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C-Reactive Protein Levels, Haplotypes, and the Risk of Incident Chronic Obstructive Pulmonary Disease

¹ Department of Respiratory Medicine, Ghent University and Ghent University Hospital, Ghent, Belgium; ² Department of Epidemiology, ³ Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, The Netherlands; ⁵ Inspectorate of Healthcare, The Hague, The Netherlands; ⁴ The Netherlands Consortium on Healthy Aging (NCHA), Rotterdam, The Netherlands

Correspondence and requests for reprints should be addressed to Bruno H.C. Stricker, M.B., Ph.D., Department of Epidemiology & Biostatistics, Erasmus University Medical Center, PO Box 2040, 3000 DR Rotterdam, The Netherlands. E-mail: b.stricker{at}erasmusmc.nl

Rationale: Chronic obstructive pulmonary disease (COPD) is characterized by substantial chronic inflammation in the pulmonary compartment as well as in the systemic circulation.

Objectives: To investigate potentially causal association, we examined whether serum levels of high-sensitivity C-reactive protein (hsCRP) and variations in the CRP gene are associated with the risk of developing COPD.

Methods: This study is part of the Rotterdam Study, a prospective population-based cohort study among subjects aged 55 years or older. At baseline, 6,836 subjects without COPD had a blood sample available for assessment of hsCRP serum levels and haplotypes of the CRP gene. We analyzed the association between hsCRP levels, CRP gene haplotypes, and incident COPD with Cox proportional hazard models, adjusted for age, sex, and other confounders.

Measurements and Main Results: High levels of hsCRP (>3 mg/L) were associated with a significantly increased risk of incident COPD (hazard ratio [HR], 1.7; 95% confidence interval [CI], 1.16–2.49) compared with persons with low levels (<1 mg/L). The risk remained increased after adjusting for potential confounders and introducing a latency period of 3 years. The risk was most pronounced in former smokers (HR, 2.2; 95% CI, 1.12–3.74). hsCRP was not a risk factor in never smokers. No CRP single nucleotide polymorphism or haplotype was associated with a significantly increased or decreased COPD risk.

Conclusions: Increased hsCRP levels are predictive for the occurrence of COPD in smokers. However, haplotypes of the CRP gene, which influence hsCRP levels, are not associated with an altered risk of developing COPD.

Key Words: chronic obstructive pulmonary disease • C-reactive protein • genetics epidemiology

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Cross-sectional studies have linked chronic obstructive pulmonary disease (COPD) to increased levels of C-reactive protein (CRP). What This Study Adds to the Field We demonstrate that elevated levels of serum high-sensitivity (hs) CRP (>3 mg/L) are significantly associated with an increased risk of future COPD, depending on the smoking behavior. However, polymorphisms of the CRP gene, which influence hsCRP levels, are not themselves associated with an altered risk of developing COPD.