Megumi Hirokawa

A genome-wide association study identifies PLCL2 and AP3D1-DOT1L-SF3A2 as new susceptibility loci for myocardial infarction in Japanese

Despite considerable progress in preventive and therapeutic strategies, myocardial infarction (MI) is one of the leading causes of death throughout the world. A total of 55 susceptibility genes have been identified mostly in European genome-wide association studies (GWAS). Nevertheless, large-scale GWAS from other population could possibly find additional susceptibility loci. To identify as many MI susceptibility loci as possible, we performed a large-scale genomic analysis in Japanese population. To identify MI susceptibility loci in Japanese, we conducted a GWAS using 1666 cases and 3198 controls using the Illumina Human610-Quad BeadChip and HumanHap550v3 Genotyping BeadChip. We performed replication studies using a total of 11 412 cases and 28 397 controls in the Japanese population. Our study identified two novel susceptibility loci for MI: PLCL2 on chromosome 3p24.3 (rs4618210:A>G, P=2.60 × 10−9, odds ratio (OR)=0.91) and AP3D1-DOT1L-SF3A2 on chromosome 19p13.3 (rs3803915:A>C, P=3.84 × 10−9, OR=0.89). Besides, a total of 14 previously reported MI susceptibility loci were replicated in our study. In particular, we validated a strong association on chromosome 12q24 (rs3782886:A>G: P=1.14 × 10−14, OR=1.46). Following pathway analysis using 265 genes related to MI or coronary artery disease, we found that these loci might be involved in the pathogenesis of MI via the promotion of atherosclerosis. In the present large-scale genomic analysis, we identified PLCL2 and AP3D1-DOT1L-SF3A2 as new susceptibility loci for MI in the Japanese population. Our findings will add novel findings for MI susceptibility loci.

Relationship of Left Ventricular Diastolic Function to Obesity and Overweight in a Japanese Population With Preserved Left Ventricular Ejection Fraction

BACKGROUND Obesity has been found to be associated with future development of diastolic heart failure. Other evidence has indicated that the effect of obesity on left ventricular (LV) mass varies among ethnicities. However, there are few data on the relationship between body mass index (BMI) and LV diastolic dysfunction in the Japanese population. METHODSANDRESULTS We performed echocardiography in 788 subjects without valvular disease or LV systolic dysfunction. They were divided into 3 groups by BMI: normal weight, overweight, and obese. We used multivariable linear regression analysis to assess the clinical variables associated with diastolic parameters, including BMI. We also assessed the risk of diastolic dysfunction associated with BMI using multivariable logistic models. Overweight and obese subjects had significantly worse LV diastolic function and greater LV mass than normal weight subjects. In the multivariable analysis, BMI was independently associated with diastolic parameters. Furthermore, after adjusting for clinical factors, the increased risks of diastolic dysfunction in overweight subjects (adjusted odds ratio: 2.02, 95% confidence interval 1.21-3.36) and obese subjects (4.85, 3.36-16.27) were greater than those previously observed in Western populations. CONCLUSIONS The Japanese population might be more susceptible than Western subjects to the effect of BMI on LV diastolic function. Differences between ethnicities should be taken into consideration in strategies for the prevention of diastolic heart failure. (Circ J 2016; 80: 1951-1956).

Factors influencing left atrial volume in a population with preserved ejection fraction: Left ventricular diastolic dysfunction or clinical factors?

BACKGROUND Increased left atrial volume (LAV) predicts a higher incidence of cardiovascular events and is widely recognized as a major surrogate marker of left ventricular (LV) diastolic dysfunction (DD). Although the pathophysiology of LA enlargement is probably multifactorial, few studies have examined comprehensively the clinical factors that lead to LA enlargement in the absence of valvular disease or LV systolic dysfunction. Therefore, we investigated associations between LAV and several clinical and echocardiographic parameters including DD. METHODS We enrolled 557 subjects without significant valve disease or LV systolic dysfunction from the health check-up clinic retrospectively. We performed univariable and multivariable linear regression using lnLAV index as the dependent variable and the following independent variables: gender, age, smoking status, drinking habit, hypertension, diabetes, body mass index (BMI), LV ejection fraction, DD, LV mass index, hemoglobin, serum creatinine, serum total cholesterol, serum uric acid, serum sodium, and serum iron. RESULTS In multivariable analysis, LAV index was independently associated with BMI, lower hemoglobin, and moderate and severe DD compared with normal diastolic function (p<0.001), but not with mild DD (p=0.70). CONCLUSIONS LA enlargement was independently associated with moderate and severe DD, but not with mild DD. Furthermore, obesity and lower hemoglobin were associated with LAV independently of DD.

