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Acute effects of cinacalcet on arterial stiffness and ventricular function in hemodialysis patients: A randomized double-blinded crossover study.

ABSTRACT: BACKGROUND:Serum calcium concentration (Ca) plays an essential role in a vascular muscle tone and myocardial contractility. Previously, we showed that acutely lowering Ca by hemodialysis reduced arterial stiffness. Cinacalcet is a calcimimetic that lowers Ca and parathyroid hormone (PTH). The aim of the present study was to examine whether acute lowering of Ca by cinacalcet improves vascular stiffness and myocardial diastolic dysfunction. METHOD:This is a double-blinded randomized placebo-controlled crossover study that included 21 adult patients with end-stage kidney disease undergoing chronic hemodialysis. Subjects were assigned to placebo-cinacalcet (30?mg) or cinacalcet-placebo sequence. After each treatment period (7 days), aortic, brachial, and carotid stiffness were determined by examining carotid-femoral pulse wave velocity (cf-PWV), carotid-radial PWV (cr-PWV), and carotid distension. A central pulse wave profile was determined by radial artery tonometry and cardiac function was evaluated by echocardiography. RESULTS:Cinacalcet reduced PTH (483 [337-748] to 201 [71-498] ng/L, P?

SUBMITTER: Poulin A

PROVIDER: S-EPMC5457860 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Acute effects of cinacalcet on arterial stiffness and ventricular function in hemodialysis patients: A randomized double-blinded crossover study.

Poulin Aurélie A Bellemare Pierre-Luc PL Fortier Catherine C Mac-Way Fabrice F Desmeules Simon S Marquis Karine K Gaudreault Valérie V Lebel Marcel M Agharazii Mohsen M

Medicine 20170501 21

<h4>Background</h4>Serum calcium concentration (Ca) plays an essential role in a vascular muscle tone and myocardial contractility. Previously, we showed that acutely lowering Ca by hemodialysis reduced arterial stiffness. Cinacalcet is a calcimimetic that lowers Ca and parathyroid hormone (PTH). The aim of the present study was to examine whether acute lowering of Ca by cinacalcet improves vascular stiffness and myocardial diastolic dysfunction.<h4>Method</h4>This is a double-blinded randomized ...[more]

PMID: 28538380

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Project description:ObjectivesThis study sought to assess sex differences in ventricular-arterial interactions.BackgroundHeart failure with preserved ejection fraction is more prevalent in women than in men, but the basis for this difference remains unclear.MethodsEchocardiography and arterial tonometry were performed to quantify arterial and ventricular stiffening and interaction in 461 participants without heart failure (189 men, age 67 ± 9 years; 272 women, age 65 ± 10 years). Aortic characteristic impedance (Z(c)), total arterial compliance (pulsatile load), and systemic vascular resistance index (steady load) were compared between men and women, and sex-specific multivariable regression analyses were performed to assess associations of these arterial parameters with diastolic dysfunction and ventricular-arterial coupling (effective arterial elastance/left ventricular end-systolic elastance [Ea/Ees]) after adjustment for potential confounders.ResultsZ(c) was higher and total arterial compliance was lower in women, whereas systemic vascular resistance index was similar between sexes. In women but not men, higher log Z(c) was associated with mitral inflow E/A ratio (β ± SE: -0.17 ± 0.07), diastolic dysfunction (odds ratio: 7.8; 95% confidence interval: 2.0 to 30.2) and Ea/Ees (β ± SE: 0.13 ± 0.04) (p ≤ 0.01 for all). Similarly, total arterial compliance was associated with E/A ratio (β ± SE: 0.12 ± 0.04), diastolic dysfunction (odds ratio: 0.33; 95% confidence interval: 0.12 to 0.89), and Ea/Ees (β ± SE: -0.09 ± 0.03) in women only (p ≤ 0.03 for all). Systemic vascular resistance index was not associated with diastolic dysfunction or Ea/Ees.ConclusionsProximal aortic stiffness (Z(c)) is greater in women than men, and women may be more susceptible to the deleterious effects of greater pulsatile and early arterial load on diastolic function and ventricular-arterial interaction. This may contribute to the greater risk of heart failure with preserved ejection fraction in women.

Project description:BackgroundThe role of spironolactone treatment in hemodialysis patients is debated, but a survival benefit is suggested. Mineralocorticoids and chronic kidney disease have been linked to cardiovascular fibrosis. Therefore, we hypothesized that spironolactone would affect vascular stiffness, cardiac systolic, and diastolic function in hemodialysis patients.MethodsThis was a randomized crossover study in hemodialysis patients supplemented with an echocardiographic case series. All outcomes reported here were secondary in the trial and were assessed without blinding. Block randomization and allocation determined treatment order. Participants received 50 mg spironolactone daily for 12 weeks and untreated observation for another 12 weeks. Pulse wave velocity (PWV) was measured before and after treatment and observation. Doppler-echocardiography was conducted before and after treatment. Systemic arterial compliance indexed to body surface area (SACi), left ventricular ejection fraction (LVEF), the peak early diastolic mitral inflow velocity (E), the peak late diastolic mitral inflow velocity (A), and the peak early diastolic myocardial lengthening velocity (E') were measured. E/A and E/E' were then calculated. Statistical analyses were conducted per protocol. A generalized linear mixed model with random participant effects was used for PWV. The Wilcoxon signed-rank test was used for echocardiographic variables.ResultsThirty participants were recruited, 18 completed follow-up, and 17 were included in PWV-analyses. Spironolactone treatment showed a tendency toward an increase in PWV of 1.34 (95% confidence interval: -0.11 to 2.78) m/s, which was not statistically significant (P = 0.07). There were no significant changes in any of the other variables (LVEF, E/A, E/E', or SACi).ConclusionsWe found no evidence supporting an effect of 12-week administration of spironolactone 50 mg daily on vascular stiffness, cardiac systolic, or diastolic function in hemodialysis patients.

Dataset Information

Acute effects of cinacalcet on arterial stiffness and ventricular function in hemodialysis patients: A randomized double-blinded crossover study.

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Acute effects of cinacalcet on arterial stiffness and ventricular function in hemodialysis patients: A randomized double-blinded crossover study.

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