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

Published on May 1, 2016in Journal of the American College of Cardiology18.64
· DOI :10.1016/j.jacc.2016.03.530
Juan Miguel Fernández-Alvira6
Estimated H-index: 6
(Centro Nacional de Investigaciones Cardiovasculares),
Valentin Fuster MDPhD157
Estimated H-index: 157
(ISMMS: Icahn School of Medicine at Mount Sinai)
+ 6 AuthorsVicente Andrés41
Estimated H-index: 41
(Centro Nacional de Investigaciones Cardiovasculares)
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Abstract
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. 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). 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. 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). 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.
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  • References (42)
  • Citations (23)
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References42
Newest
Published on Apr 16, 2015in Circulation23.05
Leticia Fernández-Friera18
Estimated H-index: 18
(Centro Nacional de Investigaciones Cardiovasculares),
José L. Peñalvo26
Estimated H-index: 26
(Centro Nacional de Investigaciones Cardiovasculares)
+ 20 AuthorsVicente Martínez de Vega4
Estimated H-index: 4
Background —Data are limited regarding the presence, distribution and extent of subclinical atherosclerosis in middle-aged populations. Methods and Results —The PESA (Progression of Early Subclinical Atherosclerosis) study prospectively enrolled 4184 asymptomatic participants aged 40-54 years (mean age 45.8 years, 63% male) to evaluate the systemic extent of atherosclerosis in the carotid, abdominal aortic and ilio-femoral territories by 2D/3D ultrasound and coronary artery calcification (CAC) b...
Published on Apr 1, 2015in Journal of Internal Medicine6.05
Andrea Baragetti12
Estimated H-index: 12
(University of Milan),
Jutta Palmen28
Estimated H-index: 28
(UCL: University College London)
+ 7 AuthorsPhilippa J. Talmud69
Estimated H-index: 69
(UCL: University College London)
Introduction Leucocyte telomere length (LTL) is an important determinant of telomere function and cellular replicative capacity. The aim of the present study was to examine prospectively the associations between telomere shortening (TS) and both the progression of atherosclerosis and the incidence of cardiovascular events (CVEs). Materials and methods Leucocyte telomere length was measured by quantitative polymerase chain reaction to determine the ratio of telomere length to single-copy gene (T/...
Published on Feb 1, 2015in Circulation-cardiovascular Genetics4.86
Matthew J.J. D’Mello3
Estimated H-index: 3
(Population Health Research Institute),
Stephanie Ross15
Estimated H-index: 15
(Population Health Research Institute)
+ 3 AuthorsGuillaume Paré48
Estimated H-index: 48
(Population Health Research Institute)
Background —Telomeres are repetitive, gene-poor regions that cap the ends of DNA and help maintain chromosomal integrity. Their shortening is caused by inflammation and oxidative stress within the cellular environment and ultimately leads to cellular senescence. Shortened leukocyte telomere length (LTL) is hypothesized to be a novel biomarker for age and age-related diseases, yet reports on its association with cardio-metabolic outcomes in the literature are conflicting. Methods and Results —MED...
Published on Feb 1, 2015in Circulation-cardiovascular Genetics4.86
Steven C. Hunt76
Estimated H-index: 76
,
Jeremy D. Kark43
Estimated H-index: 43
(HUJI: Hebrew University of Jerusalem),
Abraham Aviv35
Estimated H-index: 35
> The greatest obstacle to discovery is not ignorance—it is the illusion of knowledge . > > D. J. Boorstin In their meta-analysis of 27 published studies, D’Mello et al1 show that shortened leukocyte telomere length (LTL) is associated with 3 primary end points: myocardial infarction, stroke, and type 2 diabetes mellitus. The meta-analysis and its findings raise several fundamental issues that are worth considering. After discussing the major findings and limitations, we focus on 3 central theme...
Published on Jan 27, 2015in Circulation23.05
Dariush Mozaffarian113
Estimated H-index: 113
,
Emelia J. Benjamin150
Estimated H-index: 150
+ 37 AuthorsVirginia J. Howard67
Estimated H-index: 67
Published on Jul 8, 2014in BMJ27.60
Philip Haycock18
Estimated H-index: 18
(University of Cambridge),
Emma E Heydon4
Estimated H-index: 4
(University of Cambridge)
+ 3 AuthorsPeter Willeit37
Estimated H-index: 37
(University of Cambridge)
Objective To assess the association between leucocyte telomere length and risk of cardiovascular disease. Design Systematic review and meta-analysis. Data sources Studies published up to March 2014 identified through searches of Medline, Web of Science, and Embase. Eligibility criteria Prospective and retrospective studies that reported on associations between leucocyte telomere length and coronary heart disease (defined as non-fatal myocardial infarction, coronary heart disease death, or corona...
