Brain-Derived Neurotrophic Factor Reduces Long-Term Mortality in Patients With Coronary Artery Disease and Chronic Kidney Disease

Cheng-Yueh Hsu; Wayne Huey-Herng Sheu; I-Te Lee

doi:10.3389/fcvm.2022.881441

Brain-Derived Neurotrophic Factor Reduces Long-Term Mortality in Patients With Coronary Artery Disease and Chronic Kidney Disease

Front Cardiovasc Med. 2022 Jun 21:9:881441. doi: 10.3389/fcvm.2022.881441. eCollection 2022.

Authors

Cheng-Yueh Hsu^{1

2}, Wayne Huey-Herng Sheu^{3

4}, I-Te Lee^{4

5

6}

Affiliations

¹ Master of Public Health, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, United States.
² Department of Medical Education, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan.
³ Department of Internal Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
⁴ School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
⁵ Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
⁶ School of Medicine, Chung Shan Medical University, Taichung, Taiwan.

Abstract

Objectives: Chronic kidney disease (CKD) is a risk factor for coronary artery disease (CAD). We examined the effects of circulating brain-derived neurotrophic factor (BDNF) on long-term mortality in patients with CAD and CKD.

Materials and methods: We enrolled patients with established CAD in the present study. Serum BDNF and estimated glomerular filtration rate (eGFR) were assessed after overnight fasting. All-cause mortality served as the primary endpoint.

Results: All 348 enrolled patients were divided into four groups according to their median BDNF level and CKD status, defined according to eGFR <60 mL/min/1.73 m². Forty-five patients reached the primary endpoint during the median follow-up time of 6.0 years. Kaplan-Meier survival analysis indicated that the group with low BDNF and CKD had a significantly higher mortality rate than the other three groups (log-rank test p < 0.001). Compared to the high BDNF without CKD group, the low BDNF with CKD group had a hazard ratio (HR) of 3.186 [95% confidence interval (CI): 1.482-6.846] for all-cause mortality according to the multivariable Cox proportional hazard regression analysis after adjusting for age and urine albumin-creatinine ratio (p = 0.003). Furthermore, there was a significantly interactive effect between BDNF and CKD status on the risk of the primary endpoint (odds ratio = 6.413, 95% CI: 1.497-27.47 in the multivariable logistic regression model and HR = 3.640, 95% CI: 1.006-13.173 in the Cox regression model).

Conclusion: We observed a synergistic effect between low serum BDNF levels and CKD on the prediction of all-cause mortality in patients with CAD.

Keywords: brain-derived neurotrophic factor; chronic kidney disease; cohort; coronary artery disease; interaction; mortality.