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Patients with cancer are at increased risk of myocardial infarction (MI) and stroke. Guidelines do not address lipid profile targets for these patients. Within the lipid profiles, we hypothesized that patients with cancer develop MI or stroke at lower low density lipoprotein cholesterol (LDL-C) concentrations than patients without cancer and suffer worse outcomes. We linked nationwide longitudinal MI, stroke and cancer registries from years 2007–2017. We identified 42,148 eligible patients with MI (2421 prior cancer; 39,727 no cancer) and 43,888 eligible patients with stroke (3152 prior cancer; 40,738 no cancer). Median LDL-C concentration was lower in the prior cancer group than the no cancer group at incident MI [2.43 versus 3.10 mmol/L, adjusted ratio 0.87 (95% CI 0.85–0.89)] and stroke [2.81 versus 3.22 mmol/L, adjusted ratio 0.93, 95% CI 0.91–0.95)]. Similarly, median triglyceride and total cholesterol concentrations were lower in the prior cancer group, with no difference in high density lipoprotein cholesterol. Prior cancer was associated with higher post-MI mortality [adjusted hazard ratio (HR) 1.48, 95% CI 1.37–1.59] and post-stroke mortality (adjusted HR 1.95, 95% CI 1.52–2.52). Despite lower LDL-C concentrations, patients with prior cancer had worse post-MI and stroke mortality than patients without cancer.

Background The COVID-19 pandemic has affected patients with ST-segment elevation myocardial infarction (STEMI) requiring primary percutaneous coronary intervention (PCI) worldwide. In this review we examine the global effect of the COVID-19 pandemic on incidence of STEMI admissions, and relationship between the pandemic and door to balloon time (D2B), all-cause mortality, and other secondary STEMI outcomes. Methods We performed a systematic review and meta-analysis to primarily compare D2B time and in-hospital mortality of STEMI patients who underwent primary PCI during and before the pandemic. Subgroup analyses were performed to investigate the influence of geographical region and income status of a country on STEMI care. An online database search included studies that compared the aforementioned outcomes of STEMI patients during and before the pandemic. Results In total, 32 articles were analyzed. Overall, 19,140 and 68,662 STEMI patients underwent primary PCI during and before the pandemic, respectively. Significant delay in D2B was observed during the pandemic (weighted mean difference, 8.10 minutes; 95% confidence interval [CI], 3.90-12.30 minutes; P = 0.0002; I2 = 90%). In-hospital mortality was higher during the pandemic (odds ratio [OR], 1.27; 95% CI, 1.09-1.49; P = 0.002; I2 = 36%), however this varied with factors such as geographical location and income status of a country. Subgroup analysis showed that low–middle-income countries observed a higher rate of mortality during the pandemic (OR, 1.52; 95% CI, 1.13-2.05; P = 0.006), with a similar but insignificant trend seen among the high income countries (OR, 1.17; 95% CI, 0.95-1.44; P = 0.13). Conclusions The COVID-19 pandemic is associated with worse STEMI performance metrics and clinical outcome, particularly in the Eastern low–middle-income status countries. Better strategies are needed to address these global trends in STEMI care during the pandemic.

Coronary artery disease (CAD) remains the leading cause of adult mortality globally. Targeting known modifiable risk factors has had substantial benefit, but there remains a need for new approaches. Improvements in invasive and noninvasive imaging techniques have enabled an increasing recognition of distinct quantitative phenotypes of coronary atherosclerosis that are prognostically relevant. There are marked differences in plaque phenotype, from the high-risk, lipid-rich, thin-capped atheroma to the low-risk, quiescent, eccentric, nonobstructive calcified plaque. Such distinct phenotypes reflect different pathophysiologic pathways and are associated with different risks for acute ischemic events. Noninvasive coronary imaging techniques, such as computed tomography, positron emission tomography, and coronary magnetic resonance imaging, have major potential to accelerate cardiovascular drug development, which has been affected by the high costs and protracted timelines of cardiovascular outcome trials. This may be achieved through enrichment of high-risk phenotypes with higher event rates or as primary end points of drug efficacy, at least in phase 2 trials, in a manner historically performed through intravascular coronary imaging studies. Herein, we provide a comprehensive review of the current technology available and its application in clinical trials, including implications for sample size requirements, as well as potential limitations. In its effort to accelerate drug development, the US Food and Drug Administration has approved surrogate end points for 120 conditions, but not for CAD. There are robust data showing the beneficial effects of drugs, including statins, on CAD progression and plaque stabilization in a manner that correlates with established clinical end points of mortality and major adverse cardiovascular events. This, together with a clear mechanistic rationale for using imaging as a surrogate CAD end point, makes it timely for CAD imaging end points to be considered. We discuss the importance of global consensus on these imaging end points and protocols and partnership with regulatory bodies to build a more informed, sustainable staged pathway for novel therapies.

BACKGROUND: Ischaemic heart disease remains the main cause of death in the world. With increasing age, frailty and comorbidities, senior patients aged 80 years old and above who undergo percutaneous coronary intervention (PCI) are at higher risk of mortality and other complications. AIMS: We aimed to examine the overall outcomes for this group of patients. METHODS: Four databases (PUBMED, EMBASE, SCOPUS and CENTRAL) were searched. Studies with patients aged 80 years old and above who underwent PCI for all indications were included. Pooled outcomes of all-cause death, cardiac death, in-hospital death, subsequent stroke/transient ischaemic attack (TIA), subsequent myocardial infarction (MI), subsequent congestive cardiac failure (CCF), and overall major adverse cardiac events (MACE) were obtained for meta-analysis. RESULTS: From 2,566,004 patients, the pooled cumulative incidence of death was 19.22%, cardiac death was 7.78%, in-hospital death was 7.16%, subsequent stroke/TIA was 1.54%, subsequent MI was 3.58%, subsequent CCF was 4.74%, and MACE was 17.51%. The mortality rate of all patients was high when followed up for 3 years (33.27%). ST-elevation myocardial infarction patients had more outcomes of in-hospital death (14.24% vs 4.89%), stroke/TIA (1.93% vs 0.12%), MI (3.68 vs 1.55%) and 1-year mortality (26.16% vs 13.62%), when compared to non-ST-elevation myocardial infarction patients. CONCLUSIONS: There was a high mortality rate at 1 year and 3 years post-PCI in the overall population of senior patients aged 80 years old and above, regardless of indication. This necessitates further studies to explore the implications of these observations.

Background Randomized controlled trials (RCTs) of lipid-lowering therapy (LLT) in which the control groups received placebo without background LLT offer unique insights into the placebo and nocebo effects of lipid-lowering RCTs. Methods and results Embase and Medline were searched for hyperlipidaemia RCTs with placebo-controlled arms. Placebo arms with background LLT were excluded. A single arm meta-analysis of proportions was used to estimate major adverse cardiovascular events (MACE) and adverse events (AE). A meta-analysis of means was used to estimate the pooled mean differences of total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoproteins (HDL) and triglycerides (TG). A total of 40 RCTs and 37 668 placebo-treated participants were included. The pooled mean changes for TC, LDL, HDL, and TG were −0.019 mmol/L, −0.028 mmol/L, 0.013 mmol/L, and 0.062 mmol/L respectively among placebo-treated participants, indicating a modest placebo effect. The pooled average nocebo effect among placebo-treated participants was 42.62% for all AEs and 3.38% for musculoskeletal-related AEs, 11.36% for gastrointestinal-related AEs, and 6.62% for headaches. Placebo-treated participants in secondary prevention RCTs had a far higher incidence of these nocebo effects than primary prevention RCTs: any AEs (OR 6.76, 95% CI: 5.56–8.24, P Conclusion Our meta-analysis of placebo-treated participants in RCTs with no background LLT indicate a modest placebo effect but prominent nocebo effect of musculoskeletal, headache, and gastrointestinal symptoms that was greatest among secondary prevention RCTs. These findings may inform the design of future LLT RCTs.

