Gender Differences of Gly972Arg Polymorphism of the IRS-1 Gene Related to Cardiovascular Disease Risk Factors Among Indonesians.

BACKGROUND: Cardiovascular disease is driven by traditional risk factors, sex, and genetic differences. The Asian population, specifically Indonesians, has been known at high risk of insulin resistance and endothelial dysfunction. A possible genetic risk factor related to cardiovascular diseases is Gly972Arg polymorphism of insulin receptor substrate 1 (IRS-1) gene, as this impairs endothelial function. To date, whether there is a gender difference in Gly972Arg polymorphism of the IRS-1 gene in Indonesians is unknown. This study aimed to to define whether there is a gender difference in Gly972Arg polymorphism of the IRS-1 gene in Indonesians. METHODS: We studied adults living in two areas (rural and urban) in Indonesia. We collected demographic and clinical data from the study subjects. Gly972Arg polymorphism of the IRS-1 gene (rs1801278) was detected using TaqMan real-time polymerase chain reaction. RESULTS: A total of 378 subjects were recruited. The wild-type allele (CC) was found in 86 (22.8%) subjects, heterozygous mutant allele (CT) in 245 (64.8%), and homozygous mutant allele in 47 (12.4%). The proportion of subjects with T alleles was significantly higher among women than men (54.6% vs. 45.4%, odds ratio: 1.89; p = 0.01). Subjects with T allele more often have hypertension (odds ratio: 1.69, p = 0.058). CONCLUSION: There were a higher proportion of women than men carrying the T allele of Gly972Arg polymorphism among Indonesians. Individuals with the T allele appeared to show a greater prevalence of hypertension. These results may explain a possible mechanism of the high prevalence of metabolic syndrome in Indonesia, especially in women.

Learning Intelligent for Effective Sonography (LIFES) Model for Rapid Diagnosis of Heart Failure in Echocardiography.

BACKGROUND: The accuracy of an artificial intelligence model based on echocardiography video data in the diagnosis of heart failure (HF) called LIFES (Learning Intelligent for Effective Sonography) was investigated. METHODS: A cross-sectional diagnostic test was conducted using consecutive sampling of HF and normal patients' echocardiography data. The gold-standard comparison was HF diagnosis established by expert cardiologists based on clinical data and echocardiography. After pre-processing, the AI model is built based on Long-Short Term Memory (LSTM) using independent variable estimation and video classification techniques. The model will classify the echocardiography video data into normal and heart failure category. Statistical analysis was carried out to calculate the value of accuracy, area under the curve (AUC), sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and likelihood ratio (LR). RESULTS: A total of 138 patients with HF admitted to Harapan Kita National Heart Center from January 2020 to October 2021 were selected as research subjects. The first scenario yielded decent diagnostic performance for distinguishing between heart failure and normal patients. In this model, the overall diagnostic accuracy of A2C, A4C, PLAX-view were 92,96%, 90,62% and 88,28%, respectively. The automated ML-derived approach had the best overall performance using the 2AC view, with a misclassification rate of only 7,04%. CONCLUSION: The LIFES model was feasible, accurate, and quick in distinguishing between heart failure and normal patients through series of echocardiography images.

Prevalence of plasma lipid disorders with an emphasis on LDL cholesterol in selected countries in the Asia-Pacific region.

