Masahiro Yamazoe

Relationship between serum uric acid levels and hypertension among Japanese individuals not treated for hyperuricemia and hypertension

The cause and effect relationship between serum uric acid levels and hypertension can be difficult to evaluate because antihypertensive drugs sometimes affect uric acid levels. This cross-sectional study investigated the relationship between serum uric acid levels and hypertension in a general, healthy Japanese population who were not receiving medication for hyperuricemia or hypertension. We retrospectively analyzed the medical records of 90 143 Japanese people (men, 49.1%; age, 46.3±12.0 years) undergoing an annual medical examination at St Luke’s International Hospital Center for Preventive Medicine, Tokyo, between January 2004 and June 2010. Of these individuals, 82 722 (91.8%) who had never taken medications for gout, hyperuricemia or hypertension were enrolled. We compared the participant characteristics and prevalence of diastolic hypertension (⩾90 mm Hg) and/or systolic hypertension (⩾140 mm Hg) by serum uric acid quartile. The odds ratio (OR) of hypertension was 1.20 for each 1 mg dl−1 increase in serum uric acid level after adjustment for age, sex, body mass index (BMI), dyslipidemia, diabetes, smoking and estimated glomerular filtration rate (eGFR). Compared with the lowest serum uric acid quartile, participants in the highest quartile had a 3.7-fold higher OR for hypertension. After adjustment for age, BMI, dyslipidemia, diabetes, smoking and eGFR, these ORs were 1.79 (1.62–1.98) in the total study population, 1.58 (1.44–1.75) in men and 1.60 (1.39–1.84) in women. The results were similar for both systolic and diastolic hypertension. Elevated serum uric acid levels may be as important as obesity, dyslipidemia, diabetes, smoking and reduced kidney function for the development of hypertension and should be considered in hypertension prevention programs.

Validation of the Get With The Guideline–Heart Failure risk score in Japanese patients and the potential improvement of its discrimination ability by the inclusion of B-type natriuretic peptide level

BACKGROUND Detailed characteristics of patients with acute heart failure (AHF) in Japan have not been elucidated. Furthermore, international application of risk models obtained in the United States has not been validated. METHODS We evaluated the Get With The Guidelines-Heart Failure (GWTG-HF) risk score performance in AHF patients enrolled in the West Tokyo Heart Failure registry, a large, ongoing, prospective, multicenter cohort registry. Variables required for the GWTG-HF risk score were race, age, systolic blood pressure, heart rate, blood urea nitrogen level, sodium concentration, and presence of chronic obstructive pulmonary disease. Score discrimination and calibration were evaluated by the c statistic, Hosmer-Lemeshow statistic, and visual plotting. We conducted additional analyses to determine whether other variables improved the performance of the score. The primary outcome was in-hospital mortality. RESULTS In total, 1,876 patients were admitted for AHF between April 2006 and August 2014. The patients were predominantly men (60.6%), with a mean age of 73.3 ± 13.6 years. Sixty-eight (3.6%) patients died during hospitalization. The GWTG-HF risk score showed acceptable discrimination; the c statistic for in-hospital mortality in this cohort was 0.763 (95% CI, 0.700-0.826). The calibration plot showed good conformance between the predicted and observed in-hospital mortality. Notably, addition of B-type natriuretic peptide level to the conventional GWTG-HF score significantly improved the discrimination (c statistic, 0.818; 95% CI, 0.771-0.865). CONCLUSIONS The GWTG-HF risk score can be applied in Japanese AHF patients with good discrimination and calibration. Furthermore, addition of B-type natriuretic peptide level improves discrimination and could be considered in future risk models.

Serum alkaline phosphatase as a predictor of worsening renal function in patients with acute decompensated heart failure

BACKGROUND Venous congestion has come into focus as an important hemodynamic factor for worsening renal function (WRF) in patients with acute decompensated heart failure (ADHF). Serum alkaline phosphatase (ALP) was reported as a biological marker of liver congestion in ADHF. The purpose of this study was to determine whether ALP is a predictor of WRF in patients with ADHF. METHODS We enrolled consecutive patients admitted to a single cardiovascular center with ADHF, and defined WRF as an increase in creatinine of >0.3 mg/dl during hospitalization and chronic kidney disease (CKD) as an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m(2). The patients were classified into tertiles by ALP level (<203, 203-278, and >278 IU/L). RESULTS A total of 972 patients (mean age, 76±13 years; 54% male) were retrospectively analyzed. WRF was identified in 132 patients (13.6%). In multivariate logistic regression analysis, baseline CKD [odds ratio (OR) 2.46, 95% confidence interval (CI) 1.48-4.08, p<0.001], serum albumin (OR 0.52, 95% CI 0.35-0.77, p=0.001), and diabetes (OR 2.07, 95% CI 1.37-3.12, p<0.001) were associated with WRF. Compared with the lowest tertile (ALP <203 IU/L), an adjusted OR of WRF was 1.69 (95% CI 1.02-2.79, p=0.04) in the middle tertile (ALP, 203-278 IU/L) and 1.95 (95% CI 1.20-3.21, p=0.008) in the highest tertile (ALP >278 IU/L). CONCLUSION Serum ALP is an independent predictor of WRF in the clinical course of ADHF.

