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In the CLEAR (Cholesterol Lowering via Bempedoic Acid, an ACL-Inhibiting Regimen) Outcomes trial, treatment of statin-intolerant patients with bempedoic acid produced a 21% decrease in low-density lipoprotein cholesterol (LDL-C) relative to placebo and a 13% relative reduction in the risk of major adverse cardiovascular events. This study sought to determine whether the relationship between LDL-C lowering and cardiovascular benefit achieved with bempedoic acid resembles that observed with statins when standardized per unit change in LDL-C. To compare the treatment effect of bempedoic acid with statins, the methodology of the Cholesterol Treatment Trialists' Collaboration (CTTC) was applied to outcomes among the 13,970 patients enrolled in the CLEAR Outcomes trial. The CTTC endpoint of "major vascular event" was a composite of coronary heart disease death, nonfatal myocardial infarction, fatal or nonfatal stroke, or coronary revascularization. HRs for CTTC-defined endpoints were normalized to 1 mmol/L differences in LDL-C levels between bempedoic acid and placebo groups. A first major vascular event occurred in 703 (10.1%) patients in the bempedoic acid group and 816 (11.7%) patients in the placebo group (HR: 0.85; 95% CI: 0.77-0.94). When normalized per 1 mmol/L reduction in LDL-C, the HR was 0.75 (95% CI: 0.63-0.90), comparable to the rate ratio of 0.78 reported for statins in the CTTC meta-analysis. Normalized risk reductions were similar for bempedoic acid and statins for the endpoints of major coronary events, nonfatal myocardial infarction, and coronary revascularization. Cardiovascular risk reduction with bempedoic acid is similar to that achieved with statins for a given absolute magnitude of LDL-C lowering. (Evaluation of Major Adverse Cardiovascular Events in Participants With, or at High Risk for, Cardiovascular Disease Who Are Statin Intolerant Treated with Bempedoic Acid [ETC-1002] or Placebo [CLEAR Outcomes]; NCT02993406). [ABSTRACT FROM AUTHOR]

Mass spectrometry (MS) is a powerful analytical technique in metabolomics, enabling the identification and quantification of metabolites. However, analyzing MS data poses challenges such as batch effects, outliers, and high-dimensional data. In this paper, we propose a comprehensive framework for MS data analysis. The framework integrates data calibration, outlier detection, and automatic classification modules. Data calibration is performed using a deep autoencoder to remove batch effects. Outlier detection combines multiple algorithms through ensemble learning to identify and remove outliers. Automatic classification utilizes a transformer model to handle high-dimensional data and capture global feature relationships. Experimental results on myocardial infarction (MI) and coronary heart disease (CHD) datasets demonstrate the effectiveness of the framework. It outperforms traditional classification models and achieves higher accuracy. The proposed framework provides a robust solution for MS data analysis, facilitating more accurate classification and enabling reliable biological insights in metabolomics research. [Display omitted] • Novel framework integrates three steps for MS data analysis. • Deep AE removes batch effects, while an ensemble approach removes outliers. • Transformer captures intrinsic relationships in MS data for accurate classification. • The framework provides a comprehensive solution to improve classification accuracy. • The framework also facilitates reliable biological insights. [ABSTRACT FROM AUTHOR]

Lipoprotein(a) (Lp[a]) is a causal genetic risk factor for atherosclerotic cardiovascular disease (ASCVD). There are limited long-term follow-up data from large U.S. population cohorts. This study examined the relationship of Lp(a) with ASCVD outcomes in a large, pooled, multi-ethnic U.S. cohort. The study included data on Lp(a) and ASCVD outcomes from 5 U.S. prospective studies: MESA (Multi-Ethnic Study of Atherosclerosis), CARDIA (Coronary Artery Risk Development in Young Adults), JHS (Jackson Heart Study), FHS-OS (Framingham Heart Study-Offspring), and ARIC (Atherosclerosis Risk In Communities). Lp(a) levels were classified on the basis of cohort-specific percentiles. Multivariable Cox regression related Lp(a) with composite incident ASCVD events by risk group and diabetes status. The study included 27,756 persons without previous ASCVD who were aged 20 to 79 years, including 55.0% women, 35.6% Black participants, and 7.6% patients with diabetes, with mean follow-up of 21.1 years. Compared with Lp(a) levels <50th percentile, Lp(a) levels in the 50th to <75th, 75th to <90th, and ≥90th percentiles had adjusted HRs of 1.06 (95% CI: 0.99-1.14), 1.18 (95% CI: 1.09-1.28), and 1.46 (95% CI: 1.33-1.59), respectively for ASCVD events. Elevated Lp(a) predicted incident ASCVD events similarly by risk group, sex, and race or ethnic groups, but more strongly in patients with vs without diabetes (interaction P = 0.0056), with HRs for Lp(a) levels ≥90th percentile of 1.92 (95% CI: 1.50-2.45) and 1.41 (95% CI: 1.28-1.55), respectively. Lp(a) also individually predicted myocardial infarction, revascularization, stroke, and coronary heart disease death, but not total mortality. The study shows, in a large U.S. pooled cohort, that higher Lp(a) levels are associated with an increased ASCVD risk, including in patients with diabetes. [Display omitted] [ABSTRACT FROM AUTHOR]

The optimal surveillance strategy after percutaneous coronary intervention (PCI) for high-risk patients with multivessel or left main coronary artery disease (CAD) remains uncertain. This study aims to determine the prognostic role of routine functional testing in patients with multivessel or left main CAD who underwent PCI. The POST-PCI (Pragmatic Trial Comparing Symptom-Oriented Versus Routine Stress Testing in High-Risk Patients Undergoing Percutaneous Coronary Intervention) trial randomized high-risk PCI patients to routine functional testing at 1 year or standard care alone during follow-up. This analysis focused on participants with multivessel or left main CAD. The primary outcome was a composite of death from any cause, myocardial infarction, or hospitalization for unstable angina at 2 years. Among 1,706 initially randomized patients, 1,192 patients with multivessel (n = 833) or left main (n = 359) were identified, with 589 in the functional testing group and 603 in the standard care group. Two-year incidences of primary outcome were similar between the functional testing group and the standard care group (6.2% vs 5.7%, respectively; HR: 1.09; 95% CI: 0.68-1.74; P = 0.73). This trend persisted in both groups of multivessel (6.2% vs 5.7%; HR: 1.09; 95% CI: 0.62-1.89; P = 0.78) and left main disease (6.2% vs 5.7%; HR: 1.09; 95% CI: 0.46-2.56; P = 0.85) (P for interaction = 0.90). Routine surveillance functional testing was associated with increased rates of invasive angiography and repeat revascularization beyond 1 year. In high-risk patients with multivessel or left main CAD who underwent PCI, there was no incremental clinical benefit from routine surveillance functional-testing compared with standard care alone during follow-up. (Pragmatic Trial Comparing Symptom-Oriented Versus Routine Stress Testing in High-Risk Patients Undergoing Percutaneous Coronary Intervention [POST-PCI]; NCT03217877) [Display omitted] [ABSTRACT FROM AUTHOR]

• Neutrophils have a pathogenetic role in various stages of atherosclerosis in humans. • High neutrophil numbers are related to increased risk of ischaemic heart disease. • Clopidogrel decreases neutrophil count,an effect independent of platelet inhibition. • Clopidogrel showed superiority over aspirin in secondary prevention trials. • Neutrophil reduction likely explains the long-term beneficial effect of clopidogrel. Complement-stimulated neutrophils are able to adhere to the endothelium and damage endothelial cells both in vitro and in vivo. These blood cells participate in the early stages, growth and complications of atherosclerotic plaques. Recent findings, based on mendelian randomization analysis, support the concept that high neutrophil counts are a causal risk factor for ischemic heart disease and myocardial infarction. Clopidogrel decreases leukocyte count and inflammatory markers in patients with acute coronary syndromes; this off-target effect, which is independent of the antiplatelet action, may help explaining secondary prevention data showing a superiority of clopidogrel over aspirin in reducing new cardiovascular events. [ABSTRACT FROM AUTHOR]

The use of drug-coated balloon in the management of true bifurcation lesions appears to be an attractive option to reduce the rate of stent thrombosis and restenosis particularly at the level of the side branch ostium. We aim to assess the safety and the efficacy of a hybrid approach combining a drug-eluting stent in the main branch and a drug-coated balloon to treat the side branch ostium in patients with de novo true bifurcation. From September 2020 to March 2022, 45 patients with a de novo true bifurcation lesion Medina (1.1.1) or Medina (0.1.1) were enrolled. All patients underwent a percutaneous coronary intervention with the hybrid approach. Clinical assessment with functional stress imaging test was scheduled at 6 months. In case of documented ischemia, coronary angiography was performed. The primary endpoint was the composite of target lesion failure at 6 months including cardiac death, target vessel MI or ischemia-driven target lesion revascularization. The secondary endpoints were technical success, defined by performing the percutaneous coronary intervention without an additional drug-eluting stent at the level of the side branch ostium, and clinical success, defined by a technical success associated with the absence of severe complications during in-hospital phase. The immediate results show a technical success of the procedure in the majority of cases (88.9 %) with a low rate of bailout side branch stenting (11.1 %). The clinical success was obtained in 86.7 % and only one patient experienced a severe in-hospital complication. A side branch ostial lesion length > 10 mm was the only independent predictor of clinical failure of the procedure (OR 12.49, 95 % CI 1.17–133.6; p = 0.037). At 6 months, the TLF was low and occurred in 1 patient (2.2 %). No cardiac death was observed. No TVMI was observed. Importantly, at 6 months, no side branch thrombosis was observed. The use of a hybrid approach combining a drug-eluting stent in the main branch and a drug-coated balloon in the side branch to treat true bifurcation lesions appears to be safe and efficient with few immediate complications and with satisfactory results at mid-term follow up. • The patients with true bifurcation lesions have worse long-term clinical outcomes • A hybrid strategy combining a drug-eluting stent in the main branch and a drug-coated balloon to treat the side branch ostium is an alternative to the 2-stent techniques • The hybrid approach is efficient and safe to treat true bifurcation lesions [ABSTRACT FROM AUTHOR]

