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

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.

The impact of CYP2C19 genotype on cardiovascular events and platelet reactivity in patients with coronary artery disease receiving clopidogrel

2013 ◽  
Vol 168 (2) ◽  
pp. 1594-1596 ◽  
Author(s):  
Dimitris Tousoulis ◽  
Gerasimos Siasos ◽  
Marina Zaromitidou ◽  
Evangelos Oikonomou ◽  
Konstantinos Maniatis ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Cardiovascular Events ◽  
Platelet Reactivity ◽  
Cyp2c19 Genotype ◽  
Artery Disease ◽  
The Impact

scholarly journals Impaired Peripheral Microvascular Function and Risk of Major Adverse Cardiovascular Events in Patients With Coronary Artery Disease

2021 ◽  
Author(s):  
An Young ◽  
Mariana Garcia ◽  
Samaah M. Sullivan ◽  
Chang Liu ◽  
Kasra Moazzami ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Cardiovascular Events ◽  
Microvascular Dysfunction ◽  
Cardiovascular Death ◽  
Major Adverse Cardiovascular Events ◽  
End Point ◽  
Artery Disease

Objective: In patients with stable coronary artery disease (CAD), the risk of major adverse cardiovascular events (MACE) remains elevated despite treatment. The role of microvascular dysfunction on MACE beyond traditional risk indicators and inflammation is not well established. We examined whether peripheral microvascular dysfunction is associated with MACE in patients with CAD. Approach and Results: Microvascular function was measured with the Reactive Hyperemia Index (RHI) using digital peripheral arterial tonometry in 546 patients with CAD, who were followed 7 years for incident MACE. The primary end point included cardiovascular death or myocardial infarction; the secondary end point included cardiovascular death, myocardial infarction, or heart failure hospitalization. Hazard models for competing risk were used to estimate the association between RHI and MACE adjusting for age, sex, race, traditional risk factors, medications, and CAD severity. We also examined the association of baseline interleukin-6, C-reactive protein, monocyte chemoattractant protein-1, and matrix metallopeptidase-9 with RHI. Mean age was 62±9 years. Mean RHI was 2.1±0.63. After adjustment, for each 1-SD decrease in RHI, there was a 40% increase in the primary end point (hazard ratio, 1.4 [95% CI, 1.1–1.9], P =0.01) and a similar increase in the secondary end point (HR, 1.3 [95% CI, 1.1–1.7], P =0.006). Inflammatory biomarker levels were associated with greater RHI impairment ( P <0.05) but did not affect the relationship between RHI and MACE. Conclusions: Peripheral microvascular dysfunction is associated with increased risk of MACE in patients with stable CAD, implicating the role of microvascular disease in the pathogenesis of adverse outcomes in patients with CAD.

scholarly journals Distinct Characteristics of VEGF‐D and VEGF‐C to Predict Mortality in Patients With Suspected or Known Coronary Artery Disease

2020 ◽  
Vol 9 (9) ◽  
Author(s):  
Hiromichi Wada ◽  
Masahiro Suzuki ◽  
Morihiro Matsuda ◽  
Yoichi Ajiro ◽  
Tsuyoshi Shinozaki ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Coronary Angiography ◽  
Cardiovascular Events ◽  
Troponin I ◽  
Cardiovascular Death ◽  
Major Adverse Cardiovascular Events ◽  
All Cause Mortality ◽  
Artery Disease ◽  
Cardiovascular Biomarkers

Background VEGF‐D (vascular endothelial growth factor D) and VEGF‐C are secreted glycoproteins that can induce lymphangiogenesis and angiogenesis. They exhibit structural homology but have differential receptor binding and regulatory mechanisms. We recently demonstrated that the serum VEGF‐C level is inversely and independently associated with all‐cause mortality in patients with suspected or known coronary artery disease. We investigated whether VEGF‐D had distinct relationships with mortality and cardiovascular events in those patients. Methods and Results We performed a multicenter, prospective cohort study of 2418 patients with suspected or known coronary artery disease undergoing elective coronary angiography. The serum level of VEGF‐D was measured. The primary outcome was all‐cause death. The secondary outcomes were cardiovascular death and major adverse cardiovascular events defined as a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke. During the 3‐year follow‐up, 254 patients died from any cause, 88 died from cardiovascular disease, and 165 developed major adverse cardiovascular events. After adjustment for possible clinical confounders, cardiovascular biomarkers (N‐terminal pro‐B‐type natriuretic peptide, cardiac troponin‐I, and high‐sensitivity C‐reactive protein), and VEGF‐C, the VEGF‐D level was significantly associated with all‐cause death and cardiovascular death but not with major adverse cardiovascular events.. Moreover, the addition of VEGF‐D, either alone or in combination with VEGF‐C, to the model with possible clinical confounders and cardiovascular biomarkers significantly improved the prediction of all‐cause death but not that of cardiovascular death or major adverse cardiovascular events. Consistent results were observed within patients over 75 years old. Conclusions In patients with suspected or known coronary artery disease undergoing elective coronary angiography, an elevated VEGF‐D value seems to independently predict all‐cause mortality.

