Risk of remnant cholesterol and chronic obstructive pulmonary disease: a mendelian randomization study.

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.