Hepatocyte Growth Factor and Incident Heart Failure Subtypes: The Multi-Ethnic Study of Atherosclerosis (MESA)

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.