Our results show that the combination of plasma orosomucoid and omentin values improved the prognostic risk stratification of de novo AHF patients. Therefore, low orosomucoid and high omentin levels were associated with the lowest risk of suffering adverse outcomes during the follow-up compared with UpDown or equal group (high orosomucoid and low omentin levels or both proteins high or low). Adding these two new biomarkers to NT-ProBNP significally improves the risk stratification of acute de novo HF patients.
To the best of our Knowledge we describe for the first time the prognostic value of these biomarkers in AHF patients. Our findings may have implications not only for the risk stratification at hospital discharge because these new biomarkers can be considered as a potential therapeutic target and useful for the development of new treatment strategies and help to improve the patient care pathway.
Nowadays de novo HF represents one third of hospitalized patients for AHF 23. Although their mortality in hospital is similar to worsening HF, they have better post-discharge follow-up, less associated comorbidities and less advance HF syndrome 24,25. However, their long-term prognosis after hospitalization for HF remains poor. Our data showed that 16 % patients had an event during the 1-year mean follow-up. Thus, many efforts are focussed on these patients with the aim of achieving hemodynamic stability, preventing recurrent HF, and reducing mortality12.
The present study shows that admitted patients for de novo AHF with high orosomucoid and low omentin levels presented the highest risk of death or requiring re-hospitalization for HF during an early or mid-term follow-up. However, any patients with low plasma orosomucoid and high omentin levels had an event within 100 days after discharge. These patients represent the 40% of the AHF patients. Therefore, there is an improvement on risk stratification of patients with de novo AHF using the combination of two proteins (high concentration of orosomucoid and low concentration of omentin).
One of the main issues, in the AHF management, is based on the identification of patients with worse prognosis for improving their management and trying to find an optimal medical treatment and an efficient follow-up plan. With this objective has been used clinical parameters (heart rate at the admission 26, blood pressure, renal failure 23, protein biomarkers (NT-proBNP 27, ST2 28, galectin-3 29) and several scores. However, all of them have some limitations. Recent data showed that a quite cardiac specific marker, DKK3, had also a limited additional prognostic value regarding NT-proBNP30. Even, a multimarker panel was suggested in patients with AHF and renal mild or moderate impairment or the combination of two biomarkers in dyspnoeic patients. However, this is the first time that a protective and a deleterious marker combination were tested in AHF the new-onset for stratifying patients according mortality risk or readmission for HF. The combination of NT-proBNP, orosomucoid and omentin took out the best predictive model for rehospitalization for HF and/or death. A nomogram strategy might change the clinical follow-up of the patients (Fig. 3).
The pathogenesis of de novo HF is not completely known and an inflammatory mechanism has been suggested 1. The association between inflammation and HF has been recognized after many studies demonstrated that pro-inflammatory biomarkers are elevated in patients with a variety of cardiomyopathies and the clinical presentation of the HF syndrome. The plasma levels of inflammatory biomarkers have correlated with the prognosis and severity of the disease in both reduced and preserved LVEF-HF patients 29 ,24, 25.
In this sense, low levels of omentin, an anti-inflammatory cytokine, have been described in chronic HF patients 14 and higher levels of orosomucoid have been related to worse outcome in AHF patients 12. These proteins have a protective effect on cardiomyoblasts, in part, mediated by an anti-lipotoxicity effect 13.
Omentin might play a cardioprotective role against an inflammatory process and high orosomucoid levels since its high levels are able to reduce the probability of death or readmission for HF in those patients with high orosomucoid levels.
The role of our discovery in the pathogenesis and prognosis of HF has potential therapeutic and diagnostic implications. We could not prove if these proteins are a direct cause of HF, but if it is confirmed in further studies, the treatment targeting this inflammatory pathway should be beneficial; however, if it is only a marker of the disease it could help us to identify patients who are in a more advanced state in the moment of the diagnosis.
The number of patients included is small but is comparable to other studies that assessed similar objectives and outcome and the results are statistically significant and we think that this issue will have future clinical relevance. The adjustment for other clinical parameters and biomarkers may influence our results.