There is a growing number of trials examining the effectiveness of pharmacotherapies for obesity, however, little is known about placebo and nocebo effect in these trials. Hence, we sought to examine the effect of placebo in obesity trials, to better understand the potential factors affecting clinical endpoints in them.Medline, Embase, and Cochrane CENTRAL were searched for articles examining weight-loss RCTs examining patients with overweight or obesity in placebo-controlled arms from inception till 25 June 2022. This paper was registered online with PROSPERO (CRD42022302482). A single arm meta-analysis of proportions was used to estimate the primary outcomes, ≥5%, ≥10%, and ≥15% total weight loss - and the adverse effects that patients experienced during the trial. A meta-analysis of means was used to estimate the pooled mean differences of the secondary outcomes including, body weight measurements, lipid levels, glycemic indices, and blood pressure over time.A total of 63 papers involving 20,454 patients and 69 trials were included. The proportion of patients that had ≥5%, ≥10%, and ≥15% weight loss was 20·4% (CI:16·1% to 25·0%), 8·3% (CI:6·1% to 10·9%), and 6·2% (CI:3·8% to 9·7%), respectively. Analysis by duration of trials showed stepwise increase in proportion of patients with ≥5% and ≥10% weight loss with increasing duration of study. Analysis of secondary outcomes found modest improvement in all analyses. The pooled average rate of overall AEs, serious AEs, and discontinuation was 73·7% (CI:68·0% to 79·0%), 3·4% (CI:2·4% to 4·5%), and 5·2% (CI:4·0% to 6·5%), respectively. In psychiatric complications, the pooled rates of anxiety and depression were 2·7% (CI:1·8% to 3·7%) and 2·5 (CI:1·7% to 3·3%).Our meta-analysis of placebo-treated participants in weight-loss RCTs indicate a significant placebo and nocebo effect. These findings are important to quantify their effect and may inform the design of future RCTs.This research did not receive additional support from organizations beyond the authors' academic institutions.

Coronavirus disease 2019 (COVID-19) predisposes patients to thrombotic and thromboembolic events, owing to excessive inflammation, endothelial cell activation and injury, platelet activation and hypercoagulability. Patients with COVID-19 have a prothrombotic or thrombophilic state, with elevations in the levels of several biomarkers of thrombosis, which are associated with disease severity and prognosis. Although some biomarkers of COVID-19-associated coagulopathy, including high levels of fibrinogen and d-dimer, were recognized early during the pandemic, many new biomarkers of thrombotic risk in COVID-19 have emerged. In this Consensus Statement, we delineate the thrombotic signature of COVID-19 and present the latest biomarkers and platforms to assess the risk of thrombosis in these patients, including markers of platelet activation, platelet aggregation, endothelial cell activation or injury, coagulation and fibrinolysis as well as biomarkers of the newly recognized post-vaccine thrombosis with thrombocytopenia syndrome. We then make consensus recommendations for the clinical use of these biomarkers to inform prognosis, assess disease acuity, and predict thrombotic risk and in-hospital mortality. A thorough understanding of these biomarkers might aid risk stratification and prognostication, guide interventions and provide a platform for future research., In this Consensus Statement, the authors delineate the thrombotic signature of COVID-19 and present the latest biomarkers and platforms to assess thrombotic risk in these patients. Consensus recommendations are made about the clinical use of these biomarkers to inform prognosis, assess disease acuity, and predict thrombosis and in-hospital mortality.

Co-prevalence and incidence of depression and/or anxiety with stroke and myocardial infarction are currently unclear. This paper explores the relationships, as these are important comorbidities affecting patient outcomes.A systematic search across five databases (PubMed, Scopus, PsycINFO, Embase, Cochrane) was conducted for observational studies reporting co-prevalence of depression or anxiety with stroke or myocardial infarction. We used random-effects models in all meta-analyses and evaluated heterogeneity using IThis analysis included 48 studies with a total of 57,342 patients. In patients with depression, the pooled prevalence of stroke was 5.9% (95% CI = 5.53-6.37). In patients with myocardial infarction, the pooled prevalence of anxiety and depression was 9.1% (95% CI = 7.07-11.40, IThis meta-analysis outlines the co-morbid burden between depression/anxiety and stroke/myocardial infarction. Future research should be done to evaluate the effectiveness of screening anxiety/depression in myocardial infarction/stroke.

Omeprazole is commonly co-prescribed with clopidogrel. Clopidogrel requires bio-activation by cytochrome P450 CYP2C19. Omeprazole may reduce clopidogrel’s antithrombotic efficacy by inhibiting CYP2C19. Studies in Caucasians receiving omeprazole with clopidogrel showed no significant increase in death and myocardial infarction with this drug–drug interaction. There are limited large-scale studies in Asians, who may have a greater prevalence of CYP2C19 loss-of-function polymorphisms. A single centre retrospective cohort study was undertaken based on a review of medication records and prescription data. Patients prescribed clopidogrel from 2009 to 2012 were followed-up with until December 2012 (median:29 months). The primary outcome was all-cause mortality and secondary outcomes were myocardial infarction (MI), cerebrovascular accidents, and subsequent coronary interventions. Of 12,440 patients prescribed clopidogrel, 62%(n = 7714) were on omeprazole (63.8% Chinese, 13.9% Malay, 12.4% Indian, 10.0% others), and 38%(n = 4726) were not on omeprazole or other proton pump inhibitors (62.6% Chinese, 13.5% Malay, 10.7% Indian, 13.2% others). Mortality after co-prescription occurred in 14.3%(n = 1101) of patients, compared to 6.3%(n = 300) of patients prescribed clopidogrel only. Multivariate analysis using propensity score adjusted analysis showed no significant increase in all-cause mortality with co-prescription (adjusted hazards ratio [AHR] 1.13, [95%CI 0.95–1.35]). Patients on co-prescription had a higher risk of subsequent MI (16% vs 3.8%; AHR 2.03 [95%CI 1.70–2.44]), but not of cerebrovascular accidents (5.0% vs 2.0%; AHR 0.98 [95%CI 0.76–1.27]) or coronary interventions (1.7% vs 0.7%; AHR 1.28 [95%CI 0.83–1.96]). The risk of a subsequent MI was higher in the Malay (AHR 2.43 [95%CI 1.68–3.52]) and Chinese (AHR 2.06 [95%CI 1.63–2.60]) population as compared to the Indian (AHR 1.56 [95%CI 1.06–2.31]) population. In conclusion, the use of clopidogrel with omeprazole is associated with an increased risk of MI, but not mortality or stroke, in this multi-ethnic Asian population. These risks appear to vary among different ethnic groups.

We recently discovered that Mfsd2b, which is the S1P exporter found in blood cells. Here, we report that Mfsd2b is critical for the release of all S1P species in both resting and activated platelets. We show that resting platelets store S1P in the cytoplasm. After activation, this S1P pool is delivered to the plasma membrane, where Mfsd2b is predominantly localized for export. Employing knockout mice of Mfsd2b, we reveal that platelets contribute a minor amount of plasma S1P. Nevertheless, Mfsd2b deletion in whole body or platelets impairs platelet morphology and functions. In particular, Mfsd2b knockout mice show significantly reduced thrombus formation. We show that loss of Mfsd2b affects intrinsic platelet functions as part of remarkable sphingolipid accumulation. These findings indicate that accumulation of sphingolipids including S1P by deletion of Mfsd2b strongly impairs platelet functions, which suggests that the transporter may be a target for the prevention of thrombotic disorders., The mechanisms by which platelets release sphingosine-1-phosphate (S1P) is not well characterized. Here the authors show that Mfsd2b is required for S1P release from both resting and activated platelets and that deletion of Mfsd2b impairs thrombotic functions of platelets.

Acute myocardial infarction (AMI) is a leading cause of mortality and morbidity worldwide. Using a validated and efficient ICP-MS/MS-based workflow, a total of 30 metallomic features were profiled in a study comprising 101 AMI patients and 66 age-matched healthy controls. The metallomic features include 12 essential elements (Ca, Co, Cu, Fe, K, Mg, Mn, Na, P, S, Se, Zn), 8 non-essential/toxic elements (Al, As, Ba, Cd, Cr, Ni, Rb, Sr, U, V), and 10 clinically relevant element-pair product/ratios (Ca/Mg, Ca×P, Cu/Se, Cu/Zn, Fe/Cu, P/Mg, Na/K, Zn/Se). Preliminary linear regression with feature selection confirmed smoking status as a predominant determinant for the non-essential/toxic elements, and revealed potential routes of action. Univariate assessments with adjustments for covariates revealed insights into the ambivalent relationships of Cu, Fe, and P with AMI, while also confirming cardioprotective associations of Se. Also, beyond their roles as risk factors, Cu and Se may be involved in the response mechanism in AMI onset/intervention, as demonstrated via longitudinal data analysis with 2 additional time-points (1-/6-month follow-up). Finally, based on both univariate tests and multivariate classification modelling, potentially more sensitive markers measured as element-pair ratios were identified (e.g., Cu/Se, Fe/Cu). Overall, metallomics-based biomarkers may have utility for AMI prediction.

