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Impact of Insulin Receptor Substrate-1 rs956115 and CYP2C19 rs4244285 Genotypes on Clinical Outcome of Patients Undergoing Percutaneous Coronary Intervention.

ABSTRACT: Background Insulin receptor substrate-1 (IRS-1) rs956115 is associated with vascular risk in patients with coronary artery disease and concomitant diabetes. CYP2C19*2 (rs4244285) modulates clopidogrel response and predicts the outcome of coronary artery disease. This study was designed to explore the association between IRS-1, CYP2C19*2 genotypes, platelet reactivity, and 1-year outcome in patients with coronary artery disease undergoing percutaneous coronary intervention. Methods and Results Genotyping was performed using an improved multiplex ligation detection reaction technique. Platelet aggregation was assessed by light transmission aggregometry. Major adverse cardiovascular events were defined as a composite of cardiovascular death, myocardial infarction, and ischemic stroke. A total of 2213 consecutive patients were screened and 1614 were recruited. At 1 month, patients with IRS-1 CG genotype had significantly lower levels of ADP-induced platelet aggregation compared with patients with CC homozygotes. Patients with IRS-1 CG or GG genotype had a 2.09-fold higher risk of major adverse cardiovascular events compared with those with CC homozygotes (95% CI, 1.04-4.19; P=0.0376). By comparison, patients with CYP2C19*2 GA or AA genotype had higher ADP-induced platelet aggregation compared with patients with GG homozygotes. Although there was no significant difference in risk of major adverse cardiovascular events between patients with GA/AA and GG genotypes, patients with GA genotype had a 2.19-fold higher risk than those with GG homozygotes (95% CI, 1.13-4.24; P=0.0200). No interaction between IRS-1 and CYP2C19*2 genotypes was observed. Conclusions In patients following percutaneous coronary intervention, IRS-1 GG/CG and CYP2C19*2 GA genotypes were associated with 2.09- and 2.19-fold increased cardiovascular risk, respectively, at 1-year follow-up. The association between IRS-1 genotypes and major adverse cardiovascular events appeared to be independent of known clinical predictors. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01968499.

SUBMITTER: Zong J

PROVIDER: S-EPMC9496289 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Impact of Insulin Receptor Substrate-1 rs956115 and CYP2C19 rs4244285 Genotypes on Clinical Outcome of Patients Undergoing Percutaneous Coronary Intervention.

Zong Jiaxin J Tang Yingdan Y Wang Tong T Ullah Inam I Xu Ke K Wang Jing J Chen Pengsheng P Chen Zengguang Z Zhu Tiantian T Chen Jun J Li Jimin J Wang Fei F Yang Lu L Fan Yuansheng Y Shi Lu L Gong Xiaoxuan X Eikelboom John W JW Zhao Yang Y Li Chunjian C

Journal of the American Heart Association 20220805 16

Background Insulin receptor substrate-1 (IRS-1) rs956115 is associated with vascular risk in patients with coronary artery disease and concomitant diabetes. CYP2C19*2 (rs4244285) modulates clopidogrel response and predicts the outcome of coronary artery disease. This study was designed to explore the association between IRS-1, CYP2C19*2 genotypes, platelet reactivity, and 1-year outcome in patients with coronary artery disease undergoing percutaneous coronary interven ...[more]

PMID: 35929455

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Project description:BackgroundThrombocytopenia was intuitively considered to be associated with higher risk of bleeding and multiple comorbidities after percutaneous coronary intervention (PCI). However, controversial results exist, and the real-world clinical impact of thrombocytopenia in patients undergoing PCI is largely unknown. The aim of this study was to evaluate the influence of baseline thrombocytopenia on the prognosis of patients undergoing PCI.MethodsUsing the West China Hospital Inpatient Sample database, patients who underwent PCI were identified from August 2012 to January 2019. Baseline thrombocytopenia was defined as a preprocedural platelet count of 100 × 109/L or less obtained from a routine blood sample taken within 48 hours before coronary PCI. The clinical effect of the advanced thrombocytopenia group (≤85 × 109/L), according to the median value of platelet count in the thrombocytopenia cohort, was further assessed. The primary outcome was a composite of in-hospital death, bleeding events, and post-PCI transfusion.ResultsOf 9531 patients enrolled in our study, 936 had baseline thrombocytopenia and 8595 patients did not have. There were no significant differences in the primary outcome between the two groups. However, advanced thrombocytopenia was independently associated with higher risk of primary outcome (OR 1.67, 95% CI 1.06 to 2.65, p = 0.029). Acute coronary syndrome (ACS) patients with thrombocytopenia were associated with higher odds of major bleeding (BARC ≥ 2) (OR 2.56, 95% CI 1.24 to 5.44, p = 0.011). Compared with the nonthrombocytopenia group, the thrombocytopenia group with ticagrelor use had higher odds of major bleeding (OR 9.7, 95% CI 1.57 to 60.4 versus OR 0.22, 95% CI 0.03 to 1.69, interaction p = 0.025).ConclusionsIt seems feasible for patients with thrombocytopenia to receive PCI, but close attention should be paid to advanced thrombocytopenia, the risk of postprocedure bleeding in ACS patients, and the use of more potent P2Y12 inhibitor.

