Value of soluble Urokinase plasminogen activator receptor over age as a biomarker of impaired myocardial relaxation

Koh, Angela S.; Velmurugan, Bhaarathy; Gao, Fei; Tan, Ru San; Wong, Jane Cq; Teo, Louis; Keng, Bryan M.H.; Chua, Serene Jm; Yuan, Jian‐Min; Koh, Woon‐Puay; Cheung, Christine

doi:10.1186/s12877-017-0668-0

Cited by 4 publications

(5 citation statements)

References 15 publications

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“…Our observations regarding sUPAR are novel in the context of cardiovascular aging, expanding our previous observations which associated impairments in myocardial relaxation in the LV [18] with increases in sUPAR level. In contrast to hs-CRP [35], sUPAR is considered a marker of low-grade inflammation [36], where it is released by activated immune cells at the sites of inflammation to mediate chemotactic effects [37,38].…”

Section: Discussionsupporting

confidence: 76%

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Left Atrial Phasic Function in Older Adults Is Associated with Fibrotic and Low-Grade Inflammatory Pathways

et al. 2022

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Introduction: Concomitant risk factors challenge the mechanistic understanding of cardiac aging. We determined the degree to which the left atrial function could be distinguished by advanced cardiac magnetic resonance (CMR) imaging in older adults and assessed associations between the left atrial function and the plasma biomarkers related to biological aging and cardiovascular disease [serum monocyte chemoattractant protein-1 (MCP1), matrix metallopeptidase 9 (MMP-9), B-type natriuretic peptides (BNPs), galectin-3 (Gal-3), high-sensitivity cardiac troponin I (hsTn1), high-sensitivity C-reactive protein (hs-CRP), and soluble urokinase plasminogen activator receptor (sUPAR)]. Methods: Among a cross-sectional population-based cohort of older adults, longitudinal LA strain including reservoir strain (εs), conduit strain (εe), and booster strain (εa) as well as peak strain rates (SRs, SRe, SRa) were determined using CMR and studied in association with blood biomarkers. Results: We studied 243 community adults (42.8% female, mean age 70.3 ± 9.5 years). In bivariate analysis, εe and SRe were reduced in gradation with increasing risk factors (all p values <0.0001). Corresponding levels of sUPAR (ng/mL) were quantitatively higher in older adults with <2 risk factors (2.5 ± 1.6 vs. 1.7 ± 1.3, p = 0.0005), in those with ≥2 risk factors (3.3 ± 2.4 vs. 1.7 ± 1.3, p < 0.0001), compared to young adults; including between older adults with ≥2 risk factors and older adults with <2 risk factors (3.3 ± 2.4 vs. 2.5 ± 1.6, p = 0.017). Based on multivariate analysis, sUPAR was significantly associated with both εe (OR 1.52, p = 0.006) and SRe decline (OR 1.5, p = 0.019). The associations between Gal-3 and εe reduction (OR 1.2, p = 0.022) and between BNP and SRe decline were generally weaker (OR 1.03, p = 0.027). The addition of sUPAR to a model consisting of age, risk factors, Gal-3, and BNPs increased the area under the curve of εe from 0.72 to 0.77 (p = 0.015). Conclusion: By advanced CMR imaging, a panel of circulating biomarkers comprising galectin, MMP-9 and sUPAR were associated with left atrial dysfunction in older adults. Higher levels of Gal-3 and MMP-9 may be suggestive of fibrotic mechanisms in left atrial aging while impairments in left atrial strain seen in association with circulating sUPAR may be related to immune activation in the left atrium in response to left atrial remodeling and fibrotic processes.

