Application of Genetic Testing for CYP 450 Polymorphism to Predict Response to Clopidogrel Inpatient Undergoing PCI

AbstractIntroduction: The anti-platelet agent clopidogrel is a commonly prescribed medication in patients in patients who are undergoing percutaneous coronary intervention. Response to clopidogrel varies substantially due to genetic and acquired factors. Patients who experience recurrent cardiovascular ischemic or thrombotic events while taking clopidogrel are typically described as non-responsive or resistant. In our study was planned to assess the utility of pharmaco-genetic testing (CYP2C19) for clopidogrel response and application of the data for modification of anti-platelet regimen accordingly. Methods: This is a prospective nonrandomized ethical committee approved study from our institute. We included the post PCI patients presented with chronic stable angina and acute coronary syndrome (who has less bleeding risk score) with good left ventricular function. Along with the demographic and clinical features, we collected the data of platelet aggregation test (light transmission of aggregometry), CYP2C19 genetic analysis test and clinical outcome at the time of discharge, at 15days of discharge and end of 3 months. CYP2C19 genetic analysis is done by method of DNA based clopidogrel resistance genotyping test. We grouped the cases as extensive metabolizers (EM) and intermediate metabolizers (IM) depending on CYP2C19genetic analysis into two groups.Results: A total of 33 patients are included in this study. Among 33 cases, 25(75.7%) cases are male patients and 8(24.2%) cases are female patient, 18 (54.5%) patients are diabetic Mellitus, 20(60.6%) patient are hypertensives, 7(21.2%) cases are smokers and 5 (15.1%) case are alcoholic. We have diagnosed 20(60.6%) cases of unstable angina and 13(39.4%) cases of chronic stable angina. The average Meheran bleeding risk score is 9.8. Age, risk factors are comparable between the the EM and IM group. But presentation of ACS is more in IM (p=0.001).Follow up at 3 months, one died suddenly (probable stent thrombosis) in EM group. No other MACE occurred in both the groups. Multivariate analysis with binary logistic regression showed that only presentation as ACS is statistically significant in IM (p=0.001). Platelet aggregation showed tendency towards statistical significance (p=0.08) in EM patient. With all other parameters including MACE (p=0.3), there is no statistical significance by multivariate analysis.Conclusion: In our small prospective clinical and genetic analysis of clopidogrel metabolizer status has shown that intermediate metabolizer status of the patient is statistically more in unstable angina (p=0.003). There is tendency for statistically significance between the platelet aggregation test (p=0.08) and extensive metabolizer status of the patient. Whatever may be the status of the clopidogrel metabolizing condition, there is no difference in MACE.

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Diagnostic Role of Plasma MicroRNA-21 in Stable and Unstable Angina Patients and Association with Aging

Cardiology Research and Practice ◽

10.1155/2020/9093151 ◽

2020 ◽

Vol 2020 ◽

pp. 1-7

Author(s):

Md Sayed Ali Sheikh

Keyword(s):

Unstable Angina ◽

Stable Angina ◽

Healthy Subjects ◽

Age Groups ◽

Chronic Stable Angina ◽

Roc Curves ◽

Circulating Microrna ◽

Clinical Value ◽

Coronary Patients ◽

Plasma Microrna

The present study explored the clinical value of plasma microRNA-21 as a novel biomarker for early prediction of stable and unstable angina patients and its relationship with aging. A total of 255 participants, 123 patients with chronic stable angina, 82 patients with unstable angina, and 50 healthy subjects, were included in our study. Stable coronary and unstable coronary patients were confirmed following AHA/ACC clinical protocols. Total RNA was extracted from plasma by using miRNA-based TRIzol reagent. Plasma miR-21 expression levels were determined by real-time polymerase chain reaction. To evaluate the diagnosis accuracy, the receiver operating characteristic (ROC) curves were used. Plasma microRNA-21 concentration levels were significantly elevated in stable and unstable angina patients as compared with control subjects P<0.001. The area under the ROC curves of circulating microRNA-21 was accurately distinguished in stable angina patients (AUC 0.921) and unstable angina patients (AUC 0.944) from healthy subjects. MicroRNA-21 expression gradually elevated with increasing aging in all the populations. Moreover, the current study also demonstrated that the expression of plasma miR-21 levels was significantly associated with different age groups within healthy subjects and stable and unstable angina patients P<0.001. This research finding suggested that plasma microRNA-21 may be considered as a suitable new biomarker for early detection of stable and unstable angina patients, and it has a strong correlation with aging.

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Comparison of the histopathology of culprit lesions in chronic stable angina, unstable angina, and myocardial infarction

Clinical Cardiology ◽

10.1002/clc.4960200712 ◽

1997 ◽

Vol 20 (7) ◽

pp. 651-655 ◽

Cited By ~ 9

Author(s):

Jacob I. Haft ◽

Domenic L. Mariano ◽

Jonathan Goldstein ◽

Bruce Waller

Keyword(s):

Myocardial Infarction ◽

Unstable Angina ◽

Stable Angina ◽

Chronic Stable Angina

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Pre-operative aspirin decreases platelet aggregation and increases post-operative blood loss — a prospective, randomised, placebo controlled, double-blind clinical trial in 100 patients with chronic stable angina

European Journal of Cardio-Thoracic Surgery ◽

10.1016/1010-7940(94)90081-7 ◽

1994 ◽

Vol 8 (8) ◽

pp. 404-409 ◽

Cited By ~ 100

Author(s):

P KALLIS ◽

J TOOZE ◽

S TALBOT ◽

D COWANS ◽

D BEVAN ◽

...