Impact of the augmentation time ratio on direct measurement of central aortic pressure in the presence of coronary artery disease.

The augmentation index measured by using the central artery pressure is associated with an increased risk of coronary artery disease (CAD). However, no study has examined the role of the time duration of the central artery pressure on CAD. Therefore, we evaluated the relationship between the central blood pressure time duration and the presence of CAD. All patients without a history of revascularization or prior myocardial infarction who underwent an elective coronary angiography at one of the two hospitals from January to September 2013 were analyzed. CAD was defined as a significant stenosis in one of the main coronary branches. The augmentation time ratio was defined as the ratio of the reflection to peak systolic time T2T1 duration divided by the peak systolic time to aortic notch T3T2 duration. We analyzed the relationship between the central pressure waveform (not only augmentation pressure) and the presence of CAD. A total of 146 (57.3%) out of 255 patients had a significant CAD. T2T1 duration was longer in the CAD group than the no CAD group, and the T3T2 duration was shorter in the CAD group than the no CAD group. The augmentation time ratio (T2T1/T3T2) was significantly larger in the CAD group than in the no CAD group. The augmentation index and augmentation pressure were lower in the no CAD group, but this difference was not statistically significant. The augmentation time ratio was an independent factor related to no CAD, especially in patients with a high augmentation index (odds ratio, 2.17; 95% confidence interval, 1.02–4.63). The augmentation time ratio was an independent factor related to the presence of CAD.

Combined Analysis of Human and Experimental Murine Samples Identified Novel Circulating MicroRNAs as Biomarkers for Atrial Fibrillation

BACKGROUND Recent experimental studies have demonstrated that several microRNAs (miRNAs) expressed in atrial tissue promote a substrate of atrial fibrillation (AF). However, because it has not been fully elucidated whether these experimental data contribute to identifying circulating miRNAs as biomarkers for AF, we used a combined analysis of human serum and murine atrial samples with the aim of identifying these biomarkers for predicting AF.Methods and Results:Comprehensive analyses were performed to screen 733 miRNAs in serum from 10 AF patients and 5 controls, and 672 miRNAs in atrial tissue from 6 inducible atrial tachycardia model mice and 3 controls. We selected miRNAs for which expression was detected in both analyses, and their expression levels were changed in the human analyses, the murine analyses, or both. This screening identified 11 candidate miRNAs. Next, we quantified the selected miRNAs using a quantitative RT-PCR in 50 AF and 50 non-AF subjects. The individual assessment revealed that 4 miRNAs (miR-99a-5p, miR-192-5p, miR-214-3p, and miR-342-5p) were significantly upregulated in AF patients. A receiver-operating characteristics curve indicated that miR-214-3p and miR-342-5p had the highest accuracy. The combination of the 4 miRNAs modestly improved the predictive accuracy for AF (76% sensitivity, 80% specificity). CONCLUSIONS Novel circulating miRNAs were upregulated in the serum of AF patients and might be potential biomarkers of AF.

Edema index measured by bioelectrical impedance analysis as a predictor of fluid reduction needed to remove clinical congestion in acute heart failure.

No abstract available Keywords: Bioelectrical impedance analysis; Congestion; Edema index; Heart failure.

Endomyocardial Biopsy and Magnetic Resonance Imaging of Acute Myocarditis with Adult-Onset Still's Disease.

