INTRODUCTION
Statin therapy is a basis for the primary and secondary prevention of cardiovascular diseases. Drugs administered in this group of diseases account for approximately 37.5-48.6% of the total number of administered drugs in the population [1, 2].
As a result of a large number of studies and meta-analyses, statins seem to be safe and well tolerated by patients [3-6]. According to experts, total statin intolerance, which requires withdrawal of a statin, affects < 5% of patients with symptoms of statin intolerance [7, 8]. Statin therapy is fraught with a low risk of side effects. Statin-related side effects include muscle pain (3-5%), myopathy (0.1-0.2%), hepatotoxicity (< 1%), and prodiabetogenic effects (9-27%) [9, 10].
The European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS) consensus “Adverse Effects of Statin Therapy” emphasized there is no evidence that long-term statin use negatively affects cognitive function, contributes to cataracts, or increases the risk of haemorrhagic stroke in people without cerebrovascular disease [10, 11].
A U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) analysis showed that people on statin therapy reported abnormalities during sleep such as increased time needed to fall asleep, more frequent nocturnal awakenings, and parasomnias [12]. Some studies indicate that statins can cause sleep disorders, which can be manifested by nightmares, hallucinations, and insomnia [13, 14]. Furthermore, people requiring statin therapy were more likely to use hypnotic drugs [12]. However, neither the ESC nor EAS has presented their opinion on the effect of statin use on sleep disorders [11].
Sleep disorders are a problem especially in the elderly, in whom they can affect not only the quality of life but can also have negative health consequences, such as weight gain or insulin resistance [7]. It is suggested that the use of statins with a high degree of lipophilicity may be associated with frequent occurrence of central nervous system disorders compared to hydrophilic statin therapy. Hydrophilic statins (rosuvastatin and pravastatin) appear to induce fewer symptoms of statin intolerance, which is especially important in elderly patients [15, 16].
The introduction and use of standardized scales of subjective sleep quality assessment such as the Pittsburgh Sleep Quality Index (PSQI), the Athens Insomnia Scale (AIS), and the Insomnia Severity Index (ISI) allow us to assess sleep quality disorders and can be a useful tool for monitoring the safety of statin therapy.
The aim of the study was to assess the association between use of statins (atorvastatin and rosuvastatin) and the risk of sleep disturbances compared with a group of patients not receiving statin therapy. Additionally, we compared the effect of atorvastatin and rosuvastatin on sleep quality.
MATERIAL AND METHODS
The study included 200 patients (85 males and 115 females, mean age: 69.4 ± 11 years) hospitalized in the Department of Internal Medicine and Clinical Pharmacology of the Wladyslaw Bieganski Hospital in Lodz in the years 2016-2018. The study group consisted of 135 people (62 males and 73 females, mean age: 71.1 ± 10.2 years) requiring chronic statin therapy, of whom 50 patients took rosuvastatin (RP) and 85 took atorvastatin (AP). The control group (CG) consisted of 65 people (23 males and 42 females, mean age: 65.8 ± 11.6 years) who were not administered drugs.
Patients qualified for the control group did not have indications for statin therapy, in the future we will want to conduct an analysis with patients who have indications for statin therapy and do not take the drug.
While analysing the group of patients included in the study, we could not modify the chronic pharmacotherapy.
PATIENT SELECTION CRITERIA
Criteria for inclusion in the study: informed consent of the patient, chronic (> 3 months) intake of atorvastatin or rosuvastatin, and age > 18 years.
Criteria for exclusion from the study: prostatic hyperplasia, sleep apnoea syndrome, decompensated heart failure, decompensated diabetes, acute coronary syndrome, cerebrovascular disease, transient ischaemic attack in the last 3 months, hospitalization due to a surgery or acute, severe illness, active or past cancer, depression, Parkinson’s disease, Alzheimer’s disease, and MMSE score < 24.
We excluded patients with decompensated diabetes type 2 from the study due to the effect of the symptoms of decompensated diabetes on sleep quality. We did not include patients with pre-diabetes.
