Telomere length, risk of coronary heart disease, and statin treatment in the West of Scotland Primary Prevention Study: a nested case-control study
The LancetPublished 1 January 2007
Scott Brouilette, J. Moore, Alex D. McMahon, John R. Thompson, Ian Ford, James Shepherd
Citations748
SJR quartileQ1
SJR score12.11
SNIP22.72
Generate an AI Snapshot to get a quick, structured summary of this paper.
Study Snapshot
ObjectiveStudy objective
MethodsResearch methodology
PopulationPopulation studied
Sample sizeSample sizes
OutcomesStudy outcomes here
ResultsStudy results comes here
LimitationsResearch study limitations comes here
A concise AI-generated summary of the paper will appear here once you click Generate AI Snapshot.
TL;DR
Mean leucocyte telomere length is a predictor of future coronary heart disease events in middle-aged, high-risk men and could identify individuals who would benefit most from statin treatment.
Abstract
Mean leucocyte telomere length is a predictor of future coronary heart disease events in middle-aged, high-risk men and could identify individuals who would benefit most from statin treatment. Our findings lend support to the hypothesis that differences in biological ageing might contribute to the risk--and variability in age of onset--of coronary heart disease.
Keywords
Medicine
New England Journal of MedicineAtherosclerosis — An Inflammatory Disease
21,594 Citations1999Russell Ross
The LancetEffect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study
11,970 Citations2004Salim Yusuf, Steven Hawken +9 more
Abnormal lipids, smoking, hypertension, diabetes, abdominal obesity, psychosocial factors, consumption of fruits, vegetables, and alcohol, and regular physical activity account for most of the risk of myocardial infarction worldwide in both sexes and at all ages in all regions.
New England Journal of MedicinePrevention of Coronary Heart Disease with Pravastatin in Men with Hypercholesterolemia
7,453 Citations1995James Shepherd, Stuart M. Cobbe +6 more
Treatment with pravastatin significantly reduced the incidence of myocardial infarction and death from cardiovascular causes without adversely affecting the risk of death from noncardiovascular causes in men with moderate hypercholesterolemia and no history of my Cardiac Infarction.
NatureTelomeres shorten during ageing of human fibroblasts
5,690 Citations1990Calvin B. Harley, A. B. Futcher +1 more
The amount and length of telomeric DNA in human fibroblasts does in fact decrease as a function of serial passage during ageing in vitro and possibly in vivo.
Nucleic Acids ResearchTelomere measurement by quantitative PCR
3,526 Citations2002Richard Cawthon
A primer pair is presented that eliminates the problem of presumed impossible to measure telomeres in vertebrate DNA by PCR amplification with oligonucleotide primers designed to hybridize to the TTAGGG and CCCTAA repeats, allowing simple and rapid measurement of telomere length in a closed tube, fluorescence-based assay.
Proceedings of the National Academy of SciencesAccelerated telomere shortening in response to life stress
2,981 Citations2004Elissa S. Epel, Elizabeth H. Blackburn +5 more
Proceedings of the National Academy of SciencesTelomere length predicts replicative capacity of human fibroblasts.
2,216 Citations1992Richard Allsopp, Homayoun Vaziri +6 more
Telomere length is a biomarker of somatic cell aging in humans and is consistent with a causal role for telomere loss in this process, and fibroblasts from Hutchinson-Gilford progeria donors had short telomeres, consistent with their reduced division potential in vitro.
Journal of Theoretical BiologyA theory of marginotomy
1,797 Citations1973A. M. Olovnikov
Marginotomy is responsible for the loss with age of various cell clones of the body, including some endocrine cell clones, and may be the primary cause of various disorders of age of the ageing of multicellular organisms.
The LancetAssociation between telomere length in blood and mortality in people aged 60 years or older
1,753 Citations2003Richard Cawthon, Ken R. Smith +3 more
The results lend support to the hypothesis that telomere shortening in human beings contributes to mortality in many age-related diseases.
The LancetObesity, cigarette smoking, and telomere length in women
1,349 Citations2005Ana M. Valdes, Toby Andrew +6 more
It is found that telomere length decreased steadily with age at a mean rate of 27 bp per year, and the pro-ageing effects of obesity and cigarette smoking are emphasised.
