(Stroke. 1996;27:1319-1327.)
© 1996 American Heart Association, Inc.
Articles |
Nocturnal Blood Pressure and Silent Cerebrovascular Lesions in Elderly Japanese
The Second Department of Internal Medicine (N.W., Y.I., M.S., H.S., J.K., N.O.-K., M.Y., F.A., K.A.), Public Health (I.T., S.H.), and Environmental Health Science (H.S.), Tohoku University School of Medicine, Sendai, and Ohasama Hospital (K.N.), Iwate, Japan.
Correspondence to Yutaka Imai, MD, The Second Department of Internal Medicine, Tohoku University School of Medicine, Seiryomachi, Sendai, 980-77, Japan.
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Abstract |
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Background and Purpose We conducted a cross-sectional epidemiological survey using ambulatory blood pressure monitoring and brain MRI in a cohort from northern Japan to determine whether an inappropriately low nocturnal blood pressure, or an excess fall in nocturnal blood pressure, might be responsible for silent cerebrovascular lesions in the elderly.
Methods Untreated subjects over 55 years and under 64 years of age (late middle age; 24 men and 46 women, 60% of eligible people) and over 65 years and under 75 years of age (elderly; 29 men and 52 women, 91% of eligible people) participated in the study. We evaluated the relationship between the amplitude (Daytime Average-Nighttime Average) or the rate ([Daytime Average-Nighttime Average]/Daytime Average) of the fall in nocturnal blood pressure and the incidence of silent cerebrovascular lesions on MRI (number of lacunar infarctions or extent of periventricular hyperintensity).
Results The amplitude or the rate of the fall in nocturnal blood pressure in elderly women with one or two lacunar infarctions was significantly higher than that in those without such infarctions. There was a significant positive correlation between the amplitude or the rate of the fall in nocturnal blood pressure and the extent of periventricular hyperintensity in the elderly women. This relationship was observed in women, but not in men, of late middle age; this was not seen in elderly men.
Conclusions Results indicate that an inappropriately low nocturnal blood pressure, or an excessive fall in nocturnal blood pressure, is associated with ischemic silent cerebrovascular lesions, at least in elderly women. Treatment of hypertension in such women should be administered with care and with regard to nocturnal blood pressure.
Key Words: blood pressure • cerebrovascular disorders • magnetic resonance imaging
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Introduction |
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Hypertension is a major risk factor for stroke and vascular dementia.1 2 The screening for and treatment of hypertension have dramatically reduced the incidence of stroke mortality in Japan, Europe, and the United States.3 This reduction is mainly attributable to a decrease in the incidence of cerebral hemorrhage.3 Although the mortality from cerebral infarction has decreased in Japan, a statistical report from the Ministry of Health and Welfare of Japan indicates no decrease in the prevalence of cerebral infarction and that the incidence of nonfatal cerebral infarction has in fact increased.4 Recent intervention trials have demonstrated little benefit of antihypertensive treatment on the incidence of coronary heart disease.5
Previous epidemiological studies on hypertension were based on casual measurements of BP. There is, of course, a limit to the amount of information provided by such measurements. We require information on short-term and long-term BP variability, average BP over 24 hours, average daytime and nighttime BP, BP load, amplitude of the fall in nocturnal BP, and other information. Several authors reported that BP variability is an important marker for the prognosis of hypertension.6 7 Recent studies demonstrated that a high nocturnal BP level with a slight fall in nocturnal BP is an apparent risk factor for left ventricular hypertrophy8 9 as well as cerebrovascular disease.10 11 12 Patients with a normal fall in nocturnal BP are termed "dippers," while those with only a slight fall in nocturnal BP are termed "nondippers."10 It was concluded that a sustained elevation of nocturnal BP is responsible for end-organ damage.8 9 10 11 12 A fall in nocturnal BP is generally observed in normotensive subjects as well as in those with mild to moderate essential hypertension, regardless of the level of daytime BP and age.13 The amplitude of the fall in nocturnal BP is decreased or even lost in men over the age of 70 years14 as well as in hypertensive patients with advanced atherosclerotic or arteriosclerotic vascular lesions such as silent cerebrovascular lesions, dementia due to vascular disease, and left ventricular hypertrophy.8 9 10 11 12 15 Thus, it is possible that the circadian BP variation in patients with an early stage of essential hypertension without end-organ damage is initiated in the dippers and that accelerated end-organ damage accompanies the nondipper type of circadian BP variation. Questions arise as to whether the nondipper represents the cause or the effect of end-organ damage and whether the dipper condition is beneficial or harmful to patients with cerebrovascular and cardiovascular disorders.