Intracoronary brachytherapy (ICB) has mainly been used to treat in-stent restenosis following percutaneous coronary intervention and was virtually abandoned about 20 years ago. However, patients treated with this strategy are still alive and some teams continue to perform this therapy. We aimed to investigate the very long-term clinical outcome of patients treated with ICB. A total of 173 consecutive patients who had been treated with ICB at a large tertiary referral centre between 1998 and 2003 were included. The primary endpoint of the study was all-cause mortality. The secondary endpoints were as follows: occurrence of major adverse cardiac events (MACE, defined as all-cause death, non-fatal myocardial infarction, or target vessel revascularization), cardiac death, and presence of angina at the end of follow-up. Patients' mean age at the time of ICB was 64 ± 10 years and 77 % were male. Restenosis (bare metal stent vs. balloon angioplasty) was the only indication for ICB. Unstable angina was present in 34 % of the patients. Follow-up was available for 166 patients. After a mean follow-up of 20 ± 1.3 years, 66 % of the patients had died (including 74 patients (67 %) with cardiac death). Cumulative MACE rate at 20 years was 96 %. Very long-term follow-up of patients with in-stent restenosis treated with ICB confirmed a high all-cause mortality rate mainly due to cardiac causes and MACEs. • A mean follow-up of 20 years is the longest assessed for intracoronary brachytherapy (ICB). • Long term high all-cause mortality after ICB was mainly due to cardiac death. • A high cumulative major adverse cardiac event (MACE) of 96 % was found at 20 years of follow up after ICB. [ABSTRACT FROM AUTHOR]

This meta-analysis aimed to examine the association of child abuse with adult coronary heart disease risk and separately by abuse subtypes, including emotional abuse, sexual abuse, and physical abuse. Data were extracted from studies published up through December 2021 and on the basis of research from PubMed, Embase, CINAHL, and PsycINFO. Studies were selected if they included adults with or without any type of child abuse and measured the risk of any type of coronary heart disease. Statistical analyses were conducted in 2022. The random effects model was used to pool the effect estimates presented by RRs with 95% CIs. Heterogeneity was assessed using Q and I2 statistics. The pooled estimates were synthesized using 24 effect sizes from 10 studies with a sample size of 343,371 adults. Adults with child abuse were associated with a higher risk of coronary heart disease than those without (RR=1.52; 95% CI=1.29, 1.79), and the association was similar for myocardial infarction (RR=1.50; 95 % CI=1.08, 2.10) and unspecified coronary heart disease (RR=1.58; 95% CI=1.23, 2.02). Moreover, emotional (RR=1.48; 95% CI=1.29, 1.71), sexual (RR=1.47; 95% CI=1.15, 1.88), and physical (RR=1.48; 95% CI=1.22, 1.79) abuse were associated with increased risk of coronary heart disease. Child abuse was associated with an increased risk of adult coronary heart disease. Results were generally consistent across abuse subtypes and sex. This study advocates further research on biological mechanisms linking child abuse to coronary heart disease as well as improvement in coronary heart disease risk prediction and targeted prevention approaches. [ABSTRACT FROM AUTHOR]

Mendelian randomization confirmed multiple risk factors for primary events of coronary artery disease (CAD), but no such studies have been performed on recurrent major coronary events despite interesting insights derived from other designs. We examined the associations between genetically-influenced classical cardiovascular risk factors and the risk of recurrent major coronary events in a cohort of CAD patients. We included all first-time CAD cases (defined as angina pectoris, chronic ischemic heart disease or acute myocardial infarction) of European ancestry from the UK Biobank. Cases were followed till the end of follow-up, death or when they developed a recurrent major coronary event (chronic ischemic heart disease or acute myocardial infarction). Standardized weighted genetic risk scores were calculated for body mass index (BMI), systolic blood pressure, LDL cholesterol and triglycerides. From a total of 22,949 CAD patients (mean age at first diagnosis 59.8 (SD 7.3) years, 71.1% men), 12,539 (54.6%) reported a recurrent major coronary event within a period of maximum 17.8 years. One standard deviation higher genetically-determined LDL cholesterol was associated with a higher risk of a recurrent major coronary event (odds ratio: 1.08 [95% confidence interval: 1.05, 1.11]). No associations were observed for genetically-influenced BMI (1.00 [0.98, 1.03]), systolic blood pressure (1.01 [0.98, 1.03]) and triglycerides (1.02 [0.995, 1.05]). Despite the use risk-reducing medications following a first coronary event, this study provided genetic evidence that, of the classical risk factors, mainly high LDL cholesterol was associated with a higher risk of developing recurrent major coronary events. [Display omitted] • Most Mendelian randomization studies were performed on primary disease. • In atherosclerosis patients, LDL cholesterol associated with secondary disease. • Other classical cardiovascular disease did not associate with secondary disease. • LDL cholesterol should be mainly targeted to reduce secondary disease risk. [ABSTRACT FROM AUTHOR]

Previous studies have failed to show a cardioprotective benefit of beta-blockers in patients with stable coronary artery disease (CAD). This study sought to determine the association between beta-blockers and cardiovascular events in patients with stable CAD using a new user design. All patients aged >66 years undergoing elective coronary angiography in Ontario, Canada, from 2009 to 2019 with diagnosed obstructive CAD were included. Exclusion criteria included heart failure or a recent myocardial infarction, as well as having a beta-blocker prescription claim in the previous year. Beta-blocker use was defined as having at least 1 beta-blocker prescription claim in the 90 days preceding or after the index coronary angiography. The main outcome was a composite of all-cause mortality and hospitalization for heart failure or myocardial infarction. Inverse probability of treatment weighting using the propensity score was used to account for confounding. This study included 28,039 patients (mean age: 73.0 ± 5.6 years; 66.2% male), and 12,695 of those (45.3%) were newly prescribed beta-blockers. The 5-year risks of the primary outcome were 14.3% in the beta-blocker group and 16.1% in the no beta-blocker group (absolute risk reduction: −1.8%; 95% CI: −2.8 to −0.8; HR: 0.92; 95% CI: 0.86-0.98 ; P = 0.006). This result was driven by reductions in myocardial infarction hospitalization (cause-specific HR: 0.87; 95% CI: 0.77-0.99 ; P = 0.031), whereas no differences were observed in all-cause death or heart failure hospitalization. In patients with angiographically documented stable CAD without heart failure or a recent myocardial infarction, beta-blockers were associated with a small but significant reduction in cardiovascular events at 5 years. [Display omitted] [ABSTRACT FROM AUTHOR]

Intracoronary pressure wire is useful to guide revascularization in patients with coronary artery disease. To evaluate changes in diagnosis (coronary artery disease extent), treatment strategy and clinical results after intracoronary pressure wire study in real-life patients with intermediate coronary artery stenosis. Observational, prospective and multicenter registry of patients in whom pressure wire was performed. The extent of coronary artery disease and the treatment strategy based on clinical and angiographic criteria were recorded before and after intracoronary pressure wire guidance. 12-month incidence of MACE (cardiovascular death, non-fatal myocardial infarction or new revascularization of the target lesion) was assessed. 1414 patients with 1781 lesions were included. Complications related to the procedure were reported in 42 patients (3.0 %). The extent of coronary artery disease changed in 771 patients (54.5 %). There was a change in treatment strategy in 779 patients (55.1 %) (18.0 % if medical treatment; 68.8 % if PCI; 58.9 % if surgery (p < 0.001 for PCI vs medical treatment; p = 0.041 for PCI vs CABG; p < 0.001 for medical treatment vs CABG)). In patients with PCI as the initial strategy, the change in strategy was associated with a lower rate of MACE (4.6 % vs 8.2 %, p = 0.034). The use of intracoronary pressure wire was safe and led to the reclassification of the extent of coronary disease and change in the treatment strategy in more than half of the cases, especially in patients with PCI as initial treatment. • In a non-controlled, real-life setting, the pressure wire is safe, with an extremely low complications rate. • Following pressure wire use, we have demonstrated a very significant change in assessment of the extent of coronary disease. • Following pressure wire use, we have evidenced a very significant change not only in treatment modality (medical, PCI or CABG) but also in management strategy. • We have shown that the change in treatment modality and/or strategy has prognostic implications, particularly in those patients in which the initial intention was to perform PCI. • These results are different from those observed in previous studies conducted in populations with very limited representation of patients with ACS and in reimbursement-based healthcare systems. [ABSTRACT FROM AUTHOR]

Approximately half of the patients presenting with ST-segment elevation myocardial infarction have also significant atherosclerotic disease affecting coronary segments other than the infarct-related artery. Optimal management of residual lesions in this clinical setting has been a topic of intense research in the last decade. On the one hand, a large body of evidence has consistently shown the benefit of complete revascularization for the reduction of adverse cardiovascular outcomes. On the other hand, some crucial aspects such as the optimal timing or the best strategy of the complete treatment approach remain a matter of controversy. In this review, we aim to provide a thorough critical appraisal of the available literature regarding this topic, by discussing areas of relative certainty, gaps in the knowledge, approach to specific clinical subsets and future research directions. • Complete revascularization of STEMI and multivessel disease is beneficial. • Best timing of complete revascularization is uncertain. • Optimal strategy for non-culprit lesions selection is controversial. [ABSTRACT FROM AUTHOR]

