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A3124 - Higher Levels of Growth Differentiation Factor 15 (GDF-15) Are Associated with Lower Walking Distance and Exercice Capacity in COPD: An Analysis of the SPIROMICS Cohort
Author Block: W. W. Labaki1, C. H. Martinez1, C. M. Freeman1, F. J. Martinez2, J. M. Wells3, S. P. Bhatt3, M. T. Dransfield3, C. B. Cooper4, N. Putcha5, N. N. Hansel5, E. R. Bleecker6, D. A. Meyers6, C. S. Pirozzi7, R. E. Kanner7, R. Paine III7, D. J. Couper8, W. K. O'Neal9, R. G. Barr10, P. G. Woodruff11, E. J. Ampleford12, V. E. Ortega12, J. L. Curtis1, M. K. Han1; 1Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI, United States, 2Division of Pulmonary and Critical Care Medicine, Cornell University, New York, NY, United States, 3Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL, United States, 4Department of Physiology, University of California Los Angeles, Los Angeles, CA, United States, 5Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, MD, United States, 6Division of Genetics, Genomics and Precision Medicine, University of Arizona, Tucson, AZ, United States, 7Division of Pulmonary Medicine, University of Utah, Salt Lake City, UT, United States, 8Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States, 9Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States, 10Division of Pulmonary, Allergy and Critical Care Medicine, Columbia University, New York, NY, United States, 11Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California San Francisco, San Francisco, CA, United States, 12Section on Pulmonary, Critical Care, Allergy and Immunologic Diseases, Wake Forest University, Winston Salem, NC, United States.
Rationale: Growth differentiation factor-15 (GDF-15) contributes to the loss of muscle mass in COPD. Whether increased levels of this cytokine translate into decreased exercise capacity in subjects with COPD has not been fully investigated. We hypothesized that higher GDF-15 levels are associated with a lower six-minute walking distance (6MWD).
Methods: We analyzed data from participants in the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) with GOLD stages 1-4 who had a plasma GDF-15 concentration measured by ELISA and who completed a six-minute hall walk test. We examined the association between plasma GDF-15 levels (reported in tertiles) and 6MWD (dichotomized at 350 meters) using a logistic regression model adjusted for age, gender, race, mMRC score, current smoking, body mass index, FEV1 % predicted and self-reported cardiovascular disease (coronary artery disease, angina, myocardial infarction, congestive heart failure, stroke and peripheral vascular disease). Subgroup analyses were performed in subjects with GOLD stages 1-2 and in those without a history of cardiovascular disease. Additionally, all analyses were replicated using an alternative measure of exercise capacity, the Veterans Specific Activity Questionnaire (VSAQ), which is a validated tool to predict metabolic equivalents of activity (METs).
Results: We identified 932 participants (mean age 66.2 years; 40.2% women). Compared to participants in the lowest GDF-15 tertile, those in the highest tertile were older, had a greater smoking history and reported chronic bronchitis, coronary artery disease and congestive heart failure more frequently, but had similar FEV1, dyspnea severity and exacerbation history. Adjusted logistic regression models showed that the odds of being in the low walking distance group were doubled among participants in the highest GDF-15 tertile compared to those in the lowest tertile (odds ratio [OR] 2.17, 95% CI 1.43-3.30, p=0.001). When VSAQ was used to assess physical activity, participants in the highest GDF-15 tertile were also more likely to have low exercise capacity defined as 0-4 METs (OR 1.48, 95% CI 1.00-2.20; p=0.05). The GDF-15 and walking distance associations were maintained in subgroup analyses restricted to participants with GOLD 1-2 spirometry and those without cardiovascular disease.
Conclusions: Higher levels of GDF-15 are associated with lower walking distance and physical activity as assessed by VSAQ in COPD, even among subjects with milder airflow obstruction and those free of cardiovascular disease. Further study is needed to determine whether GDF-15 can be used as a longitudinal biomarker following exercise interventions in subjects with COPD.