Telomere length and arterial stiffness in patients with rheumatoid arthritis

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2020

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Zidan, Eman Salem

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Background. Chronic inflammation increases cell replication and thereby accelerates relative leukocyte telomere length shortening. Telomere attrition is associated with cardiovascular disease. However, a direct relationship between telomere length and atherosclerosis was recently reported in patients with rheumatoid arthritis (RA) and lupus. Whether telomere length is associated with other markers of sub-clinical cardiovascular disease in patients with rheumatic disease awaits elucidation. Objective. This study aimed to determine whether relative leukocyte telomere length is associated with aortic function in RA. Methods. Arterial function and relative leukocyte telomere length was assessed in 145 (99 white, 25 Asian, 17 black and 4 mixed race) patients with RA. Arterial function markers was determined by applanation tonometry using SphygmoCor software and included carotid femoral pulse wave velocity (PWV), central systolic and pulse pressure, central augmentation pressure, pulse pressure amplification and the magnitude and timing of the forward and reflected waves. Relative leukocyte telomere length was determined by quantitative real-time polymerase chain reaction (PCR). Relationships between telomere length and comprehensively evaluated arterial function markers were determined in confounder adjusted, multivariate regression models. Sensitivity analysis was performed in white patients with RA. Results. In demographic characteristic adjusted analysis, relative telomere length was associated with abatacept use (partial r=0.19, p=0.02), but not with traditional cardiovascular disease risk factors in all patients (all p>0.05). In sensitivity analysis in white African patients, relative telomere length was associated with body mass index and waist circumference (both partial r=0.21; p=0.05), with disease activity score in 28 joints (partial r=-0.21, p=0.05), deformed joints (partial r=-0.20, p=0.05) and with sulphasalazine (partial r=-0.24, p=0.02) and abatacept (partial r=0.24, p=0.02) use. In known confounder adjusted backward regression models, relative telomere length was associated with central pulse pressure (std β(SE)=0.13(0.07), p=0.05), central augmentation pressure (std β(SE)=0.13(0.07), p=0.05), backward wave pressure (std β(SE)=0.13(0.06), p=0.04) and reflection magnitude (std β(SE)=0.14(0.07), p=0.05) in all patients. In fully adjusted regression analysis, the results remained materially unaltered. In sensitivity analysis in white African patients, relative telomere length was associated only with central pulse pressure in known confounder (std β(SE)=0.18(0.09), p=0.04) and fully adjusted models (std β(SE)=0.18(0.08), p=0.04). Leukocyte telomere length was not associated with any marker of arterial function in sensitivity analysis in women. Conclusions. This study documents a paradoxically direct relationship between relative telomere length and central pressure and wave reflection in RA. The role of relative telomere length in cardiovascular disease in RA requires further longitudinal and mechanistic investigation

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A dissertation submitted in fulfilment of the requirements for the degree of Master of Science in Medicine to the Faculty of Health Sciences, School of Physiology, University of the Witwatersrand, Johannesburg, 2020

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