Abstract
BACKGROUND: Despite being a major global cause of mortality, the exact underlying mechanisms of cardiovascular diseases (CVDs) remain uncertain. This study aimed to elucidate the possible pathological connection between circulating activated immune cell types and the advancement of CVD. METHODS: A two-sample Mendelian randomization analysis was performed on publicly available genetic databases to examine the potential causal relationships among 731 immune phenotypes and CVD risks. The study focused on four distinct immune signatures: relative cell counts (RC), absolute cell counts (AC), morphological parameters (MP), and median fluorescence intensities (MFI). A sensitivity analysis was performed to assess the findings' consistency, robustness, and potential pleiotropic effects. RESULTS: Significant associations between CVD and various immunophenotypes were observed in this study. Specifically, two phenotypes exhibited protective effects against CVD. The odds ratio (OR) for activated and secretory CD4(+) regulatory T-cells (Tregs) was 0.757 [95% confidence interval (CI): 0.628-0.913; p = 0.004], whereas that for B-cell activating factor receptor on IgD(-)CD38(+) memory B-cells was 0.654 (95% CI: 0.468-0.915; p = 0.013). Conversely, three major immunophenotypes were linked to heightened risks of CVD: CD80 on myeloid dendritic cells (OR: 1.181; 95% CI: 1.015-1.376; p = 0.032), the proportion of CD28(+) CD45RA(+) CD8(+) T-cells in total T-cell population (OR: 1.064; 95% CI: 1.002-1.128; p = 0.041), and the proportion of CD28(-)CD45RA(+) CD8(+) T-cells in total T-cell population (OR: 1.005; 95% CI: 1.000-1.011; p = 0.045). CONCLUSION: This study underscores significant correlations between specific immune phenotypes and the risks associated with CVD onset, thus providing valuable perspectives for forthcoming clinical inquiries.