Morning Hypertension

I recently began measuring my blood pressure (BP) at home as part of a study of a new type of home monitor, which is programmed to take 3 readings automatically at each session and enables the patient to store morning and evening BPs separately, as is now being recommended by recent guidelines.1 The first procedure of the study involved measuring BP in the clinic, with readings taken both with a mercury sphygmomanometer and with the device. These readings, which were taken late in the afternoon, were well within the normal range, as they had always been in the past. When I took readings at home on waking up, however, they ranged between 150 and 160 mm Hg systolic and remained elevated (above 135/85 mm Hg) on repeated hourly measurements throughout the morning and early afternoon. By about 4 PM, they became lower and remained close to normal for the rest of the evening (Figure). This pattern was reproducible on subsequent days, indicating a diagnosis of morning hypertension. This is a term that is not yet in general use, but it has been popularized by my colleague Dr Kario in Japan,2 on the grounds that the BP measured in the first 2 hours after waking may have special pathologic significance and hence may be a therapeutic target. It clearly has major implications for the use of home BP monitoring. The proposed definition of morning hypertension is an elevation of BP (ie, above 135/85 mm Hg) during the first 2 hours after waking, but not in the evening (the last 2 hours before going to bed). The diurnal rhythm of BP has been recognized for many years, and most studies have shown that the morning pressure tends to be higher than the pressure measured in the evening. The changes over 24 hours appear to be rather closely related to the cycle of wakefulness and activity. When these are maintained at a constant level, as in an experiment in which subjects were kept on bed rest for 24 hours with constant lighting and hourly feeding, there is no detectable diurnal BP rhythm. On the other hand, a dip in the heart rate still occurs during the nighttime, indicating that the heart rate rhythm is more closely controlled by the biologic clock.3 The diurnal BP rhythm is closely paralleled by the incidence of most types of cardiovascular events, which peak during the hours between 6 AM and noon.4, 5 Whether or not the morning or evening BP is higher may depend on where the study was done: at least 4 Japanese studies have reported that evening BP tends to be lower (by 3–10 mm Hg),6-9 whereas 3 Western studies found the opposite.10-12 An example of this is a study of individuals with untreated hypertension,13 in which the average home BP was 147/86 mm Hg at 8 am and 152/86 mm Hg at 10 pm. At least 2 reasons have been suggested to explain these differences: first, Japanese often bathe in the evening, which may lower the BP for at least 1 hour.14 Second, the participants in the Western studies tended to take the BP reading before the evening meal (6–10 pm), whereas in the Japanese studies they usually recorded the BP just before going to bed. In the general population, the differences between morning and evening BPs are usually small, but a number of factors appear to accentuate these differences. The Japanese studies have reported that the differences may be more pronounced in patients with hypertension and in men rather than women.6 Patients who drink alcohol regularly are also more likely to have a relative elevation of the morning BP,15 possibly because alcohol raises the morning pressure and lowers the evening pressure.16 One report found that in men with sleep apnea, a relationship existed between the severity of the sleep apnea (as measured by the apnea-hypopnea index or AHI) and the difference between the morning and evening pressure.17 In patients taking antihypertensive drugs, the selective elevation of the morning pressure is often more pronounced.18 In the Ohasama study,18 subjects had 24-hour BP recordings as well as home monitoring, and the high morning BP was defined as a difference of more than 10 mm Hg between the morning BP and the average for the whole day. Subjects who had morning hypertension by this definition were most likely to be patients with treated hypertension (the study also included many subjects who were normotensive), males, and elderly, and to show a nondipping pattern on the 24-hour recording. The morning hours are a time of generalized sympathetic arousal. Marfella et al19 found that patients with a pronounced morning peak of BP also showed an enhanced morning peak of urine catecholamines. In this study, the researchers also monitored the electrocardiogram over 24 hours and found that the rate-corrected QT interval (QTc) increased in the morning hours and a greater degree of QTc dispersion occurred. Both of these changes have been related to ventricular arrhythmias and sudden cardiac death in patients with hypertension.20 The morning low-frequency/high-frequency ratio of heart rate was higher in the morning peak group, which would be consistent with increased sympathetic activity. Research has found some evidence that the morning pressure is of greater prognostic significance than the evening pressure, which might be expected because the morning is the time when the incidence of cardiovascular events is at its peak. There are 2 ways of examining this question. The first is to see if the. morning pressure is more closely related to target organ damage; the second is to see whether morning pressure predicts cardiovascular outcomes better than other measures. Several studies have looked at target organ damage. Jula et al21 compared multiple office and home BPs and ambulatory BPs in the clinical evaluation of hypertension using a sample of 239 adults with untreated hypertension. The researchers found that office and home BPs, when averaged over 4 carefully controlled duplicate measurements, predicted albuminuria and left ventricular hypertrophy at least equally to ambulatory BP monitoring. Left ventricular mass index correlated slightly more strongly with morning home systolic and diastolic BPs than evening systolic and diastolic BPs (r=0.46/.43; P<.001 and r=0.41/.37; P<.001, respectively). A study by Marfella et al19 found that patients with hypertension who had a morning BP peak (defined as an increase of at least 50/22 mm Hg in the first 2 hours after waking compared with the