Published on Dec 1, 2013in American Heart Journal4.02
Antonio Fernández-Ortiz51
Estimated H-index: 51
(Centro Nacional de Investigaciones Cardiovasculares),
L. Jesús Jiménez-Borreguero1
Estimated H-index: 1
(Centro Nacional de Investigaciones Cardiovasculares)
+ 17 AuthorsJosé Mendiguren8
Estimated H-index: 8
Background The presence of subclinical atherosclerosis is a likely predictor of cardiovascular events; however, factors associated with the early stages and progression of atherosclerosis are poorly defined. Objective The PESA study examines the presence of subclinical atherosclerosis by means of noninvasive imaging and prospectively analyzes the determinants associated with its development and progression in a middle-aged population. Methods The PESA study is an observational, longitudinal and ...
Published on Oct 1, 2013in European Journal of Human Genetics3.65
Linda Broer28
Estimated H-index: 28
,
Veryan Codd26
Estimated H-index: 26
+ 24 AuthorsEco J. C. de Geus103
Estimated H-index: 103
Telomere length (TL) has been associated with aging and mortality, but individual differences are also influenced by genetic factors, with previous studies reporting heritability estimates ranging from 34 to 82%. Here we investigate the heritability, mode of inheritance and the influence of parental age at birth on TL in six large, independent cohort studies with a total of 19713 participants. The meta-analysis estimate of TL heritability was 0.70 (95% CI 0.64‐0.76) and is based on a pattern of ...
Published on Aug 1, 2013in Atherosclerosis4.25
Jeremy D. Kark7
Estimated H-index: 7
(HUJI: Hebrew University of Jerusalem),
Hisham Nassar4
Estimated H-index: 4
(St. Joseph Hospital)
+ 6 AuthorsAbraham Aviv35
Estimated H-index: 35
(RU: Rutgers University)
Abstract Objective Shorter leukocyte telomere length (LTL) is associated with higher incidence of coronary heart disease (CHD) and increased mortality. We examined the association of LTL with coronary artery calcification (CAC), which reflects the cumulative burden of coronary atherosclerosis, in an urban Arab sample of Palestinians, a population at high risk of CHD. Methods Using a cross-sectional design, a random sample of East Jerusalem residents, comprising 250 men aged 45–77 and women aged ...
Published on May 1, 2013in Nature Reviews Cardiology17.42
Frej Fyhrquist45
Estimated H-index: 45
,
Outi Saijonmaa23
Estimated H-index: 23
,
Timo E. Strandberg60
Estimated H-index: 60
Telomere shortening, along with various other endogenous and environmental factors, can drive cells into senescence, which is involved in the complex process of biological ageing. In this Review, Fyhrquist and colleagues discuss the associations between cardiovascular risk factors and telomere shortening, and whether cellular senescence has a causal role in conditions such as atherosclerosis, heart failure, and hypertension.
Cited By23
Newest
Published on Jul 1, 2019in Biochimica et Biophysica Acta3.79
Sai Ma2
Estimated H-index: 2
(Fourth Military Medical University),
Li Fan3
Estimated H-index: 3
(Chinese PLA General Hospital),
Feng Cao12
Estimated H-index: 12
(Chinese PLA General Hospital)
Abstract Cellular senescence is the permanent cell cycle arrest induced either by chronological ageing or extrinsic stimuli. Recent researches have identified cellular senescence as an important mechanism for atherosclerosis, which is the essential pathophysiological contributor to cardiovascular diseases (CVDs). The sirtuins are a family of cellular deacetylases with fundamental abilities to regulate cellular metabolism and a variety of physiological activities. Previous studies have revealed t...
Published on Jun 4, 2019in Journal of the American Heart Association4.66
Minh Thien Nguyen (University of Melbourne), Regan Vryer2
Estimated H-index: 2
(University of Melbourne)
+ 7 AuthorsMelissa Wake58
Estimated H-index: 58
(University of Auckland)
Published on May 6, 2019in BioMed Research International2.20
Xiaofeng Xu1
Estimated H-index: 1
(NBU: Ningbo University),
Haochang Hu2
Estimated H-index: 2
(NBU: Ningbo University)
+ 6 AuthorsShiwei Duan15
Estimated H-index: 15
(NBU: Ningbo University)
Coronary heart disease (CHD) is one of the most common causes of death in the world. Numerous studies have shown that as the degree of atherosclerotic disease increases, leukocyte telomere length gradually decreases. Short telomeres increase the risk of all-cause death and cardiovascular death. However, the reported results are not consistent, since the experimental design method, the measurement method, and the disease outcome are different. Therefore, we searched five major literature database...
