Increased expression of blood muscarinic receptors in patients with reflex syncope.

AIMS: Pathophysiology of reflex syncope is not fully understood but a vagal overactivity might be involved in this syncope. Previously, overexpression of muscarinic M2 receptors and acetylcholinesterase was found in particular in the heart and in lymphocytes of rabbits with vagal overactivity as well as in hearts of Sudden Infant Death Syndromes. The aim of this present study was to look at M2 receptor expression in blood of patients with reflex syncope. The second objective was to measure acetylcholinesterase expression in these patients. METHODS AND RESULTS: 136 subjects were enrolled. This monocenter study pooled 45 adults exhibiting recurrent reflex syncope compared with 32 healthy adult volunteers (18-50 years) and 38 children exhibiting reflex syncope requiring hospitalization compared with 21 controls (1-17 years). One blood sample was taken from each subject and blood mRNA expression of M2 receptors was assessed by qRT-PCR. Taking into account the non-symmetric distributions of values in both groups, statistical interferences were assessed using bayesian techniques. A M2 receptor overexpression was observed in adult and pediatric patients compared to controls. The medians [q1;q3] were 0.9 [0.3;1.9] in patients versus 0.2 [0.1;1.0] in controls; the probability that M2 receptor expression was higher in patients than in controls (Pr[patients>controls]) was estimated at 0.99. Acetylcholinesterase expression was also increased 0.7 [0.4;1.6] in patients versus 0.4 [0.2;1.1] in controls; the probability that acetylcholinesterase expression was higher in patients than in controls (Pr[patients>controls]) was estimated at 0.97. Both in adults and children, the expression ratio of M2 receptors over acetylcholinesterase was greater in the patient group compared with the control group. CONCLUSION: M2 receptor overexpression has been detected in the blood of both, adults and children, exhibiting reflex syncope. As in our experimental model, i.e. rabbits with vagal overactivity, acetylcholinesterase overexpression was associated with M2 receptor overexpression. For the first time, biological abnormalities are identified in vagal syncope in which only clinical signs are, so far, taken into account for differential diagnosis and therapeutic management. Further work will be needed to validate potential biomarkers of risk or severity associated with the cholinergic system.

Carotid plaques, but not common carotid intima-media thickness, are independently associated with aortic stiffness.

OBJECTIVE: It has been suggested that non-invasive aortic stiffness measurements can be used as an indicator of atherosclerosis. The relationships of arterial stiffness with arterial wall hypertrophy and atherosclerosis however, have rarely been investigated in large-scale studies. The present study reports the associations of carotid arterial structure assessed by B-mode ultrasound with carotid-femoral pulse-wave velocity in hypertensive and non-hypertensive subjects. DESIGN AND METHODS: Free health examinations were performed on 564 subjects (age 58.2 +/- 10.8 years, 31.9% of women, 53.2% of all were hypertensive). Carotid-femoral pulse-wave velocity (PWV) was used to assess aortic stiffness. Carotid ultrasound examination included measurements (at sites free of plaques) of intima-media thickness (IMT) at the common carotid arteries (CCA), CCA-lumen diameter, and assessment of atherosclerotic plaques in the extracranial carotid arteries. RESULTS: Subjects with carotid plaques had significantly higher mean sex-adjusted values of PWV than those without carotid plaques (12.7 +/- 0.2 versus 11.1 +/- 0.1 m/s, P < 0.001). Multivariate analyses showed that this association was independent of sex, age, height, body mass index, mean blood pressure, pulse pressure, diabetes, hypercholesterolaemia and smoking habits (P < 0.009). PWV was positively associated with CCA-IMT and CCA-lumen diameter in sex-adjusted analysis (partial correlation coefficients (r ) were respectively 0.39 and 0.42, P < 0.001 for each). However, the association of PWV with CCA-IMT, but not that with CCA-lumen diameter, disappeared after further adjustment for age and blood pressure measurements (mean blood pressure and/or pulse pressure). CONCLUSION: This study shows that there is a differential association of PWV with CCA-IMT and carotid plaques. The nature of the independent positive association between atherosclerosis and arterial stiffness should be thoroughly investigated.