Circulating secretoneurin concentrations predict heart failure and mortality in elderly myocardial infarction survivors: data from the OMEMI Trial

Background

Secretoneurin (SN) is a 33-amino acid peptide that has been shown to directly influence intracellular cardiomyocyte calcium handling (ref). Circulating SN concentrations predict clinical outcome in patients with established heart failure (HF), but whether SN concentrations can predict incident HF and mortality in elderly patients with myocardial infarction is not known.

Aims

To assess whether SN concentrations are associated with incident HF and mortality in elderly post-myocardial infarction survivors without clinically diagnosed HF.

Methods

Circulating SN concentrations were measured 2-8 weeks after myocardial infarction with an automated SN chemiluminescence immunoassay in 1013 patients included into the OMEMI trial. The OMEMI trial randomized elderly patients (70-82 years) surviving myocardial infarction to omega-3 fatty acids or placebo for two years and monitored cardiovascular events. We adjusted for age, sex, body-mass index, heart rate, systolic blood pressure, hypertension, heart failure, and baseline estimated glomerular filtration rate (eGFR) in multivariable analysis.

Results

Median SN concentration was 36 pmol/L (quartile 1-3 29-44 pmol/L) and baseline patient characteristics according to SN quartiles are presented in the Table. SN concentrations were positively correlated with age, female sex, heart rate, troponin concentration during the index myocardial infarction, and NYHA functional class. SN concentrations were inversely correlated with body-mass index, systolic blood pressure, left ventricular ejection fraction and eGFR. During 24 months follow-up, 45 patients were hospitalized for incident HF and 56 patients died. Patients with the highest SN concentrations had higher prevalence of HF hospitalizations and deaths (Figure). In multivariable analysis, SN concentrations were associated with HF hospitalizations (hazard ratio 5.40 [95% confidence interval 1.91-15.29], p=0.001) and mortality (3.48 [1.35-8.96], p=0.010). The optimal cutoff for SN to predict HF hospitalization or mortality was 44 pmol/L with sensitivity 54% and specificity 77%. There was no interaction between baseline SN concentration and treatment effect by omega-3 in the OMEMI trial (p=0.37 for interaction).

Conclusion

Circulating SN concentrations measured the first weeks after myocardial infarction in elderly subjects are associated with both HF hospitalizations and mortality during follow-up. Patients with SN concentrations >44 pmol/L have an exceptionally high risk of HF hospitalization or death, suggesting the need for closer monitoring and potentially more aggressive management strategies in this high-risk group.

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