scholarly journals New genetic variants associated with major adverse cardiovascular events in patients with acute coronary syndromes and treated with clopidogrel and aspirin

2018 ◽  
Author(s):  
Xiaomin Liu ◽  
Hanshi Xu ◽  
Huaiqian Xu ◽  
Qingshan Geng ◽  
Wai-Ho Mak ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Acute Coronary Syndromes ◽  
Cardiovascular Events ◽  
Large Scale ◽  
Predictive Accuracy ◽  
Major Adverse Cardiovascular Events ◽  
Sequencing Data ◽  
Clinical Trial Registry ◽  
Coronary Syndromes ◽  
High Depth

AbstractImportanceAlthough a few studies have reported the effects of several polymorphisms on major adverse cardiovascular events (MACE) in patients with acute coronary syndromes (ACS) and those undergoing percutaneous coronary intervention (PCI), these genotypes account for only a small fraction of the variation and evidence is insufficient. This study aims to identify new genetic variants associated with MACE by large-scale sequencing data.ObjectiveTo identify the genetic variants that caused MACE.DesignAll patients in this study were allocated to dual antiplatelet therapy for up to 12 months and have the follow-up duration of 18 months.SettingA two-stage association study was performed.ParticipantsWe evaluated the associations of genetic variants and MACE in 1961 patients with ACS undergoing PCI (2009-2012), including high-depth whole exome sequencing of 168 patients in the discovery cohort and high-depth targeted sequencing of 1793 patients in the replication cohort.Main Outcomes and MeasureThe primary clinical efficacy endpoint was the major adverse cardiovascular events (MACE) composite endpoint, including cardiovascular death, myocardial infarction (MI), stroke (CT or MR scan confirmed) and repeated revascularization (RR).ResultsWe discovered and confirmed six new genotypes associated with MACE in patients with ACS. Of which, rs17064642 at MYOM2 increased the risk of MACE (hazard ratio [HR] 2.76; P = 2.95 × 10-9) and reached genome-wide significance. The other five suggestive variants were KRTAP10-4 (rs201441480), WDR24 (rs11640115), ECHS1 (rs140410716), AGAP3 (rs75750968) and NECAB1 (rs74569896). Notably, the expressions of MYOM2 and ECHS1 are down-regulated in both animal models and patients with phenotypes related to MACE. Importantly, we developed the first superior classifier for predicting MACE and achieved high predictive accuracy (0.809).Conclusions and RelevanceWe identified six new genotypes associated with MACE and developed a superior classifier for predicting MACE. Our findings shed light on the pathogenesis of cardiovascular outcomes and may help clinician to make decision on the therapeutic intervention for ACS patients.Trial RegistrationThis study has been registered in the Chinese Clinical Trial Registry (http://www.chictr.org.cn, Registration number: ChiCTR-OCH-11001198).

scholarly journals New genetic variants associated with major adverse cardiovascular events in patients with acute coronary syndromes and treated with clopidogrel and aspirin

2021 ◽  
Author(s):  
Xiaomin Liu ◽  
Hanshi Xu ◽  
Huaiqian Xu ◽  
Qingshan Geng ◽  
Wai-Ho Mak ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Acute Coronary Syndromes ◽  
Cardiovascular Events ◽  
Large Scale ◽  
Predictive Performance ◽  
Coronary Intervention ◽  
Major Adverse Cardiovascular Events ◽  
Sequencing Data ◽  
Coronary Syndromes ◽  
High Depth

AbstractAlthough a few studies have reported the effects of several polymorphisms on major adverse cardiovascular events (MACE) in patients with acute coronary syndromes (ACS) and those undergoing percutaneous coronary intervention (PCI), these genotypes account for only a small fraction of the variation and evidence is insufficient. This study aims to identify new genetic variants associated with MACE end point during the 18-month follow-up period by a two-stage large-scale sequencing data, including high-depth whole exome sequencing of 168 patients in the discovery cohort and high-depth targeted sequencing of 1793 patients in the replication cohort. We discovered eight new genotypes and their genes associated with MACE in patients with ACS, including MYOM2 (rs17064642), WDR24 (rs11640115), NECAB1 (rs74569896), EFR3A (rs4736529), AGAP3 (rs75750968), ZDHHC3 (rs3749187), ECHS1 (rs140410716), and KRTAP10-4 (rs201441480). Notably, the expressions of MYOM2 and ECHS1 are downregulated in both animal models and patients with phenotypes related to MACE. Importantly, we developed the first superior classifier for predicting 18-month MACE and achieved high predictive performance (AUC ranged between 0.92 and 0.94 for three machine-learning methods). Our findings shed light on the pathogenesis of cardiovascular outcomes and may help the clinician to make a decision on the therapeutic intervention for ACS patients.

