苅尾 七臣

It remains uncertain whether abnormal dipping patterns of nocturnal blood pressure influence the prognosis for stroke. We studied stroke events in 575 older Japanese patients with sustained hypertension determined by ambulatory blood pressure monitoring (without medication). They were subclassified by their nocturnal systolic blood pressure fall (97 extreme-dippers, with greater than or equal to 20% nocturnal systolic blood pressure fall; 230 dippers, with greater than or equal to 10% but <20% fall; 185 nondippers, with <greater than or equal to>0% but <10% fall, and 63 reverse-dippers, with <0% fall) and were followed prospectively for an average duration of 41 months. Baseline brain magnetic resonance imaging (MRI) disclosed that the percentages with multiple silent cerebral infarct were 53% in extreme-dippers, 29% in dippers, 41% in nondippers, and 49% in reverse-dippers. There was a J-shaped relationship between dipping status and stroke incidence (extreme-dippers, 12%; dippers, 6.1%; nondippers, 7.6%, and reverse-dippers, 22%), and this remained significant in a Cox regression analysis after controlling for age, gender, body mass index, 24-hour systolic blood pressure, and antihypertensive medication. Intracranial hemorrhage was more common in reverse-dippers (29% of strokes) than in other subgroups (7.7% of strokes, P=0.04). In the extreme-dipper group, 27% of strokes were ischemic strokes that Occurred during sleep (versus 8.6% of strokes in the other 3 subgroups, P=0.11). In conclusion, in older Japanese hypertensive patients, extreme dipping of nocturnal blood pressure may be related to silent and clinical cerebral ischemia through hypoperfusion during sleep or an exaggerated morning rise of blood pressure, whereas reverse dipping may pose a risk for intracranial hemorrhage.

Objectives We investigated whether white-coat hypertension is a risk factor for stroke in relation to silent cerebral infarct (SCI) in an older Japanese population. Background It remains uncertain whether white-coat hypertension in older subjects is a benign condition or is associated with an increased risk of stroke. Methods We studied the prognosis for stroke in 958 older Japanese subjects (147 normotensives [NT], 236 white-coat hypertensives [WCHT] and 575 sustained hypertensives [SHT]) in whom ambulatory blood pressure monitoring was performed in the absence of antihypertensive treatment. In 585 subjects (61%), we also assessed SCI using brain magnetic resonance imaging. Results Silent cerebral infarcts were found in 36% of NT (n = 70), 42% of WCHT (n = 154), and 53% of SHT (n = 361); multiple SCIs (the presence of greater than or equal to2 SCIs) were found in 24% of NT, 25% of WCHT and 39% of SHT. During a mean 42-month follow-up period, clinically overt strokes occurred in 62 subjects (NT: three [2.0%]; WCHT: five [2.1%]; SHT: 54 [9.4%]), with 14 fatal cases (NT: one [0.7%]; WCHT: 0 [0%]; SHT: 13 [2.3%]). A Cox regression analysis showed that age (p = 0.0001) and SHT (relative risk, [RR] [95% confidence interval, CI]: 4.3 [1.3-14.2], p = 0.018) were independent stroke predictors, whereas WCHT was not significant. When we added presence/absence of SCI at baseline into this model, the RR (95% CI) for SCI was 4.6 (2.0-10.5) (p = 0.003) and that of SI-IT was 5.5 (1.8-18.9) versus WCHT (p = 0.004) and 3.8 (0.88-16.7) versus NT (p = 0.07). Conclusions In older subjects the incidence of stroke in WCHT is similar to that of NT and one-fourth the risk in SHT. Although SCI is a strong predictor of stroke, the difference in stroke prognosis between ST-IT and WCHT was independent of SCI. It is clinically important to distinguish WCHT from SHT even after assessment of target organ damage in the elderly. (J Am Coll Cardiol 2001;38:238-45) (C) 2001 by the American College of Cardiology.

