Noboru Tamaki

Miyazaki University, Миядзаки, Miyazaki, Japan

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Publications (13)32.14 Total impact

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    ABSTRACT: This study assesses whether presence of cognitive dysfunction can be a marker associated with the development of cardiovascular disease (CVD) events independent of ambulatory blood pressure (BP) or other indices of target organ damage (TOD) in elderly hypertensive patients. We recruited 585 hypertensive patients (mean age, 73 years; 41% men) who were ambulatory, lived independently, and were without clinically overt dementia. Cognitive function was assessed by Mini-Mental State Examination (MMSE) at baseline, and CVD events (coronary artery disease, stroke, congestive heart failure, and sudden death) were prospectively ascertained. Cognitive dysfunction was defined as the lowest quartile of MMSE scores (n = 183, median 24 points). CVD events occurred in 42 people over an average of 2.8 years (1644 person-years). The prevalence of cognitive dysfunction was higher in patients with CVD events than those without (57 vs. 29%; both P <0.001) at baseline. Cognitive dysfunction was associated with CVD events, after adjustment for nocturnal SBP and evidence of TOD [i.e. albuminuria, cardiac hypertrophy, and carotid-artery intima-media thickness (IMT)], hazard ratio 2.5-2.9 (all P <0.01). Incorporation of MMSE in the risk model (including age, estimated glomerular filtration rate, and preexisting CVD) improved the C-statistics (from 0.691 to 0.741) and resulted in a net reclassification improvement of 17.6% (P = 0.02). In contrast, incorporation of albuminuria, cardiac hypertrophy, and high carotid-artery IMT added little further improvement in the risk prediction. Cognitive dysfunction is an independent marker associated with increased risk of CVD events in elderly hypertensive patients.
    Journal of Hypertension 12/2013; · 4.22 Impact Factor
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    ABSTRACT: To examine the effects of alogliptin, a dipeptidyl peptidase-4 inhibitor, on glucose parameters, the advanced glycation end product (AGE)-receptor for AGE (RAGE) axis, and albuminuria in Japanese type 2 diabetes patients. Sixty-one patients whose HbAlc >6.1% (mean age 64.7 years; 67% men; mean HbAlc 7.4%; 57% were pharmacologically treated) underwent blood and urine sampling and analysis before and after 12 weeks of treatment with alogliptin (25 mg once daily). Alogliptin treatment significantly reduced fasting glucose (160.3 mg/dL at baseline vs. 138.0 mg/dL at 12 weeks), glycoalbumin (21.1% at baseline vs. 18.9% at 12 weeks), HbAlc (7.4% at baseline vs. 6.9% at 12 weeks), circulating soluble form of RAGE (sRAGE) concentrations (847.3pg/mL at baseline vs. 791.4pg/mL at 12 weeks), and urine albumin to creatinine ratio (UACR, 31.6 mg/g·Cr at baseline vs. 26.5 mg/g·Cr at 12weeks), whereas 1,5-anhydroglucitol concentrations (1,5-AG) were significantly increased (7.5 µg/mL at baseline vs. 11.6 µg/mL at 12 weeks; all P<0.05). Circulating AGEs concentrations were reduced only in patients with baseline AGEs >7U/mL (n=33, from 8.2U/mL to 7.2U/mL; P<0.01) after alogliptin treatment. The treatment-induced change of sRAGE concentrations was associated with changes of 1,5-AG and HbAlc concentrations (rho= -0.32 and 0.29, respectively). Meanwhile, the treatment-induced change of UACR was associated with a change in the fasting glucose concentration (rho=0.25; all P<0.05). During the intervention, alogliptin treatment was well tolerated without any hypoglycemia or side effects. Alogliptin treatment improved the AGE-RAGE axis and reduced albuminuria in Japanese type 2 diabetes patients. This article is protected by copyright. All rights reserved.