Cardiovascular disease (CVD) is a major cause of mortality and morbidity within the Asia-Pacific region, with the prevalence of CVD risk factors such as plasma lipid disorders increasing in many Asian countries. As members of the Cardiovascular RISk Prevention (CRISP) in Asia network, the authors have focused on plasma lipid disorders in the six countries within which they have clinical experience: Indonesia, Malaysia, Philippines, Thailand, Vietnam, and Australia. Based on country-specific national surveys, the prevalence of abnormal levels of total cholesterol, low- and high-density lipoprotein cholesterol (LDL-C and HDL-C, respectively), and triglycerides (TG) are reported. An important caveat is that countries have used different thresholds to define plasma lipid disorders, making direct comparisons difficult. The prevalence of abnormal lipid levels was as follows: high total cholesterol (30.2-47.7%, thresholds: 190-213 mg/dL); high LDL-C (33.2-47.5%; thresholds: 130-135 mg/dL); low/abnormal HDL-C (22.9-72.0%; thresholds: 39-50 mg/dL); and high/abnormal TG (13.9-38.7%; thresholds: 150-177 mg/dL). Similarities and differences between country-specific guidelines for the management of plasma lipid disorders are highlighted. Based on the authors' clinical experience, some of the possible reasons for suboptimal management of plasma lipid disorders in each country are described. Issues common to several countries include physician reluctance to prescribe high-dose and/or high-intensity statins and poor understanding of disease, treatments, and side effects among patients. Treatment costs and geographical constraints have also hampered disease management in Indonesia and the Philippines. Understanding the factors governing the prevalence of plasma lipid disorders helps enhance strategies to reduce the burden of CVD in the Asia-Pacific region.

Association of plasma pentraxin 3 concentration with angiographic and clinical outcomes in patients with acute ST-segment elevation myocardial infarction treated by primary angioplasty.

OBJECTIVE: To evaluate the association of plasma long pentraxin 3 (PTX3) concentration with angiographic and clinical outcomes in patients with acute ST-segment elevation myocardial infarction (STEMI) treated by primary angioplasty. BACKGROUND: Whether concentration of PTX3, a sensitive marker of inflammation, associates with angiographic and clinical outcomes in STEMI patients treated by primary angioplasty is unknown. METHODS: We prospectively enrolled 335 consecutive patients with acute STEMI undergoing primary angioplasty. Blood samples for plasma PTX3 measurement were drawn in all patients at the emergency department before primary angioplasty, and were measured by ELISA method. RESULTS: The median PTX3 concentrations were higher in patients with thrombus burden grade 4 and 5 versus grade <4 on initial coronary angiogram (0.29 ng/ml vs. 0.24 ng/ml, p = .02), thrombolysis in myocardial infarction (TIMI) grade <3 vs. TIMI grade-3 flow after primary angioplasty (0.31 ng/ml vs. 0.24 ng/ml, p < .001), incomplete versus complete ST-segment resolution within 12 hr after angioplasty (0.29 ng/ml vs. 0.22 ng/ml, p = .001) and in patients who did not survive versus those who survived at 30 days (0.44 ng/ml vs. 0.26 ng/ml, p = .001). A linear correlation was observed between PTX3 concentration and baseline leukocyte count (Spearman correlation = 0.21, p < .001). After adjustment for laboratory and selected clinical variables, patients in the highest quartile of PTX3 concentration (≥0.4 ng/ml) were associated with increased risk of 30-day mortality (hazard ratio = 11.83; 95% confidence interval = 1.52-92.27, p = .01). CONCLUSION: This study suggests that higher plasma PTX3 concentration associates with worse angiographic and clinical outcomes in STEMI patients treated by primary angioplasty.

Combined transepicardial and transseptal implantation of autologous CD 133+ bone marrow cells during bypass grafting improves cardiac function in patients with low ejection fraction.

OBJECTIVES: Autologous CD133+ bone marrow stem cells may improve cardiac function. This randomized, single-blind clinical trial inquired whether a combined transepicardial and transseptal implantation of CD133+ stem cells during coronary artery bypass grafting (CABG) improve cardiac function with ejection fraction (EF) changes as a primary endpoint in patients with low EF. METHODS: Thirty patients with coronary heart disease and EF <35% were randomized to undergo CABG alone or CABG with transseptal and transepicardial implantation of CD133+. Cardiac function was evaluated using cardiac magnetic resonance imaging (MRI) before and 6 months after CABG. RESULTS: Preoperative EF was lower in the intervention group (25.88% ± 5.66%) than in the control group (30.18% ± 3.85%; P = .04). The adverse event incidence was similar between both groups. At 6 months, EF changes were significantly higher (8.69% ± 9.49; P = .04) in the CD133+ group than in the CABG-only group. Compared to the control group, significant improvements were seen in the wall motion score index (P = .003) and scar size proportion (P = .047) in the CD133+ group. The quality of life (QOL), assessed by a 6-minute walking test, showed considerable improvement in the CD133+ group compared to that in the control group (P = .03). The Minnesota Living with Heart Failure Questionnaire (MLHFQ) scale did not show improvement in the intervention group (P = .09, vs control). CONCLUSION: Combined transepicardial and transseptal autologous CD133+ BMC implantation during bypass grafting improved cardiac function in low EF coronary artery disease patients.

