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Biomedical subjects

Shuichi Takishita

Publications and source records attributed to Shuichi Takishita.

At least 19 recordsLinked to original sources

Significance of coronary artery calcification score (CACS) for the detection of coronary artery disease (CAD) in chronic dialysis patients.

BACKGROUND: Coronary artery disease (CAD) is a principal cause of death in patients with end-stage renal disease (ESRD). The coronary artery calcification score (CACS), determined by electron-beam computed tomography (EBCT), is useful for the detection of CAD in non-ESRD patients. There are few reports on the usefulness of EBCT for the detection of CAD, however, in ESRD patients. We examined the relation between CACS and CAD in ESRD patients. METHODS: Coronary angiography (CAG) was used to diagnose CAD in patients with significant coronary artery stenosis (>or=50%). We examined 76 ESRD patients on chronic dialysis therapy from 1997 to 2005, of which 51 are men, 25 are women, mean (S.D.) age of 57.9 (12.1) years and mean (S.D.) HD duration of 7.7 (6.6) years. There were 50 (35 men, 15 women) patients with CAD and 26 (16 men, 10 women) without CAD. RESULTS: The median CACS was 1290 in all patients, 1689 in the CAD group and 527 in the non-CAD group; the mean (S.D.) CACS was 1833 (2003) in all patients, 2338 (2209) in the CAD group and 861 (991) in the non-CAD group. CACS was significantly higher in the CAD group than in the non-CAD group. The CACS cutoff values for predicting CAD were calculated at intervals of 100. At the cutoff values of >or=100, >or=500, >or=1000, >or=2000, and >or=3000, the sensitivity was 98%, 90%, 68%, 42%, and 32% and the specificity was 35%, 50%, 69%, 85%, and 96%, respectively. CONCLUSIONS: EBCT is not adequate for screening asymptomatic ESRD patients. Because EBCT is less invasive than CAG, further study is necessary to determine whether CAG should be performed in all high-risk ESRD patients on chronic dialysis.

Calcinosis↗

Increased pulse wave velocity is associated with low creatinine clearance and proteinuria in a screened cohort.

BACKGROUND: Chronic kidney disease (CKD) is a risk factor for future cardiovascular disease. Although pulse wave velocity (PWV), which reflects arterial stiffness, was increased in subjects with CKD, little is known regarding whether renal function is associated with PWV in a low-risk population and whether proteinuria and decreased renal function synergistically affect PWV. METHODS: Subjects are 3,387 persons (mean age, 52 years) who attended a health checkup program in Okinawa, Japan. We measured brachial-ankle PWV (baPWV) by using an automatic oscillometric method. Proteinuria was semiquantified by using the dipstick method. Creatinine clearance (CCr) was estimated by using the Cockcroft-Gault formula. RESULTS: baPWV was accelerated with increases in age, systolic blood pressure, fasting glucose level, and total cholesterol level; male sex; presence of proteinuria; and decrease in CCr. All these factors independently predicted baPWV in multiple regression analysis. When subjects were divided into 6 groups according to CCr of 90 or greater, 60 to 89, or 30 to 59 mL/min (> or =1.50, 1.00 to 1.48, or 0.50 to 0.98 mL/s) and the absence or presence of proteinuria, baPWV, after adjustment for age, sex, and systolic blood pressure, increased in a stepwise fashion corresponding to decreases in CCr regardless of proteinuria, with the relationship exaggerated in the presence of proteinuria. CONCLUSION: Arterial stiffness increases with a decrease in renal function or with proteinuria independently of other risk factors.

Adult↗

Plasma aldosterone in hypertensive patients on chronic hemodialysis: distribution, determinants and impact on survival.