This study did not analyse the effect of physical activity on sleep quality. The patients enrolled in the study were fully independent with no restrictions in daily physical activity.
DESCRIPTION OF LIPID PROFILE ASSESSMENT
The lipid profile in the serum of patients chronically using statins and in the control group was determined using the colorimetric assay. The lipid profile included total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides.
SCALES AND QUESTIONNAIRES
Sleep quality was examined using scales and questionnaires applicable in the diagnostics of sleep disorders.
The Athens Insomnia Scale evaluates the quality of sleep and the quality of the following day. A score equal to or higher than 8 indicates insomnia [17].
The Pittsburgh Sleep Quality Index assesses the following components of sleep quality, i.e. subjective sleep quality, duration of sleep, and ability to function during the day. The total number of points obtained is interpreted as poor sleep quality (score > 5) or good sleep quality (≤ 5) [18].
The Insomnia Severity Index assesses the severity of both nighttime and daytime components of insomnia. Achieving ≥ 14 points indicates insomnia [19].
Cognitive skills were assessed using the revised Mini-Mental State Examination (MMSE). A score < 24 points is identified as dementia, 24–26 points as mild cognitive impairment, and > 27 points as normal.
STATISTICAL ANALYSIS
The obtained data were subjected to a statistical analysis. The results were expressed as the average value ± the standard deviation (for quantitative variables) and the structure of the indicator (for qualitative variables). Statistical significance between the 2 groups was determined using the nonparametric Mann-Whitney test. A p-value < 0.05 was considered statistically significant. The χ2 independence test was used to compare qualitative variables; in the case of non-compliance with assumptions of this test, the exact Fisher test was used.
All analyses were performed using STATISTICA v 12.5 (StatSoft, Inc., Krakow, Poland).
ETHICAL APPROVAL AND CONSENT TO PARTICIPATE
The study received a positive opinion of the Bioethics Committee of the Medical University of Lodz: Consent number RNN/148/18/EC of 12.06.2018.
All participants received study material informing about the study objectives, the voluntariness of participation, and data protection. All participants gave written consent prior to their participation.
RESULTS
The study group consisted of 135 people (62 males and 73 females, aged between 45 and 90 years; mean age: 71.1 ± 10.2 years) who had been administered a statins for at least 3 months. Of this number, 50 patients took rosuvastatin (RP) and 85 patients took atorvastatin (AP). Doses of rosuvastatin ranged between 5 and 40 mg (mean 15.1±8.8 mg), and atorvastatin between 10 and 80 mg (mean 23.25 ± 13 mg). Patients > 65 years of age accounted for 70% of the entire group who had been taking statins for at least 3 months. The average Mini-Mental State Examination (MMSE) score equalled 26.3 ± 3.2.
The control group (CG) (i.e. not taking statin drugs) consisted of 65 people (23 males and 42 females, aged between 45 and 90 years; mean age: 65.8 ± 11.6). Patients aged > 65 years accounted for 58% of the non-statin group. The average score on the Mini-Mental State Examination (MMSE) was 27 ± 3.3.
Patients took atorvastatin and patients took rosuvastatin demonstrated significantly lower levels of total cholesterol (161.9 ± 50 atorvastatin and 162.1 ± 51.2 rosuvastatin) compared to the CG (181.45 ± 40.7), p < 0.05 and low-density lipoprotein (LDL) cholesterol levels (89.5 ± 38.4 atorvastatin and 85.8 ± 37.5 rosuvastatin) compared to the CG (101 ± 30.9), p < 0.05. High-density lipoprotein (HDL) cholesterol levels were significantly lower in the AP compared to RP and in the CG (p < 0.05). Triglycerides (TG) values did not differ significantly between the groups. There was no difference in LDL cholesterol concentration in patients chronically using atorvastatin or rosuvastatin.
The age difference was not significant between the AP (72.1 ± 1) and RP (69.3 ± 9.8) therapy compared to the CG 65.8 ± 11.6, p > 0.05 (Table 1).
