Short Telomere Load, Telomere Length, and Subclinical Atherosclerosis: The PESA Study

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• 作者：Juan M. Ferná ; ndez-Alvira ; PhD^a ; Valentin Fuster ; MD ; PhD^a ; ^b ; ^{valentin.fuster@mssm.edu" class="auth_mail" title="E-mail the corresponding author} ; Beatriz Dorado ; PhD^a ; Nora Soberó ; n ; PhD^c ; Ignacio Flores ; PhD^a ; Mercedes Gallardo ; PhD^c ; Stuart Pocock ; PhD^a ; ^d ; Marí ; a A. Blasco ; PhD^c ; Vicente André ; s ; PhD^a ; ^{vandres@cnic.es" class="auth_mail" title="E-mail the corresponding author}
• 关键词：cardiovascular disease ; leukocyte telomere length ; short telomeres
• 刊名：Journal of the American College of Cardiology
• 出版年：2016
• 出版时间：31 May 2016
• 年：2016
• 卷：67
• 期：21
• 页码：2467-2476
• 全文大小：1728 K

文摘

Leucocyte telomere length (LTL) shortening is associated with cardiovascular ischemic events and mortality in humans, but data on its association with subclinical atherosclerosis are scarce. Whether the incidence and severity of subclinical atherosclerosis are associated with the abundance of critically short telomeres, a major trigger of cellular senescence, remains unknown.

Objectives

The authors conducted a cross-sectional exploration of the association between subclinical atherosclerosis burden and both average LTL and the abundance of short telomeres (%LTL<3 kb).

Methods

Telomere length was assessed by high-throughput quantitative fluorescence in situ hybridization in circulating leukocytes from 1,459 volunteers without established cardiovascular disease (58% men, 40 to 54 years of age) from the PESA (Progression of Early Subclinical Atherosclerosis) study. Subclinical atherosclerosis was evaluated by coronary artery calcium scan and 2-dimensional/3-dimensional ultrasound in different aortic territories. Statistical significance of differences among multiple covariates was assessed with linear regression models. Independent associations of telomere parameters with plaque presence were evaluated using general linear models.

Results

In men and women, age was inversely associated with LTL (Pearson’s r = −0.127, p < 0.001) and directly with %LTL<3 kb (Pearson’s r = 0.085; p = 0.001). Short LTL reached statistical significance as a determinant of total and femoral plaque in men, but not in women. However, this association was not sustained after adjustment for age or additional adjustment for cardiovascular risk factors. No significant independent association was found between %LTL<3 kb and plaque burden. Serum-oxidized low-density lipoprotein levels were directly associated with %LTL<3 kb in men (p = 0.008) and women (p < 0.001).

Conclusions

In a cross-sectional study of a middle-aged population, average LTL and short telomere load are not significant independent determinants of subclinical atherosclerosis. Longitudinal follow-up of PESA participants will assess long-term associations between telomere length and progression of subclinical atherosclerosis.