Reiko Matsuoka

Association of six genetic variants with myocardial infarction

Although various genes that confer susceptibility to myocardial infarction (MI) have been identified for Caucasian populations in genome-wide association studies (GWAS), genetic variants related to this condition in Japanese individuals have not been identified definitively. The aim of the present study was to examine an association of MI in Japanese individuals with 29 polymorphisms identified as susceptibility loci for MI or coronary artery disease in Caucasian populations by meta-analyses of GWAS. The study subjects comprised 1,824 subjects with MI and 2,329 controls. Genotypes of the polymorphisms were determined by Luminex bead-based multiplex assay. To compensate for multiple comparisons, we adopted the criterion of a false discovery rate (FDR) of <0.05 for statistical significance for association. Comparisons of allele frequencies by the χ(2) test revealed that rs9369640 of the phosphatase and actin regulator 1 gene (PHACTR1, FDR=0.0007), rs4977574 of the CDKN2B antisense RNA 1 gene (CDKN2B-AS1, FDR=0.0038), rs264 of the lipoprotein lipase gene (LPL, FDR=0.0061), rs599839 of the proline/serine-rich coiled-coil 1 gene (PSRC1, FDR=0.0118), rs9319428 of the fms-related tyrosine kinase 1 gene (FLT1, FDR=0.0118) and rs12413409 of the cyclin and CBS domain divalent metal cation transport mediator 2 gene (CNNM2, FDR=0.0300) were significantly associated with MI. Multivariate logistic regression analysis with adjustment for covariates revealed that rs9369640 (P=0.0005; odds ratio, 0.89), rs4977574 (P=0.0001; odds ratio, 1.50), rs264 (P=0.0405; odds ratio, 0.85), rs599839 (P=0.0003; odds ratio, 0.68), rs9319428 (P=0.0155; odds ratio, 1.20) and rs12413409 (P=0.0076; odds ratio, 0.66) were significantly (P<0.05) associated with MI. PHACTR1, CDKN2B-AS1, LPL, PSRC1, FLT1 and CNNM2 may thus be susceptibility loci for MI in Japanese individuals.

Association of a polymorphism of the interleukin 6 receptor gene with chronic kidney disease in Japanese individuals.

Various loci and genes that confer susceptibility to coronary artery disease (CAD) have been identified in Caucasian populations by genome‐wide association studies (GWASs). The aim of the present study was to examine a possible association of chronic kidney disease (CKD) with 29 polymorphisms previously identified as susceptibility loci for CAD by meta‐analyses of GWASs.

Association of genetic variants with dyslipidemia.

Although genetic variants, which regulate lipid metabolism, have been extensively investigated in Caucasian populations, the genes, which confer susceptibility to dyslipidemia in Japanese individuals, remain to be elucidated. The aim of the present study was to examine a possible association among hypertriglyceridemia, hypo‑high density lipoprotein (HDL)‑cholesterolemia or hyper‑low density lipoprotein (LDL)‑cholesterolemia in Japanese individuals with 29 polymorphisms observed to confer susceptibility for coronary heart disease. This was performed through meta‑analyses of genome‑wide association studies in Caucasian populations. The study population comprised 2,354 individuals with dyslipidemia (hypertriglyceridemia, hypo‑HDL‑cholesterolemia or hyper‑LDL‑cholesterolemia) and 3,106 control individuals. To compensate for multiple comparisons of genotypes, a false discovery rate (FDR) of <0.05 was adopted to determine the statistical significance of the associations. Comparisons of allele frequencies using the χ2 test revealed that rs964184 of zinc finger gene (ZPR1; FDR=2.1x10‑7), rs4845625 of interleukin 6 receptor (IL6R; FDR=0.032), rs46522 of ubiquitin‑conjugating enzyme E2Z gene (UBE2Z; FDR=0.032) and rs17514846 of furin (FDR=0.041) were significantly associated with hypertriglyceridemia. The χ2 test revealed that rs599839 of proline/serine‑rich coiled‑coil 1 (PSRC1; FDR=0.004) and rs2075650 of translocase of outer mitochondrial membrane 40 homolog (TOMM40; FDR=0.004) were significantly associated with hyper‑LDL‑cholesterolemia. Multivariate logistic regression analysis with adjustment for age, gender and body mass index revealed that rs964184 of ZPR1 (P=5.1x10‑7; odds ratio, 1.37; dominant model), rs4845625 of IL6R (P=0.0019, odds ratio, 1.25; dominant model) and rs46522 of UBE2Z (P=0.0039, odds ratio, 1.19; dominant model) were significantly associated with hypertriglyceridemia, and that rs599839 of PSRC1 (P=0.0004, odds ratio, 0.70; dominant model) and rs2075650 of TOMM40 (P=0.0004, odds ratio, 1.43; dominant model) were significantly associated with hyper‑LDL‑cholesterolemia. Therefore, ZPR1, IL6R, and UBE2Z may be susceptibility loci for hypertriglyceridemia, whereas PSRC1 and TOMM40 may be such loci for hyper-LDL-cholesterolemia in Japanese individuals.

