Shoichi Senda

Left Ventricular Diastolic Dysfunction as Assessed by Echocardiography in Metabolic Syndrome

The purpose of the present study was to elucidate the cardiac structure and function in patients who have metabolic syndrome but no history of cardiovascular disease by analyzing echocardiographic findings. Echocardiographic examination was performed to screen for cardiovascular disease in 135 patients who were in their sixties. Patients were divided into metabolic syndrome (n=65, age: 65±2.7 years) and non–metabolic syndrome (n=70, age: 66±2.5 years) groups based on the criteria for metabolic syndrome proposed by the Japanese Society of Hypertension and seven other societies in 2005. The left ventricular (LV) wall thickness and dimension were measured by M-mode echocardiography. The relative wall thickness, LV mass index, and LV ejection fraction (LVEF) were calculated. LV diastolic function was assessed by the peak velocity of early rapid filling (E velocity) and the peak velocity of atrial filling (A velocity), and the ratio of E to A (E/A) was assessed by the transmitral flow. The Tei index, which reflects both LV diastolic and systolic function, was also calculated. There were no differences in relative wall thickness, LV mass index, or LVEF between the two groups. However, both the E/A and Tei index were significantly different between the metabolic syndrome (0.66±0.14 and 0.36±0.07, respectively) and non–metabolic syndrome (0.88±0.25 and 0.29±0.09) groups (p<0.001). These results indicate that patients with metabolic syndrome can have cardiac diastolic dysfunction even if they have neither LV hypertrophy nor systolic dysfunction.

Visit-to-visit variability in blood pressure over a 1-year period is a marker of left ventricular diastolic dysfunction in treated hypertensive patients.

Although visit-to-visit variability in systolic blood pressure (SBP) has recently been demonstrated to be a strong predictor of stroke, there are no data about relationships between SBP variability and cardiac damage in hypertensive patients. We compared relationships between visit-to-visit variability in SBP and left ventricular (LV) diastolic dysfunction with the relationships between the mean SBP value and cardiac parameters in treated patients. Forty treated hypertensive patients (69±9 years of age) had their blood pressure measured at outpatient clinics every 1 or 2 months over a 1-year period. The standard deviation (s.d.) of SBP and the difference between the maximum and minimum SBPs during this year were calculated to assess visit-to-visit variability. The mean SBP during the year was also calculated. LV diastolic function was assessed by the ratio (E/A) of early (E) and late (A) diastolic transmitral flows, early diastolic mitral annular velocity (e′) and the ratio (E/e′) of E to e′ using Doppler echocardiography. E/A only correlated with the s.d. of SBP (r=−0.327, P=0.040), whereas e′ correlated with s.d. of SBP (r=−0.496, P=0.001) and maximum–minimum SBP difference (r=−0.490, P=0.001). E/e′ correlated with s.d. of SBP (r=0.384, P=0.014), maximum–minimum SBP difference (r=0.410, P=0.009), and the mean value of SBP (r=0.349, P=0.028). Multiple regression analysis demonstrated only the maximum–minimum SBP difference independently associated with E/e′ (β=0.410, P=0.009). Thus, the visit-to-visit variability of SBP showed better correlation with LV diastolic dysfunction than mean values of SBP. High visit-to-visit variability of SBP was associated with LV diastolic dysfunction and may constitute a high risk for diastolic heart failure in hypertensive patients.

Antioxidant Effect of a New Calcium Antagonist, Azelnidipine, in Cultured Human Arterial Endothelial Cells

Azelnidipine is a novel dihydropyridine-type calcium antagonist with long-acting anti-hypertensive action and a low reported incidence of tachycardia. We aimed to evaluate its antioxidant activity in cultured human arterial endothelial cells under oxidative stress. Endothelial cells were exposed to 1 mM H2O2 and treated with 100 μM α-tocopherol, 1 nM, 10 nM or 100 nM azelnidipine, 100 nM nifedipine or 100 nM amlodipine. After 3 h, the cell number and level of lipid peroxidation were evaluated by measuring the total protein and 8-iso-PGF2α concentrations, respectively. The total protein concentration was similar with each treatment. Inhibition of 8-iso-PGF2α was greatest with 10 nM azelnidipine (compared with the other drugs); the difference between 10 nM and 100 nM azelnidipine was not significant. We conclude that azelnidipine has a potent antioxidative effect that could be of significant clinical benefit when combined with its long-lasting anti-hypertensive action and low incidence of tachycardia.

