Effect of statins on sepsis and inflammatory factors: A Mendelian randomization study.

ABSTRACT

BACKGROUND: As inhibitors of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), statins can reduce the synthesis of low-density lipoptrotein cholesterol (LDL-C), and are clinically used as first-line lipid-lowering drugs to prevent cardiovascular diseases. However, the effect of statins on sepsis is controversial. Therefore, we intend to explore the effects of statins on sepsis and inflammatory factors through Mendelian randomization (MR). METHOD: We obtained sepsis, inflammatory factors, and LDL-C data from open and free genome-wide association study (GWAS) for subsequent analysis. Inverse-variance weighted (IVW) was the main method, MR-Egger, MR-PRESSO and Cochrane's Q-test were used as sensitive analysis to evaluate the robustness of MR results. RESULTS: Statins were associated with a reduced risk of sepsis under 75 (sepsis in individuals under 75 years old) (OR .716, 95% CI .572-.896, p = .003), elevated circulating IL-18 (OR .762, 95% CI .643-.903, p = .002) and elevated circulating CCL2 (OR .416, 95% CI .279-.620, p = 1.685e-5). CONCLUSION: Statins may have a protective effect on sepsis and this may provide a new idea for the treatment of sepsis.