Left ventricular thrombus (LVT) is a common complication of acute myocardial infarction and is associated with morbidity from embolic complications. Predicting which patients will develop death or persistent LVT despite anticoagulation may help clinicians identify high-risk patients. We developed a random forest (RF) model that predicts death or persistent LVT and evaluated its performance. This was a single-center retrospective cohort study in an academic tertiary center. We included 244 patients with LVT in our study. Patients who did not receive anticoagulation (n = 8) or had unknown (n = 31) outcomes were excluded. The primary outcome was a composite outcome of death, recurrent LVT and persistent LVT. We selected a total of 31 predictors collected at the point of LVT diagnosis based on clinical relevance. We compared conventional regularized logistic regression with the RF algorithm. There were 156 patients who had resolution of LVT and 88 patients who experienced the composite outcome. The RF model achieved better performance and had an AUROC of 0.700 (95% CI 0.553-0.863) on a validation dataset. The most important predictors for the composite outcome were receiving a revascularization procedure, lower visual ejection fraction (EF), higher creatinine, global wall motion abnormality, higher prothrombin time, higher body mass index, higher activated partial thromboplastin time, older age, lower lymphocyte count and higher neutrophil count. The RF model accurately identified patients with post-AMI LVT who developed the composite outcome. Further studies are needed to validate its use in clinical practice.

Objective: Obesity has been shown to be associated with adverse outcomes in viral infections such as influenza, but previous studies on coronavirus disease 2019 (COVID-19) had mixed results. The aim of this systematic review is to investigate the relationship between COVID-19 and obesity. Methods: We performed a systematic review and meta-analysis. A literature search of MEDLINE, EMBASE, Scopus, Web of Science, CENTRAL, OpenGrey and preprint servers medRxiv and bioRxiv was performed, with no restriction on language or date of publication. Primary outcomes of this study were intensive care unit (ICU) admission or critical disease, severe disease and mortality. Secondary outcome was a positive COVID-19 test. Meta-analysis was performed using OpenMeta-Analyst software, and heterogeneity was tested using Cochran’s Q test and I2 statistic. The study protocol was registered on PROSPERO (CRD42020184953). Results: A total of 1,493 articles were identified and 61 studies on 270,241 patients were included. The pooled prevalence of obesity was 27.6% (95% confidence interval [CI] 22.0–33.2) in hospitalised patients. Obesity was not significantly associated with increased ICU admission or critical illness (odds ratio [OR] 1.25, 95% CI 0.99–1.58, P=0.062, I2=31.0) but was significantly associated with more severe disease (OR 3.13, 95% CI 1.41–6.92, P=0.005, I2=82.6), mortality (OR 1.36, 95% CI 1.09–1.69, P=0.006, I2=88.5) and a positive COVID-19 test (OR 1.50, 95% CI 1.25–1.81, P

BackgroundPrognostic biomarkers for patients admitted for a myocardial infarction (MI) episode are of great interest for risk stratification and follow-up care after discharge. Multi-omics analysis is a standard approach for the discovery of diagnostic and prognostic biomarkers, but few studies have evaluated the prognostic potential of molecular markers in combination with echocardiographic imaging variables.MethodsWe measured the plasma proteome and lipidome in patients discharged from an acute MI and followed for secondary outcomes in New Zealand for a median time of 4.85 years (CDCS, N=741 for network inference, N=464 for predictive analysis) and in Singapore for a median time of 2.0 years (IMMACULATE, N=190 for validation). Using a network-based integrative analysis framework iOmicsPASS+, we mapped proteins, lipids, echocardiographic imaging variables and clinical biomarkers to a unified network and identified predictive subnetwork signatures of major adverse cardiac events (MACE) and heart failure hospitalization (HFH) in CDCS, with validation in IMMACULATE.ResultsSpecific plasma proteins and lipids showed direct connections to cardiac imaging variables in the network. The gold standard biomarker, NT-proBNP, remained one of the best prognostic marker of MACE and HFH, but a number of plasma proteins involved in extracellular matrix organization, chemotaxis, inflammation, and apoptosis were also strong predictors of both outcomes. Hub proteins of subnetwork signatures were enriched in the heart, arteries, kidneys, liver and lungs. BMP10, CAPG, EFEMP1, FSTL3, RSPO4, and RELT were those directly connected to the echocardiographic variables and natriuretic peptides. In particular, EFEMP1 and FSTL3 in combination with diastolic function (E/e’) were strongly predictive of HFH in both CDCS (AUC 0.78, 95%CI 0.72-0.83) and IMMACULATE (AUC 0.72, 0.61-0.84).ConclusionsOur integrative analysis revealed competing signatures beyond established biomarkers of post-MI HFH, comprised of plasma proteins correlated with impaired diastolic function after the primary MI episode.

Key summary points Aims To establish if dependency in basic activities of daily living (bADL) amongst moderately frail older adults predict poorer health outcomes including mortality and institutionalisation. We also examined the utility of subgrouping category 6 of the Clinical Frailty Scale (CFS) by level of functional dependency to improve predictive performance. Findings We observed a wider range in functional dependency among CFS 6 patients when compared to other frail categories. Incorporating CFS 6 subcategories based on bADL functional status increased predictive performance for longitudinal adverse outcomes compared with the original CFS scoring. Message This study corroborates the heterogeneity of bADL functional status in CFS 6 individuals and validates the use of a modified approach to subgrouping the CFS via bADL dependency for improved predictive performance. Electronic supplementary material The online version of this article (10.1007/s41999-020-00418-8) contains supplementary material, which is available to authorized users., Purpose Moderately frail individuals [Clinical Frailty Scale (CFS) 6] demonstrate heterogeneity in basic activities of daily living (bADL). We aimed to establish whether functional dependency in moderate frailty predicts poorer outcomes and examined the utility of subgrouping the CFS in predicting mortality and institutionalisation. Methods We prospectively studied 201 hospitalised frail patients (89.5 ± 4.7 years, female 70.1%). We examined Katz Index (KI) against adverse outcomes in CFS6 (n = 106). We then compared predictive performances of a modified CFS version 1 (mCFS-1; category 6A: CFS6 and KI ≥ 2; 6B: CFS6 and KI ≤ 1) and modified CFS version 2 (mCFS-2; category 6A: CFS6 and KI ≥ 2; 6B1: CFS6, KI ≤ 1 and feeding independent; 6B2: CFS6, KI ≤ 1 and feeding dependent) against the CFS. Multivariate analysis was used to compare each tool against mortality and institutionalisation. Receiver operator characteristic analysis was performed to determine area under curve and optimal cut-points for each tool. Results KI ≤ 1 in CFS6 was associated with higher 12-month mortality (39.3% vs. 15.6%, p = 0.01); amongst KI items, feeding dependent predicted 12-month mortality (p

Left ventricular thrombosis (LVT) is a potentially devastating complication in post-acute myocardial infarction (AMI) patients. Previous studies have demonstrated that inflammation may contribute to thrombus formation, but its role on thrombus resolution is uncertain. The neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) are easily accessible haematological markers of inflammation.We aimed to identify differences between post-AMI LVT patients with and without LVT resolution, and to evaluate the utility of NLR and PLR in predicting LVT resolution.We included 289 consecutive post-AMI patients with LVT. Acute LVT was diagnosed based on echocardiogram. Patients were stratified based on LVT resolution. Logistic regression was performed to evaluate for independent predictors of thrombus resolution.Compared to post-AMI patients with eventual LVT resolution, those with unresolved LVT had more co-morbidities such as hypertension (p = 0.003) and ischaemic heart disease (p 0.001), fewer underwent percutaneous coronary intervention (PCI) (p 0.001) or were treated with triple therapy (p 0.001). NLR (p = 0.064) and PLR (p = 0.028) were higher in unresolved LVT patients. In non-PCI patients, NLR (OR 0.818, 95% CI 0.674-0.994, p = 0.043) and PLR (OR 0.989, 95% CI 0.979-0.999, p = 0.026) were independent predictors of thrombus resolution after adjustment for age and anticoagulation use.Post-AMI patients not receiving PCI may have a greater inflammatory response and a higher NLR and PLR, which is associated with less LVT resolution despite anticoagulation. Further studies are required to study this association.

