苅尾 七臣

Objectives To study the impact of the dosing time of an angiotensin II receptor blocker (ARB) titrated by self-measured home blood pressure (HBP) on cardiorenal damage in hypertensives. Methods We conducted an open-label multicenter trial, the J-TOP study, that enrolled 450 hypertensives with self-measured systolic HBP more than 135 mm Hg. The study patients were stratified into three groups according to the difference between their morning and evening SBPs difference: a morning hypertension group (morning and evening difference at least 15 mm Hg; n=170), a morning and evening hypertension group (0 mm Hg <= morning and evening difference <15 mm Hg; n=198), and an evening hypertension group (morning and evening difference <0 mm Hg; n=82). Individuals were then randomly allocated to receive bedtime dosing or awakening dosing of candesartan (+/-diuretic as needed) titrated to achieve a target systolic HBP less than 135 mm Hg. The 6-month change in the urinary albumin/creatinine ratio (UACR) was assessed. Results In total patients, the UACR was more markedly reduced in the bedtime-dosing group than in the awakening-dosing group (-45.7 vs. -34.5%, P=0.02), whereas there were no differences in the reduction of any of the HBPs including the sleep blood pressures (BPs) between the two groups. Among the three subgroups stratified by the morning and evening difference, the difference in the UACR reduction between the bedtime-dosing and awakening-dosing groups was only significant in the morning hypertension group (-50.6 vs. -31.3%, P=0.02). Conclusion In HBP-guided antihypertensive treatment in hypertensives, bedtime dosing of an ARB may be superior to awakening dosing for reducing microalbuminuria. J Hypertens 28: 1574-1583 (C) 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Background: It is reported that blood pressure (BP) variability increases with aging, and cognitive dysfunction may be related to BP variability; however, there are no data showing that exaggerated BP variability is associated with cognitive dysfunction or quality of life (QOL) in the older elderly. We investigated the relationships and the differences between ambulatory BP variability and cognitive function or QOL in younger elderly and very elderly. Methods: We recruited both 101 very elderly (aged >= 80 years) and 101 younger elderly (aged 61 to 79 years). Twenty-four-hour ambulatory blood pressure monitoring, mini-mental state examinations (MMSE), and Medical Outcome Study Short-Form 36 Items Health Survey (SF-36) were performed for all subjects. Results: The mean standard deviation (SD) of daytime systolic BP in young elderly was 17.2 +/- 4.6 mm Hg (mean SD SD of mean SD), and that in very elderly was 21.2 +/- 4.3 mm Hg. The MMSE score significantly decreased with the tertile of SD of daytime systolic BP in very elderly (P = .004) and young elderly (P = .03). In very elderly, there was no significant association between the SD of daytime systolic BP and each of eight SF-36 categories. On the other hand, in younger elderly, two of eight SF-36 categories decreased with the tertile of SID of daytime systolic BP (P = .001 for Vitality and P = .003 for Role emotion). Conclusions: Very elderly had larger BP variability than younger elderly. Exaggerated ambulatory BP variability was related to cognitive dysfunction in the elderly, especially in the very elderly, and was related to lower QOL in the younger elderly. Am J Hypertens 2007;20: 720-727 (c) 2007 American Journal of Hypertension, Ltd.

Background: Masked hypertension (MHT: normal office blood pressure [BP] + elevated BP out of the office) is a significant predictor of target organ damage and cardiovascular disease. The purpose of this study was to investigate the subclinical arterial damage in unmedicated subjects with MHT detected by home BP measurement. Methods: We recruited 282 subjects not taking antihypertensive medication, who had at least one of the following five cardiovascular risk factors: high BP, hyperlipidemia, diabetes mellitus, current smoking, and chronic kidney disease. Furthermore, we classified them into four groups (normotension [NT], white-coat hypertension [WCHT], MHT, and sustained hypertension [SHT]) by office BP (140/90 mm Hg) and home BP (135/85 mm Hg) measurements. Arterial damage was evaluated by measuring carotid intima-media thickness (IMT) and brachial-ankle pulse wave velocity (baPWV). Results: Subjects with MHT had a higher prevalence of habitual alcohol drinkers than the other groups, and higher pulse rates at home than those with NT and WCHT. After adjustment for covariates, carotid IMT was the highest in MHT among the four groups (mean: 1.01 v 0.83 mm for NT, 0.86 mm for WCHT, and 0.91 mm for SHT, all P<.01). The baPWV was also significantly higher in MHT than NT and WCHT (mean: 1940 v 1663 and 1733 cm/sec, all P<.01), whereas the difference between MHT and SHT (2023 cm/sec) was not significant. Conclusions: This study shows that masked hypertensives detected by home BP are at higher risk for increased arterial damage than normotensives or white-coat hypertensives, and potentially than sustained hypertensives.

Background and Purpose - High-sensitivity C-reactive protein (hsCRP), a marker of inflammation, is associated with atherosclerosis, hypertensive target organ damage, and cardiovascular events. In the general Japanese population, the level of hsCRP is reported to be lower than that in Western countries, and the relationships among hsCRP, silent cerebral infarcts (SCIs), and clinical stroke events in older Japanese hypertensives remain unclear. Methods - We conducted brain MRI and measured hsCRP at baseline in 514 older Japanese hypertensives ( clinic blood pressure >= 140/90 mm Hg, age >= 50 years old) who were enrolled in the Jichi Medical School ABPM Study, wave 1. They were followed up for an average of 41 months ( range: 1 to 68 months, 1751 person-years) and the incidence of subsequent clinical stroke events was evaluated. Results - The subjects with SCIs at baseline (n = 257) had a higher hsCRP level than those without SCIs ( geometric mean hsCRP [SD range];0.19 [0.18 to 0.21] versus 0.14 [0.13 to 0.16] mg/L, P = 0.007) after adjustment for confounding factors, and the OR for the presence of SCIs was increased with the quartile of hsCRP levels. In Cox regression analysis, the patients with above median hsCRP level (>= 0.21 mg/L) (hazard ratio [HR]: 2.50, 95% CI: 1.24 to 5.00, P = 0.01) and those with SCIs ( HR: 4.60, 95% CI: 1.91 to 11.03, P = 0.001) at baseline had independently higher risks for clinical stroke events after adjustment for age, smoking status, antihypertensive medication use, and 24-hour systolic blood pressure level. Compared with the patients with below median hsCRP level without SCIs, those with above median hsCRP level and SCIs at baseline had a higher risk for clinical stroke events ( HR: 7.32, 95% CI: 2.17 to 24.76, P = 0.001), although those with below median hsCRP level and SCIs ( HR: 2.46, 95% CI: 0.64 to 9.47, P = 0.19) and those with above median hsCRP level without SCIs ( HR: 1.11, 95% CI: 0.22 to 5.55, P = 0.90) did not have significant risks. Conclusion - High-sensitivity C-reactive protein is a risk factor for clinical stroke events in addition to silent cerebral infarcts in Japanese older hypertensives, indicating that the risk for clinical stroke events increases with preexisting hypertensive target organ damage in the brain and additionally with ongoing low-grade inflammation.