Enhanced ventricular‐arterial coupling during a 2‐year physical activity programme in patients with rheumatoid arthritis: a prospective substudy of the physical activity in rheumatoid arthritis 2010 trial

Sarajlic, Philip; Fridén, Cecilia; Lund, Lars H.; Manouras, Aristomenis; Venkateshvaran, Ashwin; Larsson, Susanna C.; Nordgren, Birgitta; Opava, Christina H.; Lundberg, Ingrid E.; Bäck, Magnus

doi:10.1111/joim.12715

Cited by 22 publications

(30 citation statements)

References 43 publications

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“…A specific effect on calcification as opposed to other vascular changes is further supported by the lack of association of chemerin with Aix which in addition to calcification also depends on other structural changes of the vasculature, such as fibrosis and endothelial dysfunction as well as diastolic heart function . However, our finding that chemerin did not associate with arterial stiffness is in contrast to studies in nonrenal patients , suggesting a differential association between chemerin not only between CAC and Aix but possibly also between renal and nonrenal patients.…”

Section: Discussionsupporting

confidence: 58%

Chemerin inhibits vascular calcification through ChemR23 and is associated with lower coronary calcium in chronic kidney disease

Carracedo¹,

Witasp

Qureshi

et al. 2019

J Intern Med

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Background Chemerin is an adipokine that signals through the G protein‐coupled receptor ChemR23 and is associated with inflammation, glucose homeostasis, lipid metabolism and renal function, all of which strongly influence cardiovascular risk. However, elevated chemerin provides a survival advantage in patients with chronic kidney disease (CKD), but how this relates to the cardiovascular phenotype is unknown. Objectives The aim of the present study was to establish the association of chemerin with coronary calcification and to determine the effects of chemerin signalling, through ChemR23, in vascular smooth muscle cell (VSMC) calcification. Methods Plasma chemerin was measured in 113 patients with CKD and 50 healthy controls. All patients underwent computed tomography to determine coronary artery calcium (CAC) score. VSMCs were isolated from wild‐type and ChemR23 knock‐out mice and treated with chemerin. Results Multivariate analyses established creatinine, cholesterol, body mass index and tumour necrosis factor as significant confounders for circulating chemerin levels. Despite these positive associations with renal function, cardiometabolic risk factors and inflammation, chemerin was inversely associated with CAC both in an age‐ and sex‐adjusted analysis and in a multivariate analysis adjusting for the aforementioned confounders. In addition, circulating chemerin levels were associated with the calcification inhibitors matrix gla protein (MGP) and fetuin‐A. Finally, chemerin significantly reduced phosphate‐induced calcification and increased MGP expression in VSMCs, whereas chemerin was devoid of these effects in VSMCs lacking ChemR23. Conclusion In conclusion, these results suggest that chemerin signalling through ChemR23 in VSMCs protects against vascular calcification in CKD.

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Section: Discussionsupporting

confidence: 58%

Chemerin inhibits vascular calcification through ChemR23 and is associated with lower coronary calcium in chronic kidney disease

Carracedo¹,

Witasp

Qureshi

et al. 2019

J Intern Med

Self Cite

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“…Moreover, anti‐tumour necrosis factor‐α therapy resulted in reduced PWV after a 3‐month follow‐up period in patients with inflammatory arthropathy . Additionally, the Physical Activity in RA (PARA) trial has shown that moderate intensity physical activity resulted in increased E/A and a trend towards decreased PWV and augmentation index, suggesting the reversal of ventricular–arterial decoupling. Finally, in psoriatic patients, novel biological agents reduced arterial stiffness, central aortic pressure and wave reflections, and improved LV longitudinal deformation and LV twisting‐untwisting within 4 months, through inflammatory and oxidative stress burden reduction …”

Section: Ventricular–arterial Coupling In Systemic Inflammatory Diseasementioning

confidence: 99%

The role of ventricular–arterial coupling in cardiac disease and heart failure: assessment, clinical implications and therapeutic interventions. A consensus document of the European Society of Cardiology Working Group on Aorta & Peripheral Vascular Diseases, European Association of Cardiovascular Imaging, and Heart Failure Association

