Abstract 16704: Leukocyte Telomere Length and Risk of Stroke: The Strong Heart Family Study

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Caroline Goode ◽  
Jinying Zhao ◽  
Richard B Devereux ◽  
Santosh Murthy ◽  
Alexander E Merkler ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Risk Factors ◽  
Atrial Fibrillation ◽  
Telomere Length ◽  
Family Study ◽  
Leukocyte Telomere Length ◽  
Potential Biomarker ◽  
Primary Model ◽  
Strong Heart Family Study

Introduction: Leukocyte telomere length (LTL) is a potential biomarker of aging and associated with several age-related diseases. Current research on an association between LTL and incident stroke has had inconclusive results. We hypothesized that LTL is associated with incident stroke among American Indians (AI) in the Strong Heart Family Study (SHFS). Methods: The SHFS is a population-based cohort study of cardiovascular disease (CVD) and its risk factors. Participants (n=2,769) recruited from regions in Arizona, Oklahoma and the Dakotas were assessed for LTL and CVD risk factors during a clinic visit between 2001 and 2003. Incident stroke events were identified through the end of 2018 (mean follow-up: 16.4 years). We assessed the association between LTL and incident stroke using frailty models based on the proportional hazards, accounting for family relatedness and established stroke risk factors that include sex, geographical location, education, smoking, atrial fibrillation, diabetes mellitus, and hypertension. Results: Among 2,769 participants, the mean age was 40.6±17.2 and 41.4% were male. During follow-up, there were 79 (2.9%) incident stroke cases. In the primary model, which adjusted for demographic variables (sex, location and education), the hazard ratios (HR) for stroke in participants in the first and second LTL quartiles were significantly higher than those in the highest (longest) LTL quartile, with HRs of 3.1 (95%CI: 1.4 - 6.6) and 3.5 (95%CI: 1.7 - 7.5), respectively. After adjusting for smoking, atrial fibrillation, diabetes mellitus, and hypertension, the association between LTL and stroke was attenuated, but remained significant when comparing the second shortest LTL quartile to the longest LTL quartile, HR: 2.3 (95% CI: 1.1 – 5.0). Conclusions: In summary, LTL was associated with incident stroke among SHFS participants. Those with shorter LTL have higher risk of stroke. Longer follow-up time may add more power to data analyses since the SHFS is relatively young, with an average baseline age of 40 years. If results are confirmed in other populations, LTL may serve as a biomarker identifying high risk individuals for the purpose of stroke prevention.

Abstract P012: Short Leukocyte Telomere Length is Associated With Obesity in American Indians: The Strong Heart Family Study

Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Shufeng Chen ◽  
Jue Lin ◽  
Tet Matsuguchi ◽  
Elizabeth Blackburn ◽  
Elisa T Lee ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Waist Circumference ◽  
Telomere Length ◽  
American Indians ◽  
Family Study ◽  
Leukocyte Telomere Length ◽  
Hip Circumference ◽  
Waist To Hip Ratio ◽  
Strong Heart Family Study

Background: Obesity is an independent risk factor for diabetes and cardiovascular disease. Telomere length shortens progressively with age, and shorter leukocyte telomere length (LTL) has been associated with a wide range of age-related disorders. However, the association between LTL and obesity has not been well established. Objective: To examine the association of LTL with obesity and related traits in American Indians participating in the Strong Heart Family Study (SHFS, 2001-2003), independent of known risk factors. Methods: A total of 3,162 participants (18-93 years old, 1,938 women) from 94 multigenerational families were included in this analysis. Obesity-related traits included body mass index (BMI), waist circumference, hip circumference, and waist-to-hip ratio. LTL was measured by quantitative PCR. Association of LTL (continuous or in quintiles) with each adiposity index was examined using generalized linear mixed model, adjusting for age, sex, study center, education, lifestyle factors (current smoking, current drinking, physical activity, and total energy intake), hypertension (yes/no) and diabetes (yes/no). The association of LTL with prevalent obesity (BMI ≥30 kg/m2) was examined by multivariate logistic regression using the GLIMMIX procedure in SAS 9.3. Results: Prevalence of obesity was 59.6% (1,883 of 3,162). LTL was negatively correlated with age (r=-0.3, P<0.0001). Obese participants had significantly shorter LTL than non-obese participants (age-adjusted P=0.0004). Multivariate regression analyses demonstrated that, LTL was significantly and inversely associated with all obesity indices (β= -2.68 [95% confidence interval (CI), -3.96 [[Unable to Display Character: &#8210;]] -1.40] for BMI; -6.28 [95% CI, -9.29 [[Unable to Display Character: &#8210;]] -3.27] for waist circumference; -3.95 [95% CI, -6.61 [[Unable to Display Character: &#8210;]] -1.29] for hip circumference; and -0.02 [95% CI, -0.03 [[Unable to Display Character: &#8210;]] -0.01] for waist-to-hip ratio). Participants with shorter LTL had significantly larger BMI (P trend across quintiles =0.0006), waist circumference (P trend =0.0005), hip circumference (P trend =0.01), and waist-to-hip ratio (P trend =0.002) compared to those with longer LTL. Multivariate-adjusted odds ratio (95% CI) for prevalent obesity was 1.32 (1.05-1.67), 1.29 (0.99-1.67), 1.29 (1.01-1.65) and 1.18 (0.89-1.57), respectively, for the 1st through 4th quintiles of LTL in comparison with the 5th quintile (P for trend =0.02). Excluding participants with diabetes and cardiovascular disease did not change our results. Conclusion: Shorter LTL was significantly associated with obesity and related measures in American Indians, independent of known risk factors. Our results may shed light on the complex pathophysiology of obesity and its related disorders.

