Telomere length and arterial stiffness in patients with rheumatoid arthritis
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Date
2020
Authors
Zidan, Eman Salem
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Abstract
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
Description
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