The role of clopidogrel resistance-related genetic and epigenetic factors in major adverse cardiovascular events among patients with acute coronary syndrome after percutaneous coronary intervention.

Despite patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) and receiving clopidogrel therapy, some patients still experience major adverse cardiovascular events (MACEs). Clopidogrel resistance, which may be regulated by genetic and epigenetic factors, may play a role in MACEs. This study aimed to determine the association between genetic (CYP2C19 and P2Y12 polymorphisms) and epigenetic (DNA methylation of CYP2C19 and P2Y12 and miRNA-26a expression) factors and their effects on MACEs among post-PCI patients. Post-PCI patients who received a standard dosage of clopidogrel at Harapan Kita Hospital between September 2018 and June 2020 were included in this study. MACEs were observed in patients within 1 year after PCI. Platelet aggregation was assessed using light transmission aggregometry (LTA). DNA methylation of CYP2C19 and P2Y12 was assessed using the bisulfite conversion method. CYP2C19 and P2Y12 polymorphisms and miRNA-26a expression were evaluated using quantitative real-time polymerase chain reaction (qRT-PCR). Among a total of 201 subjects, 49.8% were clopidogrel-resistant, and 14.9% experienced MACEs within 1 year after PCI (death was 7.5%). Hypomethylation of CYP2C19 (p = 0.037) and miRNA-26a upregulation (p = 0.020) were associated with clopidogrel resistance. CYP2C19*2/*3 polymorphisms (p = 0.047) were associated with MACEs in 1 year. This study demonstrated that hypomethylation of CYP2C19 and miRNA-26a upregulation increased the risk of clopidogrel resistance in post-PCI patients, but there was no correlation between clopidogrel resistance and MACEs. However, CYP2C19*2/*3 polymorphisms were the factors that predicted MACEs within 1 year.

Prothrombotic Effect of Anti-beta-2 Glycoprotein-1 Antibodies on the Expression of Tissue Factor, Thrombomodulin, and Plasminogen Activator Inhibitor-1 in Endothelial Cells.

AIM: to analyse the effects of immunoglobulin(Ig)G and IgM anti-beta-2 glycoprotein-1 (anti-2GP1) on the expression of tissue factor (TF), thrombomodulin (TM), and plasminogen activator inhibitor-1(PAI-1) of endothelial cells in the messenger RNA level. METHODS: laboratory experimental study in human umbilical vein endothelial cells (HUVEC) was done at Cipto Mangunkusumo Hospital/Faculty of Medicine, Universitas Indonesia. Samples are purified IgG anti-2GP1 from six antiphospholipid syndrome (APS) patients serum and IgM anti-2GP1 from six APS patients serum. For controls, purified IgG from six normal human serum (IgM-NHS) and purified IgM from six normal human serum (IgM-NHS) were used. HUVEC were treated with purified IgG anti-2GP1, IgM anti-2GP1, IgG-NHS, IgM-NHS for four hours of incubation. We measured TF, TM, and PAI-1 of HUVEC in mRNA relative expression levels (before and after treatment) by real time reverse transcription polymerase chain reaction. RESULTS: the mean value of TF, TM, and PAI-1 mRNA levels in HUVEC after treated with IgG anti-2GP1 compared to Ig-NHS were 3.14 (0.93)-, 0.31 (0.13)-, 5.33 (2.75)-fold respectively. In other hand, after treated with IgM anti-2GP1 compared to IgM-NHS, mRNA levels of TF, TM, and PAI-1 were 4.33 (1.98)-, 0.33 (0.22)-, 5.47 (2.64)-fold respectively. Before and after treatment with IgG anti-2GP1 showed significant differences of TF mRNA levels {1.09 (0.76) versus 3.14 (0.93), p=0.003}, TM mRNA levels {0.91 (0.11) versus 0.31(0.13), p=0.001}, and PAI-1 mRNA levels 0.93 (0.13) versus 5.33 (2.75), p=0.013}. Before and after treatment with IgM anti-2GP1 showed significant differences of TF mRNA levels {1.03 (0.11) versus 4.33 (1.98), p=0.008}, TM mRNA levels {0.93 (0.08) versus 0.33 (0.22, p=0.003}, and PAI-1 mRNA levels {1.02 (0.10) versus 5.47 (2.64), p=0.01}. CONCLUSION: IgG anti-2GP1 and IgM anti-2GP1 increased TF and PAI-1 mRNA levels. However, IgG anti-2GP1 and IgM anti-2GP1 decreased TM mRNA levels. It proved that the mechanism of thrombosis in APS occurs through coagulation activation, reduction of fibrinolysis activity, and reduction of anticoagulant activity.

The role of lipid profile as a risk factor indicator for ischemic stroke at Cipto Mangunkusumo Hospital, Jakarta.

AIM: to determine the role of low HDL-cholesterol, and high total cholesterol, LDL-Cholesterol and triglyceride as risk factors for ischemic stroke at Dr. Cipto Mangunkusumo Hospital. METHOD: a study was conducted on 76 patients with an age range of 40-70 years. Subjects consisted of 38 post ischemic stroke patients and 38 control subjects with a diagnosis other than stroke. The study sample consisted of serum for lipid profile assessment. Total cholesterol and triglyceride were assessed using enzymatic method, while HDL-cholesterol and LDL-cholesterol using direct homogenous enzymatic method. Statistical analysis was performed using chi-square and multivariate analysis using logistic regression. RESULTS: low HDL-cholesterol was found in ischemic stroke patients and demonstrated a significant difference compared to control subjects (p<0.05). The results of total cholesterol, triglyceride, LDL-cholesterol did not demonstrate a significant difference. The odds ratio (3.09; CI 95%: 1.04; 8.73) demonstrates that low HDL-cholesterol is a risk factor for ischemic stroke. CONCLUSION: a low HDL-cholesterol level is a risk factor for ischemic stroke, with an odds ratio of 3.09, while total cholesterol, triglyceride and high LDL-cholesterol levels were not risk factors for ischemic stroke.

The role of persistent anticardiolipin antibody as risk factor of ischemic stroke.

AIM: To determine the role of persistent ACA and hyperviscosity as risk factor of ischemic stroke. METHODS: A study was conducted on 76 subjects whose age 40 to 70 years. Subjects consisted of 38 patients of post ischemic stroke and 38 controls with diagnosis other than stroke. Fresh blood samples were taken and mixed with EDTA for viscosity examination and serum for ACA IgM and IgG examination. The laboratory examination for persistent ACA IgM and IgG used ELISA method, while viscosity analysis was using viscometer. Statistic analysis used chi-square and multivariate analysis with logistic regression. RESULTS: In this study we found persistent ACA IgG in 25% of case group , and 2.63% in control group. Multivariate analysis showed persistent ACA IgG as risk factor for ischemic stroke with p < 0.05 and OR 14.11 (CI 95%:1.64;121.11). We found persistent ACA IgM in 2.78% of case group and 5.26% in control group. High blood viscosity was found in 15.79% case group and 10.53% in a control group. Statistical analysis showed no significant difference of viscosity (p = 0.740) and persistent ACA IgM (p = 1.000) between case and control group. CONCLUSION: study showed that persistent ACA IgG in stroke ischemic was higher than in control subjects. Blood viscosity examination and persistent ACA IgM did not show significant difference. While persistent ACA IgG with OR 14.11 (CI: 1.64; 121.11) was the risk factor for ischemic stroke. Blood viscosity and persistent ACA IgM were not risk factors for ischemic stroke.