Postprandial Hypotension Is Associated With Asymptomatic Cerebrovascular Damage in Essential Hypertensive Patients
Abstract—To elucidate the relationship between postprandial hypotension (PPH) and asymptomatic cerebrovascular damage, we evaluated changes in blood pressure after a meal by 24-hour blood pressure monitoring in 70 hospitalized essential hypertensive patients aged ≥50 years. They received a diet containing standard nutritional ingredients with 120 mmol (7 g) NaCl and were free from medication for at least 1 week. PPH was defined as the mean reduction of systolic blood pressure during 2 hours after a meal. Patients were divided into three groups according to mean values of PPH after 3 meals: PPH-1 (n=16, 5 mm Hg≤PPH<10 mm Hg), PPH-2 (n=18, PPH≥10 mm Hg), and normal (n=36, PPH<5 mm Hg). As asymptomatic cerebrovascular damage, lacunae and leukoaraiosis were evaluated by magnetic resonance imaging. PPH did not correlate with daytime or nighttime blood pressure or the nondipper phenomenon; however, PPH was significantly related to asymptomatic cerebrovascular damage. The prevalence of lacunae in the normal, PPH-1, and PPH-2 groups was 44%, 69%, and 83%, respectively (χ2=8.22, P<0.05). The number of lacunae in the normal, PPH-1, and PPH-2 groups was 1.0±1.3, 1.3±1.2, and 1.9±1.4, respectively (F[2,67]=3.2, P<0.05). The prevalence of advanced leukoaraiosis in the normal, PPH-1, and PPH-2 groups was 44%, 50%, and 83%, respectively (χ2=7.63, P<0.05). Severity score of leukoaraiosis in the normal, PPH-1, and PPH-2 groups was 1.5±0.7, 1.7±0.8, and 2.1±0.7, respectively (F[2,67]=4.3, P<0.05). These findings indicate that elderly hypertensive patients with marked PPH should be considered to have advanced cerebrovascular damage even in the absence of abnormal neurological findings.
- blood pressure monitoring
- hypotension, postprandial
- blood pressure variability
Alteration of the diurnal change in blood pressure (BP) has been shown to be related to several clinical abnormalities, including advanced end-organ damage,1 2 3 secondary hypertension,4 and autonomic nervous system dysfunction.5 Several studies have demonstrated a linkage between asymptomatic brain damage and alteration of the diurnal change in BP.2 6 7 8 Recently, it has also been shown that dysregulation of postural change in BP is associated with advanced silent cerebrovascular damage in hypertension in the elderly.9
Asymptomatic cerebrovascular damage, often found in elderly hypertensive individuals, is associated with cognitive dysfunction,9 depression of mood,10 and reduced capacity of the cerebral circulation.11 12 It has also been shown that patients with asymptomatic lacunae have a significantly higher incidence of future stroke than normal subjects.13
Postprandial hypotension (PPH) is a relatively common phenomenon frequently observed in elderly hypertensive patients.14 However, only a few studies have investigated the effect of PPH on the diurnal change in BP in hypertensive patients.15 16 In our previous study,16 we evaluated PPH with ambulatory BP monitoring (ABPM) and showed that PPH contributed to the variability of BP in the daytime and the morning surge of BP, independent of the dipper and nondipper phenomena. Clinically, PPH can cause light-headedness, fainting, falls, or even transient ischemic attack.14 Recently, it has also been shown that PPH is an independent risk factor for future mortality, coronary events, and stroke.17 These findings suggest the relevance of PPH to cerebrovascular damage.
The objective of the present study was to elucidate whether PPH is associated with asymptomatic cerebral damage. Since daily activity, including the awake and sleeping times, as well as the contents of meals could significantly influence diurnal change in BP, the present study was performed on hospitalized essential hypertensive patients with standardized daily activities and meals.
Seventy hospitalized essential hypertensive patients aged ≥50 years participated in the study. They were recruited from consecutive cases admitted to the Second Department of Internal Medicine, Ehime University Hospital, for the evaluation of hypertension and agreed to undergo brain magnetic resonance imaging (MRI). All of the participants were free from any abnormal neurological findings. Patients with autonomic nervous dysfunction, congestive heart failure, previous myocardial infarction, or history of symptomatic cerebrovascular accident including transient ischemic attack were excluded from the study. The contents of meals, times of meals, and daily activities were standardized. Total caloric intake for the patients was 126 kJ/kg (30 kcal/kg) ideal body wt per day. The dietary composition was 66% carbohydrate, 16% protein, and 18% fat for each patient. Meal times were 8 to 8:30 am for breakfast, noon to 12:30 pm for lunch, and 6 to 6:30 pm for dinner. Snacks and drinks, including coffee after meals, were prohibited.16 All procedures were approved by the ethics committee of Ehime University Hospital. Informed consent to the procedure was obtained from each patient.
