Abstract
Background—Because systemic inflammation and endothelial dysfunction lead to heart failure with preserved ejection fraction, we characterized plasma levels of inflammatory and cardiac remodeling biomarkers in patients with Fabry disease (FD). Methods and Results-—Plasma biomarkers were studied in multicenter cohorts of patients with FD (n=68) and healthy controls (n=40). Plasma levels of the following markers of inflammation and cardiac remodeling were determined: tumor necrosis factor (TNF), TNF receptor 1 (TNFR1) and 2 (TNFR2), interleukin-6, matrix metalloprotease-2 (MMP-2), MMP-8, MMP-9, galectin-1, galectin-3, B-type natriuretic peptide (BNP), midregional pro–atrial natriuretic peptide (MR-proANP), and globotriaosylsphingosine. Clinical profile, cardiac magnetic resonance imaging, and echocardiogram were reviewed and correlated with biomarkers. Patients with FD had elevated plasma levels of BNP, MR-proANP, MMP-2, MMP-9, TNF, TNFR1, TNFR2, interleukin-6, galectin-1, globotriaosylsphingosine, and analogues. Plasma TNFR2, TNF, interleukin-6, MMP-2, and globotriaosylsphingosine were elevated in FD patients with left ventricular hypertrophy, whereas diastolic dysfunction correlated with higher BNP, MR-proANP, and MMP-2 levels. Patients with late gadolinium enhancement on cardiac magnetic resonance imaging had greater levels of BNP, MR-proANP, TNFR1, TNFR2, and MMP-2. Plasma BNP, MR-proANP, MMP-2, MMP-8, TNF, TNFR1, TNFR2, galectin-1, and galectin-3 were elevated in patients with renal dysfunction. Patients undergoing enzyme replacement therapy who have more severe disease had higher MMP-2, TNF, TNFR1, TNFR2, and globotriaosylsphingosine analogue levels. Conclusions-—Inflammatory and cardiac remodeling biomarkers are elevated in FD patients and correlate with disease progression. These features are consistent with a phenotype dominated by heart failure with preserved ejection fraction and suggest a key pathogenic role of systemic inflammation in FD.
| Original language | English |
|---|---|
| Article number | e009098 |
| Journal | Journal of the American Heart Association |
| Volume | 7 |
| Issue number | 21 |
| DOIs | |
| Publication status | Published - Nov 1 2018 |
Bibliographical note
Funding Information:Yogasundaram is supported by an Alberta Innovates Health Solutions (AIHS) Summer Studentship (Grant No. 201300994). Oudit is supported by operating grants from the Canadian Institute of Health Research (Grant No. 205413) and the Heart and Stroke Foundation of Canada (Grant No. 88453).
Funding Information:
Khan is president of Metabolics and Genetics in Calgary (MAGIC) Clinic Ltd, is a member of the International Collaborate Gaucher Group (ICGG) and Pompe Registry (both sponsored by Sanofi-Genzyme), is a recipient of a Revenue Distribution Agreement with the University Health Network related to Fabry Gene Therapy, and has received travel grants, speaker fees, research grants, and unrestricted educational funds from Sanofi-Gen-zyme and Shire. Auray-Blais has received research funding, honoraria, and travel funds from Amicus Therapeutics, BioMarin Pharmaceuticals Inc, Sanofi-Genzyme, and Shire. West has received research funding, honoraria, and/or consultant fees from Alexion, Amicus Therapeutics, Excelsior Pharma, Idorsia, Sanofi-Genzyme, Glaxo Smith Kline Inc, Shire Inc, and Sumitomo Pharma. Oudit has received speaker honoraria and research funding from Sanofi-Genzyme and Shire Inc. The remaining authors have no disclosures to report.
Publisher Copyright:
© 2018 The Authors.
ASJC Scopus Subject Areas
- Cardiology and Cardiovascular Medicine