Kaiyo Oiwa

Adverse Effect of Nighttime Blood Pressure on the Outcome of Lacunar Infarct Patients

BACKGROUND AND PURPOSE Antihypertensive therapy has dramatically reduced the incidence of stroke recurrence; however, recent studies have suggested that the excessive lowering of blood pressure (BP) could cause ischemic cerebral lesions. We conducted a prospective study using MRI and ambulatory blood pressure monitoring to elucidate the appropriate BP control level for the prevention of silent and symptomatic cerebral infarction. METHODS We studied 105 patients with symptomatic lacunar infarcts who underWent repeated MRI and 24-hour BP monitoring in the period between the two MRI examinations. The patients were divided into five groups according to their outcome as follows: group 1, those who showed neither symptomatic episodes nor the development of new silent lesions detected by repeated MRI; group 2, those who only showed the development of silent lacunae; group 3, those who showed development of diffuse white matter lesions only; group 4, those who showed the development of both silent lacunae and diffuse white matter lesions; and group 5, those who showed symptomatic cerebrovascular disease. Groups 2 through 5 were then compared with group 1 with respect to the ambulatory BP values. RESULTS The average follow-up period was 3.2 +/- 2.6 years (mean +/- SD). In all patients in group 4 and group 5, nighttime systolic BPs were significantly higher than in group 1 (both P<.01), and the magnitude of the nocturnal systolic BP dip and diastolic BP dip in group 4 and group 5 were significantly smaller than in group 1 (all P<.01). In patients who took antihypertensive agents, the 24-hour systolic and diastolic BPs and nighttime systolic and diastolic BPs in group 4 were significantly higher than in group 1 (P<.01, P<.01, P<.001, P<.01, respectively). The magnitude of the nocturnal systolic and diastolic BP dip in group 5 was significantly smaller than in group 1 (both P<.01). CONCLUSIONS A high average ambulatory BP, especially nighttime BP, and a reduced nocturnal BP dip may have an adverse effect on the development of silent ischemic lesions and symptomatic stroke attack in patients with lacunar infarcts.

Diminished Nocturnal Blood Pressure Decline and Lesion Site in Cerebrovascular Disease

BACKGROUND AND PURPOSE Many studies have suggested that diminished nocturnal blood pressure decline in hypertensive cardiovascular disease is associated with the extent of hypertensive vascular disease. In our previous observation of cerebrovascular disease, however, we found reduced nocturnal blood pressure decline to be associated not only with the extent of hypertensive vascular disease but also with the specific location of cerebrovascular lesions. The purpose of this study was to elucidate the mechanism of nocturnal blood pressure decline in cerebrovascular disease. Moreover, to clarify whether reduced nocturnal blood pressure decline occurs before cerebrovascular disease, we examined patients with recurring episodes. METHODS Ambulatory blood pressure monitoring was carried out every 30 minutes in 14 control subjects, 15 hypertensive subjects, 90 patients with cerebrovascular disease (16 single lacunar infarctions, 15 multiple lacunar infarctions, 10 putaminal hemorrhages, 14 thalamic hemorrhages, 11 pontine base infarctions, 15 pontine tegmentum infarctions, 8 pontine hemorrhages, 13 wide cortical infarctions), and 7 patients with recurring stroke episodes. The percentage of nocturnal blood pressure decline and the correlations for systolic blood pressure and heart rate were calculated. RESULTS The percentage of nocturnal blood pressure decline was significantly smaller in the groups with multiple lacunar infarction (systolic, P < .001; diastolic, P < .01), thalamic hemorrhage (P < .01, P < .05), pontine tegmentum infarction (P < .01, P < .05), and pontine hemorrhage (both P < .05). The correlation between systolic blood pressure and heart rate was not significant for almost all the groups with diminished blood pressure decline. CONCLUSIONS Diminished nocturnal blood pressure decline in cerebrovascular disease is thought to be caused by specific injury to the central autonomic nervous system such as the striatum, diencephalon, midbrain, and pontine tegmentum and their connecting fibers.