EFFECT OF ATORVASTATIN AND ROSUVASTATIN ON THE AIS COMPARED TO THE CONTROL GROUP
Patients took atorvastatin or patients took rosuvastatin scored significantly higher on the AIS 10.3 ± 4.7 vs. 6.7 ± 2.9 (p < 0.001), respectively; 9.1 ± 4.4 vs. 6.7 ± 2.9 (p < 0.001) (Figure 1A). AP or RP therapy scored significantly higher on the AIS in the first 5 questions about symptoms that occur at night compared to the CG of 6.4 ± 3.3 (p < 0.001) 5.3 ± 3.1 (p < 0.05) vs. 3.7 ± 2.3, respectively (Figure 1B).
EFFECT OF ATORVASTATIN AND ROSUVASTATIN ON THE PSQI COMPARED TO THE CONTROL GROUP
Patients took atorvastatin or patients took rosuvastatin scored significantly higher in the PSQI compared to the CG of 8.9 ± 3.9, respectively; 8.4 ± 4.6 vs. 6.2 ± 3.3, p < 0.001 (Figure 2).
EFFECT OF ATORVASTATIN AND ROSUVASTATIN ON THE ISI COMPARED TO THE CONTROL GROUP
Patients took atorvastatin or patients took rosuvastatin scored significantly higher in the ISI compared to the CG 11.0 ± 5.5 vs. 7.1 ± 3.7 (p < 0.001), respectively; 9.3 ± 5.3 vs. 7.1 ± 3.7 (p < 0.05) (Figure 3).
EFFECT OF ROSUVASTATIN AND ATORVASTATIN ON SLEEP QUALITY
Patients taking 20 mg of rosuvastatin (p < 0.05) received more points on all scales assessing sleep quality disorders. There was no relationship between the dose of atorvastatin (20 mg and 40 mg), the dose of rosuvastatin (10 mg), and the number of points obtained on scales assessing sleep quality disorders (Table 2).
DISCUSSION
Statins are drugs commonly applied in the treatment of hypercholesterolaemia. Generally, they are well tolerated and rarely induce side effects (which mainly affect muscles [pain, weakness, and fatigue], liver, and kidneys) [9, 10]. The literature shows, however, that certain statins (lovastatin, simvastatin, rosuvastatin) may be associated with an increased risk of sleep disorders [20, 21].
The quality of sleep in this study was assessed using scales and sleep questionnaires (subjective methods): AIS, ISI, and PSQI. Our study revealed that patients taking atorvastatin or rosuvastatin scored significantly higher on all sleep scales than patients who did not receive statin treatment. Additionally, AIS showed that these disorders caused significantly higher levels of daytime sleepiness more often than in control patients. It should be emphasized that the PSQI and AIS scales complement the results of polysomnography [18, 22, 23]. The available literature proves that subjective methods present a sensitivity between 73.0% and 97.7%, while their specificity ranges in the interval 50-96%. Objective methods such as actigraphy or polysomnography present a sensibility higher than 90%. However, their specificity is low compared to their sensitivity, being one of the limitations of such technology. The factors such as the patient’s perception of her or his sleep can be provided only by subjective methods [24].
The conclusions that we drew from our work correspond to those included in the European MHRA review. It assessed evidence of adverse effects associated with the use of statins and showed negative effects of all statins on sleep disorders [25]. Similar conclusions were presented by the US Food and Drug Administration (FDA), which revealed a link between statin use and sleep disorders. The FDA confirmed the occurrence of insomnia in patients who were administered 40 mg of atorvastatin (5.3% vs. 2.9% in the placebo group) [26, 27]. Takada et al. in an analysis of the FDA database: FAERS (US Food and Drug Administration [FDA] Adverse Event Reporting System [formerly AERS)]) and JMIRI (Japan Medical Information Research Institute, Inc., Japan) claim that statins, regardless of lipophilicity, induce insomnia. In his analysis, he emphasized that there is no evidence implying that hydrophilic statins reduce the risk of insomnia [12]. On the other hand, there are some reports confirming that use of rosuvastatin causes disturbances in the initiation and maintenance of sleep and parasomnia [20, 21].
