Multimarker approach including CRP, sST2 and GDF‐15 for prognostic stratification in stable heart failure

Abstract

Aims Inflammation and cardiac remodelling are common and synergistic pathways in heart failure (HF). Emerging biomarkers such as soluble suppression of tumorigenicity 2 (sST2) and growth differentiation factor-15 (GDF-15), which are linked to inflammation and fibrosis process, have been proposed as prognosis factors. However, their potential additive values remain poorly investigated. Methods and results Here, we aimed at evaluating inflammatory and remodelling biomarkers to predict both short-term and long-term mortality in a population with chronic HF in comparison with other classical clinical or biological markers (i.e. N terminal pro brain natriuretic peptide, hs-cTnT, C-reactive protein) alone or using meta-analysis global group in chronic HF risk score in a cohort of 182 patients followed during 80 months (interquartile range: 12.3-90.0). Proportional hazard assumption does not hold for sST2 and C-reactive protein, and follow-up was split into short term (less than 1 year), midterm (between 1 and 5 years), and long term (after 5 years). In univariate analysis, C-reactive protein and sST2 were predictive of short-term mortality but not of middle term and long term whereas GDF-15 was predictive of short and mid-term but not of long-term mortality. In a multivariate model after adjustment for meta-analysis global group in chronic HF score including the three markers, only sST2 was predictive of short-term mortality (P = 0.0225), and only GDF-15 was predictive of middle term mortality (P = 0.0375). None of the markers was predictive of long-term mortality. Conclusions Our results demonstrate that both sST2 and GDF-15 significantly improve the prognosis evaluation of HF patients and suggest that the value of GDF-15 is more sustained overtime and could predict middle term events.

Prognostic Value of GDF-15 in Predicting Prolonged Intensive Care Stay following Cardiac Surgery: A Retrospective Case-Control Study

“…It shows promise as a biomarker following STelevation acute myocardial infarction, predicting both short-and long-term outcomes (6). Another recent study by Kuster et al demonstrated that GDF-15 is useful in predicting middle term events in stable heart failure (7). One previous study by Heringlake et al could demonstrate that preoperatively raised levels of GDF-15 were an independent predictor of outcome following cardiac bypass surgery (9).…”

“…A novel approach of improving these models could be the inclusion of biomarkers for pre-interventional risk strati cation. The use of established and emerging biomarkers, such as CRP and GDF-15, has shown signi cant promise as predictors of outcome in myocardial infarction and heart failure (6,7). Additionally, the measurement of biomarkers would be a reliable variable, i.e.…”

sST2 Protein Serum Levels in Patients with Chronic Heart Failure

“…(11) Ultimately, a high level of sST2 in blood plasma leads to myocardial fibrosis and dysfunction of the ventricles of the heart. (15) The main sources of sST2 are cardiac fibroblasts and cardiomyocytes in response to stress or injury. Recent studies have demonstrated soluble ST2 to be a strong predictor of cardiovascular outcomes in both chronic and acute heart failure.…”

“…(16) The weaknesses of the NT-proBNP diagnostic capabilities, namely that its representativeness depends on some comorbid conditions of patients (impaired renal function, anemia, COPD, obesity), encourages scientists to search for a more stable diagnostic marker for patients with a different EF of CHF. Despite the fact that separate studies have already been conducted (7,15,17) to assess the relationship of sST2 with other characteristics of CHF patients with different LVEF, the results obtained are contradictory.…”

Soluble urokinase-type Plasminogen Activator Receptor Strongly Predicts Global Mortality in Acute Heart Failure Patients: Insight From the STADE-HF Registry

“…sST2 was identified as a new prognostic biomarker in HF, independent from age, kidney function, anemia or BMI [ 6 , 8 ]. Recently, our team demonstrated that another biomarker GDF-15 added substantial information on patients’ prognosis [ 9 ]. Urokinase-type plasminogen activator receptor (UPAR) is a glycoprotein involved in tissue reorganization events and regulation of plasminogen [ 10 , 11 ].…”