Abstract 17850: Elevated Inflammatory Plasma Biomarkers in Patients With Anderson-Fabry Disease: A Critical Link to Heart Failure With Preserved Ejection Fraction
Introduction: Anderson-Fabry disease (AFD) is a multisystem X-linked recessive lysosomal storage disorder with an estimated global prevalence of 1 in 3000 individuals. AFD is characterized by accumulation of sphingolipid in tissues and cardiomyopathy is the most common cause of death.
Hypothesis: As systemic inflammation and endothelial dysfunction leading to HFpEF are features of AFD, patients with AFD will have elevated plasma levels of inflammatory and cardiac remodelling biomarkers.
Methods: Plasma biomarkers were studied in multicentre cohorts of AFD (n=68) and healthy controls (n=40). Plasma levels of the following markers of inflammation and cardiac remodeling were determined: tumour necrosis factor (TNF), TNF receptors 1 (TNFR1) and 2 (TNFR2), interleukin-6 (IL-6), matrix metalloprotease-2 (MMP-2), MMP-8, MMP-9, Galectin-1, Galectin-3, B-type natriuretic peptide (BNP), mid-regional pro-atrial natriuretic peptide (MR-proANP), and globotriaosylsphingosine (Lyso-Gb3). Clinical profile and cardiac MRI were reviewed and correlated to biomarkers.
Results: Relative to healthy controls, patients with AFD had significantly elevated plasma levels of BNP, MR-proANP, MMP-2, MMP-9, TNF, TNFR1, TNFR2, IL-6, Galectin-1, and Lyso-Gb3 (p=0.006, p=0.013, p=0.027, p<0.001, p=0.008, p=0.003, p<0.001, p=0.021, p<0.001, and p<0.001, respectively). Receiver operator characteristic curves for Lyso-Gb3 and TNFR2 versus a diagnosis of AFD demonstrated C-statistics of 0.998 and 0.785, respectively. Plasma TNF and Lyso-Gb3 were significantly elevated in AFD patients with left-ventricular hypertrophy. Plasma BNP, MR-proANP, MMP-2, MMP-8, TNF, TNFR1, TNFR2, Galectin-1, and Galectin-3 were elevated in patients with renal dysfunction. In addition, patients undergoing enzyme replacement therapy (ERT), who typically have more severe disease, had higher MMP-2, TNF, TNFR1, TNFR2, and Lyso-Gb3 levels than non-ERT AFD patients.
Conclusions: Inflammatory and cardiac remodeling biomarkers are elevated in AFD patients and are also elevated with surrogates of disease progression. These features are consistent with a phenotype dominated by HF with preserved ejection fraction and suggest a key pathogenic role of systemic inflammation in AFD.
Author Disclosures: H. Yogasundaram: None. B.N. Putko: None. M. Boutin: None. R. Basu: None. M.E. Irwin: None. A. Khan: None. C. Auray-Blais: None. M.L. West: None. G.Y. Oudit: None.
- © 2016 by American Heart Association, Inc.