Ductal stenting vs. surgical shunting in late presenting duct-dependent pulmonary circulation: a single-center experience.

Introduction: PDA stenting is an option to mBTT shunt for younger patients; nevertheless, few reports of this palliative approach have been made for the late presenter population, especially for patients who are older than 30 days but under 5 years. This study aimed to evaluate the clinical result and intra-hospital costs of ductal stenting in late-presenting patients in comparison to surgical shunting. Methods: A single-center, retrospective cohort study was conducted from August 2016 to August 2022. This study included patients with pulmonary duct dependent CHD who were hospitalized for palliative therapy. The extracted data were baseline characteristics, clinical findings, supportive examination findings, complications, outcomes, and length of stay of the patients. Monitoring was carried out during treatment up to 30 days after the procedure. Results: A total of 143 patients were included in the analysis; 43 patients underwent PDA stent and 100 patients underwent mBTT shunt with median age of PDA stent group 110 (31-1,498) days and mBTT shunt group 174.5 (30-1,651) days. Primary outcome composite was not significant in both groups including 30 days mortality [6 (14%) vs. 14 (14%), p = 1.000], reintervention [1 (2.3%) vs. 7 (7%), p = 0.436], and 30 days rehospitalization [0 (0%) vs. 2 (2%), p = 0.319]. Secondary outcome analysis showed shorter ICU length of stay in the PDA stent group [2 (0-16) days vs. 4 (1-63) days, p = 0.002]. Conclusions: PDA stent has an outcome that is non inferior from the mBTT shunt procedure in the composite outcome including 30 days mortality, reintervention, and 30 days rehospitalization but significantly lower in ICU length of stay.

Relationship between Hemoglobin Concentration at Admission with the Incidence of No-Reflow Phenomenon and In-Hospital Mortality in Acute Myocardial Infarction with Elevation of ST Segments in Patients who underwent Primary Percutaneous Coronary Intervention.

Anemia in acute ST-segment elevation myocardial infarction (STEMI) is associated with a pro-coagulant state, contributing to the incidence of no-reflow phenomenon and increased mortality following primary percutaneous coronary intervention (PPCI). However, clinical data remain contradictory. The objective of our study was to evaluate the association of admission hemoglobin (Hb) concentration and in-hospital mortality of STEMI patients' post-PPCI, as well as final thrombolysis in myocardial infarction (TIMI) flow. A cross-sectional study was performed from the database of Jakarta Acute Coronary Syndrome Registry, consisting of 3,071 STEMI patients who underwent PPCI between January 2014 and December 2019. No-reflow phenomenon was defined as final TIMI flow <3 of the infarct-related artery. Outcome measures were the occurrence of no-reflow and in-hospital mortality. Anemia criteria were based on the World Health Organization. Anemia was found in 550 patients (17.9%). Patients with anemia were older (60 ± 10 years, p < 0.001), predominantly women (20.7 vs. 11.2%, p < 0.001), TIMI risk score >4 (45.8 vs. 30.4%, p < 0.00), and Killip classification >1 (25.8 vs. 20.8%, p < 0.009). Anemia at admission was not associated with no-reflow phenomenon (odds ratio [OR] = 0.889; 95% confidence interval [CI] = 0.654-1.209, p = 0.455). Multivariate regression models showed that anemia was not associated with in-hospital mortality (OR = 0.963; 95% CI = 0.635-1.459, p = 0.857) and with no-reflow phenomenon (OR = 0.939; 95% CI = 0.361-2.437, p = 0.896). Anemia upon admission was not related to the no-reflow phenomena or in-hospital mortality in STEMI patients undergoing PPCI.

Plasma brain derived neurotrophic factor level as a modifying factor for trans fat intake and hypertension.

