Abstract 19264: Wnt Inhibitory Factor-1 is Elevated and Predicts Mortality in Symptomatic Aortic Stenosis
Purpose: Calcific aortic stenosis (AS) shares histopathologic features with atherosclerosis, including active calcification and ossification. Wnt inhibitory factor-1 (WIF-1), a secreted Wnt-antagonist, regulates differentiation of bone and cartilage in vitro, but the clinical significance remains unresolved. We therefore sought to investigate a possible role for WIF-1 in AS.
Methods: One hundred and forty five patients with symptomatic AS, evaluated for aortic valve surgery, were enrolled in the study and compared to twenty age- and sex-matched controls. All participants underwent routine echocardiographic examinations upon study inclusion. Plasma WIF-1 levels were determined by enzyme immunoassay.
Results: AS patients had markedly elevated plasma WIF-1 levels compared to controls (median 114 pg/ml, interquartile range [86, 171] vs 58 [32, 71] pg/ml; p<0.001). Plasma WIF-1 correlated with NT-proBNP (r=0.30; p<0.001), left ventricular (LV) internal dimension in systole, LV posterior wall diameter and LV end systolic volume (r=0.27, 0.17 and 0.19; p<0.05 for all). An inverse relationship was found for LV fractional shortening and LV ejection fraction (r=-0.30 and -0.20; p=0.001 and 0.018). WIF-1 correlated with ultrasound backscatter (r=0.26; p=0.003). During a mean follow up of 42 months (range 35–47), 34 patients (23%) died. We observed a markedly reduced survival for patients with WIF-1 levels in the fourth quartile compared to the lower three quartiles (p=0.002). WIF-1 added no significant independent predictive information for risk estimation beyond established risk factors in multivariate analyses. However, combining the fourth quartiles of WIF-1 and NT-proBNP proved superior to either of the parameters alone in predicting all-cause mortality (Conditional Cox-adjusted HR 6.24, CI 2.59–14.99; p<0.001).
Conclusion: Plasma levels of WIF-1 are elevated in patients with symptomatic AS. WIF-1 correlates with ultrasound backscatter, possibly reflecting a relationship between WIF-1 and degree of valvular calcification. In multivariate analyses a model of combined WIF-1 and NT-proBNP proved superior to either of the parameters alone in predicting all-cause mortality in AS patients.
- © 2010 by American Heart Association, Inc.