THE IMPACT OF CYP2C19 GENOTYPE ON ENDOTHELIAL FUNCTION, ARTERIAL STIFFNESS AND CARDIOVASCULAR EVENTS IN PATIENTS WITH CORONARY ARTERY DISEASE RECEIVING CLOPIDOGREL

Abstract Background Lipoprotein-associated Phospholipase A2 (Lp-PLA2), has inflammatory and atherogenic actions in the vascular wall. We investigate the impact of high Lp-PLA2 levels on endothelial function and arterial stiffness on patients with coronary artery disease (CAD). Methods We enrolled 374 consecutive patients with stable CAD (mean age 61±11 years). Endothelial function was evaluated by flow-mediated dilation (FMD) and reflected waves with augmentation index (AIx) of the central aortic pressure. Serum levels of Lp-PLA2 were measured with ELISA. Results In the studied population the median values of Lp-PLA2 levels was 125 (96–152) μg/L. There was no difference between subjects with Lp-PLA2 levels above and below 125μg/L concerning classical risk factors for CAD. Importantly, subjects with Lp-PLA2 values ≥125μg/L had significantly impaired FMD (4.44±2.19% vs. 4.89±2.07%, p=0.04) and AIx values (25.21±8.70% vs. 23.06±9.47%, p=0.03), compared to participants with lower Lp-PLA2 serum levels. A linear regression analysis revealed that Lp-PLA2 ≥125μg/L negatively relates to impaired FMD [b=−0.54 (95% CI: −1.05 to −0.02), p=0.04] and AIx values [b=2.14 (95% CI: 0.18–4.01), p=0.03] independently of cofounders. Conclusions Elevated Lp-PLA2 relates to endothelial dysfunction and arterial stiffness in CAD patients. These findings highlight the significant role of Lp-PlA2 in the process of atherosclerosis. Funding Acknowledgement Type of funding source: None

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The Impact of Cytochrome P450 2C19 Polymorphism on Cardiovascular Events in Indonesian Patients with Coronary Artery Disease

Clinical Cardiology and Cardiovascular Medicine ◽

10.33805/2639.6807.104 ◽

2017 ◽

pp. 18-24

Author(s):

Muzakkir Amir ◽

Mirnawati Mappiare ◽

Paskalis Indra

Keyword(s):

Myocardial Infarction ◽

Coronary Artery Disease ◽

Platelet Aggregation ◽

Cardiovascular Events ◽

Cardiovascular Death ◽

Cyp2c19 Genotype ◽

Cyp2c19 Polymorphism ◽

Cytochrome P450 2C19 ◽

Artery Disease ◽

The Impact

Background: The polymorphism of cytochrome P450 2C19 (CYP2C19) has been documented as the determinant variability in the antiplatelet effect of clopidogrel. The relation between CYP2C19 polymorphism and the antiplatelet efficacy of clopidogrel in Indonesian patients with coronary artery disease (CAD) is unknown. To address this issue, we examined the distribution of CYP2C19 genotypes and platelet aggregation, and assessed the impact of CYP2C19 polymorphism on response to clopidogrel and cardiovascular events. Methods: This observational analytic study with prospective cohort approach was conducted in Wahidin Sudirohusodo and Hasanuddin University Hospital, Makassar. We measured the CYP2C19 genotype by polymerase chain reaction-restriction fragment linked polymorphism (PCR-RFLP) method and platelet aggregation by optical platelet aggregometry with 10 μmol of adenosine diphosphate (ADP) in 69 patients with stable CAD who were treated with clopidogrel. Platelet hyperaggregation was defined as maximal platelet aggregation > 94.3%. The patients were followed up every month at the outpatient department for 6 months or at end point. The end point was acute myocardial infarction, ischemic stroke, or cardiovascular death. Results: Distribution of CYP2C19 alleles were 89.8%, 40.6%, and 11.6%, in CYP2C19*1, CYP2C19*2, and CYP2C19*3, respectively. Distribution of CYP2C19 genotype were 50.7%, 29.0%, 8.7%, 8.7%, and 2.9% in CYP2C19*1/*1, *1/*2, *1/*3, *2/*2, and *2/*3, respectively. Platelet hyper aggregation was more in patients with polymorphism than wild type (p 0.034; OR 3.707) and was associated with cardiovascular events (p 0.030; OR 13.250). There was acute myocardial infarction in 2 patients, ischemic stroke in 1 patient, and cardiovascular death in 1 patient. All of these patients were carrying at least one variant allele of CYP2C19; details of genotype were in two patients with CYP2C19*1/*2, one patient with *2/*2, and one with *2/*3 alleles. Conclusion: CYP2C19*2 and *3 were associated with cardiovascular events due to platelet hyper aggregation.