BACKGROUND & AIM: Long-term consumption of trans-fat has been linked with its incorporation in brain neural membrane that could lead into alteration of signalling pathways, including Brain Derived Neurotrophic Factor (BDNF). As an ubiquitous neurotrophin, BDNF is believed to play a role in the regulation of blood pressure yet prior studies shown conflicting results to its effect. Moreover, direct effect of trans fat intake to hypertension has not yet been elucidated. This study aimed to investigate the role of BDNF and its association between trans-fat intake and hypertension. MATERIALS & METHODS: We conducted a population study in Natuna Regency which once reportedly has the highest prevalence of hypertension from Indonesian National Health Survey. Subjects with hypertension and those without hypertension were recruited for the study. Demographic data, physical examination, and food recall were collected. The level of BDNF from all subjects were obtained through analysis of blood samples. RESULTS: A total of 181 participants were included in this study, comprising 134 (74%) hypertensive subjects and 47 (26%) normotensive subjects. Median of daily trans-fat intake of hypertensive subjects was higher compared to normotensive subjects (0,013 [0,0003-0,07] vs 0,010 [0,0006-0,06] % of total energy/day, p = 0,021). Interaction analysis showed significant results for plasma BDNF level in relationship of trans-fat intake and hypertension (p = 0,011). Trans-fat intake association to hypertension in overall subjects showed odds ratio (OR) of 1,85 95%CI 1,05-3,26 (p = 0,034), while in those with low-middle tercile BDNF level the OR was 3,35 95%CI 1,46-7,68 (p = 0,004). CONCLUSION: Plasma BDNF level has a modifying effect in the association between trans-fat intake and hypertension. Subjects with high trans-fat intake, while having low BDNF level, have the highest probability for hypertension.

A Novel Peptide Elabela is Associated with Hypertension-Related Subclinical Atherosclerosis.

INTRODUCTION: Elabela is a newly identified peptide which, alongside apelin, acts as an endogenous ligand that activates the angiotensin receptor-like 1 receptor. Previous studies have shown the association of elabela with hypertension, but information about the role of elabela in hypertension-related subclinical atherosclerosis is scarce. AIM: We aimed to determine the elabela levels in hypertensive patients and explore its association with subclinical atherosclerosis. METHODS: A total of 104 subjects with hypertension were included in the study. Elabela levels were measured using an enzyme-linked immunosorbent assay, by first extracting the peptide following the manufacturer's instructions. Subclinical atherosclerosis was assessed by measuring the carotid intima-media thickness (IMT) using ultrasound. RESULTS: Compared to stage 1, elabela levels decreased in stage 2 hypertension (0.23 [0.13, 0.45] ng/ml vs. 0.14 [0.09, 0.23] ng/ml; P = 0.000), and in the group with increased carotid IMT compared to normal IMT (0.24 [0.13, 0.38] ng/ml vs. 0.15 [0.10, 0.23] ng/ml; P = 0.005). Additionally, a linear correlation analysis showed that elabela had a significant negative correlation with systolic blood pressure (r = - 0.340, P = 0.000) and carotid IMT (r = - 0.213; P = 0.030). In multivariate analysis, lower elabela levels were associated with a higher cardiovascular risk group in this study (OR 5.0, 95% CI 1.8-13.5, P < 0.001). CONCLUSIONS: This study demonstrated for the first time that circulating elabela declined in a higher stage of hypertension and hypertensive patients with increased carotid IMT, implicating that elabela may be involved in the pathogenesis of hypertension-associated subclinical atherosclerosis.

Comparison between Visual Assessment and Longitudinal Strain during Dobutamine Stress Echocardiography.

