期刊
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
卷 182, 期 6, 页码 826-833出版社
AMER THORACIC SOC
DOI: 10.1164/rccm.201001-0020OC
关键词
sleep apnea; thrombosis; cardiovascular disease
资金
- NIH National Heart Lung Blood Institute [46380, K23 HL079114, K08 HL081385]
- NIH [M01 RR00080]
- American Heart Association [0530188N]
- Central Society of Clinical Research
- NCI [1 U54CA116867]
- National Center for Research Resources (NCRR), National Institutes of Health (NIH) [UL1 RR024989]
- American Heart Association
- American College of Chest Physicians/ASP
- Case School of Medicine
- Columbia University
- Health Right Products
- ATS
- Dymedix Inc.
Rationale Individuals with sleep-disordered breathing (SDB) are at increased cardiovascular risk, possibly due to SDB-related stresses contributing to atherosclerosis. Objectives: 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(O2) less than 90% (< 2%, >= 2%). Measurements and Main Results: Nonlinear associations were demonstrated: morning and evening PAI-1 increased by 12% (95% confidence interval [Cl], 5-20%; P < 0.001) and 11% (95% Cl, 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% Cl, 3-17%; P < 0.01). Morning fibrinogen increased on average by 8.4 mg/dl (95% Cl, 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 SOB 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 SOB were not observed with D-dimer.
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