ST2 is reduced by high-dose omega-3 fatty acid treatment following acute MI and is correlated with reduction of the extracellular volume fraction of non-infarcted myocardium

Background

ST2, a member of the interleukin-1 receptor family, has been shown to be independently associated with myocardial strain and adverse cardiac events in patients with both ST-elevation and non-ST elevation myocardial infarction (MI). We sought to determine whether high-dose omega-3 fatty acid therapy (O-3FA) would reduce serum levels of ST2 following acute MI and whether ST2 levels correlated directly with measures of diffuse myocardial fibrosis within non-infarcted myocardium.

Methods

We evaluated 358 patients who were enrolled in a randomized, double-blinded, placebo-controlled trial of high-dose O-3FA therapy post acute MI. All patients underwent 3T CMR (Tim Trio/Verio, Siemens, Germany) and evaluation of serum biomarkers at enrollment and after 6-months of randomized study therapy. Patients were followed for adverse cardiac events by study physicians at 6-month intervals thereafter.

Results

Patients who received O-3FA treatment were more likely to have a history of coronary bypass surgery than placebo patients (p = 0.02), otherwise there were no baseline differences between treatment arms. ST2 levels were significantly reduced by O-3FA therapy as compared with placebo (Figure 1). By intention-to-treat analysis, O-3FA treatment was associated with a -7.9% reduction of ST2 (P = 0.03), and in adjusted analysis for covariates by -8.0% (P = 0.03). Amongst O-3FA treated patients, reduction of ST2 demonstrated a strong correlation with reduction of extracellular volume fraction within non-infarcted myocardium (r = 0.65, P < 0.0001, Figure 2). Baseline ST2 levels were the strongest unadjusted predictor (HR 5.2, 95% confidence interval 2.3-11.7, p < 0.0001) for all-cause mortality and congestive heart failure after a median of 2.3 years of follow-up.

Figure 1

Percent Change of Serum Biomarker ST2 Levels Post Treatment. Percent change from baseline to post treatment (6 months) of ST2 levels for the high-dose omega-3 fatty acid treated group and placebo arm. P values are for comparisons of percent change in ST2 levels between the randomized treatment arms.

Figure 2

Scatter Plot of Percent Change in Serum Biomarker ST2 versus Percent Change of Remote Myocardial Fibrosis Post Treatment. Percent change from baseline to post treatment of the serum biomarker ST2 correlated against percent change in remote myocardial fibrosis by cardiac magnetic resonance imaging following 6 months of treatment with high-dose omega-3 fatty acids. P value is for Pearson correlation coefficient shown in figure.

Conclusions

Serum ST2 level following acute MI is a strong prognostic marker of post-MI death and congestive heart failure. O-3FA treatment reduced ST2 levels, which were strongly correlated with reduction of the extracellular volume fraction within non-infarcted myocardium. ST2 may serve as a non-invasive serum biomarker of myocardial fibrosis, as well an independent predictor of adverse cardiac events following acute MI.