Twenty-Four–Hour BP Determination
Twenty-four–hour BP was measured by a cuff-oscillometric method (TM-2421, A/D Ltd). BP was measured every 30 minutes from 6 am to 10 pm and every 60 minutes from 10 pm to 6 am on the following day.5 16 Daytime and nighttime BPs were obtained as the average values during the awake period between 6 am and 10 pm and during the sleep period between 10 pm and 6 am, respectively.5 16 Patients were allowed to move freely but asked to sit quietly on a bed or chair during BP measurement. The waking time, time needed to fall asleep, and quality of sleep were assessed by interview with each patient.
Postprandial change in BP was defined as the difference between mean systolic BP (SBP) during 1 hour before and during 2 hours after a meal.16 BP values during the meal were excluded to avoid the influence of postural or eating-related change in BP. Patients were divided into the following three groups according to the mean postprandial change in SBP for three meals: PPH-1 (n=16, 5 mm Hg≤PPH<10 mm Hg), PPH-2 (n=18, PPH≥10 mm Hg), and normal (n=36, PPH<5 mm Hg).
Magnetic Resonance Imaging
MRI was performed using a superconducting magnet with a main field strength of 1.5 T. As asymptomatic cerebrovascular damage, the presence of lacunae was evaluated in all patients. A lacuna was defined as a low-signal-intensity area (>0.3 cm and <1.5 cm) on T1-weighted images that was also visible as a hyperintense lesion on T2-weighted images. The number of lacunae per patient was counted. Leukoaraiosis, deep white matter lesions, depicted on T2-weighted images was classified into four grades: grade I, no abnormality or minimal periventricular signal hyperintensities in the form of caps confined exclusively to the anterior horns or rims lining the ventricles; grade II, hyperintensities in both the anterior and posterior horns of the lateral ventricles or periventricular unifocal patches; grade III, multiple periventricular hyperintense punctate lesions and their early confluence; and grade IV, multiple areas of high signal intensity reaching confluence in the periventricular region.9 White matter lesions were scored from 1 to 4 according to the grade. One author who was blinded to the clinical status of the subjects interpreted all MRI scans.
All values are expressed as mean±SD if not specified otherwise. Differences among groups were evaluated by analysis of variance followed by Duncan’s multiple range test. Difference in prevalence was analyzed by χ2 test. A probability less than 0.05 was defined as significant.
Postprandial Change in SBP
Figure 1⇓ summarizes daytime changes in SBP in the normal, PPH-1, and PPH-2 groups. A decline in SBP was observed after each meal. It was also notable that PPH contributed to the fluctuation of SBP.
Table 1⇓ summarizes demographic and hemodynamic parameters in the three groups. Among the three groups, there were no difference in sex, body mass index, duration of hypertension, and other risk factors, including smoking, hyperlipidemia, and diabetes mellitus. The prevalence of previous antihypertensive treatment also did not differ among the three groups (81% for normal, 75% for PPH-1, and 72% for PPH-2). However, patients in the PPH-2 group were significantly older than those in the normal and PPH-1 groups. Daytime and nighttime BPs as well as nocturnal change in SBP also did not differ among the three groups.
Asymptomatic Brain Damage and PPH
Table 2⇓ summarizes asymptomatic cerebrovascular damage in each group of patients. There was a significant difference in the prevalence of lacunae (χ2=8.22, P<0.05), number of lacunae (F[2,67]=3.2, P<0.05), prevalence of advanced leukoaraiosis (grade≥II) (χ2=7.63, P<0.05), and the severity score of leukoaraiosis (F[2,67]=4.3, P<0.05) among the three groups. The prevalence and severity of asymptomatic cerebrovascular damage were significantly greater in the PPH-2 group.
To further clarify the relationship between PPH and asymptomatic brain damage, mean postprandial change in SBP was evaluated according to the number of lacunae and the grade of leukoaraiosis (Figure 2⇓). There was a severity-dependent augmentation of mean PPH according to the severity of both lacunae and leukoaraiosis.
The circadian alteration of BP has been shown to be closely related to asymptomatic cerebrovascular damage in elderly hypertensive patients. The nondipper phenomenon2 and the extreme dipper phenomenon6 have been reported to be related to asymptomatic cerebrovascular damage. Recently, Matsubayashi et al9 reported that postural dysregulation of BP was associated with asymptomatic cerebrovascular damage in elderly subjects. Elderly subjects who showed orthostatic hypotension as well as orthostatic hypertension had advanced asymptomatic brain lesions.9 They speculated that long-standing excessively altered changes in BP may impair cerebral perfusion and bring about changes, such as lacunae and leukoaraiosis, in the elderly.
