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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. Source

Yano Y.,Saigo National Health Insurance Hospital | Yano Y.,Jichi Medical University | Hoshide S.,Jichi Medical University | Tamaki N.,Tamaki Clinic | And 5 more authors.
JRAAS - Journal of the Renin-Angiotensin-Aldosterone System | Year: 2011

Introduction: 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. Materials and methods: 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. Results: 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. Conclusions: 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. © 2011 The Author(s). Source

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. Source

Tamaki N.,Tamaki Clinic
Nippon rinsho. Japanese journal of clinical medicine | Year: 2010

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. Source

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. Source

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