A high plasma aldosterone concentration (PAC) is known to be associated with poor outcome in patients with cardiac disease. However, the prognostic value of PAC in chronic hemodialysis (HD) patients is unknown. In 1996 we examined 128 hypertensive patients treated with antihypertensive drugs, excluding angiotensin-converting enzyme inhibitors, who were undergoing chronic HD (ages 61.8+/-13.8 years, 62% male), and for whom PAC (ng/dl) data were obtained. We followed up these patients until November 2003. During the follow-up period, 30 patients died. About half of all patients (48%) had PAC values above the normal range. We assigned the 128 patients to a lower (<22.9) or higher (> or = 22.9) PAC group according to the median baseline PAC. The survival rate as calculated by the Kaplan-Meier method was 90.6% in the higher PAC group and 62.5% in the lower PAC group (p=0.003). In multivariate analysis, serum potassium and plasma renin activity were independent determinants of PAC. Cox proportional hazards analysis, with adjustment for other variables including diabetes, showed that lower PAC was independently predictive of death. The adjusted hazard ratio (95% confidence interval) of the lower PAC group was 2.905 (1.187-7.112, p=0.020). The significance of PAC became marginal by adjustment with albumin or potassium. These results indicate that higher PAC is common, but not associated with an increase in total and cardiovascular deaths among hypertensive patients undergoing chronic HD. The association between lower PAC and poor survival may be driven by volume retention and/or lower potassium.

Aged↗

Sympathetic hyperreactivity to air-jet stress in the chromosome 1 blood pressure quantitative trait locus congenic rats.

A chromosome 1 blood pressure quantitative trait locus (QTL) was introgressed from the stroke-prone spontaneously hypertensive rats (SHRSP) to Wistar-Kyoto (WKY) rats. This congenic strain (WKYpch1.0) showed an exaggerated pressor response to both restraint and cold stress. In this study, we evaluated cardiovascular and sympathetic response to an air-jet stress and also examined the role of the brain renin-angiotensin system (RAS) in the stress response of WKYpch1.0. We measured mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA) responses to air-jet stress in WKYpch1.0, WKY, and SHRSP. We also examined effects of intracerebroventricular administration of candesartan, an ANG II type 1 receptor blocker, on MAP and HR responses to air-jet stress. Baseline MAP in the WKYpch1.0 and WKY rats were comparable, while it was lower than that in SHRSP rats. Baseline HR did not differ among the strains. In WKYpch1.0, air-jet stress caused greater increase in MAP and RSNA than in WKY. The increase in RSNA was as large as that in SHRSP, whereas the increase in MAP was smaller than in SHRSP. Intracerebroventricular injection of a nondepressor dose of candesartan inhibited the stress-induced pressor response to a greater extent in WKYpch1.0 than in WKY. Intravenous injection of phenylephrine caused a presser effect comparable between WKYpch1.0 and WKY. These results suggest that the chromosome 1 blood pressure QTL congenic rat has a sympathetic hyperreactivity to an air-jet stress, which causes exaggerated pressor responses. The exaggerated response is at least partly mediated by the brain RAS.

Animals↗

Relationship between dyslipidemia and the risk of developing end-stage renal disease in a screened cohort.

BACKGROUND: Disturbances in lipid metabolism are often observed in patients with renal failure and could be a risk factor for end-stage renal disease (ESRD). However, few studies have examined abnormal lipid metabolism as a risk factor for the development of ESRD in the general population. METHODS: We examined the cumulative incidence of ESRD based on the results of a community-based mass screening in Okinawa, Japan, which was conducted in 1993 by the Okinawa General Health Maintenance Association. Screenees who developed ESRD by the end of 2000 were identified through the Okinawa Dialysis Study registry. RESULTS: Total cholesterol (TC) data were available for 133,338 (92.6%) of the total 143,948 screenees) and triglyceride (TG) data were available for 132,094 (91.8%). Dyslipidemia was defined as TC > or = 220 mg/dl or TG > or = 150 mg/dl. The cumulative incidences of ESRD, per 1000 screenees, were 1.12 for those without dyslipidemia and 2.53 for those with dyslipidemia. The adjusted hazard ratio (95% confidence interval) for dyslipidemia was 0.856 (0.484-1.516) for men and 1.260 (0.661-2.400) for women; neither was significant when adjustment was made for age, systolic blood pressure, diastolic blood pressure, body mass index, creatinine clearance, diabetes mellitus, and proteinuria. CONCLUSIONS: The present study showed dyslipidemia to be an insignificant predictor of development of ESRD in the general Okinawa population.

Adult↗

Effects of blood pressure levels on case fatality after acute stroke.

