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Comparative validation of an epigenetic mortality risk score with three aging biomarkers for predicting mortality risks among older adult males.

ABSTRACT: BACKGROUND:A 'mortality risk score' (MS) based on ten prominent mortality-related cytosine-phosphate-guanine (CpG) sites was previously associated with all-cause mortality, but has not been verified externally. We aimed to validate the association of MS with mortality and to compare MS with three aging biomarkers: telomere length (TL), DNA methylation age (DNAmAge) and phenotypic age (DNAmPhenoAge) to explore whether MS can serve as a reliable measure of biological aging and mortality. METHODS:Among 534 males aged 55-85?years from the US Normative Aging Study, the MS, DNAmAge and DNAmPhenoAge were derived from blood DNA methylation profiles from the Illumina HumanMethylation450 BeadChip, and TL was measured by quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS:A total of 147 participants died during a median follow-up of 9.4?years. The MS showed strong associations with all-cause, cardiovascular disease (CVD) and cancer mortality. After controlling for all potential covariates, participants with high MS (>5 CpG sites with aberrant methylation) had almost 4-fold all-cause mortality (hazard ratio: 3.84, 95% confidence interval: 1.92-7.67) compared with participants with a low MS (0-1 CpG site with aberrant methylation). Similar patterns were observed with respect to CVD and cancer mortality. MS was associated with TL and DNAmPhenoAge acceleration but not with DNAmAge acceleration. Although the MS and DNAmPhenoAge acceleration were independently associated with all-cause mortality, the former exhibited a higher predictive accuracy of mortality than the latter. CONCLUSIONS:MS has the potential to be a prominent predictor of mortality that could enhance survival prediction in clinical settings.

SUBMITTER: Gao X

PROVIDER: S-EPMC6929530 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Comparative validation of an epigenetic mortality risk score with three aging biomarkers for predicting mortality risks among older adult males.

Gao Xu X Colicino Elena E Shen Jincheng J Just Allan C AC Nwanaji-Enwerem Jamaji C JC Wang Cuicui C Coull Brent B Lin Xihong X Vokonas Pantel P Zheng Yinan Y Hou Lifang L Schwartz Joel J Baccarelli Andrea A AA

International journal of epidemiology 20191201 6

<h4>Background</h4>A 'mortality risk score' (MS) based on ten prominent mortality-related cytosine-phosphate-guanine (CpG) sites was previously associated with all-cause mortality, but has not been verified externally. We aimed to validate the association of MS with mortality and to compare MS with three aging biomarkers: telomere length (TL), DNA methylation age (DNAmAge) and phenotypic age (DNAmPhenoAge) to explore whether MS can serve as a reliable measure of biological aging and mortality.<h ...[more]

PMID: 31038702

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Project description:ObjectiveOlder emergency department (ED) patients are at high risk of mortality, and it is important to predict which patients are at highest risk. Biomarkers such as lactate, high-sensitivity cardiac troponin T (hs-cTnT), N-terminal pro-B-type natriuretic peptide (NT-proBNP), D-dimer and procalcitonin may be able to identify those at risk. We aimed to assess the discriminatory value of these biomarkers for 30-day mortality and other adverse outcomes.DesignProspective cohort study. On arrival of patients, five biomarkers were measured. Area under the curves (AUCs) and interval likelihood ratios (LRs) were calculated to investigate the discriminatory value of the biomarkers.SettingED in the Netherlands.ParticipantsOlder (≥65 years) medical ED patients, referred for internal medicine or gastroenterology.Primary and secondary outcome measures30-day mortality was the primary outcome measure, while other adverse outcomes (intensive care unit/medium care unit admission, prolonged length of hospital stay, loss of independent living and unplanned readmission) were the composite secondary outcome measure.ResultsThe median age of the 450 included patients was 79 years (IQR 73-85). In total, 51 (11.3%) patients died within 30 days. The AUCs of all biomarkers for prediction of mortality were sufficient to good, with the highest AUC of 0.73 for hs-cTnT and NT-proBNP. Only for the highest lactate values, the LR was high enough (29.0) to be applicable for clinical decision making, but this applied to a minority of patients. The AUC for the composite secondary outcome (intensive and medium care admission, length of hospital stay >7 days, loss of independent living and unplanned readmission within 30 days) was lower, ranging between 0.58 and 0.67.ConclusionsAlthough all five biomarkers predict 30-day mortality in older medical ED patients, their individual discriminatory value was not high enough to contribute to clinical decision making.Trial registration numberNCT02946398; Results.

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Comparative validation of an epigenetic mortality risk score with three aging biomarkers for predicting mortality risks among older adult males.

Publications

Comparative validation of an epigenetic mortality risk score with three aging biomarkers for predicting mortality risks among older adult males.

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