    Diabetes/Metabolism Research and Reviews 07/2013; · 2.97 Impact Factor
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    ABSTRACT: Abstract Although blockade of the renin-angiotensin system by increasing the dose of angiotensin II receptor blockers (ARBs) is recommended to achieve clinical benefits in terms of blood pressure (BP) control and cardiovascular and renal outcomes, the effect of this increased dose on ambulatory BP monitoring has not been evaluated completely in Japanese patients with uncontrolled hypertension undergoing medium-dose ARB therapy. The primary objective of this study was to examine the effect of the relatively high dose of the ARB candesartan (12 mg/day) on 24-h systolic BP and the attainment of target BP levels in uncontrolled hypertension treated with a medium dose of ARBs. A total of 146 hypertensive patients (age: 69.9 ± 9.3 years; females: 65.8%) completed the study. After switching to candesartan at 12 mg/day, all these BP measurements decreased significantly (p < 0.001). Attainment of the target office BP (p = 0.0014) and 24-h BP levels (p = 0.0296) also improved significantly. Subgroup analysis indicated that the reduction of 24-h systolic BP was larger in patients treated with diuretics than those without (p = 0.0206). Multivariate analysis revealed a significant correlation between the combined ARB and diuretic therapy, and the change in 24-h systolic BP irrespective of preceding ARBs. In conclusion, the switching therapy to increased dose of candesartan caused significant reductions in office and ambulatory BP levels, and improved the attainment of target BP levels in patients with uncontrolled hypertension treated with a medium dose of ARBs. Combination with diuretics enhanced this effect.
    Clinical and Experimental Hypertension 05/2013; · 1.28 Impact Factor
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    ABSTRACT: We conducted the Miyazaki Olmesartan Therapy for Hypertension in the EldeRly (MOTHER) study, which suggested that there are preferable effects of an angiotensin receptor blocker (ARB), olmesartan, plus a calcium channel blocker (CCB) over the ARB plus a diuretic, in elderly patients with hypertension. In this subanalysis, we examined whether obesity influences the efficacies of these combination therapies. The study subjects were 58 hypertensive patients ages 65 to 85, who had been randomly assigned to either group treated with olmesartan plus a CCB or a diuretic and completed the treatment for 6 months. Systolic and diastolic blood pressures were reduced following these combination treatments in nonobese and obese patients. In the CCB combination, blood pressure reductions in nonobese patients were larger than in obese patients at 1 and 3 months, and serum creatinine remained unchanged despite the greater reduction of blood pressure. Meanwhile, such differences were not noted in the diuretic groups. Plasma aldosterone was significantly reduced in nonobese patients of two combination groups, but not in those with obesity. ARB plus CCB combination therapy might be preferably chosen for nonobese elderly patients, whereas the influence of obesity seems smaller in the efficacy of ARB plus a diuretic.
    Journal of the American Society of Hypertension (JASH) 10/2012;
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    ABSTRACT: Concerns about metabolic complications often disturb prolonged use of diuretics in Japan. We investigated 3-year safety and efficacy in Japanese patients with hypertension who were uncontrolled with angiotensin receptor blocker or angiotensin-converting enzyme inhibitor regimens and then switched to losartan (50 mg)/hydrochlorothiazide (12.5 mg; HCTZ) combinations. Blood pressure decreased favorably and maintained a steady state for 3 years (157 ± 16/88 ± 11 mm Hg to 132 ± 13/75 ± 9 mm Hg, P < .0001). Metabolic parameters maintained a limited range of changes after 3 years, and adverse events were markedly decreased after 1-year treatment. The losartan/HCTZ combination minimized diuretic-related adverse effects and thus may be useful for the treatment of Japanese patients with hypertension.
    Clinical and Experimental Hypertension 04/2012; · 1.28 Impact Factor
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    ABSTRACT: Ezetimibe reduces serum low-density lipoprotein cholesterol (LDL-C) levels by inhibiting intestinal cholesterol absorption; however, the effects of ezetimibe, including its pleiotropic effects, have not been fully clarified. The aims of our study were to examine the efficacy of ezetimibe for hypercholesterolemia and its pleiotropic effects. Outpatients with hyper LDL-C levels were treated with 10 mg ezetimibe once a day for 12 weeks. Serum lipid profiles, atherosclerotic and inflammatory markers, glucose, insulin, liver function, and cholesterol absorption and synthesis markers were measured before and after treatment. Seventy-five patients treated with ezetimibe monotherapy and 16 patients treated with combined therapy of ezetimibe with different statins completed this study. Following 12 weeks of ezetimibe monotherapy, serum LDL-C, triglyceride, remnant-like particles cholesterol, matrix metalloproteinase-9, insulin, homeostasis model assessment of insulin resistance, high-sensitivity C-reactive protein, the relative mobility of the peak of the LDL fraction, and cholesterol absorption markers were significantly decreased, and high-density lipoprotein cholesterol and lathosterol were significantly increased. In the combined therapy group, LDL-C and cholesterol absorption markers were significantly decreased after treatment. In patients with a high basal ALT level that were treated with monotherapy, ALT and the AST/ALT ratio were significantly decreased and increased, respectively, after treatment. Ezetimibe ameliorated not only atherogenic lipid profiles but also atherosclerotic and inflammatory markers, insulin sensitivity, and liver dysfunction in Japanese hypercholesterolemia patients, suggesting that ezetimibe treatment is a beneficial and effective strategy for the treatment of hypercholesterolemia, especially patients with obesity, metabolic syndrome, and/or fatty liver.