• This meta-analysis evaluated six studies of the cardiovascular risks associated with endometriosis. • Endometriosis was found to be associated with an increased risk of coronary and cerebrovascular disease. • Further studies are required to evaluate the risk of cardiovascular mortality in women with endometriosis. Endometriosis is a benign, estrogen-dependent, chronic inflammatory disease and is the commonest cause of chronic pelvic pain in younger women. Cardiovascular disease is the main cause of death worldwide. Because the relationship between endometriosis and CV disease is not well established, we performed a systematic review of longitudinal studies that assessed the occurrence of cardiovascular events in women with endometriosis compared to those without endometriosis. Systematic review with meta-analysis of longitudinal cohort/nested case-control studies with endometriosis patients and controls. A search was conducted of the MEDLINE, CENTRAL, and Embase databases from inception to November 2022. Random-effects meta-analysis was performed to estimate pooled hazard ratios (HR) and 95 % confidence intervals (95%CI). Cardiovascular outcomes such as ischemic heart disease and cerebrovascular disease. Six cohort studies were included, with a total of 254,929 participants. Meta-analysis showed that endometriosis was associated with a significantly increased risk of ischemic heart disease (HR 1.50, 95%CI 1.37–1.65; I2 = 0 %) and cerebrovascular disease (HR 1.17, 95%CI 1.07–1.29; I2 = 0 %). The one study that examined the relationship between cardiovascular mortality and endometriosis found a decreased risk in women with endometriosis relative to women without endometriosis (HR 0.55 (95%CI 0.47–0.65)). Endometriosis is associated with a significantly increased risk of cardiovascular disease, namely ischemic heart disease and cerebrovascular disease. Further studies are required to determine if endometriosis and/or its treatments are risk factors (particularly for cardiovascular mortality), and whether preventive measures could reduce the burden of cardiovascular disease in women with endometriosis. Study protocol registered at PROSPERO: CRD42022298830. [ABSTRACT FROM AUTHOR]

Rational design and fabrication of small interfering RNA (siRNA) delivery system with simple production scheme, specific targeting capability, responsiveness to endogenous stimuli and potential multi-functionalities remains technically challenging. Herein, we screen and design a virus-mimicking polysaccharide nanocomplex that shows specific gene delivery capability in a selective subset of leukocytes. A virus-inspired poly (alkyl methacrylate- co -methacrylic acid) fragment was conjugated on barley β-glucans (EEPG) to endow the nanocomplex with pH-dependent endosomal membrane destabilization capabilities, as confirmed both biologically and computationally. siRNA loaded EEPG nanocomplex is feasibly fabricated in a single-step manner, which exhibit efficient gene silencing efficacy towards Dectin-1+ monocytes/macrophages. The inherent targeting affinity and feasible gene silencing potency of EEPG nanocomplex are investigated in three independent murine inflammation models, including myocardial infarction, lung fibrosis and acute liver damage. Significant enhanced accumulation level of EEPG nanocomplex is observed in cardiac lesion site, indicating its exclusive targeting capability for ischemic heart diseases. As a proof of concept, siTGF-β based gene therapy is confirmed in murine model with heart fibrosis. Overall, our findings suggest the designed EEPG nanocomplex is favorable for siRNA delivery, which might have translational potential as a versatile platform in inflammation-related diseases. A virus-mimicking polysaccharide-based multifunctional nanocomplex shows considerable endosomal escape activity for siRNA delivery, which is manifested via computational and biological tools. In vivo , the inherent targeting capability and feasible gene silencing potency of produced nanocomplex are confirmed in three independent inflammation murine models, suggesting the potential value of this versatile platform for inflammation-related diseases. Created with BioRender.com. [Display omitted] • On-demand designed, screen and synthesis of β-glucan-based nanoparticles for gene delivery. • Computational simulation to understand the mechanism of endosome escape capability from the developed nanosystem. • One-step production scheme without further surface chemical modification to achieve potent in vivo targeting. • Targeting efficiency and gene silencing capability were tested in three independent inflammatory murine models. • As a proof of concept, siTGF-β based nanoformulation showed potential therapeutic effect in murine cardiac fibrosis model. [ABSTRACT FROM AUTHOR]

• Myocardial infarction with non-obstructed coronary arteries (MINOCA) is a 'working diagnosis'. • A comprehensive diagnostic evaluation unravels the pathophysiology of MINOCA in the majority of cases. • Intravascular imaging and coronary physiology are needed in Myocardial ischemia with non-obstructed coronary arteries • Magnetic resonance, computed tomography and coagulation testing are fundamental diagnostic complements in MINOCA/INOCA. [ABSTRACT FROM AUTHOR]

The imbalance of mitochondrial fission and fusion dynamics causes ischemic cardiomyocyte apoptosis and heart injury by affecting mitophagy. Regulation of mitochondrial dynamics is an important therapeutic strategy for ischemic heart diseases. Considering the important roles of MORN motifs in heart diseases and chloroplast fission, we aimed to investigate the possible role of MORN repeat-containing protein 4 (MORN4) in the progression of myocardial infarction (MI), ischemic cardiomyocyte apoptosis, mitochondrial dynamics, and mitophagy. We found that in the MI mouse, MORN4 knockdown remarkably accelerated cardiac injury and fibrosis with deteriorating cardiac dysfunction. Sphingosylphosphorylcholine (SPC) alleviated ischemic cardiomyocyte apoptosis and heart injury through increased level of MORN4, indicating a vital function of MORN4 in heart with SPC used to clarify the molecular mechanisms underlying the functions of MORN4. Mechanistically, we found that MORN4 directly binds to MFN2 and promotes the phosphorylation of MFN2 S442 through Rho-associated protein kinase 2 (ROCK2), which mediates beneficial mitophagy induced by mitochondrial dynamics, while SPC promoted the binding of MORN4 and MFN2 and the process. Taken together, our data reveal a new perspective role of MORN4 in ischemic heart injury, and report that SPC could regulate myocardial mitochondrial homeostasis by activating the MORN4-MFN2 axis during the ischemic situation, this finding provides novel targets for improving myocardial ischemia tolerance and rescue of acute myocardial infarction. [Display omitted] • MORN motif protein MORN4 is an endogenous protective factor of ischemic cardiomyocytes. • MORN4 interacts with MFN2 and promotes MFN2 phosphorylation in a complex with ROCK2. • MORN4 mediates mitochondrial dynamics-induced mitophagy by promoting the phosphorylation of MFN2 S442. • Sphingosylphosphorylcholine (SPC) can act as an agonist of MORN4 to evoke its protective effect on ischemic cardiomyocytes. [ABSTRACT FROM AUTHOR]

Multiple randomized clinical trials and observational studies in patients with chronic coronary artery disease have evaluated whether revascularization, in particular PCI, can reduce the incidence of future cardiovascular events and relieve angina. Perhaps the two most widely quoted trials are COURAGE and ISCHEMIA. In both trials revascularization did not reduce the incidence of cardiovascular death or non-fatal events. In both, revascularization did relieve angina, particularly in patients with severe pain. From the time of COURAGE to ISCHEMIA there were also multiple developments. In particular improved stent technology with second and third generation drug eluting stents in ISCHEMIA compared to bare metal stents in COURAGE. There was also the development of new methods to evaluate ischemia, in particular the potential surrogate fractional flow reserve. This period also saw improvement and maturation of coronary computed tomography angiography to assess coronary anatomy non-invasively. There was also greater emphasis on more intensive, guideline directed medical therapy to treat dyslipidemia and hypertension. There has also been greater recognition that not all angina is due to epicardial obstructive disease. Microvascular disease and coronary spasm are responsible for much of the symptom burden of ischemia. These data have led to a paradigm shift toward a more nuanced approach to treating stable ischemic heart disease, with less need for revascularization except in cases of particularly severe anatomic disease or unremitting symptoms while on optimal medial therapy. In recognition of the importance of disparities in cardiovascular health, it is crucial to implement preventive strategies with optimal medical therapy in the community. • Multiple studies in patients with CAD have evaluated whether PCI can reduce the incidence of future cardiovascular events and relieve angina. • In COURAGE and ISCHEMIA revascularization did not reduce cardiovascular events but relieve angina, particularly in patients with severe pain. • From the time of COURAGE to ISCHEMIA there were also multiple scientific advances. • Microvascular disease and coronary spasm are responsible for much of the symptom burden of ischemia. • Due to disparities in cardiovascular health, it is crucial to implement optimal preventive strategies in the community. [ABSTRACT FROM AUTHOR]

The homeostatic chemokines CCL21 and CCL19 have been explored as biomarkers in cardiovascular disease prediction in patients with established cardiovascular disease, but associations between these chemokines and first-time coronary event incidence have not been investigated before. Here, we explored associations between CCL21 or CCL19 and first-time incident coronary events in the general population-based Malmö Diet and Cancer cohort with two decades of follow-up. CCL21 and CCL19 levels in plasma were analysed with ELISA and proximity extension assay and associations with disease incidence were explored with conditional logistic regression in a nested case-control cohort (CCL21; n = 676) and with Cox regression in a population-based cohort (CCL19; n = 4636). High CCL21 levels in plasma were associated with incident first-time coronary events independently of traditional risk factors (odds ratio of 2.64 with 95% confidence interval 1.62–4.31, p < 0.001, comparing the highest versus the lowest tertile of CCL21), whereas CCL19 was not. CCL19 was, however, associated with incident heart failure, as well as increased all-cause, cardiovascular and cancer mortality independently of age and sex. Even though CCL21 and CCL19 both signal through CCR7, these chemokines may not be interchangeable as disease predictors and CCL21 could be used for prediction of future coronary events in individuals without any previous coronary heart disease history. [Display omitted] • Higher CCL21 & CCL19 levels at baseline in patients who suffered a coronary event. • High levels of CCL21 are associated with increased risk of incident coronary events. • High levels of CCL19 are associated with increased risk of mortality & heart failure. [ABSTRACT FROM AUTHOR]

