Leukocyte telomere length and risk of coronary heart disease and stroke mortality: prospective evidence from a Russian cohort

Stefler, Dénes; Malyutina, Sofia; Максимов, В. Н.; Орлов, П. С.; Ivanoschuk, D. E.; Nikitin, Y; Гафаров, В. В.; Ryabikov, Andrey; Воевода, М. И.; Bobák, Martin; Holmes, Michael V.

doi:10.1038/s41598-018-35122-y

Cited by 20 publications

(9 citation statements)

References 30 publications

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“…In our study, an epigenetic predictor of telomere length predicted time-to-onset of ischemic heart disease. A shorter leukocyte telomere length has been shown to associate with heart disease in diverse populations, suggesting that the DNAm Telomere Length predictor may capture key facets of this clinical association [42][43][44]. Our rich resource of genome-wide DNA methylation and longitudinal health data is the first to show the association of epigenetic measures of ageing with a wide range of common disease states, even after accounting for major confounding influences.…”

Section: Discussionmentioning

confidence: 99%

Epigenetic measures of ageing predict the prevalence and incidence of leading causes of death and disease burden

et al. 2020

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Background: Individuals of the same chronological age display different rates of biological ageing. A number of measures of biological age have been proposed which harness age-related changes in DNA methylation profiles. These measures include five 'epigenetic clocks' which provide an index of how much an individual's biological age differs from their chronological age at the time of measurement. The five clocks encompass methylation-based predictors of chronological age (HorvathAge, HannumAge), all-cause mortality (DNAm PhenoAge, DNAm GrimAge) and telomere length (DNAm Telomere Length). A sixth epigenetic measure of ageing differs from these clocks in that it acts as a speedometer providing a single time-point measurement of the pace of an individual's biological ageing. This measure of ageing is termed DunedinPoAm. In this study, we test the association between these six epigenetic measures of ageing and the prevalence and incidence of the leading causes of disease burden and mortality in high-income countries (n ≤ 9537, Generation Scotland: Scottish Family Health Study). Results: DNAm GrimAge predicted incidence of clinically diagnosed chronic obstructive pulmonary disease (COPD), type 2 diabetes and ischemic heart disease after 13 years of follow-up (hazard ratios = 2.22, 1.52 and 1.41, respectively). DunedinPoAm predicted the incidence of COPD and lung cancer (hazard ratios = 2.02 and 1.45, respectively). DNAm PhenoAge predicted incidence of type 2 diabetes (hazard ratio = 1.54). DNAm Telomere Length associated with the incidence of ischemic heart disease (hazard ratio = 0.80). DNAm GrimAge associated with all-cause mortality, the prevalence of COPD and spirometry measures at the study baseline. These associations were present after adjusting for possible confounding risk factors including alcohol consumption, body mass index, deprivation, education and tobacco smoking and surpassed stringent Bonferroni-corrected significance thresholds. Conclusions: Our data suggest that epigenetic measures of ageing may have utility in clinical settings to complement gold-standard methods for disease assessment and management.

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Section: Discussionmentioning

confidence: 99%

Epigenetic measures of ageing predict the prevalence and incidence of leading causes of death and disease burden

et al. 2020

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“…In our study, an epigenetic predictor of telomere length predicted time-toonset of ischemic heart disease. A shorter leukocyte telomere length has been shown to associate with heart disease in diverse populations, suggesting that the DNAm Telomere Length predictor may capture key facets of this clinical association (32)(33)(34). Our rich resource of genome-wide DNA methylation and longitudinal health data is the first to show the association of epigenetic clocks with a wide range of common disease states, even after accounting for major confounding influences.…”

Section: Discussionmentioning

confidence: 98%

Epigenetic clocks predict prevalence and incidence of leading causes of death and disease burden

