Investigation of the Proarrhythmic Effects of Antidepressants according to QT Interval, QT Dispersion and T Wave Peak-to-End Interval in the Clinical Setting.

OBJECTIVE: Some antidepressants have been implicated as risk factors for QT prolongation, which is a predictor of sudden cardiac death. However, the QT interval is considered an imperfect biomarker for proarrhythmic risk. Therefore, we reevaluated the risk of sudden cardiac death due to antidepressants using improved. METHODS: , namely, QT dispersion (QTD), T wave peak-to-end interval (Tp-e), and Tp-e/QT ratio. METHODS: We compared the effects of antidepressants on QTc (QT/RR1/3), QTD, Tp-e, and Tp-e/QT ratio in 378 patients with mood disorder. We also compared each index between 165 healthy controls and 215 randomly selected age-matched patients. RESULTS: Age (p<0.01), sex (p<0.05), tricyclic antidepressant (TCA) use (p<0.05), and clomipramine (p<0.01) and mianserin (p<0.05) use in particular, significantly associated with a prolonged QTc. We also found that age (p<0.01), TCA use (p<0.05), and clomipramine (p<0.01) and mianserin (p<0.05) use in particular, significantly prolonged QTD. However, there was no correlation between each variable and Tp-e or Tp-e/QT ratio. Significant differences in QTc and QTD were found between the patients and healthy controls. CONCLUSION: From our results, prediction of risk of sudden cardiac death by QTD, Tp-e, or Tp-e/QT ratio was inconsistent. Increased QTD may be more suitable for predicting sudden cardiac death due to antidepressants.

Lower birth weight is associated with higher resting heart rate during boyhood.

There is substantial evidence that low birth weight is associated with the development of cardiovascular disease in adult life. Moreover, resting heart rate is a prognostic factor of cardiovascular morbidity and mortality. However, there are scarce data regarding the association between birth weight and resting heart rate in later life. Therefore, we investigated the association of anthropometric data at birth and hemodynamic indices including resting heart rate in Japanese boys. The data of 1,107 male students of a junior high school in Tokyo, Japan, who underwent a medical check-up in the year of admission to the school (12 or 13 years old) were used. Information on anthropometric data at birth based on "The Maternal and Child Health Handbook" was obtained from 573 students. From a standard 12-channel resting electrocardiogram, 8 cardiac cycles were used to estimate heart rate. Resting heart rate correlated positively with body mass index at the same age (r=0.100, p=0.017) and correlated negatively with birth weight (r=-0.102, p=0.015), height at birth (r=-0.125, p=0.003), and head circumference at birth (r=-0.095, p=0.025). The negative correlation of anthropometric data at birth with heart rate at the age of 12 or 13 was independent of body mass index at the same age. The mean value of resting heart rate at the age of 12 or 13 adjusted for body mass index at the same age was significantly higher in the lower tertile of birth weight than in the higher tertile of birth weight (81.7 vs. 78.5 beats/min, p=0.028). In conclusion, lower birth weight is associated with higher resting heart rate during boyhood, suggesting that elevated heart rate may be one mechanism linking small size at birth with the development of cardiovascular disease in future life.

Relations of plasma high-sensitivity C-reactive protein to traditional cardiovascular risk factors.

Variations of circulating C-reactive protein (CRP) levels are supposed to reflect chronic inflammatory process of the cardiovascular system. In particular, it has been reported that high-sensitivity CRP (hsCRP) is a promising marker of coronary heart disease. In the present study, we assessed the relationship between hsCRP and classic cardiovascular risk factors, such as age, blood pressure, smoking habit and serum lipids. Plasma hsCRP was measured by ELISA in 908 subjects, aged 30-79 years, who entered our health-check program. Plasma hsCRP level was 0.54+/-0.02 mg/l in 566 subjects without any disease currently treated. The level was significantly higher in patients treated for hypertension (0.74+/-0.06 mg/l, P=0.002), diabetes mellitus (0.77+/-0.09 mg/l, P=0.016) or coronary artery disease (0.99+/-0.16 mg/l, P=0.008) than in subjects without diseases. In a simple regression analyses of the 566 subjects without diseases, plasma hsCRP positively correlated with male gender, smoking, body mass index, systolic blood pressure, white blood cell count, blood hemoglobin, fasting blood glucose, serum gamma-GTP, uric acid and triglycerides, and inversely correlated with serum albumin and HDL-cholesterol. In multiple regression analysis, white blood cell count (r=0.276, P<0.001), body mass index (r=0.246, P<0.001), age (r=0.122, P=0.001) and smoking (r=0.112, P=0.009) showed independent correlations with plasma hsCRP. It is suggested that variation of circulating hsCRP, even within normal range, is involved in the interrelation of cardiovascular risk factors, such as age, smoking, obesity, high blood pressure and dyslipidemia, which are supposed to promote atherosclerosis and ultimately provoke cardiovascular diseases, such as coronary artery disease.