Despite poor cardiovascular outcomes, there are no dedicated, validated risk stratification tools to guide investigation or treatment in type 2 myocardial infarction. The goal of this study was to derive and validate a risk stratification tool for the prediction of death or future myocardial infarction in patients with type 2 myocardial infarction. The T2-risk score was developed in a prospective multicenter cohort of consecutive patients with type 2 myocardial infarction. Cox proportional hazards models were constructed for the primary outcome of myocardial infarction or death at 1 year using variables selected a priori based on clinical importance. Discrimination was assessed by area under the receiving-operating characteristic curve (AUC). Calibration was investigated graphically. The tool was validated in a single-center cohort of consecutive patients and in a multicenter cohort study from sites across Europe. There were 1,121, 250, and 253 patients in the derivation, single-center, and multicenter validation cohorts, with the primary outcome occurring in 27% (297 of 1,121), 26% (66 of 250), and 14% (35 of 253) of patients, respectively. The T2-risk score incorporating age, ischemic heart disease, heart failure, diabetes mellitus, myocardial ischemia on electrocardiogram, heart rate, anemia, estimated glomerular filtration rate, and maximal cardiac troponin concentration had good discrimination (AUC: 0.76; 95% CI: 0.73-0.79) for the primary outcome and was well calibrated. Discrimination was similar in the consecutive patient (AUC: 0.83; 95% CI: 0.77-0.88) and multicenter (AUC: 0.74; 95% CI: 0.64-0.83) cohorts. T2-risk provided improved discrimination over the Global Registry of Acute Coronary Events 2.0 risk score in all cohorts. The T2-risk score performed well in different health care settings and could help clinicians to prognosticate, as well as target investigation and preventative therapies more effectively. (High-Sensitivity Troponin in the Evaluation of Patients With Suspected Acute Coronary Syndrome [High-STEACS]; NCT01852123) [Display omitted] [ABSTRACT FROM AUTHOR]

Coronary artery calcification is prevalent in coronary heart disease with its progression being predictive of future adverse cardiac events. Its presence is considered to be a marker of interventional procedural complexity. Several adjunctive percutaneous coronary intervention tools, such as modifying balloons, atherectomy devices and intravascular lithotripsy, now exist to successfully treat calcified lesions. In this state-of-the-art review, a step-wise progression of strategies is described to modify coronary plaque, from well-recognised techniques to techniques that should only be considered when standard manoeuvres have proven unsuccessful. Technology has advanced greatly over the past few decades and we discuss how future technologies might shape percutaneous intervention. [ABSTRACT FROM AUTHOR]

Background: There is limited data on the impact of chronic total occlusions (CTOs) on the outcomes of patients presenting with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI) in the contemporary era.Methods: We queried the National Inpatient Sample between October 2015 and December 2017 using the International Classification of Diseases, Tenth revision codes to identify hospitalized AMI patients undergoing PCI. A 1:1 propensity-score matched analysis was performed to compare in-hospital outcomes of patients with and without CTOs.Results: Among 576,760 admissions identified during the study period, 51,225(8.8 %) had CTO and 525,535 (91.1 %) did not. After 1:1 propensity-score matching, each matched group contained 51,210 admissions. In-hospital mortality was significantly higher in the CTO group compared with the non-CTO group (4.7 % vs 3 %, p < 0.0001). In the CTO group, hospital length of stay was longer (median 3 vs 2 days, p = 0.001) and lower percentage of patients were discharged to home (78.8 % vs 81.1 %, p < 0.0001), compared with the non-CTO group. Median cost of hospital stay was also higher in the CTO group compared with the non-CTO group ($20,921 vs $19,856, p < 0.0001).Conclusions: In this propensity-score matched analysis of a large US inpatient database, the presence of CTOs in AMI patients undergoing PCI identified a higher risk cohort with in higher in-hospital mortality, longer hospital length of stay and higher hospitalization cost. [ABSTRACT FROM AUTHOR]

Coronary disease carries significant morbidity and mortality globally. The pandemic of obesity and diabetes combined with an aging population have resulted in a significant proportion of patients with multivessel coronary disease, the management of which poses significant challenges. A number of advancements in coronary intervention have emerged in the last few years allowing effective percutaneous management of complex coronary disease. In this review we examine the evidence base underpinning multivessel percutaneous coronary intervention across the spectrum of stable and acute coronary syndromes. [ABSTRACT FROM AUTHOR]

• Tenascin-C is expressed in diseased hearts, not in normal hearts. • Clinical utility of Tenascin-C in diseased heart is unclear. • Tenascin-C was independently associated with acute myocardial infarction, cardiomyopathy, diabetic retinopathy. • Tenascin could predict cardiovascular outcomes in patient with stable coronary heart disease. We investigated the prognostic value of tenascin-C in patients with stable coronary heart disease. A total of 666 patients were enrolled and followed for 72 months. The primary outcome was a composite of cardiac events. The secondary outcomes were all-cause death, cardiovascular death, acute myocardial infarction (AMI), and heart failure hospitalization. Results: The area under the curve of tenascin-C to discriminate the occurrence of composite cardiac events was 70 % (95 % CI: 64.2 % to 75.8 %), and the corresponding optimal cutoff value was 19.91 ng/ml. A higher concentration of tenascin-C was associated with a greater risk of composite cardiac events (P trend < 0.001). Similar results were observed in all-cause death, AMI, and heart failure hospitalization. Tenascin-C was found to be an independent predictor of total cardiovascular events in patients with stable coronary heart disease at 72 months, and also for all-cause death, AMI, and heart failure hospitalization. [ABSTRACT FROM AUTHOR]

Lipoprotein(a) is a well-known causal risk factor for cardiovascular morbidity and mortality. Little is known about the effect of age and sex on lipoprotein(a) levels, and it is largely unknown if the same elevation in lipoprotein(a) confers the same increase in risk in women and men. We investigated whether lipoprotein(a) levels and lipoprotein(a) associated risks of morbidity and mortality by age are similar in women and men. We included 37,545 women and 32,497 men from the Copenhagen General Population Study. Plasma lipoprotein(a) increased with age, and in women we found an additional increase around age 50 (age by sex interaction p = 8∙10−7). In women, levels were 27% higher after menopause (p = 4∙10−61) and 12% lower during hormone replacement therapy (p = 2∙10−19). Adjustment for estimated Glomerular Filtration Rate in both sexes and plasma estradiol in women resulted in attenuated sex differences in lipoprotein(a) levels. In sex and age stratified multivariable adjusted models, lipoprotein(a) >40 mg/dL(83 nmol/L) versus <10 mg/dL(18 nmol/L) was associated with increased risk of myocardial infarction, ischemic heart disease, aortic valve stenosis, and heart failure (men only), but not statistically significant with risk of ischemic stroke, cardiovascular mortality, or all-cause mortality. Lipoprotein(a) levels increased modestly around age 50 selectively in women; however, risk of morbidity and mortality for high lipoprotein(a) was similar in women and men above age 50. This implies that elevated lipoprotein(a) above age 50 is a relatively more common cardiovascular risk factor in women, pointing toward repeat measurements in women above age 50. [Display omitted] • Lipoprotein(a) levels increase with increasing age in women and men. • Lipoprotein(a) levels increase around age 50 selectively in women. • Risk of morbidity and mortality for high lipoprotein(a) levels was similar in women and men above age 50. • These results imply that elevated lipoprotein(a) above age 50 is a relatively more common cardiovascular risk factor in women than men. [ABSTRACT FROM AUTHOR]

Background: Understanding trends in cardiovascular (CV) risk factors and CV disease according to age, sex, race, and ethnicity is important for policy planning and public health interventions.Objectives: The goal of this study was to project the number of people with CV risk factors and disease and further explore sex, race, and ethnical disparities.Methods: The prevalence of CV risk factors (diabetes mellitus, hypertension, dyslipidemia, and obesity) and CV disease (ischemic heart disease, heart failure, myocardial infarction, and stroke) according to age, sex, race, and ethnicity was estimated by using logistic regression models based on 2013-2018 National Health and Nutrition Examination Survey data and further combining them with 2020 U.S. Census projection counts for years 2025-2060.Results: By the year 2060, compared with the year 2025, the number of people with diabetes mellitus will increase by 39.3% (39.2 million [M] to 54.6M), hypertension by 27.2% (127.8M to 162.5M), dyslipidemia by 27.5% (98.6M to 125.7M), and obesity by 18.3% (106.3M to 125.7M). Concurrently, projected prevalence will similarly increase compared with 2025 for ischemic heart disease by 31.1% (21.9M to 28.7M), heart failure by 33.0% (9.7M to 12.9M), myocardial infarction by 30.1% (12.3M to 16.0M), and stroke by 34.3% (10.8M to 14.5M). Among White individuals, the prevalence of CV risk factors and disease is projected to decrease, whereas significant increases are projected in racial and ethnic minorities.Conclusions: Large future increases in CV risk factors and CV disease prevalence are projected, disproportionately affecting racial and ethnic minorities. Future health policies and public health efforts should take these results into account to provide quality, affordable, and accessible health care. [ABSTRACT FROM AUTHOR]

