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dc.contributor.authorFernandez-Alvira, Juan Miguel 
dc.contributor.authorFuster, Valentin 
dc.contributor.authorDorado, Beatriz 
dc.contributor.authorSoberon, Nora
dc.contributor.authorFlores, Ignacio 
dc.contributor.authorGallardo, Mercedes
dc.contributor.authorPocock, Stuart 
dc.contributor.authorBlasco, MA 
dc.contributor.authorAndres, Vicente 
dc.date.accessioned2017-10-30T13:15:45Z
dc.date.available2017-10-30T13:15:45Z
dc.date.issued2016
dc.identifierISI:000376336300003
dc.identifier.citationJ Am Coll Cardiol. 2016; 67(21):2467-76
dc.identifier.issn0735-1097
dc.identifier.urihttp://hdl.handle.net/20.500.12105/5229
dc.description.abstractBACKGROUND 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.
dc.description.sponsorshipThis study was supported by Instituto de Salud Carlos III (Grant RD12/0042/0028 to Dr. Andrés), with cofunding from Fondo Europeo de Desarrollo Regional (FEDER), and by a noncompetitive, unrestricted grant shared equally between the CNIC and Banco de Santander. The PESA study is a noncommercial study that is independent of the health care and pharmaceutical industry. The Spanish Ministry of Economy and Competitiveness (MINECO) and the Pro CNIC Foundation support the CNIC. The MINECO RETOS Program and the Fundación Botín fund work in Dr. Blasco0s group. The CNIC and CNIO are recipients of Centro de Excelencia Severo Ochoa awards from MINECO (SEV-2015-0505 and SEV-2015-0510, respectively). The authors have reported that they have no relationships relevant to the contents of this paper to disclose. Peter M. Nilsson, MD, served as Guest Editor for this paper.
dc.language.isoeng
dc.publisherELSEVIER SCIENCE INC
dc.relation.isversionofPublisher's version
dc.subjectcardiovascular disease
dc.subjectleukocyte telomere length
dc.subjectshort telomeres
dc.subjectCORONARY-ARTERY CALCIFICATION
dc.subjectCARDIOVASCULAR-DISEASE RISK
dc.subjectGENERAL-POPULATION
dc.subjectVASCULAR-DISEASE
dc.subjectLIFE-SPAN
dc.subjectASSOCIATION
dc.subjectMETAANALYSIS
dc.subjectSENESCENCE
dc.subjectCELLS
dc.subjectGRANULOCYTES
dc.titleShort Telomere Load, Telomere Length, and Subclinical Atherosclerosis The PESA Study
dc.typeArtículo
dc.identifier.pubmedID27230041
dc.format.volume67
dc.format.page2467-2476
dc.identifier.doi10.1016/j.jacc.2016.03.530
dc.contributor.funderFundación ProCNIC
dc.contributor.funderInstituto de Salud Carlos III - ISCIII
dc.contributor.funderEuropean Regional Development Fund (ERDF/FEDER)
dc.contributor.funderMinisterio de Economía y Competitividad (España)
dc.contributor.funderFundación Marcelino Botín
dc.identifier.e-issn1558-3597
dc.relation.publisherversionhttps://doi.org/10.1016/j.jacc.2016.03.530
dc.identifier.journalJournal of the American College of Cardiology
dc.repisalud.orgCNICCNIC::Grupos de investigación::Antiguos CNIC
dc.repisalud.orgCNICCNIC::Grupos de investigación::Imagen Cardiovascular y Estudios Poblacionales
dc.repisalud.orgCNICCNIC::Grupos de investigación::Regeneración y envejecimiento
dc.repisalud.institucionCNIC
dc.repisalud.institucionCNIO
dc.relation.projectIDMINECO/ICTI2013-2016/SEV-2015-0505es_ES
dc.relation.projectIDMINECO/ICTI2013-2016/SEV-2015-0510es_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES


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