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Dynamics of biomarkers in relation to aging and mortality.

ABSTRACT: Contemporary longitudinal studies collect repeated measurements of biomarkers allowing one to analyze their dynamics in relation to mortality, morbidity, or other health-related outcomes. Rich and diverse data collected in such studies provide opportunities to investigate how various socio-economic, demographic, behavioral and other variables can interact with biological and genetic factors to produce differential rates of aging in individuals. In this paper, we review some recent publications investigating dynamics of biomarkers in relation to mortality, which use single biomarkers as well as cumulative measures combining information from multiple biomarkers. We also discuss the analytical approach, the stochastic process models, which conceptualizes several aging-related mechanisms in the structure of the model and allows evaluating "hidden" characteristics of aging-related changes indirectly from available longitudinal data on biomarkers and follow-up on mortality or onset of diseases taking into account other relevant factors (both genetic and non-genetic). We also discuss an extension of the approach, which considers ranges of "optimal values" of biomarkers rather than a single optimal value as in the original model. We discuss practical applications of the approach to single biomarkers and cumulative measures highlighting that the potential of applications to cumulative measures is still largely underused.

SUBMITTER: Arbeev KG

PROVIDER: S-EPMC4899173 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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Dynamics of biomarkers in relation to aging and mortality.

Arbeev Konstantin G KG Ukraintseva Svetlana V SV Yashin Anatoliy I AI

Mechanisms of ageing and development 20160429

Contemporary longitudinal studies collect repeated measurements of biomarkers allowing one to analyze their dynamics in relation to mortality, morbidity, or other health-related outcomes. Rich and diverse data collected in such studies provide opportunities to investigate how various socio-economic, demographic, behavioral and other variables can interact with biological and genetic factors to produce differential rates of aging in individuals. In this paper, we review some recent publications i ...[more]

PMID: 27138087

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Project description:BackgroundThe links between chronic kidney disease (CKD) and the high burden of cardiovascular disease remain unclear. We aimed to explore the association between selected inflammatory and angiogenic biomarkers, kidney function and long-term outcome in patients with an acute coronary syndrome (ACS) and to test the hypothesis that CKD status modifies this association.MethodsA total of 1293 ACS patients hospitalized between 2008 and 2015 were followed until 31 December 2017. Plasma was collected on days 1-3 after admission. A total of 13 biomarkers were a priori identified and analysed with two proteomic methods, proximity extension assay or multiple reaction monitoring mass spectrometry. Boxplots and multiple linear regression models were used to study associations between biomarkers and kidney function and adjusted standardized Cox regression with an interaction term for CKD was used to assess whether CKD modified the association between biomarkers and major adverse cardiovascular events and death (MACE+).ResultsThe concentrations of nine biomarkers-endothelial cell-specific molecule-1 (ESM-1), fibroblast growth factor 23 (FGF-23), fractalkine (CX3CL1), interleukin-1 receptor antagonist (IL-1RA), interleukin-18 (IL-18), monocyte chemotactic protein-1 (MCP-1), placenta growth factor (PlGF), transmembrane immunoglobulin 1 (TIM-1) and vascular endothelial growth factor A (VEGFA)-were inversely associated with kidney function. ESM-1, FGF-23 and TIM-1 showed associations with MACE+. Only FGF23 remained independently associated after adjustment for the other biomarkers (hazard ratio per standard deviation increase 1.34; 95% Bonferroni corrected confidence interval 1.19-1.50). None of the biomarkers showed an interaction with CKD.ConclusionsThe concentrations of 9 of the 13 prespecified inflammatory and angiogenic proteomic biomarkers increased when kidney function declined. Only FGF-23 demonstrated an independent association with MACE+, and this association was not modified by CKD status. These findings further support FGF-23 as an independent prognostic marker in ACS patients with and without CKD.

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Dynamics of biomarkers in relation to aging and mortality.

Publications

Dynamics of biomarkers in relation to aging and mortality.

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