Data Management And Sharing System of China National Clinical Research Center for Neurological Diseases
U-shaped association between low density lipoprotein cholesterol levels and risk of all-cause mortality mediated by post-stroke infection in acute ischemic stroke
First author：Zimo Chen,Hongqiu Gu
Corresponding author：Yongjun Wang,Zixiao Li
essential_information
- Person in charge：Zimo Chen,Hongqiu Gu
- Data Sources： CSCA
- Number of papers：CSCA20200134
- Published time：2023-06-30
2023-06-30
Published articles
Journal：Science Bulletin
Publication type: Original Contributions
IF(IF): 18.9
PMID: 37270342 Link To Pubmed Full text Download
Background And Purpose
Newer medications to lower lipid levels (ie, proprotein convertase subtilisin/kexin type 9 [PCSK9] inhibitors) have enabled unprecedented reductions in plasma LDL-C, which also supports the mantra of “lower is better” for LDL-C reduction(1). Research from both the laboratory and the clinic has provided increasing evidence for cross-talk between cholesterol metabolism and the immune system(2). And there is interest in the role of LDL-C as an important component in protecting against infectious disease, which is common and independently associated with functional outcome after acute ischemic stroke(3)(4). However, the role of LDL-C and its effect on infection after ischemic stroke remains poorly characterized. In this study, we aimed to elucidate whether the low LDL-C concetration may increase the risk of infection following IS, as well as the potential role of previous stain use in this correlation.
Method
804,855 patients of ischemic stroke were enrolled. Associations between LDL-C levels, infection, and mortality risk were estimated by multivariate logistic regression models and displayed by restricted cubic spline curves. Mediation analysis was performed under counterfactual framework to elucidate the mediation effect of post-stroke infection.
Conclusion
During the acute stage of ischemic stroke, there is a U-shaped association between LDL-C level and all-cause mortality, where post-stroke infection is an important mediating mechanism.
Main results
The association between LDL-C and mortality risk was U-shaped. The nadir in LDL-C level with the lowest mortality risk was 2.71 mmol/L. Compared with the group with LDL-C=2.50–2.99 mmol/L, the multivariable-adjusted odds ratio for mortality was 2.18 (95% CI: 1.73–2.75) for LDL-C<1.0 mmol/L and 1.19 (95% CI: 0.96–1.48) for LDL-C≥5.0 mmol/L. The association between LDL-C and all-cause mortality was 39.41% (95% CI: 4.92%–73.90%) mediated by infection. After stepwise excluding patients combined with different numbers of cardiovascular risk factors, the U-shaped association between LDL-C and all-cause mortality and the mediation effects of infection remained consistent with the primary analysis, and the LDL-C interval with the lowest mortality risk increased progressively. The mediation effects of infection were largely consistent with the primary analysis in subgroups of age≥65 years, female, BMI<25 kg/m2, and NIHSS≥16.