Sleep-disordered breathing and prothrombotic biomarkers: cross-sectional results of the Cleveland Family Study.
BACKGROUND
Individuals with sleep-disordered breathing (SDB) are at increased cardiovascular risk, possibly due to SDB-related stresses contributing to atherosclerosis.


OBJECTIVE
We postulate that pathways associated with a prothrombotic potential are up-regulated in SDB.


METHODS
Morning and evening plasminogen activator inhibitor-1 (PAI-1), morning fibrinogen, and morning D-dimer were measured in 537 Cleveland Family Study adults. Piecewise multivariable linear mixed models estimated relative mean change or mean change in the biomarker per 5-unit increase in apnea-hypopnea index (AHI) in two groups: AHI less than 15 and AHI greater than or equal to 15, and hypoxia defined as percentage of sleep time with Sa(O(2)) less than 90% (< 2%, ≥ 2%).


RESULTS
Nonlinear associations were demonstrated: morning and evening PAI-1 increased by 12% (95% confidence interval [CI], 5-20%; P < 0.001) and 11% (95% CI, 2-20%; P = 0.01), respectively per 5-unit AHI increase until an AHI of 15, when no further increase in PAI-1 was demonstrated. The association between AHI and morning PAI-1 remained significant after adjusting for evening PAI-1 level (10%; 95% CI, 3-17%; P < 0.01). Morning fibrinogen increased on average by 8.4 mg/dl (95% CI, 3.12-13.65; P = 0.002) per five-unit AHI increase until an AHI of 15. There was no association between AHI and morning D-dimer. Hypoxia severity was not associated with thrombotic marker levels.


CONCLUSIONS
PAI-1 and fibrinogen levels increase monotonically with AHI at degrees of SDB considered mildly to moderately abnormal, suggesting that even mild SDB levels may increase prothrombotic processes. There may be a plateau in this effect, occurring at levels considered to reflect only moderate SDB severity. These relationships with mild-to-moderate SDB were not observed with D-dimer.
Mehra
Reena
R
Department of Medicine, Case Comprehensive Cancer Center, Case School of Medicine, Cleveland, Ohio, USA. reena.mehra@case.edu
Xu
Fang
F
Babineau
Denise C
DC
Tracy
Russell P
RP
Jenny
Nancy S
NS
Patel
Sanjay R
SR
Redline
Susan
S
D000328:Adult; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D003430:Cross-Sectional Studies; D005192:Family Health; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis*; D005340:Fibrinogen / Q000032:analysis*; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009820:Ohio; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood*; D012307:Risk Factors; D012720:Severity of Illness Index; D012891:Sleep Apnea Syndromes / Q000097:blood*; D013927:Thrombosis / Q000097:blood*; D015854:Up-Regulation
D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; D017395:Plasminogen Activator Inhibitor 1; C036309:fibrin fragment D; D005340:Fibrinogen