Abstract 138: Procollagen I Carboxyterminal Propeptide Levels in Friedreich Ataxia and Its Relation to Subclinical Myocardial Disease
Background: Friedreich ataxia (FA) is the most common recessive hereditary ataxia. Triplet expansion (GAA) of the frataxin gene leads to intramitochondrial iron accumulation, and cardiomyopathy is the leading cause of death in FA. Histopathologic analysis of autopsy hearts has shown myocardial fibrosis and concentric left ventricular (LV) thickening, which our group has previously shown in vivo in FA patients using cardiac magnetic resonance with late gadolinium enhancement (LGE-CMR). Procollagen I carboxyterminal propeptide (PICP) is a serum marker of collagen synthesis, suggesting potential utility as a biomarker of myocardial fibrosis and remodeling. Objectives: The aims of this work were to 1) determine PICP levels in FA patients compared to similar-aged healthy controls, 2) evaluate PICP levels relative to GAA repeat length, 3) evaluate PICP in the context of cardiac remodeling and 4) compare serum PICP levels to presence or absence of fibrosis by LGE-CMR.
Methods: 30 FA patients (34.2±11.8 years) underwent measurement of serum PICP using sandwich ELISA as well as CMR examination with cine and LGE acquisitions. Southern blot analysis was performed to measure GAA repeats, recording the minimum of 2 values for each FA patient. 5 healthy volunteers (37.6±8.4 years) served as controls for PICP measurement. Cine images were analyzed at end-diastole to compute relative wall thickness (RWT), a marker of concentric remodeling.
Results: PICP values were markedly elevated in FA patients compared to normal controls (1034±76 vs. 657±89 ng/mL, p=0.004). Minimum GAA repeat length was moderately correlated with greater RWT (r=0.40, p=0.041) but did not predict PICP level. Higher PICP level modestly predicted worse concentric remodeling (r=0.39, p=0.033). However, PICP did not distinguish between 15 patients with evident myocardial fibrosis by LGE vs. 15 LGE-negative FA patients (1042±128 vs 1027±87 ng/mL, p=0.925).
Conclusions: PICP, a serum marker of collagen synthesis, is significantly elevated in FA patients with higher values indicating adverse LV remodeling. PICP may provide complementary information to direct myocardial fibrosis imaging, and warrants further evaluation as a biomarker of disease severity and treatment response.
- © 2012 by American Heart Association, Inc.