Association between butyrylcholinesterase activity and low-grade systemic inflammation.

BACKGROUND: Pro-inflammatory cytokine production is directly inhibited by acetylcholine (ACh), and a relationship between total circulating ACh hydrolytic capacity and inflammatory reactions has been previously reported. Butyrylcholinesterase (BChE) is the major ACh hydrolyzing enzyme in plasma, and the aim of our study was to evaluate its association with low-grade systemic inflammation. MATERIAL AND METHODS: A total of 4,077 patients clinically managed in the Cardiology, Hypertension, and Digestive Medicine Units were included in our study. Three subclinical chronic inflammatory degrees were established in accordance with the high-sensitivity C-reactive protein (hsCRP) concentrations proposed, for low (< 1 mg/L), average (1-3 mg/L), and high (> 3-10 mg/L) cardiovascular disease risk estimation. RESULTS: In male patients with subclinical chronic inflammation and hsCRP concentrations < 1 mg/L, a significant positive correlation was observed between BChE and hsCRP (p < 0.02); however, for hsCRP concentrations > 3 mg/L, the correlation between these variables in both sexes becomes significantly negative (p < 0.001), as in patients with acute inflammation (hsCRP > 10 mg/L). In all cases significant positive correlations were obtained between the BChE activities and albumin concentrations (p < 0.001). CONCLUSIONS: The liver production of BChE and albumin occurs in a coupled fashion, and these biochemical variables may be considered as negative inflammatory reactants, whose serum levels are inversely associated with the increasing degree of subclinical inflammation.

Circulating levels of vascular endothelial markers in obstructive sleep apnoea syndrome. Effects of nasal continuous positive airway pressure.

INTRODUCTION: Obstructive sleep apnoea syndrome (OSAS) is an important risk factor in cardiovascular disorders. Although the exact mechanism remains to be elucidated, the endothelial dysfunction process seems to be implicated. MATERIAL AND METHODS: In order to test this hypothesis, blood circulating levels of endothelial markers were measured at baseline and 1 year after treatment with continuous positive airway pressure (CPAP). We studied 37 males using polysomnography: 20 subjects with OSAS and a 17-subject control group. An OSAS-validated sleep questionnaire covering the most important cardiovascular risk factors was applied to all subjects. Furthermore, patients received a complete general physical examination and biochemistry test with lipid profile. The specific markers measured were intercellular cell adhesion molecule-1 (ICAM-1), E-selectin, endothelin-1, von Willebrand factor (vWF) and plasminogen activator inhibitor-1 (PAI-1). RESULTS: Obstructive sleep apnoea syndrome patients presented higher circulating levels of ICAM-1, endothelin-1 and PAI-1 than the control group. On the other hand, no differences were found in E-selectin and vWF. After 1 year of CPAP treatment, there was a significant decrease in circulating levels of ICAM-1 and PAI-1. On the other hand, no differences were found in endothelin-1, E-selectin and vWF. CONCLUSIONS: Obstructive sleep apnoea syndrome is associated with elevated levels of ICAM-1 and PAI-1 and these levels normalize after treatment with CPAP.

Obstructive sleep apnea syndrome is a systemic disease. Current evidence.

Obstructive sleep apnea syndrome (OSAS) is a highly prevalent sleep disorder, characterized by repeated disruptions of breathing during sleep. This disease has many potential consequences including excessive daytime sleepiness, neurocognitive deterioration, endocrinologic and metabolic effects, and decreased quality of life. Metabolic syndrome is another highly prevalence emerging public health problem that represents a constellation of cardiovascular risk factors. Each single component of the cluster increases the cardiovascular risk, but the combination of factors is much more significant. It has been suggested that the presence of OSAS may increase the risk of developing some metabolic syndrome features. Moreover, OSAS patients are at an increased risk for vascular events, which represent the greatest morbidity and mortality of all associated complications. Although the etiology of OSAS is uncertain, intense local and systemic inflammation is present. A variety of phenomena are implicated in this disease such as modifications in the autonomic nervous system, hypoxemia-reoxygenation cycles, inflammation, and coagulation-fibrinolysis imbalance. OSAS patients also present increased levels of certain biomarkers linked to endocrine-metabolic and cardiovascular alterations among other systemic consequences. All of this indicates that, more than a local abnormality, OSAS should be considered a systemic disease.

