bolus plus infusion, a catheterization laboratory-only regimen was associated with a reduction in bleeding (optimally matched adjusted odds ratio, 0.74; 95% confidence interval, 0.58-0.93; P=0.014) and need for transfusion (optimally matched adjusted odds ratio, 0.70; 95% confidence interval, 0.52-0.92; P=0.012), with no difference in mortality or myocardial infarction., Conclusions: A catheterization laboratory-only eptifibatide regimen is commonly used in clinical practice and is associated with a significant reduction in bleeding complications in patients undergoing contemporary percutaneous coronary intervention., (© 2015 American Heart Association, Inc.)

Background: Appropriate management for patients with multivessel coronary disease presenting with ST segment Elevation Myocardial Infarction (STEMI) remains to be defined., Methods and Results: Medline and Cochrane Library were searched for randomized controlled trials (RCTs) or observational studies adjusted with multivariate analysis, reporting about STEMI patients with multivessel coronary disease treated with either a culprit only or complete revascularization strategy, excluding patients in cardiogenic shock. Prespecified analysis was performed according to the strategy of complete revascularization, either during the same procedure of primary percutaneous coronary intervention (PCI) or during the index hospitalization. MACE (a composite and mutually exclusive end point of death or myocardial infarction or revascularization) at follow-up of at least one year was the primary end point. 9 studies with 4686 patients compared culprit only versus complete PCI performed during the primary PCI. Rates of MACE did not differ at 90 days (OR 0.70 [0.38, 1.27], I(2)=0%) or at 1 year (1-2.5) (OR 0.70 [0.47, 1.03], I(2)=0%). No significant difference was found for the components of the primary outcome, apart from a reduction in repeated revascularization for patients undergoing complete PCI during the STEMI procedure (OR 0.62 [0.39, 0.98], I(2)=0%). 6 studies (1 RCT) with 5855 patients compared culprit only lesions versus complete PCI performed during index hospitalization. 90 day risk of MACE did not differ nor 1 year (1-2.5) MACE (OR 0.86 [0.62, 1.08], I(2)=0%), with a similar reduction in repeated revascularization (0.60 [0.40, 0.90], I(2)=0%)., Conclusions: Complete revascularization performed during primary PCI or index hospitalizations for patients presenting with STEMI appears safe at short term follow-up and offers a reduction in repeated revascularization at one year., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: Drug-eluting stents (DES) have largely replaced bare-metal stents (BMS) for percutaneous coronary intervention (PCI). It is uncertain, however, whether introduction of DES had a significant impact on the comparative effectiveness of PCI versus coronary artery bypass graft surgery (CABG) for death and myocardial infarction (MI)., Methods: We identified Medicare beneficiaries aged ≥66 years who underwent multivessel CABG or multivessel PCI and matched PCI and CABG patients on propensity score. We defined the BMS era as January 1999 to April 2003 and the DES era as May 2003 to December 2006. We compared 5-year outcomes of CABG and PCI using Cox proportional hazards models, adjusting for baseline characteristics and year of procedure and tested for a statistically significant interaction (P(int)) of DES era with treatment (CABG or PCI)., Results: Five-year survival improved from the BMS era to the DES era by 1.2% for PCI and by 1.1% for CABG, and the CABG:PCI hazard ratio was unchanged (0.90 vs 0.90; P(int) = .96). Five-year MI-free survival improved by 1.4% for PCI and 1.1% for CABG, with no change in the CABG:PCI hazard ratio (0.81 vs 0.82; P(int) = .63). By contrast, survival-free of MI or repeat coronary revascularization improved from the BMS era to the DES era by 5.7% for PCI and 0.9% for CABG, and the CABG:PCI hazard ratio changed significantly (0.50 vs 0.57, P(int) ≤ .0001)., Conclusions: The introduction of DES did not alter the comparative effectiveness of CABG and PCI with respect to hard cardiac outcomes., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Borderline electrocardiograms represent a challenge in ST-segment elevation myocardial infarction (STEMI) management and are associated with inappropriate discharges and delays to intervention., Objectives: To assess angiographic characteristics and outcomes of patients presenting with subtle ST-elevation (STE) myocardial infarction., Methods: A total of 504 consecutive patients with suspected STEMI treated by systematic primary percutaneous coronary intervention were prospectively included. Subtle STE was defined as a maximal preinterventional STE of 0.1 to 1 mm. Angiograms were interpreted by investigators unaware of the electrocardiographic data., Results: The proportion of patients with subtle STE was 18.3%, 86% of them presented with Thrombolysis In Myocardial Infarction flow grade 0/1 and 91% underwent percutaneous coronary intervention. Despite having smaller infarcts, subtle STE patients associated more frequent multivessel disease (57% vs 44%, P = .02) and larger delays to reperfusion. During a follow-up of 19.0 ± 4.9 months, the rates of death or reinfarction were similar among groups (10.0% vs 12.6%, P = .467). Subtle STE was not associated with better outcomes neither in univariate nor after adjustment in a multivariate analysis (adjusted hazard ratio 0.79, 95% CI 0.37-1.69, P = .546)., Conclusions: Subtle STEMI is frequent in clinical practice and is usually associated with acute total coronary occlusion. Therefore, it should be diagnosed and treated in the same expeditiously manner as marked STEMI., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Periprocedural myocardial infarction (PMI) has had several definitions in the last decade, including the Society for Cardiovascular Angiography and Interventions (SCAI) definition, that requires marked biomarker elevations congruent with surgical PMI criteria., Methods and Results: The aim of this study was to examine the definition-based frequencies of PMI and whether they influenced the reported association between PMI and increased rates of late death/ myocardial infarction (MI). We studied 742 patients; 492 (66%) had normal troponin T (TnT) levels and 250 (34%) had elevated, but stable or falling, TnT levels. PMI, using the 2007 and the 2012 universal definition, occurred in 172 (23.2%) and in 99 (13.3%) patients, respectively, whereas 19 (2.6%) met the SCAI PMI definition (P<0.0001). Among patients with PMI using the 2012 definition, occlusion of a side branch ≤1 mm occurred in 48 patients (48.5%) and was the most common angiographic finding for PMI. The rates of death/MI at 2 years in patients with, compared to those without, PMI was 14.7% versus 10.1% (P=0.087) based on the 2007 definition, 16.9% versus 10.3% (P=0.059) based on the 2012 definition, and 29.4% versus 10.7% (P=0.015) based on the SCAI definition., Conclusion: In this study, PMI, according to the SCAI definition, was associated with more-frequent late death/MI, with ≈20% of all patients, who had PMI using the 2007 universal MI definition, not having SCAI-defined PMI. Categorizing these latter patients as SCAI-defined no PMI did not alter the rate of death/MI among no-PMI patients., (© 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Heart disease was an uncommon cause of death in the US at the beginning of the 20th century. By mid-century it had become the commonest cause. After peaking in the mid-1960s, the number of heart disease deaths began a marked decline that has persisted to the present. The increase in heart disease deaths from the early 20th century until the 1960s was due to an increase in the prevalence of coronary atherosclerosis with resultant coronary heart disease, as documented by autopsy studies. This increase was associated with an increase in smoking and dietary changes leading to an increase in serum cholesterol levels. In addition, the ability to diagnose acute myocardial infarction with the aid of the electrocardiogram increased the recognition of coronary heart disease before death. The substantial decrease in coronary heart disease deaths after the mid-1960s is best explained by the decreased incidence, and case fatality rate, of acute myocardial infarction and a decrease in out-of-hospital sudden coronary heart disease deaths. These decreases are very likely explained by a decrease in coronary atherosclerosis due to primary prevention, and a decrease in the progression of nonobstructive coronary atherosclerosis to obstructive coronary heart disease due to efforts of primary and secondary prevention. In addition, more effective treatment of patients hospitalized with acute myocardial infarction has led to a substantial decrease in deaths due to acute myocardial infarction. It is very likely that the 20th century was the only century in which heart disease was the most common cause of death in America., (Copyright © 2014 Elsevier Inc. All rights reserved.)