Contemporary Concise Review 2020: Sleep.

Obstructive sleep apnoea (OSA) now affects one-seventh of the world's population. Treatment of even mild OSA can improve daytime sleepiness and quality of life. Recent modifications to uvulopalatopharyngoplasty may make it a more widely applicable treatment option in selected patients with OSA. Diet and exercise have effects on sleep apnoea severity independent of weight loss. Insomnia has become increasingly common during the coronavirus disease 2019 (COVID-19) pandemic.

Lack of Association between Periodic Limb Movements during Sleep and Neuroimaging Signatures of Cerebral Small Vessel Disease in Stroke-Free Community-Dwelling Older Adults. The Atahualpa Project.

BACKGROUND: Evidence of the relationship between periodic limb movements during sleep (PLMS) and cerebral small vessel disease (cSVD) is limited and inconsistent. Here, we aimed to assess the independent association between PLMS and the different neuroimaging signatures of cSVD. METHODS: Atahualpa residents aged more than or equal to 60 years enrolled in the Atahualpa Project undergoing polysomnography and MRI with time intervals less than or equal to 6 months were included. MRI readings focused on white matter hyperintensities (WMH) of presumed vascular origin, deep cerebral microbleeds (CMB), silent lacunar infarcts (LI), and more than 10 enlarged basal ganglia-perivascular spaces (BG-PVS). Data from single-night polysomnograms were interpreted according to recommendations of the American Academy of Sleep Medicine. Associations between the PLMS index and neuroimaging signatures of cSVD (as dependent variables) were assessed by means of logistic regression models, adjusted for relevant confounders. RESULTS: A total of 146 individuals (mean age: 71.4 ± 7.5 years; 64% women) were included. A PLMS index more than or equal to 15 per hour were noted in 48 (33%) participants. Moderate-to-severe WMH were present in 33 individuals (23%), deep CMB in 9 (6%), silent LI in 16 (11%), and more than 10 BG-PVS in 44 (30%). In univariate analyses, silent LI (P = .035) and the presence of more than 10 enlarged BG-PVS (P = .034) were significantly higher among participants with a PLMS index more than or equal to 15 per hour. However, fully-adjusted multivariate models showed no significant association between PLMS index more than or equal to 15 per hour and any of the neuroimaging signatures of cSVD. CONCLUSIONS: This study shows no independent association between the PLMS index and neuroimaging signatures of cSVD in stroke-free community-dwelling older adults.

ICI-RS 2015-Is a better understanding of sleep the key in managing nocturia?

AIMS: Nocturia, or waking up at night to void, is a highly prevalent and bothersome lower urinary tract symptom. However, the applied treatment modalities do not improve symptoms in about half of the patients. The aim of this report is to generate new ideas for future nocturia research, with special emphasis on the role of sleep physiology and sleep disorders. METHODS: The following is a report of the presentations and subsequent discussion of the Nocturia Think Tank session at the annual meeting of the International Consultation on Incontinence Research Society (ICI-RS), which took place in September 2015 in Bristol. General information about the organization of the ICI-RS meeting can be found on the website "www.ici-rs.org." An overview of challenges within the existing evidence, future research ideas, and results of research with regard to nocturia and sleep were presented. RESULTS AND CONCLUSION: In order to optimize the management of nocturia and nocturnal polyuria (NP), future research has to focus on the development of unambiguous terminology regarding nocturia and NP, the role of renal function profiles and simplified frequency volume charts as guidance of individualized therapy and the role of sleep disorders such as periodic limb movements during sleep and habitual voiding as a response to awakening. Neurourol. Urodynam. 37:2048-2052, 2018. © 2016 Wiley Periodicals, Inc.

Basal sympathetic predominance in periodic limb movements in sleep after continuous positive airway pressure.

