Short leukocyte telomere length predicts incidence and progression of carotid atherosclerosis in American Indians: The Strong Heart Family Study

Chen, Shufeng; Lin, Jue; Matsuguchi, Tet; Blackburn, Elizabeth H.; Yeh, Fawn; Best, Lyle G.; Devereux, Richard B.; Lee, Elisa T.; Howard, Barbara V.; Roman, Mary J.; Zhao, Jinying

doi:10.18632/aging.100671

Cited by 60 publications

(49 citation statements)

References 41 publications

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“…1, 4, 25, 29, 30 These factors may also affect the replicative capacity of stem cells leading to increase cellular activation and possibly exhaustion. 31 Consistent with this view, several studies have used LTL as a marker of biological aging and have linked it to age-related diseases including atherosclerosis and its consequences, 32 such as peripheral vascular disease, 7, 33 CAD, 34 and importantly, cardiovascular mortality. 2, 32 Since aging is associated with decline in circulating PCs, and atherosclerosis is thought to develop as a result of an imbalance between endogenous repair mechanisms and factors causing cell injury, 35, 36 most of the studies have speculated that these observed clinical associations were related to decreased regenerative capacity.…”

Section: Discussionmentioning

confidence: 89%

Telomere Shortening, Regenerative Capacity, and Cardiovascular Outcomes

et al. 2017

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Rationale Leucocyte telomere length (LTL) is a biological marker of aging, and shorter LTL is associated with adverse cardiovascular outcomes. Reduced regenerative capacity has been proposed as a mechanism. Bone marrow-derived circulating progenitor cells (PCs) are involved in tissue repair and regeneration. Objective To examine the relationship between LTL and PCs, and their impact on adverse cardiovascular outcomes. Methods and Results We measured LTL by quantitative PCR in 566 outpatients (age 63±9 years, 76% male) with coronary artery disease (CAD). Circulating PCs were enumerated by flow cytometry. After adjustment for age, gender, race, BMI, smoking and previous myocardial infarction, a shorter LTL was associated with a lower CD34+ cell count: for each 10% shorter LTL, CD34+ levels were 5.2% lower (p<0.001). After adjustment for the aforementioned factors, both short LTL (

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Section: Discussionmentioning

confidence: 89%

Telomere Shortening, Regenerative Capacity, and Cardiovascular Outcomes

et al. 2017

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“…In cross-sectional analyses, several European cohorts showed no association of longer LTL with IMT when adjusting for conventional CVD risk factors [41–43], or found associations in only a subset of participants (for example obese males) [44]. However, in a Native American population from the Strong Heart Family Study shorter baseline LTL predicted incidence and progression of carotid plaque [11]. Some previous studies in European populations have found significant positive associations between LVM and LTL, both in cross-sectional analyses [13] and with longitudinal assessment of LVM (median 7.4 years after LTL measurement) [12], but others have found no association [41, 45].…”

Section: Discussionmentioning

confidence: 99%

“…Genetic risk scores of variants associated with shorter telomere length have been associated with increased risk of coronary artery disease events [7, 8], suggesting a potential causative role for telomere length, as expressed in LTL, in CVD and other age-related diseases. Besides clinical CVD, associations have also been observed between shorter LTL and various subclinical indices of atherosclerosis burden, such as coronary artery calcification (CAC) [9, 10] and carotid intima-media thickness (cIMT) [11]. By contrast, longer LTL has been associated with greater left ventricular hypertrophy [12, 13].…”

Section: Introductionmentioning

confidence: 99%

Leukocyte telomere length and cardiovascular disease in African Americans: The Jackson Heart Study

et al. 2017

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Background and aims In European descent populations, shorter leukocyte telomere length (LTL) has been associated with subclinical atherosclerosis, cardiovascular disease (CVD), and mortality, while longer LTL has been associated with greater left ventricular hypertrophy. We evaluated the relationship of LTL with subclinical cardiovascular disease indices and incident clinical events and mortality in African Americans (AAs). Methods Analyses were restricted to 2,518 participants of the Jackson Heart Study (JHS) with LTL measured by Southern blot in baseline blood samples. Results Adjusting for established CVD risk factors, longer LTL was significantly associated with lower prevalence of coronary artery calcification (CAC) (odds ratio (OR) =0.810 per 1 kb increase in LTL; (95% confidence interval [CI] 0.656, 0.9998), p=0.0498). Longer LTL was also associated with higher ankle brachial index (ABI) (β=0.023; (95% CI 0.004, 0.042), p=0.017) when comparing the highest to the lowest LTL quartile. There were no significant associations between LTL and abdominal aortic calcification, carotid intima-media thickness, or left ventricular mass. After a median follow-up of 9 years, longer LTL was associated with lower risk of incident ischemic stroke (hazard ratio (HR) 0.69 (95% CI 0.48, 0.99), p=0.044) and total mortality (HR 0.81 (95% CI 0.67, 0.97), p=0.026) in age and sex adjusted models, but these associations were no longer significant in fully adjusted models. Conclusions Among a community-based cohort of AAs, longer LTL was nominally associated with lower odds of CAC and increased ABI, indicative of decreased prevalence of subclinical atherosclerosis and peripheral arterial disease. These findings do not offer strong support for LTL as an independent biomarker of CVD risk in AAs

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“…In cross-sectional studies, leukocyte telomere length was inversely associated with carotid intima medial thickness, a marker of cardiovascular disease risk and atherosclerotic damage, in obese men [44]. In a longitudinal study, telomere length correlated negatively with cardiovascular disease risk, incident carotid artery plaque, and plaque progression [45]. …”

Section: Telomere Length and Dynamics In Somatic Diseasesmentioning

confidence: 99%

Telomeres, Early-Life Stress and Mental Illness

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Kao

et al. 2015

Clinical Challenges in the Biopsychosocial Interface

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Telomeres are structures of tandem TTAGGG repeats at the ends of chromosomes which preserve the encoding DNA by serving as a disposable brake to terminate DNA duplication during chromosome replication. In this process, the telomere itself shortens with each cell division, and can consequently be thought of as a cellular “clock” reflecting the age of a cell and the time until senescence. Telomere shortening, and changes in levels of telomerase, the enzyme that maintains telomeres, occur in the context of certain somatic diseases and in response to selected physical stressors. Emerging evidence indicates that telomeres shorten with exposure to psychosocial stress (including early-life stress [ELS]), and perhaps in association with some psychiatric disorders. These discoveries suggest that telomere shortening might be a useful biomarker for the overall stress response of an organism to various pathogenic conditions. In this regard, telomeres and their response to both somatic and psychiatric illness could serve as a unifying biomarker of stress response that crosses the brain/body distinction often made in medicine. Prospective studies will help to clarify whether this biomarker has broad utility in psychiatry and medicine in the evaluation of responses to psychosocial stressors. The possibility that telomere shortening can be slowed or reversed by psychiatric and psychosocial interventions could represent an opportunity for developing novel preventative and therapeutic approaches.

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Short leukocyte telomere length predicts incidence and progression of carotid atherosclerosis in American Indians: The Strong Heart Family Study

Cited by 60 publications

References 41 publications

Telomere Shortening, Regenerative Capacity, and Cardiovascular Outcomes

Telomere Shortening, Regenerative Capacity, and Cardiovascular Outcomes

Leukocyte telomere length and cardiovascular disease in African Americans: The Jackson Heart Study

Telomeres, Early-Life Stress and Mental Illness

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