Relationships between Echocardiographic Findings, Pulse Wave Velocity, and Carotid Atherosclerosis in Type 2 Diabetic Patients

The purpose of the present study was to analyze the relationships between echocardiographic findings, brachial-ankle pulse wave velocity, and carotid atherosclerosis in type 2 diabetic patients. In 70 type 2 diabetic patients without cardiovascular disease, pulse wave velocity was measured using an automatic waveform analyzer, and the carotid plaque score was obtained by carotid ultrasonography. The left ventricular wall thickness and the indexes of left ventricular diastolic function (the peak velocity of early rapid filling [E velocity], the peak velocity of atrial filling [A velocity], and the E/A ratio) were obtained by echocardiography. Brachial-ankle pulse wave velocity correlated significantly with the carotid plaque score, but the correlation was weak (r=0.37, p=0.001). The brachial-ankle pulse wave velocity demonstrated a strong correlation with the A velocity (r=0.73, p<0.001), the ratio of E to A (E/A) (r=−0.63, p<0.001), and the deceleration time of the E velocity (r=0.48, p<0.001). Stepwise regression analysis showed that the A velocity (β coefficient=0.42, p<0.001) and ventricular septal thickness at the left ventricular outflow tract (β coefficient=0.27, p=0.001) were independently associated with brachial-ankle pulse wave velocity. Stepwise regression analysis indicated that ventricular septal thickness at the left ventricular outflow tract (β coefficient=0.38, p=0.001) was independently associated with the plaque score. These results indicate that left ventricular diastolic dysfunction as revealed by increased peak velocity of atrial filling reflects arterial stiffening in type 2 diabetic patients. In addition, myocardial wall thickening at the left ventricular outflow tract reflects not only arterial stiffening but also carotid atherosclerosis. Therefore, these abnormal echocardiographic findings of left ventricular diastolic dysfunction and myocardial wall thickening may be useful markers of the presence of progressive arteriosclerosis in type 2 diabetic patients.

RELATIONSHIP BETWEEN MYOCARDIAL TISSUE DENSITY MEASURED BY MICROGRAVIMETRY AND SOUND SPEED MEASURED BY ACOUSTIC MICROSCOPY

If myocardial tissue can be assumed to be fluid-like, myocardial tissue elasticity can be estimated by the sound speed of tissue based on the equation K = rho(c)2, where K is the elastic bulk modulus, rho is density, and c is the sound speed of tissue. However, little data exist regarding the relationship between the sound speed of tissue and tissue density. The purpose of the present study was to evaluate the relationship between the sound speed of tissue and tissue density of various diseased myocardia. Myocardial tissue specimens at autopsy were obtained from 10 control patients without cardiovascular disease, 8 patients with pressure overload left ventricular hypertrophy (POLVH), and 8 patients with cardiac amyloidosis (AMD). Myocardial tissue sound speed was measured using a scanning acoustic microscope operating in the frequency of 450 MHz, and tissue density was measured by microgravimetry. The sound speed in POLVH (1639 +/- 17 m/s) was higher and that in AMD (1565 +/- 11 m/s) was lower than that in control patients (1615 +/- 15 m/s) (p < 0.001) at the temperature of 20-22 degrees C. The density in POLVH (1.087 +/- 0.004 g/cm3) was higher and that in AMD (1.072 +/- 0.003 g/cm3) was lower than that in control patients (1.082 +/- 0.003 g/cm3) (p < 0.001). Tissue density correlated with sound speed in all three groups (r = 0.96, p < 0.001). Therefore, myocardial tissue sound speed data obtained by acoustic microscopy enabled us to evaluate tissue elasticity without measuring tissue density directly.

