Freyberg Josefine, Landt Eskild M, Afzal Shoaib, Nordestgaard Børge G, Dahl Morten
Department of Clinical Biochemistry, Zealand University Hospital, Køge, Denmark.
Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
ERJ Open Res. 2023 Mar 6;9(2). doi: 10.1183/23120541.00496-2022. eCollection 2023 Mar.
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.
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.
In cross-sectional analysis, low LDL cholesterol was associated with increased risk of COPD (odds ratio for 1st 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 4th quartile, 1.21 (1.03-1.43) for 2nd 4th quartile, and 1.01 (0.85-1.20) for 3rd 4th quartile of LDL cholesterol (p-value for trend=6×10). 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.
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.
随机对照试验发现，降低低密度脂蛋白（LDL）胆固醇的他汀类药物可改善慢性阻塞性肺疾病（COPD）患者的肺功能，并可能降低其急性加重率。然而，尚不清楚高水平的LDL胆固醇是否与COPD易感性增加有关。
我们检验了以下假设：高LDL胆固醇与COPD风险增加、严重COPD急性加重和COPD特异性死亡率增加相关。我们对哥本哈根普通人群研究中的107301名成年人进行了调查。COPD结局在基线时确定，并通过全国性登记系统进行前瞻性随访。
在横断面分析中，低LDL胆固醇与COPD风险增加相关（第一四分位数与第四四分位数的比值比：1.07（95%CI 1.01-1.14））。前瞻性分析显示，低LDL胆固醇与COPD急性加重风险增加相关，LDL胆固醇第一四分位数与第四四分位数的风险比为1.43（1.21-1.70），第二四分位数与第四四分位数的风险比为1.21（1.03-1.43），第三四分位数与第四四分位数的风险比为1.01（0.85-1.20）（趋势p值=6×10）。最后，低LDL胆固醇同样与COPD特异性死亡率增加相关（对数秩检验：p=0.0009）。以死亡作为竞争风险的敏感性分析提供了类似的结果。
在丹麦普通人群中，低LDL胆固醇与严重COPD急性加重和COPD特异性死亡率增加相关。由于这与他汀类药物随机对照试验中观察到的情况相反，我们的发现可能是反向因果关系的结果，表明COPD严重表型个体由于消瘦导致血浆LDL胆固醇水平较低。