Pivotal trials of beta-blockers (BB) and angiotensin converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARB) in acute myocardial infarction (AMI) were largely conducted prior to the widespread adoption of early revascularization. A total of 15,073 patients with AMI who underwent inhospital coronary revascularization from January 2007 to December 2013 were analyzed. At 12 months, BB was significantly associated with a lower incidence of major adverse cardiovascular events (MACE, adjusted HR 0.80, 95% CI 0.70–0.93) and all-cause mortality (adjusted HR 0.69, 95% CI 0.55–0.88), while ACEI/ARB was significantly associated with lower all-cause mortality (adjusted HR 0.80, 95% CI 0.66–0.98) and heart failure (HF) hospitalization (adjusted HR 0.80, 95% CI 0.68–0.95). Combined BB and ACEI/ARB use was associated with the lowest incidence of MACE (adjusted HR 0.70, 95% CI 0.57–0.86), all-cause mortality (adjusted HR 0.55, 95% CI 0.40–0.77) and HF hospitalization (adjusted HR 0.64, 95% CI 0.48–0.86). This were consistent for left ventricular ejection fraction

Circadian patterns in ST-segment elevation myocardial infarction (STEMI) patients have been previously reported, but little is known about the impact of time dependence of symptom onset on long-term prognosis. Our study population consisted of 11,731 STEMI patients treated by primary percutaneous coronary intervention (PPCI), enrolled in the Singapore Myocardial Infarction Registry (SMIR). Analysis of STEMI incidence trends over the 24-hour period showed the highest rate of symptom onset in the morning, with the peak incidence at 09:00 am . Patients with symptom onset in between 00:00 am -5:59 am showed the highest prevalence of diabetes (P = .010) and anterior STEMI (P pm -11:59 pm and 00:00 am -05:59 am having an estimated 30% to 50% higher risk of rehospitalization for HF at 1 year. Moreover, symptom onset remained a predictor of worse prognosis only in the subgroup of patients with symptoms lasting longer than 120 minutes. The results of this study demonstrate for the first time that rehospitalization for HF in STEMI patients treated with PPCI has a dependence on the time of onset of symptoms, with prolonged ischemia time playing a pivotal role. This may be an additional risk factor to identify those who warrant closer monitoring and more rigorous optimization of their treatment at follow-up, to improve their outcomes.

BackgroundThe global coronavirus disease 2019 pandemic has highlighted the importance of understanding the cardiovascular implications of coronavirus infections, with more severe disease in those with cardiovascular co-morbidities, and resulting cardiac manifestations such as myocardial injury, arrhythmias, and heart failure.DesignA systematic review of the current knowledge on the effects of coronavirus infection on the cardiovascular system in humans was performed and results were summarized.MethodsDatabases such as MEDLINE, EMBASE, CENTRAL, Scopus, Web of Science, ClinicalTrials.gov, Chinese Knowledge Resource Integrated Database and Chinese Clinical Trial Registry were searched on 20 March 2020.ResultsIn total, 135 studies were included, involving severe acute respiratory syndrome, Middle East respiratory syndrome, coronavirus disease 2019 and other coronaviruses. Most were case reports, case series and cohort studies of poor to fair quality. In post-mortem examinations of subjects who died from infection, around half had virus identified in heart tissues in severe acute respiratory syndrome, but none in Middle East respiratory syndrome and coronavirus disease 2019. Cardiac manifestations reported include tachycardia, bradycardia, arrhythmias, and myocardial injury, secondary to both systemic infection and treatment. Cardiac injury and arrhythmias are more prevalent in coronavirus disease 2019, and elevated cardiac markers are associated with intensive care unit admission and death. In severe acute respiratory syndrome, Middle East respiratory syndrome, and coronavirus disease 2019, comorbidities such as hypertension, diabetes mellitus, and heart disease are associated with intensive care unit admission, mechanical ventilation, and mortality. There were cases of misdiagnosis due to overlapping presentations of cardiovascular diseases and coronavirus infections, leading to hospital spread and delayed management of life-threatening conditions.ConclusionThis review highlighted the ways in which coronaviruses affect cardiovascular function and interacts with pre-existing cardiovascular diseases.

BACKGROUND Myocardial infarction (MI) is a high-risk condition especially when filling pressure is raised, and earlier reports have suggested that E/e' is associated with poor outcome. However, whether E/e' predicts risk better than LVEF, which is the current standard of practice, is not known. We investigated this question in the largest and most rigorous study of MI patients so far. METHODS AND RESULTS We studied 660 patients with ST-elevation MI (STEMI) treated with primary percutaneous coronary intervention and related E/e' to short-term mortality (in-hospital death), as well as long-term events at 2 years comprising (a) a composite of MI, stroke, heart failure, and death, and (b) death alone. Short-term models were adjusted for age, sex, and LVEF. Long-term models were adjusted for age, sex, diabetes, revascularization procedure, history of MI, hypertension, renal function, drugs on discharge, and LVEF. Elevated E/e'> 15 indicated higher risk of short-term events (n = 19:7.0% (95% confidence interval 3.4-10.8%) vs. 1.0% (0.3 - 2.3%); adjusted odds ratio 3.7 (1.3-10.5)). While elevated E/e' was also associated with long-term outcomes (n = 103 composite events: 15.9% (11.9% - 21.4%) vs 6.8% (5.2% - 8.7%), P

Coronary artery disease is a leading cause of morbidity and mortality worldwide. Despite significant advances in revascularization strategies and antiplatelet therapy with aspirin and/or P2Y12 receptor antagonist, patients with acute coronary syndrome (ACS) continue to be at long-term risk of further cardiovascular events. Besides platelet activation, the role of thrombin generation (TG) in atherothrombotic complications is widely recognized. In this study, we hypothesized that there is an elevation of coagulation activation persists beyond 12 months in patients with ACS and chronic coronary syndrome (CCS) when compared with healthy controls. We measured TG profiles of patients within 72 h after percutaneous coronary intervention, at 6-month, 12-month and 24-month. Our results demonstrated that TG of patients with ACS (n = 114) and CCS (n = 40) were persistently elevated when compared to healthy individuals (n = 50) in peak thrombin (ACS 273.1 nM vs CCS 287.3 nM vs healthy 234.3 nM) and velocity index (ACS 110.2 nM/min vs CCS 111.0 nM/min vs healthy 72.9 nM/min) at 24-month of follow-up. Our results suggest a rationale for addition of anticoagulation to antiplatelet therapy in preventing long-term ischemic events after ACS. Further research could clarify whether the use of TG parameters to enable risk stratification of patients at heightened long-term procoagulant risk who may benefit most from dual pathway inhibition.

Myocarditis is commonly associated with viruses. However, we present a novel case of a teenager with pneumococcal pneumonia and bacteremia complicated by myocarditis and rhabdomyolysis, presenting with features of acute ST-elevation myocardial infarction and cardiogenic shock. Physicians should be aware that Streptococcus pneumoniae infection, like Group A Streptococcus, can mimic acute myocardial infarction in young males without cardiovascular risk factors.

Quantitative MS of human plasma lipids is a promising technology for translation into clinical applications. Current MS-based lipidomic methods rely on either direct infusion (DI) or chromatographic lipid separation methods (including reversed phase and hydrophilic interaction LC). However, the use of lipid markers in laboratory medicine is limited by the lack of reference values, largely because of considerable differences in the concentrations measured by different laboratories worldwide. These inconsistencies can be explained by the use of different sample preparation protocols, method-specific calibration procedures, and other experimental and data-reporting parameters, even when using identical starting materials. Here, we systematically investigated the roles of some of these variables in multiple approaches to lipid analysis of plasma samples from healthy adults by considering: 1) different sample introduction methods (separation vs. DI methods); 2) different MS instruments; and 3) between-laboratory differences in comparable analytical platforms. Each of these experimental variables resulted in different quantitative results, even with the inclusion of isotope-labeled internal standards for individual lipid classes. We demonstrated that appropriate normalization to commonly available reference samples (i.e., "shared references") can largely correct for these systematic method-specific quantitative biases. Thus, to harmonize data in the field of lipidomics, in-house long-term references should be complemented by a commonly available shared reference sample, such as NIST SRM 1950, in the case of human plasma.

International audience; Cardiac remodelling refers to changes in left ventricular structure and function over time, with a progressive deterioration that may lead to heart failure (HF) development (adverse remodelling) or vice versa a recovery (reverse remodelling) in response to HF treatment. Adverse remodelling predicts a worse outcome, whilst reverse remodelling predicts a better prognosis. The geometry, systolic and diastolic function and electric activity of the left ventricle are affected, as well as the left atrium and on the long term even right heart chambers. At a cellular and molecular level, remodelling involves all components of cardiac tissue: cardiomyocytes, fibroblasts, endothelial cells and leucocytes. The molecular, cellular and histological signatures of remodelling may differ according to the cause and severity of cardiac damage, and clearly to the global trend toward worsening or recovery. These processes cannot be routinely evaluated through endomyocardial biopsies, but may be reflected by circulating levels of several biomarkers. Different classes of biomarkers (e.g. proteins, non-coding RNAs, metabolites and/or epigenetic modifications) and several biomarkers of each class might inform on some aspects on HF development, progression and long-term outcomes, but most have failed to enter clinical practice. This may be due to the biological complexity of remodelling, so that no single biomarker could provide great insight on remodelling when assessed alone. Another possible reason is a still incomplete understanding of the role of biomarkers in the pathophysiology of cardiac remodelling. Such role will be investigated in the first part of this review paper on biomarkers of cardiac remodelling.

