Meteorin-like protein plasma levels are associated with worse outcomes in de novo heart failure

Abstract

Background and aims: Meteorin-like protein (Metrnl) has been recently suggested as a new adipokine with protective cardiovascular effects. Its circulating levels in patients seem to be associated with heart failure (HF), although with contradictory results. Our aim was to ascertain whether this adipokine could estimate the prognosis of HF in de novo HF (DNHF) patients.

Methods: Metrnl plasma levels of 400 patients hospitalized with DNHF (55% of patients with HF with reduced ejection fraction, 17.3% HF with mid-range ejection fraction, 27.8% HF with preserved ejection fraction) were measured by enzyme-linked immunosorbent assay. We performed both sex-pooled and sex-specific analyses. A 12-month follow-up was conducted, during which clinical outcomes such as all-cause mortality, cardiovascular death and re-hospitalization due to HF were collected.

Results: After a 12-month follow up, higher plasma Metrnl levels were associated with an increased risk for all-cause death and cardiovascular death after adjusting by sex, age, LVEF, hypertension, diabetes, ischemic aetiology, chronic renal failure, NT-proBNP and troponin (hazard ratio [HR] = 1.003, 95% confidence interval [CI] = 1.000-1.005; p-value<.05 and HR = 1.004, 95% CI = 1.001-1.007, p-value<.05, respectively). In line with this, DNHF patients with increased levels of circulating Metrnl had a higher number of occurrences of cardiovascular events. Regarding Metrnl associations with parameters implicated in the development and progression of HF, we found that Metrnl circulating levels were positively correlated with age (r = .322, p-value<.0001), NT-proBNP (r = .281, p-value<.0001) and with the renal dysfunction markers urea (r = .322, p-value<.0001) and creatinine (r = .353, p-value<.0001) and higher in women than men (473.7 [385.9-594.0] pg/mL vs. 428.7 [349.1-561.3] pg/mL, p-value<.006). Finally, concerning the subtype of HF, Metrnl plasma levels were higher in HF with preserved ejection fraction.

Conclusion: Patients with higher Metrnl levels have a worse prognosis in DNHF. Our results reinforce the association of Metrnl plasma levels with HF progression and outcomes.

Keywords: adipokine; cardiovascular risk; de novo heart failure; meteorin‐like protein; sex.