Project description:PurposeMalnutrition has been shown to be related to adverse clinical outcomes in patients with heart failure, hypertension, atrial fibrillation and other cardiovascular diseases. However, in the patients with coronary artery disease (CAD) undergoing percutaneous coronary interventions (PCI), especially in the elderly, the association of nutritional state and all-cause mortality remains unknown. We aimed to investigate the association of malnutrition with all-cause mortality in the elder patients undergoing PCI.Patients and methodsBased on the largest retrospective and observational cohort study from January 2007 to December 2017, the Controlling Nutritional Status (CONUT) score was applied to 21,479 consecutive patients with age ≥60 who undergoing PCI for nutritional assessment. Participants were classified as absent, mild, moderate and severe malnutrition by CONUT score. The Kaplan-Meier method was used to compare all-cause mortality among the above four groups. Multivariable Cox proportional hazard regression analyses were performed to examine the association of malnutrition with all-cause mortality.ResultsAccording to the CONUT score, 48.19%, 15.08% and 0.94% patients were mildly, moderately and severely malnourished, respectively. During a median follow-up of 5.16 years (interquartile range: 3.02 to 7.89 years), 3173 (14.77%) patients died. Kaplan-Meier analysis showed that the risk of all-cause mortality was significantly higher in patients with a worse nutritional status. Compared with normal nutritional state, malnutrition was associated with significantly increased risk for all-cause mortality (adjusted hazard ratio for mild, moderate and severe degrees of malnutrition, respectively: 1.20 [95% confidence interval (CI): 1.09 to 1.33], 1.32 [95% CI: 1.17 to 1.49] and 1.76 [95% CI: 1.33 to 2.33]).ConclusionMalnutrition is prevalent among elderly patients with CAD undergoing PCI, and is strongly related to the all-cause mortality increasing. For elderly patients with CAD undergoing PCI, it is necessary to assess the status of nutrition, and evaluate the efficacy of nutritional interventions.

Project description:ObjectivesAnaemia has an adverse impact on the outcome in the general patient population undergoing percutaneous coronary intervention (PCI). The aim of this study was to analyse the impact of anaemia on the 12-month clinical outcome of patients with atrial fibrillation (AF) undergoing PCI and therefore requiring intense antithrombotic treatment. We hypothesised that anaemia might be associated with a worse outcome and more bleeding in these anticoagulated patients.SettingData were collected from 17 secondary care centres in Europe.ParticipantsConsecutive patients with AF undergoing PCI were enrolled in the prospective, multicenter AFCAS (Atrial Fibrillation undergoing Coronary Artery Stenting) registry. Altogether, 929 patients participated in the study. Preprocedural haemoglobin concentration was available for 861 (92.7%; 30% women). The only exclusion criteria were inability or unwillingness to give informed consent. Anaemia was defined as a haemoglobin concentration of <12 g/dL for women and <13 g/dL for men.Outcome measuresThe primary endpoint was occurrence of major adverse cardiac and cerebrovascular events (MACCE) or bleeding events.Results258/861 (30%) patients had anaemia. Anaemic patients were older, more often had diabetes, higher CHA2DS2-VASc scores, prior history of heart failure, chronic renal impairment and acute coronary syndrome. Anaemic patients had more MACCE than non-anaemic (29.1% vs 19.4%, respectively, p=0.002), and minor bleeding events (7.0% vs 3.3%, respectively, p=0.028), with a trend towards more total bleeding events (25.2% vs 21.7%, respectively, p=0.059). No difference was observed in antithrombotic regimens at discharge. In multivariate analysis, anaemia was an independent predictor of all-cause mortality at 12-month follow-up (hazard ratio 1.62, 95% CI 1.05 to 2.51, p=0.029).ConclusionsAnaemia was a frequent finding in patients with AF referred for PCI. Anaemic patients had a higher all-cause mortality, more thrombotic events and minor bleeding events. Anaemia seems to be an identification of patients at risk for cardiovascular events and death.Trial registrationClinicalTrials.gov number NCT00596570.

Dataset Information

Impact of Insulin Receptor Substrate-1 rs956115 and CYP2C19 rs4244285 Genotypes on Clinical Outcome of Patients Undergoing Percutaneous Coronary Intervention.

Publications

Impact of Insulin Receptor Substrate-1 rs956115 and CYP2C19 rs4244285 Genotypes on Clinical Outcome of Patients Undergoing Percutaneous Coronary Intervention.

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