Background: Real world data on clinical outcomes and quality of care for patients with coronary artery disease (CAD) are fragmented. We describe the rationale and design of the Singapore Cardiovascular Longitudinal Outcomes Database (SingCLOUD). Methods and Results: We designed a health data grid to integrate clinical, administrative, laboratory, procedural, prescription and financial data from all public-funded hospitals and primary care clinics, which provide 80% of health care in Singapore. Here, we explain our approach to harmonize real-world data from diverse electronic medical and non-medical platforms to develop a robust and longitudinal dataset. We present pilot data on patients with myocardial infarction (MI) treated with percutaneous coronary intervention (PCI) between 2012 and 2014. The initial data set had 53,395 patients. Of these, 35,203 had CAD confirmed on coronary angiography, of whom 21,521 had PCI. Eventually, limiting to 2012-2014, 3,819 patients had MI with PCI, while 5,989 had MI. Compared with the quality improvement registry, Singapore Cardiac Data Bank, which had 189 fields for analysis, the SingCLOUD platform generated an additional 313 additional data fields, and was able to identify an additional 250 heart failure events, 664 major adverse cardiovascular events at 2 years, and low-density lipoprotein levels to 1 year for 3,747 patients. Conclusions: By integrating multiple incongruent data sources, SINGCLOUD enables in-depth analysis of real-world cardiovascular "big data".

Randomized controlled trials (RCTs) comparing percutaneous coronary intervention (PCI) with drug-eluting stents and coronary artery bypass grafting (CABG) for patients with left main coronary artery disease (LMCAD) have reported conflicting results. We performed a systematic review up to May 23, 2021, and 1-stage reconstructed individual patient data meta-analysis (IPDMA) to compare outcomes between both groups. The primary outcome was 10-year all-cause mortality. Secondary outcomes included myocardial infarction (MI), stroke, and unplanned revascularization at 5 years. We performed individual patient data meta-analysis using published Kaplan-Meier curves to provide individual data points in coordinates and numbers at risk were used to increase the calibration accuracy of the reconstructed data. Shared frailty model or, when proportionality assumptions were not met, a restricted mean survival time model were fitted to compare outcomes between treatment groups. Of 583 articles retrieved, 5 RCTs were included. A total of 4,595 patients from these 5 RCTs were randomly assigned to PCI (n = 2,297) or CABG (n = 2,298). The cumulative 10-year all-cause mortality after PCI and CABG was 12.0% versus 10.6%, respectively (hazard ratio [HR] 1.093, 95% confidence interval [CI] 0.925 to 1.292; p = 0.296). PCI conferred similar time-to-MI (restricted mean survival time ratio 1.006, 95% CI 0.992 to 1.021, p=0.391) and stroke (restricted mean survival time ratio 1.005, 95% CI 0.998 to 1.013, p = 0.133) at 5 years. Unplanned revascularization was more frequent after PCI than CABG (HR 1.807, 95% CI 1.524 to 2.144, p0.001) at 5 years. This meta-analysis using reconstructed participant-level time-to-event data showed no statistically significant difference in cumulative 10-year all-cause mortality between PCI versus CABG in the treatment of LMCAD.

An increasing number of studies have shown an association between migraine and cardiovascular disease, in particular cardio- and cerebro-vascular events.Three electronic databases (PubMed, Embase and Scopus) were searched from inception to May 22, 2021 for prospective cohort studies evaluating the risk of myocardial infarction, stroke and cardiovascular mortality in migraine patients. A random effects meta-analysis model was used to summarize the included studies.A total of 18 prospective cohort studies were included consisting of 370,050 migraine patients and 1,387,539 controls. Migraine was associated with myocardial infarction (hazard ratio, 1.36; 95% CI, 1.23-1.51; p = 0.001), unspecified stroke (hazard ratio, 1.30; 95% CI, 1.07-1.60; p = 0.01), ischemic stroke (hazard ratio, 1.35; 95% CI, 1.03-1.78; p = 0.03) and hemorrhagic stroke (hazard ratio, 1.43; 95% CI, 1.07-1.92; p = 0.02). Subgroup analysis of migraine with aura found a further increase in risk of myocardial infarction and both ischemic and hemorrhagic stroke, as well as improved substantial statistical heterogeneity. Migraine with aura was also associated with an increased risk of cardiovascular mortality (hazard ratio, 1.27; 95% CI, 1.14-1.42; p = 0.001).Migraine, especially migraine with aura, is associated with myocardial infarction and stroke. Migraine with aura increases the risk of overall cardiovascular mortality.

We evaluated the association between early coronary angiography (CAG) and outcomes in resuscitated out-of-hospital cardiac arrest (OHCA) patients, by linking data from the Singapore Pan-Asian Resuscitation Outcomes Study, with a national registry of cardiac procedures. The 30-day survival and neurological outcome were compared between patients undergoing early CAG (within 1-calender day), versus patients not undergoing early CAG. Inverse probability weighted estimates (IPWE) adjusted for non-randomized CAG. Of 976 resuscitated OHCA patients of cardiac etiology between 2011–2015 (mean(SD) age 64(13) years, 73.7% males), 337 (34.5%) underwent early CAG, of whom, 230 (68.2%) underwent PCI. Those who underwent early CAG were significantly younger (60(12) vs. 66(14) years old), healthier (42% vs. 59% with heart disease, 29% vs. 44% with diabetes), more likely males (86% vs. 67%), and presented with shockable rhythms (69% vs. 36%), compared with those who did not. Early CAG with PCI was associated with better survival and neurological outcome (adjusted odds ratio 1.91 and 1.82 respectively), findings robust to IPWE adjustment. The rates of bleeding and stroke were similar. CAG with PCI within 24 h was associated with improved clinical outcomes after OHCA, without increasing complications. Further studies are required to identify the characteristics of patients who would benefit most from this invasive strategy.

Background: Infectious control measures during the COVID-19 pandemic have led to the propensity toward telemedicine. This study examined the impact of telemedicine during the pandemic on the long-term outcomes of ST-segment elevation myocardial infarction (STEMI) patients.Methods: This study included 288 patients admitted 1 year before the pandemic (October 2018–December 2018) and during the pandemic (January 2020–March 2020) eras, and survived their index STEMI admission. The follow-up period was 1 year. One-year primary safety endpoint was all-cause mortality. Secondary safety endpoints were cardiac readmissions for unplanned revascularisation, non-fatal myocardial infarction, heart failure, arrythmia, unstable angina. Major adverse cardiovascular events (MACE) was defined as the composite outcome of each individual safety endpoint.Results: Despite unfavorable in-hospital outcomes among patients admitted during the pandemic compared to pre-pandemic era, both groups had similar 1-year all-cause mortality (11.2 vs. 8.5%, respectively, p = 0.454) but higher cardiac-related (14.1 vs. 5.1%, p < 0.001) and heart failure readmissions in the pandemic vs. pre-pandemic groups (7.1 vs. 1.7%, p = 0.037). Follow-up was more frequently conducted via teleconsultations (1.2 vs. 0.2 per patient/year, p = 0.001), with reduction in physical consultations (2.1 vs. 2.6 per patient/year, p = 0.043), during the pandemic vs. pre-pandemic era. Majority achieved guideline-directed medical therapy (GDMT) during pandemic vs. pre-pandemic era (75.9 vs. 61.6%, p = 0.010). Multivariable Cox regression demonstrated achieving medication target doses (HR 0.387, 95% CI 0.164–0.915, p = 0.031) and GDMT (HR 0.271, 95% CI 0.134–0.548, p < 0.001) were independent predictors of lower 1-year MACE after adjustment.Conclusion: The pandemic has led to the wider application of teleconsultation, with increased adherence to GDMT, enhanced medication target dosing. Achieving GDMT was associated with favorable long-term prognosis.