OBJECTIVE: We evaluated the relationship between admission blood pressure (BP) and early prognosis in patients with acute stroke in a single cohort. DESIGN: The subjects comprised 1004 cases of brain infarction and 1097 cases of brain hemorrhage, who were admitted to hospitals on the day of stroke onset. Death within 30 days after onset was evaluated in relation to admission BP levels. RESULTS: In brain infarction, a U-shaped relationship was found between BP levels and mortality rate, with a nadir at systolic blood pressure (SBP) of 150-169 mmHg and at diastolic blood pressure (DBP) of 100-110 mmHg. After adjustments for age and sex, the highest relative risks (RR) was observed in the lowest BP levels compared with nadir groups, and were 2.69 [95% confidence interval (CI), 1.43-5.07] in SBP and 3.49 (95% CI, 1.58-7.74) in DBP. In subjects with previous hypertension, the relationship between prognosis and SBP level shifted significantly toward higher pressure by about 10 mmHg compared with those without previous hypertension. In subjects with brain hemorrhage, the relationship between BP levels and mortality rate showed a J-shape in SBP and a U-shape in DBP. Highest BP levels had the poorest prognoses (>/= 230 mmHg in SBP, RR = 4.13, 95% CI = 2.45-6.94; >/= 120 mmHg in DBP, RR = 1.83, 95% CI = 1.11-3.04). CONCLUSION: Lower and higher BP after brain infarction and higher BP after brain hemorrhage were predictors for poor early prognosis. In subjects with brain infarction, patients with previous hypertension had better outcomes at higher admission BP level than did normotensive patients.

Acute Disease↗

Autologous peripheral blood mononuclear cell implantation for patients with peripheral arterial disease improves limb ischemia.

BACKGROUND: Implantation of bone marrow mononuclear cells, including endothelial progenitor cells, into ischemic limbs has been shown to improve collateral vessel formation. In the present study the safety and feasibility of autologous peripheral blood mononuclear cells (PBMNCs) implantation after granulocyte-colony stimulating factor (G-CSF)-induced mobilization was investigated in patients with severe peripheral arterial disease. METHODS AND RESULTS: Six cases were enrolled: 5 of thromboangitis obliterans and 1 of arteriosclerosis obliterans. Following administration of G-CSF (10 microg . kg(-1) . day(-1)), PBMNCs were harvested and injected intramuscularly (5 legs and 1 arm) for 2 days for the patients with ischemia of the legs. No serious adverse events related to G-CSF administration, harvest or implantation were observed during this study period. Improvement in the ankle - brachial pressure index (ABI: >0.1) was seen in 4 patients at 4 weeks and ischemic ulcers improved in 3 of 3 patients. The mean maximum walking distance significantly increased from 203 m to 559 m (p=0.031) at 4 weeks and was sustained for 24 weeks. Significant improvement was seen in physiological functioning subscale of Short Form-36. CONCLUSION: Implantation of PBMNCs collected after G-CSF administration could be an alternative to therapeutic angioplasty in patients with severe peripheral arterial disease.

Adult↗

The combination therapy of hypertension to prevent cardiovascular events (COPE) trial: rationale and design.

A number of major clinical trials have demonstrated the clinical benefits of lowering blood pressure and have indicated that a majority of patients with hypertension will require more than one drug to achieve optimal blood pressure control. However, there is little data showing which antihypertensive combination best protects patients from cardiovascular events and which best achieves the target blood pressure with the fewest adverse events. The Combination Therapy of Hypertension to Prevent Cardiovascular Events (COPE) trial is the first large-scale investigator-initiated multicenter study with a prospective, randomized, open, blinded endpoint evaluation (PROBE) design to directly compare cardiovascular mortality and morbidity, incidence of adverse drug reaction, and degree of blood pressure reduction in Japanese hypertensive patients for a combination of angiotensin receptor blockers, beta-blockers or thiazide diuretics in addition to a calcium antagonist, benidipine hydrochloride, with a response-dependent dose titration scheme. The COPE trial is being conducted with the cooperation of more than 100 centers and clinics in Japan and involves 3,000 patients, who will be followed for 3 years. Eligible patients are being enrolled from May 2003 until May 2006. Results from the COPE trial should provide new evidence for selecting optimal combination therapies for hypertensive patients.