Background: The relationship between visual assessment and longitudinal strain during dobutamine stress echocardiography (DSE) remains poorly investigated. This study assessed wall motion segments visually graded as normokinetic, hypokinetic, and akinetic at baseline and the peak of DSE and compared with longitudinal strain between segments with and without induced impaired contractility and improved contractility during DSE. Methods: This study included 112 patients examined by DSE, consisting of 58 patients referred for diagnostic study and 54 patients referred for viability study. Regional left ventricular (LV) contractility was assessed visually and longitudinal strain was measured using echocardiography transthoracic. Results: At baseline, the strain of LV segments was -16.33 ± 6.26 in visually normokinetic, 13.05 ± 6.44 in visually hypokinetic, and -8.46 ± 5.69 in visually akinetic segments. During peak dose, the strain of LV segments was -15.37 ± 6.89 in visually normokinetic, -11.37 ± 5.11 in visually hypokinetic, and -7.37 ± 3.92 in visually akinetic segments. In segments with visually observed impaired contractility, the median longitudinal strain was significantly lower than in segments without impaired contractility. For segments with visually observed improved contractility, the median longitudinal strain was significantly higher than for segments without improved contractility. In diagnostic study, sensitivity of visual assessment for absolute decrease of >2% longitudinal strain was 77%, respectively. In the viability study, the sensitivity was 82% for an absolute decrease of ≥2% longitudinal strain. Conclusions: There is good association between strain analysis value and visually assessed wall motion contractility.

The association of apolipoprotein in the risk of ST-elevation myocardial infarction in patients with documented coronary artery disease.

Introduction: Cardiovascular disease (CVD) is the number one cause of death worldwide, in this case, acute coronary syndrome (ACS) or acute myocardial infarction (AMI) that developed from coronary artery disease (CAD). Several risk factors contribute to AMI. Non-modifiable risk factors are age, sex, race, and family history. Modifiable risk factors include dyslipidemia, hypertension, smoking, diabetes mellitus, as well as recent factors that are considered more specific such as homocysteine, lipoprotein a [Lp(a)], high sensitivity C- reactive protein (hs-CRP), and apolipoprotein. This study aimed to determine the role of apolipoprotein as a risk factor for STEMI. Methods: This study combines three epidemiological designs: a descriptive and cross-sectional correlative study with 62 STEMI patients at the National Cardiovascular Center Harapan Kita and a comparative study of 62 STEMI patients and 20 non-ACS CAD patients at the Universitas Indonesia Hospital. Results and conclusion: The descriptive study showed the level of apoB 80.71 ± 28.3, apoA1 104.93 ± 27.8, apoB/apoA1 ratio 0.78 ± 0.22, and Lp(a) 6.85 (1.0-48.1). ApoB moderately correlates with LDLc (p < 0.001; r = 0.571). ApoA1 weakly correlates with HDLc (p = 0.005; r = 0.379). In comparative study, there were significant differences between the STEMI and non-ACS CAD groups on apoA1 (104.93 ± 27.8 vs. 137.48 ± 26.46), apoB/apoA1 ratio (0.78 ± 0.22 vs. 0.59 ± 0.15), and hs-CRP (2.88 [0.4-215] vs. 0.73 [0.15-8.9]). Multivariate analysis showed that the most significant risk factors for STEMI in this study were hypertension for modifiable factors and apoA1 for apolipoprotein. The apoA1 and apoB/apoA1 ratio examination can be suggested for people who have experienced plaque formation and are at risk for myocardial infarction.

Case Report: Successful results of direct varicose vein ablation with EVLA in chronic venous insufficiency patient in Indonesia.

Background: Varicose veins are considered a chronic venous disease. Delaying treatment might cause several late complications that contribute to a high burden on healthcare systems. It may be treated with endovenous laser ablation (EVLA) and stab avulsion as additional procedures. Varicose direct ablation has been promoted to replace stab avulsion in certain conditions. Here we report the case of a 71-year-old female who presented with chronic venous insufficiency managed by an endovascular therapeutic approach using direct varix ablation for the first time in National Cardiovascular Center - Harapan Kita, Jakarta, Indonesia. Case report: A 71-year-old female came to the outpatient clinic with a large bulging vein in her leg. Duplex ultrasound showed that the great saphenous vein (GSV) was incompetent with a varicose vein in the medial part of proximal GSV below the knee. The patient underwent EVLA with direct varicose ablation using Utoh's technique. Duplex sonography evaluation showed the right GSV was utterly obliterated, including the varicose vein. The patient was discharged two days after the procedure without significant complaints nor pain medication. Conclusions: Direct varicose ablation was proposed as a better alternative than stab avulsion. The varicose vein can be managed with EVLA without a scalpel, incision, avulsion, or phlebectomy. In this case presentation, the endovascular therapeutical approach with Utoh's ablation technique showed promising results, and no complication was found in the patient.

