Abstract
Myeloperoxidase is a strong oxidant stored in primary granules of neutrophils with potent antibacterial and proatherogenic properties. Myeloperoxidase has been implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, the relationship of myeloperoxidase to health outcomes in COPD is not well known. We measured serum myeloperoxidase levels from 4,677 subjects with mild to moderate airflow limitation in the Lung Health Study. Using a Cox proportional hazards model, we determined the relationship of serum myeloperoxidase concentration to the risk of all-cause and disease specific causes of mortality. We found that serum myeloperoxidase concentrations were significantly related to accelerated decline in forced expiratory volume in 1 second (FEV1) over 11 years of follow-up (p<0.0001), and this association persisted after adjustments for age, sex, race, baseline FEV1, and smoking status (p = 0.048). Serum myeloperoxidase concentrations were also associated with increased risk of cardiovascular mortality (p = 0.036). Individuals in the highest quintile of myeloperoxidase had a hazard ratio of cardiovascular mortality of 1.90 (95% confidence interval 1.00–3.58; p = 0.049) compared with those in the lowest quintile, which was particularly notable in patients who continued to smoke (adjusted p-value of 0.0396). However, serum myeloperoxidase concentration was not related to total mortality, respiratory mortality, or deaths from malignancies. In conclusion, increased serum myeloperoxidase levels are associated with rapid lung function decline and poor cardiovascular outcomes in COPD patients, which support the emerging role of myeloperoxidase in the pathogenesis of COPD progression and cardiovascular disease.
Highlights
Chronic obstructive pulmonary disease (COPD) is a major global health problem, affecting over 10% of the population aged 40 years and older [1] and contributing to 3 million deaths annually [2]
Even though baseline forced expiratory volume in 1 second (FEV1)% predicted was similar across quintiles of serum MPO levels, FEV1% predicted at blood draw and year 11 was inversely related to serum MPO levels
The overall effects of MPO on lung function declines were relatively small. This is the first investigation that has investigated the relationship of serum MPO concentrations to cardiovascular mortality and lung function decline over 11 years in a very large cohort of COPD patients with mild to moderate airflow limitation
Summary
Chronic obstructive pulmonary disease (COPD) is a major global health problem, affecting over 10% of the population aged 40 years and older [1] and contributing to 3 million deaths annually [2]. COPD is associated with low-grade systemic inflammation, which in turn is related to accelerated decline in lung function and extra-pulmonary complications and co-morbidities such as cardiovascular disease and skeletal muscle dysfunction [4,5,6]. MPO is a lysosomal enzyme that neutrophils use to kill microbes by generating a potent oxidant, hypochlorous acid [10]. It is heavily expressed in primary (azurophilic) granules of neutrophils. Using a large cohort of COPD patients [15], we assessed whether serum MPO is associated with an accelerated decline in lung function as measured by forced expiratory volume in 1 second (FEV1), and important COPD outcome such as total mortality and CVD mortality
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