The Relationship between 24-Hour Blood Pressure Readings, Subcortical Ischemic Lesions and Vascular Dementia

Background: Twenty-four-hour blood pressure (BP) readings have been found to correlate with hypertensive target organ damage. Lacunar infarcts (LI) and white matter lesions (WML) probably represent manifestations of cerebral hypertensive target organ damage. This study was conducted to better delineate the relationships between 24-hour BP measurements, LI/WML and small vessel disease cognitive impairment/vascular dementia (CI/VD). Methods: Two hundred patients with first-time symptomatic LI were examined with 24-hour BP monitoring. The degree of nocturnal BP dip, (daytime BP – nighttime BP)/daytime BP, was categorized into three groups: dippers (>0.1), nondippers (0–0.1) and reverse dippers (<0). WML were subdivided into periventricular hyperintensities (PVH) and subcortical hyperintensities. Results: The breakdown of patients was: 50% nondippers, 27.5% reverse dippers and 22.5% dippers. Forty-one patients (20.5%) were found to have CI and dementia. Male sex (OR 3.35; 95% CI 1.20–9.34), advanced PVH (OR 14.42; 95% CI 5.62–36.98) and absence of a dipping status (nondipper: OR 12.62; 95% CI 1.37–115.95; reverse dipper: OR 11.95; 95% CI 1.27–112.11) were independently associated with CIVD after multivariate analysis. High nighttime systolic BP (OR 3.93; 95% CI 1.38–11.17), high daytime (OR 2.06; 95% CI 1.03–4.04) and nighttime diastolic BP (OR 2.48; 95% CI 1.13–5.45) and absence of a dipping status (nondipper: OR 2.7; 95% CI 1.03–7.05; reverse dipper: OR 3.78; 95% CI 1.38–10.34) were significantly associated with PVH. Conclusions: High prevalence of a nondipping status was found in the LI cohort. A nondipping status appears to be directly associated with CIVD independent of PVH. This study indicates the need for further studies to investigate whether or not controlling nighttime BP will help reduce the risk for CI/VD development.

Twenty-Four-Hour Blood Pressure Changes in the Course of Lacunar Disease

Background: Changes in blood pressure (BP) over time have not been considered in investigations on the relationship between BP and cerebrovascular disease (CVD). Objective: To investigate BP changes throughout a 24-hour period in lacunar infarct patients with different outcomes. Methods: Twelve control subjects (group 1) and 56 patients with symptomatic lacunar infarcts were studied. The infarct patients were divided into three groups: group 2, 25 patients with a fair outcome without any cerebrovascular attack or progressive dementia (mean follow-up period: 4.4 years); group 3, 14 patients with worsening of clinical dementia rating and silent lesions, which included lacunae and diffuse white matter lesions (4.5 years), and group 4, 17 patients who developed symptomatic infarcts (1.7 years). MRIs and ambulatory BP monitoring were performed for each patient on two separate occasions. No patient was treated with antihypertensive agents during the course of the study. Results: In group 2, the second measurements were significantly higher than the first for 24-hour systolic BP (SBP), daytime SBP, 24-hour diastolic BP (DBP), daytime DBP (p < 0.01, for all) and nighttime DBP (p < 0.05). In group 3, the second measurements were significantly lower than the first for 24-hour SBP, daytime SBP, 24-hour DBP, and daytime DBP (p < 0.01, for all). In group 4, the second measurements were significantly lower than the first for 24-hour SBP and daytime SBP (p < 0.01). The correlation between BP and pulse rate became positive for group 2 in second measurements, but was not positive for groups 3 and 4. Conclusions: BP tended to elevate over time in patients with a fair outcome. In contrast, BP tended to decrease in those who developed dementia and symptomatic infarct. Autonomic functions including sympathetic activity might play a role in changes in BP in lacunar infarct patients during the course of disease.

Effect of the angiotensin-converting enzyme inhibitor perindopril on 24-hour blood pressure in patients with lacunar infarction: comparison between dippers and non-dippers.

