Diastolic Left Ventricular Function in Relation to Urinary and Serum Collagen Biomarkers in a General Population

Zhen-Yu Zhang, Susana Ravassa, Wen-Yi Yang, Thibault Petit, Martin Pejchinovski, Petra Zuerbig, Begona Lopez, Fang-Fei Wei, Claudia Pontillo, Lutgarde Thijs, Lotte Jacobs, Arantxa Gonzalez, Thomas Koeck, Christian Delles, Jens-Uwe Voigt, Peter Verhamme, Tatiana Kuznetsova, Javier Diez, Harald Mischak, Jan A. Staessen*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

17 Citations (Web of Science)

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
Original languageEnglish
Article numbere0167582
Pages (from-to)1-17
JournalPLOS ONE
Volume11
Issue number12
DOIs
Publication statusPublished - 13 Dec 2016

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