Association Between Polysomnographic Measures of Disrupted Sleep and Prothrombotic Factors

doi:10.1378/chest.06-2006

Chest

Volume 131, Issue 3, March 2007, Pages 733-739

https://doi.org/10.1378/chest.06-2006 Get rights and content

Abstract

Background:Subjective sleep disturbances have been associated with increased risk of coronary artery disease (CAD). We hypothesized that disrupted sleep as verified by polysomnography is associated with increased levels of prothrombotic hemostasis factors previously shown to predict CAD risk.

Methods:Full-night polysomnography was performed in 135 unmedicated men and women (mean age ± SD, 36.8 ± 7.8 years) without a history of sleep disorders. Morning fasting plasma levels of von Willebrand Factor (VWF) antigen, soluble tissue factor (sTF) antigen, d-dimer, and plasminogen activator inhibitor (PAI)-1 antigen were determined. Statistical analyses were adjusted for age, gender, ethnicity, body mass index, BP, and smoking history.

Results:Higher total arousal index (ArI) was associated with higher levels of VWF (β = 0.25, p = 0.011, ΔR²= 0.045), and longer wake after sleep onset was associated with higher levels of sTF (β = 0.23, p = 0.023, ΔR²= 0.038). More nighttime spent at mean oxygen saturation < 90% (β = 0.20, p = 0.020, ΔR²= 0.029) and higher apnea-hypopnea index (AHI) [β = 0.19, p = 0.034, ΔR²= 0.024] were associated with higher PAI-1. There was a trend for a relationship between mean oxygen desaturation < 90% and PAI-1 (p = 0.053), even after controlling for AHI. Total ArI (β = 0.28, p = 0.005, ΔR²= 0.056) and WASO (β = 0.25, p = 0.017, ΔR²= 0.042) continued to predict VWF and sTF, respectively, even after controlling for AHI.

Conclusions:Polysomnographically verified sleep disruptions were associated with prothrombotic changes. Measures of sleep fragmentation and sleep efficiency were related to VWF and sTF, respectively. Apnea-related measures were related to PAI-1. Our findings suggest that sleep disruptions, even in a relatively healthy population, are associated with potential markers of prothrombotic cardiovascular risk.

Section snippets

Study Participants

All subjects gave informed written consent on the study protocol approved by the University of California San Diego Institutional Review Board. Participants consisted of employed (≥ 30 h/wk) men and women recruited from the community by advertisement, by word of mouth, or by referral from local medical practitioners to participate in a study on BP, cardiovascular physiology, and sleep as described in more detail elsewhere.30, 31Recruitment strategies yielded a total of 385 individuals who

Subject Characteristics

Table 1 provides the demographic and sleep characteristics as well as plasma levels of hemostasis factors of the entire sample of 135 subjects. Nineteen subjects (14%) were found to have an AHI > 15 events/h and were considered to have OSA.

Bivariate Associations Between Subject Characteristics and Hemostasis

Levels of d-dimer correlated with age (r= 0.26, p = 0.002) and were higher in women than in men (341 ± 318 ng/mL vs 223 ± 147 ng/mL, p < 0.001) and in African Americans than in whites (328 ± 315 ng/mL vs 233 ± 155 ng/mL, p = 0.011). PAI-1 correlated with BMI (

Discussion

The aim of this study was to examine the notion that disrupted sleep may confer a prothrombotic state. We found that poor general sleep efficiency (longer WASO and lower sleep efficiency) predicted sTF. Measures that relate to perturbed sleep architecture and increased sleep fragmentation (less percentage of SWS and more arousals) were related to higher VWF. Measures reflecting apnea severity (higher AHI and more nighttime spent with Spo₂< 90%), were related to PAI-1. Different types of sleep

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This research was supported in part by National Institutes of Health grants HL44915, AG08415, M01 RR00827, HL36005, and K23 HL04056–01.

The authors have no financial or other potential conflicts of interest to disclose.

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Chest

Original ResearchAssociation Between Polysomnographic Measures of Disrupted Sleep and Prothrombotic Factors

Abstract

Section snippets

Study Participants

Subject Characteristics

Bivariate Associations Between Subject Characteristics and Hemostasis

Discussion

Prog Cardiovasc Dis

Chest

Chest

J Psychosom Res

Curr Probl Cardiol

Thrombogenic risk factors for atherothrombosis

Rev Cardiovasc Med

Overview of hemostatic factors involved in atherosclerotic cardiovascular disease

Lipids

Hemostatic risk factors for atherothrombotic disease: an epidemiologic view

Thromb Haemost

Sleep-disordered breathing and cardiovascular disease: cross-sectional results of the Sleep Heart Health Study

Am J Respir Crit Care Med

Sleep-disordered breathing and coronary artery disease: long-term prognosis

Am J Respir Crit Care Med

Respiratory disturbance index: an independent predictor of mortality in coronary artery disease

Am J Respir Crit Care Med

A path model of chronic stress, the metabolic syndrome, and coronary heart disease

Psychosom Med

Fibrinogen levels and obstructive sleep apnea in ischemic stroke

Am J Respir Crit Care Med

Morning increase of whole blood viscosity in obstructive sleep apnea syndrome

Clin Hemorheol Microcirc

Blood viscosity and platelet function in patients with obstructive sleep apnea syndrome treated with nasal continuous positive airway pressure

Clin Hemorheol Microcirc

Circulating cardiovascular risk factors in obstructive sleep apnoea: data from randomised controlled trials

Thorax

In vivoplatelet activation is increased during sleep in patients with obstructive sleep apnea syndrome

Respiration

Platelet function and fibrinolytic activity in hypertensive and normotensive sleep apnea patients

Sleep

Original Research
Association Between Polysomnographic Measures of Disrupted Sleep and Prothrombotic Factors