Endovascular management of aortic aneurysm with severe neck angulation and/or iliac artery tortuosity using multiple stiff wire technique: a case series.

Background: Suitable aortic neck is one of the essential components for thoracic endovascular aortic repair (TEVAR) and endovascular aortic repair (EVAR). Advanced techniques were developed to adjust and compromise the aneurysm neck angulation but with adding additional devices and complexity to the procedure. We proposed a simple technique to modify severe neck angulation and/or iliac artery tortuosity by using the multiple stiff wire (MSW) technique. Method: Two femoral accesses were required for the MSW technique. A guidewire with a support catheter was inserted through the right and left femoral arteries and positioned in the abdominal or thoracic aorta. Wire exchanges were done with extra stiff wire in both femoral accesses. It can be considered to add multiple stiff wires to align the torturous neck / iliac artery. Delivery of the stent graft main body can be done via one of the accesses. Result: Six patients with different aortic pathology were admitted to our hospital. Four patients undergo EVAR procedure and two patients undergo TEVAR procedure. All patients had aortic neck angulation problems with one patient having iliac artery tortuosity. MSW technique was performed on the patients with good results. Follow-up CTA after 3 months revealed a good stent position without stent migration and no endoleak was found in all but one patient. Conclusion: MSW technique is a simple and effective technique to modify aortic neck/iliac artery angulation in TEVAR or EVAR procedure.

Dyslipidemia management for primary prevention of cardiovascular events: Best in-clinic practices.

Dyslipidemia is a fundamental risk factor for cardiovascular diseases (CVDs) and can worsen the prognosis, if unaddressed. Lipid guidelines are still evolving as dyslipidemia is affecting newer patient subsets. However, these guidelines are governed by regional demographics and ethnic data. Primary care practitioners (PCPs) are the first to offer treatment, and hence placed early in the healthcare continuum. PCPs shoulder a huge responsibility in early detection of dyslipidemia for primary prevention of future cardiovascular (CV) events. Therefore, as members of Cardiovascular RISk Prevention (CRISP) in Asia network, the authors intend to align and shape-up the daily clinical practice workflow for PCPs and have a goal-directed strategy for managing dyslipidemia. This paper reviews the major international lipid guidelines, namely the American and European guidelines, and the regional guidelines from Indonesia, Malaysia, Philippines, Thailand, and Vietnam to identify their commonalities and heterogeneities. The authors, with a mutual consensus, have put forth, best in-clinic practices for screening, risk assessment, diagnosis, treatment, and management of dyslipidemia, particularly to reduce the overall risk of CV events, especially in the Asian context. The authors feel that PCPs should be encouraged to work in congruence with patients to decide on best possible therapy, which would be a holistic approach, rather than pursuing a "one-size-fits-all" approach. Since dyslipidemia is a dynamic field, accumulation of high-quality evidence and cross-validation studies in the future are warranted to develop best in-clinic practices at a global level.

Operability of atrial septal defect with borderline pulmonary vascular resistance index: A study in developing country.

Background: Pulmonary arterial hypertension secondary to atrial septal defect (ASD) is an important determinant of morbidity and mortality in defect closure. We aimed to compare perioperative outcome between preoperative borderline and low pulmonary vascular resistance index (≥4 WU.m2 and <4 WU.m2, respectively) in surgical closure of secundum atrial septal defect with concomitant pulmonary arterial hypertension. Methods and results: This was a single-center retrospective cohort study between January 2015 and January 2020. We classified patients with low and borderline PVRI who underwent ASD closure and recorded the perioperative outcomes. Results: We analyzed a total of 183 patients with atrial septal defect and pulmonary arterial hypertension; 92 patients with borderline PVRI and 91 patients with low PVRI. Borderline pulmonary vascular resistance index was not associated with increased risk of postoperative mortality (p = 0.621; OR0.48, 95% CI 0.04-5.48), but associated with higher risk of overall morbidity in bivariate analysis (p = 0.002; OR3.28, 95% CI 1.5-6.72). Multivariate analysis showed positive association of borderline pulmonary vascular resistance index (p = 0.045; OR2.63, 95% CI 1.02-6.77) and preoperative tricuspid valve gradient ≥64 mmHg (p = 0.034; OR2.77, 95% CI 1.08-7.13) with overall morbidity. Conclusion: There is no difference in incidence of in-hospital mortality between preoperative borderline and low pulmonary vascular resistance index patients. However, preoperative borderline pulmonary vascular resistance index and tricuspid valve gradient ≥64 mmHg are associated with increased overall morbidity after surgical closure in secundum atrial septal defect patients with pulmonary arterial hypertension.