Published on Mar 1, 2019in Journal of Cellular Physiology4.52
Taru Aggarwal1
Estimated H-index: 1
(Amity Institute of Biotechnology),
Ridhima Wadhwa1
Estimated H-index: 1
(Amity Institute of Biotechnology)
+ 3 AuthorsPawan K. Maurya1
Estimated H-index: 1
(Suffolk University)
Abstract A large body of evidence indicates that chronic obstructive pulmonary disorder (COPD) is accompanied by oxidative stress and inflammatory and genetic pathways. Epidemiological studies indicate that COPD is a major cause of mortality and morbidity in the world. Recent research development in COPD focuses on accelerated aging and various oxidative stress biomarkers. It involves the clinical manifestation of the disease process and may also contain biochemical, immunological, physiological...
Published on Jan 31, 2019
Simon Toupance5
Estimated H-index: 5
,
Athanase Benetos70
Estimated H-index: 70
Nicholas L. DePace3
Estimated H-index: 3
,
Joseph Colombo3
Estimated H-index: 3
To ensure that the supplements recommended with the Mind-Body Wellness Program do not add to stress through contraindications, the contraindications are described. For example, alpha-lipoic acid may lower resting blood pressure, contraindicating it for patients with low resting pressure. The recommended supplements and lifestyles form this kernel of a Wellness Program. The weight of scientifically rigorous and statistically significant evidence behind this program is brought to bear in this chap...
Published on Nov 2, 2018in Cells
Bruna Silva Oliveira3
Estimated H-index: 3
,
Catherine M. Pirkle3
Estimated H-index: 3
+ 3 AuthorsRicardo Oliveira Guerra20
Estimated H-index: 20
This study assessed whether telomere length is related to chronic conditions, cardiovascular risk factors, and inflammation in women aged 65 to 74 from Northeast Brazil. Participants were selected from two sources, a representative sample of the International Mobility in Aging Study (n = 57) and a convenience sample (n = 49) recruited at senior centers. Leukocyte telomere length was measured by quantitative polymerase chain reaction from blood samples in 83 women. Natural log-transformed telomer...
Published on Oct 18, 2018in Brain Sciences
Corona Solana , Diana Pereira , Raquel Tarazona27
Estimated H-index: 27
Schizophrenia is a severe, chronic mental disorder characterized by delusions and hallucinations. Several evidences support the link of schizophrenia with accelerated telomeres shortening and accelerated aging. Thus, schizophrenia patients show higher mortality compared to age-matched healthy donors. The etiology of schizophrenia is multifactorial, involving genetic and environmental factors. Telomere erosion has been shown to be accelerated by different factors including environmental factors s...
Published on Oct 1, 2018in JACC: Basic to Translational Science
Hao Yin9
Estimated H-index: 9
(Robarts Research Institute),
Oula Akawi2
Estimated H-index: 2
(Robarts Research Institute)
+ 12 AuthorsLinrui Guo3
Estimated H-index: 3
(UWO: University of Western Ontario)
Highlights •Short leukocyte telomeres have been associated with adverse cardiovascular outcomes in population studies, but this relationship has not translated to patient care. The authors report a telomere length autologous referencing strategy that has the potential to mark biological aging and to identify high-risk individuals. •Among 163 patients who underwent cardiovascular surgery, telomeres in leukocytes and skeletal muscle displayed age-related shortening, whereas the telomere length in ...
Published on Aug 1, 2018in Journal of the American College of Cardiology18.64
Tim De Meyer33
Estimated H-index: 33
(UGent: Ghent University),
Tim S. Nawrot45
Estimated H-index: 45
(University of Hasselt)
+ 3 AuthorsVicente Andrés41
Estimated H-index: 41
(Ciber)
Abstract Telomeres shorten with age, the major risk factor for atherosclerotic cardiovascular disease (aCVD). The observation of shorter telomeres in aCVD patients thus suggested that critical telomere shortening may contribute to premature biological aging and aCVD. Therefore, telomere length often is suggested as a causal aCVD risk factor, a proposal supported by recent Mendelian randomization studies; however, epidemiological research has shown disappointingly low effect sizes. It therefore r...