Endotrophin is associated with chronic multimorbidity and all-cause mortality in a cohort of elderly women
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Endotrophin is associated with chronic multimorbidity and all-cause mortality in a cohort of elderly women. / Staunstrup, Line Mærsk; Bager, Cecilie Liv; Frederiksen, Peder; Helge, Jørn Wulff; Brunak, Søren; Christiansen, Claus; Karsdal, Morten.
In: EBioMedicine, Vol. 68, 103391, 2021.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Endotrophin is associated with chronic multimorbidity and all-cause mortality in a cohort of elderly women
AU - Staunstrup, Line Mærsk
AU - Bager, Cecilie Liv
AU - Frederiksen, Peder
AU - Helge, Jørn Wulff
AU - Brunak, Søren
AU - Christiansen, Claus
AU - Karsdal, Morten
N1 - Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.
PY - 2021
Y1 - 2021
N2 - BACKGROUND: The signalling peptide endotrophin is derived through proteolytic cleavage of the carboxyl-terminal during formation of type VI collagen. It is expressed by most descendants of the mesenchymal stem cells lineage, including adipocytes and fibroblasts, and have been proposed to be a central extracellular matrix hormone associated with several age-related diseases. We aimed to assess the association of endotrophin with chronic disease incidence and death in older women.METHODS: 5,602 elderly Danish women from the observational, prospective cohort: The Prospective Epidemiological Risk Factor (PERF) study were included in the analysis which covered baseline (BL) and follow-up (FU) 14 years later. An elastic net was used to investigate the relative importance of 58 variables to serum endotrophin-levels. 20 chronic diseases were defined on the basis of clinical variables available along with diagnoses extracted from both the National Patient Register, the National Diabetes Register and the Danish Cancer Registry. The cross-sectional associations between endotrophin-levels and these 17 chronic age-related diseases were investigated using logistic regression and a set-analysis explored disease-combinations within multimorbidity. The association of endotrophin with mortality was assessed by Cox proportional hazard models.FINDINGS: Formation of type III collagen (PRO-C3), age and creatine-levels were the most influential variables of endotrophin-levels. Several chronic diseases were significantly associated with endotrophin-levels independent of age and BMI including chronic kidney disease (BL OR=3.7, p < 0.001; FU OR = 7.9 p < 0.001), diabetes (BL OR = 1.5, p = 0.0015, FU OR=1.6, p = 0.004) and peripheral arterial disease (BL OR = 1.3, p = 0.029; FU OR=2.4, p < 0.001). Lastly, endotrophin-levels were significantly rising with number of morbidities (p < 0.001) and a predictor of death after adjusting for age and BMI (BL HR=1.95; FU HR = 2.00).INTERPRETATION: Endotrophin was associated with death and increased with number of morbidities. Endotrophin may be a central hormone of fibroblast that warrant investigation and possible targeted intervention in several chronic diseases.
AB - BACKGROUND: The signalling peptide endotrophin is derived through proteolytic cleavage of the carboxyl-terminal during formation of type VI collagen. It is expressed by most descendants of the mesenchymal stem cells lineage, including adipocytes and fibroblasts, and have been proposed to be a central extracellular matrix hormone associated with several age-related diseases. We aimed to assess the association of endotrophin with chronic disease incidence and death in older women.METHODS: 5,602 elderly Danish women from the observational, prospective cohort: The Prospective Epidemiological Risk Factor (PERF) study were included in the analysis which covered baseline (BL) and follow-up (FU) 14 years later. An elastic net was used to investigate the relative importance of 58 variables to serum endotrophin-levels. 20 chronic diseases were defined on the basis of clinical variables available along with diagnoses extracted from both the National Patient Register, the National Diabetes Register and the Danish Cancer Registry. The cross-sectional associations between endotrophin-levels and these 17 chronic age-related diseases were investigated using logistic regression and a set-analysis explored disease-combinations within multimorbidity. The association of endotrophin with mortality was assessed by Cox proportional hazard models.FINDINGS: Formation of type III collagen (PRO-C3), age and creatine-levels were the most influential variables of endotrophin-levels. Several chronic diseases were significantly associated with endotrophin-levels independent of age and BMI including chronic kidney disease (BL OR=3.7, p < 0.001; FU OR = 7.9 p < 0.001), diabetes (BL OR = 1.5, p = 0.0015, FU OR=1.6, p = 0.004) and peripheral arterial disease (BL OR = 1.3, p = 0.029; FU OR=2.4, p < 0.001). Lastly, endotrophin-levels were significantly rising with number of morbidities (p < 0.001) and a predictor of death after adjusting for age and BMI (BL HR=1.95; FU HR = 2.00).INTERPRETATION: Endotrophin was associated with death and increased with number of morbidities. Endotrophin may be a central hormone of fibroblast that warrant investigation and possible targeted intervention in several chronic diseases.
U2 - 10.1016/j.ebiom.2021.103391
DO - 10.1016/j.ebiom.2021.103391
M3 - Journal article
C2 - 34044221
VL - 68
JO - EBioMedicine
JF - EBioMedicine
SN - 2352-3964
M1 - 103391
ER -
ID: 271975235