Relationship between fatty liver disease and intracranial main artery stenosis.

OBJECTIVE: The aim of this study was to evaluate the relationship between fatty liver disease (FLD) and cerebrovascular disease. METHODS: We conducted a cross-sectional study of 76 consecutive healthy subjects who participated in a two-day hospitalized health checkup program. The maximal intima-media thickness (IMT) of the common carotid artery and bifurcation of the carotid artery as well as the plaque score (PS) were evaluated on carotid artery ultrasonography. Fluid attenuated inversion recovery brain MRI was used to determine the presence of asymptomatic cerebral lesions and periventricular hyperintensity. Brain MR angiography was used to evaluate the degree of intracranial main artery stenosis (ICAS). FLD was diagnosed based on the ultrasonographic pattern. RESULTS: The PS and IMT did not differ between the FLD (n=24) and non-FLD (n=52) groups. There was a tendency toward a higher percentage of multiple lacunar lesions in the non-FLD group than in the FLD group. ICAS was significantly more frequent in subjects in the FLD group than those in the non-FLD group (25.0% vs. 5.8%). A logistic regression analysis revealed that age and FLD were significant determinants of ICAS. CONCLUSION: Our study findings suggest a significant association between ICAS and FLD.

Association of metabolic syndrome with urinary albumin excretion, low-grade inflammation, and low glomerular filtration rate among non-diabetic Japanese subjects.

OBJECTIVE: Several studies have reported a significant association of metabolic syndrome with urinary albumin excretion, high-sensitivity C-reactive protein, or chronic kidney disease; however, no study has investigated the association of metabolic syndrome with these 3 factors together in the same individual. Therefore, we conducted the present study to obtain more information on this association. METHODS: We enrolled 712 Japanese subjects without diabetes, macroalbuminuria, or medications, who entered our hospitalized health check-up program (180 women and 532 men; mean age, 53.2 years; mean body mass index, 24.1 kg/m(2)). Metabolic syndrome was diagnosed by 4 major definitions. Low glomerular filtration rate was defined as an estimated glomerular filtration rate of <60 mL/min/1.73 m(2). RESULTS: Both urinary albumin excretion and high-sensitivity C-reactive protein were significantly higher in those with metabolic syndrome than without, and metabolic syndrome was an independent determinant of both. In contrast, estimated glomerular filtration rate and the prevalence of low glomerular filtration rate did not differ significantly between those with and without metabolic syndrome. Among the 5 components of metabolic syndrome and other clinical variables, systolic blood pressure was an independent determinant of urinary albumin excretion; the 5 components and low-density lipoprotein cholesterol were all independent determinants of high-sensitivity C-reactive protein; systolic blood pressure was an independent determinant of low glomerular filtration rate. CONCLUSION: Metabolic syndrome is associated with vascular dysfunction and low-grade inflammation and the latter association is strong, whereas the association of metabolic syndrome with low glomerular filtration rate may be less apparent among those without diabetes, macroalbuminuria, and medications.

Relationship between markers of inflammation and brachial-ankle pulse wave velocity in Japanese men.

The objective of the present study was to examine the relationship between markers of inflammation, such as high-sensitivity C-reactive protein (hsCRP) and erythrocyte sedimentation rate (ESR), and brachial-ankle pulse wave velocity (baPWV), an indicator of arterial stiffness, in Japanese men. We studied 269 male subjects (mean age, 53 years) who entered our health check-up program. Subjects who were receiving any medication were excluded from the study. baPWV was measured using a volume-plethysmographic apparatus (Form /ABI; Colin, Co. Ltd., Komaki, Aichi, Japan). In addition to routine laboratory tests including ESR, serum levels of hsCRP were determined by a highly sensitive ELISA technique. baPWV was significantly correlated with age (r = 0.41, P < 0.0001), height (r = - 0.21, P = 0.0006), body weight (r = - 0.17, P = 0.007), mean blood pressure (r = 0.66, P < 0.0001), pulse pressure (r = 0.56, P < 0.0001), heart rate (r = 0.25, P < 0.0001), ln (ESR) (r = 0.20, P = 0.001), fasting blood glucose (r = 0.23, P = 0.0001), and ln (serum hsCRP) (r = 0.23, P = 0.0002). baPWV in the highest tertile of ESR was significantly higher than that in the lowest tertile of ESR (P = 0.005). baPWV in the highest tertile of serum hsCRP was significantly higher than those in the lowest tertile (P = 0.002) and the middle tertile of serum hsCRP (P = 0.02). In multiple regression analysis, baPWV significantly correlated with ln (serum hsCRP) independently of other clinical variables that showed a significant correlation with baPWV. baPWV is significantly associated with serum levels of hsCRP in Japanese men, suggesting that inflammation is involved in arterial stiffening.

Urinary excretion of liver fatty acid-binding protein in health-check participants.