    Journal of atherosclerosis and thrombosis 02/2012; 19(6):532-8. · 2.93 Impact Factor
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    ABSTRACT: Evidence is now available about the association between chronic kidney disease (CKD) and stroke. However, less is known about the underlying mechanisms, and there is currently no reliable marker for identifying stroke-prone high-risk patients among CKD patients. A total of 514 hypertensive patients aged >50 years (mean, 72.3 years; 37% men) underwent 24-h BP monitoring and measurement of circulatory high-sensitivity C-reactive protein (hs-CRP) and norepinephrine at baseline. CKD was defined as eGFR<60 ml/min/1.73 m(2) using the Cockcroft-Gault equation. During an average of 41 months (1751 person-years), there were 43 stroke events. Compared with hypertensive patients without CKD, those with CKD (n=225) had higher levels of sleep systolic BP (SBP) (125 mmHg vs. 129 mmHg), circulatory hs-CRP (0.12 mg/L vs. 0.20 mg/L) and norepinephrine (332.2 pg/ml vs. 372.8 pg/ml; all P<0.05). On multivariable analysis, the hazard ratio (HR) (95% CI) for stroke in CKD vs. non-CKD was 2.7 (1.2-6.9) (P<0.05). CKD, as well as the baseline presence of silent cerebral infarction, sleep SBP increase, and high hs-CRP level (highest quartile: ≥0.42 mg/L) were independently and additively associated with stroke events; above all, there was a synergistic effect of CKD and high norepinephrine level (highest quartile: ≥538 pg/ml) on stroke risk (all P<0.05). Among hypertensive patients with CKD, those within the highest quartiles of norepinephrine had a greater stroke risk compared to those who were in the lower quartiles of norepinephrine (HR (95% CI): 2.2 (1.0-4.5); P=0.045). In conclusion, CKD is an independent predictor of stroke in Japanese hypertensive patients; in particular, hypertensive patients with CKD and a high norepinephrine level have a synergistically augmented stroke risk.
    Atherosclerosis 06/2011; 219(1):273-9. · 3.71 Impact Factor
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    ABSTRACT: We assessed the additional effects of eplerenone to angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) on 24-h blood pressure (BP) level, fibrinolytic activity, and cardiovascular protection in elderly (>60 years) hypertensive patients. In total, 20 patients (mean age 74 years, 25% men), whose BP was uncontrolled despite the use of anti-hypertensive drugs including ACEIs or ARBs (average 2.4 drugs), received eplerenone once daily (mean 37.5 mg) for 24 weeks. Eplerenone treatment significantly reduced mean 24-h systolic/diastolic BP levels (143/80 mmHg to 132/74 mmHg, both p < 0.002). The reduction of 24-h systolic BP levels, especially night-time BP, was significantly associated with the reduction of atrial natriuretic peptide and brain natriuretic peptide levels (all p < 0.05). Furthermore, after eplerenone treatment, the mean plasminogen activator inhibitor-1 antigen level was significantly reduced (35 ng/ml to 25 ng/ml, p < 0.05), and the median level of plasma procollagen type III aminoterminal peptide and the urinary albumin excretion rate were also significantly reduced (0.8 U/ml to 0.6 U/ml, p < 0.003 and 53 mg/g·Cr to 23 mg/g·Cr, p < 0.05, respectively). During the intervention, eplerenone treatment was well tolerated with no reports of hyperkalaemia or hypotension. Addition of eplerenone to ACEIs or ARBs in elderly hypertensive patients offers significant benefits in terms of 24-h BP levels, fibrinolysis, and cardiovascular protection.