Heart failure (HF) is one of the leading causes of mortality worldwide. Heart failure is also one of the most common presentations of cardiac amyloidosis (CA). Contemporary epidemiological data of CA in HF patients is lacking. Hence, this systematic review and meta-analysis was conducted to determine the prevalence of amyloidosis in HF patients, and to clarify the risk factors of concomitant CA and HF.A systematic review and meta-analysis was performed. Studies were retrieved from Medline, EMBASE, Scopus and Cochrane library. The search was not restricted in time, type or language of publication. The prevalence of CA in HF grouped according to diagnostic techniques and risk factors of CA with HF was analysed.Eleven (11) studies were included, involving 3,303 patients. The pooled prevalence of CA in HF was 13.7%. The overall prevalence of CA in HF with preserved ejection fraction was 15.1%, and that of HF with reduced ejection fraction was 11.3%. The main factors associated with the diagnosis of CA in HF included older age, males, raised NT pro-BNP, increased interventricular septal thickness in diastole, apical sparing, and reduced left ventricular systolic function.A high index of clinical suspicion is required to identify HF patients with CA. Supportive investigations may be helpful when clinically correlated. A considerable proportion of HF patients have CA and certain risk factors may be helpful in increasing suspicion of CA in HF.

IMPORTANCEThere are growing concerns that patients suffering from acute coronary syndrome (ACS) without standard modifiable cardiovascular risk factors (SMuRFs), including hypertension, hypercholesterolemia, diabetes and smoking, have increased mortality.OBJECTIVEThis study examined the outcomes of ACS in patients without SMuRFs (termed SMuRF-less) in a multi-ethnic Asian population which remains unknown.DESIGNThis retrospective study was conducted from 1st January 2011 to 31st March 2021.SETTINGThis study was conducted in a tertiary healthcare institution in Singapore.PARTICIPANTSConsecutive patients presenting with ACS disease were recruited in the study.EXPOSUREThe outcomes of SMuRF-less patients were compared with SMuRF patients.MAIN OUTCOMES AND MEASURESThe primary outcome was cardiovascular mortality. Secondary outcomes were all-cause mortality, readmission, cardiogenic shock, stroke and heart failure. Multivariable regression analysis adjusted for covariates including age, sex, ethnicity, chronic kidney disease, ACS type, cardiac arrest, and left main and/or left anterior descending coronaryRESULTSOf the 8680 patients studied, 8.6% were SMuRF-less patients. SMuRF-less patients were significantly younger and had fewer comorbidities including stroke and chronic kidney disease, but higher rates of ventricular arrhythmias and inotropic or invasive ventilation requirement compared to the SMuRF group. Multivariable analysis showed higher rates of cardiovascular mortality (HR 1.48, 95% CI 1.09–1.86, p=0.048), cardiogenic shock (RR: 1.31, 95% CI 1.09–1.52, p=0.015) and stroke (RR: 2.51, 95% CI 1.67–3.34, p=0.030) in SMuRF-less patients compared to SMuRF patients. Both groups had similar readmission (RR: 1.10, 95% CI 0.87–1.39, p=0.413) and heart failure (RR: 0.82, 95% CI 0.56–1.21, p=0.326) rates. Kaplan-Meier curve showed higher 30-day cardiovascular mortality in the SMuRF-less group compared to SMuRF group (HR: 1.84, 95% CI 1.45-2.33, pCONCLUSION AND RELEVANCEAlthough the proportion of ACS patients without standard risk factors in our Asian population is lower than those reported in the West, they also have worse short-term mortality compared to those with SMuRF. This calls for a global focus on the management of this unexpectedly high-risk subgroup of patients.

Emerging reports raise concerns on the potential association between the COVID-19 vaccines and cardiac manifestations. We sought to evaluate cardiac complications associated with COVID-19 vaccination in a pooled analysis from our institution’s cohort study and systematic review. Consecutive patients admitted to a tertiary hospital in Singapore between 1 January 2021 and 31 March 2021, with the onset of cardiac manifestations within 14 days following COVID-19 vaccination, were studied. Furthermore, a systematic review was performed, with PubMed, Embase, Research Square, MedRxiv and LitCovid databases accessed from inception up to 29 June 2021. Relevant manuscripts reporting individual patient data on cardiac complications following COVID-19 vaccination were included. Thirty patients were included in the study cohort, with 29 diagnosed with acute myocardial infarction (AMI) and 1 with myocarditis. Five patients developed heart failure, two had cardiogenic shock, three intubated, and one had cardiovascular-related mortality. In the systematic review, 16 studies were included with 41 myocarditis and 6 AMI cases. In the pooled analysis of the study cohort and the systematic review, 35 patients had AMI and 42 had myocarditis. Majority were men, and myocarditis patients were younger than AMI patients. Myocarditis patients tended to present 72 h postvaccination, while AMI patients were older and typically presented 24 h postvaccination. Majority with AMI or myocarditis developed symptoms after the first and second vaccination dose, respectively. This pooled analysis of patients presenting with cardiac manifestations following COVID-19 vaccination highlights the differences between myocarditis and AMI presentations in temporal association with the vaccination.

Background The Asia Pacific Evaluation of Cardiovascular Therapies (ASPECT) Collaboration was established to better understand the characteristics of patients undergoing PCI and cardiac interventions across the Asia Pacific region, including STEMI. The aim of this study was to compare STEMI patient characteristics across Asia Pacific (AP) countries in order to understand regional differences. Methods Each site across Australia, Singapore, Malaysia, Vietnam and Hong Kong provided de-identified individual patient data. Comparison of characteristics by sites were performed using one-way ANOVA, Kruskal-Wallis or Chi-squared tests, using Stata 14.2. Results Of the 12,620 cases, there were more males (p Conclusions Patient characteristics varied significantly across AP countries. On-going analyses will focus on the impact of varying patient characteristics on clinical outcomes. Key messages As characteristics varied, prevention and procedural strategies need to be adapted carefully. Additional input from other AP countries will better inform these strategies.

Background Stress-induced hyperglycaemia at time of hospital admission has been linked to worse prognosis following acute myocardial infarction (AMI). The stress-hyperglycaemia ratio (SHR) index normalises the acute increase in blood glucose values to background glycaemic status. However, the optimal cut-off blood glucose and SHR values for predicting adverse outcomes post-AMI are unknown. As such, we determined the optimal blood glucose and SHR cut-offs for predicting 1-year all cause mortality in diabetic and non-diabetic non-ST-segment elevation myocardial infarction (NSTEMI) and ST-segment elevation myocardial infarction (STEMI) patients. Methods We undertook a national, registry-based study of patients with AMI from January 2008 to December 2015. We determined the optimal blood glucose and SHR cut-off values using the Youden’s formula for 1-year all-cause mortality. We subsequently analyzed the sensitivity, specificity, positive and negative predictive values of the cut-offs in the diabetic and non-diabetic subgroups, stratified by the type of AMI. Results There were 5,841 STEMI and 4,105 NSTEMI in the study. In STEMI patients, both glucose and SHR were independent predictors of 1-year all-cause mortality [Glucose: OR 2.19 (95% CI 1.74–2.75); SHR: 2.19 (95% CI 1.73–2.78)]. However, in NSTEMI patients, glucose and SHR were not independently associated with 1-year all-cause mortality [Glucose: OR 1.37 (95% CI 1.00-1.89); SHR: 1.27 (95% CI 0.91–1.78)]. In STEMI patients, ROC analysis showed that SHR performed better than glucose (AUC for glucose 0.633 versus AUC for SHR 0.692, P

ObjectiveST segment elevation myocardial infarction (STEMI) is associated with significant mortality leading to loss of productive life years, especially in younger patients. This study aims to compare the characteristics and outcomes of young versus older patients with STEMI undergoing primary percutaneous coronary intervention (PPCI) to help focus public health efforts in STEMI prevention.MethodsData from the Coronary Care Unit database of the National University Hospital, Singapore from July 2015 to June 2019 were reviewed. Patients were divided into young (ResultsOf the 1818 consecutive patients with STEMI who underwent PPCI, 465 (25.6%) were ConclusionYoung patients with STEMI are more often smokers, of Indian ethnicity and had family history of IHD, although cardiometabolic risk factors are also prevalent. Mortality is lower, but not negligible, among the young patients with STEMI. Public health efforts are needed to reduce the prevalence of these risk factors among the constitutionally susceptible population.

The genomic regulatory networks underlying the pathogenesis of non-ST-segment elevation acute coronary syndrome (NSTE-ACS) are incompletely understood. As intermediate traits, protein biomarkers report on underlying disease severity and prognosis in NSTE-ACS. We hypothesized that integration of dense microRNA (miRNA) profiling with biomarker measurements would highlight potential regulatory pathways that underlie the relationships between prognostic biomarkers, miRNAs, and cardiovascular phenotypes. We performed miRNA sequencing using whole blood from 186 patients from the TRILOGY-ACS trial. Seven circulating prognostic biomarkers were measured: NH2-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein, osteopontin (OPN), myeloperoxidase, growth differentiation factor 15, monocyte chemoattractant protein, and neopterin. We tested miRNAs for association with each biomarker with generalized linear models and controlled the false discovery rate at 0.05. Ten miRNAs, including known cardiac-related miRNAs 25-3p and 423-3p, were associated with NT-proBNP levels (min. P = 7.5 × 10−4) and 48 miRNAs, including cardiac-related miRNAs 378a-3p, 20b-5p and 320a, -b, and -d, were associated with OPN levels (min. P = 1.6 × 10−6). NT-proBNP and OPN were also associated with time to cardiovascular death, myocardial infarction (MI), or stroke in the sample. By integrating large-scale miRNA profiling with circulating biomarkers as intermediate traits, we identified associations of known cardiac-related and novel miRNAs with two prognostic biomarkers and identified potential genomic networks regulating these biomarkers. These results, highlighting plausible biological pathways connecting miRNAs with biomarkers and outcomes, may inform future studies seeking to delineate genomic pathways underlying NSTE-ACS outcomes.