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LIPOPROTEIN-ASSOCIATED PHOSPHOLIPASE A2 LEVELS ARE ASSOCIATED WITH ENDOTHELIAL FUNCTION AND ARTERIAL STIFFNESS IN PATIENTS WITH STABLE CORONARY ARTERY DISEASE

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(16)32336-1 ◽

2016 ◽

Vol 67 (13) ◽

pp. 2335

Author(s):

Gerasimos Siasos ◽

Evangelos Oikonomou ◽

Marina Zaromitidou ◽

Sotirios Tsalamandris ◽

Konstantinos Mourouzis ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Arterial Stiffness ◽

Endothelial Function ◽

Phospholipase A2 ◽

Stable Coronary Artery Disease ◽

Artery Disease

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INCREMENTAL SIGNIFICANCE OF ENDOTHELIAL FUNCTION ASSESSED BY REACTIVE HYPEREMIA PERIPHERAL ARTERIAL TONOMETRY FOR PREDICTING CARDIOVASCULAR EVENTS IN STABLE PATIENTS WITH CORONARY ARTERY DISEASE

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(12)61494-6 ◽

2012 ◽

Vol 59 (13) ◽

pp. E1493

Author(s):

Yasushi Matsuzawa ◽

Seigo Sugiyama ◽

Eiichi Akiyama ◽

Satoshi Umemura ◽

Kazuo Kimura ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Endothelial Function ◽

Cardiovascular Events ◽

Reactive Hyperemia ◽

Peripheral Arterial Tonometry ◽

Arterial Tonometry ◽

Artery Disease ◽

Peripheral Arterial

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Effects of Hydroxychloroquine on endOthelial function in eLDerly with sleep apnea (HOLD): study protocol for a randomized clinical trial

10.21203/rs.3.rs-345739/v1 ◽

2021 ◽

Author(s):

Letícia Maria Tedesco Silva ◽

Antonio Cortes ◽

Beatriz Rossi ◽

Liliana Boll ◽

Gustavo Waclawovsky ◽

...

Keyword(s):

Coronary Artery Disease ◽

Clinical Trial ◽

Coronary Artery ◽

Sleep Apnea ◽

Endothelial Dysfunction ◽

Endothelial Function ◽

Randomized Clinical Trial ◽

Cardiovascular Events ◽

Gold Standard Method ◽

Artery Disease

Abstract BACKGROUND: Sleep apnea and coronary artery disease are prevalent and relevant diseases. The mechanism by which sleep apnea leads to coronary artery disease remains unclear. Intermittent hypoxia, caused by sleep apnea, leads to inflammation and consequent endothelial dysfunction. Endothelial dysfunction precedes the development of atherosclerotic disease and the occurrence of cardiovascular events. Agents that potentially act to improve endothelial function can help prevent cardiovascular events. Patients using immunomodulators due to rheumatic diseases have a lower prevalence of cardiovascular diseases. However, the potential cardio protective effect of these drugs in patients without autoimmune diseases is not clear. Hydroxychloroquine (HCQ) is an immunomodulator used to treat rheumatoid arthritis and systemic lupus erythematosus. In addition to its anti-inflammatory properties, HCQ reduces cholesterol and blood glucose levels and has antithrombotic effects. The drug is inexpensive and widely available. Adverse effects of HCQ are rare and occur more frequently with high doses.OBJECTIVE: In this randomized clinical trial, the effect of HCQ treatment on endothelial function will be tested in seniors with sleep apnea.METHODS: We will recruit participants over the age of 65 and with moderate-severe sleep apnea from an ongoing cohort. We chose to use this sample already evaluated for sleep apnea for reasons of convenience, but also because the elderly with sleep apnea are vulnerable to heart disease. Endothelial function will be assessed by examining flow-mediated dilation of the brachial artery, the gold standard method, considered an independent predictor of cardiovascular events in the general population and by peripheral arterial tonometry, the most recent and most easily obtained method. Hydroxychloroquine will be used at a dose of 400 mg/daily for eight weeks.DISCUSSION: Our study aim to obtain evidence, albeit preliminary, of the efficacy of hydroxychloroquine in improving endothelial function and reducing cardiovascular risk markers. If the improvement occurs, we plan to design a randomized multicenter clinical trial to confirm the findings.TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04161339

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