Do High Levels of HDL Cholesterol Increase COPD Risk?

September 20, 2016

Findings reported at the European Respiratory Society meeting point to "yes;" the effect size of decline in FEV1 may surprise you.

A new study presented by Elizabeth Oelsner, MD, of Columbia University, New York City, and colleagues at the 2016 European Respiratory Society (ERS) International Congress in London, raises interesting questions about the relationship between the lipid biology of the lung and development of chronic obstructive pulmonary disease (COPD). Oelsner’s results suggest specifically that there may be an association between lung function decline and higher levels of high-density lipoprotein (HDL) cholesterol.

According to Oelsner, among a general population-based sample of 32,350 adults, those who had higher HDL cholesterol levels at baseline had a 9 mL greater decline in forced expiratory volume in 1 second (FEV1) compared with those who had the lowest HDL cholesterol level at baseline (P <.0001). Study authors indicated that the effect size of the decline was equivalent to that of a 10-year increment in pack-years smoking.

Data from National Heart, Lung and Blood Institute's Pooled Cohorts Study-a pool of 6 large studies that measured both HDL cholesterol levels and spirometry readings-were examined.

The findings expand on a previous study by Oelsner and colleagues published in 2014, which showed that the expression of the gene for apolipoprotein M (APOM)-a component of HDL cholesterol-was related to FEV1/forced vital capacity (FVC) ratio and per cent emphysema. Researchers found that higher HDL levels were associated with lower FEV1/FVC ratio and greater per cent emphysema and suggested a novel role for the apolipoprotein M/HDL pathway in the pathogenesis of COPD and emphysema.

In her presentation at the 2016 ERS International Congress, Oelsner reviewed the study measures and methods used to analyze the latest study’s data. Enzymatic methods and mixed models (with cohort-specific covariance structure adjusted for baseline age, sex, race/ethnicity, smoking pack-years, hypertension, low-density lipoprotein and total cholesterol, cohort, and time-varying height, weight, and smoking status) were used to measure HDL cholesterol. The researchers followed guidelines of the American Thoracic Society/ERS for use of pre-bronchodilator spirometry. Each study participant had 2 to 5 spirometry readings, on average, over a period of 4 to 24 years. Only spirometry readings that were reproducible on 2 or more acceptable curves within 200 mL were included.

Of the 32,350 adults with longitudinal spirometry measures, mean age was 49 ± 19 years, 45% had never smoked, 25% were obese, and 14% had airflow limitation (median 2 measures). The mean HDL cholesterol level was 1.4 ± 0.4 mmol L, and the mean rate of FEV1 decline was 29.2 ± 0.1 mL/year.

High levels of HDL cholesterol were associated with a greater rate of decline in FEV1 (P <.0001) and FEV1/FVC (P <.0001) in adjusted models. When stratifying analyses, results were similar among men and women, participants who never smoked, non-obese participants, and those without airflow limitations.



Oelsner E, Balte P, Schwartz JE, et al. High density lipoprotein cholesterol (HDL-C) and longitudinal lung function in six United States (US) cohorts. Abstract presented at: European Respiratory Society International Congress 2016. September 5, 2016. London, UK.  Accessed September 8, 2016.

 Manichaikul A, Wilk JB, et al. APOM and high-density lipoprotein cholesterol are associated with lung function and per cent emphysema. Eur Respir J. 2014;43(4):1003-1017. doi: 10.1183/09031936.00147612.