Antihypertensive Agents↗

[Therapeutic strategy for morning blood pressure elevation in elderly hypertensives].

Although the cardiovascular events such as stroke, angina pectoris and myocardial infarction can occur at any time of day, it has been known that the peak incidence of the cardiovascular events increases during the morning period. In elderly hypertensives, a greater morning blood pressure surge is associated with an advanced silent cerebrovascular disease as well as a higher incidence of stroke. Thus, the blood pressure control of the early morning period may become an important therapeutic strategy for preventing the cardiovascular events. In this review, we focused on the recent strategy for morning blood pressure rising in the elderly hypertensives.

Adrenergic alpha-Antagonists↗

Functional characterization of a trafficking-defective HCN4 mutation, D553N, associated with cardiac arrhythmia.

Hyperpolarization-activated cyclic nucleotide-gated channel 4 gene HCN4 is a pacemaker channel that plays a key role in automaticity of sinus node in the heart, and an HCN4 mutation was reported in a patient with sinus node dysfunction. Expression of HCN4 in the heart is, however, not confined to the sinus node cells but is found in other tissues, including cells of the conduction system. On the other hand, mutations in another cardiac ion channel gene, SCN5A, also cause sinus node dysfunction as well as other cardiac arrhythmias, including long QT syndrome, Brugada syndrome, idiopathic ventricular fibrillation, and progressive cardiac conduction disturbance. These observations imply that HCN4 abnormalities may be involved in the pathogenesis of various arrhythmias, similar to the SCN5A mutations. In this study, we analyzed patients suffering from sinus node dysfunction, progressive cardiac conduction disease, and idiopathic ventricular fibrillation for mutations in HCN4. A missense mutation, D553N, was found in a patient with sinus node dysfunction who showed recurrent syncope, QT prolongation in electrocardiogram, and polymorphic ventricular tachycardia, torsade de pointes. In vitro functional study of the D553N mutation showed a reduced membranous expression associated with decreased If currents because of a trafficking defect of the HCN4 channel in a dominant-negative manner. These data suggest that the loss of function of HCN4 is associated with sinus nodal dysfunction and that a consequence of pacemaker channel abnormality might underlie clinical features of QT prolongation and polymorphic ventricular tachycardia developed under certain conditions.

Amino Acid Sequence↗

Impact of high coronary artery calcification score (CACS) on survival in patients on chronic hemodialysis.

BACKGROUND: Electron-beam computed tomography (EBCT) is a noninvasive measure of coronary artery calcification and, therefore, could be a marker of developing cardiovascular disease. Whether the coronary artery calcification score (CACS) is a prognostic marker in chronic dialysis patients is not known. METHODS: In the present study, the mortality rate was observed in relation to the baseline CACS. EBCT was performed in 104 chronic hemodialysis patients (62 men and 42 women) in one dialysis unit. The mean (SD) duration of hemodialysis was 48.7 (62.6) months at the time of EBCT. The mean (SD) age at EBCT was 55.9 (13.6) years, ranging from 23 to 88 years. The duration of follow-up was 43.8 (19.3) months after the EBCT. Cox proportional hazard analysis was performed to examine the impact of CACS on survival after adjusting for age, sex, duration of dialysis, diabetes mellitus, hypertension, serum albumin, and dyslipidemia. RESULTS: The CACS was distributed from zero to 5896, with a median of 200. During the study period, 24 patients (15 men and 9 women) died, 7 in the low CACS group (<200) and 17 in the high CACS group (> or =200). The 5-year cumulative survival rate was 84.2% in the low CACS group and 67.9% in the high CACS group. The adjusted relative risk (95% confidence interval) of death was 1.001 (1.000-1.002); P = 0.0003, for the absolute value of CACS. CONCLUSIONS: The present study suggested that CACS was an independent predictor of death in patients on chronic hemodialysis. Patients with a high CACS should be carefully monitored and evaluated for reversible prognostic factors such as dyslipidemia and, probably, hyperphosphatemia and a high value for the calcium x phosphate product.Electron-beam computed tomography (EBCT) is a noninvasive measure of coronary artery calcification and, therefore, could be a marker of developing cardiovascular disease. Whether the coronary artery calcification score (CACS) is a prognostic marker in chronic dialysis patients is not known.

