Circulating Fibronectin to C-reactive Protein Ratio and Mortality: A Biomarker In COPD?

¹ The James Hogg iCAPTURE Center for Cardiovascular and Pulmonary Research and St. Paul's Hospital, Vancouver, British Columbia, Canada; and Dept of Medicine (Pulmonary Division), University of British Columbia, Vancouver, British Columbia, Canada
² The James Hogg iCAPTURE Center for Cardiovascular and Pulmonary Research and St. Paul's Hospital, Vancouver, British Columbia, Canada
³ University of Minnesota School of Public Health, Minneapolis, MN, USA
⁴ Dept of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
⁵ Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
⁶ University of California at Los Angeles School of Medicine, Los Angeles, California, USA
⁷ Discovery Medicine, High Throughput Biology and Biomedical Data Sciences, GlaxoSmithKline R& D, King of Prussia, Pennsylvania, USA
⁸ Pulmonary and Critical Care Division, Caritas St Elizabeth's Medical Center, Tufts University School of Medicine, Boston, MA, USA

^* To whom correspondence should be addressed. E-mail: dsin{at}mrl.ubc.ca.

	Abstract

The balance between inflammatory and repair processes is important in maintaining lung homeostasis in chronic obstructive pulmonary disease (COPD). We determined whether or not an integrated index of a biomarker involved in inflammation, C-reactive protein (CRP), and another involved in wound repair, fibronectin, may be a good measure to predict clinical outcomes in COPD.

We measured circulating blood levels of CRP and fibronectin in 4,787 individuals with mild to moderate COPD, who were prospectively followed for more than 7 years after blood collection as part of the Lung Health Study. To assess the balance between repair and inflammation, we developed a simple ratio by dividing fibronectin by CRP levels and used a Cox proportional hazards model to determine the relationship between this ratio and all-cause and disease-specific causes of mortality.

The relationship between fibronectin to CRP ratio and all-cause mortality was L-shaped. There was an exponential decay in the adjusted hazard function (i.e. the risk of mortality) as the ratio decreased until a value of 148 was reached, beyond which point the hazard function did not significantly change. Similar results were observed for the risk of coronary and cardiovascular mortality.

Circulating fibronectin to CRP ratio is significantly associated with all-cause mortality of COPD patients. However, dissimilar to other biomarkers, the relationship appears to be L-shaped (and not linear) suggesting a threshold at 150. While promising, future studies are needed to validate this simple index as a biomarker in COPD.

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