Background-Cardiovascular events occur most frequently in the morning hours. We prospectively studied the association between the morning blood pressure (BP) surge and stroke in elderly hypertensives. Methods and Results-We studied stroke prognosis in 519 older hypertensives in whom ambulatory BP monitoring was performed and silent cerebral infarct was assessed by brain MRI and who were followed up prospectively. The morning BP surge (MS) was calculated as follows: mean systolic BP during the 2 hours after awakening minus mean systolic BP during the 1 hour that included the lowest sleep BP. During an average duration of 41 months (range 1 to 68 months), 44 stroke events occurred. When the patients were divided into 2 groups according to MS, those in the top decile (MS group; MS Ն55 mm Hg, nϭ53) had a higher baseline prevalence of multiple infarcts (57% versus 33%, Pϭ0.001) and a higher stroke incidence (19% versus 7.3%, Pϭ0.004) during the follow-up period than the others (non-MS group; MS Ͻ55 mm Hg, nϭ466). After they were matched for age and 24-hour BP, the relative risk of the MS group versus the non-MS group remained significant (relative riskϭ2.7, Pϭ0.04). The MS was associated with stroke events independently of 24-hour BP, nocturnal BP dipping status, and baseline prevalence of silent infarct (Pϭ0.008). Conclusions-In older hypertensives, a higher morning BP surge is associated with stroke risk independently of ambulatory BP, nocturnal BP falls, and silent infarct. Reduction of the MS could thus be a new therapeutic target for preventing target organ damage and subsequent cardiovascular events in

Normotensive nondipping may not reflect renal damage, but may have a predominant effect on cardiac damage. Nondipping of nocturnal BP seems to be a determinant of cardiac hypertrophy and remodeling, and may result in a cardiovascular risk independent of ambulatory BP levels in normotensives.

Silent cerebrovascular disease is advanced in elderly hypertensives having OHT. Elderly hypertensives with OHT or OHYPO may have an elevated risk of developing hypertensive cerebrovascular disease.

Older age, beta-blocker use, and regular alcohol drinking were significant determinants of the exaggerated ME difference in medicated hypertensive patients.

on behalf of the J-RHYTHM Registry Investigators* Background--To clarify the influence of hypertension and blood pressure (BP) control on thromboembolism and major hemorrhage in patients with nonvalvular atrial fibrillation, a post hoc analysis of the J-RHYTHM Registry was performed.

Exaggerated MBPS, adjusted for physical activity, is associated with cardiac hypertrophy independent of ambulatory BP level in a community-dwelling population.

Early-morning blood pressure is generally viewed as an important therapeutic target, for two reasons. First, for antihypertensive agents taken once daily in the morning, the timing of the trough plasma drug level, and thereby the lowest pharmacodynamic effect, often coincides with the early morning rise in blood pressure and heart rate. Evidence has been accumulated to suggest that blood pressure control throughout the 24 h period may be necessary to gain complete benefit from antihypertensive medication. In fact, in a longitudinal study, the regression of cardiac hypertrophy in patients with hypertension was more accurately predicted by treatment-induced changes in average 24 h ambulatory blood pressure than by clinic or home-monitored blood pressure readings. The other reason for the importance of morning blood pressure is that cardiovascular risk is heightened at this time of day. A morning surge in sympathetic activity alters haemodynamic forces and predisposes vulnerable coronary atherosclerotic plaques to rupture. At the same time as this risk of plaque rupture is greatest, circadian variations in haemostatic and fibrinolytic factors result in morning hypercoagulability and hypofibrinolysis, promoting the formation of intraluminal thrombi. We recently showed that, in older hypertensives, a greater morning blood pressure surge, mediated at least in part by an exaggerated alpha-sympathetic activity, is associated with more advanced silent cerebrovascular disease as well as a higher future incidence of stroke. The early morning surge in blood pressure could become a new therapeutic target for preventing target-organ damage and subsequent cardiovascular events in hypertension. Of greatest interest is the potential benefit of a chronotherapeutic approach, involving, for example, long-acting chronoformulations, which has not yet been extensively studied.

There are inconsistent reports that the angiotensinogen (ATG) variant Met235-->Thr (T235) allele and angiotensin-converting enzyme (ACE) insertion/deletion (I/D) variants are associated with hypertension and related target organ damage. Both high blood pressure (BP) and abnormal diurnal BP variation patterns are related to target organ damage, but it is not known whether the above genetic variants of the renin-angiotensin system are related to 24 h BP and the diurnal BP pattern in Japanese. We studied the association of the ATG T235 allele and ACE D allele with 24 h BP and diurnal BP variation in 235 of 262 consecutive untreated (or off medication) elderly Japanese hypertensives who underwent 24 h ambulatory BP monitoring. There was no significant association between the T235 or ACE D allele with office BP, but the T235 allele was significantly associated with 24 h BP and day BP, and the D allele was significantly associated with increased 24 h BP, day BP, and night BP. There were no effects of the T235 or D alleles on any BP parameters. Those with white-coat hypertension had a significantly lower T235 allele frequency (0.68) than those with sustained hypertension (0.79, p=0.010), but the difference in D allele frequency was marginal (0.30 vs. 0.38, p=0.057). In conclusion, in elderly Japanese hypertensive individuals, both the ATG T 235 and ACE D alleles are associated with increased 24 h BP and day BP, while only the ACE D allele is associated with increased night BP.