The Frontal Assessment Battery (FAB) is a reliable and valid bedside tool for testing executive function in dementia. Given the increasing interest in utility of FAB as a screening tool in early cognitive impairment (ECI), there is a surprising lack of studies evaluating its psychometric property and factor structure, nor the influence of factors such as age, education and gender, in ECI.This study aims to investigate the psychometric properties and factor structure of FAB in older adults with ECI, as well as the influence of age, gender and education.This is a retrospective, observational cross-sectional study with 300 community dwelling, predominantly Chinese older adults (14 normal, 130 mild cognitive impairment (MCI), and 156 mild dementia) who presented to Memory Clinic from January 2011 to December 2013. Measurements and Analysis: We collected data on demographic, cognitive, functional and behavioral evaluation. To examine the psychometric properties of FAB, we examined the concurrent, convergent, and discriminant validity; internal consistency by Cronbach's alpha; and factor structure by exploratory factor analysis. The influence of age, education and gender was examined using unadjusted and adjusted correlational analyses with CDR-SOB. We performed analysis for the whole group and for MCI subgroup.FAB total score decreases significantly from normal to dementia group attesting to concurrent validity. It correlated significantly with digit span backwards and Chinese Mini Mental State Examination (r=0.38 and 0.47 respectively, p0.01) and poorly with Neuropsychiatric Inventory-Questionnaire and depression (r=0.004 and -0.02 respectively), supporting its convergent and discriminant validity. Factor analysis yielded a single-factor solution for FAB with fair Internal consistency (alpha=0.610). FAB is relatively unaffected by age, gender and education level. These good psychometric properties extend to MCI, albeit with greater influence by education level. FAB items of conceptualization and mental flexibility have good discriminatory ability between MCI and normal subjects.FAB has good concurrent, convergent and discriminant validity with fair internal consistency in ECI that is premised on a one-factor structure. It is relatively unaffected by age, gender or education. Taken together, FAB is a useful bedside screening tool for executive function in ECI.

We aimed to identify independent predictors of cardiac mortality and hospitalization for heart failure (HHF) from a real-world, multi-ethnic Asian registry [the Singapore Myocardial Infarction Registry] of ST-segment elevation myocardial infarction (STEMI) patients treated by primary percutaneous coronary intervention. 11,546 eligible STEMI patients between 2008 and 2015 were identified. In-hospital, 30-day and 1-year cardiac mortality and 1-year HHF rates were 6.4%, 6.8%, 8.3% and 5.2%, respectively. From the derivation cohort (70% of patients), age, Killip class and cardiac arrest, creatinine, hemoglobin and troponin on admission and left ventricular ejection fraction (LVEF) during hospitalization were predictors of in-hospital, 30-day and 1-year cardiac mortality. Previous ischemic heart disease (IHD) was a predictor of in-hospital and 30-day cardiac mortality only, whereas diabetes was a predictor of 1-year cardiac mortality only. Age, previous IHD and diabetes, Killip class, creatinine, hemoglobin and troponin on admission, symptom-to-balloon-time and LVEF were predictors of 1-year HHF. The c-statistics were 0.921, 0.901, 0.881, 0.869, respectively. Applying these models to the validation cohort (30% of patients) showed good fit and discrimination (c-statistic 0.922, 0.913, 0.903 and 0.855 respectively; misclassification rate 14.0%, 14.7%, 16.2% and 24.0% respectively). These predictors could be incorporated into specific risk scores to stratify reperfused STEMI patients by their risk level for targeted intervention.

It is unclear whether universal access to primary percutaneous coronary intervention (pPCI) may reduce sex differences in 1-year rehospitalization for heart failure (HF) and myocardial infarction (MI) after ST-elevation myocardial infarction (STEMI). We studied 7,597 consecutive STEMI patients (13.8% women, n = 1,045) who underwent pPCI from January 2007 to December 2013. Cox regression models adjusted for competing risk from death were used to assess sex differences in rehospitalization for HF and MI within 1 year from discharge. Compared with men, women were older (median age 67.6 vs 56.0 years, p0.001) with higher prevalence of co-morbidities and multivessel disease. Women had longer median door-to-balloon time (76 vs 66 minutes, p0.001) and were less likely to receive drug-eluting stents (19.5% vs 24.1%, p = 0.001). Of the medications prescribed at discharge, fewer women received aspirin (95.8% vs 97.6%, p = 0.002) and P2Y

Acute ischemic stroke (AIS) is a feared complication in post-acute myocardial infarction (AMI) patients who develop left ventricular (LV) thrombus. There is limited data available on the incidence of stroke in this population, and characterisation of stroke subtypes has not been previously reported. Our study aims to evaluate the incidence of AIS in post-AMI patients with LV thrombus and to characterise the pattern of stroke subtypes. We screened 5829 patients with echocardiogram reports containing the “thrombus” keyword from August 2006 to September 2017. AIS that occurred after LV thrombosis was captured and relevant clinical data was collected. We identified 289 post-AMI patients with acute LV thrombus formation. Mean age was 59.3 ± 13.4 years. AIS occurred in 34 patients (11.8%), median duration of 20.5 days (IQR = 5.5–671.8) after LV thrombosis. Despite initial thrombus resolution, nine (5.2%) encountered AIS subsequently. Cardioembolic stroke subtype was identified in 76.5% of AIS, whilst 14.7% was small vessel disease and 8.8% was of large artery atherosclerosis subtype. Presence of thrombus protrusion (HR 3.04, 95% CI 1.25–7.41, p = 0.01), failure of initial thrombus resolution (HR 3.03, 95% CI 1.23–7.45, p = 0.02) and thrombus recurrence (HR 4.20, 95% CI 1.46–12.11, p

Background In ST-segment elevation myocardial infarction (STEMI) patients treated with primary percutaneous coronary intervention (PPCI), current oral P2Y12 platelet inhibitors do not provide maximal platelet inhibition at the time of reperfusion. Furthermore, administration of cangrelor prior to reperfusion has been shown in pre-clinical studies to reduce myocardial infarct (MI) size. Therefore, we hypothesize that cangrelor administered prior to reperfusion in STEMI patients will reduce the incidence of microvascular obstruction (MVO) and limit MI size in STEMI patients treated with PPCI. Methods The platelet inhibition to target reperfusion injury (PITRI) trial, is a phase 2A, multi-center, double-blinded, randomized controlled trial, in which 210 STEMI patients will be randomized to receive either an intravenous (IV) bolus of cangrelor (30 μg/kg) followed by a 120-minute infusion (4 μg/kg/min) or matching saline placebo, initiated prior to reperfusion (NCT03102723). Results The study started in October 2017 and the anticipated end date would be July 2020. The primary end-point will be MI size quantified by cardiovascular magnetic resonance (CMR) on day 3 post-PPCI. Secondary endpoints will include markers of reperfusion, incidence of MVO, MI size, and adverse left ventricular remodeling at 6 months, and major adverse cardiac and cerebrovascular events. Summary The aim of the PITRI trial is to assess whether cangrelor administered prior to reperfusion would reduce acute MI size and MVO, as assessed by CMR.