Sierra et al., in contrast, believe that the nature of statins (their lipophilicity) probably plays a significant role in the occurrence of sleep disorders. Their ability to cross the blood-brain barrier is one of the primary factors contributing to the above disorders. The greatest potential in this regard is shown by simvastatin (33%) and fluvastatin (28%), intermediate potential is shown by pitavastatin (13%) and lovastatin (11%), and the lowest by atorvastatin (5%), rosuvastatin (0%), and pravastatin (0%) [28]. These conclusions are confirmed by the work of Schaefer et al., who confirmed that sleep disorders were more likely to occur after administration of lovastatin (reduction of sleep duration by 18%) rather than pravastatin [29]. In a similar study, Vgontzas et al. showed an adverse effect of lovastatin compared to pravastatin, which manifested as waking immediately after falling asleep [15].
et al. in their meta-analysis emphasize that it is debatable whether statins, which are capable of crossing the blood-brain barrier, can cause sleep disorders [30]. Harrison et al. presented similar conclusions. In their work, they showed no association between statins crossing the blood-brain barrier and sleep disorders. There were no significant differences in a 4-week follow-up in patients receiving 40 mg of simvastatin or 40 mg of pravastatin compared to the placebo group [31].
In contrast, Tuccori and Galatii indicate that very often the conversion of a lipophilic statin to a hydrophilic enables the elimination of sleep disorders [32, 33]. Engelberg drew similar conclusions and highlighted the fact that statins with a higher degree of lipophilicity adversely affect the central nervous system [34].
The results of a 6-month follow-up in a randomized double blind placebo-controlled trial conducted by Golomb et al. indicate that patients taking simvastatin in a dose of 20 mg reported sleep problems much more frequently and statin therapy significantly worsened sleep quality compared to pravastatin administered at a dose of 40 mg or placebo. Additionally, no significant difference was observed between pravastatin and placebo intake regarding sleep disorders [35].
The most common side effect of statin therapy is muscle pain. A study by Ehlen et al. suggests that disturbances in skeletal muscle metabolism can lead to changes in sleep. This has been linked to a knockout of the BMAL1 gene in skeletal muscle. It has been established that the expression of BMAL1 in muscles is a key element in sleep regulation [36]. Additionally, Ehlen et al. speculate about the role of the peptide irisin, a factor of muscle origin that can affect brain function, and the peroxisome proliferator-activated gamma receptor coactivator 1-α (PGC-1α), which stimulates the release of irisin into the bloodstream [36]. Importantly, Ehlen et al. emphasize that their study does not clearly identify the mechanisms driving changes in BMAL1 expression. The relationship between statins and BMAL1 is poorly understood [36].
In a study by Stroes et al. concerning the effect of lipophilic simvastatin and hydrophilic rosuvastatin on muscle cells, simvastatin has been shown to have a significant effect on the expression in the muscle cells and the secretion of ω-3 and ω-6 eicosanoids and prostaglandins at higher levels [37]. This is associated with an increase in the intensity of the transformation of omega-n fatty acids in the muscles, which in turn causes a deterioration of the regenerative potential. This could be in part due to the prostaglandin depletion within the muscle, given that prostaglandin E2 (PGE2), which is synthesised from arachidonic acid, is responsible for muscle stem cell proliferation in response to injury [38]. This damaging effect on the muscles will lead to painful musculoskeletal sensitisation, which has been linked to worse sleep quality [39, 40]. Stroes et al. also indicate that muscle damage by statins is associated with increased serum prostaglandins, which may mildly promote sleep via the EP4 receptor in the brain [41]. Another product of the arachidonic acid metabolism, prostaglandin D2 (PGD2), is also a well-known factor influencing sleep [42]. Some studies indicate that prostaglandin D2 is the most effective eicosanoid sleep promoter [42].