scholarly journals Urinary metals and leukocyte telomere length in American Indian communities: The Strong Heart and the Strong Heart Family Study

2019 ◽  
Vol 246 ◽  
pp. 311-318 ◽  
Author(s):  
Maria Grau-Perez ◽  
Jinying Zhao ◽  
Brandon Pierce ◽  
Kevin A. Francesconi ◽  
Walter Goessler ◽  
...  
Keyword(s):  
American Indian ◽  
Telomere Length ◽  
Family Study ◽  
Leukocyte Telomere Length ◽  
Strong Heart Family Study

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

Aging ◽  
2014 ◽  
Vol 6 (5) ◽  
pp. 414-427 ◽  
Author(s):  
Shufeng Chen ◽  
Jue Lin ◽  
Tet Matsuguchi ◽  
Elizabeth Blackburn ◽  
Fawn Yeh ◽  
...  
Keyword(s):  
Telomere Length ◽  
American Indians ◽  
Carotid Atherosclerosis ◽  
Family Study ◽  
Leukocyte Telomere Length ◽  
Strong Heart Family Study

scholarly journals Association of Leukocyte Telomere Length With Perceived Physical Fatigability

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 207-208
Author(s):  
Joseph Zmuda ◽  
Joseph Lee ◽  
Lawrence Honig ◽  
Kaare Christensen ◽  
Mary Feitosa ◽  
...  
Keyword(s):  
Telomere Length ◽  
Family Study ◽  
Functional Decline ◽  
Prognostic Indicator ◽  
Health Conditions ◽  
Biological Aging ◽  
Leukocyte Telomere Length ◽  
Potential Marker ◽  
Two Generations

Abstract Leukocyte telomere length (LTL) is a potential marker of biological aging, but its relationship to fatigability, a prognostic indicator of phenotypic aging (e.g., functional decline) is unknown. We hypothesized shorter LTL would predict greater perceived physical fatigability. Two generations of participants (N=1,997; 309 probands, 1,688 offspring) were from the Long Life Family Study (age=73.7±10.4, range 60-108, 54.4% women). LTL was assayed at baseline and 8.0±1.1 years later perceived physical fatigability was measured using the validated, self-administered 10-item Pittsburgh Fatigability Scale (PFS, 0-50, higher scores=greater fatigability). Prevalence of greater physical fatigability (PFS scores≥15) was 41.9%. Using multivariate linear regression, one kilobase pair shorter LTL predicted higher PFS Physical scores (β=0.9, p=0.025), adjusted for family relatedness, generation (indicator for age), field center, follow-up time, sex, and follow-up body mass index, physical activity, health conditions. LTL, a promising marker of future fatigability, may allow for early identification of those at-risk for deleterious aging.

scholarly journals Aortic plaques in patients with atrial fibrillation: an often-forgotten risk factor for thromboembolism

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
A.F Esteves ◽  
L Parreira ◽  
M Fonseca ◽  
J.M Farinha ◽  
J Ferreira ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Risk Factors ◽  
Atrial Fibrillation ◽  
Type 2 Diabetes ◽  
P Value ◽  
Af Ablation ◽  
Aortic Plaques ◽  
Af Recurrence

