Abstract 17709: Cellular Aging as Reflected by Leukocyte Telomere Length and Incident Heart Failure Risk in Older Adults

Abstract

Background: Inter-individual differences in cellular aging could affect susceptibility to heart failure (HF). We aimed to determine if mean leucocyte telomere length (TL) predicts development of HF in older adults.

Methods: We examined 2616 participants with available measurement of TL and without HF at baseline enrolled in the Health, Aging and Body Composition Study, a population-based cohort study of well-functioning individuals aged 70-79 years. Measurement of TL was performed by quantitative polymerase chain reaction. Participants were divided into three groups based on tertiles of TL and were compared for HF risk, controlling for clinical risk factors. Leukocyte DNA was genotyped for SNPs in the telomerase RNA component (TERC) region (rs1102, rs1172, and rs2293507) that were previously associated with TL through genome-wide association studies; these alleles were further assessed for association with risk for HF. Evidence for effect modification by relevant clinical characteristics were tested.

Results: Mean age of the study population was 74±3 years; 48% were men and 59% were white. During a median follow up of 11.4 (7.1-11.7) years, 429 participants developed HF. Older participants and those with a higher body mass index had lower TL. Telomerase length was not associated with risk for HF (hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.65, 1.06; and HR 1.00, 95%CI 0.8, 1.27, for middle and low thirds of TL compared to the highest, respectively). The HR per standard deviation change in TL was 1.02 (0.92, 1.12) in adjusted models. Results were comparable across subgroups defined by age, gender, race, and history of diabetes mellitus or cardiovascular disease at baseline. Carriers of the minor allele at the TERC SNP rs2293507 had significantly shorter telomeres; however, this allele was not associated with HF risk (HR 1.07, 95% CI 0.9, 1.27).

Conclusion: In older adults, TL is not associated with risk of HF. These results were consistent across gender and race. Findings from common genetic variation at TERC associated with TL further suggest that TL may not be implicated in development of HF.