Abstract
BackgroundCirculating micro-RNAs have been proposed as a novel class of cardiovascular (CV) biomarkers, but whether they meet analytical requirements and provide additional information to establish risk indices have not been established. miR-210 levels are increased in subjects with low VO2 max, which is a recognized risk factor in patients with aortic stenosis (AS), and we hypothesized that circulating miR-210 levels may be increased in patients with AS and associated with a poor prognosis.MethodsWe measured circulating miR-210 levels by real-time PCR in 57 patients with moderate to severe AS and in 10 age- and gender-matched healthy controls. The merit of miR-210 as a biomarker was assessed according to established criteria, including by comparing miR-210 levels with NT-proBNP and miR-22 levels, which is another miRNA biomarker candidate.ResultsAll patients and control subjects had miR-210 levels within the range of detection (Cq<35) and the analytical variability was low. Circulating miR-210 levels were 2.0±0.2 [mean±SEM] fold increased in AS patients compared to controls (p = 0.002), whereas miR-22 levels were not differently expressed in the AS patients (0.12±0.06 fold increase, p = 0.45). The increase in miR-210 levels in AS patients 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. 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.ConclusionCirculating miR-210 levels are increased in patients with AS and provide independent prognostic information to established risk indices. Analytical characteristics were also excellent supporting the potential of micro-RNAs as novel CV biomarkers.
Highlights
Current risk stratification in patients with aortic stenosis (AS) is based on symptoms and the identification of aortic valve orifice narrowing by echocardiography [1]
The patients and control subjects were evenly matched on age, gender, and body mass index (BMI) (Table 1)
A minority of the AS patients were considered to be in New York Heart Association (NYHA) functional class III/IV, but N-terminal proB-type natriuretic peptide (NT-proBNP) levels were significantly increased in AS patients compared to control subjects
Summary
Current risk stratification in patients with aortic stenosis (AS) is based on symptoms (dyspnea, syncope, chest pain) and the identification of aortic valve orifice narrowing by echocardiography [1]. MiRNAs have the ability to regulate multiple downstream protein targets, and individual miRNAs have been found to be of crucial importance for myocardial function [3]. With individual miRNAs regulating multiple downstream protein pathways, it has been postulated that individual miRNAs may provide integrated information on several pathophysiological axes [3]. MiRNAs seem to have potential as CV biomarkers, it is important that all biomarker candidates are examined according to established criteria [7]. Circulating micro-RNAs have been proposed as a novel class of cardiovascular (CV) biomarkers, but whether they meet analytical requirements and provide additional information to establish risk indices have not been established. Circulating micro-RNAs have been proposed as a novel class of cardiovascular (CV) biomarkers, but whether they meet analytical requirements and provide additional information to establish risk indices have not been established. miR-210 levels are increased in subjects with low VO2 max, which is a recognized risk factor in patients with aortic stenosis (AS), and we hypothesized that circulating miR-210 levels may be increased in patients with AS and associated with a poor prognosis
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