Time for focus on morning hypertension: Pitfall of current antihypertensive medication

It is well-known that cardiovascular events occur more frequently in the morning.1 The ambulatory blood pressure (BP) level also increases during the period from night to early morning, and changes with various psychologic and physical stress conditions.2–4 Moreover, in the early morning, other cardiovascular risks such as thrombophilic tendencies and endothelial dysfunction are potentiated. Thus, the effect of high BP on cardiovascular risk is greater in the morning than during the other periods of the day. Theoretically, there are two types of morning hypertension (Fig. 1). The nondipper/riser (nocturnal hypertension) type, with persistent high BP from night-time to morning, is well-known to be associated with risk for damage to all target organs (brain, heart, and kidneys) and cardiovascular events.5 The other type, the morning BP surge type, is associated in part with the extreme-dipping status of nocturnal BP, which we have previously reported to be associated with stroke risk.6 Morning BP surge is one of the components of diurnal BP variation, and it could be considered to be the ambulatory BP variability during “morning” stress.7 Excessive morning BP surge seems to be an independent risk for cardiovascular disease, particularly in older hypertensives with impaired autoregulation of hypertensive target organs. There have been two relatively small prospective studies supporting the possible risk of morning BP surge. One was our Jichi Medical School ABPM Study (Wave 1) on 519 older hypertensive patients,8 in which we conducted 24-h ambulatory BP monitoring at baseline, and prospectively studied the prognosis for stroke during the follow-up period of 41 months. We defined the morning BP surge as the morning BP (the average of 2 h after arising) minus the night-time lowest BP (the average of the three BP). Because moderate morning BP surge is a physiologic phenomenon, we consider that excessive morning BP surge is a risk for cardiovascular disease. We classified the hypertensive patients studied into a morning surge group and a nonsurge group, using a cutoff value of 55 mm Hg (top 10th percentile of morning surge in systolic BP). When we identified one or more nonsurge subjects who could be matched for age and 24-h systolic BP level to one morning surge subject, and weighted the controls to simulate a balanced design, clinical stroke events occurred more frequently during the follow-up period in the morning surge group than in the nonsurge group. In this study, silent cerebral infarcts detected by brain magnetic resonance imaging were more common in the former group. In our recent study,9 multiple silent cerebral infarcts in the older hypertensives were significantly associated with α-adrenergic morning BP surge (defined by the reduction of the morning BP surge by an α-blocker). Another recent French prospective study on 507 hypertensive patients also found results similar to ours.10 They used the waking BP surge, defined as the morning systolic BP measured in a standing position minus the systolic BP before rising, and divided the hypertensive patients into quartiles of waking surge. Although there were no significant differences in the 24-h BP levels among each group, left ventricular hypertrophy assessed by echocardiography at baseline was more advanced and cardiovascular complications during the follow-up period occurred more frequently in the higher quartile groups. In the multivariate analysis, waking morning BP surge was significantly associated with cardiovascular risk independently of age and 24-h BP level. In a recent unique study in which ABPM was conducted for 7 days in a community-dwelling population, Murakami et al11 found significant variation of morning BP and daytime BP during the week, whereas there was no significant difference in the night-time BP among the days of the week. Morning BP level and morning BP surge were highest on Monday, compared to those on the other days of the week. This “Monday morning surge” may contribute to cardiovascular risk, which is highest on Monday. It is well-known that cardiovascular events occur most frequently on Monday.12 There has been no conclusive study on the association between diurnal BP variation and the onset time of cardiovascular events. However, the morning BP surge group had a higher incidence of stroke events in the morning than the nonsurge group, in our study on elderly hypertensive patients.8 In addition, there is a possibility that diurnal variation of onset time of cardiovascular events may be nonexistent in nondippers. In depressive patients, nocturnal onset of acute myocardial infarction is significantly more common,13 and diabetic patients exhibited less significant diurnal variation of onset time of acute myocardial infarction.14 Subclinical depression, a newly recognized cardiovascular risk factor, is associated with poor sleep quality. In our recent study, we found that depression in men is associated with a disrupted diurnal BP variation (a tendency to the nondipping pattern) that is independent of changes in physical activity.15 Once-daily antihypertensive drugs are now widely used, however, in medicated hypertensives, even those whose clinic BP is well-controlled; the morning BP level before taking medicine is frequently high.16 Therefore, morning hypertension is the blind spot in the current clinical practice for hypertension. Self-measured home BP monitoring and more specific management targeting morning hypertension17–20 will achieve a more beneficial cardiovascular outcome in hypertensive patients.