We hypothesized that inappropriately low levels of nocturnal BP in elderly hypertensive subjects that occur spontaneously or are induced by treatment may induce ischemic end-organ damage and that such damage would lead to a persistent elevation of nocturnal BP. To study this hypothesis, we conducted a cross-sectional epidemiological survey in a cohort from northern Japan using ambulatory BP monitoring and brain MRI. We tried to determine whether an inappropriately low nocturnal BP or an excessive fall in nocturnal BP would be associated with silent cerebrovascular lesions in this elderly population.
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Subjects and Methods |
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The study was conducted between 1987 and 1991 in elderly people living in the Uchikawame and Kamegamori regions in the rural community of Ohasama of the Iwate Prefecture. Geographic and economic data on these regions have been reported.16 This study was approved by the institutional review board of the Tohoku University School of Medicine.
Subjects
The total population of the two regions was 3533 (1713 men and 1820 women). A total of 235 persons in the Kamegamori region were between the ages of 55 and 64 years (108 men and 127 women); 288 individuals in the Uchikawame region were between the ages of 65 and 75 years (129 men and 159 women). We asked persons without a history or findings of neurological, cardiovascular (except for hypertension), or other major disorders (eg, diabetes mellitus or chronic renal disease) to participate in our program. It consisted of screening BP measurements, ambulatory BP monitoring over a 24-hour period, physical and laboratory examinations, and MRI of the brain. Of the 235 people in the Kamegamori region, 117 were eligible and 74 (63%) participated. Of the 288 people in the Uchikawame region, 89 were eligible and 84 (94%) participated.
Quality of sleep at night was evaluated after ambulatory BP monitoring. Data on the subjects who complained of sleep disturbances during the monitoring were excluded from evaluation (4 subjects in the Kamegamori region and 3 in the Uchikawame region). Ultimately, we evaluated in depth 70 subjects in the Kamegamori region who were between the ages of 55 and 64 years (late middle age), ie, 60% of the eligible persons in that region. We evaluated 81 subjects in the Uchikawame region who were between the ages of 65 and 75 years (elderly subjects), ie, 91% of the eligible persons in that region.
Blood Pressure Measurements
Physicians initially measured each subject's BP twice consecutively with the subject seated after at least 2 minutes of rest. Standard mercury sphygmomanometers were used. This was termed the screening BP. To measure the ambulatory BP, we used the ABPM 630 (Nippon Colin), which is fully automatic.17 The device was preset to measure BP every 30 minutes. Since the arm circumference was less than 35 cm in all subjects, we used a standard arm cuff for both the screening BP measurements and ambulatory BP monitoring.
Magnetic Resonance Imaging
MRI was performed with a superconducting magnet that had a main field strength of 0.5 T (Toshiba 50-A). The brain was imaged in the axial plane in 10-mm-thick slices. T1-weighted images were obtained using a short spin-echo sequence with a repetition time of 50 milliseconds and an echo time of 20 milliseconds. T2-weighted images were obtained using a long spin-echo pulse sequence with a repetition time of 2000 milliseconds and an echo time of 120 milliseconds. The matrix was 256x256 pixels.
Analytical Methods
For a subject's ambulatory BP data to be included in the analyzed data, we required a monitoring period of more than 8 hours during waking (daytime) and more than 4 hours while the subject was in bed at night (nighttime). These periods were estimated from data in each subject's diary. If the 24-hour ambulatory BP monitoring was incomplete, we calculated the 24-hour average ambulatory BP as follows: 24-Hour Average Ambulatory BP=(Daytime AveragexWaking Hours+Nighttime AveragexSleeping Hours)/24. Mean monitoring time was 23.6±1.7 hours; the mean number of measurements was 46.7±3.9 times (n=151). Artificial readings obtained during ambulatory BP monitoring were defined according to the criteria mentioned previously and were excluded from analysis.18
The amplitude of the fall in nocturnal BP was calculated as Daytime Average Ambulatory BP Level-Nighttime Average Ambulatory BP Level. The fall in nocturnal BP normalized by the different daytime levels, ie, the rate of the fall in nocturnal BP, was also calculated as follows: Rate of Fall in Nocturnal BP=(Daytime Average Ambulatory BP Level-Nighttime Average Ambulatory BP Level)/Daytime Average Ambulatory BP Level.