Seasonal Blood Pressure Variation and Its Relationship to Environmental Temperature in Healthy Elderly Japanese Studied by Home Measurements

The purpose of the present study was to examine seasonal blood pressure variation and its relationship to environmental temperature in healthy elderly Japanese, as studied by home measurements. Fifteen healthy elderly Japanese (79.3 ± 5.9 yrs) measured their blood pressure at home each morning for more than 25 times per month for 3 years. Monthly mean outdoor temperatures were obtained from the Takamatsu meteorological Observatory. The highest levels of systolic and diastolic blood pressure measured at home were observed in February (129 ± 14 and 81 ± 13 mmHg). The lowest levels of systolic and diastolic blood pressure measured at home were observed in August (117 ± 11 and 73 ± 10 mmHg). Likewise, the lowest and highest means of outdoor temperature were observed in February (5.0°C) and August (29.2°C), respectively. Hence, both systolic and diastolic blood pressure demonstrated a close inverse correlation with the means of outdoor temperature (r = −0.973, p < 0.001 and r = −0.985, p < 0.001, respectively). A 1°C decrease in the mean outdoor temperature was associated with rises of 0.43 mmHg in systolic blood pressure (SBP) and 0.29 mmHg in diastolic blood pressure (DBP). Seasonal variations in home blood pressure and outdoor temperature showed complete correspondence in healthy elderly Japanese, with the blood pressures being inversely related to the ambient temperature. These seasonal home blood pressure variations should be kept in mind when controlling blood pressure in elderly patients.

Efficacy of zinc administration in patients with hepatitis C virus-related chronic liver disease.

Objective. Zinc supplementation has been shown to contribute to inhibition of liver fibrosis and improvement in hepatic encephalopathy. However, little is known about the anti-inflammatory effect of zinc on hepatitis C virus (HCV)-related chronic liver disease (CLD). We therefore examined the effects of zinc administration on inflammatory activity and fibrosis in the liver of patients with HCV-related CLD. Material and methods. Polaprezinc, a complex of zinc and l-carnosine, was administrated at 225 mg/day for 6 months to 14 patients with HCV-related CLD, in addition to their ongoing prescriptions. Peripheral blood cell counts, liver-related biochemical parameters, serological markers for liver fibrosis, HCV-RNA loads, and serum levels of zinc and ferritin were evaluated before and after zinc administration. Results. Serum zinc concentrations were positively correlated with hepatic reserve before zinc supplementation. A significant increase in serum zinc level was observed after zinc supplementation (64±15 versus 78±26 mg/dl, p=0.0156). Treatment with polaprezinc significantly decreased serum aminotransferase levels (aspartate aminotransferase (AST): 92±33 versus 63±23 IU/l, p=0.0004; alanine aminotransferase (ALT): 106±43 versus 65±32 IU/l, p=0.0002), whereas alkaline phosphatase levels were significantly increased (305±117 versus 337±118 U/l, p=0.0020). Serum ferritin levels were significantly decreased by treatment with polaprezinc (158±141 versus 101±80 ng/ml, p=0.0117). The reduction rate of ALT levels by polaprezinc was positively correlated with that of ferritin (r2=0.536, p=0.0389). There was a tendency toward a decrease in serum type IV collagen 7S levels after treatment with polaprezinc. However, administration of polaprezinc did not affect peripheral blood cell counts, other liver function tests, or HCV-RNA loads. Conclusions. These findings suggest that polaprezinc exerts an anti-inflammatory effect on the liver in patients with HCV-related CLD by reducing iron overload.

Comparison of central blood pressure and cardio-ankle vascular index for association with cardiac function in treated hypertensive patients

