CORRESPONDENCE

Mechanism of Statin-Associated Mortality Reduction in COPD

A paradoxical association between cholesterol level and clinical outcome has been suggested, yet never previously established, in patients with chronic obstructive pulmonary disease (COPD).

The authors sought to investigate the interaction between long-term survival, lipid profile and statin use in patients after acute exacerbation of COPD (AECOPD).

A retrospective study evaluating demographic, clinical and laboratory data of 615 consecutive patients admitted for AECOPD over a mean follow-up period of 24.8 months. Kaplan-Meier survival curves and multivariate analysis were used to identify independent prognostic predictors for all-cause mortality.

Mean ± standard deviation (SD) age of the study population was 71.8 ± 11.4 years. Unexpectedly, mean serum cholesterol ± SD levels were significantly higher in survivors (N = 340) versus nonsurvivors (N = 275): 181.5 ± 43.6 versus 171.6 ± 57.2 mg/dL, respectively, (P = 0.0043). Median survival for patients with cholesterol levels < 150 and > 200 mg/dL were 16.0 and 64.4 months, respectively (P = 0.0173). On multivariate analysis, cholesterol level < 150 mg/dL was an independent predictor of mortality, irrespective of cardiovascular risk factors (hazard ratio [HR] = 1.8430, 95% confidence interval [CI] = 1.2547–2.7072, P = 0.0019). Statin use had an independent protective effect, regardless of cholesterol level (HR = 0.4924, 95% CI = 0.2924–0.8292, P = 0.0080).

Low cholesterol levels are significantly associated with increased mortality after AECOPD. Nonetheless, as statin treatment was associated with reduced mortality over the entire range of cholesterol levels, its use should be considered in all COPD patients.

Despite recent studies that suggested statins' beneficial effects on chronic obstructive pulmonary disease (COPD) outcomes, the impact, if any, of statins on COPD exacerbations remains unclear. This study aimed to examine the association between statin use and risk of hospitalized COPD exacerbation, and to assess whether the association varied by statin initiation, dose, or duration of use.

A retrospective nested case-control study among patients with COPD was conducted analyzing a nationwide health insurance claims database in Taiwan. Cases were subjects hospitalized for COPD exacerbations; each case was matched to 4 randomly selected controls on age, sex, cohort entry, and number of COPD-related outpatient visits by an incident-density sampling approach. Conditional logistic regressions were employed to quantify the COPD exacerbation risk associated with statin use.

The study cohort comprised 14,316 COPD patients, from which 1584 cases with COPD exacerbations and 5950 matched controls were identified. Any use of statins was associated with a 30% decreased risk of COPD exacerbation (95% confidence interval [CI], 0.56-0.88), and current use of statins was related to a greater reduced risk (adjusted odds ratio [OR] 0.60; 95% CI, 0.44-0.81). A dose-dependent reduced risk of COPD exacerbation by statins was observed (medium average daily dose: adjusted OR 0.60; 95% CI, 0.41-0.89; high daily dose: adjusted OR 0.33; 95% CI, 0.14-0.73). The reduced risk remained significant for either short or long duration of statin use.

Statin use was associated with a reduced risk of COPD exacerbation, with a further risk reduction for statins prescribed more recently or at high doses.

It is now well established that cardiovascular disease contributes significantly to both morbidity and mortality in COPD. Shared risk factors for cardiovascular disease and COPD, such as smoking, low socioeconomic class, and a sedentary lifestyle contribute to the natural history of each of these conditions. However, it is now apparent that alternative, novel mechanisms are involved in the pathogenesis of cardiovascular disease, and these may play an important role in driving the increased cardiovascular risk associated with COPD. In this article, we discuss the potential mechanisms that link COPD to an increased risk of cardiovascular disease.

We still do not know whether the successful treatment of the comorbid diseases associated with COPD, mainly cardiovascular disease, also positively influences the course of the lung disease because so far there are few definite data documenting that treatment of COPD comorbidities will reduce morbidity and mortality rates in these patients. Observational studies suggest that COPD patients treated with statins, angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor blockers, and β-adrenoceptor blockers may have improved survival and reduced hospitalisation from exacerbations. Progress in basic and translational research has led to a better understanding of pharmacological mechanisms that may explain the effects of these drugs on COPD and some small clinical trial activity is beginning to generate promising results.