BACKGROUND: Messenger RNA of liver fatty acid-binding protein (L-FABP) is expressed in proximal tubules of the kidney, and a certain amount is excreted into urine. We analyzed factors relating to the urinary L-FABP excretion in health-check participants. METHODS: We measured L-FABP in the first morning urine by ELISA in 715 men and 193 women 30-79 years of age who entered a 2-day hospitalized health checkup program. In addition to the routine physical examination and laboratory tests, plasma high-sensitivity C-reactive protein (HSCRP) was assayed. RESULTS: In 150 healthy subjects, urinary L-FABP averaged 3.6 +/- 0.2 microg/g creatinine, whereas the values were significantly increased in patients with hypertension (5.2 +/- 0.4, P = 0.010), diabetes mellitus (5.5 +/- 0.5, P < 0.001), and chronic hepatitis (5.8 +/- 1.0, P = 0.022). Urinary L-FABP excretion was significantly greater in women than in men when the value was related to creatinine. In regression analysis in men, urinary L-FABP was positively correlated with fasting plasma glucose (r = 0.103, P = 0.033) and plasma HSCRP (r = 0.135, P = 0.006). CONCLUSIONS: It is suggested that renal production and urinary excretion of L-FABP are increased in situations in which arteriosclerosis is promoted, such as hypertension, diabetes mellitus, and cardiovascular inflammation.

[Myocardial systolic function of the left ventricle along the long axis in patients with essential hypertension: a study by pulsed tissue Doppler imaging].

OBJECTIVES: Myocardial contractility of the left ventricle along the long axis in hypertensives is not well characterized. The systolic velocities of the left ventricular myocardium along the long axis were measured by pulsed tissue Doppler imaging in patients with mild to moderate essential hypertension. The relationships between the systolic velocity of left ventricular myocardium along the long axis and the blood pressure, and the left ventricular geometry were investigated. METHODS: The study included 60 untreated hypertensive patients (hypertension group) and 59 age-matched healthy subjects (control group). M-mode echocardiograms were recorded, and the relative wall thickness, left ventricular mass index and left ventricular end-systolic stress were calculated. The peak systolic velocities of the left ventricular posterior wall motion (Sw) were measured by pulsed tissue Doppler imaging. RESULTS: The Sw was significantly lower in the hypertension group than in the control group (8.3 +/- 1.9 vs 9.2 +/- 2.0 cm/sec, p < 0.05). The Sw was correlated inversely with systolic blood pressure (r = -0.31, p < 0.005), diastolic blood pressure (r = -0.25, p < 0.0001), interventricular septal thickness (r = -0.41, p < 0.0001), left ventricular posterior wall thickness (r = -0.39, p < 0.0001), relative wall thickness (r = -0.33, p < 0.001), and left ventricular mass index (r = -0.37, p < 0.001) in all subjects. CONCLUSIONS: The systolic velocity of the left ventricular myocardium along the long axis is decreased in patients with mild to moderate essential hypertension, and is negatively correlated with blood pressure and the severity of left ventricular concentric hypertrophy.

Microsatellite DNA polymorphism of human adrenomedullin gene in type 2 diabetic patients with renal failure.

BACKGROUND: Adrenomedullin (AM) is a hypotensive peptide widely produced in the cardiovascular organs and tissues such as the heart, kidney, and the vascular cells. We have previously cloned and sequenced the genomic DNA encoding human AM gene, and determined that the gene is located in the short arm of chromosome 11. The 3'-end of the gene is flanked by the microsatellite marker of cytosine adenine (CA) repeats. In this study, we investigated the association between DNA variations in AM gene and the predisposition to develop nephropathy in type 2 diabetes mellitus. METHODS: Genomic DNA was obtained from the peripheral leukocytes of 233 normal healthy subjects (NH), 139 type 2 diabetic patients on hemodialysis (DM-HD), 106 control patients with type 2 diabetes without nephropathy (DM-C) and 318 hemodialysis patients due to chronic glomerulonephritis (CGN-HD). The genomic DNA was subject to polymerase chain reaction (PCR) using a fluorescence-labeled primer, and the number of CA repeats were determined by polyacrylamide gel electrophoresis (PAGE). RESULTS: In our Japanese subjects, there existed four types of alleles with different CA-repeat number; 11, 13, 14, and 19. The frequencies of these alleles were 11: 27.7%, 13: 32.8%, 14: 35.6%, and 19: 3.9% in NH. These allele frequencies were not significantly different in DM-C and CGN-HD. However, DM-HD showed significantly different distribution of allele frequency from other groups (chi 2 = 18.9, P = 0.026). Namely, the frequency of 19-repeat allele in DM-HD was higher (9.0%) than NH, DM-C, and CGN-HD (P = 0.005, 0.041, and 0.004, respectively). CONCLUSION: The microsatellite DNA polymorphism of AM gene may be associated with the genetic predisposition to develop nephropathy in Japanese patients with type 2 diabetes mellitus.