Related Experiment Video
Updated: Nov 4, 2025
Author Spotlight: Exploring the Relationship Between Lipotoxicity and HFpEF
Published on: March 29, 2024
Hepatocyte Growth Factor and Incident Heart Failure Subtypes: The Multi-Ethnic Study of Atherosclerosis (MESA)
Richard A Ferraro1, Oluseye Ogunmoroti1, Di Zhao2
1Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Insights
Hepatocyte growth factor (HGF) is linked to increased heart failure (HF) risk, particularly HF with preserved ejection fraction (HFpEF). This cytokine may aid in predicting HFpEF, but not HF with reduced ejection fraction (HFrEF).
Area of Science:
- Cardiovascular Medicine
- Biomarkers
- Epidemiology
Background:
- Hepatocyte growth factor (HGF) is a known cytokine and cardiovascular disease (CVD) risk marker.
- Its association with incident heart failure (HF) and specific HF subtypes is less understood.
- This study investigates HGF's role in predicting new-onset HF in a diverse population.
Purpose of the Study:
- To examine the association between baseline Hepatocyte growth factor (HGF) levels and the risk of incident heart failure (HF).
- To differentiate the association of HGF with HF subtypes: HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF).
- To assess HGF as a potential biomarker for HF risk stratification.
Main Methods:
- Utilized data from 6,597 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort, free of clinical CVD and HF at baseline.
- Measured baseline HGF levels and followed participants for incident hospitalized HF over 14 years, adjudicating subtypes (HFpEF vs. HFrEF).
- Employed Cox regression models to calculate adjusted hazard ratios (HRs) for HF risk based on HGF levels, controlling for confounders.
Main Results:
- Elevated HGF levels were independently associated with an increased risk of overall incident HF.
- The highest tertile of HGF showed a significantly higher risk for HFpEF (adjusted HR: 1.90) but not for HFrEF (adjusted HR: 1.09).
- Continuous analysis indicated that each standard deviation increase in log-transformed HGF was associated with higher HF and HFpEF risk, but not HFrEF risk.
Conclusions:
- Hepatocyte growth factor (HGF) is an independent predictor of incident heart failure (HF).
- HGF shows a significant association with HF with preserved ejection fraction (HFpEF), but not with HF with reduced ejection fraction (HFrEF).
- Further research is warranted to explore HGF's underlying mechanisms in HF pathogenesis and its clinical utility in risk prediction and therapy guidance.
Background:
Hepatocyte growth factor (HGF) is a cytokine and marker of cardiovascular disease (CVD) risk. Less is known about HGF and incident heart failure (HF). We examined the association of HGF with incident HF and its subtypes in a multiethnic cohort.
Methods And Results:
We included 6597 participants of the Multi-Ethnic Study of Atherosclerosis (MESA) cohort, free of clinical CVD and HF at baseline, with HGF measured at baseline. Incident hospitalized HF was assessed and adjudicated for HF with preserved ejection fracture (HFpEF) vs HF with reduced ejection fraction (HFrEF). Cox regression models estimated hazard ratios (HR) and 95% confidence intervals (CI) for HF risk by HGF levels, adjusted for socio-demographics, CVD risk factors and N-terminal pro-B-type natriuretic peptide. The mean age was 62 ± 10 years. The median HGF level was 950 pg/mL (interquartile range, 758-1086 pg/mL); 53% were women. Over 14 years (IQR, 11.5-14.7 years), there were 324 cases of HF (133 HFpEF and 157 HFrEF). For the highest HGF tertile compared with lowest, adjusted HRs were 1.59 (95% CI, 1.10-2.31), 1.90 (95% CI, 1.03-3.51), and 1.09 (95% CI, 0.65-1.82) for overall HF, HFpEF, and HFrEF, respectively. For continuous analysis per 1-standard deviation log-transformed HGF, adjusted HRs were 1.22 (95% CI, 1.06-1.41), 1.35 (95% CI, 1.09-1.69), and 1.00 (95% CI, 0.81-1.24) for HF, HFpEF, and HFrEF, respectively.
Conclusions:
HGF was independently associated with incident HF. HGF remained significantly associated with HFpEF but not HFrEF upon subtype assessment. Future studies should examine the mechanisms underlying these associations and evaluate whether HGF can be used to improve HF risk prediction or direct therapy.
Related Concept Videos
01:17Pathophysiology of Heart Failure
01:27Heart Failure I: Introduction
01:30Heart Failure IV: Classification and Diagnostic Evaluation
01:29Heart Failure II: Pathophysiology
01:29Cardiomyopathy III: Hypertrophic Cardiomyopathy
01:30Heart Failure V: Medical Management