scholarly journals Impact of Postdilation on Intervention Success and Long-Term Major Adverse Cardiovascular Events (MACE) among Patients with Acute Coronary Syndromes

2020 ◽  
Vol 4 (3) ◽  
pp. 185-193
Author(s):  
Turan Erdoğan ◽  
Hakan Duman ◽  
Mustafa Çetin ◽  
Savaş Özer ◽  
Göksel Çinier ◽  
...  
Keyword(s):  
Acute Coronary Syndromes ◽  
Cardiovascular Events ◽  
Major Adverse Cardiovascular Events ◽  
Drug Eluting Stent ◽  
Timi Flow Grade ◽  
Coronary Interventions ◽  
Coronary Syndromes ◽  
The Impact ◽  
Myocardial Blush Grade

Postdilation is frequently used during coronary interventions to prevent stent malapposition. Currently there are contradictory findings regarding the benefits of postdilation for both intraprocedural and long-term outcomes. We evaluated the impact of postdilation among patients who presented with acute coronary syndromes (ACS) and underwent percutaneous coronary interventions (PCI). A total of 258 consecutive patients who presented with ACS and underwent PCI were included in the study. The patients were followed up for 25±1.7 months for the occurrence of major adverse cardiovascular events (MACE). During follow-up, 65 patients (25.2%) had MACE. Among patients without MACE, intracoronary nitrate infusion was less frequently used (P=0.005), myocardial blush grade was higher (P<0.001), and a drug-eluting stent was more frequently used (P=0.005). No significant differences were noted between groups regarding the predilation, recurrent dilation, postdilation, and other angiographic characteristics. In multivariate analysis, female sex (P=0.047), myocardial blush grade (P=0.038), previous coronary artery disease (P=0.030), and peak troponin level (P=0.002) were found to be predictors of MACE. In patients who were treated with PCI for ACS, performing postdilation did not predict final Thrombolysis in Myocardial Infarction (TIMI) flow grade, corrected TIMI frame count, myocardial blush grade, or MACE.

scholarly journals Multisite vascular disease in acute coronary syndromes: increased in-hospital mortality and no improvement over time

2018 ◽  
Vol 9 (7) ◽  
pp. 748-757 ◽  
Author(s):  
Marco Roffi ◽  
Dragana Radovanovic ◽  
Juan F Iglesias ◽  
Franz R Eberli ◽  
Philip Urban ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Hospital Mortality ◽  
Acute Coronary Syndromes ◽  
Cardiovascular Events ◽  
Major Adverse Cardiovascular Events ◽  
Evidence Based ◽  
Coronary Syndromes ◽  
Artery Disease ◽  
Over Time

Introduction: Limited data are available on the impact of multisite artery disease in patients with acute coronary syndromes. In particular, it is unknown whether the outcomes of those high-risk patients have improved over time. Therefore, we addressed the multisite artery disease patient population enrolled in the Swiss nationwide prospective acute coronary syndromes cohort study AMIS Plus over two decades. Methods: All patients enrolled from January 1999 to October 2016 were stratified according to the presence of isolated coronary artery disease or multisite artery disease, defined as coronary artery disease with known concomitant vascular disease (i.e. cerebrovascular disease and/or peripheral artery disease). Multisite artery disease 1 (MSAD1) and multisite artery disease 2 (MSAD2) defined patients with one and two additional vascular conditions, respectively. Primary outcome measures were in-hospital mortality and major adverse cardiovascular events (defined as re-infarction, stroke or death). Results: Among a total of 44,157 patients, 39,613 (89.7%) had coronary artery disease only while 4544 (10.3%) had multisite artery disease (4097 (9.3%) had MSAD1 and 447 (1.0%) had MSAD2). Compared with patients with coronary artery disease only, multisite artery disease patients were older, had a longer delay from symptom onset to hospital admission, had more frequently atypical presentation, presented more frequently with non-ST-segment elevation acute coronary syndromes, were more frequently in Killip class III/IV, had higher Charlson comorbidity index, more frequently had three-vessel coronary artery disease and were treated less frequently with evidence-based treatments such as aspirin, P2Y12 inhibitors, or beta-blockers. Similarly, multisite artery disease benefitted less frequently from coronary angiography as well as percutaneous coronary revascularisation. In-hospital mortality was 10.9% in multisite artery disease patients and 4.4% in coronary artery disease-only patients ( P<0.001). Corresponding major adverse cardiovascular events rates were 13.4% and 5.4% ( P<0.001). Cardiogenic shock, re-infarction and cerebrovascular events were significantly more frequent in multisite artery disease patients compared with coronary artery disease-only patients. In multivariable logistic regression analysis, multisite artery disease was identified as an independent predictor of in-hospital mortality (odds ratio 1.69, 95% confidence interval 1.47–1.94, P<0.001). Among multisite artery disease patients, mortality was the highest in MSAD2 individuals (15.4% vs. 10.4% among MSAD1 patients, P=0.001), the same was true for the major adverse cardiovascular events rates (19.1% in MSAD2 patients vs. 12.7% in MSAD1 patients, P<0.001). When stratified for the decade of enrollment, no improvement in mortality or major adverse cardiovascular events rates was observed in multisite artery disease patients. Conclusion: Patients presenting with multisite artery disease were less likely to receive evidence-based therapies than coronary artery disease-only patients and had increased in-hospital morbidity and mortality, with no improvement over time. The worse outcomes were observed among MSAD2 patients. These results should prompt awareness for multisite artery disease as a high-risk condition in the setting of multisite artery disease.