Our study showed that statins, regardless of lipophilicity, induce sleep disorders manifested by insomnia. In addition, patients taking hydrophilic rosuvastatin at a dose of 20 mg appeared to receive higher scores on all scales in comparison to a dose of 10 mg.
The cause of insomnia in older age is most often secondary, associated with chronic diseases or psychosocial factors [43]. Forty-three per cent of the respondents of an EPESE study (Established Populations for Epidemiologic Studies of the Elderly), conducted on more than 9000 outpatients over 65 years of age, demonstrated difficulty falling asleep or maintaining sleep. The sleep disorders were exacerbated in people with worse health and those taking multiple medications. The problem was more common in women, mainly those with depression and respiratory diseases [44]. In our study, patients > 65 years of age represented 70% of the group chronically (for more than 3 months) using a statin and 58% of the entire control group. No statistical significance was obtained in patients below or above 65 years of age. Cognitive function did not differ significantly between the study and control groups.
There are no conclusive studies that confirm that statins negatively affect sleep quality or worsen the next day’s well-being. Swiger’s extensive analysis summarized the effects of statins on sleep and physical function. The author concluded that the evidence of negative effects of statins is insufficient and biased [45]. In contrast, Szmyd et al. in their work highlighted the fact that sleep disorders induced by statin administration are understudied and require more research [46].
STUDY LIMITATIONS AND STRENGTHS
Our study has some limitations. Firstly, the study group included a small number of patients on low doses of statins (5-10 mg) and very high doses (40-80 mg). Secondly, there was a lack of assessment of sleep disorders using objective methods such as polysomnography or actigraphy.
The strenghts of the study: 1) There are limited data on the influence of statins on sleep quality in patients with lipid disorders. 2) The important strength of our study is that we compared the effect on sleep quality of the 2 most potent and most frequently used statins. Such a comparison had not been performed previously. 3) In this study, to assess the quality of sleep we used methods including scales and questionnaires applicable in the diagnostics of sleep disorders (subjective methods). The factors such as the patient’s perception of her or his sleep can be provided only by subjective methods.
CONCLUSIONS
The present results indicated that higher doses (20 mg) of hydrophilic statins (rosuvastatin) are more likely to cause sleep disorders than lower doses (10 mg). Statins, regardless of lipophilicity, are associated with sleep disorders and induce insomnia. The study also showed that patients taking atorvastatin or rosuvastatin for more than 3 months reported inferior quality of the night compared to the quality of the day on the AIS.
DISCLOSURE
The authors report no conflict of interest.
References
1. Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2014; 129(25 Suppl 2):S1-S45.
2.
Gluba-Brzozka A, Franczyk B, Toth PP, et al. Molecular mechanisms of statin intolerance. Arch Med Sci 2016; 12(3): 645-658.
3.
Ruscica M, Ferri N, Banach M, et al. Side effects of statins: from pathophysiology and epidemiology to diagnostic and therapeutic implications. Cardiovasc Res 2023; 118(17): 3288-3304.
4.
Mach F, Ray KK, Wiklund O, et al. Adverse effects of statin therapy: perception vs. the evidence – focus on glucose homeostasis, cognitive, renal and hepatic function, haemorrhagic stroke and cataract. Eur Heart J 2018; 39(27): 2526-2539.
5.
Cheon DY, Jo SH. Adverse effects of statin therapy and their treatment. Cardiovasc Prev Pharmacother 2022; 4(1): 1-6.
6.
Barkas F, Adamidis P, Koutsogianni AD, et al. Statin-associated side effects in patients attending a lipid clinic: evidence from a 6-year study. Arch Med Sci Atheroscler Dis 2021; 6: e182-e187.
7.
Banach M, Rizzo M, Toth PP, et al. Statin intolerance – an attempt at a unified definition. Position paper from an International Lipid Expert Panel. Expert Opin Drug Saf 2015; 14(6): 55-935.
8.
