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Variants of PEAR1 Are Associated With Outcome in Patients With ACS and Stable CAD Undergoing PCI.

ABSTRACT: Introduction: Platelet endothelial aggregation receptor 1 (PEAR1) triggers platelet aggregation and is expressed in platelets and endothelial cells. Genome-wide association studies (GWAS) showed an association between platelet function and single-nucleotide polymorphisms (SNPs) in PEAR1. Methods: In 582 consecutive patients with stable coronary artery disease (CAD) or acute coronary syndrome (ACS) scheduled for PCI and treated with ASA and Clopidogrel, Prasugrel, or Ticagrelor, SNP analysis for rs12566888, rs2768759, rs41273215, rs3737224, and rs822442 was performed. During a follow-up period of 365 days after initial PCI, all patients were tracked for a primary endpoint, defined as a combined endpoint consisting of either time to death, myocardial infarction (MI) or ischemic stroke. All cause mortality, MI and ischemic stroke were defined as secondary endpoints. Results: Multivariable Cox model analysis for the primary endpoint revealed a significantly increased risk in homozygous PEAR1 rs2768759 minor allele carriers (hazard ratio, 3.16; 95% confidence interval, 1.4-7.13, p = 0.006). Moreover, PEAR1 rs12566888 minor allele carriers also showed an increased risk in all patients (hazard ratio, 1.69; 95% confidence interval, 0.87-3.27, p = 0.122), which was marginally significant in male patients (hazard ratio, 2.12; 95% confidence interval, 1.02-4.43, p = 0.045; n = 425). Conclusions: To the best of our knowledge, this is the first study showing that distinct genetic variants of PEAR1 are associated with cardiovascular prognosis in high risk patients undergoing PCI and treated with dual anti platelet therapy.

SUBMITTER: Stimpfle F

PROVIDER: S-EPMC5962768 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Variants of PEAR1 Are Associated With Outcome in Patients With ACS and Stable CAD Undergoing PCI.

Stimpfle Fabian F Bauer Maike M Rath Dominik D Schaeffeler Elke E Schwab Matthias M Gawaz Meinrad M Winter Stefan S Geisler Tobias T

Frontiers in pharmacology 20180515

Introduction: Platelet endothelial aggregation receptor 1 (PEAR1) triggers platelet aggregation and is expressed in platelets and endothelial cells. Genome-wide association studies (GWAS) showed an association between platelet function and single-nucleotide polymorphisms (SNPs) in PEAR1. Methods: In 582 consecutive patients with stable coronary artery disease (CAD) or acute coronary syndrome (ACS) scheduled for PCI and treated with ASA and Clopidogrel, Prasugrel, or Ticagrel ...[more]

PMID: 29867494

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Project description:Bile acids play important roles in lipid metabolism and glucose homeostasis. Limited research exist on the association between serum total bile acid (TBA) levels and major adverse cardiovascular events (MACEs) in patients with acute coronary syndrome (ACS), particularly those with comorbid type 2 diabetes mellitus (T2DM). This study was conducted to examine the relationship between baseline serum TBA level and T2DM status in patients with ACS after percutaneous coronary intervention (PCI) and to identify the predictive value of TBA levels for a 2-year risk of MACEs. 425 ACS patients underwent PCI were recruited and divided into three groups based on baseline serum TBA concentration. An analysis of the association between the T2DM status and baseline serum TBA levels was conducted using univariate linear regression and multivariate linear regression. The predictive relevance of serum TBA levels was evaluated using the receiver operating characteristic (ROC) curve and Cox regression. Kaplan-Meier curves were employed to analyze the differences among groups in predicting MACEs over a 2-year follow-up period. Baseline serum TBA levels were higher in ACS patients who were diagnosed with T2DM (the median 3.6 µmol/L) than those without T2DM (the median 3.0 µmol/L). T2DM status in ACS patients was positively correlated with baseline serum TBA concentrations (β: 1.7, 95% confidence interval [CI] 0.3-3.0), particularly in the male (β: 2.0, 95% CI 0.3-3.6) and 50-69-year-old (β: 2.5, 95% CI 0.6-4.4) populations. The areas under the ROC curve of baseline serum TBA levels predicted MACEs in ACS and ACS-T2DM patients following PCI were 0.649 (95% CI 0.595-0.703) and 0.783 (95% CI 0.685-0.881), respectively. Furthermore, Cox regression analysis showed that baseline serum TBA level was associated with the occurrence of MACEs in patients with ACS after PCI over a 2-year follow-up period, especially in those diagnosed with T2DM, whose baseline TBA concentration was lower than 10.0 µmol/L. ACS Patients with T2DM had higher serum TBA levels. TBA level at baseline was an independent predictor of MACEs in ACS patients who underwent PCI, especially with comorbid T2DM.

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Dataset Information

Variants of PEAR1 Are Associated With Outcome in Patients With ACS and Stable CAD Undergoing PCI.

Publications

Variants of PEAR1 Are Associated With Outcome in Patients With ACS and Stable CAD Undergoing PCI.

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