Telomere length is associated with atrial fibrillation. (25th November 2020)

• Record Type: Journal Article
• Authors: Sinner, M; Kupka, D; Wilfert, W; Waldenberger, M; Peters, A; Holdt, L; Kaab, S
• Is Part Of: European heart journal. Volume 41:(2020)Supplement 2
• Publication Date: 2020-11-25
• Subjects: Atrial Fibrillation - Epidemiology, Prognosis, Outcome; Cardiology -- Periodicals; Heart -- Diseases -- Periodicals; 616.12005
• DOI: 10.1093/ehjci/ehaa946.0499
• Languages: English
• ISSNs: 0195-668X

Abstract

Abstract: Background: Atrial Fibrillation (AF) is common and is caused and predisposed to by a complex pathophysiology. Aging is among the most important risk factors for AF. Yet, some individuals develop AF in early years, whereas elderly individuals may remain free of AF. Aside from measurable concomitant risks, we hypothesized that a pathophysiologically relevant biological age exists, which outweighs a patient's calendar age. Telomere length is a measurable marker of age, which might reflect biological age. AF and telomere length have previously been associated, but results remained controversial. Here, we tested the relation between AF and telomere length in a well-characterized and so far largest cohort. Methods: Since 2005, we enrolled 2475 patients with AF from the prospective AFLMU cohort, preferentially if they developed AF before age 65 years, and 3077 control individuals free of AF from the community-based KORA Study between 2006–08. All participants received a detailed clinical characterization, an electrocardiogram, and a blood draw for biomarker analyses. In all participants, we determined telomere length using a qPCR-based method. In a 384 well format, we employed a multiplex TaqMan assay to determine both telomere length and the single copy gene 36B4. Telomere length was expressed by the delta-CT method and was reformatted to have lower CT values indicate shorter telomere length. We compared telomere length between cases and controls using multi-variably corrected logistic regression models. Results: Our cohort's mean age was 58 years in AFLMU and 56 years in KORA F4. Men were enrolled more commonly, with 72.3% in AFLMU and 51.7% in KORA F4. For consistency with available information, we confirmed that telomere length is continuously decreasing with age and that men have shorter telomere length compared to women. As a main result we found that AF patients have significantly shorter telomere length compared to controls (controls: telomere length 13, 10 [12.60, 13.63] versus AF: 9.81 [5.98, 13.1], p<0, 001). This relation remained significant following multi-variable adjustment for sex, body mass index, hypertension, and diabetes. The odds ratio per unit longer telomer length was 0.77 [95% confidence interval 0.74–0.77], p<0.001. We also calculated a propensity-score matched model of cases with and without AF confirming our main results (controls: telomere length 13.21 [11.65, 13.67] versus AF: 9.03 [5.35, 12.54], p<0.001). The multi-variable adjusted model revealed an odds ratio of 0, 75 [95% confidence interval 0.73–0.76], p<0.001. Conclusion: AF is significantly associated with telomere length in one of the largest cohorts to date. Assessment of telomere length may adjudicate patients with AF due to premature biological aging. The underlying reasons for such premature aging remain to be identified. Funding Acknowledgement: Type of funding source: Public grant(s) – EU funding. Main funding source(s): European Commission - Horizon 2020