MRIs were evaluated in a blinded manner by two physicians (N.W. and K.N.) who determined the number of lacunae and the extent of periventricular signal abnormalities. A lacuna was defined as an area of low signal intensity that measured <10 mm and >3 mm on T1-weighted images and was visible as a hyperintense lesion on T2-weighted images. Hyperintense punctate lesions present only on the T2-weighted images were not counted as lacunae to exclude small unidentified bright objects of little clinical significance.19 Lesions that measured <3 mm on the T1- as well as the T2-weighted images were excluded to avoid the inclusion of enlarged perivascular spaces ("etat crible").20 The number of lacunae in the supratentorial region was counted in each individual and classified as follows: no lacunar infarctions (group A), one to two lacunar infarctions (group B), and more than three lacunar infarctions (group C).
The PVH observed on the T2-weighted images was classified into five groups. When PVH was observed only in the region adjoining the lateral ventricle, it was scored as 1 point. When PVH was observed in the entire region from the lateral ventricle to the cortex, it was scored as 2 points. The frontal and occipital scores were summed, resulting in scores that ranged from grade 0 to 4 (ie, 0 point, grade 0; 1 point, grade 1; 2 points, grade 2; 3 points, grade 3; and 4 points, grade 4).
Data on the two age groups (middle-aged and elderly) were analyzed separately. Characteristics of the subjects appear in Table 1
. Screening BP levels, ambulatory BP levels, and amplitude of the fall in nocturnal BP were compared among subgroups with a differing number of lacunae or a differing extent of PVH in each age and sex category. Subjects in the elderly group were also classified according to screening BP levels and the amplitude of the fall in nocturnal BP as reported by Shimada et al12 ; screening levels 
140 mm Hg SBP and/or 90 mm Hg DBP defined hypertension. An amplitude of the fall in nocturnal SBP 10 mm Hg defined a "dipper," whereas that of <10 mm Hg defined a "nondipper." The number of lacunar infarctions and the extent of PVH were compared in normotensive versus hypertensive subjects and in dippers versus nondippers.
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Statistical Analysis
Values were expressed as mean±SE, unless otherwise stated. Differences between groups were compared using Duncan's multiple range test after one-way ANOVA. Linear regression analysis and the 
2 test were used as appropriate. A level of P<.05 was accepted as statistically significant.
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Results |
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Characteristics of Groups Studied
The screening BP tended to show the presence of pure systolic hypertension, especially in the elderly subjects (Table 1
). The 24-hour ambulatory BP was significantly lower than the screening BP in all subgroups (P<.001). Both the screening and 24-hour ambulatory BPs were significantly higher in the elderly subjects than in those of late middle age (P<.001).
Relationship Between Lacunar Infarction and Blood Pressure
The number of lacunar infarctions was significantly correlated with age (n=151; y=0.09x-5.1, r=.36, P<.01, where y is the number of lacunar infarctions and x is age). The number of lacunar infarctions was also significantly correlated with the ambulatory BP levels (n=151; SBP, y=0.05x-5.3, r=.39, P<.01, where x is the 24-hour average ambulatory SBP; DBP, y=0.07x-4.1, r=.32, P<.01, where x is the 24-hour average ambulatory DBP).
Elderly Subjects
Of the 81 elderly subjects evaluated, 41 had at least one lacunar infarction. The screening BP did not differ among subgroups classified according to the number of lacunar infarctions. The ambulatory BP of women with lacunar infarctions was higher than that of women without lacunar infarctions. The ambulatory DBP in men with one to two lacunar infarctions was higher than that of men without lacunar infarctions (Table 2). The ambulatory BP in women with one to two lacunar infarctions did not differ from that in women with more than three lacunar infarctions.