A 36-year-old female with a high-grade fever and epigastric abdominal pain was prescribed antibiotics, but developed hypoxia and dyspnea. An echocardiography revealed diffuse hypokinesis and massive pericardial effusion, after which diagnostic cardiac catheterization and an endomyocardial biopsy (EMB) were peformed to reveal fibrosis and infiltration of inflammation cells composed primarily of neutrophils. Clinical manifestation of a spiking fever, leukocytosis, elevated ferritin levels, skin rash and EMB findings led to a diagnosis of adult-onset Stills disease (AOSD) with acute myocarditis. Pulse therapy of intravenous methylprednisolone was performed for three days, followed by a daily dose of prednisone (60 mg). After a course of steroid therapy for fever and pericardial effusion, and conducting a left ventricular ejection fraction, the patient showed improvement and was discharged asymptomatic within 32 days of admission. This study is the first to report on a case of myocarditis in AOSD diagnosed by neutrophil infiltration in the myocardium.

Electrophysiological Assessment of Murine Atria with High-Resolution Optical Mapping

Recent genome-wide association studies targeting atrial fibrillation (AF) have indicated a strong association between the genotype and electrophysiological phenotype in the atria. That encourages us to utilize a genetically-engineered mouse model to elucidate the mechanism of AF. However, it is difficult to evaluate the electrophysiological properties in murine atria due to their small size. This protocol describes the electrophysiological evaluation of atria using an optical mapping system with a high temporal and spatial resolution in Langendorff perfused murine hearts. The optical mapping system is assembled with dual high-speed complementary metal oxide semiconductor cameras and high magnification objective lenses, to detect the fluorescence of a voltage-sensitive dye and Ca2+ indicator. To focus on the assessment of murine atria, optical mapping is performed with an area of 2 mm × 2 mm or 10 mm x 10 mm, with a 100 × 100 resolution (20 µm/pixel or 100 µm/pixel) and sampling rate of up to 10 kHz (0.1 ms) at maximum. A 1-French size quadripolar electrode pacing catheter is placed into the right atrium through the superior vena cava avoiding any mechanical damage to the atrium, and pacing stimulation is delivered through the catheter. An electrophysiological study is performed with programmed stimulation including constant pacing, burst pacing, and up to triple extrastimuli pacing. Under a spontaneous or pacing rhythm, the optical mapping recorded the action potential duration, activation map, conduction velocity, and Ca2+ transient individually in the right and left atria. In addition, the programmed stimulation also determines the inducibility of atrial tachyarrhythmias. Precise activation mapping is performed to identify the propagation of the excitation in the atrium during an induced atrial tachyarrhythmia. Optical mapping with a specialized setting enables a thorough electrophysiological evaluation of the atrium in murine pathological models.

Paradoxical high augmentation index in females with diabetes mellitus

The relationship between diabetes mellitus (DM) and augmentation index (AIx) remains unclear. We conducted an observational cross‐sectional study. Subjects were patients who underwent coronary angiography. We examined the relationship between high AIx and several factors. The total number of diabetic patients was 144, and median AIx was 0.256. In diabetic patients, the significant relationship between female gender and high AIx (median cut‐off value, ≥0.256) was found by the multivariate logistic analysis (adjusted odds ratio = 2.888; 95% confidence interval: 1.032‐8.081). The significant relationship between female gender and high AIx was found in patients with DM.

Long-Term Prognosis of Catecholaminergic Polymorphic Ventricular Tachycardia Patients With Ryanodine Receptor (RYR2) Mutations.

In this issue of the Journal, Kawata and colleagues7 evaluate the recurrence rate of fatal cardiac events after initiation of appropriate medical therapy in 34 CPVT patients with RyR2 mutations. During 7.4 years of follow-up, 7 of the 34 patients developed fatal cardiac events, and among them, 6 patients (85.7%) were not compliant with exercise restriction or medication therapy. In other words, the majority of CPVT patients were well controlled by appropriate medical therapy, emphasizing the importance of drug compliance and advice to the atecholaminergic polymorphic ventricular tachycardia (CPVT) is a malignant inherited arrhythmia syndrome characterized by bidirectional or polymorphic ventricular arrhythmias under conditions of increased sympathetic activity in young patients without structural heart disease.1 The common autosomal-dominant form has been linked to mutations in the gene encoding the cardiac calcium-release channel (RYR2).2 To date at least 130 unique, almost exclusively missense, mutations in RYR2 have been reported.3 A less common but more severe autosomal-recessive form is caused by mutations in the gene encoding cardiac calsequestrin (CASQ2), the major calcium-binding protein in the sarcoplasmic reticulum (SR).4 Mutations in these genes have been identified in approximately 60% of patients diagnosed as CPVT,2 and result in inappropriate calcium leakage from the SR, leading to cytosolic calcium overload generating delayed afterdepolarizations, triggered activity, and ventricular arrhythmias, particularly under increased β-adrenergic tone. CPVT has become recognized as C