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. 2020 Aug 24;9(9):2737.
doi: 10.3390/jcm9092737.

A Novel Role of Growth Differentiation Factor (GDF)-15 in Overlap with Sedentary Lifestyle and Cognitive Risk in COPD

Tsunahiko Hirano  1 , Keiko Doi  1 , Kazuto Matsunaga  1 , Shun Takahashi  2 , Tomohiro Donishi  3 , Kazuyoshi Suga  4 , Keiji Oishi  5 , Kasumi Yasuda  2 , Yusuke Mimura  6 , Misa Harada  1 , Sumiteru Suizu  1 , Keita Murakawa  1 , Ayumi Chikumoto  1 , Yuichi Ohteru  1 , Kazuki Matsuda  1 , Sho Uehara  1 , Kazuki Hamada  1 , Shuichiro Ohata  1 , Yoriyuki Murata  5 , Yoshikazu Yamaji  1 , Maki Asami-Noyama  1 , Nobutaka Edakuni  1 , Tomoyuki Kakugawa  7
Affiliations

A Novel Role of Growth Differentiation Factor (GDF)-15 in Overlap with Sedentary Lifestyle and Cognitive Risk in COPD

Tsunahiko Hirano et al. J Clin Med. .

Abstract

Sedentary behavior and cognitive impairment have a direct impact on patients' outcomes. An energy metabolic disorder may be involved in the overlap of these comorbid conditions (motoric cognitive risk (MCR)) in patients with chronic obstructive pulmonary disease (COPD). We aimed to explore the linkage between a proapoptotic protein, growth differentiation factor (GDF)-15, and MCR. Physical activity (PA), cognitive function (Japanese version of the Montreal Cognitive Assessment: MOCA-J), and the serum GDF-15 levels were assessed in healthy subjects (n = 14), asthmatics (n = 22), and COPD patients (n = 28). In the entire cohort, serum GDF-15 had negative correlations with exercise (Ex) (ρ = -0.43, p < 0.001) and MoCA-J (ρ = -0.44, p < 0.001), and Ex and MOCA-J showed a positive correlation (ρ = 0.52, p < 0.0001). Compared to healthy subjects and asthmatics, COPD patients showed the highest serum GDF-15 levels and had a significantly higher proportion of subjects with MCR (both sedentary lifestyle (EX < 1.5) and cognitive risk (MoCA-J ≤ 25)). Also, we found that serum GDF-15 has a screening potential (100% sensitivity) greater than aging (67% sensitivity) for detecting MCR in COPD patients. In conclusion, higher serum GDF-15 had interrelationships with a sedentary lifestyle and cognitive risk. This protein was not disease-specific but could be a screening biomarker to detect MCR related to poor health outcomes of COPD patients.

Keywords: COPD; GDF-15; aging; cognitive impairment; comorbidity; motoric cognitive risk; sedentary.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Comparison of GDF-15 in coexistence status with sedentary lifestyle and cognitive risk in all subjects. Data are presented as box plot including median (IQR). P-values compared among subjects by Kruskal–Wallis test. GDF-15: Growth Differentiation Factor-15, Sedentary lifestyle + : EX (MET × hours per day) < 1.5, Sedentary lifestyle − : EX (MET × hours per day) ≥ 1.5, Cognitive risk + : MoCA-J scores ≤ 25, Cognitive risk − : MoCA-J scores > 25.
Figure 2
Figure 2
Frequency of sedentary lifestyle, cognitive risk, and MCR among subjects. Data are presented as frequency. P-values show post-hoc analysis between each group. MET: Metabolic equivalent, EX: Exercise (MET × hours), MoCA-J: Japanese version of the Montreal Cognitive Assessment, MCR: Motoric cognitive risk syndrome.
Figure 3
Figure 3
Comparison of GDF-15 in coexistence status with sedentary lifestyle and cognitive risk in COPD. Data are presented as boxplot including median (IQR). P-values compared among subjects by Kruskal–Wallis test. GDF-15: Growth Differentiation Factor-15 Sedentary lifestyle +: EX (MET × hours per day) < 1.5, Sedentary lifestyle − : EX (METs × hours per day) ≥ 1.5, Cognitive risk + : MoCA-J scores ≤ 25, Cognitive risk −: MoCA-J scores > 25.
Figure 4
Figure 4
Univariable models for age with GDF-15. (a) Correlation with age and GDF-15 among healthy subjects; (b) Correlation with age and GDF-15 among asthma; (c) Correlation with age and GDF-15 among COPD. GDF-15: Growth Differentiation Factor-15. Dotted lines show 95% confidence intervals.
Figure 5
Figure 5
Diagnostic ability in GDF-15 and age to identify MCR in COPD. AUC: Area under the curve, MCR: Motoric cognitive risk syndrome. Arrows mean cut-off point to identify coexistence of sedentary lifestyle and cognitive risk (MCR).
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