Keyword(s):

Clinical Trial ◽

Platelet Aggregation ◽

Blood Loss ◽

Stable Angina ◽

Chronic Stable Angina ◽

Operative Blood Loss ◽

Double Blind ◽

Double Blind Clinical Trial

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Advantage of Trans Radial Coronary Angiography: A Study of 40 Patients

University Heart Journal ◽

10.3329/uhj.v5i2.4553 ◽

1970 ◽

Vol 5 (2) ◽

pp. 52-55

Author(s):

Mohammad Saifullah Patwary ◽

Mir Jamal Uddin ◽

Md Mukhlesur Rahman ◽

Syed Azizul Haque ◽

Md Khurshed Ahmed ◽

...

Keyword(s):

Coronary Angiography ◽

Unstable Angina ◽

Radial Artery ◽

Stable Angina ◽

Tertiary Care ◽

Chronic Stable Angina ◽

Attractive Alternative ◽

Care Hospital ◽

Femoral Approach ◽

The Mean

Percutaneous coronary catheterization and revascularization are commonly performed all over the world. Among various access sites for coronary interventions, most cardiologists favour the femoral approach, while the procedure via the radial artery is only performed by a limited number of operators. In this study, we aimed to assess the procedural outcome of the trans-radial coronary angiography (CAG) among the patients in a tertiary care hospital in Bangladesh. This prospective observational study was carried out among 40 patients underwent trans-radial coronary angiography. The study was conducted for a period of one year. Indication of CAG including chronic stable angina, unstable angina, non ST elevated myocardial infarction (MI) and ST elevated MI were observed. Procedural attempt, success rate and outcome with or without complications were mentioned. Out of 40 patients, 70% were male and 30% were female (M: F=2.3:1). Among the patients undergoing trans-radial CAG, 50% had dyslipidemia and HTN, 55% had family history of IHD, 52.5% were smoker and 20% had DM. Most of the patients underwent trans-radial CAG due to unstable angina (52.5%) and this was followed by ST elevated MI (30%), non ST elevated MI (10%) and chronic stable angina (7.5%).The mean procedural time was 19.85±1.3 minutes. The fluoroscopy time was 9.60±.9 minutes. The mean hemostasis time was 9.00±7.0 minutes. All patients were ready for discharge within 24 hours. Only 7.5% patients experienced spasm of radial artery during CAG. No other complications were detected. Trans-radial approach is an attractive alternative to conventional trans-femoral approach, in suitable patients at the hand of experienced operator, with appropriate hardwire and should be ready to cross over, to the femoral approach when needed. Keywords: Trans-radial coronary angiography; trans-femoral approach. DOI: 10.3329/uhj.v5i2.4553 University Heart Journal Vol.5(2) July 2009 pp.52-55

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Oxidative Stress and Homocysteine in Coronary Artery Disease

Clinical Chemistry ◽

10.1093/clinchem/47.5.887 ◽

2001 ◽

Vol 47 (5) ◽

pp. 887-892 ◽

Cited By ~ 90

Author(s):

Viviana Cavalca ◽

Giuliana Cighetti ◽

Fabrizia Bamonti ◽

Alessandro Loaldi ◽

Luana Bortone ◽

...

Keyword(s):

Oxidative Stress ◽

Coronary Artery Disease ◽

Lipid Peroxidation ◽

Coronary Artery ◽

Unstable Angina ◽

Stable Angina ◽

Chronic Stable Angina ◽

Cardiovascular Patients ◽

Significant Difference ◽

Artery Disease

Abstract Background: Oxidative stress is present in cardiovascular diseases (CVDs), and hyperhomocysteinemia, an independent risk factor for these diseases, may play a role by inducing production of oxygen free radicals. Methods: To evaluate the possible role of homocysteine (Hcy) in inducing oxidative stress in coronary artery disease (CAD), plasma Hcy was measured in 68 consecutive cardiovascular patients, and plasma malondialdehyde (MDA), both free and total (free + bound), was measured in 40 patients with CAD (18 with chronic stable angina and 22 with unstable angina). As controls, we tested 70 healthy volunteers. Hcy was measured by an immunoenzymatic method and MDA, an index of lipid peroxidation, by gas chromatography–mass spectrometry. Results: Plasma Hcy concentrations were significantly higher in cardiovascular patients than in controls (10.2 vs 8.9 μmol/L; P <0.0002), with no significant difference between values in the stable and unstable angina subgroups. Similarly, total MDA was significantly higher in the CAD group than in the controls (2.6 vs 1.3 μmol/L; P <0.00001), again with no significant difference between stable and unstable angina patients. By contrast, free MDA, which was significantly higher in the CAD patients than the controls (0.4 vs 0.2 μmol/L; P <0.00001), was also significantly higher in the unstable than in the stable angina group (0.5 vs 0.3 μmol/L; P <0.03). However, no correlation was observed among Hcy and free and total MDA. Conclusions: Our findings show that a moderate increase of Hcy is associated with CVD but that Hcy at the detected values cannot be considered completely responsible for oxidative damage. That lipid peroxidation is involved in CAD is shown by our observation of significantly increased plasma free and total MDA concentrations compared with controls. Moreover, free MDA values discriminated between unstable and chronic stable angina, and could thus represent a new diagnostic tool.

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