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Published on: February 20, 2019
Exploring the therapeutic potential of interleukin-6 receptor blockade in cardiovascular disease treatment through
Guangyang Ou1, Huzhi Cai2, Kunpeng Yao1
1The First Clinical College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 410007, Hunan, China.
Insights
Interleukin-6 receptor (IL-6R) blockade shows a protective effect against coronary heart disease (CHD) and myocardial infarction (MI). This therapeutic strategy did not demonstrate significant benefits for hypertension (HTN), atrial fibrillation (AF), or heart failure (HF).
Area of Science:
- Cardiovascular Medicine
- Immunology
- Genetics
Background:
- Interleukin-6 (IL-6) is implicated in cardiovascular disease (CVD) pathogenesis.
- IL-6 receptor (IL-6R) blockade is a potential therapeutic strategy for CVD.
- The efficacy of IL-6R blockade across different CVD types requires clarification.
Purpose of the Study:
- To evaluate the therapeutic effects of IL-6R blockade on various cardiovascular diseases.
- Specifically assessed were hypertension (HTN), coronary heart disease (CHD), myocardial infarction (MI), atrial fibrillation (AF), and heart failure (HF).
- Utilized a Mendelian randomization (MR) approach to investigate these associations.
Main Methods:
- Employed Mendelian randomization (MR) using genome-wide association study (GWAS) summary statistics.
- Sensitivity analyses included MR-Egger intercept, Cochran's Q test, and leave-one-out analysis.
- Bonferroni correction was applied to adjust for multiple comparisons.
Main Results:
- IL-6R blockade was significantly associated with a protective effect on CHD (OR=0.757, P=5.804×10⁻⁹) and MI (OR=0.840, P=0.005).
- No significant effects were observed for IL-6R blockade on HTN (OR=1.015, P=0.663), AF (OR=0.905, P=0.116), or HF (OR=1.012, P=0.805).
Conclusions:
- Genetically predicted IL-6R blockade offers a protective benefit for CHD and MI.
- IL-6R blockade does not appear to significantly impact HTN, AF, or HF.
- Findings support personalized IL-6R blockade treatment strategies for specific CVDs and guide future research.
Abstract:
Interleukin-6 (IL-6) plays a crucial role in the pathogenesis of cardiovascular disease (CVD), and IL-6 receptor (IL-6R) blockade has emerged as a promising therapeutic option. However, their specific therapeutic effects in different types of CVDs remain unclear. This study aimed to assess the efficacy of IL-6R blockade in the management of various CVDs, including hypertension (HTN), coronary heart disease (CHD), myocardial infarction (MI), atrial fibrillation (AF), and heart failure (HF). The Mendelian randomization (MR) approach was utilized to investigate the therapeutic impact of IL-6R blockade on HTN, CHD, MI, AF, and HF based on the genome-wide association study (GWAS) summary statistics. MR-Egger intercept test, Cochran's Q test, and leave-one-out analysis were used for sensitivity analysis to verify the reliability of the MR results. The Bonferroni method was used to correct for bias caused by multiple comparisons. Inverse variance weighted (IVW) results demonstrated that IL-6R blockade significantly influenced CHD (odds ratio (OR) = 0.757, 95% confidence interval (CI): 0.690 - 0.832, P = 5.804 × 10-9) and MI (OR = 0.840, 95% CI: 0.744 - 0.949, P = 0.005). However, IL-6R blockade had no significant effect on HTN (OR = 1.015, 95% CI: 0.950 - 1.084, P = 0.663), AF (OR = 0.905, 95% CI: 0.800 - 1.025, P = 0.116) and HF (OR = 1.012, 95% CI: 0.921 - 1.113, P = 0.805). Genetically predicted IL-6R blockade was associated with a protective effect on CHD and MI, but not HTN, AF and HF. This study's findings offer valuable insights for tailoring IL-6R blockade treatment for different types of CVD, and serve as a reference for future research.
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