Plasminogen activator inhibitor-1 in obstructive sleep apnea patients with and without hypertension.

Obstructive sleep apnea syndrome (OSAS) is an important risk factor in cardiovascular disorders. Although the precise mechanism remains to be described, hypercoagulability seems to be involved. To test the presence of decreased fibrinolysis, we measured plasma levels of plasminogen activator inhibitor-1 (PAI-1) in 96 male subjects (32 subjects with OSAS, 32 subjects with both OSAS and hypertension, and a 32 subjects in the control group). All subjects completed a sleep questionnaire and underwent a general physical examination, biochemistry test, and polysomnography study. Patients and control subjects had similar baseline clinical characteristics for age, gender, smoking habit, and levels of cholesterol and triglycerides. Patients with OSAS presented significantly higher circulating levels of PAI-1 compared with the control group, and the difference was even more marked in patients with both OSAS and hypertension. OSAS patients presented a significant inverse correlation between PAI-1 levels and apnea-hypopnea index (r= -0.71, p<0.001). In conclusion, OSAS patients presented higher circulating levels of PAI than the control group, which was even greater when patients had associated hypertension.

Plasma levels of vascular endothelial markers in obstructive sleep apnea.

Although the link between obstructive sleep apnea syndrome and risk for cardiovascular disorders has yet to be fully described, the hypothetical involvement of endothelial dysfunction is pathophysiologically plausible. In order to test this hypothesis, we measured plasma levels of endothelial markers in 82 male subjects (41 subjects with obstructive sleep apnea syndrome and a 41-subject control group). Obstructive sleep apnea syndrome patients presented higher circulating levels of intercellular cell adhesion molecule-1, E-selectin, and endothelin-1 than the control group. On the other hand, no differences were found in the von Willebrand factor. Levels of E-selectin and intercellular cell adhesion molecule-1 were significantly correlated to total oxygen desaturation. However, no significant correlation was found in either endothelin-1 or von Willebrand factor. We conclude that obstructive sleep apnea syndrome is associated with changes in levels of adhesion molecules, and that this could be the result of obstructive sleep apnea syndrome-induced hypoxia.

Angiotensin II type 1 receptor blocker irbesartan ameliorates vascular function in spontaneously hypertensive rats regardless of oestrogen status.

BACKGROUND: Angiotensin II type 1 (AT1) receptor overexpression may play a decisive role in endothelial dysfunction during oestrogen deficiency in spontaneously hypertensive rats (SHRs). Similarly, exaggerated production of angiotensin II and enhanced expression of AT1 receptor have been reported in vessels of SHRs compared with normotensive rats. OBJECTIVE: To test the hypothesis that antihypertensive treatment with the AT1 receptor antagonist, irbesartan, could not only decrease blood pressure but also ameliorate endothelial dysfunction associated with both hypertension and oestrogen deficiency. METHODS: Ovariectomized and sham-ovariectomized SHRs were treated with 50 mg/kg irbesartan per day, administered with chow for 30 weeks. Sham-ovariectomized and ovariectomized rats receiving no treatment were used as control groups. At the end of the treatment period, the vascular reactivity of aortic rings was studied. RESULTS: In the irbesartan-treated groups, vasoconstriction induced by Nomega-nitro-l-arginine methyl ester (l-NAME) was increased and the response to phenylephrine exhibited greater potentiation in the presence of l-NAME, demonstrating a greater availability of basal nitric oxide in these groups. In addition, chronic treatment with irbesartan similarly enhanced the responsiveness of aortic rings from ovariectomized or sham-ovariectomized rats to acetylcholine and sodium nitroprusside. Incubation with indomethacin did not significantly alter acetylcholine- and sodium nitroprusside-induced relaxations in the irbesartan-treated rats. However, relaxations induced by acetylcholine and sodium nitroprusside in aortic rings from non-treated rats were significantly greater in the presence of indomethacin. CONCLUSION: Our data suggest that irbesartan enhances basal nitric oxide availability and ameliorates vascular relaxations in SHRs, by decreasing the production of cyclooxygenase-dependent contracting factors in smooth muscle cells, regardless of oestrogen status.