OBJECTIVES We sought to study the association of the silent cerebral infarct (SCI), a predisposing condition of stroke, with hyperinsulinemia and hemostatic abnormalities in older hypertensive subjects. BACKGROUND Hypertension is a powerful risk factor for stroke. However, the role of other risk factors for stroke in hypertensive subjects remains incompletely understood. METHODS We performed brain magnetic resonance imaging and measured cardiovascular risk factors, by administering the 75-g oral glucose tolerance test and measuring plasma insulin and hemostatic variables, in 123 asymptomatic hypertensive subjects (mean age 69 years). RESULTS At least one SCI was detected in 80 subjects (65%), and multiple SCIs were found in 48 subjects (39%). The presence of SCIs was associated with older age, higher levels of 24-h systolic blood pressure, 2-h insulin, thrombin-generation markers (prothrombin fragment 1+2 and thrombin-antithrombin complexes), plasminogen activator inhibitor-1 (PAI-1), D-dimer and von Willebrand factor (vWF), but not with plasmin-alpha(2)-plasmin complex (PIC) levels. The 2-h insulin area under the curve (AUC) was positively correlated with PAI-1 and VWF levels (p < 0.01), and the PAI-1 level was negatively correlated with the PIC level (p < 0.02). Multiple logistic regression analysis revealed that age and the 2-h insulin AUC were significantly associated with SCIs, particularly those located in the subcortical white matter, and hemostatic abnormalities were significantly associated with the presence of multiple SCIs, particularly those located in the basal ganglia. CONCLUSIONS In older asymptomatic hypertensive subjects, hyperinsulinemia appears to be associated with lacunar-type SCIs, particularly those located in the subcortical white matter, and hemostatic abnormalities show an association with the presence of multiple SCIs, particularly those located in the basal ganglia. a Am Coil Cardiol 2001;37:871-7) (C) 2001 by the American College of Cardiology.

Abnormal nocturnal blood pressure (BP) dipping status may be partly determined by nocturnal sympathetic activity. We studied the effect of nighttime dosing of an alpha(1)-adrenergic blocker, doxazosin, on the BP dipping status of 118 hypertensives, all of whom underwent 24-hour ambulatory BP monitoring before and after treatment. The mean nighttime/daytime ratio of systolic BP was increased (0.91 after therapy versus 0.89 at baseline, P<0.05). The patients were initially divided into 4 groups on the basis of their dipping status at the baseline assessment: 18 (15%) were extreme dippers, with a nighttime systolic BP fall of at least 20% of daytime BP; 46 (39%) were dippers (fall between 10% and 20%); 48 (41%) were nondippers (fall between 0% and 10%); and 6 (5%) were risers (nocturnal increase of systolic BP). A shift in dipping status toward less nocturnal BP dipping was observed after doxazosin therapy (P<0.05). Dipping status was determined by nighttime more than by daytime BP, and this was not explained by differences in the number of daytime and nighttime readings. The effects of doxazosin on the mean nocturnal systolic BP changes were an increase of 4.3 mm Hg in extreme dippers and decreases of 0.7 mm Hg in dippers, 12 mm Hg in nondippers, and 18 mm Hg in risers; the reduction was only significant in the latter 2 groups (both P<0.01). To estimate the effects of regression to the mean on the changes in dipping status, we also defined dipping status with the average of the BPs before and after doxazosin and found no difference in the degree of nighttime BP reduction among each group. The reduction of daytime BP was now significantly greater in the subgroups with less dipping: 6.4 mm Hg for extreme dippers and 16 mm Hg for risers (P<0.05). In conclusion nighttime dosing with doxazosin markedly affects the nocturnal BP dipping status of hypertensives, but the apparently greater reduction in nighttime pressure in nondippers and risers may be, at least partly, due to the effect of regression to the mean. The most important determinants of the effect of doxazosin were the absolute BP levels, both day and night, rather than dipping status per se.