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Section: Discussionsupporting

confidence: 76%

“…Plasma levels of soluble uPAR were measured using the Human uPAR Quantikine ELISA kit (R&D Systems, cat No. DUP00), according to the manufacturer's assay procedures, as previously described [ 18 ].…”

Section: Methodsmentioning

confidence: 99%

Left Atrial Phasic Function in Older Adults Is Associated with Fibrotic and Low-Grade Inflammatory Pathways

et al. 2022

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“…These observations at the cellular level may account for clinical findings. Levels of soluble urokinase‐type plasminogen activator receptor have been useful for predicting risks of myocardial dysfunction in aged adults 65 . LPC has also been shown to be predictive of ageing phenotypes such as cognitive impairment and gait speed in older adults 66,67 …”

Section: Cardiovascular Ageingmentioning

confidence: 99%

Metabolomics and cardiovascular imaging: a combined approach for cardiovascular ageing

Koh

Kovalik

2021

ESC Heart Failure

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The purpose of this review is to explore how metabolomics can help uncover new biomarkers and mechanisms for cardiovascular ageing. Cardiovascular ageing refers to cardiovascular structural and functional alterations that occur with chronological ageing and that can lead to the development of cardiovascular disease. These alterations, which were previously only detectable on tissue histology or corroborated on blood samples, are now detectable with modern imaging techniques. Despite the emergence of powerful new imaging tools, clinical investigation into cardiovascular ageing is challenging because ageing is a life course phenomenon involving known and unknown risk factors that play out in a dynamic fashion. Metabolomic profiling measures large numbers of metabolites with diverse chemical properties. Metabolomics has the potential to capture changes in biochemistry brought about by pathophysiologic processes as well as by normal ageing. When combined with non-invasive cardiovascular imaging tools, metabolomics can be used to understand pathological consequences of cardiovascular ageing. This review will summarize previous metabolomics and imaging studies in cardiovascular ageing. These methods may be a clinically relevant and novel approach to identify mechanisms of cardiovascular ageing and formulate or personalize treatment strategies.

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“…As previously described [20,22], all participants were examined and interviewed on one study visit by trained study coordinators. Participants completed a standardized questionnaire that included medical history and coronary risk factors.…”

Section: Methodsmentioning

confidence: 99%

N-Terminal pro C-Type Natriuretic Peptide (NTproCNP) and myocardial function in ageing

et al. 2018

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Ageing-related alterations in cardiovascular structure and function are commonly associated with chronic inflammation. A potential blood-based biomarker indicative of a chronic inflammatory state is N-Terminal Pro C-Type Natriuretic Peptide (NTproCNP). We aim to investigate associations between NTproCNP and ageing-related impairments in cardiovascular function. Community-based participants underwent same-day assessment of cardiovascular function and circulating profiles of plasma NTproCNP. Associations between cardiovascular and biomarker profiles were studied in adjusted models including standard covariates. We studied 93 participants (mean age 73 ± 5.3 years, 36 women), of whom 55 (59%) had impaired myocardial relaxation (ratio of peak velocity flow in early diastole E (m/s) to peak velocity flow in late diastole by atrial contraction A (m/s) <0.84). Participants with impaired myocardial relaxation were also found to have lower peak early phase filling velocity (0.6 ± 0.1 vs 0.7 ± 0.1, p < 0.0001) and higher peak atrial phase filling velocity (0.9 ± 0.1 vs 0.7 ± 0.1, p < 0.0001). NTproCNP levelswere significantly lower among participants with impaired myocardial relaxation (16.4% vs 39.5% with NTproCNP ≥ 19, p = 0.012). After multivariable adjustments, NTproCNP was independently associated with impaired myocardial relaxation (OR 2.99, 95%CI 1.12–8.01, p = 0.029). Community elderly adults with myocardial ageing have lower NTproCNP levels compared to those with preserved myocardial function. Given that impaired myocardial relaxation probably represents early changes within the myocardium with ageing, NTproCNP may be useful as an ‘upstream’ biomarker useful for charting myocardial ageing.

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Value of soluble Urokinase plasminogen activator receptor over age as a biomarker of impaired myocardial relaxation

Cited by 4 publications

References 15 publications

Left Atrial Phasic Function in Older Adults Is Associated with Fibrotic and Low-Grade Inflammatory Pathways

Left Atrial Phasic Function in Older Adults Is Associated with Fibrotic and Low-Grade Inflammatory Pathways

Metabolomics and cardiovascular imaging: a combined approach for cardiovascular ageing

N-Terminal pro C-Type Natriuretic Peptide (NTproCNP) and myocardial function in ageing

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