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.

The effect of external counterpulsation on intrinsic myocardial function evaluated by speckle tracking echocardiography in refractory angina patients: a randomized controlled trial.

External Counterpulsation (ECP) is one of the therapeutic options in patients with refractory angina inadequately controlled by medical, interventional, or surgical therapy. The 2D Speckle Tracking Echocardiography (2D-STE) method is considered superior in assessing clinical improvement. We would like to evaluate any improvement of myocardial intrinsic function using 2D-STE in patients underwent standard ECP protocol (35 sessions). We conducted a double-blind randomized controlled trial. Patients with refractory angina who could not be revascularized conventionally were randomized into two groups: (1) the ECP group (300 mmHg) and (2) the Sham/control group (75 mmHg). ECP standard therapy was given for 35 sessions (1 h/day/session). The 2D-STE data, including longitudinal strain and post systolic index (PSI) were obtained before and after therapy. 43 subjects were analyzed, with 22 subjects in ECP group and 21 control subjects (Sham group). A homogenous baseline strain was found either globally (12.42 ± 4.55 vs 12.00 ± 4.92 [- %]; P = 0.774) or segmentally/regionally (12.63 (0.01-25.16) vs 12.43 (0.01-27.20) [- %]; P = 0.570). There was no statistically significant improvement between groups in the left ventricle longitudinal strain globally (P = 0.535) and segmentally/regionally (P = 0.434). PSI parameters showed improvement in the ECP group (P = 0.049), and segments with PSI ≥ 20% seemed to improve longitudinal strains in the ECP group after therapy (P = 0.042). In conclusion, 35 ECP therapy sessions did not improve either global or segmental/regional left ventricular mechanical function in patients with refractory angina. However, the mechanical function of myocardial segments with PSS tends to improve after ECP therapy.

Increase in the risk of clopidogrel resistance and consequent TIMI flow impairment by DNA hypomethylation of CYP2C19 gene in STEMI patients undergoing primary percutaneous coronary intervention (PPCI).

Clopidogrel resistance is an important risk factor of ischemic event recurrence after optimal antiplatelet therapy. This study aims to investigate the role of CYP2C19 gene DNA methylation as one of the epigenetic factors for the risk of clopidogrel resistance in STEMI patients undergoing PPCI. ST-segment elevation myocardial infarction (STEMI) patients undergoing PPCI were pretreated with clopidogrel, and their platelet function was measured using VerifyNow™ assay. The criteria for high on-treatment platelet reactivity (HPR) were defined according to the expert consensus criteria (PRU >208). DNA methylation of the CYP2C19 gene was performed using bisulfite genomic sequencing technology. Furthermore, clinical, laboratory, and angiographic data including TIMI flow were collected. Among 122 patients, clopidogrel resistance was found in 22%. DNA methylation level percentage was lower in the clopidogrel resistance group (76.7 vs. 88.8, p-value .038). But, the <50% methylation group was associated with increased risk of clopidogrel resistance (OR =4.5, 95%CI =2.1-9.3, p-value = .018). This group was also found to have suboptimal post-PCI TIMI flow (OR =3.4 95%CI =1.3-8.7, p-value =.045). The lower DNA methylation level of the CYP2C19 gene increases the risk of clopidogrel resistance and subsequent poorer clinical outcome.