average nighttime level) had a greater carotid intima-media thickness (IMT) despite similar daytime and nighttime average BPs. The third study used a sample of 113 patients with hypertension and nondiabetic chronic kidney disease, who were followed for 3 years, and found that home BP measured in the morning was a better predictor of the decline in glomerular filtration rate than evening BP (r=0.64 vs 0.56).23 In this study, the morning BP was about 10 mm Hg higher than the evening pressure. It has been reported that in patients with diabetes, home BP, particularly when measured in the morning, correlates better with target organ damage than office BP24; however, evening BP was not measured in this study. So far, only the Ohasama study18 has looked at the separate prediction of risk of the morning vs the evening BP. The original reports were based on readings taken in the morning; a later analysis that included evening readings found that both measures predicted strokes equally well in the general population, but morning readings were superior in patients taking antihypertensive medications.25 The Ohasama study, which also included ambulatory BP monitoring, has reported that the average BP during the first 2 hours after waking is an independent predictor of risk.26 These findings emphasize the importance of taking BP readings first thing in the morning. An important distinction is between the morning surge, which has received quite a lot of attention, and morning hypertension, which is a newer concept. This distinction is of both theoretical and practical interest. On the theoretical side, uncertainty exists as to the extent to which the phasic components of BP (such as the morning surge) as opposed to the level of BP (the tonic phase) are responsible for triggering cardiovascular events. On the practical side, measurement of the morning surge can only be done with ambulatory 24-hour monitoring, whereas morning hypertension can be assessed just with home monitoring. Patients may have morning hypertension as a result of an exaggerated morning surge, but they may also be nondippers, as shown in the Ohasama study.18 We attempted to see if the morning surge or the morning BP would give the better prediction of risk in an analysis of 519 elderly patients with hypertension followed for an average of 41 months. In the first publication,27 we defined the morning surge as the difference between the average BP in the 2 hours after waking minus the lowest BP during sleep; we found that the patients with the greatest morning surge were at the highest risk of stroke, independently of the average 24-hour level. In the second analysis,2 we focused on the morning BP (again measured as the average of the first 2 hours after waking) and the evening pressure (measured as the average of the last 2 hours before going to bed). Defined in this way, the morning pressure emerged as the strongest predictor of strokes in an analysis that included the office, average daytime, nighttime, and evening BP. When compared with the morning surge, the result was a draw—both predicted risk equally well, but not independently of the other. This is not perhaps surprising, because the same measure of morning pressure was used in both instances. In other words, the morning level was as good as the morning surge, and adding the sleep BP did not improve the prediction of risk. The importance of this, and a point worth emphasizing, is that these data can be obtained just as well with home monitoring as with ambulatory BP monitoring. If it is true that morning BP tends to be higher than at other times of day in patients with treated hypertension, and that this reading is related to increased risk, 2 important implications arise. The first relates to BP measurement. It is generally recommended that home BP should be measured both in the morning and the evening,1, 28 but of the 2 readings, the morning may be more important, because it may predict risk better. One reason for this may be that the morning readings are taken before the various activities of the day have started, which could confound the measurements, as seen with the effects of bathing on the evening readings noted in Japanese subjects. The second issue is whether antihypertensive treatment should focus on lowering the morning pressure. Clearly, we are not doing a very good job on this at the present time. A survey of 219 patients with treated hypertension who had good control according to their office BP (less than 140/90 mm Hg) found that nearly half of the patients had morning pressures that were above the threshold level of 135/85 mm Hg.29 Later in the day, the control rates were much better. One possible consequence of this failure to control the morning pressures was identified in a study of patients with chronic kidney disease who were randomized to additional treatment with guanabenz or placebo. The clinic BP showed no change, but the morning BP did decrease in the treated group; there was also regression of left ventricular hypertrophy and less rapid decline of renal function.30 The most convincing study to date showing that selectively lowering the morning BP is beneficial has been reported by Marfella et al,19 who randomized 128 patients with hypertension and a morning BP peak to treatment with either carvedilol or metoprolol. The researchers evaluated the effects of treatment not only on BP, but also on carotid IMT and inflammatory markers. The carvedilol lowered morning BP more than metoprolol and also caused greater regression of IMT. The effects of the 2 drugs on the average daytime and nighttime pressure were, however, the same. Measurement of the BP soon after getting up in the morning is now highly practical, given the widespread and increasing use of home monitors. In comparison with measurements made at other times of day (including at the physician's office), the early morning BP may be less susceptible to the confounding influences of activity and behavior, although the evidence reviewed above does suggest that drinking alcohol the night before or having sleep apnea may elevate the morning BP. The morning hours are the time of the greatest risk for cardiovascular events, and it could be argued that paradoxically, also the time when BP control is at its worst. The incorporation of routine measurement of the morning BP in patients with hypertension would appear to have a lot to offer.