Mancini GB, Baker S, Bergeron J, et al. Diagnosis, prevention, and management of statin adverse effects and intolerance: Canadian Consensus Working Group Update (2016). Can J Cardiol 2016; 32 (7 Suppl): S35-S65.
9.
Stulc T, Ceška R, Gotto Jr AM. Statin intolerance: the clinician’s perspective. Curr Atheroscler Rep 2015; 17(12): 69.
10.
Pinal-Fernandez I, Casal-Dominguez M, Mammen AL. Statins: pros and cons. Med Clin (Barc) 2018; 150(10): 398-402.
11.
Mach F, Ray KK, Wiklund O, et al. Adverse effects of statin therapy: perception vs. the evidence – focus on glucose homeostasis, cognitive, renal and hepatic function, haemorrhagic stroke and cataract. Eur Heart J 2018; 39(27): 2526-2539.
12.
Takada M, Fujimoto M, Yamazaki K, et al. Association of statin use with sleep disturbances: data mining of a spontaneous reporting database and a prescription database. Drug Saf 2014; 37(6): 421-431.
13.
Tuccori M, Lapi F, Testi A, et al. Statin-associated psychiatric adverse events: a case/non-case evaluation of an Italian database of spontaneous adverse drug reaction reporting. Drug Saf 2008; 31(12): 1115-1123.
14.
Boriani G, Biffi M, Strocchi E, Branzi A. Nightmares and sleep disturbances with simvastatin and metoprolol. Ann Pharmacother 2001; 35(10): 1292.
15.
Vgontzas AN, Kales A, Bixler EO, et al. Effects of lovastatin and pravastatin on sleep efficiency and sleep stages. Clin Pharmacol Therap 1991; 50(6): 730-737.
16.
Saheki A, Terasaki T, Tamai I, Tsuji A. In vivo and in vitro blood - brain barrier transport of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors. Pharmaceut Res 1994; 11(2): 305-311.
17.
Fornal-Pawłowska M, Wołyńczyk-Gmaj D, Szelenberger W. Validation of the Polish version of the Athens Insomnia Scale. Psychiatr Pol 2011; 45(2): 211-221.
18.
Buysse DJ, Reynolds 3rd CF, Monk TH, et al. The Pittsburgh sleep quality index: a new instrument for psychiatric practice and research. Psychiatry Res 1989; 28(2): 193-213.
19.
Morin CM, Belleville G, Bélanger L, Ivers H. The Insomnia Severity Index: psychometric indicators to detect insomnia cases and evaluate treatment response. Sleep 2011; 34(5): 601-608.
20.
King DS, Wilburn AJ, Wofford MR, et al. Cognitive impairment associated with atorvastatin and simvastatin. Pharmacotherapy 2003; 23(12): 1663-1667.
21.
Roth T, Richardson GR, Sullivan JP, et al. Comparative effects of pravastatin and lovastatin on nighttime sleep and daytime performance. Clin Cardiol 1992; 15(6): 426-432.
22.
Backhaus J, Junghanns K, Broocks A, et al. Test-retest reliability and validity of the Pittsburgh Sleep Quality Index in primary insomnia. J Psychosom Res 2002; 53(3): 737-740.
23.
Tsai PS, Wang SY, Wang MY, et al. Psychometric evaluation of the Chinese version of the Pittsburgh Sleep Quality Index (CPSQI) in primary insomnia and control subjects. Qual Life Res 2005; 14(8): 1943-1952.
24.
Ibáñez V, Silva J, Cauli O. A survey on sleep assessment methods. PeerJ 2018; 6: e4849.
25.
MHRA public assessment report. Statins: updates to product safety information. Available from: https://www.gov.uk/government/organisations/medicines-and-healthcare-products-regulatory-agency (accessed: 30 March 2023).
26.
Sakaeda T, Tamon A, Kadoyama K, Okuno Y. Data mining of the public version of the FDA Adverse Event Reporting System. Int J Med Sci 2013; 10(7): 796-803.
27.
Food and Drug Administration. LIPITOR® (atorvastatin calcium). Highlights of prescribing information. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/ 020702s056lbl.pdf (accessed: 30 March 2023).
