Juan M Fernández-Alvira1, Valentin Fuster2, Beatriz Dorado1, Nora Soberón3, Ignacio Flores1, Mercedes Gallardo3, Stuart Pocock4, María A Blasco3, Vicente Andrés5. 1. Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain. 2. Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain; Mount Sinai School of Medicine, New York, New York. Electronic address: valentin.fuster@mssm.edu. 3. Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Research Centre (CNIO), Madrid, Spain. 4. Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain; London School of Hygiene & Tropical Medicine, London, United Kingdom. 5. Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain. Electronic address: vandres@cnic.es.
Abstract
BACKGROUND: 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.
BACKGROUND: 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.
Authors: Stanford Mwasongwe; Yan Gao; Michael Griswold; James G Wilson; Abraham Aviv; Alexander P Reiner; Laura M Raffield Journal: Atherosclerosis Date: 2017-09-15 Impact factor: 5.162
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Authors: Muhammad Hammadah; Ibhar Al Mheid; Kobina Wilmot; Ronnie Ramadan; Naser Abdelhadi; Ayman Alkhoder; Malik Obideen; Pratik M Pimple; Oleksiy Levantsevych; Heval M Kelli; Amit Shah; Yan V Sun; Brad Pearce; Michael Kutner; Qi Long; Laura Ward; Yi-An Ko; Kareem Hosny Mohammed; Jue Lin; Jinying Zhao; J Douglas Bremner; Jinhee Kim; Edmund K Waller; Paolo Raggi; David Sheps; Arshed A Quyyumi; Viola Vaccarino Journal: Circ Res Date: 2016-12-12 Impact factor: 17.367