Decreased nocturnal synthesis of melatonin in patients with coronary artery disease

Abstract

In human beings, cardiovascular activity has a distinct circadian variation: Heart rate, blood pressure, and vascular tone decrease at night. Nocturnal cardiovascular blunting is at least partially linked to the autonomic activity and increased risk of cardiac and cerebral events. To assess whether decreased nocturnal melatonin synthesis and secretion in coronary artery disease (CAD), we investigated nocturnal secretion pattern of melatonin in patients with CAD and healthy subjects. The present study performed in 16 patients with angiographically documented CAD (aged 46–71 years) and in nine healthy controls (aged 36–66 years). Blood samples were collected every 2 h between 22:00 and 08:00 h. Melatonin levels were measured with a commercially available radioimmunoassay kit. We found large interindividual variation in the pattern of melatonin secretion in both groups. Patients with CAD secreted less nocturnal melatonin at 02:00, 04:00 and 08:00 h than control subjects (P=0.014, P=0.04 and P=0.025, respectively). Peak and Δ melatonin (peak–lowest melatonin) were found lower in patients with CAD (48.6 [19.1–75.4] vs. 131.4 [67.8–137.2] pg/ml, P=0.006 and 43 [10.5–68.5] vs. 107.6 [55.7–113.1] pg/ml, P=0.002, respectively). Peak time of melatonin secretion was observed earlier in patients with CAD (02:00 h [23:00–02:00 h] vs. 03:45 h [02:00–05:00 h], P=0.04). Our study provides useful and preliminary information about decreased nocturnal melatonin synthesis and release in patients with CAD might help physicians in managing these patients.

Introduction

In human beings, cardiovascular activity has a distinct circadian variation: Heart rate, blood pressure, and vascular tone decrease at night [1], [2]. Nocturnal cardiovascular blunting is at least partially linked to the autonomic activity and increased risk of cardiac and cerebral events [3], [4], [5], [6]. Pineal hormone melatonin is secreted with a circadian variation in body fluids, and its circulating concentrations are found to be high at night and low during daytime in humans, and influences several important endocrine and biologic functions. Previous studies have suggested that melatonin possibly influences autonomic cardiovascular regulations in human [7], [8], [9]. These studies showed that oral administration of melatonin increases cardiac vagal tone, decreases blood pressure and vascular reactivity and norepinephrine level [7], [8], [9].

A decrease in nocturnal synthesis of melatonin was recently reported in patients with coronary artery disease (CAD) [10], [11], [12]. Brugger et al. [10] firstly reported it, but they only measured serum melatonin at 02:00 h in the night period. There is large interindividual variation in the pattern of melatonin release, for this reason analysis of fixed time may give wrong result [13], [14]. Other investigators studied nocturnal urinary excretion of 6-sulfatoxymelatonin (aMT6s), major melatonin metabolite, in patients with CAD [11], [12]. They hypothesized that aMT6s level reflects pineal melatonin production and secretion rate. These studies did not give any knowledge about nocturnal melatonin secretion pattern of patients with CAD. From these points of view, to assess whether impaired nocturnal melatonin synthesis and secretion in CAD, we investigated nocturnal secretion pattern of melatonin in patients with CAD and healthy subjects.