Abstract 15183: Circulating MicroRNA-210 Levels Are Increased in Patients With Moderate to Severe Aortic Stenosis and Provide Independent Prognostic Information Regarding Mortality
Background: Micro-RNA(miR)-210 production is increased by cellular hypoxia, and circulating miR-210 levels have been found inversely correlated to maximal oxygen uptake. As poor physical capacity is an established risk factor in patients with aortic stenosis (AS), we hypothesized that circulating miR-210 levels are increased in patients with AS and associated with a poor prognosis.
Methods: Circulating miR-210 levels were measured by RT-qPCR in 57 patients with moderate to severe AS and in 10 age- and gender-matched healthy controls. MiR-210 levels were normalized to miR-425 levels, and RNA extraction was controlled by measuring the spike-in control cel-miR-39. Myocardial structure and function were characterized by echocardiography and the prognostic utility of miR-210 was compared to established risk indices.
Results: All patients and control subjects had miR-210 levels within the range of detection (Cp<35). The coefficient of variation (CV) for the samples run in triplet was 0.6% for both AS patients and the control subjects. CV for the spike-in control cel-miR-39 was 2.4% for AS patients and 2.2% for the control subjects. Circulating miR-210 levels were 2.0±0.2 [mean±SEM] fold increased in AS patients compared to controls (p=0.002). The increase in circulating miR-210 levels in patients with AS was comparable to the increment in NT-proBNP levels: [AUC] 0.82 (95% CI 0.70-0.90) vs. 0.85 (0.75-0.93), respectively, p=0.71. Elevated circulating miR-210 levels were not significantly associated with clinical variables, echocardiographic indices, creatinine clearance, or NT-proBNP levels in regression analyses. During a median follow-up of 1287 days, 15 patients (26%) died. There was a significant association between higher circulating levels of miR-210 and increased mortality during follow-up: hazard ratio [supra- vs. inframedian levels] 3.3 (95% CI 1.1-10.5), p=0.039. Adjusting for other risk indices in multivariate analysis did not attenuate the prognostic merit of circulating miR-210 levels.
Conclusion: Circulating miR-210 levels are increased in patients with AS and higher levels are associated with poor prognosis. Our data suggest that miR-210 levels reflect additional pathology in AS than measured by conventional risk indices.
- © 2013 by American Heart Association, Inc.