Hillary

Stevenson

McCartney

et al. 2020

Preprint

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Individuals of the same chronological age display different rates of biological ageing. A number of measures of biological age have been proposed which harness age-related changes in DNA methylation profiles. These include methylation-based predictors of chronological age (HorvathAge, HannumAge), all-cause mortality (DNAm PhenoAge, DNAm GrimAge) and telomere length (DNAm Telomere Length). In this study, we test the association between these epigenetic markers of ageing and the prevalence and incidence of the leading causes of disease burden and mortality in highincome countries. Furthermore, we test the clocks' relationships with phenotypic measures associated with these conditions, including spirometric and biochemical traits. We carry out these analyses in 9,537 individuals from the Generation Scotland: Scottish Family Health Study. We find that DNAm GrimAge outperforms other epigenetic clocks in its associations with self-report disease prevalence and related clinical traits. DNAm GrimAge associates with chronic obstructive pulmonary disease (COPD) prevalence (Odds Ratio = 3.29, P = 3.0 x 10 -4 ) and pulmonary spirometry tests (β = [-0.10 to -0.15], P = [1.4 x 10 -4 to 1.4 x 10 -6 ]) at study baseline after adjusting for possibly confounding risk factors including alcohol, body mass index, deprivation, education and smoking. After adjusting for these confounding risk factors, DNAm GrimAge, DNAm PhenoAge and DNAm Telomere Length, measured at study baseline, predict incidence of ICD-10-coded disease states including COPD, type 2 diabetes and cardiovascular disease after thirteen years of follow-up (Hazard Ratios = [0.80 (telomere length)to 2.19 (GrimAge)], P = [9.9 x 10 -4 , 1.9 x 10 -14 ]). Our data show that despite accounting for several possible confounding variables, epigenetic markers of ageing predict incidence of common disease.This may have significant implications for their potential utility in clinical settings to complement goldstandard methods of clinical assessment and management.

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“…In addition, among a community-based cohort of African Americans, after a median follow-up of 9 years, longer telomere length was associated with a lower risk of incident ischemic stroke and total mortality in age- and sex-adjusted models, but these associations were no longer significant in fully adjusted models [21]. However, there were also a large number of studies that suggested telomere length relating to all-cause mortality in different population [22,23].…”

Section: Discussionmentioning

confidence: 99%

The association of mean telomere length with all-cause, cerebrovascular and cardiovascular mortality

Huang

Feng

et al. 2019

Bioscience Reports

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Mean telomere length (MLT) is a marker of cell aging and may associate with age-related diseases. However, the relationship between MLT and mortality risk remains unclear. We aimed to investigate the relationship between MLT and all-cause, cerebrovascular and cardiovascular mortality among adults in United States. We analyzed data were from National Health and Nutrition Examination Survey (NHANES, 1999–2002) with follow-up data through 31 December 2015. Based on MLT, participants were categorized into low, middle and high groups. Multivariate Cox proportional hazards regression, subgroup analysis and generalized additive model (GAM) were performed by using hazard ratios (HRs) and 95% confidence intervals (CIs). A total of 7827 participants were included in analysis (48.18% male). After 158.26 months of follow-up on average, there were 1876 (23.97%), 87 (1.11%) and 243 (3.10%) onset of all-cause, cerebrovascular and cardiovascular mortality. After adjustment for potential confounders, using the low group as the reference, HRs for all-cause (0.87 and 0.86), cerebrovascular (0.75 and 0.75) and cardiovascular mortality (1.01 and 0.69) for the middle to high groups were not statistically significant (all P>0.05 for trend). MLT was non-linearly related to all-cause mortality but not to cerebrovascular and cardiovascular mortality. It was the first study to demonstrate the non-linear relationship between MLT and all-cause mortality.

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Leukocyte telomere length and risk of coronary heart disease and stroke mortality: prospective evidence from a Russian cohort

Cited by 20 publications

References 30 publications

Epigenetic measures of ageing predict the prevalence and incidence of leading causes of death and disease burden

Epigenetic measures of ageing predict the prevalence and incidence of leading causes of death and disease burden

Epigenetic clocks predict prevalence and incidence of leading causes of death and disease burden

The association of mean telomere length with all-cause, cerebrovascular and cardiovascular mortality

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