Ikonomidis

Aboyans

Blacher³

et al. 2019

European J of Heart Fail

238

243

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Ventricular–arterial coupling (VAC) plays a major role in the physiology of cardiac and aortic mechanics, as well as in the pathophysiology of cardiac disease. VAC assessment possesses independent diagnostic and prognostic value and may be used to refine riskstratification and monitor therapeutic interventions. Traditionally, VAC is assessed by the non‐invasive measurement of the ratio of arterial (Ea) to ventricular end‐systolic elastance (Ees). With disease progression, both Ea and Ees may become abnormal and the Ea/Ees ratio may approximate its normal values. Therefore, the measurement of each component of this ratio or of novel more sensitive markers of myocardial (e.g. global longitudinal strain) and arterial function (e.g. pulse wave velocity) may better characterize VAC. In valvular heart disease, systemic arterial compliance and valvulo–arterial impedance have an established diagnostic and prognostic value and may monitor the effects of valve replacement on vascular and cardiac function. Treatment guided to improve VAC through improvement of both or each one of its components may delay incidence of heart failure and possibly improve prognosis in heart failure. In this consensus document, we describe the pathophysiology, the methods of assessment as well as the clinical implications of VAC in cardiac diseases and heart failure. Finally, we focus on interventions that may improve VAC and thus modify prognosis.

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“…A two-year program of Physical Activity in RA (PARA) 2010 was designed to investigate its feasibility and to study changes in self-reported variables, physical capacity measurements, in ammation, pain modulation and cardiovascular risk 11 . Positive changes during the two-year study period were observed for HEPA participants concerning symptoms and physical capacity [12][13] and cardiovascular risk factors [14][15] , while pain modulation did not change 16 . In this context we performed a pilot study with focus on protein adaptations in muscle tissue in a subgroup of people with RA who consented to repeated muscle biopsies.…”

Section: Introductionmentioning

confidence: 90%

Effects of a two-year health-enhancing physical activity program on skeletal muscle protein profiles in people with rheumatoid arthritis

Ossipova

Idborg

Fridén

et al. 2020

Preprint

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Background Rheumatoid arthritis (RA) induces loss of muscle mass and impairments, which discourage physical activity. Consequently, RA is associated with decreased levels of exercise. Positive effects of exercise on physical and mental health without increasing pain or disease activity have been demonstrated but the influence of moderate-intensity physical activity on the molecular effects in skeletal muscle in people with RA remains unclear. In this pilot study we investigated the impact of a two-year health-enhancing physical activity (HEPA) program on protein profiles in skeletal muscle biopsies from people with RA based on a unique set of interdisciplinary variables. Methods Six people with RA participated. Muscle biopsies were taken from m. vastus lateralis, and perceived disease impact, anthropometrics and physical capacity tests were assessed at baseline and year 1 and 2. Mass spectrometry-based quantitative proteomics and immunohistochemistry analysis were employed to examine molecular changes in the skeletal muscle in response to long-term HEPA. Results The study participants had moderate to low adherence to the HEPA program, the perceived disease impact and anthropometric parameters were not altered. Among the physical capacity tests, the Timed-stands test showed a significant improvement after one year. Mean pressure pain threshold was significantly reduced after 1- and 2-year HEPA participation. Proteome analysis of the muscle biopsies showed an up-regulation of proteins in the mitochondrial respiratory chain and predicted increased ATP production and improved muscle contractility in response to HEPA. Molecular pathways identified by proteome analysis revealed correlations to pain variables. Conclusions Our results indicate that long-term physical activity in people with RA may up-regulate proteins in the mitochondrial respiratory chain predicting increased ATP production and muscle contractility similar to what has been reported in healthy young men and might have a positive impact on muscle tissue by decreased muscle cell death.

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Enhanced ventricular‐arterial coupling during a 2‐year physical activity programme in patients with rheumatoid arthritis: a prospective substudy of the physical activity in rheumatoid arthritis 2010 trial

Abstract: Abstract. Sarajlic P, Frid en C, Lund LH, Manouras A, Venkateshvaran A, Larsson SC, Nordgren B, Opava CH, Lundberg IE, B€ ack M

Cited by 22 publications

References 43 publications

Chemerin inhibits vascular calcification through ChemR23 and is associated with lower coronary calcium in chronic kidney disease

Chemerin inhibits vascular calcification through ChemR23 and is associated with lower coronary calcium in chronic kidney disease

Effects of a two-year health-enhancing physical activity program on skeletal muscle protein profiles in people with rheumatoid arthritis

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