Telomeres are shorter in myocardial infarction patients compared to healthy subjects: correlation with environmental risk factors (original) (raw)
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W56 Telomeres Are Shorter in Patients with Polygenic and Monogenic Forms of Coronary Heart Disease
Atherosclerosis Supplements, 2010
Introduction: Leukocyte telomere length (LTL) has been previously associated with coronary heart disease (CHD). The aim of our study was to confirm this association in cases of different CHD etiology; the common polygenic form and, for the first time, with CHD caused by familial hypercholesterolaemia (FH). Methods: Two CHD case-control studies, consisted of 598 white male patients who survived a first myocardial infarction (MI) (<60 years) recruited from four European countries and 413 coronary artery bypass graft (CABG) patients recruited in the UK compared to 653 region matched controls, were used. Additionally, two groups of 367 and 94 FH patients of whom 145 and 17 respectively had premature CHD were recruited from the UK. Leukocyte telomere length (LTL) was measured using a quantitative PCR-based method. Results: Age-adjusted LTL was significantly shorter in premature MI cases (7.85 kb, SD 4.01) compared to controls (8.04 kb, SD 4.46) (p = 0.04) as well as in CABG cases (6.89 kb, SD 4.14) compared to controls (7.53 kb, SD 5.29) (p = 0.007). In the combined sample of the two FH studies, age-adjusted LTL was shorter in the patients with CHD (8.68 kb, SD 4.65) compared to those without (9.23 kb, SD 4.83) (p = 0.012). Apart from a consistent negative correlation with age, no other CHD risk factor was associated with LTL across the studies. Conclusion: The present data confirms the shortened telomeres as a marker of CHD, possibly reflecting the ageing of vascular wall, and extends this association to those with monogenic and polygenic forms of CHD.
Association between telomere length and heart disease in a narrow age cohort of older people
Experimental Gerontology, 2007
Telomere shortening is a feature of cellular ageing common to a range of human tissues. Shorter telomeres are associated with an increased likelihood of mortality, including death from heart disease. We examined the association between telomere length and heart disease (present in 33%) in a well-characterised, narrow age cohort of older people (n = 190, all born in 1921), and tested for any concomitant effects of medication use. Mean telomere length was significantly shorter in participants who reported heart disease (p = .001). Participants with ischemic changes on ECG had shorter telomere lengths (6.67 versus 7.65 kb, p = .021) after adjusting for other ECG abnormalities. This finding adds to the growing body of evidence for an association between telomere shortening and ischemic heart disease. Telomere shortening in peripheral blood leukocytes is a promising index of ischemic heart disease risk in older people and deserves further investigation as a potential mechanism.
Association between shortened leukocyte telomere length and cardio-metabolic outcomes
Circulation. Cardiovascular genetics, 2015
I n their meta-analysis of 27 published studies, D'Mello et al 1 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 themes: the reliability of LTL measurements, the biological meaning of the association of LTL with cardio-metabolic outcomes, and future directions of telomere research with respect to cardiovascular disease (CVD) and longevity in humans.
Journal of Human Hypertension, 2011
Short telomeres are associated with aging and agerelated diseases. Our aim was to determine whether short leukocyte telomere length is associated with risk factors and cardiovascular diseases in a high-risk hypertensive population. We measured leukocyte telomere lengths at recruitment in 1271 subjects with hypertension and left ventricular hypertrophy (LVH) participating in the Lifestyle Interventions and Independence for Elders (LIFE) study. At baseline, short mean telomere length was associated with coronary artery disease in males (odds ratio (OR) 0.61, 95% confidence interval (CI) 0.39-0.95), and transient ischemic attack in females (OR 0.62 95% CI 0.39-0.99). Proportion of short telomeres (shorter than 5 kb) was associated with Framingham risk score (r ¼ 0.07, Po0.05), cerebrovascular disease (OR 1.18, 95% CI 1.01-1.15) and type 2 diabetes in men (OR 1.07, 95% CI 1.02-1.11). During follow-up, proportion of short telomeres was associated with combined cardiovascular mortality, stroke or angina pectoris (hazard ratio 1.04, 95% CI 1.01-1.07). Telomere length was not associated with smoking, body mass index, pulse pressure or selfreported use of alcohol. Our data suggest that reduced leukocyte telomere length is associated with cardiovascular risk factors and diseases as well as type 2 diabetes, and is a predictor of cardiovascular disease in elderly patients with hypertension and LVH.