28.
Sierra S, Ramos MC, Molina P, et al. Statins as neuroprotectants: a comparative in vitro study of lipophilicity, blood-brain-barrier penetration, lowering of brain cholesterol, and decrease of neuron cell death. J Alzheimers Dis 2011; 23(2): 307-318.
29.
Schaefer EJ. HMG-CoA reductase inhibitors for hypercholesterolemia. N Engl J Med 1988; 319(18): 1222-1223.
30.
Broncel M, Gorzelak-Pabiś P, Sahebkar A, et al. Sleep changes following statin therapy: a systematic review and meta-analysis of randomized placebo-controlled polysomnographic trials. Arch Med Sci 2015; 11(5): 915-926.
31.
Harrison R, Ashton C. Do cholesterol-lowering agents affect brain activity? A comparison of simvastatin, pravastatin, and placebo in healthy volunteers. Br J Clin Pharmacol 1994; 37(3): 231-236.
32.
Tuccori M, Montagnani S, Mantarro S, et al. Neuropsychiatric adverse events associated with statins: epidemiology, pathophysiology, prevention and management. CNS Drugs 2014; 28(3): 249-272.
33.
Galatti L, Polimeni G, Salvo F, et al. Short-term memory loss associated with rosuvastatin. Pharmacotherapy 2006; 26(8): 1190-1192.
34.
Engelberg H. Low serum cholesterol and suicide. Lancet 1992; 339(8795): 727-729.
35.
Golomb BA, Kwon EK, Criqui MH, Dimsdale JE. Simvastatin but not pravastatin affects sleep: findings from the UCSD statin study. Circulation 2007; 116: II-847.
36.
Ehlen JC, Brager AJ, Baggs J, et al. Bmal1 function in skeletal muscle regulates sleep. Elife 2017; 6: e26557.
37.
Grunwald SA, Popp O, Haafke S, et al. Statin-induced myopathic changes in primary human muscle cells and reversal by a prostaglandin F2 alpha analogue. Sci Rep 2020; 10(1): 2158.
38.
Ho ATV, Palla AR, Blake MR, et al. Prostaglandin E2 is essential for efficacious skeletal muscle stem-cell function, augmenting regeneration & strength. Proc Natl Acad Sci USA 2017; 114(26): 6675- 6684.
39.
Sutton BC, Opp MR. Musculoskeletal sensitization and sleep: chronic muscle pain fragments sleep of mice without altering its duration. Sleep 2014; 37(3): 505-513.
40.
Keskindag B, Karaaziz M. The association between pain and sleep in fibromyalgia. Saudi Med J 2017; 38(5): 465-475.
41.
Oishi Y, Yoshida K, Scammell TE, et al. The roles of prostaglandin E2 and D2 in lipopolysaccharide-mediated changes in sleep. Brain Behav Immun 2015; 47: 172-177.
42.
Sri Kantha S, Matsumura H, Kubo E, et al. Effects of prostaglandin D2, lipoxins and leukotrienes on sleep and brain temperature of rats. Prostaglandins Leukot Essent Fat Acids 1994; 51(2): 87-93.
43.
Wojtas A, Ciszewski S. Epidemiologia bezsenności [Epidemiology of insomnia]. Psychiatria 2011; 8(3): 79-83.
44.
Bidzan L. Zaburzenia snu w wieku podeszłym [Sleep disorders in the elderly]. Geriatria 2011; 5: 34-40.
45.
Swiger KJ, Manalac RJ, Blaha MJ, et al. Statins, mood, sleep, and physical function: a systematic review. Eur J Clin Pharmacol 2014; 70(12): 1413-1422.
46.
Szmyd B, Rogut M, Białasiewicz P, Gabryelska A. The impact of glucocorticoids and statins on sleep quality. Sleep Med Rev 2021; 55: 101380.
This is an Open Access journal, all articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0). License (http://creativecommons.org/licenses/by-nc-sa/4.0/), allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license.
