Circulating antiangiogenic proteins in obstructive sleep apnea and hypertension

Obstructive sleep apnea (OSA) causes endothelial dysfunction and is an independent risk factor for hypertension and cardiovascular diseases. Although vasoactive agents and sympathoexcitation have been implicated and operational in the pathogenesis of hypertension associated with OSA the exact mechanisms underlying hypertension have not been established. Soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng) are released under hypoxic stress and cause endothelial dysfunction and hypertension in humans and animals. The present study was conducted to investigate the role of these antiangiogenic proteins in OSA and to determine their clinical significance.

In 22 untreated OSA patients with apnea-hypopnea index ≥30 events/h (11 with hypertension and 11 without hypertension) we measured plasma concentrations of endothelin-1, epinephrine, norepinephrine, nitric oxide metabolites, sFlt-1 and sEng.

The apnea-hypopnea indices were 81±11 and 76±9 events/h (P=ns) and the sleep times with SaO(2)<90% were 42±13 and 39±13 min (P=ns) for normotensives and hypertensives, respectively. Both groups had similarly elevated levels of catecholamines with normal endothelin-1 levels. Nitric oxide metabolites were depressed in both groups with no inter-group differences. On the other hand, both sFlt-1 (90.0±4.6 pg/ml vs. 74.0±4.4 pg/ml, P=0. 018) and sEng (4.9±0.34 ng/ml vs. 3.50±0.42 ng/ml, P=0.016) were significantly elevated in the hypertensive patients compared to the normotensive subjects.

These data show that sFlt-1 and sEng are increased in the circulation of patients with OSA and hypertension and suggest that they may be involved in the pathogenesis of hypertension.