External Counterpulsation Improves Angiogenesis by Preserving Vascular Endothelial Growth Factor-A and Vascular Endothelial Growth Factor Receptor-2 but Not Regulating MicroRNA-92a Expression in Patients With Refractory Angina.

Objective: External counterpulsation (ECP) provides long-term benefits of improved anginal frequency and exercise tolerance in patients with refractory angina (RA). This is postulated as a result of improved angiogenesis and endothelial function through an increase in shear stress. Angiogenesis is mainly represented by vascular endothelial growth factor-A (VEGF-A) and its receptor, vascular endothelial growth factor receptor-2 (VEGFR-2). The microRNA-92a (miR-92a) is a flow-sensitive miRNA that regulates atherosclerosis and angiogenesis in response to shear stress. Thus, ECP beneficial effect might be achieved through interaction between VEGF-A, VEGFR-2, and miR-92a. This study aims to evaluate the ECP effect on VEGF-A, VEGFR-2, and miR-92a in patients with RA in a sham-controlled manner. Methods: This was a randomized sham-controlled trial, enrolling 50 patients with RA who have coronary artery disease (CAD). Participants were randomized (1:1 ratio) to 35 sessions of either ECP (n = 25) or sham (n = 25), each session lasting for 1 h. Plasma levels of VEGF-A and VEGFR-2 were assayed by the ELISA technique. The quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed to measure miR-92a circulating levels in plasma. Result: External counterpulsation significantly preserved VEGF-A and VEGFR-2 level compared to sham [ΔVEGF-A: 1 (-139 to 160) vs.-136 (-237 to 67) pg/ml, p = 0.026; ΔVEGFR-2: -171(-844 to +1,166) vs. -517(-1,549 to +1,407) pg/ml, p = 0.021, respectively]. Circulating miR-92a increased significantly in ECP [5.1 (4.2-6.4) to 5.9 (4.8-6.4), p < 0.001] and sham [5.2 (4.1-9.4) to 5.6 (4.8-6.3), p = 0.008] post-intervention. The fold changes tended to be higher in ECP group, although was not statistically different from sham [fold changes ECP = 4.6 (0.3-36.5) vs. sham 2.8 (0-15), p = 0.33)]. Conclusion: External counterpulsation improved angiogenesis by preserving VEGF-A and VEGFR-2 levels. Both ECP and sham increased miR-92a significantly, yet the changes were not different between the two groups. (Study registered on www.clinicaltrials.gov, no: NCT03991871, August 8, 2019, and received a grant from the National Health Research and Development of Ministry of Health of Indonesia, No: HK.02.02/I/27/2020).

Methylenetetrahydrofolate Reductase C677T Gene Polymorphism as a Risk Factor for Hypertension in a Rural Population.

Hypertension remains a public health burden despite advances in its management. Hence, the search for further risk stratification tools and prevention and new treatment approaches continues. Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism is associated with hypertension. Interestingly, riboflavin, as a cofactor of MTHFR, may control blood pressure in patients with mutant MTHFR variants. These double benefits of a risk stratification tool and treatment approach make it interesting. Because this polymorphism depends on ethnicity and geographic region, we aimed to determine the association between MTHFR C677T gene polymorphism and hypertension in a rural Indonesian-Sundanese population. This population-based case-control study included 213 hypertensive subjects and 202 nonhypertensive subjects as controls. The TaqMan assay was used to determine the MTHFR C677T genotypes. The odds ratio (OR) with 95% confidence interval (CI) was used to assess the risk of association. There was a significant difference in MTHFR C677T allele frequencies between the hypertensive and control groups (62.9% CC, 34.3% CT, 2.8% TT vs. 77.7% CC, 20.8% CT, 1.5% TT; p=0.004) and between mutant (TT and CT) and wild-type genotypes (CC) (p=0.001). The mutant genotype was associated with a risk of hypertension (OR 2.1; 95% CI 1.3-3.5) when adjusted for age, body mass index, waist circumference, and diabetes mellitus. The mutant of the MTHFR C677T gene increases the risk of hypertension in rural Indonesian-Sundanese population. These findings may be used in future studies to evaluate the effect of riboflavin supplementation in this population.