Low-density lipoprotein-cholesterol and risk of chronic obstructive pulmonary disease: A prospective study of 107.301 participants

Randomized controlled trials investigating the effect of statins on chronic obstructive pulmonary disease (COPD) have found statins to increase lung function and decrease rate of exacerbations in individuals with COPD. However, it is unknown whether this is due to off-target effects or lowering of low-density lipoprotein-cholesterol (LDL-c). We investigated the hypothesis that elevated plasma levels of LDL-c are associated with increased risk of COPD exacerbation and COPD-specific mortality using the Copenhagen General Population Study with outcomes ascertained prospectively through nationwide registries Lower levels of LDL-c were associated with increased risk of spirometric COPD (odds ratio for 1st vs 4th quartile of LDL-c: 1.07 (95 % CI: 1.01-1.14)). In prospective analyses, lower levels of LDL-c were associated with increased risk of COPD exacerbations with hazard ratios of 1.43 (1.21-1.70) for 1st vs 4th quartile of LDL-c, 1.21 (1.03-1.43) for 2nd vs 4th quartile of LDL-c, and 1.01 (0.85-1.20) for 3rd vs 4th quartile of LDL-c (p for trend: 6x10-6). Lower levels of LDL-c at baseline were likewise associated with increased risk of COPD-specific mortality in a stepwise manner (log-rank test p < 0.009). Sensitivity analyses with death as competing risk provided similar results. In conclusion, lower levels of LDL-c were associated with an increased risk of COPD exacerbation and COPD-specific mortality in the Danish general population. These findings might be a result of reverse causation indicating that individuals with severe phenotypes of COPD have lower plasma levels of LDL-c.