Abstract
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.
Highlights
Aging is one of the main risk factors for cardiovascular disease, resulting in a progressive organ and cell decline [1,2]
A total of 52% had a previous myocardial infarction (MI), and a previous revascularization was performed in 14% of the patients
When the correlation between leucocyte telomere length (LTL) and mtDNA4977 deletion in two different age groups was analyzed, the results remained significant across the subgroups (Figure S1 in Supplemental Materials)
Summary
Aging is one of the main risk factors for cardiovascular disease, resulting in a progressive organ and cell decline [1,2]. At an individual level, genetic and environmental factors may impact the biological aging process, resulting in a significant heterogeneity among subjects with the same age [3]. Chronological age alone may be a poor indicator of disease risk and mortality compared with biological age, which assesses the physiological state of an organism, resulting from the cumulative burden of endogenous and exogenous stressors, such as oxidative stress, inflammation, and lifestyle factors [3,4]. A series of environmental stressors can accelerate telomere shortening [8,9]
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