Acute myocardial infarction (AMI) remains a leading cause of death worldwide. Increased formation of reactive oxygen species (ROS) during the early reperfusion phase is thought to trigger lipid peroxidation and disrupt redox homeostasis, leading to myocardial injury. Whilst the mitochondrial enzyme aldehyde dehydrogenase 2 (ALDH2) is chiefly recognised for its central role in ethanol metabolism, substantial experimental evidence suggests an additional cardioprotective role for ALDH2 independent of alcohol intake, which mitigates myocardial injury by detoxifying breakdown products of lipid peroxidation including the reactive aldehydes, malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE). Epidemiological evidence suggests that an ALDH2 mutant variant with reduced activity that is highly prevalent in the East Asian population increases AMI risk. Additional studies have uncovered a strong association between coronary heart disease and this ALDH2 mutant variant. It appears this enzyme polymorphism (in particular, in ALDH2*2/2 carriers) has the potential to have wide-ranging effects on thiol reactivity, redox tone and therefore numerous redox-related signaling processes, resilience of the heart to cope with lifestyle-related and environmental stressors, and the ability of the whole body to achieve redox balance. In this review, we summarize the journey of ALDH2 from a mitochondrial reductase linked to alcohol metabolism, via pre-clinical studies aimed at stimulating ALDH2 activity to reduce myocardial injury to clinical evidence for its protective role in the heart. [ABSTRACT FROM AUTHOR]

Ischemic heart disease (IHD) is a condition where the heart muscle does not receive enough blood flow, leading to cardiac dysfunction. Restoring blood flow to the coronary artery is an effective clinical therapy for myocardial ischemia. This strategy helps lower the size of the myocardial infarction and improves the prognosis of patients. Nevertheless, if the disrupted blood flow to the heart muscle is restored within a specific timeframe, it leads to more severe harm to the previously deprived heart tissue. This condition is referred to as myocardial ischemia/reperfusion injury (MIRI). Until now, there is a dearth of efficacious strategies to prevent and manage MIRI. Hormones are specialized substances that are produced directly into the circulation by endocrine organs or tissues in humans and animals, and they have particular effects on the body. Hormonal medications utilize human or animal hormones as their active components, encompassing sex hormones, adrenaline medications, thyroid hormone medications, and others. While several studies have examined the preventive properties of different endocrine hormones, such as estrogen and hormone analogs, on myocardial injury caused by ischemia-reperfusion, there are other hormone analogs whose mechanisms of action remain unexplained and whose safety cannot be assured. The current study is on hormones and hormone medications, elucidating the mechanism of hormone pharmaceuticals and emphasizing the cardioprotective effects of different endocrine hormones. It aims to provide guidance for the therapeutic use of drugs and offer direction for the examination of MIRI in clinical therapy. [Display omitted] [ABSTRACT FROM AUTHOR]

The discovery of regulatory cell death processes has driven innovation in cardiovascular disease (CVD) therapeutic strategies. Over the past decade, ferroptosis, an iron-dependent form of regulated cell death driven by excessive lipid peroxidation, has been shown to drive the development of multiple CVDs. This review provides insights into the evolution of the concept of ferroptosis, the similarities and differences with traditional modes of programmed cell death (e.g., apoptosis, autophagy, and necrosis), as well as the core regulatory mechanisms of ferroptosis (including cystine/glutamate transporter blockade, imbalance of iron metabolism, and lipid peroxidation). In addition, it provides not only a detailed review of the role of ferroptosis and its therapeutic potential in widely studied CVDs such as coronary atherosclerotic heart disease, myocardial infarction, myocardial ischemia/reperfusion injury, heart failure, cardiomyopathy, and aortic aneurysm but also an overview of the phenomenon and therapeutic perspectives of ferroptosis in lesser-addressed CVDs such as cardiac valvulopathy, pulmonary hypertension, and sickle cell disease. This article aims to integrate this knowledge to provide a comprehensive view of ferroptosis in a wide range of CVDs and to drive innovation and progress in therapeutic strategies in this field. [Display omitted] • Ferroptosis is crucial in numerous cardiovascular diseases (CVDs). • Ferroptosis interacts with other cell death modes in CVDs. • Modulating iron, lipid metabolism, and antioxidants can inhibit ferroptosis in CVDs. • Ferroptosis inhibitor development brings new hope for CVD treatment. • Ferroptosis mechanisms in various CVDs must be further revealed. [ABSTRACT FROM AUTHOR]

The PROMINENT trial, a cardiovascular outcome trial of the triglyceride- and remnant cholesterol-lowering agent pemafibrate, has shown neutral results despite reduction in plasma triglycerides and remnant cholesterol. We tested the hypothesis that absolute mass changes in remnant cholesterol, LDL cholesterol, and apolipoprotein B explain the results of the PROMINENT trial. Among 108,431 individuals from the Copenhagen General Population Study (CGPS), those who met the key inclusion criteria of the PROMINENT trial were analyzed to mimic the trial design. Endpoint atherosclerotic cardiovascular disease (ASCVD) was cardiovascular death, myocardial infarction, ischemic stroke, and coronary revascularization as defined in PROMINENT. In the PROMINENT trial, treatment with pemafibrate resulted in -7 mg/dL (−0.18 mmol/L; -18 %) change in remnant cholesterol, +10 mg/dL (+0.26 mmol/L; +12 %) LDL cholesterol, and +5 mg/dL (+0.05 g/L; +5 %) apolipoprotein B. In the CGPS mimicking PROMINENT, the estimated hazard ratios for ASCVD were 0.97 (95 % confidence interval: 0.94–0.99) for a -7 mg/dL (−0.18 mmol/L) change in remnant cholesterol, 1.04 (1.01–1.07) for a +10 mg/dL (+0.26 mmol/L) change in LDL cholesterol, and 1.02 (1.01–1.03) for a +5 mg/dL (+0.05 g/L) change in apolipoprotein B. When combining absolute changes in remnant cholesterol, LDL cholesterol, and apolipoprotein B, the estimated hazard ratio for ASCVD was 1.05 (0.96–1.14) in the CGPS mimicking PROMINENT compared to 1.03 (0.91–1.15) in the PROMINENT trial. Absolute mass changes in remnant cholesterol, LDL cholesterol, and apolipoprotein B can explain results of the PROMINENT trial. The 3 mg/dL (0.08 mmol/L) higher total atherogenic cholesterol together with 5 mg/dL (0.05 g/L) higher apolipoprotein B seem to explain the trend toward more ASCVD in the pemafibrate arm. [Display omitted] • Absolute mass changes in remnant cholesterol, LDL cholesterol, and apo B can explain results of the PROMINENT trial. • To reduce ASCVD lipid lowering drugs, total atherogenic cholesterol and total number of atherogenic particles need to be reduced. • Understanding the potential for causing ASCVD, lipoproteins should be judged by their absolute mass of cholesterol content. [ABSTRACT FROM AUTHOR]

[Display omitted] • This paper constructs a novel vaccine that utilizes virus-like particles in combination with peptides to induce high titers of antibody production in vivo. • This vaccine inhibits the binding of interleukin-1 and its receptor by targeting the interleukin-1 receptor type I and inhibits the downstream signaling pathway. • This novel vaccine reduces the progression of atherosclerosis, maintains cardiac function after myocardial infarction and reduces inflammation levels in animals. • This immunotherapy drug will largely improve the way coronary atherosclerotic heart disease is treated and improve patient compliance. There is mounting evidence indicating that atherosclerosis represents a persistent inflammatory process, characterized by the presence of inflammation at various stages of the disease. Interleukin-1 (IL-1) precisely triggers inflammatory signaling pathways by binding to interleukin-1 receptor type I (IL-1R1). Inhibition of this signaling pathway contributes to the prevention of atherosclerosis and myocardial infarction. The objective of this research is to develop therapeutic vaccines targeting IL-1R1 as a preventive measure against atherosclerosis and myocardial infarction. ILRQβ-007 and ILRQβ-008 vaccines were screened, prepared and then used to immunize high-fat-diet fed ApoE-/- mice and C57BL/6J mice following myocardial infarction. Progression of atherosclerosis in ApoE-/- mice was assessed primarily by oil-red staining of the entire aorta and aortic root, as well as by detecting the extent of macrophage infiltration. The post-infarction cardiac function in C57BL/6J mice were evaluated using cardiac ultrasound and histological staining. ILRQβ-007 and ILRQβ-008 vaccines stimulated animals to produce high titers of antibodies that effectively inhibited the binding of interleukin-1β and interleukin-1α to IL-1R1. Both vaccines effectively reduced atherosclerotic plaque area, promoted plaque stabilization, decreased macrophage infiltration in plaques and influenced macrophage polarization, as well as decreasing levels of inflammatory factors in the aorta, serum, and ependymal fat in ApoE-/- mice. Furthermore, these vaccines dramatically improved cardiac function and macrophage infiltration in C57BL/6J mice following myocardial infarction. Notably, no significant immune-mediated damage was observed in immunized animals. The vaccines targeting the IL-1R1 would be a novel and promising treatment for the atherosclerosis and myocardial infarction. [ABSTRACT FROM AUTHOR]