Global Registry of Acute Coronary Events risk score predicts mortality and neurological outcome in out-of hospital cardiac arrest

Purpose: The aim of this study was to assess the usefulness of the Global Registry of Acute Coronary Events (GRACE) risk score in predicting in‐hospital mortality and neurological outcome of patients resuscitated after out‐of‐hospital cardiac arrest (OHCA). Methods: We retrospectively analyzed the data of patients admitted to our hospital between October 2009 and October 2015 with OHCA and shockable initial cardiac rhythm who were resuscitated via conventional cardiopulmonary resuscitation. We calculated the GRACE risk score on admission and assessed its usefulness in predicting in‐hospital mortality and neurological outcome. Results: Among 91 patients, 42 (46%) had acute myocardial infarction (AMI), 19 (21%) died in‐hospital, and 52 (57%) had favorable neurological outcome. Among all the study patients, GRACE risk score was lower in survivors than in non‐survivors (median 211 [interquartile range 176–240] vs. 266 [219–301], p < 0.001, respectively) and in favorable than in unfavorable neurological outcome group (202 [167–237] vs. 242 [219–275], p < 0.001, respectively). Multivariate analysis showed significant association between GRACE risk score and favorable neurological outcome (odds ratio, 0.975; 95% confidence interval, 0.961–0.990). Areas under receiver‐operating characteristic curves, that describe the accuracy of GRACE risk score in predicting in‐hospital mortality and favorable neurological outcome, were both 0.79. Conclusion: GRACE risk score may predict the in‐hospital mortality and neurological outcome associated with resuscitated patients with OHCA and shockable initial cardiac rhythm, regardless of the cause of arrest.

D-dimer predicts bleeding complication in out-of-hospital cardiac arrest resuscitated with extracorporeal membrane oxygenation

Purpose In out‐of‐hospital cardiac arrest (OHCA) patients resuscitated with veno‐arterial extracorporeal membrane oxygenation (VA‐ECMO), known as extracorporeal cardiopulmonary resuscitation (ECPR), bleeding is a common complication. The purpose of this study was to assess the risk factors for bleeding complications in ECPR patients. Methods We retrospectively analyzed the data for OHCA patients admitted to our hospital and resuscitated with ECPR between October 2009 and December 2016. We compared patients with and without major bleeding (i.e. the Bleeding Academic Research Consortium class ≥ 3 bleeding) within 24 h of hospital admission. Patients, whose bleeding complication was not evaluated, were excluded. Results During the study period, 133 OHCA patients were resuscitated with ECPR, of whom 102 (77%) were included. In total, 71 (70%) patients experienced major bleeding. There were significant differences in age (median 65 vs. 50 years, P < 0.001), prior antiplatelet therapy (25% vs. 3%, P = 0.008), hemoglobin (median 11.6 vs. 12.6 g/dL, P = 0.003), platelet count (median 125 vs. 155 × 103/&mgr;L, P = 0.001), and D‐dimer levels on admission (median 18.8 vs. 6.7 &mgr;g/mL, P < 0.001) among patients with and those without major bleeding. Multivariate analysis showed significant associations between major bleeding and D‐dimer levels (odds ratio, 1.066; 95% confidence interval, 1.018–1.116). Area under receiver‐operating characteristic curve, which describes the accuracy of D‐dimer levels in predicting major bleeding, was 0.76 (95% confidence interval, 0.66–0.87). Conclusion D‐dimer levels may predict major bleeding in ECPR patients, suggesting that hyperfibrinolysis may be related to bleeding.

LEFT ATRIAL STRUCTURE AND FUNCTION IN HYPERTENSIVE PATIENTS ASSESSED BY REAL-TIME THREE-DIMENSIONAL SPECKLE TRACKING ECHOCARDIOGRAPHY: A COMPARATIVE STUDY WITH NORMAL SUBJECTS AND TWO-DIMENSIONAL SPECKLE TRACKING

Major advantage of 3-dimensional speckle tracking echocardiography (3-DSTE) is the improvement of accuracy in the evaluation of cardiac chamber volume without any geometrical assumption. However, there have been few studies regarding to left atrial (LA) structure and function using 3-DSTE. The aim

LEFT ATRIAL PHASIC FUNCTION ASSESSED BY SPECKLE TRACKING ECHOCARDIOGRAPHY IS A USEFUL PREDICTOR FOR FIRST ATRIAL FIBRILLATION: RESULTS OF PROSPECTIVE STUDY OF 2 YEARS FOLLOW-UP

Methods: LA total, passive and active emptying function (EF) as a global function and LA strain rate (SR) at systole, early diastole and atrial contraction as a regional function were measured in apical 4-chamber view by speckle tracking in consecutive 420 adults without mitral valve disease and atrial arrhythmia (age 68±14, 251 men). LA volume, left ventricular (LV) mass, ejection fraction, and E/e’ as a diastolic function were measured.

DIFFERENTIATION OF LEFT ATRIAL VOLUME BY TIME (DV/DT) IS A NOVEL AND USEFUL ECHO INDEX TO ASSESS LEFT ATRIAL GLOBAL AND PHASIC FUNCTION

Background: Left atrial (LA) strain rate (SR) which represents a regional function is proposed to assess LA active relaxation, conduit function and active contraction. However, analysis of LA global and phasic function using differentiation of LA volume by time (dV/dt) has not yet been elucidated. Using velocity vector imaging (Siemens), timeLA volume and dV/dt curve can be automatically and rapidly provided. Thus, the aim of this study was to evaluate the usefulness of LA dV/dt as a new index of LA global and phasic function by comparing it with SR.