The influence of abdominal visceral fat on inflammatory pathways and mortality risk in obstructive lung disease.
BACKGROUND
Low-grade systemic inflammation, particularly elevated IL-6, predicts mortality in chronic obstructive pulmonary disease (COPD). Although altered body composition, especially increased visceral fat (VF) mass, could be a significant contributor to low-grade systemic inflammation, this remains unexplored in COPD.


OBJECTIVE
The objective was to investigate COPD-specific effects on VF and plasma adipocytokines and their predictive value for mortality.


METHODS
Within the Health, Aging, and Body Composition (Health ABC) Study, an observational study in community-dwelling older persons, we used propensity scores to match n = 729 persons with normal lung function to n = 243 persons with obstructive lung disease (OLD; defined as the ratio of forced expiratory volume in 1 s to forced vital capacity < lower limit of normal). Matching was based on age, sex, race, clinic site, BMI, and smoking status. Within this well-balanced match, we compared computed tomography-acquired visceral fat area (VFA) and plasma adipocytokines, analyzed independent associations of VFA and OLD status on plasma adipocytokines, and studied their predictive value for 9.4-y mortality.


RESULTS
Whereas whole-body fat mass was comparable between groups, persons with OLD had increased VFA and higher plasma IL-6, adiponectin, and plasminogen activator inhibitor 1 (PAI-1). Both OLD status and VFA were independently positively associated with IL-6. Adiponectin was positively associated with OLD status but negatively associated with VFA. PAI-1 was no longer associated with OLD status after VFA was accounted for. Participants with OLD had increased risk of all-cause, respiratory, and cardiovascular mortality, of which IL-6 was identified as an independent predictor.


CONCLUSIONS
Our data suggest that excessive abdominal visceral fat contributes to increased plasma IL-6, which, in turn, is strongly associated with all-cause and cause-specific mortality in older persons with OLD.
NUTRIM School for Nutrition, Toxicology and Metabolism, Department of Respiratory Medicine, Maastricht University Medical Center, Maastricht, The Netherlands. b.vdborst@maastrichtuniversity.nl
Bram
B
van den Borst
Harry R
HR
Gosker
Annemarie
A
Koster
Binbing
B
Yu
Stephen B
SB
Kritchevsky
Yongmei
Y
Liu
Bernd
B
Meibohm
Thomas B
TB
Rice
Michael
M
Shlipak
Sachin
S
Yende
Tamara B
TB
Harris
Annemie M W J
AM
Schols
D052242:Adiponectin / Q000097:blood*; D000368:Aged; D004032:Diet / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D050152:Intra-Abdominal Fat / Q000276:immunology* / Q000473:pathology; D008297:Male; D016555:Matched-Pair Analysis; D009043:Motor Activity; D010414:Pennsylvania / Q000453:epidemiology; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood*; D015995:Prevalence; D057216:Propensity Score; D016016:Proportional Hazards Models; D029424:Pulmonary Disease, Chronic Obstructive / Q000276:immunology* / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D012189:Retrospective Studies; D012306:Risk; D013714:Tennessee / Q000453:epidemiology
C499918:ADIPOQ protein, human; D052242:Adiponectin; C508600:IL6 protein, human; D015850:Interleukin-6; D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human