C-Reactive Protein Is a Strong Predictor of COPD Outcomes

Key Point

Serum C-reactive protein level is a strong and independent predictor of COPD-related hospitalization and death.

HERLEV, DENMARK—Research has established that chronic systemic inflammation is a component of COPD. However, whether this inflammation significantly affects clinical outcomes is still a matter of debate. To shed light on this question, a group of researchers, including Børge G. Nordestgaard, MD, conducted a cohort study on the ability of C-reactive protein (CRP) to accurately predict prognosis in persons with chronic airway obstruction.¹

The investigators decided to look at CRP’s prognostic potential because the biomarker is a commonly monitored acute-phase reactant that appears to be useful in detecting the presence of systemic inflammation, said Dr. Nordestgaard, Chief Physician in the Department of Clinical Biochemistry at Herlev University Hospital in Denmark. “We found that a simple blood measurement of C-reactive protein in people with shortness of breath can determine who has a high risk of severe chronic obstructive lung disease and death,” Dr. Nordestgaard told Pulmonary Reviews.

Copenhagen City Heart Study Subgroup

To reach that conclusion, Dr. Nordestgaard and associates determined rates of COPD-related hospitalization and death for 1,302 persons with chronic airway obstruction, defined as FEV1/FVC of less than 0.7. These patients were a subgroup of the more than 10,000 participants in the ongoing Copenhagen City Heart Study.² The Danish National Hospital Discharge Register indicated that they had not previously been diagnosed with COPD nor had they previously been hospitalized for COPD or asthma.

Patients were followed for a median of eight years. During that time, there were 185 hospitalizations and 83 deaths due to COPD in the study population. As expected, patients with either of those outcomes were older, had a lower FEV₁ at baseline, and reported greater daily tobacco use than those who were not hospitalized and survived the follow-up period.

In addition, patients who were hospitalized or who died had significantly higher baseline serum CRP levels than those who did not have those outcomes. The largest difference in CRP level was observed between patients who died and those who did not (4.3 vs 2.3 mg/L).

A baseline CRP level that exceeded 3 mg/L was associated with more cumulative incidences of COPD-related hospitalization and death than was a level of 3 mg/L or lower. Among patients with baseline levels of less than 1 mg/L and among those with levels of 1 to 3 mg/L, the equivalent cumulative incidences of those outcomes were directly related to CRP level; however, the difference between these groups was not statistically significant, the investigators noted.

The crude hazard ratios for COPD-related hospitalization and death were 1.7 and 2.7, respectively, for patients with baseline CRP levels of more than 3 mg/L and and those with levels of 3 mg/L or less. After adjustment for age, the hazard ratios were 1.6 and 2.5, respectively; after adjustment for age, sex, FEV₁, tobacco use, and ischemic heart disease, the hazard ratios were 1.4 and 2.2, respectively. Baseline CRP levels that exceeded 3 mg/L were also associated with increased all-cause mortality.

In cross-sectional analyses with matching for FEV₁ and adjustment for sex, age, tobacco consumption, and ischemic heart disease, baseline CRP levels increased by an average of 1.2 mg/L in patients who were hospitalized for COPD, by 4.1 mg/L in those who died of COPD, and by an average of 1.9 mg/L in those who died of any cause. The researchers concluded that CRP level is “a significant predictor of clinical COPD outcomes adding to the prognostic value of FEV₁.”

They added, “The absolute 10-year risks for COPD hospitalization and death in individuals with C-reactive protein above 3 mg/L were 54% and 57%, respectively, among those older than 70 years with a tobacco consumption above 15 g/d and a percent predicted FEV1 of less than 50.”

Not an Independent Risk Factor?

Although the study findings agree with prospective data showing that CRP strongly predicts mortality among COPD patients, one cannot necessarily conclude that it is an independent risk factor, asserted Gavin C. Donaldson, PhD, in an accompanying editorial.³ “[S]uch a statement requires that predictive variables in the regression model not be correlated with each other and that all potential confounders be included,” stressed Dr. Donaldson, Lecturer in Respiratory Medicine at the Royal Free and University College Medical School in London.

He gave several other reasons for caution in linking CRP and COPD outcomes: “First, C-reactive protein increases in response to a number of infectious and inflammatory conditions and therefore it is not specific to COPD. Second, it has been estimated that 40% to 50% of the variation in serum C-reactive protein levels is due to inherited characteristics. Third, although inhaled corticosteroids can dramatically lower C-reactive protein levels by up to 50%, the evidence that they reduce COPD mortality is much less clear cut.”   

—Timothy Begany

Reference
1. Dahl M, Vestbo J, Lange P, et al. C-reactive protein as a predictor of prognosis in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2007;175: 250-255.
2. Schnohr P, Jensen G, Lange P, et al. The Copenhagen City Heart Study—Østerbroundersøgelsen: tables with data from the third examination, 1991-1994. Eur Heart J Suppl. 2001;3:H1-H83.
3. Donaldson GC. C-reactive protein: does it predict mortality? Am J Respir Crit Care Med. 2007;175:209-210.

Return to table of contents