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Risk of remnant cholesterol and chronic obstructive pulmonary disease: a mendelian randomization study
Wei-Yi Feng1,2,3, Jun-Huang Zheng1,2,3, Jia-Qi Xiao1,2,3
1Department of Allergy and Clinical Immunology, Department of Respiratory and Critical Care Medicine, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
Insights
Higher remnant cholesterol (RC) levels are linked to an increased risk of chronic obstructive pulmonary disease (COPD). Further research is needed to determine if lowering RC can reduce COPD incidence.
Area of Science:
- Cardiovascular Research
- Pulmonary Medicine
- Genetic Epidemiology
Background:
- Remnant cholesterol (RC) is the cholesterol component of triglyceride-rich lipoproteins, distinct from HDL-C and LDL-C.
- Elevated RC levels are associated with increased inflammation.
- While lipid metabolism disorders contribute to inflammation, the specific link between RC and chronic obstructive pulmonary disease (COPD) remains unexplored.
Purpose of the Study:
- To investigate the potential association between remnant cholesterol (RC) levels and the pathogenesis of chronic obstructive pulmonary disease (COPD).
Main Methods:
- A two-sample Mendelian randomization (MR) analysis was conducted using pooled data from European ancestry populations.
- Data were sourced from the Integrative Epidemiology Unit (IEU) OpenGWAS project and the FinnGen Biobank.
- Inverse variance weighting (IVW) was the primary MR method employed.
Main Results:
- Mendelian randomization analysis revealed a significant positive association between higher remnant cholesterol (RC) levels and increased risk of chronic obstructive pulmonary disease (COPD).
- The odds ratio for COPD risk associated with RC was 1.222 (95% CI: 1.092-1.368, P<0.001) using the IVW method.
- No significant heterogeneity or horizontal pleiotropy was detected, supporting the robustness of the findings.
Conclusions:
- Elevated remnant cholesterol (RC) levels may contribute to an increased risk of developing chronic obstructive pulmonary disease (COPD).
- Further clinical studies are warranted to explore whether interventions aimed at reducing RC levels can mitigate COPD risk in the general population.
Background:
Remnant cholesterol (RC) represents the cholesterol of triglyceride (TG)-rich lipoproteins and is the portion of cholesterol other than both high-density (HDL-C) and low-density lipoprotein cholesterol (LDL-C). Higher RC levels have been associated with heightened inflammation. Chronic obstructive pulmonary disease (COPD) has been attributed mostly to cigarette smoking or environmental pollution. Disorders of lipid metabolism contribute to inflammation, but no studies have shown an association between RC and COPD. We aimed to investigate the association between RC levels and the pathogenesis of COPD.
Methods:
Pooled statistics for the associations between RC and COPD were obtained from published data of individuals of European ancestry, primarily sourced from the Integrative Epidemiology Unit (IEU) Open Genome-Wide Association Studies (OpenGWAS) project (including 115,078 European populations) and the FinnGen Biobank (including 16,410 COPD cases and 283,589 controls). To evaluate the causal relationship between RC and COPD, a two-sample Mendelian randomization (MR) analysis was employed. The primary MR method was inverse variance weighting (IVW). Statistical analysis and data visualization were performed using R software.
Results:
RC levels were positively associated with COPD risk according to MR analysis [IVW, odds ratio (OR): 1.222, 95% confidence interval (CI): 1.092-1.368; P<0.001; MR-Egger, OR: 1.279, 95% CI: 1.065-1.536; P=0.01; weighted median, OR: 1.208, 95% CI: 1.048-1.393; P=0.008]. No significant heterogeneity or horizontal pleiotropy was detected.
Conclusions:
High RC levels might increase the risk of developing COPD. Whether reducing RC levels among the population contributes to a lower risk of COPD remains to be investigated.
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