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The amplitude of the fall in nocturnal SBP in the elderly women with one to two lacunar infarctions (group B) significantly exceeded that of the women without a lacunar infarction (group A). The amplitude of the fall in nocturnal BP in the elderly women with one to two lacunar infarctions also tended to be higher than that in women with more than three lacunar infarctions (group C), but the difference was not statistically significant (Fig 1).
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Because the basal ambulatory BP of the elderly women in group B was significantly higher than those in group A, we compared the rate of the fall in nocturnal BP between groups A and B. The rate of the fall in nocturnal SBP in group B (0.16±0.11) was significantly higher than that in group A (0.10±0.07, P<.05). There was no difference in the amplitude or rate of the fall in nocturnal DBP among the subgroups of elderly women (Fig 1). In addition, there was no difference in the amplitude or the rate of the fall in nocturnal BP among the subgroups of elderly men (Fig 1).
Subjects of Late Middle Age
The basal screening or ambulatory BP among subgroups of each sex did not differ significantly (data not presented). As shown in Fig 2, the relationship between the number of lacunar infarctions and the amplitude of the fall in nocturnal BP in women of late middle age resembled that in the elderly women.
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Because only one of the men of late middle age had more than three lacunar infarctions, we combined groups B and C for evaluation. Although the amplitude of the fall in nocturnal BP in men with lacunar infarctions tended to be smaller than that in men without lacunar infarction, the difference was not statistically significant.
Relationship Between PVH and BP
The extent of PVH was significantly correlated with age (n=151; y=0.08x-3.9, r=.41, P<.01, where y is the extent of PVH and x is age) and BP levels (n=151; SBP, y=0.03x-3.1, r=.36, P<.01, where x is the 24-hour average ambulatory SBP level; DBP, y=0.06x-2.9, r=.35, P<.01, where x is the 24-hour average ambulatory DBP level).
Elderly Subjects
Of the 81 elderly subjects, 59 had PVH above grade 1. The screening BP did not differ among subgroups with a differing extent of PVH, considering both men and women. The ambulatory BP in subgroups of elderly women with PVH, except for the group with grade 2 PVH, was significantly higher than in those without PVH (Table 3).
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The amplitude of the fall in nocturnal SBP in the elderly women increased with an increase in the extent of PVH (Fig 3; y=0.04x+1.1, r=.32, P<.05, where y is the extent of PVH and x is the amplitude of the fall in nocturnal BP). The rate of the fall in nocturnal SBP in elderly women also increased with an increase in the extent of PVH (y=4.6x+1.1, r=.28, P<.05, where y is the extent of PVH and x is the rate of the fall in nocturnal SBP). However, there was no relationship between the extent of PVH and either the amplitude or rate of the fall in nocturnal DBP.
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Because fewer than five men had PVH of grades 3 and 4, their data were combined. The ambulatory BP in the subgroup of men with grade 2 PVH was significantly higher than that in the other subgroups (Table 3).
The amplitude of the fall in nocturnal DBP in the elderly men with PVH greater than grade 3 tended to be smaller, but not significantly so, than that in the remaining groups (Fig 3). The rate of the fall in nocturnal DBP in the group with PVH greater than grade 3 (0.07±0.02) was significantly smaller than that in the group with grade 2 PVH (0.12±0.05, P<.05). There was no difference in the amplitude or rate of the fall in nocturnal SBP in men among subgroups with differing grades of PVH (Fig 3).
Subjects of Late Middle Age
Because fewer than five men of late middle age had PVH greater than grade 2, we compared those with and without PVH. Also, since fewer than two women of late middle age had PVH of grades 3 and 4, PVH of grades 3 and 4 were combined.
The screening BP did not differ between men with and without PVH (Table 4). The screening BP in women with grade 2 PVH significantly exceeded that of women without PVH. The former value did not differ from that in the other groups with PVH (Table 4). The ambulatory BP in subgroups of women with PVH was significantly higher than that in those without PVH, while that in subgroups with PVH did not differ (Table 4). The amplitude of the fall in nocturnal BP increased with an advance in the extent of PVH in women of late middle age (Fig 4; SBP, y=0.04x-0.05, r=.43, P<.01; DBP, y=0.06x-0.05, r=.42, P<.01, where y is the amplitude of the fall in nocturnal BP and x is the extent of PVH).
