Diastolic left ventricular function in relation to urinary and serum collagen biomarkers in a general population

Zhang, Z.-y. et al. (2016) Diastolic left ventricular function in relation to urinary and serum collagen biomarkers in a general population. PLoS ONE, 11(12), e0167582. (doi: 10.1371/journal.pone.0167582) (PMID:27959898) (PMCID:PMC5154519)

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Abstract

Current knowledge on the pathogenesis of diastolic heart failure predominantly rests on case-control studies involving symptomatic patients with preserved ejection fraction and relying on invasive diagnostic procedures including endomyocardial biopsy. Our objective was to gain insight in serum and urinary biomarkers reflecting collagen turnover and associated with asymptomatic diastolic LV dysfunction. We randomly recruited 782 Flemish (51.3% women; 50.5 years). We assessed diastolic LV function from the early and late diastolic peak velocities of the transmitral blood flow and of the mitral annulus. By sequencing urinary peptides, we identified 70 urinary collagen fragments. In serum, we measured carboxyterminal propeptide of procollagen type 1 (PICP) as marker of collagen I synthesis and tissue inhibitor of matrix metalloproteinase type 1 (TIMP-1), an inhibitor of collagen-degrading enzymes. In multivariable-adjusted analyses with Bonferroni correction, we expressed effect sizes per 1-SD in urinary collagen I (uCI) or collagen III (uCIII) fragments. In relation to uCI fragments, e’ decreased by 0.183 cm/s (95% confidence interval, 0.017 to 0.350; p = 0.025), whereas E/e’ increased by 0.210 (0.067 to 0.353; p = 0.0012). E/e’ decreased with uCIII by 0.168 (0.021 to 0.316; p = 0.018). Based on age-specific echocardiographic criteria, 182 participants (23.3%) had subclinical diastolic LV dysfunction. Partial least squares discriminant analysis contrasting normal vs. diastolic LV dysfunction confirmed the aforementioned associations with the uCI and uCIII fragments. PICP and TIMP-1 increased in relation to uCI (p<0.0001), whereas these serum markers decreased with uCIII (p≤0.0006). Diastolic LV dysfunction was associated with higher levels of TIMP-1 (653 vs. 696 ng/mL; p = 0.013). In a general population, the non-invasively assessed diastolic LV function correlated inversely with uCI and serum markers of collagen I deposition, but positively with uCIII. These observations generalise previous studies in patients to randomly recruited people, in whom diastolic LV function ranged from normal to subclinical impairment, but did not encompass overt diastolic heart failure.

Item Type:Articles
Additional Information:Funding: The European Union (HEALTH-FP7- 278249-EUMASCARA, HEALTH-F7-305507 HOMAGE) and the European Research Council (Advanced Researcher Grant 2011-294713- EPLORE and Proof-of-Concept Grant 713601-Funding: The European Union (HEALTH-FP7- 278249-EUMASCARA, HEALTH-F7-305507 HOMAGE) and the European Research Council (Advanced Researcher Grant 2011-294713- EPLORE and Proof-of-Concept Grant 713601-Funding: The European Union (HEALTH-FP7- 278249-EUMASCARA, HEALTH-F7-305507 HOMAGE) and the European Research Council (Advanced Researcher Grant 2011-294713- EPLORE and Proof-of-Concept Grant 713601-uPROPHET) and the Fonds voor Wetenschappelijk Onderzoek Vlaanderen, Ministry of the Flemish Community, Brussels, Belgium (G.0881.13, G.088013, and 11Z0916N) currently support the Studies Coordinating Centre in Leuven.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Delles, Professor Christian and Mischak, Professor Harald and Pontillo, Ms Claudia
Authors: Zhang, Z.-y., Ravassa, S., Yang, W.-Y., Petit, T., Pejchinovski, M., Zürbig, P., López, B., Wei, F.-F., Pontillo, C., Thijs, L., Jacobs, L., González, A., Koeck, T., Delles, C., Voigt, J.-U., Verhamme, P., Kuznetsova, T., Díez, J., Mischak, H., and Staessen, J. A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:PLoS ONE
Publisher:Public Library of Science
ISSN:1932-6203
ISSN (Online):1932-6203
Published Online:13 December 2016
Copyright Holders:Copyright © 2016 2016 Zhang et al.
First Published:First published in PLoS ONE 11(12):e0167582
Publisher Policy:Reproduced under a creative commons license

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
601881HOMAGE: Heart OMics in AGEingChristian DellesEuropean Commission (EC)305507RI CARDIOVASCULAR & MEDICAL SCIENCES