Investigators Find Causal Link Between Apolipoprotein A-I and COPD

Investigators established a causal link between apolipoprotein A-I (apoA-I) and chronic obstructive pulmonary disease (COPD), according to results of a study published in International Journal of Chronic Obstructive Pulmonary Disease. The authors of the study found a potential link between lipid metabolism and COPD in preliminary data; therefore, in this study, the investigators used a Mendelian randomization to analyze the potential causal link.¹

Chronic Obstructive Pulmonary Disease, Cholesterol, ApoA-I | Image Credit: surasak | stock.adobe.com

COPD is a respiratory disease associated with demographic factors such as smoking rates and air pollution. In results from another study published in BMC Pulmonary Medicine, investigators found that cigarette smoke extract can simulate bronchial epithelial cells, which can disrupt lipid metabolism and result in accumulation of lipids. This can cause an increase in oxidative stress levels, damage lung tissue, and lead to COPD. From these findings, the authors of the current study stated that it could indicate “risk factors of COPD are also factors that affect lipid metabolism in the body.”^1,2

Additionally, blood lipids are known to be associated with inflammation. In a review published in Frontiers in Cardiovascular Medicine, the authors state that lipids and inflammation can cause chronic illnesses, especially when lipoproteins become oxidized and are activated in the immune system. They found that reducing oxidative stress would reduce the retention of lipid proteins, thus reducing inflammation and halting atherogenesis. There is a clear link between lipids and inflammation as well as COPD and pulmonary inflammation. IL-6 and total cholesterol also have positive correlations with those who have severe COPD, but IL-10 and high-density lipoprotein cholesterol (HDL-C) have a negative correlation.^1,3

The authors of the study aimed to explore the potential causal links between circulating lipid concentration with the progression and treatment of COPD. They hoped that the results could lay groundwork for additional studies into this potential link.¹

In the analysis, the investigators included 22 independent single nucleotide polymorphisms (SNPs) for total cholesterol, 372 for triglyceride, 80 for low-density lipoprotein cholesterol, 80 for HDL-C, 160 for apoA-I, and 91 for apoB. The results showed an inverse relationship between LDL-C and COPD (OR = 0.994, 95% CI (0.989, 0.999), P = 0.019). ApoA-I showed a negative correlation with COPD, and triglyceride had a positive association with COPD, therefore, the study authors stated that LDL-C and apoA-I suppressed the risk while triglyceride promoted the risk. HDL-C, total cholesterol, and apoB did not have significant correlations with COPD.¹

The investigators also conducted a multivariable Mendelian randomization analysis. In this analysis, the investigators adjusted for confounding variables and potential mediators in the causal pathway in order to link the targeted risk factors to the outcome of interest. The risk factors included were triglyceride, LDL-C, apoA-I, and COPD. The results showed that there were no significant associations between either triglyceride and LDL-C with COPD (OR = 0.997, 95% CI [0.992–1.002], P=0.233) (OR = 0.997, 95% CI [0.992–1.003]), but apoA-I remained negatively linked to COPD (OR = 0.994, 95% CI [0.990–0.999], P=0.008).¹

REFERENCES

1. Huang P, Zhao Y, Wei H, et al. Causal Relationships Between Blood Lipid Levels and Chronic Obstructive Pulmonary Disease: A Mendelian Randomization Analysis. Int J Chron Obstruct Pulmon Dis. 2025;20:83-93. Published 2025 Jan 8. doi:10.2147/COPD.S476833

2. Zhou H, Zhang L, Li Y, et al. Cigarette smoke extract stimulates bronchial epithelial cells to undergo a SUMOylation turnover. BMC Pulm Med. 2020;20(1):276. Published 2020 Oct 23. doi:10.1186/s12890-020-01300-w

3. Bale BF, Doneen AL, Leimgruber PP, Vigerust DJ. The critical issue linking lipids and inflammation: Clinical utility of stopping oxidative stress. Front Cardiovasc Med. 2022;9:1042729. Published 2022 Nov 9. doi:10.3389/fcvm.2022.1042729