Wednesday, February 20, 2008
statins and sleep disturbance
Study Results
Groups were comparable at baseline on all variables, including both sleep measures. At 6 months, both the statin treatment groups showed the expected reductions in LDL-C compared with placebo, although reductions in total cholesterol, LDL-C, and triglycerides were greater with simvastatin than with pravastatin ( Table 4 ).
Simvastatin use was associated with worse sleep quality, and greater reported sleep problems than either pravastatin or placebo ( Table 5 ). Although the differences on the rating scale were small, subjects on pravastatin actually perceived their sleep quality as being better than average (> 15 on the rating scale) whereas those on simvastatin perceived theirs to be slightly worse. Similar results were seen for sleep problems.
These differences between simvastatin and pravastatin or placebo were significant when analyzed by t-test of mean on-treatment sleep scores across randomization groups by t-test and regression analyses adjusted for baseline values of the respective sleep assessment ( Table 6 ). Pravastatin did not differ significantly from placebo on any sleep outcome. In a subset of patients who reported much worse or better sleep in terms of sleep problems, only half of the patients on simvastatin as on placebo reported a "much better" rating, and 2.7 times as many reported that their sleep problems were much worse.
Sleep quality and problems were all found to be associated with tiredness, irritability, and cognition, with stronger relationships between sleep quality and tiredness and between sleep problems and irritability and cognitive impairment.
Comment
Dr. Golomb acknowledged the study limitations: only 1 lipophilic and 1 hydrophilic statin were investigated, dose response was not examined; and it remains unknown whether the effects are modified in groups excluded from the study, such as subjects with diabetes or heart disease. However, she suggested that the difference observed between simvastatin and pravastatin in this study may due to their respective lipophilic or hydrophilic properties, although the differences in lipid reduction or other differences may be involved in the differences in sleep disturbance.
Asked about the mechanisms that might be involved, Dr. Golomb noted that in primates cholesterol lowering, although not by statins, has been shown to reduce levels of central serotonin, a precursor of melatonin, the sleep-regulating hormone; statins have also been shown to alter the ratio of omega-3 to omega-6 fatty acids (omega-3 fatty acids are believed to be important for sleep); or, as observed by Dr. Golomb's group, in some patients statins lead to mitochondrial dysfunction, which is associated with sleep-disordered breathing.
Medscape Cardiology. 2008; ©2008 Medscape
