Methods for Loss of Circadian Rhythm of Blood Pressure Following Acute Stroke

Hypertension is a well documented treatable single risk factor for stroke[5]. It is associated with an increased risk of all major subtypes of strokes. The reduction of blood pressure in primary prevention studies appears to reduce the relative risk of all types of stroke. The role of hypertension as a chief risk factor has been documented in Indian studies as well. The younger age of stroke in India studies has been stressed and is possibly related to a prolonged period of undetected untreated hypertension.

The development of devices capable of monitoring blood pressure noninvasively for 24 hours or more has been a major advance in blood pressure measurement. The large number of readings obtained by these devices reduces the variability and abolishes the observer bias encountered with casually recorded blood pressure[6]. Reducing variability also improves the precision with which blood pressure reduction can be quantified. ABPM devices have been used to assess the BP changes after stroke. Lip et al [6]studied the blood pressure variability in patients with acute stroke with oscillometric method and found that the readings comparable to those obtained with stethoscope and mercury manometer. ABPM increases the precision of recordings and minimize error compared to manual measurement. Many studies from western countries [3,4] are available on the use of ambulatory blood pressure monitoring devices in patients with acute stroke. However, to the best of our knowledge, this is the first study on the use of ABPM in stroke from India.

In contrast to normotensive patients or patients with primary hypertension, who show a biphasic circadian BP pattern with physiological nocturnal BP decreases in excess of 10%, a pathologically reduced or abolished circadian BP variation has been described after stroke. The significant reduction of circadian blood pressure variation after thromboembolic infarction was initially reported by Sander et al[3].

This study has clearly demonstrated that nondipping in blood pressure occurs in majority of patients with stroke irrespective of the underlying nature or site of stroke. However, the interpretation of the reduced day night difference or nondipping is complicated by some factors. 20% of the hypertensive patients exhibit nondipping[6]. The phenomenon has also been described in diverse medical conditions including renal disease, diabetes with autonomic neuropathy, heart failure and Cushing's syndrome. Though it is possible that abnormal diurnal variation in blood pressure existed in some of these patients due to co-morbid medical conditions like diabetes mellitus, coronary artery disease and previous transient ischemic attacks, it was not possible to predict or identify this subgroup of patients, as this study was prospective. Moreover, the sleep patterns in any patient population are highly variable. This, apart from the appreciable arousal from sleep on cuff inflation in some patients is another inherent limitation in all studies done on ABPM device. However in our study, the difference in the incidence of nondipping and dipping was highly significant and these factors can be discounted. Yamamoto et al[7] had proposed that the reduced nocturnal blood pressure decline might be associated not only with extent and type of the stroke but also with the specific location of intracranial lesion.

Diminished nocturnal blood pressure decline would be caused by an injury to the central autoimmune nervous system that reduces sympathetic activity during the night and increases parasympathetic activity. However we could not find any association with the site of stroke and status of dipping. None of the risk factors, clinical or laboratory variables or blood pressure changes differed significantly between the two subgroups of dippers and non-dippers. However, a reduction in diurnal change with thromboembolic infarction and the presence of a reversed dip in subjects with involvement of insular cortex has been reported[3]. Lip et al[6] have observed highest daytime blood pressure by ABPM and a trend toward higher nocturnal blood pressure in patients with intracranial hemorrhage. It has been reported that patients with involvement of insular cortex show a nocturnal rise of blood pressure more frequently and had higher norepinephrine levels than patients without insular cortex infarction, indicating increased sympathetic activity in these patients. The lack of fall of blood pressure in acute phase may by due to an increased secretion of epinephrine and cortisol in the acute phase of stroke. We could not find such an association, as nondipping was present equally in both the subgroups, though the incidence was higher in patients with intracranial hemorrhage than those with infarct.

In this study, admission BP was higher in patients with a previous history of hypertension. Britton et al[8] have shown that a history of hypertension was common amongst patients of stroke than controls (46% vs 26%). Wallace et al[9] showed that the majority of stroke patients were hypertensive during the first 24 hours. Half of them had a history of hypertension or were on antihyhpertensive therapy. Patients with acute stroke often have high blood pressure levels at the time of hospital admission, but it declines soon afterwards. The reasons for this high blood pressure are not exactly known. Many investigators have found elevated levels of plasma catecholamines in acute phase of stroke, which may be secondary to the brain lesion[10]. Various factors responsible for an elevated blood pressure include a decreased perfusion in ischemic border zone, stress reaction to hospital admission, technique of blood pressure measurement, Cushing's reflex or white coat effect [11,12]. Morfis et al [4] showed that the transient elevation in blood pressure at admission did not appear to be due to stress of hospitalization since it was not present in patients admitted to hospital in a range of medical conditions other than stroke.

In our study, the average admission SBP was 166 ± 32 mm Hg and admission DBP was 98 ± 20 mm Hg. These values were higher in patients with intracranial hemorrhage than those with infarcts (p < 0.01). These findings are consistent with other studies. Admission SBP, in our study had shown a positive correlation with the age of the patient. Carlberg et al[13] also found a correlation of age with SBP, but not DBP at admission only in patients with hemorrhage. In our study the admission SBP or DBP was not influenced by previous history of coronary artery disease, smoking, diabetes mellitus, transient ischemic attack or level of consciousness at admission. Admission SBP and DBP showed a negative correlation to the time after the onset of stroke to the admission. The inclusion criterion in the present study was that the time period between the onset of stroke to the monitoring should be less than 120 hours. However, the mean time interval of application of ABPM after the stroke was only 35 ± 18 hrs (range 2–90 hrs). This was not statistically significant between dippers versus non-dippers thereby suggesting that the status of dipping was not related to the time of admission within this time interval. Rather a long time interval from the onset of stroke to the enrolment in the present study was planned at the time of the design of the study due to long and a delay in the transport of the patients from the remote areas to our tertiary care center.

In studies of patients with stroke, abnormal pattern of circadian rhythm of blood pressure using ambulatory blood pressure monitoring (ABPM) has been reported [3,7]. In a study, Dawson et al[14] found a significant reduction in diurnal variation in systolic blood pressure in cortical infarct and intracerebral hemorrhage subgroups, compared with control subjects. The subcortical infarct subgroup demonstrated only minimal reduction in normal circadian variation. Fujishima et al[10] reported that blood pressure was elevated in the acute phase of a single lacunar infarction and it declined with time. No night time fall was noted in acute phase, but the circadian variation in blood pressure normalized in the subacute and chronic phase. Some studies done by ambulatory blood pressure monitoring in acute phase of stroke suggested that cerebrovascular diseases also cause a prognostically unfavorable suppression of heart rate variability[15]. Both the sympathetically and parasympathetically mediated components of heart rate variability are diminished as a consequence of acute stroke.

However, in view of suggested poor prognosis of nondippers and a significant incidence of nondipping and reverse dipping in our patients, it is proposed that patients with acute stroke require close monitoring of blood pressure especially at night.

Competing interests

None declared.

Authors' contributions