The Effect of Creatine Kinase Inhibition on Contractile Properties of Human Resistance Arteries

Creatine kinase (CK) is a main predictor of blood pressure, and this is thought to largely depend on high resistance artery contractility. We previously reported an association between vascular contractility and CK in normotensive pregnancy, but pregnancy is a strong CK inducer, and data on human hypertension are lacking. Therefore, we further explored CK-dependency of vascular contractility outside the context of pregnancy in normotensive and hypertensive women. Nineteen consecutive women, mean age 42 years (SE 1.3), mean systolic/diastolic blood pressure respectively 142.6 (SE 5.9)/85.6 (3.4) mm Hg (9 hypertensive), donated an omental fat sample during abdominal surgery. We compared vasodilation after the specific CK inhibitor 2,4-dinitro-1-fluorobenzene (DNFB; 10(-6) mol/l) to sodium nitroprusside (10(-6) mol/l) in isolated resistance arteries using a wire myograph. Additionally, we assessed predictors of vasoconstrictive force. DNFB reduced vascular contractility to 24.3% (SE 4.4), P < 0.001, compared to baseline. Sodium nitroprusside reduced contractility to 89.8% (SE 2.3). Maximum contractile force correlated with DNFB effect as a measure of CK (r = 0.8), and with vessel diameter (r = 0.7). The increase in contractile force was 16.5 mN [9.1-23.9] per unit DNFB effect in univariable and 10.35 mN [2.10-18.60] in multivariable regression analysis. This study extends on our previous findings in pregnant normotensive women of CK-dependent microvascular contractility, indicating that CK contributes significantly to resistance artery contractility across human normotension and primary hypertension outside the context of pregnancy. Further studies should explore the effect of CK inhibitors on clinical blood pressur

Creatine kinase as a marker of obesity in a multi-ethnic population

Creatine kinase (CK), the central regulatory enzyme of energy metabolism, is particularly high in type II skeletal muscle fibers, which are associated with insulin resistance and obesity. As resting plasma CK is mainly derived from skeletal muscle, we assessed whether plasma CK is associated with markers of obesity. In this cross-sectional study, we analyzed a random sample of the multi-ethnic population of Amsterdam, the Netherlands, consisting of 1444 subjects aged 34-60 years. The primary outcome was the independent association between plasma CK after rest and waist circumference. Other outcomes included waist-to-hip ratio and body mass index. Mean waist circumference increased from the first through the third CK tertile, respectively 90.3 (SD 13.4), 93.2 (SD 14.3), and 94.4 (SD 13.3) cm (p < 0.001 for differences between tertiles). The increase in waist circumference was 8.91 (95% CI 5.35 to 12.47) cm per log CK increase after adjustment for age, sex, African ethnicity, educational level, physical activity and plasma creatinine. Similarly, CK was independently associated with waist-to-hip ratio and body mass index, with an increase of respectively 0.05 (95% CI 0.03 to 0.07) and 3.6 (95% CI 2.3 to 5.0) kg/m(2) per log CK increase. Plasma CK is independently associated with measures of obesity in a multi-ethnic population. This is in line with the central role of type II skeletal muscle fibers in energy metabolism and obesity. Prospective studies should assess whether resting plasma CK could be an easy accessible marker of CK rich type II fiber predominance that helps identify individuals at risk for obesit

Resistance artery creatine kinase mRNA and blood pressure in humans

Hypertension remains the main risk factor for cardiovascular death. Environmental and biological factors are known to contribute to the condition, and circulating creatine kinase was reported to be the main predictor of blood pressure in the general population. This was proposed to be because of high resistance artery creatine kinase-BB rapidly regenerating ATP for vascular contractility. Therefore, we assessed whether creatine kinase isoenzyme mRNA levels in human resistance arteries are associated with blood pressure. We isolated resistance-sized arteries from omental fat donated by consecutive women undergoing uterine fibroid surgery. Blood pressure was measured in the sitting position. Vessels of 13 women were included, 6 normotensive and 7 hypertensive, mean age 42.9 years (SE, 1.6) and mean systolic/diastolic blood pressure, 144.8 (8.0)/86.5 (4.3) mm Hg. Arteriolar creatine kinase isoenzyme mRNA was assessed using quantitative real-time polymerase chain reaction. Normalized creatine kinase B mRNA copy numbers, ranging from 5.2 to 24.4 (mean, 15.0; SE, 1.9), showed a near-perfect correlation with diastolic blood pressure (correlation coefficient, 0.9; 95% confidence interval, 0.6-1.0) and were well correlated with systolic blood pressure, with a 90% relative increase in resistance artery creatine kinase B mRNA in hypertensives compared with normotensives, normalized copy numbers were, respectively, 19.3 (SE, 2.0) versus 10.1 (SE, 2.1), P=0.0045. To our knowledge, this is the first direct evidence suggesting that resistance artery creatine kinase mRNA expression levels concur with blood pressure levels, almost doubling with hypertension. These findings add to the evidence that creatine kinase might be involved in the vasculature's pressor response

Creatine kinase and renal sodium excretion in African and European men on a high sodium diet

+-ATPase driven sodium retention throughout the kidney. Therefore, we assessed whether resting plasma CK is associated with sodium retention after a high sodium diet. Sixty healthy men (29 European and 31 African ancestry) with a mean age of 37.2 years (SE 1.2) were assigned to low sodium intake ( 200 mmol/d). Sodium excretion (mmol/24-h) after high sodium was 260.4 (28.3) in the high CK tertile versus 415.2 (26.3) mmol/24-h in the low CK tertile (P < .001), with a decrease in urinary sodium excretion of 98.4 mmol/24-h for each increase in log CK, adjusted for age and African ancestry. These preliminary results are in line with the energy buffering function of the CK system, but more direct assessments of kidney CK will be needed to further establish whether this enzyme enhances sodium sensitivit

Exploring cardiovascular health: the Healthy Life in Suriname (HELISUR) study. A protocol of a cross-sectional study

Obesity, hypertension and diabetes are on a dramatic rise in low-income and middle-income countries, and this foretells an overwhelming increase in chronic disease burden from cardiovascular disease. Therefore, rapid action should be taken through preventive population-based programmes. However, in these regions, data on the population distribution of cardiovascular risk factors, and of intermediate and final end points for cardiovascular disease are scarce. The Healthy Life in Suriname (HELISUR) study is a cardiovascular population study in Suriname, which is part of the Caribbean Community. The HELISUR study is dedicated to provide data on risk factors and prevalent cardiovascular disease in the multiethnic population, which is mainly of African and Asian descent. In a cross-sectional, observational population-based setting, a random representative sample of 1800 citizens aged between 18 and 70 years will be selected using a cluster household sampling method. Self-reported demographic, socioeconomic and (cardiovascular) health-related data will be collected. Physical examination will include the assessment of cardiovascular risk factors and prevalent cardiovascular disease. In addition, we will study cardiovascular haemodynamics non-invasively, as a novel intermediate outcome. Finally, fasting blood and overnight urine samples will be collected to monitor cardiometabolic risk factors. The main outcome will be descriptive in reporting the prevalence of risk factors and measures of (sub) clinical end organ damage, stratified for ethnicity and sex-age groups. Ethical approval has been obtained from the State Secretary of Health. Data analysis and manuscript submission are scheduled for 2016. Findings will be disseminated in peer-reviewed journals, and at national, regional and international scientific meetings. Importantly, data will be presented to Surinamese policymakers and healthcare workers, to develop preventive strategies to combat the rapid rise of cardiovascular diseas