Abstract Background CHA2DS2-VASc risk score is the main determinant for maintaining anticoagulation after atrial fibrillation (AF) ablation, irrespective of the procedure outcome. The presence of aortic plaques is included in the score, but isn't regularly assessed previously to AF ablation. This way, risk factors for coronary artery disease (CAD) other than arterial hypertension and diabetes mellitus may influence stroke risk in patients with AF, albeit not being included in the CHA2DS2-VASc score. Purpose We sought to evaluate the prevalence of aortic plaques diagnosed during transesophageal echocardiography (TOE) in patients submitted to AF ablation and to assess its determinants and clinical impact on the CHA2DS2-VASc score. Methods Retrospective study of patients submitted to AF ablation that performed TOE prior to the procedure, with assessment of aortic plaques. CHA2DS2-VASc risk score was evaluated in the pre-ablation patient evaluation and reassessed after TOE. Demographic, clinical and echocardiographic data, including cardiovascular risk factors, were analyzed. We assessed AF recurrence rate, cerebrovascular events and death during follow-up. Results 120 patients were submitted to TOE prior to AF ablation from November 2015 to December 2020, mean age 66.6 (±9.55) years, 48% male. In 30 (25%) patients aortic plaques were identified in TOE. Mean CHA2DS2-VASc was 2.2 (±1.47) in pre-ablation evaluation and 2.5 (±1.69) post-TOE, increasing in all patients with aortic plaques and prompting beginning of oral anticoagulation in 5 patients. AF was paroxysmal in 74% and persistent in 26% of patients, mean duration of 6.28 (±3.76) years. Arterial hypertension was present in 79 (66%) of patients, type 2 diabetes mellitus in 24 (20%) and dyslipidemia in 67 (56%). 17 (14%) patients had a prior stroke. During a mean follow-up of 30 (±18.3) months, 32 (27%) patients had AF recurrence and 10 (8%) were submitted to redo procedures. 107 (89%) patients remained under oral anticoagulation, stroke occurred in 1 patient and 2 patients died. In univariate analysis, age, type 2 diabetes mellitus and dyslipidemia predicted an increase in CHA2DS2-VASc score after TOE (respectively, OR 1.113, 95% CI 1.041–1.190, p-value 0.002; OR 2.907, 95% CI 1.145–7.379, p-value 0.025; and OR 2.442, 95% CI 1.016–5.868, p-value 0.046). In multivariate analysis, age is the only independent predictor of increased CHA2DS2-VASc score after TOE (OR 1.095, 95% CI 1.013–1.185, p-value 0.023). No risk factor for CAD was independently associated with the presence of aortic plaques (Table 1). Conclusion In this population, single CAD risk factors were not independent predictors of aortic plaques. If TOE had not been performed prior to AF ablation, 25% of patients would have had an underestimated CHA2DS2-VASc score and would be off anticoagulation after the procedure, unprotected from thromboembolic events. FUNDunding Acknowledgement Type of funding sources: None. Table 1

73Hemoglobin a1c levels and the risk of ischemic stroke and mortality in individuals with diabetes mellitus and atrial fibrillation

EP Europace ◽  
2020 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
L Kezerle ◽  
M A Tsadok ◽  
A Akriv ◽  
B Feldman ◽  
M Leventer-Roberts ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Risk Factors ◽  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Dependent Manner ◽  
Historical Cohort ◽  
Increased Risk ◽  
Dose Dependent ◽  
Hba1c Levels

