Creatine Kinase Activity Is Associated With Blood Pressure

Abstract

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.

Resistance Artery Creatine Kinase mRNA and Blood Pressure in Humans

“…We had shown previously that circulating CK is the main predictor of blood pressure in a random sample of a multiethnic population, with an adjusted blood pressure increase of 7.98 [3.27-12.68] SBP and 4.69 [1.88-7.50] mm Hg DBP per log CK increase 6 ; this was replicated in case control and independent population studies. 17,18 Furthermore, we reported that human isolated resistance artery contractility depends on CK and that specific CK inhibitors greatly attenuate human vascular contractility in vitro.…”

“…CK is thus thought to fuel highly energy-demanding processes, such as sodium retention, cardiovascular contractility, and remodeling of arteries. [5][6][7][8][9][10] In accord with this, serum CK was found to be the main predictor of blood pressure in the general population. 6 This was proposed to be because of high tissue CK, primarily the resistance artery CK-BB isoenzyme rapidly regenerating ATP for vascular contractility.…”

“…In particular, high CKB activity in resistance arteries was thought to lead to greater vascular contractility and higher blood pressures. 6 Now, we have provided the first direct evidence that resistance artery CK mRNA expression is strongly associated with blood pressure, with a 90% relative increase in CK mRNA in hypertension.…”

“…6 This was proposed to be because of high tissue CK, primarily the resistance artery CK-BB isoenzyme rapidly regenerating ATP for vascular contractility. 6 However, hitherto, there were no data to substantiate this proposal. The main objective of this study was to assess whether resistance artery CK mRNA levels are associated with blood pressure.…”

“…[1][2][3][4] We proposed that creatine kinase (CK), the central regulatory enzyme of energy metabolism, is the final common pathway leading to pressor responses. 5,6 The enzyme regenerates and distributes ATP to subcellular locations of energy demands, catalyzing the reaction: MgADP+Pcreatine+H + ↔MgATP+creatine.…”