P3765Low vascular endothelial growth factor-C was a predictor for cardiovascular events in patients with atrial fibrillation and suspected or known coronary artery disease: a subanalysis of the ANOX study

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Iguchi ◽  
M Suzuki ◽  
M Matsuda ◽  
Y Ajiro ◽  
T Shinozaki ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiovascular Events ◽  
High Sensitivity ◽  
Cardiovascular Death ◽  
Vascular Endothelial ◽  
Median Level ◽  
History Of ◽  
Artery Disease ◽  
Factor C ◽  
Endothelial Growth Factor

Abstract Background Lymphatic system has been considered to play an important role in cardiovascular disease. We recently reported that vascular endothelial growth factor-C (VEGF-C), a central player in lymphangiogenesis, predicted all-cause mortality in patients with suspected or known coronary artery disease (CAD). However, relationship between VEGF-C and atrial fibrillation (AF) remains unclear. Methods The ANOX study is a multicenter, prospective cohort study of 2,418 patients with suspected CAD, to determine the predictive value of possible novel biomarkers related to angiogenesis or oxidative stress for major adverse cardiovascular events (MACE) among patients undergoing elective angiography. Blood samples were collected from the arterial catheter sheath at the beginning of coronary angiography. Serum levels of VEGF-C, as well as N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitivity troponin-I (cTnI), and high-sensitivity C-reactive protein (hsCRP), were measured. The outcome was a MACE defined as a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke. Results Of a total of 2,418 patients, 261 patients had AF at baseline. AF group were older, and had more chronic kidney disease, history of heart failure, and history of stroke, but less diabetes, dyslipidemia, and CAD. The median level of NT-proBNP, cTnI, and hsCRP were higher in AF group [AF vs non-AF: NT-proBNP, 1048 pg/ml vs 162 pg/ml (p<0.0001); cTnI, 0.0003 ng/ml, vs 0.0 ng/ml (p<0.0001); hsCRP, 1.43 ug/ml vs 0.88 ug/ml (p=0.0005)], whereas median level of VEGF-C was lower in AF group [3107 pg/ml vs 3590 pg/ml (p<0.0001)]. AF was associated with lower VEGF-C and higher hsCRP after adjustment for potential confounders. During the 3-year follow-up, 29 (11.1%) patients in AF group and 136 (6.3%) patients in non-AF group developed MACE (p=0.007). Incidence of stroke was higher in AF group (17 (6.5%) vs 52 (2.4%); p<0.0009), despite that the incidence of cardiovascular death and myocardial infarction were similar between the groups. We divided the entire cohort into two groups based on the lowest quartile of VEGF-C or highest quartile of other biomarkers, lowest quartile of VEGF-C (log rank p=0.0004), as well as highest quartile of cTnI (log rank p=0.0009), were significantly associated with MACE in AF group. After adjustment for established risk factors and these biomarkers, both lowest quartile of VEGF-C (HR, 2.73; 95% CI, 1.27–6.06) and highest quartile of cTnI (HR, 2.54; 95% CI, 1.08–6.09) were significantly associated with MACE in AF group. Conclusions AF was associated with lower level of VEGF-C, and low VEGF-C as well as high cTnI might serve as an independent predictor of MACE in patients with AF and suspected or known CAD.