Adult↗

Prevalence of high fasting plasma glucose and risk of developing end-stage renal disease in screened subjects in Okinawa, Japan.

BACKGROUND: The number of diabetic dialysis patients is increasing worldwide. Only a few studies, however, have examined the effect of diabetes mellitus (DM) as a risk factor for the development of end-stage renal disease (ESRD) in the general population. METHODS: We examined the cumulative incidence of ESRD based on the results of community-based mass screening in Okinawa, Japan, performed in 1993 by the Okinawa General Health Maintenance Association. Fasting plasma glucose (FPG) data were available for 78 529 screenees (37 197 men and 41 332 women). DM was diagnosed when the FPG was 126 mg/dl or more. Screenees who developed ESRD by the end of 2000 were identified through the Dialysis Registry, Okinawa Dialysis Study. RESULTS: The mean (SD) FPG was 96.5 (22.8) mg/dl, ranging from 45 to 577 mg/dl. The prevalence of DM among the screenees was 4089 (5.2%). A total of 133 screenees (82 men and 51 women) developed ESRD during the 7.75-year study period. The adjusted odds ratio (95% confidence interval [CI]) in the high-FPG group for the risk of developing ESRD was 3.098 (95% CI, 1.738-5.525; P = 0.0001), when adjusted for age, sex, systolic blood pressure, diastolic blood pressure, body mass index, total cholesterol, triglyceride, hematocrit, serum creatinine, hematuria, and proteinuria. CONCLUSIONS: The results of the present study indicated that FPG is a significant, independent predictor of ESRD. FPG and proteinuria measurements are euqally important in detecting individuals at high risk for developing ESRD.

Adult↗

Body mass index and the risk of development of end-stage renal disease in a screened cohort.

BACKGROUND: Obesity is associated with proteinuria and could be a risk factor for end-stage renal disease (ESRD). However, few studies have examined the significance of body mass index (BMI) as a risk factor for the development of ESRD in the general population. METHODS: We examined the relationship between BMI and the development of ESRD using data from a 1983 community-based screening in Okinawa, Japan. Screenees who developed ESRD by the end of 2000 were identified through the Okinawa Dialysis Study registry. BMI data were available for 100,753 screenees (47,504 men and 53,249 women) aged >/=20 years. The cumulative incidence of ESRD was analyzed according to the quartile of BMI: <21.0, 21.0 to 23.1, 23.2 to 25.4, and >/=25.5 kg/m(2). RESULTS: The mean (SD) BMI of the screenees was 23.4 (3.3) kg/m(2) (range 7.9 to 59.1 kg/m(2)); the mean was 23.4 kg/m(2) for both men and women. During the follow-up period, 404 screenees (232 men and 172 women) developed ESRD. The cumulative incidences of ESRD per 1000 screenees were, from the lowest to highest BMI quartile, 2.48, 3.79, 3.86, and 5.81. The odds ratio (95% CI) of BMI for developing ESRD, after adjustment for age, sex, systolic blood pressure, and proteinuria, was 1.273 (1.121-1.446, P= 0.0002) for men and 0.950 (0.825-1.094, not significant) for women. CONCLUSION: We found that BMI was associated with an increased risk of the development of ESRD in men in the general population in Okinawa. The maintenance of optimal body weight may reduce the risk of ESRD.

Adult↗

Effects of repeated alcohol intake on blood pressure and sodium balance in Japanese males with hypertension.