    Journal of Renin-Angiotensin-Aldosterone System 03/2011; 12(3):340-7. · 2.29 Impact Factor
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    ABSTRACT: Effects of dietary n-3 polyunsaturated fatty acids (n-3 PUFA) intake on the cardiovascular system have been reported, and thus we hypothesized that the prevalence of hypertensive cardiovascular remodeling would be lower in a fishing than a farming community. We recruited 263 essential hypertensives from a fishing and 333 from a farming village; all subjects were ≥40 years (mean 73 years; 42% men). They were cross-sectionally examined for serum eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), asymmetric dimethylarginine (ADMA) levels, left ventricular mass index (LVMI), and common-carotid artery (CCA) and internal-carotid artery (ICA) intima-media thickness (IMT). Compared to the patients in the farming village, those in the fishing village had higher serum EPA and DHA levels (63.3 vs.70.9 µg/ml, 137.2 vs.157.8 µg/ml) and lower ADMA levels (0.49 vs.0.47 nmol/ml; all P < 0.05). LVMI and both CCA-IMT and ICA-IMT levels were lower in the fishing than the farming village (113.2 vs.121.6 g/m(2), 0.88 vs.0.94 mm, 1.10 vs.1.17 mm: all P < 0.01) even after adjustment for age, sex, body mass index (BMI), duration of hypertensive medication, number of antihypertensive medications, and 24-h systolic blood pressure (SBP) level. The differences in LVMI and IMT levels between these communities also remained unchanged (all P < 0.01) after additional adjustment for the regional differences in EPA, DHA, and ADMA levels. A multivariable linear regression analysis showed that the difference in place of residence was independently associated with LVMI as well as with both CCA-IMT and ICA-IMT levels (all P < 0.01). The prevalence of cardiovascular remodeling was significantly lower in patients in the fishing community than in those in the farming community. Further investigations are required to explain the mechanisms underlying this association.
    American Journal of Hypertension 02/2011; 24(4):437-43. · 3.67 Impact Factor
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    ABSTRACT: The blood pressure goals set for the treatment of hypertensive patients have been lowered in recent guidelines. To reduce blood pressure levels sufficiently, combination therapies are often needed, but there is little evidence about which combination should be chosen. The present study was carried out to compare the effects of combination therapies, including the angiotensin receptor blocker olmesartan and either a calcium channel blocker (CCB) or a thiazide diuretic, in elderly patients with hypertension. A total of 65 patients aged 65-85 years, with blood pressures of 140/90 mmHg or higher for those taking antihypertensive medication or 160/100 mmHg or higher for those not on medication, were randomly assigned to either the group treated with olmesartan plus a dihydropyridine CCB or the group treated with olmesartan plus a thiazide diuretic; 58 patients completed the treatment for 6 months. Systolic and diastolic blood pressures (SBP and DBP) were reduced during the treatment period in both the groups. The reductions in SBP at 1 and 6 months were significantly (P<0.05) greater in the CCB combination group than in the diuretic group (-29 vs. -18 mmHg, respectively, at 1 month; -32 vs. -23 mmHg, respectively, at 6 months). Despite greater reduction in SBP in the CCB group, the serum creatinine level and the estimated glomerular filtration rate (eGFR) remained unchanged, whereas in the diuretic group, creatinine was elevated (+0.06 mg per 100 ml, P<0.05) and eGFR was reduced (-4.5 mlmin(-1) per 1.73 m(2)). In addition, high-density lipoprotein cholesterol levels were reduced in the diuretic group (-5.0 mg per 100 ml, P<0.01). These results suggest that olmesartan plus a CCB is the preferable combination therapy in comparison with olmesartan plus a thiazide diuretic for elderly patients with hypertension.
    Hypertension Research 12/2010; 34(3):331-5. · 2.79 Impact Factor
  • Noboru Tamaki, Yuichiro Yano, Kazuomi Kario
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    ABSTRACT: Hypertension is a major risk factor for cardiovascular disease. About forty million people are estimated to have hypertension. But, only 50% of hypertensive patients achieve well control of blood pressure. To prevent cardiovascular disease, more careful attention to hypertension is needed. Diagnostic level for hypertension in clinic is > or = 140/90mmHg. On the other hand, home blood pressure and 24-h ambulatory blood pressure are necessary for distinguish masked hypertension, white coat hypertension and sustained hypertension. Blood pressure is classified into optimal, normal and high-normal, and the corresponding levels are classified into grade I, grade II and grade III hypertension, respectively. Hypertensive patients are stratified into low-, moderate- and high-risk groups according to the presence or absence of risk factors other than blood pressure, hypertensive target organ damage and cardiovascular disease. In particular, the presence of diabetes mellitus and chronic kidney disease increases the risk. Attention to metabolic syndrome including a high-normal pressure as a component is also necessary. The treatment program should be prepared according to stratification of the risk; all patients must be guided to modify their lifestyle, and hypertensive medication should be started if necessary to achieve the target blood pressure level. In this paper most recommended timing to start medication for hypertensive patients is discussed.
