Vazirpanah, N. et al. (2017) Patients with gout have short telomeres compared with healthy participants: association of telomere length with flare frequency and cardiovascular disease in gout. Annals of the Rheumatic

Aim and background: Chronic inflammation associates with increased senescence, which is a strong predictor for cardiovascular disease. We hypothesised that inflammation accelerates senescence and thereby enhances the risk of cardiovascular disease in gout. Methods: We assessed replicative senescence by quantifying telomere length (TL) in a discovery cohort of 145 Dutch patients with gout and 273 healthy individuals and validated our results in 474 patients with gout and 293 healthy participants from New-Zealand. Subsequently, we investigated the effect of cardiovascular disease on TL of all participants. Also, we measured TL of CD4+ and CD8+ T lymphocytes, B lymphocytes, monocytes, natural killer (NK) cells and plasmacytoid dendritic cells (pDCs). Additionally, we assessed the potential temporal difference in TL and telomerase activity. Results: TL in PBMCs of healthy donors decreased over time reflecting normal ageing. Patients with gout demonstrated shorter telomeres (P=0.001, R2=0.01873). In fact, the extent of telomere erosion in patients with gout was higher at any age as compared to healthy counterparts at any age (P<0.0001, R2=0.02847). Patients with gout with cardiovascular disease had the shortest telomeres and TL was an independent risk factor for cardiovascular disease in patients with gout (P=0.001). TL was inversely associated with the number of gouty flares (P=0.005). Conclusions: Patients with gout have shorter telomeres than healthy participants, reflecting increased cellular senescence. Telomere shortening was associated with the number of flares, and with cardiovascular disease in people with gout.