The impact of glucocorticoids and statins on sleep quality

Most physiology and behavior of mammalian organisms follow daily oscillations. These rhythmic processes are governed by environmental cues (e.g., fluctuations in light intensity and temperature), an internal circadian timing system, and the interaction between this timekeeping system and environmental signals. In mammals, the circadian timekeeping system has a complex architecture, composed of a central pacemaker in the brain's suprachiasmatic nuclei (SCN) and subsidiary clocks in nearly every body cell. The central clock is synchronized to geophysical time mainly via photic cues perceived by the retina and transmitted by electrical signals to SCN neurons. In turn, the SCN influences circadian physiology and behavior via neuronal and humoral cues and via the synchronization of local oscillators that are operative in the cells of most organs and tissues. Thus, some of the SCN output pathways serve as input pathways for peripheral tissues. Here we discuss knowledge acquired during the past few years on the complex structure and function of the mammalian circadian timing system.

Shift work is a risk factor for hypertension, inflammation, and cardiovascular disease. This increased risk cannot be fully explained by classic risk factors. One of the key features of shift workers is that their behavioral and environmental cycles are typically misaligned relative to their endogenous circadian system. However, there is little information on the impact of acute circadian misalignment on cardiovascular disease risk in humans. Here we show-by using two 8-d laboratory protocols-that short-term circadian misalignment (12-h inverted behavioral and environmental cycles for three days) adversely affects cardiovascular risk factors in healthy adults. Circadian misalignment increased 24-h systolic blood pressure (SBP) and diastolic blood pressure (DBP) by 3.0 mmHg and 1.5 mmHg, respectively. These results were primarily explained by an increase in blood pressure during sleep opportunities (SBP, +5.6 mmHg; DBP, +1.9 mmHg) and, to a lesser extent, by raised blood pressure during wake periods (SBP, +1.6 mmHg; DBP, +1.4 mmHg). Circadian misalignment decreased wake cardiac vagal modulation by 8-15%, as determined by heart rate variability analysis, and decreased 24-h urinary epinephrine excretion rate by 7%, without a significant effect on 24-h urinary norepinephrine excretion rate. Circadian misalignment increased 24-h serum interleukin-6, C-reactive protein, resistin, and tumor necrosis factor-α levels by 3-29%. We demonstrate that circadian misalignment per se increases blood pressure and inflammatory markers. Our findings may help explain why shift work increases hypertension, inflammation, and cardiovascular disease risk.

Corticosteroids have been used for the treatment of inflammatory bowel disease since the late 1940s. Upwards of 80% of patients may respond acutely to treatment with these medications, although 20% or more may be refractory and others become dependent on corticosteroid use to suppress disease activity. Side effects in the acute situation are relatively minor, although significant side effects (e.g., psychosis) have been encountered; the long-term use of corticosteroids is more problematic. This creates a milieu for the potential for serious and irreversible problems. These side effects are discussed in detail. The side effects from corticosteroids emulate from exogenous hypercortisolism, which is similar to the clinical syndrome of Cushing's disease. PubMed search for years 1966-2000, author's personal manuscript/abstract files, and citations of known references. Short-term corticosteroid use is associated with generally mild side effects, including cutaneous effects, electrolyte abnormalities, hypertension, hyperglycemia, pancreatitis, hematologic, immunologic, and neuropsychologic effects, although occasionally, clinically significant side effects may occur. Long-term corticosteroid use may be associated with more serious sequel, including osteoporosis, aseptic joint necrosis, adrenal insufficiency, gastrointestinal, hepatic, and ophthalmologic effects, hyperlipidemia, growth suppression, and possible congenital malformations.