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The amplitude of the fall in nocturnal BP in men did not differ in the groups with versus without PVH. The rate of fall in nocturnal BP in women also increased with an advance in the extent of PVH (SBP, y=4.46x+0.02, r=.37, P<.05; DBP, y=3.77x+0.07, r=.34, P<.05, where y is the rate of fall in the nocturnal BP and x is the extent of PVH).
Ischemic Cerebrovascular Lesions Based on Amplitude of the Fall in Nocturnal BP
Although the number of lacunar infarctions did not differ between the normotensive and hypertensive elderly women (Table 5), the extent of PVH was significantly greater in the elderly hypertensive women than in the elderly normotensive women (2=5.65, P<.02). However, the extent of PVH in dippers among elderly women did not differ significantly from that of nondippers (2=0.95). In men, the number of lacunar infarctions or the extent of PVH tended to be greater in the nondippers versus dippers, although the difference was not statistically significant. The normotensive men had significantly fewer lacunar infarctions than the hypertensive men (P<.01).
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Discussion |
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MRI of normal individuals often reveals silent cerebrovascular lesions such as asymptomatic lacunar infarctions11 21 and PVH.22 23 Such cerebral changes have also been associated with aging,21 23 24 25 hypertension,21 22 25 26 27 atherosclerosis,25 diabetes mellitus,22 26 or a history of stroke.25 28 29 The presence of silent lacunar infarctions suggests a decrease in the cerebral circulation.21 30 PVH has been correlated with mental dysfunction.23 To reduce the risk of stroke and vascular dementia, it is important to evaluate the relationships between asymptomatic cerebrovascular changes and hypertension, circadian variation in BP (dipper and nondipper), and short-term variation in BP.
Investigators who have studied the relationship between nondippers and left ventricular hypertrophy8 9 or between nondippers and cerebrovascular lesions10 11 12 have concluded that a high nocturnal BP causes target-organ damage. If the diurnal BP of the nondippers resembles that of the dippers, the net BP load on the cardiovascular system is obviously greater in the former. Thus, more extensive cardiovascular and cerebrovascular lesions may occur in nondippers. Although the present study was cross-sectional and thus cannot conclusively demonstrate a cause-and-effect relationship between the fall in nocturnal BP and silent cerebrovascular lesions, we observed the presence of more extensive silent cerebrovascular lesions in the elderly women with the extreme dipper type of circadian BP variation than in those with the ordinary or nondipper type of circadian variation. Our findings do not support the conclusion that a sustained elevation of nocturnal BP (nondipper) causes such ischemic cerebrovascular lesions, at least in elderly women.
Hypertension is a major risk factor for atherosclerosis and arteriosclerosis. Regional CBF is reduced by aging30 31 and hypertension.30 32 33 A decrease in CBF with a decrease in BP is observed in normal subjects during sleep stages II and III.34 Regional CBF is decreased more markedly during sleep in elderly subjects with than those without leukoaraiosis.35 Elderly hypertensive subjects with silent cerebrovascular lesions and those with vascular dementia of the Binswanger type are reportedly nondippers.11 12 15 Nondippers have also been observed to have end-organ damage (eg, hypertensive patients with advanced left ventricular hypertrophy, arteriosclerosis obliterans, and other conditions and after myocardial infarction or cerebral infarction).36 37 Such reports suggest the existence of compensatory mechanisms that would diminish or eliminate the fall in nocturnal BP in patients with organ ischemia attributable to advanced atherosclerosis and/or arteriosclerosis, protecting against the end-organ damage that would be caused by a decrease in blood flow during sleep. We thus hypothesize that a diminished fall in nocturnal BP in patients with some types of hypertension is caused by end-organ damage. Interestingly, Kario and Shimada38 have described an elderly hypertensive patient whose diurnal BP variability changed from that of an extreme dipper to a nondipper after a small lacunar infarction. They concluded that nondipper hypertension in elderly patients with ischemic cerebrovascular lesions may be secondary to minor cerebrovascular damage. The present study confirmed that the number of lacunar infarctions and the extent of PVH were each correlated with age and BP. Hypertension causes atherosclerosis in the carotid and main cerebral arteries, and it causes hemodynamic and atherothrombotic infarctions in the cortical and external watershed regions.39 Hypertension may also alter the deep penetrating arteries, leading to circulatory failure and lacunar infarctions.39 Prolonged hypertension can thus produce hypertensive, atherosclerotic, and arteriosclerotic cerebrovascular changes. In elderly hypertensive patients with such cerebrovascular changes, a slight decrease in the perfusion pressure can easily reduce the CBF.30 40 In elderly hypertensive patients with PVH, the CBF is decreased during sleep and its autoregulation disturbed.34 35 Thus, an inappropriately low or excessive fall in the nocturnal BP may cause silent cerebrovascular lesions, at least in elderly hypertensive women.