Recent automated applanation tonometry can measure radial pulse wave-derived central blood pressure (CBP), which has shown a prognostic value independently of peripheral blood pressure. However, CBPs clinical significance has not been fully established. We examined the associations between CBP and cardiac structure and function by comparing them with those of arterial stiffness assessed by cardio-ankle vascular index (CAVI) in treated hypertensive patients. Enrolled in the study were 102 patients (71±7 years) with treated hypertension. The transmitral early-to-atrial velocity ratio (E/A), peak systolic (S′), early diastolic (E′) mitral annular velocities and the Tei index were measured as indexes of cardiac function derived from conventional and tissue Doppler echocardiography. Left ventricular mass index (LVMI) was measured as an index of LV hypertrophy. CBP and CAVI were measured just after echocardiographic examination. CBP, but not CAVI, correlated with LVMI (r=0.306, P<0.01). Although CBP correlated only with the Tei index (r=0.201, P<0.05), CAVI correlated with E/A (r=−0.387, P<0.001), S′ (r=−0.270, P<0.01), E′ (r=−0.362, P<0.01) and the Tei index (r=0.339, P<0.01). Stepwise regression analysis revealed that neither CBP nor CAVI was independently associated with E/A, S′ or E′. However, CAVI, but not CBP, was independently associated with the Tei index (β coefficient=0.311, P<0.001), reflecting both LV systolic and diastolic function. In conclusion, CBP may be suitable for detecting LV hypertrophy. In contrast, CAVI may be suitable for detecting LV dysfunction. This difference, suggesting the clinical value of each parameter, should be kept in mind when we use CBP and CAVI for assessing arteriosclerosis in treated hypertension.

Diagnostic workup for fever of unknown origin: a multicenter collaborative retrospective study.

Objective Fever of unknown origin (FUO) can be caused by many diseases, and varies depending on region and time period. Research on FUO in Japan has been limited to single medical institution or region, and no nationwide study has been conducted. We identified diseases that should be considered and useful diagnostic testing in patients with FUO. Design A nationwide retrospective study. Setting 17 hospitals affiliated with the Japanese Society of Hospital General Medicine. Participants This study included patients ≥18 years diagnosed with ‘classical fever of unknown origin’ (axillary temperature ≥38°C at least twice over a ≥3-week period without elucidation of a cause at three outpatient visits or during 3 days of hospitalisation) between January and December 2011. Results A total of 121 patients with FUO were enrolled. The median age was 59 years (range 19–94 years). Causative diseases were infectious disease in 28 patients (23.1%), non-infectious inflammatory disease in 37 (30.6%), malignancy in 13 (10.7%), other in 15 (12.4%) and unknown in 28 (23.1%). The median interval from fever onset to evaluation at each hospital was 28 days. The longest time required for diagnosis involved a case of familial Mediterranean fever. Tests performed included blood cultures in 86.8%, serum procalcitonin in 43.8% and positron emission tomography in 29.8% of patients. Conclusions With the widespread use of CT, FUO due to deep-seated abscess or solid tumour is decreasing markedly. Owing to the influence of the ageing population, polymyalgia rheumatica was the most frequent cause (9 patients). Four patients had FUO associated with HIV/AIDS, an important cause of FUO in Japan. In a relatively small number of cases, cause remained unclear. This may have been due to bias inherent in a retrospective study. This study identified diseases that should be considered in the differential diagnosis of FUO.

Selenium deficiency is associated with insulin resistance in patients with hepatitis C virus–related chronic liver disease

The relationship between selenium (Se) deficiency and insulin resistance has not much been established in persistent hepatitis C virus (HCV) infection, although Se deficiency is often observed in patients with liver cirrhosis. We hypothesized that the decreased serum Se levels were associated with the severity of hepatic fibrosis or insulin resistance in patients with HCV-related chronic liver disease (CLD). To test the hypothesis, 52 patients with HCV-related CLD including chronic hepatitis and liver cirrhosis were enrolled in this study. The severity of hepatic fibrosis was divided into 4 categories (F(1) through F(4)) according to the new Inuyama classification. Insulin resistance was defined by the homeostasis model for assessment of insulin resistance value. Serum Se levels significantly declined in proportion to the severity of hepatic fibrosis and were positively correlated with serum albumin (r = 0.372, P = .0065) and zinc (r = 0.403, P = .0081) concentrations. Serum Se levels were also linked to glutathione peroxidase activities in the sera of the enrolled patients (r = 0.374, P = .0148). By contrast, serum Se levels were inversely correlated with the homeostasis model for assessment of insulin resistance values (r = -0.304, P = .0338). However, serum Se levels were independent of HCV genotype and loads of HCV-RNA. These findings suggest that Se deficiency was associated with the severity of hepatic fibrosis in patients with HCV-related CLD and that Se deficiency was likely to be one of the factors contributing to insulin resistance in those patients.