    Nippon rinsho. Japanese journal of clinical medicine 09/2010; 68(9):1753-62.
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    ABSTRACT: Objective: For elderly persons, the fastest-growing segment of the population, frailty has become a critical issue because it results in excess disability and mortality. Our previous report showed that leanness among elderly hypertensive patients was associated with cognitive impairment (Am J Hypertens 2008;21:627). In that study, the association between leanness and cerebrovascular disease remained examined. Design: Cross-sectional study. Methods: We conducted 24-hour ambulatory blood pressure (BP) monitoring and brain MRI in 514 Japanese hypertensives aged 50 years (mean 72 years; 33% men) who had no history of stroke. Subjects were classified into three groups based on their BMI: lean: BMI<22 kg/m2 (mean BMI;19.9 kg/m2, n = 134); normal-weight: BMI 22–25 kg/m2 (mean BMI; 23.6 kg/m2, n = 188); and obese: BMI> 25 kg/m2 (mean BMI: 27.7 kg/m2, n = 192). Results: There was a significant difference in the number of silent cerebral infarcts (SCIs) among lean patients, normal-weight patients, and obese patients (mean number (95%CI) of SCIs: 1.9 (1.5–2.2) vs. 1.2 (0.9–1.5) vs. 1.4 (1.0–1.7), respectively; P = 0.023 by ANCOVA) even after adjustment for age, sex, current smoking, use of anti-hypertensive drugs, and 24-hour BP levels. When our patients were subdivided into six groups according to their BMI and 24-hour BP levels (<130/80 mmHg or >130/80 mmHg), the lean patients with high 24-hour BP levels (n = 83) showed the highest prevalence of multiple SCIs (45%) (Figure 1A, P = 0.006 by x2-test) and the greatest increase in the number of SCIs (Figure 1B, P = 0.015 by ANCOVA). Conclusion: In our elderly hypertensive patients, there was a significant association between leanness and SCIs. The association was especially strong in lean patients with high 24-hour BP levels, about half of whom had multiple SCIs. Our data indicate that the impact of BP level on cerebrovascular disease may be more pronounced in lean patients than obese patients.
    Journal of Hypertension 05/2010; 28:e35. · 4.22 Impact Factor
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    ABSTRACT: The long-term antihypertensive efficacy and safety of losartan/hydrochlorothiazide (HCTZ) combinations have not been appropriately evaluated in Japan. In this study, treated hypertensive patients taking angiotensin-receptor blocker (ARB) or angiotensin-converting enzyme inhibitor (ACEI) regimens not at blood pressure (BP) goals proposed by the Japanese Society of Hypertension (JSH) were switched to losartan/HCTZ combinations and followed for 1 year. Data analysis included 244 patients aged 64.5+/-10.7 years, 56% male, 27% with diabetes mellitus and 36% with dyslipidemia. Pre-switching BP 157+/-16/88+/-10 mm Hg promptly decreased and maintained a steady state, reaching 132+/-15/77+/-9 mm Hg (P<0.001) 1 year later. After 1 year of treatment, 50% of patients cleared the goals of the JSH guideline for systolic BP and 79% for diastolic BP. Patients with maximal doses of ARBs tended to show larger decreases in BP (159+/-11/90+/-10 to 128+/-10/75+/-8 mm Hg, P<0.001, n=32). Clinical and laboratory adverse events were reported for 29 patients (11%), but serious abnormalities were not observed. In particular, plasma levels of uric acid (UA) were well-maintained for 1 year, and significant decreases in UA were observed in patients with higher levels of UA (>/=7.0 mg dl(-1)). Losartan/HCTZ combinations showed strong and steady hypotensive abilities and acceptable safety and tolerability in patients currently not at BP goals with regimens including ARBs or ACEIs in Japan.
    Hypertension Research 04/2010; 33(4):320-5. · 2.79 Impact Factor