The present results demonstrated sex differences in the relationship between the fall in nocturnal BP and the presence of silent cerebrovascular lesions. Verdecchia et al41 recently reported that a diminished fall in nocturnal BP is an apparent risk factor for cardiovascular mortality in women. Whereas those authors investigated cardiovascular mortality, we investigated silent cerebrovascular lesions in the present study. The latter seemed to be associated with relatively mild end-organ changes. Several differences between the present study and that of Shimada et al12 should be noted. These authors observed that the diminished fall in nocturnal BP in elderly hypertensive persons was associated with silent cerebrovascular lesions. They evaluated silent cerebrovascular lesions in a group of men and women and in a group of elderly hypertensive subjects aged from 59 to 83 years. Those subjects had received antihypertensive drugs, which were discontinued 4 weeks before the study was started.12 The present investigation evaluated patients by sex in a narrow age range who had not received any antihypertensive medication. Shimada et al12 classified the hypertensive patients as dippers and nondippers and compared the severity of silent cerebrovascular lesions between these groups.12 We also compared the extent of the silent cerebrovascular lesions in the dippers and nondippers. The extent of PVH was significantly greater in the elderly hypertensive women than in the elderly normotensive women in the present study. However, the extent of PVH in the elderly women who were dippers did not differ significantly from that in the nondippers, suggesting that at least the extent of PVH in nondippers was no greater than that in dippers. The extent of PVH in the elderly women was positively correlated with the amplitude of the fall in nocturnal BP. The differences between our results and those of Verdecchia et al and Shimada et al appear to be attributable to differences in the subjects' age, severity of hypertension, and sex. However, it is unclear why such phenomena were observed only in the elderly women. The circadian BP variation in elderly women differs from that in elderly men a priori.14 The circadian BP variation of some elderly women was of the extreme dipper type, whereas the elderly men were nondippers.14 Until the reason for the difference in circadian BP variation between the elderly men and women can be explained, the cause of the relationship between the fall in nocturnal BP and silent cerebrovascular lesions will remain unclear. The fall in nocturnal BP is generally considered to be mediated by a decrease in cardiac output36 as well as by a potentiation of the baroreflex function during sleep.42 The baroreflex function acts to maintain BP via an increase in peripheral vascular resistance36 during a decrease in cardiac output. It is possible that a rapid progression of atherosclerosis after menopause disturbs the baroreflex function and the responsiveness of resistance vessels with a decrease in cardiac output during sleep, which leads to a marked fall in nocturnal BP.43 However, it is difficult to explain why an exaggerated fall in nocturnal BP was observed in the elderly women with mild lacunar infarction, whereas the nocturnal BP fall approached normal in those with advanced lacunar infarctions. As mentioned above, a worsening of cerebral ischemia may lead to an acceleration of lacunar infarctions so that the nocturnal BP level may become elevated as a means of preventing an exacerbation. An episode of apnea accompanies an increase in the CBF with the elevation of BP in the sleep-apnea syndrome, in which cerebral ischemia has been observed.44 This suggests that organ ischemia may induce a signal that leads to an elevation of BP during sleep. The observations by Shimada et al12 and Verdecchia et al,41 as well as the present observations in men, can be explained by this mechanism.
