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Open AccessArticle

Independent and Combined Effects of Telomere Shortening and mtDNA4977 Deletion on Long-term Outcomes of Patients with Coronary Artery Disease

CNR Institute of Clinical Physiology, Via Moruzzi 1, 56124 Pisa, Italy
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Int. J. Mol. Sci. 2019, 20(21), 5508; https://doi.org/10.3390/ijms20215508
Received: 19 September 2019 / Revised: 30 October 2019 / Accepted: 1 November 2019 / Published: 5 November 2019
(This article belongs to the Special Issue Targeting Mitochondria in Aging and Disease)
Aging is one of the main risk factors for cardiovascular disease, resulting in a progressive organ and cell decline. This study evaluated a possible joint impact of two emerging hallmarks of aging, leucocyte telomere length (LTL) and common mitochondrial DNA deletion (mtDNA4977), on major adverse cardiovascular events (MACEs) and all-cause mortality in patients with coronary artery disease (CAD). We studied 770 patients (673 males, 64.8 ± 8.3 years) with known or suspected stable CAD. LTL and mtDNA4977 deletion were assessed in peripheral blood using qRT-PCR. During a median follow-up of 5.4 ± 1.2 years, MACEs were 140 while 86 deaths were recorded. After adjustments for confounding risk factors, short LTLs and high mtDNA4977 deletion levels acted independently as predictors of MACEs (HR: 2.2, 95% CI: 1.2–3.9, p = 0.01 and HR: 1.7, 95% CI: 1.1–2.9, p = 0.04; respectively) and all-cause mortality events (HR: 2.1, 95% CI: 1.1–4.6, p = 0.04 and HR: 2.3, 95% CI: 1.1–4.9, p = 0.02; respectively). Patients with both short LTLs and high mtDNA4977 deletion levels had an increased risk for MACEs (HR: 4.3; 95% CI: 1.9–9.6; p = 0.0006) and all-cause mortality (HR: 6.0; 95% CI: 2.0–18.4; p = 0.001). The addition of mtDNA4977 deletion to a clinical reference model was associated with a significant net reclassification improvement (NRI = 0.18, p = 0.01). Short LTL and high mtDNA4977 deletion showed independent and joint predictive value on adverse cardiovascular outcomes and all-cause mortality in patients with CAD. These findings strongly support the importance of evaluating biomarkers of physiological/biological age, which can predict disease risk and mortality more accurately than chronological age. View Full-Text
Keywords: major adverse cardiac events; all-cause mortality; leucocyte telomere length; mtDNA4977 common deletion; coronary artery disease major adverse cardiac events; all-cause mortality; leucocyte telomere length; mtDNA4977 common deletion; coronary artery disease
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MDPI and ACS Style

Vecoli, C.; Borghini, A.; Pulignani, S.; Mercuri, A.; Turchi, S.; Picano, E.; Andreassi, M.G. Independent and Combined Effects of Telomere Shortening and mtDNA4977 Deletion on Long-term Outcomes of Patients with Coronary Artery Disease. Int. J. Mol. Sci. 2019, 20, 5508. https://doi.org/10.3390/ijms20215508

AMA Style

Vecoli C, Borghini A, Pulignani S, Mercuri A, Turchi S, Picano E, Andreassi MG. Independent and Combined Effects of Telomere Shortening and mtDNA4977 Deletion on Long-term Outcomes of Patients with Coronary Artery Disease. International Journal of Molecular Sciences. 2019; 20(21):5508. https://doi.org/10.3390/ijms20215508

Chicago/Turabian Style

Vecoli, Cecilia; Borghini, Andrea; Pulignani, Silvia; Mercuri, Antonella; Turchi, Stefano; Picano, Eugenio; Andreassi, Maria G. 2019. "Independent and Combined Effects of Telomere Shortening and mtDNA4977 Deletion on Long-term Outcomes of Patients with Coronary Artery Disease" Int. J. Mol. Sci. 20, no. 21: 5508. https://doi.org/10.3390/ijms20215508

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