Proceedings of the National Academy of SciencesEvidence for a mitotic clock in human hematopoietic stem cells: loss of telomeric DNA with age.
1,150 Citations1994Homayoun Vaziri, Wieslawa H. Dragowska +4 more
It is shown that candidate human stem cells with a CD34+CD38lo phenotype that were purified from adult bone marrow have shorter telomeres than cells from fetal liver or umbilical cord blood and that cells produced in cytokine-supplemented cultures of purified precursor cells show a proliferation-associated loss of telomeric DNA.
CirculationEndothelial Cell Senescence in Human Atherosclerosis
1,039 Citations2002Tohru Minamino, Hideaki Miyauchi +4 more
CirculationIncrease in Circulating Endothelial Progenitor Cells by Statin Therapy in Patients With Stable Coronary Artery Disease
1,016 Citations2001Mariuca Vasa, Stephan Fichtlscherer +5 more
A novel mechanism of action of statin treatment in patients with stable CAD is defined: the augmentation of circulating EPCs with enhanced functional activity.
CirculationStatin Therapy Accelerates Reendothelialization
915 Citations2002Dirk Walter, Kilian Rittig +8 more
These findings establish additional mechanisms by which statins may specifically preempt disordered vascular wall pathology and constitute physiological evidence that EPC mobilization represents a functionally relevant consequence of statin therapy.
New England Journal of MedicineLipoprotein-Associated Phospholipase A<sub>2</sub>as an Independent Predictor of Coronary Heart Disease
813 Citations2000Chris J. Packard, D S O’Reilly +12 more
Elevated levels of lipoprotein-associated phospholipase A2 appear to be a strong risk factor for coronary heart disease, a finding that has implications for atherogenesis and the assessment of risk.
PubMedGenetic determination of telomere size in humans: a twin study of three age groups.
751 Citations1994P. Eline Slagboom, Simone Droog +1 more
The individual differences in mean TRF length in blood, therefore, seem to a large extent to be genetically determined.
Proceedings of the National Academy of SciencesTelomere length and replicative aging in human vascular tissues.
632 Citations1995Edwin Chang, Calvin B. Harley
Observations extend the use of telomere size as a marker for the replicative history of cells and are consistent with a role for focal replicative senescence in cardiovascular diseases.
The LancetTelomere shortening in atherosclerosis
607 Citations2001Nilesh J. Samani, Rachel Louise. Boultby +3 more
This pilot study compared mean length of terminal restriction fragments (TRF), a measure of average telomere size, in leucocyte DNA of patients with severe coronary artery disease with that of 20 controls without CAD, finding cases had mean TRF lengths shorter than those of controls.
Philosophical Transactions of the Royal Society B Biological SciencesTelomeres and telomerase
593 Citations2004Simon R. W. L. Chan, Elizabeth H. Blackburn
The molecular consequences of telomeres failure, and the molecular contributors to telomere function, with an emphasis on telomerase, are discussed here.
Arteriosclerosis Thrombosis and Vascular BiologyWhite Cell Telomere Length and Risk of Premature Myocardial Infarction
590 Citations2003Scott Brouilette, Ravi Singh +3 more
The findings support the concept that biological age may play a role in the etiology of coronary heart disease and have potentially important implications for the understanding of its genetic etiology, pathogenesis, and variable age of onset.
Annals of the New York Academy of SciencesRole of Oxidative Stress in Telomere Length Regulation and Replicative Senescence
439 Citations2000Thomas von Zglinicki
An integrative model of telomere shortening and signaling is developed and suggests that t‐loop formation hinders access of repair proteins to telomeres, leading to accumulation of abasic sites and single‐strand breaks which might contribute to accelerated telomer shortening.
Experimental Cell ResearchEvidence for a Critical Telomere Length in Senescent Human Fibroblasts
388 Citations1995Richard Allsopp, Calvin B. Harley
Initial telomere length cannot account for all of the interclonal variability in replicative capacity, but observations support the existence of a critical telomeres length in senescing cells and a causal role ofTelomere shortening in cell senescence.