Cell-Derived Microparticles and Acute Coronary Syndromes: Is there a Predictive Role for Microparticles?

2020 ◽  
Vol 27 (27) ◽  
pp. 4440-4468 ◽  
Author(s):  
Effimia Zacharia ◽  
Konstantinos Zacharias ◽  
George-Angelo Papamikroulis ◽  
Dimitrios Bertsias ◽  
Antigoni Miliou ◽  
...  
Keyword(s):  
Clinical Studies ◽  
Acute Coronary Syndromes ◽  
Cardiovascular Events ◽  
Large Scale ◽  
Coagulation Cascade ◽  
Circulating Biomarkers ◽  
Increased Risk ◽  
Coronary Syndromes ◽  
Predictive Role

Background: Despite the recent advances in the treatment of Acute Coronary Syndromes (ACS), patients with ACS are still exposed to an increased risk for adverse cardiovascular events, while their prognosis is difficult to determine. Experimental and clinical studies have shown that cell-derived Microparticles (MPs) are associated with the underlying pathophysiological processes that are responsible for atherogenesis and may be causally implicated in the induction of atherothrombosis. Objective: In the present article, we aimed to review the available evidence regarding the predictive role of MPs in patients with ACS. Results: Evidence suggests that endothelial MPs are associated with future adverse cardiovascular events in patients with ACS. Platelet-derived MPs have been excessively studied, since they have been found to trigger the coagulation cascade; however, their role as predictors of future cardiovascular events remains debatable. The role of red blood cell-derived MPs is more intriguing; they have been proposed as markers of ongoing thrombosis in patients with ACS, while previous studies have shown that they have anti-coagulant properties in healthy individuals. Leukocyte-derived MPs may also have a predictive role, although the studies regarding these are still limited. Last but not least, it was an interesting discovery that circulating MPs can provide information regarding the angiographic lesions in patients with ACS. Conclusion: The concept of MPs as potential circulating biomarkers in patients with ACS holds much promise. However, large-scale clinical studies are required to evaluate whether the measurement of plasma MPs could be of clinical significance and, thus, dictate a more aggressive treatment strategy in patients with high levels of circulating MPs.

scholarly journals The role of Neopterin in cardiovascular disease

2016 ◽  
Vol 68 (2) ◽  
Author(s):  
Mario Pacileo ◽  
Plinio Cirillo ◽  
Salvatore De Rosa ◽  
Grazia Ucci ◽  
Gianluca Petrillo ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Acute Coronary Syndromes ◽  
Cardiovascular Events ◽  
Major Adverse Cardiovascular Events ◽  
Chronic Coronary Artery Disease ◽  
Immune System Activation ◽  
Coronary Syndromes ◽  
Artery Disease

Inflammation plays a key role in the initiation and progression of atherosclerosis but also in the pathophysiology of atheromatous plaque disruption and the development of acute coronary syndromes. Neopterin is a marker of inflammation and of immune system activation, it is synthesized by macrophages, that, once activated, release this substance. Indeed, in clinical evaluation of patients, measurements of plasma levels of neopterin are usually used to evaluate progression of viral infections, renal transplant rejection, severe systemic inflammatory diseases, nephritic syndrome and several autoimmune diseases. This mediator is able to induce a pro-atherothrombotic phenotype in cells of the coronary circulation. Recent data indicate that serum levels of neopterin are elevated in patients with coronary and peripheral artery disease and seem to be a prognostic marker for major adverse cardiovascular events. In particular, neopterin levels predict future major cardiac and vascular adverse events in patients presenting with chronic coronary artery disease, with acute coronary syndromes, and in those with critical limb ischemia. This renders this molecule a useful marker of atherosclerotic plaque activity, permitting the identification of the subjects at highest risk for major adverse cardiovascular events. In line with the above mentioned evidences, patients with high neopterin levels may require aggressive risk factor modification and intensive medical treatment irrespective of the severity of their coronary artery disease. This data suggest a potential clinical use of neopterin as a marker for disease activity in patients with cardiovascular disease.

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