Background: Circadian system plays an important role in cardiovascular health. Experimental studies have also identified sex differences in circadian system. We aim to explore the impact of sex on the association between symptom-onset pattern of STEMI and in-hospital adverse outcomes in Chinese population.Methods: Data were used from the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome Project. 18271 STEMI patients undergoing primary percutaneous coronary intervention entered the study, including 14785 (80.9%) men and 3486 (19.1%) women. The outcomes included all-cause mortality and a composite of major adverse cardiovascular and cerebrovascular events (MACCE) during hospitalization.Results: Most participants experienced STEMI onset during 06:00 h to noon, and there was no difference in onset pattern between men and women (p = 0.582). Logistic regression showed that, after adjustment for cardiovascular risk factors, symptom onset time was significantly associated with in-hospital mortality in men, but not in women or the total population. The odds ratios (ORs) for male patients were 1.86 (95% CI 1.05 to 3.27) for midnight to 06:00 h, 1.58 (95% CI 0.95 to 2.64) for 06:00 h to noon, and 0.80 (95% CI 0.49 to 1.73) for 18:00 h to midnight as compared with STEMI presenting during noon to 18:00 h. But symptom onset time was not associated with MACCE in both sexes or the entire cohort.Conclusions: These findings show that STEMI onset time was independently associated with in-hospital mortality in male Chinese patients, indicating that sex should be taken into account in studying impact of circadian system on myocardial infarction. [ABSTRACT FROM AUTHOR]

Robotic-assisted percutaneous coronary intervention (PCI) has emerged as an alternative to manual PCI to mitigate the risk of occupational hazards for operators, and to increase precision of device placement. Previous studies have reported the safety and efficacy of robotic-assisted PCI in simpler lesions, and recently the safety and efficacy of robotic-assisted chronic total occlusion PCI have been reported. Herein, we report two cases with three-vessel disease, including total occlusions, successfully treated robotically utilizing newer guidewire and device automation. [ABSTRACT FROM AUTHOR]

Background: Elevated remnant cholesterol causes ischemic heart disease.Objectives: We tested the hypothesis that the inclusion of elevated remnant cholesterol will lead to appropriate reclassification of individuals who later experience myocardial infarction and ischemic heart disease.Methods: For >10 years we followed up 41,928 white Danish individuals from the Copenhagen General Population Study without a history of ischemic cardiovascular disease, diabetes, and statin use. Using predefined cut points for elevated remnant cholesterol, we calculated net reclassification index (NRI) from below to above 5%, 7.5%, and/or 10% 10-year occurrence of myocardial infarction and ischemic heart disease defined as a composite of death from ischemic heart disease, myocardial infarction, and coronary revascularization.Results: For individuals with remnant cholesterol levels ≥95th percentile (≥1.6 mmol/L, 61 mg/dL), 23% (P < 0.001) of myocardial infarction and 21% (P < 0.001) of ischemic heart disease were reclassified correctly from below to above 5% for 10-year occurrence when remnant cholesterol levels were added to models based on conventional risk factors, whereas no events were reclassified incorrectly. Consequently, the addition of remnant cholesterol levels yielded NRI of 10% (95% CI: 1%-20%) for myocardial infarction and 5% (95% CI: -3% to 13%) for ischemic heart disease. Correspondingly, when reclassifications were combined from below to above 5%, 7.5%, and 10% risk of events, 42% (P < 0.001) of individuals with myocardial infarction and 41% (P < 0.001) with ischemic heart disease were reclassified appropriately, leading to NRI of respectively 20% (95% CI: 9%-31%) and 11% (95% CI: 2%-21%).Conclusions: Elevated remnant cholesterol levels considerably improve myocardial infarction and ischemic heart disease risk prediction. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) confers a high risk for poor cardiovascular outcomes. We conducted a systematic review and meta-analysis to estimate the effects of revascularization as the initial management strategy compared with medical therapy among patients with CKD and coronary artery disease. A Medline/PubMed literature research was conducted to identify randomized studies comparing early coronary revascularization with optimal medical therapy or medical therapy alone in patients with CKD (estimated glomerular filtration rate <60 mL/min/1.73 m2 or maintenance dialysis). The primary outcome was myocardial infarction. The secondary outcomes were all-cause mortality or progression to kidney failure. The risk ratio (RR) was estimated using a random-effects model. Eleven randomized trials were included (3422 patients). Revascularization was associated with lower incidence of myocardial infarction compared with medical therapy in patients with CKD: RR 0.71 (95% confidence interval [CI] 0.54–0.94; p= 0.02). This result was mainly driven from a significantly lower incidence of myocardial infarction with early revascularization among patients with stable coronary artery disease: RR 0.59; 95% CI 0.37–0.93. A similar incidence of all-cause mortality was observed with both treatment strategies: RR 0.88 (95% CI 0.72–1.08; p= 0.22). A trend towards lower incidence of all-cause mortality was observed with revascularization in the subgroup of patients presenting with NSTE-ACS: RR 0.73 (95% CI 0.51–1.04; p= 0.08) but not among patients with stable coronary disease. There was no difference in progression to kidney failure between the two strategies. Coronary revascularization may be superior to medical therapy among patients with CKD and coronary disease. [Display omitted] • In patients with coronary artery disease (CAD) and chronic kidney disease (CKD), coronary revascularization may be superior to medical therapy for myocardial infarction (MI) prevention. • A trend towards lower all-cause mortality was observed with early revascularization among patients with non-ST segment elevation acute coronary syndrome (NSTE-ACS) and CKD. • A patient-level data meta-analysis is needed to identify the optimal management strategy in patients with CAD and CKD. [ABSTRACT FROM AUTHOR]

Sodium glucose cotransporter-2 (SGLT2) inhibitors improve cardiorenal outcomes in patients with type 2 diabetes mellitus, chronic kidney disease, and chronic heart failure. SGLT2 inhibitors also reduce the risk of cardiovascular mortality and hospitalization for heart failure among patients with type 2 diabetes mellitus and a remote history of myocardial infarction (MI). As a result of the growing body of evidence in diverse disease states, and the hypothesized mechanisms of action, it is reasonable to consider the potential of SGLT2 inhibition to improve outcomes in patients with acute MI as well if initiated early after presentation. Whether these therapies are efficacious and safe to use early in the course of acute coronary heart disease remains relatively unexplored. Here, we describe the contemporary data and continuing evidence gap for considering the use of SGLT2 inhibitors early following an acute MI to reduce cardiovascular morbidity and mortality. [ABSTRACT FROM AUTHOR]

Background: Patients with diabetes mellitus (DM) have a high prevalence of coronary chronic total occlusions (CTOs). We conducted a systematic review and meta-analysis to characterize outcomes after CTO percutaneous coronary intervention (PCI) in patients without or with DM.Methods: PubMed, EMBASE, Cochrane, and Google Scholar were queried for studies comparing non-DM vs. DM patients undergoing attempted CTO PCI. The primary outcome was all-cause mortality at longest follow-up (at least 6 months). Secondary outcomes were major adverse cardiovascular events (MACE) which is a composite endpoint including myocardial infarction, cardiac or all-cause mortality and any revascularization in patients after CTO PCI, target vessel revascularization (TVR), myocardial infarction (MI), Japanese chronic total occlusion (J-CTO) score and prevalence of multivessel (MV) CTO disease. We used a random effects model to calculate odds ratios (ORs) and 95% confidence intervals (CIs).Results: Sixteen studies, including 2 randomized control trials and 14 observational studies, met inclusion criteria. At longest follow-up, all-cause mortality (OR 0.54 [95% CI 0.37-0.80], p < 0.0001) and MACE (OR 0.82 [95% CI 0.72-0.93], p < 0.00001) were significantly lower in non-DM CTO patients. MV CTO disease was less prevalent in patients without DM (OR 0.80 [95% CI 0.69-0.93], p = 0.004). However, there were no differences in MI, TVR and J-CTO score.Conclusions: Non-diabetics undergoing CTO PCI have lower all-cause mortality and MACE than diabetics. Future research may determine if DM control improves diabetics' CTO PCI outcomes. [ABSTRACT FROM AUTHOR]

Background: A polymer-free biolimus-eluting stent (PF-BES) and a zotarolimus-eluting stent (ZES) recently showed similar clinical profiles and appear to be competing options in specific clinical settings of patients undergoing percutaneous coronary intervention (PCI). Whether they perform similarly also in complex procedural settings as coronary bifurcation lesions remains unaddressed.Methods: All consecutive patients undergoing coronary bifurcation PCI with PF-BES or the new iteration of the ZES from three large multicenter real-world registries were included. The primary outcome was major adverse cardiovascular events (MACE), a composite of all-cause death, myocardial infarction (MI), target lesion revascularization (TLR) and stent thrombosis (ST). Multiple analyses to adjust for baseline differences were carried out including propensity-score matching, propensity-score stratification and inverse-probability-weighting. Outcomes are reported according to Cox proportional hazard models censored at 400-day follow-up.Results: 1169 patients treated with PF-BES (n = 440) or ZES (n = 729) on the main branch of a coronary bifurcation lesion were included (mean age 69 ± 11 years, 75.4% male, 53.8% acute coronary syndrome at presentation, 26.6% left main bifurcation, median dual antiplatelet therapy duration 12 [range 12-12] months). MACE, all-cause death, TLR and ST tended towards non-statistically higher rates with the PF-BES as compared to the ZES. Higher MI and target vessel revascularization occurrence was observed with PF-BES.Conclusions: In this large contemporary cohort of patients undergoing coronary bifurcation PCI, the occurrence of MACE was non-statistically different with the use of PF-BES and ZES devices. However, differences favoring the ZES device that may entail clinical relevance were observed. Further studies are needed to confirm these findings and explore whether they remain valid when a short dual antiplatelet therapy is adopted. [ABSTRACT FROM AUTHOR]