In the present study, we observed a significant correlation between PPH and asymptomatic brain damage. Although PPH has been reported to be more common than orthostatic hypotension,18 a close relationship between the two conditions has also been reported.19 Since we did not evaluate orthostatic hypotension in the present study, we could not exclude the possibility that our finding was a mere reflection of the higher prevalence of orthostatic hypotension in patients with advanced PPH.
The preprandial BP level was significantly higher in the PPH-2 group for all meals than in the normal group (Table 1⇑). It is possible that the daytime BP would be higher in patients with PPH if they did not eat a meal. If the preprandial BP level was assumed as the daytime BP (ie, elimination of the effect of PPH), patients with marked PPH might have a profound decrease in nighttime BP. These findings may indicate that patients with PPH had an excessive change in BP not only after meals but also at night, and this change might contribute to the impairment of cerebral perfusion. Krajewski et al20 measured blood flow velocity of the middle cerebral artery in elderly patients with PPH by the transcranial Doppler method after a test meal. Although the meal did not change mean blood flow velocity, the pulsatility index was significantly increased after the meal, suggesting vasoconstriction of cerebral arteries after meals.20 They speculated that postprandial vasoconstriction led to cerebral ischemia. Several lines of evidence suggest that leukoaraiosis reflects the decrease in cerebral circulation. These findings, together with the finding of the present study that patients with PPH had a higher prevalence of organic brain damage, further support the impairment of cerebral circulation in patients with PPH.
The definition of PPH in the present study was rather arbitrary.14 Although we defined PPH as the difference in SBP before and after a meal,16 there is no definition of PPH when BP is evaluated by ABPM. Accordingly, we also evaluated the relationship between the degree of asymptomatic cerebrovascular damage and PPH. We observed a severity-dependent augmentation of PPH according to the severity of both lacunae and leukoaraiosis.
BP assessment by ABPM provides more useful information than assessment of 24-hour mean BP. ABPM can also assess diurnal change of BP, including the dipper and nondipper phenomena, white coat hypertension, and BP variability. Recently, Aronow and Ahn17 reported the prognosis of elderly patients with PPH in their prospective study. They found that PPH was an independent risk factor for future mortality, coronary events, and stroke. The present study further suggests the usefulness of evaluating PPH by ABPM, since PPH could also indicate the presence of asymptomatic cerebrovascular damage in addition to the prognosis of future cardiovascular events.
In summary, we showed that PPH was significantly related to asymptomatic cerebrovascular damage in essential hypertension in the elderly, even in the absence of abnormal neurological findings. It may be worthwhile to evaluate postprandial change in BP measured by ABPM for further information about asymptomatic brain damage in elderly hypertensive patients.
- Received September 16, 1998.
- Revision received October 22, 1998.
- Accepted November 2, 1998.
Kohara K, Nishida W, Maguchi M, Hiwada K. Autonomic nervous function in non-dipper essential hypertensive subjects: evaluation by power spectral analysis of heart rate variability. Hypertension. 1995;26:808–814.
Kario K, Matsuo T, Kobayashi H, Imiya M, Matsuo M, Shimada K. Nocturnal fall of blood pressure and silent cerebrovascular damage in elderly hypertensive patients: advanced silent cerebrovascular damage in extreme dippers. Hypertension. 1996;27:130–135.
Watanabe N, Imai Y, Nagai K, Tsuji I, Satoh H, Sakuma M, Sakuma H, Kato J, Onodera-Kikuchi N, Yamada M, Abe F, Hisamichi S, Abe K. Nocturnal blood pressure and silent cerebrovascular lesions in elderly Japanese. Stroke. 1996;27:1319–1327.
Kohara K, Igase M, Yinong J, Fukuoka T, Maguchi M, Okura T, Kitami Y, Hiwada K. Asymptomatic cerebrovascular damages in essential hypertension in the elderly. Am J Hypertens. 1997;10:829–835.
Matsubayashi K, Okumiya K, Wada T, Osaki Y, Fujisawa M, Doi Y, Ozawa T. Postural dysregulation in systolic blood pressure is associated with worsened scoring on neurobehavioral function tests and leukoaraiosis in the older elderly living in a community. Stroke. 1997;28:2169–2173.
Fujikawa T, Yamawaki S, Touhouda Y. Incidence of silent cerebral infarction in patients with major depression. Stroke. 1993;24:1631–1634.
Kobayashi S, Okada K, Koide H, Bokura H, Yamaguchi S. Incidence of silent lacunar lesion in normal adults and its relation to cerebral blood flow and risk factors. Stroke. 1991;22:1379–1383.
Pantoni L, Garcia JH. Pathogenesis of leukoaraiosis: a review. Stroke. 1997;28:652–659.
Kobayashi S, Okada K, Koide H, Bokura H, Yamaguchi S. Subcortical silent brain infarction as a risk factor for clinical stroke. Stroke. 1997;28:1932–1939.