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

Overexpression of a truncated Kv1.1 channel transgene in the heart (Kv1DN) resulted in mice with a prolonged action potential duration due to marked attenuation of a rapidly activating, slowly inactivating potassium current (I(K,slow1)) in ventricular myocytes. Optical mapping and programmed electrical stimulation revealed inducible ventricular tachycardia due to spatial dispersion of repolarization and refractoriness. Here we show that a delayed rectifier with slower inactivation kinetics (I(K,slow2)) was selectively upregulated in Kv1DN cardiocytes. This electrical remodeling was spatially restricted to myocytes derived from the apex of the left ventricle. Biophysical and pharmacological studies of I(K,slow2) indicate that it resembles Kv2-encoded currents. Northern blot analyses and real-time PCR revealed upregulation of Kv2.1 transcript in Kv1DN mice. Crossbreeding of Kv1DN mice with mice expressing a truncated Kv2.1 polypeptide (Kv2DN) eliminated I(K,slow2). In summary, our data indicate that the spatially restrictive upregulation of Kv2.1-encoded currents underlies the increased dispersion of the repolarization observed in Kv1DN mice.