Chest
Volume 121, Issue 5, May 2002, Pages 1541-1547
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Clinical Investigations
Sleep
Adhesion Molecules in Patients With Coronary Artery Disease and Moderate-to-Severe Obstructive Sleep Apnea

https://doi.org/10.1378/chest.121.5.1541Get rights and content

Study objectives

It has been suggested that obstructive sleep apnea (OSA)-induced hypoxic stress might contribute to cardiovascular disorders by promoting expression of soluble adhesion molecules. The reported increase of circulating adhesion molecules in patients with OSA remains controversial because confounders such as cardiovascular risk factors and left ventricular function have not been adequately controlled for. We hypothesized that soluble intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, L-selectin, and E-selectin levels are correlated with OSA independent of coexisting coronary artery disease (CAD).

Settings

University-affiliated teaching hospitals.

Design and participants

A prospective study of 61 consecutive subjects with angiographically proven CAD deemed to have stable angina.

Interventions

Fifteen patients (mean ± SD) 61.2 ± 1.9 years old with moderate-to-severe OSA (apnea-hypopnea index [AHI] ≥ 20/h) were matched to a control group (AHI ≤ 5/h) for age, gender, body mass index, and severity of CAD. Venous blood samples were collected the morning of the sleep study and assayed for human ICAM-1, VCAM-1, L-selectin, and E-selectin with commercially available enzyme-linked immunosorbent assay kits.

Results

All but L-selectin were significantly increased in the OSA group compared to the control subjects (ICAM-1, 367.4 ± 85.2 ng/mL vs 252.8 ± 68.4 ng/mL, p = 0.008; VCAM-1, 961.5 ± 281.7 ng/mL vs 639.1 ± 294.4 ng/mL, p = 0.004; E-selectin, 81.0 ± 30.4 ng/mL vs 58.1 ± 23.2 ng/mL, p = 0.03, respectively). The increased levels of adhesion molecules correlated with the AHI and the oxygen desaturation index but not with the severity of hypoxemia or the frequency of arousals.

Conclusions

These findings suggest that OSA modulates the expression of proinflammatory mediators. Further studies should evaluate the influence of adhesion molecules on cardiovascular outcome in CAD patients with OSA.

Section snippets

Subjects

Seventy-two consecutive patients referred for evaluation of CAD at the Veterans Affairs Medical Center of Western New York were recruited for participation in the study. All study participants were free from previous stroke, transient ischemic attack, and cancer at study entry. Patients with valvular heart disease, cardiomyopathy (left ventricular ejection fraction ≤ 45%), malignant arrhythmias, severe pulmonary disease (FEV1 < 1.0 L), or those who were receiving oxygen or continuous positive

Results

Baseline clinical characteristics of patients and control subjects were similar for age, gender, anthropometric measurements, and major risk factors (Table 1). Patients with OSA and those without OSA did not differ in the use of β-blockers, calcium channel blockers, angiotensin-converting enzyme inhibitors, or lipid-lowering agents. The angiographic data were comparable in the two groups after controlling for the number of coronary arteries diseased (Table 2). In particular, the difference in

Discussion

The results of this study demonstrate the following: (1) circulating adhesion molecules are significantly elevated in CAD patients with moderate-to-severe OSA compared to those without OSA, and (2) the concentration of circulating adhesion molecules correlated with the severity of sleep apnea and the desaturation index but not with the severity of hypoxemia or the frequency of arousals.

Epidemiologic studies17,18 have suggested an association between OSA and systemic hypertension independent of

References (32)

  • Y Peker et al.

    An independent association between obstructive sleep apnoea and coronary artery disease

    Eur Respir J

    (1999)
  • Y Peker et al.

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

    Am J Respir Crit Care Med

    (2000)
  • M Pertinen et al.

    Long-term outcome for obstructive sleep apnea syndrome patients

    Chest

    (1988)
  • E Ohga et al.

    Increased levels of circulating ICAM-1, VCAM-1, and L-selectin in obstructive sleep apnea syndrome

    J Appl Physiol

    (1999)
  • R Ross

    The pathogenesis of atherosclerosis: a perspective for the 1990s

    Nature

    (1993)
  • JS Pober et al.

    Overlapping patterns of activation of human endothelial cells by interleukin-1, tumor necrosis factor, and immune interferon

    J Immunol

    (1986)
  • Cited by (0)

    This study was supported by a grant from the Research for Health in Erie County and Veterans Affairs enhancement funds.

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