Background-We previously hypothesized that high activity of creatine kinase, the central regulatory enzyme of energy metabolism, facilitates the development of high blood pressure. Creatine kinase rapidly provides adenosine triphosphate to highly energy-demanding processes, including cardiovascular contraction, and antagonizes nitric oxide-mediated functions. Relatively high activity of the enzyme, particularly in resistance arteries, is thought to enhance pressor responses and increase blood pressure. Tissue creatine kinase activity is reported to be high in black people, a population subgroup with greater hypertension risk; the proposed effects of high creatine kinase activity, however, are not "race dependent." We therefore assessed whether creatine kinase is associated with blood pressure in a multiethnic population. Methods and Results-We analyzed a stratified random sample of the population of Amsterdam, the Netherlands, consisting of 1444 citizens (503 white European, 292 South Asian, 580 black, and 69 of other ethnicity) aged 34 to 60 years. We used linear regression analysis to investigate the association between blood pressure and normal serum creatine kinase after rest, as a substitute measure of tissue activity. Creatine kinase was independently associated with blood pressure, with an increase in systolic and diastolic pressure, respectively, of 8.0 (95% CI, 3.3 to 12.7) and 4.7 (95% CI, 1.9 to 7.5) mm Hg per log creatine kinase increase after adjustment for age, sex, body mass index, and ethnicity. Conclusions-Creatine kinase is associated with blood pressure. Further studies are needed to explore the nature of this association, including how variation in cardiovascular creatine kinase activity may affect pressor responses.

Abstract-Patients with essential hypertension have disturbed autonomic cardiovascular regulation and circadian pacemaker function. Recently, the biological clock was shown to be involved in autonomic cardiovascular regulation. Our objective was to determine whether enhancement of the functioning of the biological clock by repeated nighttime melatonin intake might reduce ambulatory blood pressure in patients with essential hypertension. We conducted a randomized, double-blind, placebo-controlled, crossover trial in 16 men with untreated essential hypertension to investigate the influence of acute (single) and repeated (daily for 3 weeks) oral melatonin (2.5 mg) intake 1 hour before sleep on 24-hour ambulatory blood pressure and actigraphic estimates of sleep quality. Repeated melatonin intake reduced systolic and diastolic blood pressure during sleep by 6 and 4 mm Hg, respectively. The treatment did not affect heart rate. The day-night amplitudes of the rhythms in systolic and diastolic blood pressures were increased by 15% and 25%, respectively. A single dose of melatonin had no effect on blood pressure. Repeated (but not acute) melatonin also improved sleep. Improvements in blood pressure and sleep were statistically unrelated. In patients with essential hypertension, repeated bedtime melatonin intake significantly reduced nocturnal blood pressure. Future studies in larger patient group should be performed to define the characteristics of the patients who would benefit most from melatonin intake. The present study suggests that support of circadian pacemaker function may provide a new strategy in the treatment of essential hypertension. Key Words: blood pressure monitoring Ⅲ circadian rhythm Ⅲ hormones Ⅲ human Ⅲ hypertension T he endogenous circadian pacemaker, located in the suprachiasmatic nucleus (SCN), imposes 24-hour biological rhythms by endocrine and autonomic mechanisms. 1 For example, the circadian rhythm in adrenal cortex activity is regulated via an endocrine and a sympathetic route, 2,3 that of heart and liver via sympathetic and parasympathetic control, 4 -6 and of the pineal gland via the sympathetic nervous system. 7 Thus, the SCN promotes adaptation to the rest and activity periods by regulating, for example, the morning increase in cortisol, heart rate, and glucose, and the evening increase in melatonin.Evidence for disturbed circadian pacemaker function in essential hypertension is accumulating. Patients with hypertension show blunted day-night rhythms in sympathetic and parasympathetic heart tone. 8,9 Patients with coronary heart disease, a major complication of chronic hypertension, show a blunted day-night rhythm in vasodilatation 10 and suppressed nighttime melatonin levels. 11 We demonstrated recently that in comparison with normotensive subjects, the levels of three important SCNneurotransmitters are reduced by more than 50% in patients with essential hypertension, 12 corroborating its functional impairment. Furthermore, we provided anatomical support for a changed SCN output to the symp...

In conclusion, our study shows that the lifetime cumulative incidence of syncope in the general population is high. Females experience syncope more often than males. The majority of the syncope triggers were related to conditions that affect orthostatic blood pressure regulation and vasomotor responses.