Abstract Funding Acknowledgements Pfizer Israel Background Diabetes mellitus (DM) is associated with increased risk of embolic complications in non-valvular atrial fibrillation (NVAF). Whether the risk of stroke in AF patients remains the same among the wide spectrum of disease is yet to be determined. Aim Among individuals with AF and DM, to assess the incidence rates and risk of ischemic stroke and mortality by baseline HbA1C levels. Methods We conducted a prospective, historical cohort study using the Clalit Health Services (CHS) electronic medical records database. The study population included all CHS members ≥ 21 years old, with a first diagnosis of NVAF between January 1, 2010 to December 31, 2016 and a minimal follow-up period of 1 year. Among those patients identified as diabetics, we compared three groups of patients according to HBA1C levels at the time of AF diagnosis: &lt;7.0%, between 7-9% and ≥ 9%. Results A total of 44,451 cases were identified. The median age was 75 years (IQR 65-83) and 52.5% were women. During a mean follow up of 38 months, the incidence of stroke per 100 person-years in the three study groups was: 1.9 in patients with HBA1C &lt;7%, 2.37 in the intermediary group and 2.72 in those with HBA1C &gt;9%. In both univariate and multivariate analyses, higher levels of HBA1C were associated with an increased risk of stroke compared with a dose-dependent response when compared to individuals with HBA1C &lt;7% (Adjusted Hazard Ratio (AHR) = 1.32 {95% CI 1.12-1.55}for levels between 7-9% and AHR 1.64 {95% CI 1.28-2.09}) even after adjusting for CHA2DS2-VASC individual risk factors and use of oral anti-coagulants. The risk for overall mortality did not differ significantly between groups, with a slight elevation in the HBA1C &gt;9% group after adjusted analysis {aHR = 1.17 (1.07- 1.28)} Conclusion: In this observational cohort of patients with incident newly diagnosed nonvalvular atrial fibrillation, HBA1C levels were associated with an increased risk of stroke in a dose-dependent manner even after accounting for other recognized risk factors for stroke in this population. Abstract Figure. Kaplan-Meier for stroke-free survival

scholarly journals QTL mapping of leukocyte telomere length in American Indians: The Strong Heart Family Study

Aging ◽  
2013 ◽  
Vol 5 (9) ◽  
pp. 704-716 ◽  
Author(s):  
Yun Zhu ◽  
V. Saroja Voruganti ◽  
Jue Lin ◽  
Tet Matsuguchi ◽  
Elizabeth Blackburn ◽  
...  
Keyword(s):  
Qtl Mapping ◽  
Telomere Length ◽  
American Indians ◽  
Family Study ◽  
Leukocyte Telomere Length ◽  
Strong Heart Family Study

Abstract P276: Metabolic Profiles of Biological Aging in American Indians: The Strong Heart Family Study

Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Yun Zhu ◽  
Jiang He ◽  
Jue Lin ◽  
Tet Matsuguchi ◽  
Elizabeth Blackburn ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Telomere Length ◽  
American Indians ◽  
Multiple Testing ◽  
Family Study ◽  
Biological Aging ◽  
Metabolic Profiles ◽  
Leukocyte Telomere Length ◽  
Age Related ◽  
Strong Heart Family Study

Background: Telomere length is an emerging biomarker for cellular senescence or biological aging. Short leukocyte telomere length (LTL) has been associated with a wide range of age-related metabolic disorders such as diabetes and cardiovascular disease. Telomere attrition induces profound metabolic dysfunction in animal models, but no study has examined the metabolic profiles of biological aging assessed by telomere length in human. Objective: To identify metabolic profiles of leukocyte telomere length in American Indians participating in the Strong Heart Family Study (SHFS, 2001-2003). Methods: This study included 432 SHFS participants free of cardiovascular disease and type 2 diabetes. LTL was measured by quantitative polymerase chain reaction (qPCR). Plasma metabolites were detected using an untargeted metabolomics approach by high-resolution liquid chromatography-mass spectrometry (LC/MS). The association of leukocyte telomere length with concentration of each metabolite was examined using generalized estimating equation (GEE), adjusting for age, sex, study center, body mass index, fasting glucose and fasting insulin. Multiple testing was corrected by Bonferroni correction (significance level 2.8х10-6). Results: After adjusting for covariates and multiple testing, three metabolites including cytosine, selenophosphate and pentyl propanoate, were significantly associated with LTL. Of these, cytosine was positively associated with LTL (β=0.0476, 95% CI, 0.0474 to 0.0478, P=1.90х10-7), and selenophosphate (β =-0.1522, 95% CI, -0.1525 to -0.1519, P=2.48х10-8) and pentyl propanoate (β =-0.0644, 95% CI, -0.0683 to -0.0606, P=1.08х10-8) were negatively associated with LTL. Multivariate analysis demonstrated that participants with longer (top telomere tertile) and shorter (bottom telomere tertile) LTL can be clearly separated by partial least square discriminant analysis (PLS-DA) using these three metabolites. Multiple unknown compounds were also independently associated with LTL. Conclusions: This study, for the first time, identifies metabolites and metabolic profiles associated with interindividual variability in leukocyte telomere length, independent of potential confounders. Our findings provide novel insights into understanding of telomere biology and metabolic mechanisms underlying age-related disorders.

Sign in / Sign up

Export Citation Format

Share Document