Antihypertensive therapy based on the angiotensin-converting enzyme (ACE) inhibitor perindopril reduced the incidence of recurrent stroke in the Perindopril Protection against Recurrent Stroke Study (PROGRESS). The present study assessed the effect of perindopril on the 24-h blood pressure (BP) in hypertensive patients with lacunar infarction using ambulatory BP monitoring (ABPM). There was a 4-week observation period, a 4-week treatment period 1 (perindopril at 2 mg/day), and a 4-week treatment period 2 (perindopril at 4 mg/day). Twenty-seven hypertensive patients with lacunar infarction (10 dippers and 17 non-dippers) were enrolled. The average 24-h BP values were significantly decreased after both treatment periods. When the patients were divided into dippers and non-dippers, perindopril exhibited a different BP-lowering effect in the groups with these two circadian BP patterns. In dippers, daytime BP was significantly decreased, whereas nighttime BP was not, so an excessive fall of nighttime BP was not observed. In non-dippers, both daytime and nighttime BP were decreased, with a stronger BP-lowering effect at night. There was a significant inverse correlation between the magnitude of the change in nighttime BP and the night/day ratio. These results suggested that perindopril could induce a sustained decrease of the 24-h BP in patients with lacunar infarction. In particular, a more pronounced nighttime BP-lowering effect was observed in non-dippers. As the incidence of non-dippers is reported to be high among patients with cerebrovascular disease, better nighttime BP control by perindopril might have helped to improve the outcome of such patients in PROGRESS.

Changes of blood pressure variation patterns after Nilvadipine administration in patients with lacunar infarction.

ラクナ梗塞慢性期の患者35例に24時間血圧測定を行い, 収縮期血圧の夜間降圧度により, dipper (7%以上) (D群), non-dipper (0～7%) (N群), reversed (0%以下) (R群) の3群に分類した.Nilvadipineを投与し, それぞれの群で降圧パターンを検討した.D群では, 日中血圧は有意に (p<0.05) 低下したが夜間血圧は有意の低下はみられなかった.一方, N群では逆に, 日中血圧は有意の低下がみられず夜間血圧は有意に (p<0.01) 低下した.R群でも, N群と同様の傾向にあった.N群, R群の内11例について, 123I-SPECT持続動脈血採血法により, Nilvadipine投与前後で脳血流量測定を行ったところ, 有意の (p<0.05) 増加がみられた.Nilvadipine投与により, 夜間血圧非下降型が夜間血圧下降型へと変化した機序として, Nilvadipineによる脳血流量改善作用等により中枢性の自律神経系機能障害が改善された可能性が推察された.

Correlation of cerebral angiographic and CT/MRI findings in transient ischemic attack.

一過性脳虚血発作 (TIA) の病態をより明らかにするため, 内頸動脈系TIA45例 (心原性塞栓を除外) について, 脳血管撮影所見とCT・MRI所見とを併せ検討した.主幹動脈に25%以上狭窄を有するもの {angiographically abnormal, 以下AGA (+)} が26例, 狭窄がそれ以下ないし正常のもの {AGA (-)} が19例であった.AGA (+) で9例 (34.6%), AGA (-) で16例 (84.2%) にCT・MRIで小梗塞 (基底核領域/皮質下白質) を認め, その差は有意であった (P<0.001).これらのことから, TIA発作は, AGA (+) では主にmicroembolismの機序が, AGA (-) では穿通枝レベルでの虚血が関与している可能性が考えられた.AGA (+) とAGA (-) で, 発作回数, 発作持続時間に有意差は認めなかった.また, 高血圧, 糖尿病, 高脂血症, Hctなどの危険因子についても差がみられなかった.これらを追跡したところ (平均追跡期間5.0±2.4年, 全例追跡可), 7例が脳梗塞を発症し, 高齢で発生率が高い傾向にあった.

Cerebrovascular disease and circadian blood pressure change. Influence of site of lesion on nocturnal blood pressure fall and the correlation of heart rate and blood pressure.

脳血管障害各種病型について, 血圧, 脈拍24時間測定を30分毎に行い, 夜間降圧度, 血圧・脈拍相関について検討した.夜間降圧度については, 健常者, 軽症高血圧症, 穿通枝系単発梗塞および皮質広汎梗塞で夜間降圧現象が保たれるものが多かったが, 穿通枝系多発梗塞, 視床出血, 脳幹梗塞, 橋出血では, 健常対照群に対し夜間降圧度が有意に低く, 夜間降圧現象が消失する傾向にあった.血圧・脈拍相関については, 健常者, 軽症高血圧症および穿通枝系単発梗塞, 橋出血で有意の相関がみられたが, 穿通枝系多発梗塞, 内頸動脈閉塞症, 視床出血, 脳幹梗塞では有意の相関が見られなかった.相関の無い群は夜間降圧現象が消失した群にほぼ一致した.また夜間降圧現象はADL障害の少ない穿通枝系多発梗塞よりむしろADLが高度に障害されている皮質広汎梗塞で保たれており, この現象についてはADLの関与より脳障害部位による影響の方が大であると考えられた.