Air pollution is emerging as an important risk factor for acute coronary syndrome (ACS). In this study, we investigated the association between short-term air pollution exposure and mechanisms of coronary plaque instability evaluated by optical coherence tomography (OCT) imaging in ACS patients. Patients with ACS undergoing OCT imaging were retrospectively selected. Mechanism of culprit lesion instability was classified as plaque rupture (PR) or intact fibrous cap (IFC) by OCT. Based on each case's home address, the mean daily exposures to several pollutants, including particulate matter 2.5 (PM 2.5), on the same day of ACS and in the immediate days (up to 6 days) prior to the index ACS, were collected. 139 ACS patients were included [69 (49.6%) had PR and 70 (50.4%) IFC]. Patients with PR, compared to those with IFC, had higher PM 2.5 exposure levels on the same day of ACS, without differences in the immediate 6 days before index ACS. At multivariate analysis, PM 2.5 exposure on the same day of ACS was the only independent predictor of PR [OR = 1.912 per SD (8.6 μg/m3), CI95 % (1.087–3.364), p = 0.025]. Patients with PR presented a steady increase in PM 2.5 daily exposure levels in the days preceding the occurrence of ACS, with a peak the day of ACS (p for trend = 0.042) This study demonstrates for the first time that a higher short-term PM2.5 exposure, on the same day of ACS, is associated with an increased risk of PR as a pathobiological mechanism of coronary plaque instability. [Display omitted] • Air pollution is emerging as an important risk factor for acute coronary syndrome (ACS). • Acute PM 2.5 exposure, especially on the same day of ACS, is associated with an increased risk of plaque rupture as mechanism of coronary plaque instability. • Mitigation strategies are crucial to reduce the burden of ischemic heart disease, especially in patients with a higher risk of cardiovascular events. [ABSTRACT FROM AUTHOR]

Background: Each year, nearly 790.000 new cases of myocardial infarction (MI) are recorded in the United States. Better knowledge of the modifiable risk factors for this cardiovascular disease remains a major public health issue. In this perspective, the aim of this systematic review and meta-analysis was to estimate the relationship between post-traumatic stress disorder (PTSD) and risk of subsequent myocardial infarction (MI).Methods: A systematic review using PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analysis) guidelines was performed by searching four bibliographic databases (PubMed/Medline, PsycINFO, Science Direct and Proquest Dissertations and Theses).Results: A total of 14 articles were included. Nine of these included depression as a covariate. Among 13 studies (N = 848.903), the pooled HR for the magnitude of the relationship between PTSD and MI was 1.49 (95% CI 1.31-1.69) before adjustment for depression. The pooled HR estimate for the 9 depression-adjusted estimates (N = 814.441) was 1.32 (95% CI 1.12-1.56).Limitations: These results should be considered with caution because there is high heterogeneity between studies and possible publication bias; thus, further research is required to support these results.Conclusions: Further research is still needed to identify in more precise terms the mediating factors involved in the direct association between PTSD and the subsequent occurrence of ischemic heart disease. [ABSTRACT FROM AUTHOR]

[Display omitted] • Type 2 diabetes (T2DM) increases the risk of recurrence in myocardial infarction patients. • A gut microbiota profile is associated to the further T2DM development. • Microbiome data improved the prediction of T2DM development when added to clinical parameters. • A risk score including the most predictive genera was associated with the probability of T2DM. • A high risk score was associated with a higher hepatic insulin resistance and β-cell dysfunction. A distinctive gut microbiome have been linked to type 2 diabetes mellitus (T2DM). We aimed to evaluate whether gut microbiota composition, in addition to clinical biomarkers, could improve the prediction of new incident cases of diabetes in patients with coronary heart disease. All the patients from the CORDIOPREV (Clinical Trials.gov.Identifier: NCT00924937) study without T2DM at baseline were included (n = 462). Overall, 107 patients developed it after a median of 60 months. The gut microbiota composition was determined by 16S rRNA gene sequencing and predictive models were created using hold-out method. A gut microbiota profile associated with T2DM development was determined through a microbiome-based predictive model. The addition of microbiome data to clinical parameters (variables included in FINDRISC risk score and the diabetes risk score of the American Diabetes Association, HDL, triglycerides and HbA1c) improved the prediction increasing the area under the curve from 0.632 to 0.946. Furthermore, a microbiome-based risk score including the ten most discriminant genera, was associated with the probability of develop T2DM. These results suggest that a microbiota profile is associated to the T2DM development. An integrate predictive model of microbiome and clinical data that can improve the prediction of T2DM is also proposed, if is validated in independent populations to prevent this disease. [ABSTRACT FROM AUTHOR]

Ischemic heart disease is rarely reported in people with cystic fibrosis (PwCF) despite multiple potential risk factors. Here we report two cases of ST elevation myocardial infarction (STEMI), both in young women with cystic fibrosis (CF) and cystic fibrosis related diabetes (CFRD). These cases illustrate the importance of considering myocardial injury/infarction in the differential diagnosis of patients with CF and chest pain or shortness of breath, and addressing the growing risk of cardiovascular disease (CVD). [ABSTRACT FROM AUTHOR]

Aim: We sought to investigate the impact of IVUS use on chronic total occlusion (CTO) PCI using data from a contemporary registry of consecutive patients and applying a propensity score matching analysis.Methods and Results: We evaluated 514 successful CTO-PCIs, median age: 67 years (IQR: 58-73), 83.5% males. IVUS-guided PCI was performed in 184 (35.8%) of cases. After using 1:1 propensity matching score analysis, two groups of 182 patients each (IVUS-guided vs. angiography-guided CTO-PCI group) were produced to form the study population. In the IVUS-guided group the median maximum stent diameter was larger and the median total stented segment was longer compared to the angiography-guided group [(3.5 mm, IQR: 3.0-4.0 vs. 3.2 mm, IQR: 3.0-3.5, p < 0.001) and (60.0 mm, IQR: 38.0-91.3 vs. 38.0 mm, IQR: 32.0-70.5, p < 0.001), respectively]. In the IVUS-guided group, retrograde recanalization was more frequently encountered compared to the angiography-guided PCI group (30.2% vs. 20.9%, p = 0.04). Procedural time was significantly longer in the IVUS-guided group, without any difference in fluoroscopy time, radiation dose and contrast volume. Multivariate linear regression analysis showed that IVUS use was the strongest independent factor associated with larger maximum diameter stents (p < 0.001) and a strong independent predictor for total stented segment length during CTO-PCI (p < 0.001). Up to 8 years follow-up, there was no difference in the incidence of the composite endpoint of all-cause death, cardiac death, myocardial infarction and target vessel revascularization between the IVUS-guided PCI and the angiography-guided PCI groups (hazard ratio: 13.7% vs. 15.9%, respectively, log-rank: p = 0.67, median follow-up time: 49.0 months, IQR: 33.0-67.0).Conclusions: Use of IVUS in CTO-PCI was associated with larger stent diameter and longer stented segments. Despite more frequent use of IVUS in retrograde CTO-PCI, there was no difference in long-term adverse events between IVUS and angiography CTO-PCI groups; nevertheless, the study was not powered to assess clinical outcomes. [ABSTRACT FROM AUTHOR]

Background: Increasingly, fractional flow reserve (FFR) is employed to assess coronary artery stenoses although there is limited real world long-term outcome data with a recent report questioning its safety. This study aimed to assess the in-hospital complications and clinical outcomes up to 10 years after FFR-guided revascularisation at a tertiary Australian hospital.Methods: The cohort comprised 274 consecutive patients undergoing FFR from 2010 to 2015 with follow-up to 2020. In-hospital complications and long-term outcomes were compared between patients with FFR≤0.80 and FFR>0.80. Major adverse cardiac events (MACE) comprised cardiac death, myocardial infarction (MI) and target vessel revascularisation (TVR).Results: The FFR was ≤0.80 in 166 and >0.80 in 108 patients. Stable coronary disease was present in 95%. Revascularisation was undertaken in 86.7% of the FFR≤0.80 group and in 2.8% of the group with an FFR>0.80. In-hospital adverse events were 3.3% with no pressure wire-related coronary dissection, stroke or death. At median follow-up of 5 years, patients with FFR≤0.80 and FFR>0.80 had a similar rate of cardiac death (2.6% versus 5.0%, p=0.335) and MI (2.6% versus 6.9%, p=0.154). In the FFR>0.80 group, MACE (17.8% v 7.9%; p=0.018) and TVR (12.9% v 5.3%; p=0.033) were significantly higher.Conclusion: This observational study highlights the safety and long-term effectiveness of FFR-guided coronary revascularisation in patients with predominantly stable disease. [ABSTRACT FROM AUTHOR]

Ischemic heart disease and the resulting heart failure continue to carry high morbidity and mortality, and a breakthrough in our understanding of this disorder is needed. The adult spiny mouse (Acomys cahirinus) has evolved the remarkable capacity to regenerate full-thickness skin tissue, including microvasculature and cartilage, without fibrosis or scarring. We hypothesized that lack of scarring and resulting functional regeneration also applies to the adult Acomys heart. We compared responses of the Acomys heart to CD1 outbred Mus heart following acute left anterior descending coronary artery ligation to induce myocardial infarction. Both Acomys and Mus hearts showed decreased ejection fraction (EF) after ligation. However, Acomys hearts showed significant EF recovery to pre-ligation values over four weeks. Histological analysis showed comparable infarct area 24-h after ligation with a similar collateral flow in both species' hearts, but subsequently, Acomys displayed reduced infarct size, regenerated microvasculature, and increased cell proliferative activity in the infarcted area. These observations suggest that adult Acomys displays remarkable cardiac recovery properties after acute coronary artery occlusion and may be a useful model to understand functional recovery better. Adult Acomys provides a novel mammalian model to further investigate the cardioprotective and regenerative signaling mechanisms in adult mammals. This opens the door to breakthrough treatment strategies for the injured myocardium and help millions of patients with heart failure secondary to tissue injury with irreversible damage. • The adult spiny mouse (Acomys) has evolved the capacity to regenerate full-thickness skin tissue without scarring. • We investigated response of the Acomys heart to myocardial injury. • Acomys hearts showed significant EF recovery to pre-ligation values over 4 weeks. • Reduced infarct size, regenerated microvasculature, and increased cell proliferative activity were seen. • Adult Acomys provides a novel model for cardioprotective and regenerative signaling mechanisms in adult mammals. [ABSTRACT FROM AUTHOR]

