Mechanisms of aspirin resistance

Background 
The PlA2 polymorphism of glycoprotein IIIa (GPIIIa) has been previously identified as being associated with myocardial infarction (MI), but whether this represents a true association is entirely unclear due to differences in findings from different studies. We performed a meta-analysis to evaluate whether this polymorphism is a risk factor for MI.


Methods 
Electronic databases (MEDLINE and EMBASE) were searched for all articles evaluating genetic polymorphisms of GPIIIa. For studies where acute coronary events were recorded in association with genetic analysis, pooled odds ratios (ORs) were calculated using fixed-effects and random-effects models. The primary outcome measure was MI, and a secondary analysis was also performed for acute coronary syndromes (ACS) more generally.


Findings 
57 studies were eligible for statistical analysis and included 17,911 cases and 24,584 controls. Carriage of the PlA2 allele was significantly associated with MI (n = 40,692; OR 1.077, 95% CI 1.024–1.132; p = 0.004) but with significant publication bias (p = 0.040). The degree of association with MI increased with decreasing age of subjects (≤45 years old: n = 9,547; OR 1.205, 95% CI 1.067–1.360; p = 0.003) and with adjustment of data for conventional cardiovascular risk factors (n = 12,001; OR 1.240, 95% CI 1.117–1.376; p<0.001). There was a low probability of publication bias for these subgroup analyses (all p<0.05).


Conclusions 
The presence of significant publication bias makes it unclear whether the association between carriage of the PlA2 allele and MI is true for the total population studied. However for younger subjects, the relative absence of conventional cardiovascular risk factors results in a significant association between carriage of the PlA2 allele and MI.

/pdf/the-pla1-a2-polymorphism-of-glycoprotein-iiia-as-a-risk-2jr3i2wo9x.pdf

The PlA1/A2 polymorphism of glycoprotein IIIa as a risk factor for myocardial infarction: a meta-analysis.

AIM Aspirin resistance (AR) is common in Chinese stroke patients taking antiplatelet medications; however, few studies have documented the role of cyclooxygenase (COX)-1 C50T and COX-2 G765C polymorphisms in AR. The aim of this study was to investigate the prevalence of AR in Chinese stroke patients and the relationships between AR and COX-1 C50T and COX-2 G765C polymorphisms, and to evaluate the effect of these polymorphisms on platelet response to aspirin. METHODS We prospectively enrolled 634 Chinese stroke patients. Platelet aggregation testing was performed before and after aspirin administration. The pre- and post-aspirin levels of 11-dehydrothromboxane B(2) (11-dTxB(2)) were determined in urine samples. COX-1 C50T and COX-2 G765C genotypes were determined by a polymerase chain reaction-allelic restriction assay. RESULTS AR was detected in 129 patients (20.4%), aspirin semi-resistance (ASR) was detected in 28 patients (4.4%), and aspirin sensitivity (AS) was detected in 477 patients (75.2%). There was no association between COX-1 C50T or COX-2 G765C polymorphisms and ASR+AR. Aspirin could efficiently reduce 11-dTxB(2) production by approximately 75%. In addition, platelet aggregation, both in response to arachidonic acid (AA) and adenosine 5'-diphosphate (ADP), was inhibited by more than 80% and 40%, respectively; however, the percentage reduction in platelet aggregation and 11-dTxB(2) levels was not significantly different between the COX-1 C50T and COX-2 G765C genotypes (p＞0.05). CONCLUSIONS There was no association between COX-1 C50T and COX-2 G765C polymorphisms and AR in Chinese stroke patients. In addition, COX-1 C50T and COX-2 G765C polymorphisms had no effect on the platelet response to aspirin.

Platelet response to aspirin in Chinese stroke patients is independent of genetic polymorphisms of COX-1 C50T and COX-2 G765C.