Aging Cell, 2007
Evidence assembled over the last decade shows that average telomere length (TL) acts as a biomarker for biological aging and cardiovascular disease (CVD) in particular. Although essential for a more profound understanding of the underlying mechanisms, little reference information is available on TL. We therefore sought to provide baseline TL information and assess the association of prevalent CVD risk factors with TL in subjects free of overt CVD within a small age range. We measured mean telomere restriction fragment length of peripheral blood leukocytes in a large, representative Asklepios study cohort of 2509 community-dwelling, Caucasian female and male volunteers aged approximately 35-55 years and free of overt CVD. We found a manifest age-dependent telomere attrition, at a significantly faster rate in men as compared to women. No significant associations were established with classical CVD risk factors such as cholesterol status and blood pressure, yet shorter TL was associated with increased levels of several inflammation and oxidative stress markers. Importantly, shorter telomere length was associated with an increasingly unhealthy lifestyle, particularly in men. All findings were age and gender adjusted where appropriate. With these cross-sectional results we show that TL of peripheral blood leukocytes primarily reflects the burden of increased oxidative stress and inflammation, whether or not determined by an increasingly unhealthy lifestyle, while the association with classical CVD risk factors is limited. This further clarifies the added value of TL as a biomarker for biological aging and might improve our understanding of how TL is associated with CVD.
European heart journal, 2014
Cross-sectional studies reported associations between short leucocyte telomere length (LTL) and measures of vascular and cardiac damage. However, the contribution of LTL dynamics to the age-related process of cardiovascular (CV) remodelling remains unknown. In this study, we explored whether the rate of LTL shortening can predict CV phenotypes over 10-year follow-up and the influence of established CV risk factors on this relationship. All the participants from the MRC National Survey of Health and Development (NSHD) with measures of LTL and traditional CV risk factors at 53 and 60-64 years and common carotid intima-media thickness (cIMT), cardiac mass and left ventricular function at 60-64 years were included. LTL was measured by real-time polymerase chain reaction and available at both time points in 1033 individuals. While LTL at 53 years was not linked with any CV phenotype at 60-64 years, a negative association was found between LTL and cIMT at 60-64 years (β = -0.017, P = 0.01...
2014
Conclusion: In a Chinese Han population, NAF1 gene encoding proteins with known function in telomere biology may influence both the possibility of and the age at onset of CHD, as previously reported in European studies. Read this original research and sign up to receive Clinical Interventions in Aging journal here: http://www.dovepress.com/articles.php?article\_id=17006
Leukocyte Telomere Length and Cardiovascular Disease in the Cardiovascular Health Study
American Journal of Epidemiology, 2006
The telomere length of replicating somatic cells is inversely correlated with age and has been reported to be associated cross-sectionally with cardiovascular disease (CVD). Leukocyte telomere length, as expressed by mean terminal restriction fragment (TRF) length, was measured in 419 randomly selected participants from the Cardiovascular Health Study, comprising a community-dwelling cohort recruited in four US communities. The authors investigated associations between TRF length and selected measures of subclinical CVD/risk factors for CVD (data were collected at the 1992/1993 clinic visit) and incident CVD (ascertained through June 2002). In these participants (average age ¼ 74.2 years (standard deviation, 5.2)), mean TRF length was 6.3 kilobase pairs (standard deviation, 0.62). Significant or borderline inverse associations were found between TRF length and diabetes, glucose, insulin, diastolic blood pressure, carotid intima-media thickness, and interleukin-6. Associations with body size and C-reactive protein were modified by gender and age, occurring only in men and in participants aged 73 years or younger. In younger (but not older) participants, each shortened kilobase pair of TRF corresponded with a threefold increased risk of myocardial infarction (hazard ratio ¼ 3.08, 95% confidence interval: 1.22, 7.73) and stroke (hazard ratio ¼ 3.22, 95% confidence interval: 1.29, 8.02). These results support the hypotheses that telomere attrition may be related to diseases of aging through mechanisms involving oxidative stress, inflammation, and progression to CVD.
Telomere length and cardiovascular disease
Archives of Cardiovascular Diseases, 2010
Telomeres are structures composed of deoxyribonucleic acid repeats that protect the end of chromosomes, but shorten with each cell division. They have been the subject of many studies, particularly in the field of oncology, and more recently their role in the onset, development and prognosis of cardiovascular disease has generated considerable interest. It has already been shown that these structures may deteriorate at the beginning of the atherosclerotic process, in the onset and development of arterial hypertension or during myocardial infarction, in which their length may be a predictor of outcome. As telomere length by its nature is a marker of cell senescence, it is of particular interest when studying the lifespan and fate of endothelial cells and cardiomyocytes, especially so because telomere length seems to be regulated by various factors notably certain cardiovascular risk factors, such as smoking, sex and obesity that are associated with high levels of oxidative stress. To gain insights into the links between telomere length and cardiovascular disease, and to assess the usefulness of telomere length as a new marker of cardiovascular risk, it seems essential to review the considerable amount of data published recently on the subject. ; BMI, body mass index; CAD, coronary artery disease; DNA, deoxyribonucleic acid; Rad54, eukaryotic homologue of the prokaryotic RecA protein 54; RNA, ribonucleic acid; ROS, reactive oxygen species; TERC, telomerase ribonucleic acid component; TERT, telomerase reverse transcriptase; TRF2, TATA binding protein-related factor 2.