Masamichi Hayashi

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

BACKGROUND AND PURPOSEnAntihypertensive 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.nnnMETHODSnWe 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.nnnRESULTSnThe 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).nnnCONCLUSIONSnA 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.

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.