Omeprazole is commonly co-prescribed with clopidogrel. Clopidogrel requires bio-activation by cytochrome P450 CYP2C19. Omeprazole may reduce clopidogrel's antithrombotic efficacy by inhibiting CYP2C19. Studies in Caucasians receiving omeprazole with clopidogrel showed no significant increase in death and myocardial infarction with this drug-drug interaction. There are limited large-scale studies in Asians, who may have a greater prevalence of CYP2C19 loss-of-function polymorphisms. A single centre retrospective cohort study was undertaken based on a review of medication records and prescription data. Patients prescribed clopidogrel from 2009 to 2012 were followed-up with until December 2012 (median:29 months). The primary outcome was all-cause mortality and secondary outcomes were myocardial infarction (MI), cerebrovascular accidents, and subsequent coronary interventions. Of 12,440 patients prescribed clopidogrel, 62%(n = 7714) were on omeprazole (63.8% Chinese, 13.9% Malay, 12.4% Indian, 10.0% others), and 38%(n = 4726) were not on omeprazole or other proton pump inhibitors (62.6% Chinese, 13.5% Malay, 10.7% Indian, 13.2% others). Mortality after co-prescription occurred in 14.3%(n = 1101) of patients, compared to 6.3%(n = 300) of patients prescribed clopidogrel only. Multivariate analysis using propensity score adjusted analysis showed no significant increase in all-cause mortality with co-prescription (adjusted hazards ratio [AHR] 1.13, [95%CI 0.95-1.35]). Patients on co-prescription had a higher risk of subsequent MI (16% vs 3.8%; AHR 2.03 [95%CI 1.70-2.44]), but not of cerebrovascular accidents (5.0% vs 2.0%; AHR 0.98 [95%CI 0.76-1.27]) or coronary interventions (1.7% vs 0.7%; AHR 1.28 [95%CI 0.83-1.96]). The risk of a subsequent MI was higher in the Malay (AHR 2.43 [95%CI 1.68-3.52]) and Chinese (AHR 2.06 [95%CI 1.63-2.60]) population as compared to the Indian (AHR 1.56 [95%CI 1.06-2.31]) population. In conclusion, the use of clopidogrel with omeprazole is associated with an increased risk of MI, but not mortality or stroke, in this multi-ethnic Asian population. These risks appear to vary among different ethnic groups.

The unique characteristics of patients with acute coronary syndrome in the Asia-Pacific region mean that international guidelines on the use of dual antiplatelet therapy (DAPT) cannot be routinely applied to these populations. Newer generation P2Y12 inhibitors (i.e. ticagrelor and prasugrel) have demonstrated improved clinical outcomes compared with clopidogrel. However, low numbers of Asian patients participated in pivotal studies and few regional studies comparing DAPTs have been conducted. This article aims to summarise current evidence on the use of newer generation P2Y12 inhibitors in Asian patients with acute coronary syndrome and provide recommendations to assist clinicians, especially cardiologists, in selecting a DAPT regimen. Guidance is provided on the management of ischaemic and bleeding risks, including duration of therapy, switching strategies and the management of patients with ST-elevation and non-ST-elevation MI or those requiring surgery. In particular, the need for an individualised DAPT regimen and considerations relating to switching, de-escalating, stopping or continuing DAPT beyond 12 months are discussed.

Introduction: Acute myocardial infarction (MI) and acute ischaemic stroke (AIS) are leading causes of morbidity and mortality. There is scarce data examining the interplay between post-MI left ventricular systolic dysfunction (LVSD), with or without atrial fibrillation (AF), and subsequent AIS, especially in patients with milder degrees of LVSD (ejection fraction 40-49%). Evidence of an association would be helpful in developing new strategies of reducing AIS after MI. As such, we sought to study this relationship in a real-world population-based registry. Methods: This study involved linking national-level data from the Singapore Myocardial Infarction Registry with the Singapore Stroke Registry from 1st January 2007 to 31st December 2018. Both data sets have similar definitions for patient demographics. The ejection fraction (EF) and AF status were recorded during the MI episode. The outcome studied was the first instance of AIS that developed after the MI episode. We also studied the relationship between EF, AF and the severity of AIS as measured by the NIH Stroke Scale (NIHSS). Results: There were 64,512 patients available for analysis. The median age was 65.7 (IQR 56.1-76.5) and 69.5% were male. The median duration post-MI to develop AIS was 16.9 (IQR 1.6-46.1) months. There was an independent association between LVSD and the outcome of AIS (adjusted HR 1.18, 95% CI 1.10-1.27); this was evident even in mild forms of LVSD (adjusted HR 1.16, 95% CI 1.06-1.27). AF was not a statistically significant predictor of AIS in post-MI patients with LVSD. Amongst patients without AF, post-MI LVSD was associated with a more severe stroke and higher NIHSS. Conclusion: Post-MI LVSD is associated with the occurrence of subsequent AIS. Although this relationship was independent of AF status, patients with LVSD but no AF had suffered a more severe AIS. These findings support the need to develop effectives therapies to prevent AIS post-MI, especially among those with LVSD.

Colchicine has received emerging interest due to its cardiovascular benefits in patients with coronary artery disease (CAD). We conducted a one-stage meta-analysis of reconstructed individual patient data (IPD) from randomized-controlled trials to summarize the effects of colchicine on cardiovascular outcomes in patients with CAD. Four databases (PubMed, Embase, Cochrane, SCOPUS) were searched for articles published from inception to 30th September 2020, examining the effect of colchicine on cardiovascular outcomes in patients with CAD, yielding 10 randomized-controlled trials with a combined cohort of 12,781 patients. IPD was reconstructed from Kaplan–Meier curves published in 3 studies and analysed using the shared-frailty Cox model. Aggregate data meta-analysis of all 10 studies was performed for outcomes unsuitable for IPD reconstruction. In patients receiving colchicine compared to placebo, one-stage meta-analysis demonstrated a hazard ratio of 0.70 (95% CI 0.61–0.80) for the composite outcome of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and urgent hospitalization for angina requiring coronary revascularization. Aggregate data meta-analysis demonstrated a significant reduction in hazard rate for stroke (HR 0.45; 95% CI 0.27–0.75) and urgent revascularization (HR 0.59; 95% CI 0.38–0.91); and a relative risk reduction for myocardial infarction (RR 0.72; 95% CI of 0.52–1.00) and post-operative atrial fibrillation (RR 0.64; 95% CI 0.48–0.86). Given the significant benefits of colchicine demonstrated on IPD, and its consistent benefits when analyzed using aggregate data meta-analysis, we propose that colchicine may be considered as an additional pharmacological adjunct to the first line therapy for patients with coronary artery disease.

Obesity has been shown to be associated with adverse outcomes in viral infections such as influenza, but previous studies on coronavirus disease 2019 (COVID-19) had mixed results. The aim of this systematic review is to investigate the relationship between COVID-19 and obesity.We performed a systematic review and meta-analysis. A literature search of MEDLINE, EMBASE, Scopus, Web of Science, CENTRAL, OpenGrey and preprint servers medRxiv and bioRxiv was performed, with no restriction on language or date of publication. Primary outcomes of this study were intensive care unit (ICU) admission or critical disease, severe disease and mortality. Secondary outcome was a positive COVID-19 test. Meta-analysis was performed using OpenMeta-Analyst software, and heterogeneity was tested using Cochran's Q test and I2 statistic. The study protocol was registered on PROSPERO (CRD42020184953).A total of 1,493 articles were identified and 61 studies on 270,241 patients were included. The pooled prevalence of obesity was 27.6% (95% confidence interval [CI] 22.0-33.2) in hospitalised patients. Obesity was not significantly associated with increased ICU admission or critical illness (odds ratio [OR] 1.25, 95% CI 0.99-1.58,Obesity increased the risk of severe disease, mortality and infection with COVID-19. Higher body mass index was associated with ICU admission and critical disease. Patients who are obese may be more susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and infected patients should be monitored closely for adverse outcomes.

Background Because of a nonresponse to aspirin (aspirin resistance), patients with acute coronary syndrome (ACS) are at increased risk of developing recurrent event. The in vitro platelet function tests have potential limitations, making them unsuitable for the detection of aspirin resistance. We investigated whether miR‐19b‐1‐5p could be utilized as a biomarker for aspirin resistance and future major adverse cardio‐cerebrovascular (MACCE) events in patients with ACS. Methods and Results In this cohort study, patients with ACS were enrolled from multiple tertiary hospitals in Christchurch, Hong Kong, Sarawak, and Singapore between 2011 and 2015. MiR‐19b‐1‐5p expression was measured from buffy coat of patients with ACS (n=945) by reverse transcription quantitative polymerase chain reaction. Platelet function was determined by Multiplate aggregometry testing. MACCE was collected over a mean follow‐up time of 1.01±0.43 years. Low miR‐19b‐1‐5p expression was found to be related to aspirin resistance as could be observed from sustained platelet aggregation in the presence of aspirin (‐Log‐miR‐19b‐1‐5p, [unstandardized beta, 44.50; 95% CI, 2.20–86.80; P P P =0.01) on the risk of MACCE. Conclusions Lower miR‐19b‐1‐5p expression was found to be associated with sustained platelet aggregation on aspirin, and a higher risk of MACCE in patients with ACS. Therefore, miR‐19b‐1‐5p could be a suitable marker for aspirin resistance and might predict recurrence of MACCE in patients with ACS.