Experimental GerontologyTelomere lengths are characteristic in each human individual
344 Citations2002Kaiyo Takubo, Naotaka Izumiyama‐Shimomura +6 more
Telomere lengths did not show clear correlation with tissue renewal times in vivo, but rather were characteristic for individuals.
Aging CellTelomere length in white blood cells is not associated with morbidity or mortality in the oldest old: a population‐based study
319 Citations2005Carmen Martín-Ruiz, Jacobijn Gussekloo +3 more
It is concluded that blood monocyte telomere length is not a predictive indicator for age‐related morbidity and mortality at ages over 85 years, possibly because of a high degree of telomeres length instability in this group.
The American Journal of Human GeneticsMapping of a Major Locus that Determines Telomere Length in Humans
256 Citations2004Mariuca Vasa‐Nicotera, Scott Brouilette +9 more
Mapping of the first locus that determines mean telomere length in humans is reported, and preliminary analysis of a strong candidate gene in the region, the DNA helicase DDX11, is presented.
The American Journal of Human GeneticsMapping Genetic Loci That Determine Leukocyte Telomere Length in a Large Sample of Unselected Female Sibling Pairs
252 Citations2006Toby Andrew, Abraham Aviv +8 more
This is the first report of loci, mapped in a sample of healthy individuals, that influence mean telomere variation in humans, and significant linkage was observed on chromosome 14.
HeartMorphology of the endothelium over atherosclerotic plaques in human coronary arteries.
240 Citations1988Michael J. Davies, N. J. Woolf +2 more
The right coronary arteries of six hearts removed from patients with atherosclerosis, who were undergoing cardiac transplantation, were perfused with 2% buffered glutaraldehyde for 20 minutes before preparation for scanning electron microscopy to accord with the endothelial damage and platelet adhesion seen in hyperlipidaemic animals fed a high lipid diet.
CirculationStatins Enhance Migratory Capacity by Upregulation of the Telomere Repeat-Binding Factor TRF2 in Endothelial Progenitor Cells
229 Citations2004Ioakim Spyridopoulos, Judith Haendeler +6 more
Ex vivo culturing of EPCs leads to “uncapping” of telomeres, indicated by the loss of TRF2, the first time a beneficial effect of statins on telomere biology has been described.
DiabetesShortened telomere length in white blood cells of patients with IDDM.
216 Citations1998Elisabeth Jeanclos, Andrzej S. Królewski +5 more
The shortened TRF length of WBCs of patients with IDDM likely reflects a marked reduction in the TRFlength of subsets of W BCs that play a role in the pathogenesis of IDDM.
Arteriosclerosis and Thrombosis A Journal of Vascular BiologyThe endothelium of advanced arteriosclerotic plaques in humans.
175 Citations1991Karl‐Friedrich Bürrig
The functional morphology of the endothelial cells (ECs) covering advanced but uncomplicated sclerotic plaques in humans was studied in carotid endarterectomy specimens and in coronary arteries from hearts explanted because of advanced ischemic heart disease.
Journal of Biological ChemistryStochastic Variation in Telomere Shortening Rate Causes Heterogeneity of Human Fibroblast Replicative Life Span
136 Citations2004Carmen Martín-Ruiz, Gabriele Saretzki +6 more
GeneA novel gene family induced by acute inflammation in endothelial cells
80 Citations2004Kristina Warton, Natasha C. Foster +2 more
It is proposed that NLF1 and NLF2 belong to a novel gene family encoding nuclear factors with a role in regulating genes which control cellular architecture which might increase vascular permeability in acute inflammation.
The American Journal of CardiologyScreening experience and baseline characteristics in the West of Scotland coronary prevention study
61 Citations1995
Compared with previous primary prevention studies of cholesterol-lowering drugs, the WOSCOPS recruits are, on average, 7 to 9 years older than subjects in other trials and have average total cholesterol levels 0.5 mmol/L lower than those in the Helsinki Heart Study and the Lipid Research Clinics-Coronary Primary Prevention Trial.
PubMedOxidative stress and coronary artery disease.
11 Citations1998David G. Harrison
This update focuses on data implicating oxidative inactivation of nitric oxide in atherosclerosis and hypercholesterolemia.