Cardiac outcomes of raltitrexed in the treatment of colorectal cancer patients with 5-fluorouracil (5-FU) cardiotoxicity.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e14607-e14607
Author(s):  
Aryan Firouzbakht ◽  
Daniel John Renouf ◽  
Leo Chen ◽  
Winson Y. Cheung
Keyword(s):  
Colorectal Cancer ◽  
Myocardial Infarction ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Cancer Patients ◽  
Cardiovascular Events ◽  
Regression Analyses ◽  
History Of ◽  
Artery Disease ◽  
Colorectal Cancer Patients

e14607 Background: Both 5-FU and raltitrexed are thymidylate synthase inhibitors, but the latter has a toxicity profile that is distinct from 5-FU. Therefore, it is commonly used as an alternative to 5-FU in the treatment of colorectal cancer patients who have a history of cardiac problems or prior 5-FU cardiotoxicity. To date, the population-based risk of cardiac effects from raltitrexed is uncertain. Our aim was to characterize the patterns of treatment and outcomes of patients receiving raltitrexed-based chemotherapy. Methods: We conducted a retrospective study of all patients diagnosed with colorectal cancer from 1988 to 2012, evaluated at 1 of 5 regional cancer centers in British Columbia, Canada and treated with raltitrexed at any point during their disease. At the institutions in our province, raltitrexed use is limited to those in whom 5-FU is contraindicated. Using chi-squared tests and logistic regression analyses, we evaluated the associations between use of raltitrexed and various cardiovascular events, such as angina, myocardial infarction, hypertension and arrhythmias, as well as other toxicity outcomes, including nausea, vomiting and diarrhea. Results: A total of 186 patients were included: median age was 63 years (IQR 55-70), 97 (52%) were men, and 21 (11%) experienced at least one cardiovascular outcome. Only 4 (2%) patients had a documented cardiac history prior to receipt of any systemic therapy. Among the 21 cases of cardiovascular events, 10 reported angina, 1 suffered a myocardial infarction, 6 had hypertension, and 6 experienced arrhythmias. A significant number of patients also presented with other general toxicities: 25 (13%) reported fever, 11 (6%) suffered mucositis, 75 (40%) had nausea, and 51 (27%) experienced diarrhea. On regression analyses, patients with a previous history of coronary artery disease had a higher risk of cardiovascular events than those without (50 vs 11%, p=0.01). Exposure to 5-FU before raltitrexed did not increase cardiovascular outcomes (p=0.81). Conclusions: Raltitrexed is associated with a low risk of cardiovascular events, but its use should be monitored closely in those with prior coronary artery disease.

Abstract 19748: CD39-associated SNP and Secondary Cardiovascular Events

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Burcu Gul ◽  
Jessica T Delaney ◽  
Yanna Song ◽  
Erica A Bowton ◽  
Cara B Sutcliffe ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Language Processing ◽  
Cardiovascular Events ◽  
Smooth Muscles ◽  
End Point ◽  
Study Population ◽  
Artery Disease ◽  
Record Selection

Introduction: CD39 (ectonucleoside triphosphate diphosphohydrolase) is a nucleotidase expressed on endothelial cells, vascular smooth muscles cells, leukocytes, and platelets. CD39 plays a key role in vascular homeostasis, hydrolyzing extracellular ATP or ADP to AMP. Prior work has demonstrated that the genotype at the single nucleotide polymorphism (SNP) rs10748643 correlates with CD39 expression on HapMap lymphocytes (GG: high, GA: intermediate, AA: baseline). Hypothesis: The aim of this study was to determine if an association exists between the rs10748643 genotype and secondary cardiovascular events. Methods: Subjects treated with placement of an intracoronary stent and on clopidogrel therapy for coronary artery disease were identified in the BioVU DNA repository that links DNA to Synthetic Derivative, a de-identified electronic health record. Selection of the study population was based on a combination of ICD 9th edition, Current Procedural Terminology codes, laboratory values, and natural language processing in physician notes. “Case” or “control” status was assigned depending on recurrence of a secondary cardiovascular event (myocardial infarction, revascularization and/or death) within two years. Genotyping for rs10748643 was performed using TaqMan. Results: The study population included 189 cases and 379 controls, with comparable demographics. There were 47 MIs, 14 deaths, and 166 revascularizations. We compared the composite outcomes of MI and/or death or MI, death and/or revascularization. We found no difference in the composite end-point of MI, death and revascularization, however the GG-genotype at rs10748443 was associated with an increase in the composite end-point of MI and/or death (HR GG:AA: 3.82 95% CI 1.10 - 13.29; P=0.039). Conclusions: The GG genotype, was associated with an increased incidence of the composite end-point of myocardial infarction and death in patients who received intracoronary stents for coronary artery disease and were treated with clopidogrel. This is the first study to demonstrate an association of a CD39-associated SNP with human cardiac pathology. Confirmatory studies are underway in a larger cohort.

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