Original clinical science
Advanced chronic obstructive pulmonary disease is associated with high levels of high-density lipoprotein cholesterol

https://doi.org/10.1016/j.healun.2010.12.010Get rights and content

Background

Chronic obstructive pulmonary disease (COPD) is an inflammatory systemic disease associated with numerous extrapulmonary manifestations. Amongst these is an increased risk for cardiovascular disease. The mechanisms for this association remain unclear. We sought to examine lipid trends in a well-characterized cohort of patients with severe COPD.

Methods

We conducted a retrospective prospective analysis of 126 consecutive individuals evaluated for lung transplantation with a diagnosis of COPD in whom lipid values were available. Observed lipid values were compared with a reference population without severe COPD.

Results

Compared with the reference population, mean low-density lipoprotein cholesterol (LDL-C) levels were slightly reduced at 108 ± 44 vs 117 ± 29.5 mg/dl (p = 0.02) in men but were no different in women. Mean high-density lipoprotein cholesterol (HDL-C) levels were significantly elevated at 62 ± 24 vs 45 ± 12 mg/dl (p < 0.0001) in men and at 83 ± 27 vs 59 ± 16 mg/dl in women (p < 0.0001). Prednisone use correlated with higher HDL-C levels but did not fully explain the extent of elevation. Angiographically proven coronary artery disease was found in 61% of individuals and was unrelated to HDL-C levels.

Conclusions

Severe COPD is associated with increased levels of HDL-C, which is partially attributable to oral steroid use. HDL-C in this population is not associated with reduced risk of angiographically proven coronary artery disease.

Section snippets

Methods

The methods of this study were reviewed and approved by The Johns Hopkins Hospital investigational review board. A total of 289 consecutive COPD patients evaluated at our center for consideration of lung transplantation from 1995 to 2009 were screened for inclusion in the analysis. Fasting lipid profiles were available in 126 of these patients. Patients were sequentially enrolled in a pre-transplant evaluation protocol. The following data were recorded: demographics, anthropometrics, pulmonary

Statistical analysis

Continuous data are expressed as mean ± SD, and categoric data are presented as counts and percentages. Univariate analyses to assess associations with HDL-C included the t test for comparing dichotomous variables, and the Pearson correlation was used to assess the relationship between continuous variables. Assumptions were checked graphically. Comparisons across tertiles of HDL-C were made with analysis of variance, chi-square, and Fisher exact tests, as appropriate. To assess independence of

Results

Clinical characteristics of the 126 study participants are described in Table 1. Patients were primarily white with severe COPD reflected by a mean FEV1 % predicted of 22% ± 10%, and 91% used supplemental oxygen. Left heart catheterization data were available in 88 (70%), and 61% had CAD-A. Despite HDL-C levels >70 mg/dl, 6 patients (5 women) had severe angiographic stenosis of >50% stenosis in the left main coronary or >70% stenosis in another epicardial artery. Two patients with this degree

Discussion

HDL-C levels were elevated in our cohort with severe COPD compared with a reference population without severe COPD or known CAD. Similar trends in HDL-C have been reported in smaller samples of COPD patients.14, 15, 16 Tisi et al15 described 29 men with COPD in whom HDL-C levels were compared with controls matched for age, obesity index, alcohol intake, smoking history, and race. Mean HDL-C values were elevated in the COPD patients at 72 ± 4 vs 54 ± 3 mg/dl for controls.15 Although they found

Study limitations

Although the prospective evaluation of patients through a transplant evaluation protocol strengthens the study and reduces bias, the cohort is still highly selected, with underrepresentation of active tobacco abuse, alcohol abuse, mild to moderate COPD, and heart failure. Only 6 patients carried the diagnosis of heart failure, and there were none with a left ventricular ejection fraction <35%. An association of heart failure with reduced levels of HDL-C has been observed,21 but we found no

Clinical implications

Most smokers do not develop COPD,22 suggesting that a combination of exposure and susceptibility is required. HDL has been shown to exert various anti-inflammatory effects in the lung,9 including binding α-1 anti-trypsin and manifesting its anti-elastase activity.23 HDL also appears to play an important role in COPD by effects on the production, trafficking, and function of surfactant,10, 11 which in turn reciprocally affects HDL24 in a fashion resembling an endocrine system. In a cohort of

Disclosure statement

None of the authors has a financial relationship with a commercial entity that has an interest in the subject of the presented manuscript or other conflicts of interest to disclose.

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