TY - JOUR

T1 - Low-density lipoprotein cholesterol and risk of COPD

T2 - Copenhagen General Population Study

AU - Freyberg, Josefine

AU - Landt, Eskild M.

AU - Afzal, Shoaib

AU - Nordestgaard, Børge G.

AU - Dahl, Morten

N1 - Publisher Copyright: © The authors 2023.

PY - 2023

Y1 - 2023

N2 - Background Randomised controlled trials found that low-density lipoprotein (LDL) cholesterol-lowering statins increase lung function and possibly decrease rate of exacerbations in individuals with COPD. However, it is unknown whether high levels of LDL cholesterol are associated with increased susceptibility to COPD. Methods We tested the hypothesis that high LDL cholesterol is associated with increased risk of COPD, severe COPD exacerbation and COPD-specific mortality. We examined 107 301 adults from the Copenhagen General Population Study. COPD outcomes were ascertained at baseline and prospectively through nationwide registries. Results In cross-sectional analysis, low LDL cholesterol was associated with increased risk of COPD (odds ratio for 1st versus 4th quartile: 1.07 (95% CI 1.01–1.14)). Prospectively, low LDL cholesterol was associated with increased risk of COPD exacerbations with hazard ratios of 1.43 (1.21–1.70) for 1st versus 4th quartile, 1.21 (1.03–1.43) for 2nd versus 4th quartile, and 1.01 (0.85–1.20) for 3rd versus 4th quartile of LDL cholesterol ( p-value for trend=6×10−6). Finally, low LDL cholesterol was likewise associated with increased risk of COPD-specific mortality (log-rank test: p=0.0009). Sensitivity analyses with death as competing risk provided similar results. Conclusion Low LDL cholesterol was associated with increased risks of severe COPD exacerbation and COPD-specific mortality in the Danish general population. As this is opposite of that observed in randomised controlled trials with statins, our findings might be a result of reverse causation indicating that individuals with severe phenotypes of COPD have lower plasma levels of LDL cholesterol due to wasting.

AB - Background Randomised controlled trials found that low-density lipoprotein (LDL) cholesterol-lowering statins increase lung function and possibly decrease rate of exacerbations in individuals with COPD. However, it is unknown whether high levels of LDL cholesterol are associated with increased susceptibility to COPD. Methods We tested the hypothesis that high LDL cholesterol is associated with increased risk of COPD, severe COPD exacerbation and COPD-specific mortality. We examined 107 301 adults from the Copenhagen General Population Study. COPD outcomes were ascertained at baseline and prospectively through nationwide registries. Results In cross-sectional analysis, low LDL cholesterol was associated with increased risk of COPD (odds ratio for 1st versus 4th quartile: 1.07 (95% CI 1.01–1.14)). Prospectively, low LDL cholesterol was associated with increased risk of COPD exacerbations with hazard ratios of 1.43 (1.21–1.70) for 1st versus 4th quartile, 1.21 (1.03–1.43) for 2nd versus 4th quartile, and 1.01 (0.85–1.20) for 3rd versus 4th quartile of LDL cholesterol ( p-value for trend=6×10−6). Finally, low LDL cholesterol was likewise associated with increased risk of COPD-specific mortality (log-rank test: p=0.0009). Sensitivity analyses with death as competing risk provided similar results. Conclusion Low LDL cholesterol was associated with increased risks of severe COPD exacerbation and COPD-specific mortality in the Danish general population. As this is opposite of that observed in randomised controlled trials with statins, our findings might be a result of reverse causation indicating that individuals with severe phenotypes of COPD have lower plasma levels of LDL cholesterol due to wasting.

U2 - 10.1183/23120541.00496-2022

DO - 10.1183/23120541.00496-2022

M3 - Journal article

C2 - 36891075

AN - SCOPUS:85150187438

VL - 9

JO - ERJ Open Research

JF - ERJ Open Research

SN - 2312-0541

IS - 2

M1 - 00496-2022

ER -