Exploring the therapeutic potential of interleukin-6 receptor blockade in cardiovascular disease treatment through Mendelian randomization

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.