Alcohol consumption causes biphasic changes in blood pressure (BP) in Asians. The aim of the present study was to investigate the effects of repeated alcohol intake on BP and sodium metabolism. Fourteen Japanese males with hypertension (37-67 years old) were examined under standardized conditions (Na intake 120 mmol/day). After 1 week of alcohol restriction, the patients consumed a control drink with dinner for 3 days, 1 ml/kg of alcohol for the next 7 days, then the control drink for 3 days. Supine BP and heart rate were measured 5 times daily, and urinary excretion of water and sodium was determined throughout the study period. Average BP decreased initially, then returned to the baseline level during the alcohol period. Evening BP decreased significantly throughout the alcohol period, although the reduction was attenuated during the late phase. Morning and afternoon BP did not change significantly, but tended to be elevated during the late phase. Heart rate increased both in the morning and evening during the alcohol period. Urine volume did not change during the early phase, but increased significantly during the late phase. Urinary sodium excretion decreased initially, but increased during the middle phase of the alcohol period. In conclusion, BP decreases initially with sodium retention, then returns to the baseline level with restoration of sodium balance during repeated alcohol intake in Japanese males with hypertension. Sodium retention during the early phase appears to be the consequence of BP reduction and may contribute to the subsequent changes in BP.

Adult↗

Hyperuricemia and cardiovascular risk factor clustering in a screened cohort in Okinawa, Japan.

The relation between serum uric acid level and cardiovascular risk factors is complex and has been investigated mainly in men. We examined the correlation between serum uric acid level and obesity, hypertension, dyslipidemia, and diabetes mellitus (DM) in both men and women of a screened cohort in Okinawa, Japan. A total of 9,914 individuals (6,163 men and 3,751 women ranging in age from 18 to 89 years) who were screened at Okinawa General Health Maintenance Association were subjects in this study. Hyperuricemia was defined as a serum uric acid level > or = 7.0 mg/dl in men and > or = 6.0 mg/dl in women. The odds ratios (95% confidence intervals) for the presence of hyperuricemia in men were 1.75 (1.56-1.97) for obesity, 1.42 (1.25-1.62) for hypertension, 1.16 (1.02-1.30) for hypercholesterolemia, 1.80 (1.60-2.03) for hypertriglyceridemia, 1.19 (1.02-1.40) for hypo-high density lipoprotein (HDL) cholesterolemia, and 0.61 (0.49-0.75) for DM; in women, they were 2.02 (1.62-2.53) for obesity, 1.64 (1.29-2.10) for hypertension, 1.31 (1.04-1.65) for hypercholesterolemia, 1.95 (1.51-2.51) for hypertriglyceridemia, 1.53 (0.96-2.44) for hypo-HDL cholesterolemia, and 1.20 (0.76-1.90) for DM. Hyperuricemic subjects had higher rates of coexistence of two or more of these cardiovascular risk factors than non-hyperuricemic subjects (63.8% vs. 43.2% in men; 58.9% vs. 27.6% in women). The present study revealed that hyperuricemia is positively associated with obesity, hypertension, and dyslipidemia in both men and women, and that hyperuricemic subjects tend to have a clustering of these cardiovascular risk factors.

Adult↗

Hyperuricemia as a predictor of hypertension in a screened cohort in Okinawa, Japan.

Several epidemiological studies have shown a positive association between serum uric acid levels and the risk of hypertension. However, subjects in these studies were mostly men, or were incompletely examined for lifestyle-related variables. We prospectively examined the relation between hyperuricemia and the risk of developing hypertension with consideration for alcohol consumption and smoking habits in a large screened cohort of men and women. A total of 4,489 individuals (2,927 men and 1,562 women) who did not have hypertension and were not currently using antihypertensive medication were examined at the Okinawa General Health Maintenance Association in 1977. Subjects were re-examined in 2000. Hyperuricemia was defined as a serum uric acid level >or=7.0 mg/dl in men and >or=6.0 mg/dl in women. Hypertension was defined as systolic blood pressure (SBP) >or=140 mmHg, and/or diastolic blood pressure (DBP) >or=90 mmHg. A total of 289 subjects (201 men and 88 women) were hypertensive (SBP >or=140 mmHg, and/or DBP >or=90 mmHg) in 2000. Multivariate analysis was performed for development of hypertension in hyperuricemic subjects, adjusted for age, family history of hypertension, alcohol consumption, cigarette smoking, obesity, hypercholesterolemia, hypertriglyceridemia, low high-density lipoprotein cholesterol, and diabetes mellitus. The adjusted odds ratio (95% confidence interval) in men was 1.48 (1.08-2.02) and in women was 1.90 (1.03-3.51) (p <0.05, respectively). The results showed hyperuricemia to be a new predictor of hypertension development in both men and women.

Adolescent↗