The aim of this study was to investigate the association among the PlA1/A2 gene polymorphism, laboratory aspirin resistance and adverse clinical outcomes in coronary artery disease (CAD) patients who were on aspirin maintainance therapy. A comprehensive literature search was performed and 35 eligible clinical trials including 19025 CAD patients were recruited. Adverse clinical outcomes involving all-cause death, non-fatal myocardial infarction (MI), ischemic stroke and target vessel revascularization (TVR) were analyzed. The definition of aspirin resistance in each study was accepted. Meta-analysis was performed using the Review Manager 5.3.5 System. In CAD patients, the PlA2 gene carriers had similar incidence of laboratory aspirin resistance compared to those with PlA1/A1 genotype [29.7% vs 28.3%, OR = 0.94 (95% CI 0.63 to 1.40, P = 0.74)], and there were no significant differences in the adverse clinical outcomes between the PlA2 carriers and the PlA1/A1 genotype patients. However, the laboratory aspirin non-responders had higher risks of death [7.9% vs. 2.5%, OR = 2.42 (95% CI 1.86 to 3.15, P < 0.00001)] and TVR [4.5% vs. 1.7%, OR = 2.20 (95% CI 1.19 to 4.08, P = 0.01)] compared to the responders. In aspirin-treated CAD patients, the laboratory aspirin resistance predicts all-cause death and TVR. However, the PlA1/A2 gene polymorphism predicts neither the laboratory aspirin response nor the clinical outcomes.

/pdf/association-among-pla1-a2-gene-polymorphism-laboratory-35i3mb3ygj.pdf

Association among PlA1/A2 gene polymorphism, laboratory aspirin resistance and clinical outcomes in patients with coronary artery disease: An updated meta-analysis

Genomics and its related fields have expanded rapidly, primarily because of the potential utility for clinical decision making and improving our understanding of the pathophysiology of complex conditions. The state of the science and technology associated with this field is such that current and future health care providers, when consulting with new patients about their acquired brain injury and options for rehabilitation, will use genetic information as a routine part of the process, which may include information received from a laboratory report that uses transcriptomic data, informs regarding patient prognosis, and makes recommendations for individualized therapeutic approaches to optimize recovery. This may sound like science fiction, but, in the field of oncology, it is the norm for breast cancer and, more recently, for colon cancer, with expansion to other types of cancer on the horizon as research data continue to contribute to the understanding of the pathophysiology of these conditions. Something similar for rehabilitation after acquired brain injury is much further off on the horizon. However, it is a possibility that will never be realized if the community of scientists and health care providers who work with these patients do not have the knowledge or expertise to embrace genomics and related approaches. This article discusses these approaches, some practical considerations for using such approaches, and what is currently published in this area with regard to brain injury.

Genomic, transcriptomic, and epigenomic approaches to recovery after acquired brain injury.

Platelet glycoprotein IIb/IIIa is a membrane receptor which plays a key role in coronary artery disease and thrombotic events. However, there is a considerable controversy regarding the clinical impact of glycoprotein IIIa platelet antigen 1 (PlA1)/platelet antigen 2 (PlA2) polymorphism as a risk factor for myocardial infarction. To evaluate the association between glycoprotein IIIa PlA1/PlA2 polymorphism and 1-year cardiovascular events occurrence in aspirin-treated patients with stable coronary artery disease. We prospectively included 188 postacute coronary syndrome patients (183 men) aged 59 ± 10 years and receiving aspirin (250 mg/day). The clinical outcome at 1 year was the composite end point of nonfatal myocardial infarction, stroke, recurrent unstable angina or cardiac death. Genotyping for PlA1/PlA2 polymorphism was conducted using PCR and restriction fragment length polymorphism analysis. The genotype distribution of glycoprotein IIIa PlA1/PlA2 polymorphism was PlA1/PlA1, 55.3%; PlA1/PlA2, 39.3% and PlA2/PlA2, 4%. Incidence of composite end point in homozygous PlA1/PlA1 carriers was significantly higher than in PlA2/PlA2 and PlA1/PlA2 patients [14.4 vs. 3.6% odds ratio 4.5 (1.2-16.6, 95% confidence interval); P = 0.012]. Multivariate analysis identified three strong predictive factors of cardiac death: age more than 65 years [odds ratio = 6.8, (1.4-34, 95% confidence interval); P = 0.018], ventricular ejection fraction less than 50% [odds ratio = 8.6, (1.7-42.6, 95% confidence interval); P = 0.008] and homozygous PlA1/PlA1 genotype [odds ratio = 8.8, (1.0-78.6, 95% confidence interval); P = 0.014]. Our results demonstrated that glycoprotein IIIa PlA1/PlA1 genotype carriers have a significantly increased risks of acute vascular ischemic events associated with a poor prognosis at 1 year. These postacute coronary syndrome patients might require an optimized secondary antithrombotic prophylaxis strategy.

