Growth Differentiation Factor-15 Combined with N-terminal Prohormone of Brain Natriuretic Peptide Increase 1-Year Prognosis Prediction Value for Patients with Acute Heart Failure: A Prospective Cohort Study
Heart failure (HF) is a critical end-stage condition of various cardiovascular diseases, characterized by high mortality, hospitalization costs, and disability rates. In China, the in-hospital mortality rate for acute heart failure (AHF) is reported to be 4.1%, highlighting the urgent need for improved diagnostic and prognostic tools. Biomarkers play a pivotal role in the clinical assessment and management of HF, with brain natriuretic peptide (BNP) and its N-terminal prohormone (NT-proBNP) being the most widely used. However, the limitations of these biomarkers necessitate the exploration of additional markers, such as growth differentiation factor-15 (GDF-15), to enhance prognostic accuracy.
This study aimed to evaluate the prognostic value of GDF-15 and NT-proBNP in patients with AHF and to determine whether their combination could improve the prediction of 1-year mortality. The research was conducted as a prospective cohort study involving 260 patients admitted for AHF at the First Affiliated Hospital of Nanjing Medical University from April 2012 to May 2016. The primary endpoint was all-cause mortality within one year of admission.
The study population consisted of patients diagnosed with AHF based on the Chinese Guidelines for Diagnosis and Treatment of AHF. Blood samples were collected within 24 hours of admission, and serum levels of GDF-15 and NT-proBNP were measured. Other clinical and demographic data, including medical history, comorbidities, and echocardiographic parameters, were also recorded. Patients were followed up for one year, with mortality data obtained through outpatient visits and telephone interviews.
Baseline characteristics revealed that the mean age of the participants was 61.0 years, with a majority being male (65.0%). Most patients were in New York Heart Association (NYHA) Functional Classification III at admission. The median levels of NT-proBNP and GDF-15 were 2100.5 ng/L and 2449.0 ng/L, respectively. By the end of the follow-up period, 46 patients (17.7%) had died.
Statistical analyses demonstrated that both GDF-15 and NT-proBNP levels were significantly higher in the deceased group compared to survivors. Receiver-operator characteristic (ROC) curve analyses were performed to assess the predictive value of these biomarkers. The area under the curve (AUC) for GDF-15 in predicting 1-year mortality was 0.707, while for NT-proBNP, it was 0.682. There was no significant difference between the two markers in terms of predictive value. However, combining GDF-15 and NT-proBNP increased the AUC to 0.743, indicating improved prognostic accuracy.
Kaplan-Meier survival curves further illustrated the relationship between elevated biomarker levels and increased mortality risk. Patients with GDF-15 levels above the optimal cut-off value of 4526.0 ng/L had a mortality rate of 38.2%, compared to 10.4% in those with lower levels. Similarly, patients with NT-proBNP levels above 1978.0 ng/L had a mortality rate of 25.5%, compared to 8.9% in those with lower levels. When both biomarkers were elevated, the mortality rate surged to 46.0%.
Cox regression analyses were conducted to identify independent predictors of 1-year mortality. The combination of elevated GDF-15 and NT-proBNP emerged as a significant predictor, with a hazard ratio of 5.623. Other significant predictors included serum sodium levels and red cell distribution width.
The findings of this study underscore the prognostic value of GDF-15 in patients with AHF, demonstrating that it is not inferior to NT-proBNP. The combination of these two biomarkers provides a more robust tool for identifying high-risk patients and improving long-term prognosis prediction. This is particularly relevant given the diverse pathophysiology of HF and the limitations of using a single biomarker.
GDF-15, a member of the transforming growth factor-beta superfamily, is involved in various regulatory pathways, including inflammation, hypoxia, and injury. Its elevation in HF is associated with myocardial remodeling and adverse outcomes. NT-proBNP, on the other hand, is primarily secreted by ventricular cardiomyocytes in response to volume or pressure overload and is widely used for HF diagnosis and prognosis. However, both biomarkers can be influenced by other conditions, such as coronary heart disease, atrial fibrillation, and sepsis, which limits their standalone utility.
The study’s results align with previous research indicating that GDF-15 and NT-proBNP provide complementary information, reflecting different aspects of HF pathophysiology. The combination of these markers offers a more comprehensive assessment, enabling early identification of high-risk patients and guiding personalized treatment strategies.
Despite its strengths, the study has several limitations. The single-center design and relatively small sample size may affect the generalizability of the findings. Larger, multicenter studies are needed to validate the results and explore the underlying mechanisms linking GDF-15 and NT-proBNP to HF outcomes. Additionally, the study did not investigate serial measurements of these biomarkers, which could provide further insights into their prognostic utility during the course of the disease.
In conclusion, this prospective cohort study highlights the prognostic value of GDF-15 in patients with AHF, demonstrating that it is not inferior to NT-proBNP. The combination of these biomarkers significantly enhances the prediction of 1-year mortality, offering a valuable tool for risk stratification and early intervention in AHF patients. Future research should focus on larger, multicenter studies and serial biomarker measurements to further elucidate their roles in HF management.
doi.org/10.1097/CM9.0000000000000449
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