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Miyazaki-shi, Japan

Yano Y.,Jichi Medical University | Hoshide S.,Jichi Medical University | Etoh T.,Etoh Cardiology and Internal Medicine Clinic | Tamaki N.,Tamaki Clinic | And 2 more authors.
Atherosclerosis | Year: 2011

Objective: 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. Methods: 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<60ml/min/1.73m 2 using the Cockcroft-Gault equation. Results and conclusion: 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. © 2011 Elsevier Ireland Ltd.

Yano Y.,University of Chicago | Yano Y.,Jichi Medical University | Bakris G.L.,University of Chicago | Inokuchi T.,Chikamorikai Medical Group | And 9 more authors.
Journal of Hypertension | Year: 2014

Objectives: 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. Methods: 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). Results: 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. Conclusion: Cognitive dysfunction is an independent marker associated with increased risk of CVD events in elderly hypertensive patients. © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Sakata K.,University of Miyazaki | Hayakawa M.,University of Miyazaki | Yano Y.,Jichi Medical University | Tamaki N.,Tamaki Clinic | And 14 more authors.
Diabetes/Metabolism Research and Reviews | Year: 2013

Background: 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. Methods: Sixty-one patients whose HbAlc≥6.1% (mean age 64.7years; 67% men; mean HbAlc 7.4%; 57% were pharmacologically treated) underwent blood and urine sampling and analysis before and after 12weeks of treatment with alogliptin (25mg once daily). Results: Alogliptin treatment significantly reduced fasting glucose (160.3mg/dL at baseline versus 138.0mg/dL at 12weeks), glycoalbumin (21.1% at baseline versus 18.9% at 12weeks), HbAlc (7.4% at baseline versus 6.9% at 12weeks), circulating soluble form of RAGE concentrations (847.3pg/mL at baseline versus 791.4pg/mL at 12weeks) and urine albumin to creatinine ratio (31.6mg/g Cr at baseline versus 26.5mg/g Cr at 12weeks), whereas 1,5-anhydroglucitol concentrations were significantly increased (7.5μg/mL at baseline versus 11.6μg/mL at 12weeks; 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 soluble form of sRAGE concentrations was associated with changes of 1,5-anhydroglucitol and HbAlc concentrations (rho=-0.32 and 0.29, respectively). Meanwhile, the treatment-induced change of urine albumin to creatinine ratio 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. Conclusion: Alogliptin treatment improved the AGE-RAGE axis and reduced albuminuria in Japanese type 2 diabetes patients. © 2013 John Wiley & Sons, Ltd.

Sakima A.,University of Ryukyus | Kita T.,University of Miyazaki | Nakada S.,Keiaikai Chibana Clinic | Yokota N.,Yokota Naika | And 5 more authors.
Clinical and Experimental Hypertension | Year: 2014

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. © 2014 Informa Healthcare USA, Inc.

Kita T.,University of Miyazaki | Sakima A.,University of Ryukyus | Yokota N.,Yokota Naika | Tamaki N.,Tamaki Clinic | And 5 more authors.
Clinical and Experimental Hypertension | Year: 2015

Blood pressure (BP) control throughout the entire day is recommended for cardiovascular protection. Angiotensin-II receptor blockers (ARBs) are widely used in hypertensive patients because of beneficial class effects. It is uncertain, however, whether are there any differences in 24-h BP profiles among ARBs. We examined ambulatory blood pressure monitoring (ABPM) among 211 Japanese hypertensive patients (age, 69.4 ± 9.6 years; female, 59.2%) under treatment with five different ARBs. Patients were divided into five groups according to ARBs prescribed. Patient backgrounds were almost identical in all the groups and there were no differences in office, 24-h and daytime BP; however, nighttime BP with olmesartan was significantly lower than with other ARBs. Office BPs with candesartan and telmisartan, but not other ARBs, correlated well with 24-h BP (p < 0.01). Also, there were higher correlations between daytime and nighttime BP with candesartan and telmisartan. In all patients, pulse pressure with office BP was significantly correlated with ambulatory arterial stiffness index (p = 0.001) and fluctuation of systolic BP on ABPM (p = 0.002). In conclusion, different ARB treatments produced meaningful differences in 24-h profiles. © 2015 Taylor & Francis Group, LLC.

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