Prognostic impact of venous thromboembolism in patients with Duchenne muscular dystrophy: Prospective multicenter 5-year cohort study

Please cite this article as: Kimura Koichi, Morita Hiroyuki, Daimon Masao, Kawata Takayuki, Nakao Tomoko, Lee Seitetsu L., Hirokawa Megumi, Ebihara Aya, Nakajima Takashi, Ozawa Tetsuo, Yonemochi Yosuke, Aida Izumi, Motoyoshi Yasufumi, Mikata Takashi, Uchida Idai, Komori Tetsuo, Kitao Ruriko, Nagata Tetsuya, Takeda Shin’ichi, Komaki Hirofumi, Segawa Kazuhiko, Takenaka Katsu, Komuro Issei, Prognostic Impact of Venous Thromboembolism in Patients with Duchenne Muscular Dystrophy: Prospective Multicenter 5-Year Cohort Study, International Journal of Cardiology (2015), doi: 10.1016/j.ijcard.2015.04.244

Prognostic Value of a Simple Echocardiographic Parameter, the Right Ventricular Systolic to Diastolic Duration Ratio, in Patients with Advanced Heart Failure with Non-Ischemic Dilated Cardiomyopathy

The prognostic value of the right ventricular (RV) systolic to diastolic duration ratio (S/D ratio) in patients with advanced heart failure is not clear.We enrolled 45 patients with DCM (40 ± 13 years, 33 male) who were admitted to our hospital for evaluation or treatment of heart failure. The RV systolic and diastolic durations were measured using continuous Doppler imaging of tricuspid regurgitation, and the RV S/D ratio was calculated. Cardiac events were defined as cardiac death or left ventricular assist device implantation within the first year. Twenty-eight cardiac events occurred. The RV S/D ratio was significantly higher in the event group than in the event-free group (1.8 ± 0.8 versus 1.2 ± 0.5, P = 0.008). Univariate analysis showed that the RV S/D ratio, plasma brain natriuretic peptide concentration, left atrial volume index, and mitral deceleration time were associated with these events. Receiver operating characteristic curve analysis revealed that the optimal RV S/D cutoff value to predict events was 1.2 (sensitivity 79%, specificity 65%, area under the curve 0.745). Kaplan-Meier analysis indicated a significantly higher event rate in patients with an RV S/D ratio > 1.2 (log-rank test, P = 0.003). The addition of an RV S/D ratio > 1.2 improved the prognostic utility of a model that included conventional variables (P = 0.014).In patients with advanced heart failure with DCM, the RV S/D ratio was higher in patients with events than in those without events. The addition of the RV S/D ratio to conventional parameters may provide better prognostic information.

Reconsideration of Inferior Vena Cava Parameters for Estimating Right Atrial Pressure in an East Asian Population ― Comparative Simultaneous Ultrasound-Catheterization Study ―

BACKGROUND Ultrasound measurements of the inferior vena cava (IVC) diameter (IVCD), together with its respiratory variation, provide a noninvasive estimate of right atrial pressure (RAP). However, there is a paucity of studies that have compared this technique with simultaneous catheterization. We explored the best cut-off values of IVC parameters for elevated RAP in comparison with RAP measured by catheterization.Methods and Results:We prospectively enrolled 120 East Asian patients who were scheduled for catheterization. The IVCD and IVC collapsibility index (IVCCI) were measured according to the current guidelines. The optimal maximum IVCD (IVCDmax) and IVCCI cut-offs for detecting elevated RAP (RAP ≥10 mmHg) were 17 mm and 40%, respectively. When we combined both in proportion to the guidelines, the sensitivity and specificity for detecting elevated RAP were 75% and 94%, respectively. When the cut-off values from the current guidelines (>21 mm and <50%) were applied, the respective sensitivity and specificity were 42% and 99%. Interestingly, the cut-off value of the optimal IVCDmax indexed by body surface area (11 mm/m2) was similar to previous Western population data. When we combined both cut-off values (11 mm/m2and 40%), the sensitivity and specificity were 75% and 95%, respectively. CONCLUSIONS The optimal absolute IVCDmax and IVCCI cut-offs to detect elevated RAP were smaller than those in the current guidelines. Indexed IVCDmax may be an IVC parameter that can be used internationally.