Platelet glycoprotein IIIa (platelet antigen 1/platelet antigen 2) polymorphism and 1-year outcome in patients with stable coronary artery disease.

In this study, we evaluate the relationships between aspirin nonresponsiveness and the cyclooxygenase-1 (Cox-1) gene C50T polymorphism in stable coronary artery disease (CAD) in Tunisian patients. ...

The Cyclooxygenase-1 C50T Polymorphism Is Not Associated with Aspirin Responsiveness Status in Stable Coronary Artery Disease in Tunisian Patients

Background: Mitral stenosis is the most common valvular heart lesion found in pregnancy. When severe, it leads to significant risk of mortality for both mother and fetus, since the hemodynamic adaptations to pregnancy are badly tolerated. Many pregnant women with mitral stenosis present in a critically ill condition. The role of Balloon Mitral Valvotomy (BMV) in such patients is ill-defined.

Purpose: We sought to evaluate the feasibility, efficacy and safety of emergent BMV in pregnant patients with refractory pulmonary edema and to determine maternal and fetal outcome.

Methods: Of 88 patients undergoing BMV during pregnancy from January 1990 to December 2011 in Cardiology A Department of Monastir Hospital, 28 women were in New York Heart Association functional class IV and underwent emergent BMV. During the procedure, radiation exposure was minimized by means of total abdominal and pelvic shielding.

Results: The mothers's mean age at the time of BMV was 28.86±5.7 (range 19–43) years, and the gestation period was 30±5.1 (range 20 –39) weeks. Ten patients were primiparas. Mitral valve (MV) was assessed using the Wilkins score which averaged 7.4±1.8 (range 4 to 14). Fluoroscopy time was 7.8±1.9 minutes.

The BMV procedure was successful in 25 (89.3%) patients with a dramatic improvement in patient symptoms.

The mitral valve area increased from 0.8±0.2 cm2 to 2.2±0.42 cm2 (p < 0.0001). The mitral valve pressure gradient decreased from 22.2±9.3 to 5.7±4 mm Hg (p < 0.0001). The left atrial pressure decreased from 29.4±9.3 to 15.4±7.3 mm Hg (p < 0.0001). The pulmonary artery pressure decreased from 58.8±21.1 to 37.2±14.3 mm Hg (p < 0.0001).

One patient developed severe mitral regurgitation and required urgent mitral valve replacement. There was no maternal mortality or significant foetal morbidity.

Pregnancy was uneventful in all patients, all babies were born at full term by spontaneous vaginal delivery in 24 cases (85.7%) and by cesarian section for obstetrical reasons in 4 (14.3%), with no obvious malformations (4 of them were twin babies). None of the babies needed intensive care monitoring. The average Apgar scores at 1 min were 8.6±1. The mean birth weight was 3.1 Kilograms ranged from 1.9 to 3.8 kg.

Conclusion: During pregnancy, emergent BMV is safe and feasible in patients with symptomatic mitral stenosis and severe pulmonary edema. There is marked symptomatic relief, along with excellent maternal and fetal outcomes.

https://academic.oup.com/eurheartj/article-pdf/34/suppl_1/P2124/9255368/eht308.P2124.pdf

Emergent balloon mitral valvotomy in pregnant women presenting with refractory pulmonary edema

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

M. Hassine

Author Tools

Chat about Author

Papers

Platelet glycoprotein IIIa (platelet antigen 1/platelet antigen 2) polymorphism and 1-year outcome in patients with stable coronary artery disease.

The Cyclooxygenase-1 C50T Polymorphism Is Not Associated with Aspirin Responsiveness Status in Stable Coronary Artery Disease in Tunisian Patients

Emergent balloon mitral valvotomy in pregnant women presenting with refractory pulmonary edema