Several limitations of this study should be considered. We examined the relationship between asymptomatic cerebrovascular lesions on MRI and the fall in nocturnal BP but not the relationship between MRI and the pathology of such lesions. This presented a potential source for error in the interpretation of our results. Several postmortem studies have described the relationship between MRI and pathological findings of lacunar infarction.20 25 Fisher45 has defined lacunae as infarctions caused by occlusion of branches in perforating arteries. Awad et al25 reported that "etat crible," which is characterized by sclerosis of the small arteries and arterioles, vascular ectasia, and dilated perivascular spaces, is difficult to distinguish precisely from lacunar infarction by MRI and that such lesions often coexist. Therefore, to exclude etat crible in the present study, we did not count as lacunar infarctions any lesions that measured <3 mm on the T1- and T2-weighted images. It is possible, however, that some lesions counted as lacunar infarction included unidentified punctate lesions.20
The relationship between the PVH on MRI and the postmortem pathological findings has been evaluated by several authors. Dilated periventricular spaces, gliosis, demyelination, arteriosclerosis, and vascular ectasia have been demonstrated in such MRI lesions.25 46 47 Some authors have shown that the presence of PVH around the anterior horns of the lateral ventricles was nonpathological, while hyperintensities of the deep and subcortical white matter reflected the ischemic tissue damage.46 48 However, accelerated PVH has been observed on MRI of patients with Alzheimer's disease49 and normal pressure hydrocephalus,50 which suggests that it does not necessarily reflect ischemic tissue damage.
The correlation between the amplitude of the fall in nocturnal BP and MRI lesions was only marginally significant in the elderly women and not significant in men. Thus, caution is needed when interpreting the present results. It is possible that a difference in the number of male and female participants and in the baseline BP profiles contributed to the relationships between gender, the fall in nocturnal BP, and silent cerebrovascular lesions.
An increased risk of silent cerebrovascular lesions has been reported in patients with elevated ambulatory BP levels.11 It is possible that the nocturnal dipper is consistent with a diurnal "peaker."51 The BP response to mental and physical stimuli is exaggerated in menopausal women,52 which suggests the presence of diurnal peaking in elderly women. In the present study, the daytime ambulatory BP in the elderly women with silent cerebrovascular lesions was significantly higher than that in elderly women without such lesions. If diurnal peaking contributes to the development of silent cerebrovascular lesions, the difference between the sexes in the relationship between the amplitude of the fall in nocturnal BP and the severity of MRI lesions would be explained in part by the diurnal peaking in the elderly women.
The present study indicated that an excess or an inappropriate difference between daytime and nighttime BP levels was related to the presence of asymptomatic lacunar infarctions and PVH in the elderly women. Thus, antihypertensive medications that reduce nocturnal BP should be administered with care to elderly hypertensive women who show a low nocturnal BP (dippers). One should also be aware of a shift from the "nondipper" type of circadian BP variation to that of the "dipper" type in elderly hypertensive persons with accelerated target-organ damage. Nakamura et al53 recently demonstrated that stroke survivors with the dipper pattern who were given antihypertensive drugs showed a higher incidence of recurrent stroke and of symptomatic and asymptomatic brain lesions than the nondippers. Kario et al54 observed advanced silent cerebrovascular damage in elderly hypertensive patients with an extreme dip in nocturnal BP. Although the present study emphasized the fall in nocturnal BP and the nocturnal BP levels in relation to asymptomatic cerebrovascular lesions, it is recognized that elevated 24-hour ambulatory BP levels are associated with increased risks of clinically significant cerebrovascular disorders,11 15 left ventricular hypertrophy,8 55 56 and renal disorders.57 58 The information provided by ambulatory BP monitoring also includes the 24-hour average BP, daytime average BP, short-term BP variability, and other parameters. Measurements of average ambulatory BP and BP variability reportedly predict the risk of cardiovascular events and the prognosis of hypertension more reliably than that of casual BP.6 7 59 60 Therefore, when diagnosing and treating hypertension, one should focus on such BP information in addition to the fall in nocturnal BP and nocturnal BP level. Our findings indicate that the physician should be aware of the patient's circadian variation in BP when elderly hypertensive patients receive antihypertensive treatment.
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Acknowledgments |
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This work was supported by a research grant from the Miyagi Prefectural Kidney Association; a research grant from Takeda Medical Research Foundation; research grants for cardiovascular disease (No. 4C-3, 5C-2) from the Ministry of Health and Welfare; a research grant entitled "Evaluation of the Effect of Drug Treatment on Hypertension and Other Chronic Disease Conditions in the Elderly" from the Ministry of Health and Welfare; and research grants for scientific research (07670746 and 07670420) from the Ministry of Education, Science, and Culture of Japan.
Received September 21, 1995; revision received March 28, 1996; accepted May 2, 1996.
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References |
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