Plasma levels of bone morphogenic protein-4 are downregulated in elderly hypertensive patients with heart failure with preserved ejection fraction

Abstract

Objective: This study aimed to evaluate the association between plasma bone morphogenic protein-4 (BMP-4) levels and heart failure (HF) with preserved ejection fraction (HFpEF) or mildly reduced ejection fraction (HFmrEF) in elderly hypertensive patients.

Methods: A total of 222 hypertensive individuals meeting the inclusion criteria were enrolled from October 2021 to July 2022. Data were collected including clinical characteristics, laboratory tests and echocardiogram measurements. Plasma BMP-4 levels were tested using enzyme-linked immunosorbent assay analysis.

Results: Among 222 elderly hypertensive patients, 149 were without HF, 59 had HFpEF, and 14 had HFmrEF. Plasma BMP-4 levels were strikingly downregulated in hypertensive patients with HFpEF/HFmrEF [median (25th, 75th percentile): 15.89 (7.69, 23.12) pg/mL vs. 19.67 (10.60, 33.04) pg/mL; P = 0.002]. After univariate and multivariate logistic regression analysis, the risk of HFpEF/HFmrEF was declined in the 4th quartile BMP-4 group when compared with the 1st quartile BMP-4 group (odds ratio, 0.20, 95% confidence interval (CI), 0.04 to 1.00; P = 0.050, P for trend = 0.025). Receiver operating characteristic curve analysis revealed that BMP-4 ≤ 28.5 pg/mL exhibited a sensitivity of 95.9% and a specificity of 28.2% in HFpEF/HFmrEF diagnosis. Furthermore, the area under the curve (AUC) was 0.619 (95% CI:0.540-0.698, P < 0.001). The corresponding AUC for brain natriuretic peptide (BNP) was 0.781 (95% CI: 0.710-0.852), P < 0.001. Adding BMP-4 to BNP increased the AUC to 0.790 (95% CI: 0.724-0.856), vs. BMP-4, P < 0.001; vs. BNP, P = 0.730, respectively.

Conclusions: Plasma BMP-4 levels are downregulated in elderly hypertensive patients with HFpEF. BMP-4 is a promising biomarker for diagnosing HFpEF/HFmrEF during hypertension.

Keywords: Bone morphogenic protein-4; Heart failure with mildly reduced ejection fraction; Heart failure with preserved ejection fraction; Hypertension.