[Display omitted] Acute myocardial infarction (MI), one of the most common cardiovascular emergencies, is a leading cause of morbidity and mortality. Ample evidence has revealed an essential role for inflammasome activation and autophagy in the pathogenesis of acute MI. Tax1-binding protein 1 (TAX1BP1), an adaptor molecule involved in termination of proinflammatory signaling, serves as an important selective autophagy adaptor, but its role in cardiac ischemia remains elusive. This study examined the role of TAX1BP1 in myocardial ischemic stress and the underlying mechanisms involved. Levels of TAX1BP1 were significantly downregulated in heart tissues of patients with ischemic heart disease and in a left anterior descending (LAD) ligation-induced model of acute MI. Adenovirus carrying TAX1BP1 was delivered into the myocardium. The acute MI induced procedure elicited an infarct and cardiac dysfunction, the effect of which was mitigated by TAX1BP1 overexpression with little effect from viral vector alone. TAX1BP1 nullified acute MI-induced activation of the NLRP3 inflammasome and associated mitochondrial dysfunction. TAX1BP1 overexpression suppressed NLRP3 mitochondrial localization by inhibiting the interaction of NLRP3 with mitochondrial antiviral signaling protein (MAVS). Further investigation revealed that ring finger protein 34 (RNF34) was recruited to interact with TAX1BP1 thereby facilitating autophagic degradation of MAVS through K27-linked polyubiquitination of MAVS. Knockdown of RNF34 using siRNA nullified TAX1BP1 yielded protection against hypoxia-induced MAVS mitochondrial accumulation, NLRP3 inflammasome activation and associated loss of mitochondrial membrane potential. Taken together, our results favor a cardioprotective role for TAX1BP1 in acute MI through repression of inflammasome activation in a RNF34/MAVS-dependent manner. [ABSTRACT FROM AUTHOR]

Background: Evidence regarding lignan consumption in relation to coronary heart disease (CHD) risk remains limited and mixed.Objectives: The aim of this study was to prospectively examine associations between lignan intake and CHD risk in U.S. men and women.Methods: We prospectively followed 214,108 men and women in 3 cohorts who did not have cardiovascular disease or cancer at baseline. Diet was repeatedly assessed using a validated food frequency questionnaire every 2-4 years since baseline.Results: During 5,517,225 person-years of follow-up, we documented 10,244 CHD cases, including 6,283 nonfatal myocardial infarction and 3,961 fatal CHD cases. In multivariable-adjusted analyses, comparing extreme quintiles, the pooled hazard ratios of CHD were 0.85 (95% CI: 0.79-0.92) for total lignans, 0.76 (95% CI: 0.71-0.82) for matairesinol, 0.87 (95% CI: 0.81-0.93) for secoisolariciresinol, 0.89 (95% CI: 0.83-0.95) for pinoresinol, and 0.89 (95% CI: 0.83-0.95) for lariciresinol (all P values for trend ≤0.003). Nonlinear relationships were found for total lignan, matairesinol, and secoisolariciresinol: the risk reduction plateaued at intakes above approximately 300 μg/d, 10 μg/d, and 100 μg/d, respectively (P < 0.01 for all nonlinearity). The inverse associations for total lignan intake appeared to be more apparent among participants with higher total fiber intake (P = 0.04 for interaction). In addition, lignan intake was more strongly associated with plasma concentrations of enterolactone when fiber intake was higher.Conclusions: Increased long-term intake of lignans was associated with a significantly lower risk of total CHD in both men and women. Possible synergistic effects may exist between lignan and fiber intake in relation to CHD risk reduction, possibly through enhancing the production of enterolignans. [ABSTRACT FROM AUTHOR]

Strategies for stem cell-based cardiac regeneration and repair are key issues for the ischemic heart disease (IHD) patients with chronic complications related to ischemic necrosis. Cardiac stem cells (CSCs) have demonstrated high therapeutic efficacy for IHD treatment owing to their specific cardiac-lineage commitment. The therapeutic potential of CSCs could be further enhanced by designing a cellular spheroid formulation. The spheroid culture condition of CSCs was optimized to ensure regulated size and minimal core necrosis in the spheroids. The CSC spheroids revealed mRNA profiles of the factors related to cardiac regeneration, angiogenesis, anti-inflammatory, and cardiomyocyte differentiation with a higher expression level than the CSCs. Intramyocardially delivered CSC spheroids in the rat IHD model resulted in a significant increase in retention rate by 1.82-fold (day 3) and 1.98-fold (day 14) compared to CSCs. Endothelial cell differentiation and neovascularization of the engrafted CSC spheroids were noted in the infarcted myocardium. CSC spheroids significantly promoted cardiac regeneration: i.e. , decreased infarction and fibrotic area (11.22% and 4.18%) and increased left ventricle thickness (0.62 mm) compared to the untreated group. Cardiac performance was also improved by 2.04-fold and 1.44-fold increase in the ejection fraction and fractional shortening, respectively. Intramyocardial administration of CSC spheroids might serve as an advanced therapeutic modality with enhanced cell engraftment and regenerative abilities for cardiac repair after myocardial infarction. [Display omitted] • The fabrication method of cardiac stem cell (CSC) spheroids were optimally designed. • CSC spheroids exhibited enhanced paracrine function and differentiation potential. • Intramyocardially injected CSC spheroids were highly engrafted in the ischemic heart. • CSC spheroid improved cardiac function of a rat myocardial infarction model. [ABSTRACT FROM AUTHOR]

Purpose: Mean heart dose (MHD) over 10 Gy and left anterior descending (LAD) coronary artery volume (V) receiving 15 Gy (V15Gy) greater than 10% can significantly increase the risk of major adverse cardiac events (MACE) in patients with non-small cell lung cancer (NSCLC). We sought to characterize the discordance between MHD and LAD dose and the association of this classification on the risk of MACE after radiation therapy.Methods and Materials: The coefficient of determination for MHD and LAD V15Gy was calculated in this retrospective analysis of 701 patients with locally advanced NSCLC treated with radiation therapy. Four groups were defined on the basis of high or low MHD (≥10 Gy vs <10 Gy) and LAD V15Gy (≥10% vs <10%). MACE (unstable angina, heart failure, myocardial infarction, coronary revascularization, and cardiac death) cumulative incidence was estimated, and Fine and Gray regressions were performed.Results: The proportion of variance in LAD V15Gy predictable from MHD was only 54.5% (R2 = 0.545). There was discordance (where MHD was high [≥10 Gy] and LAD low [V15Gy < 10%], or vice versa) in 23.1% of patients (n = 162). Two-year MACE estimates were 4.2% (MHDhigh/LADlow), 7.6% (MHDhigh/LADhigh), 1.8% (MHDlow/LADlow), and 13.0% (MHDlow/LADhigh). Adjusting for pre-existing coronary heart disease and other prognostic factors, MHDhigh/LADlow (subdistribution hazard ratio [SHR], 0.34; 95% CI, 0.13-0.93; P = .036) and MHDlow/LADlow (SHR, 0.24; 95% CI, 0.10-0.53; P < .001) were associated with a significantly reduced risk of MACE.Conclusions: MHD is insufficient to predict LAD V15Gy with confidence. When MHD and LAD V15Gy dose exposure is discordant, isolated low LAD V15Gy significantly reduces the risk of MACE in patients with locally advanced NSCLC after radiation therapy, suggesting that the validity of whole heart metrics for optimally predicting cardiac events should be reassessed. [ABSTRACT FROM AUTHOR]

• The agreement between hs-cTn T (Roche) and hs-cTn I (Abbott) is weak. • This disagreement is in favor of underdiagnosis with hs-cTn I and overdiagnosis with hs-cTn T. • The use of sex-specific 99th percentile reduces significantly this disagreement. • No impact was seen for circadian rhythm on the agreement while the disagreement increased with decreasing renal function. Many reports noted a disagreement between High sensitivity cardiac Troponin (hs-cTn) assays on the diagnosis of Acute Coronary Syndrome (ACS). We conducted a retrospective study aiming to assess the agreement between hs-cTn T (Roche) and hs-cTn I (Abbott) in patients presenting with a suspected ACS to the emergency department at Hotel-Dieu hospital between September 2017 and October 2019 using overall, sex-specific, and age-adjusted sex-specific cut-off values. This was measured using Cohen's Kappa. We explored whether renal function, circadian rhythm, age and sex influenced the discordance. And we analyzed the trend of agreement between baseline and repeated measurements. 4856 patients who had simultaneous hs-cTn I and T values were retained for the analysis. 53.5% had a hs-cTn T above the overall 99th percentile, compared to 19.9% for hs-cTn I. The numbers were significantly reduced when applying age-adjusted sex-specific 99th percentile. A disagreement was seen in 34% of cases using overall 99th percentile. Using sex-specific cut off values did not impact this discordance; however, age-adjusted sex-specific cut-off values reduced the percentage of discrepancies to 15.8%. The decreased renal function had a negative effect on the agreement while the circadian rhythm had minimal effect. This initial discordance was carried forward into repeated measurements. The disagreement between hs-cTn T and I assays could be imputed to the choice of cut-off values. The use of age-adjusted sex specific 99th percentile reduced majorly these discordances. Further studies are needed in order to evaluate their clinical utility in patients presenting with ACS. [ABSTRACT FROM AUTHOR]