Matrix metalloproteinase-9 as a messenger in the crosstalk between obstructive sleep apnea and comorbid systemic hypertension, cardiac remodeling, and ischemic stroke: a literature review

Patients with obstructive sleep apnea syndrome (OSAS) showed higher prevalence in cardiovascular diseases due to aberrant hypoxia and oxidative stress. However, not all OSAS patients end up with cardiovascular disorders, and identification of novel biomarker will be invaluable for differentiating patients at risk. Here we tested the serum matrix metalloproteinase-9 (MMP-9) levels in 47 untreated OSAS patients and found that the MMP-9 level was positively correlated with severity of OSAS, which was consistent with hypoxia degree and duration. Besides, the MMP-9 level was higher in patients complicated with systematic hypertension (P < 0.001). Furthermore, we selected those OSAS patients without any cardiovascular dysfunction (n=35) and followed up for up to five years. By the end of follow-up, 12 patients had hypertension onset and 3 patients had left ventricular hypertrophy. By analyzing the clinical outcomes with MMP-9 expression, we demonstrated that high serum MMP-9 in OSAS patients was a risk factor for occurrence of cardiovascular diseases. In addition, we cultured the vascular endothelial cells (VEC) from rat aorta in hypoxia condition to investigate whether MMP-9 was elevated due to hypoxia in OSAS patients. Cellular results revealed that the expression, secretion, and activity of MMP-9 were all upregulated by hypoxia and can cleave the beta2-adrenergic receptor (β2AR) on VEC surface. Our results not only determined MMP-9 as a risk factor for cardiovascular diseases in OSAS patients, but also showed the possible involvement of hypoxia-MMP-9-β2AR signaling axis.

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Abstract TP221: Using Berlin Questionnaire and Epworth Sleepiness Scale to Identify Stroke Patients at Risk for the Sleep Apnea Syndrome

Stroke ◽

10.1161/str.44.suppl_1.atp221 ◽

2013 ◽

Vol 44 (suppl_1) ◽

Author(s):

Millene Camilo ◽

Alan Eckeli ◽

Heidi Sander ◽

Regina Fernandes ◽

Joao Leite ◽

...

Keyword(s):

Obstructive Sleep Apnea ◽

Ischemic Stroke ◽

Sleep Apnea ◽

Positive Predictive Value ◽

Negative Predictive Value ◽

Predictive Value ◽

Epworth Sleepiness Scale ◽

Berlin Questionnaire ◽

Stroke Patients ◽

Obstructive Sleep

Background: Sleep-disordered breathing (SDB) is frequent in the acute phase of stroke. Obstructive sleep apnea (OSA) has been found in 62% of stroke patients. The impact of OSA is significant after ischemic stroke, including early neurological deterioration, poor functional outcome and increased long-term mortality. However, performing polysomnography (PSG) for all patients with acute stroke for diagnose OSA is still impracticable. Therefore clinical tools to select patients at higher risk for OSA would be essential. The aim of this study was to determine the validity of the Berlin Questionnaire (BQ) and the Epworth Sleepiness Scale (ESS) to identify stroke patients in whom the PSG would be indicated. Methods: Subjects with ischemic stroke were stratified into high and low risk groups for SDB using a BQ. The ESS ≥ 10 was used to define excessive daytime sleepiness. The BQ and ESS were administered to the relatives of stroke patients at hospital admission. All patients were submitted to a full overnight PSG at the first night after symptoms onset. OSA severity was measured by the apnea-hypopnea index (AHI). Results: We prospectively studied 40 ischemic stroke patients. The mean age was 62 ± 12.1 years and the obstructive sleep apnea (AHI ≥ 15) was present in 67.5%. On stratifying risk of OSA in these patients based on the QB, 77.5% belonged to the high-risk and 50% to the ESS ≥ 10. The sensitivity of QB was 85%, the specificity 35%, the positive predictive value 74% and the negative predictive value 55%. For ESS was respectively 63%, 85%, 89% and 52%. The diagnostic value of the BQ and ESS in combination to predict OSA had a sensitivity of 58%, a specificity of 89%, a positive predictive value of 95% and a negative predictive value of 38%. Conclusions: The QB even applied to the bed-partners of stroke patients is a useful screening tool for OSA.

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