PURPOSE: This study investigated the basal autonomic regulation in patients with obstructive sleep apnea (OSA) showing periodic limb movements in sleep (PLMS) emerging after therapy with continuous positive airway pressure (CPAP). METHODS: Data of patients with OSA undergoing a first polysomnography for diagnosis and a second polysomnography for therapy with CPAP were reviewed. Patients with OSA showing PLMS on the first polysomnography were excluded. By using heart rate variability analysis, epochs without any sleep events and continuous effects from the second polysomnography were retrospectively analyzed. RESULTS: Of 125 eligible patients, 30 with PLMS after therapy with CPAP (PLMS group) and 30 not showing PLMS on both polysomnography (non-PLMS group) were randomly selected for the analysis. No significant differences in the demographic characteristics and variables of polysomnographies were identified between the groups. Although one trend of low root mean square of successive differences (RMSSD) between intervals of adjacent normal heart beats (NN intervals) in the PLMS group was observed, patients in the PLMS group had significantly low normalized high-frequency (n-HF) and high-frequency (HF) values, but high normalized low frequency (n-LF) and high ratio of LF to HF (LF/HF ratio). After adjustment for confounding variables, PLMS on the second polysomnography was significantly associated with RMSSD (ß = - 6.7587, p = 0.0338), n-LF (ß = 0.0907, p = 0.0148), n-HF (ß = - 0.0895, p = 0.0163), log LF/HF ratio (ß = 0.4923, p = 0.0090), and log HF (ß = - 0.6134, p = 0.0199). CONCLUSIONS: Patients with OSA showing PLMS emerging after therapy with CPAP may have a basal sympathetic predominance with potential negative cardiovascular effects.

Sleep-related movement disorders and disturbances of motor control.

PURPOSE OF REVIEW: Review of the literature pertaining to clinical presentation, classification, epidemiology, pathophysiology, diagnosis, and treatment of sleep-related movement disorders and disturbances of motor control. RECENT FINDINGS: Sleep-related movement disorders and disturbances of motor control are typically characterized by positive motor symptoms and are often associated with sleep disturbances and consequent daytime symptoms (e.g. fatigue, sleepiness). They often represent the first or main manifestation of underlying disorders of the central nervous system, which require specific work-up and treatment. Diverse and often combined cause factors have been identified. Although recent data provide some evidence regarding abnormal activation and/or disinhibition of motor circuits during sleep, for the majority of these disorders the pathogenetic mechanisms remain speculative. The differential diagnosis is sometimes difficult and misdiagnoses are not infrequent. The diagnosis is based on clinical and video-polysomnographic findings. Treatment of sleep-related motor disturbances with few exceptions (e.g. restless legs/limbs syndrome) are based mainly on anecdotal reports or small series. SUMMARY: More state-of-the-art studies on the cause, pathophysiology, and treatment of sleep-related movement disorders and disturbances of motor control are needed.

Restless legs syndrome and periodic leg movements in patients with movement disorders: Specific considerations.

Restless legs syndrome is a frequent neurological disorder with potentially serious and highly distressing treatment complications. The role and potential implications of periodic leg movements during sleep range from being a genetic risk marker for restless legs syndrome to being a cardiovascular risk factor. The diagnosis of restless legs syndrome in patients with daytime movement disorders is challenging and restless legs syndrome needs to be differentiated from other sleep-related movement disorders. This article provides an update on the diagnosis of restless legs syndrome as an independent disorder and the role of periodic leg movements and reviews the association of restless legs syndrome with Parkinson's disease and other movement disorders. © 2017 International Parkinson and Movement Disorder Society.

Post-stroke restless leg syndrome and periodic limb movements in sleep.

OBJECTIVES: Primary restless leg syndrome (RLS) and periodic limb movements in sleep (PLMS) frequently co-exist, obscuring the boundaries between the two conditions. In such instances, a study of secondary cases with focal lesions such as post-stroke RLS and PLMS (psRLS and psPLMS, respectively) can be helpful in identifying characteristics of the individual conditions. MATERIALS AND METHODS: Patients who had suffered strokes and who subsequently developed psRLS or psPLMS were recruited. To determine the overall features of psRLS/PLMS, historical cases were selected from the literature. All cases with either psRLS or psPLMS alone were further analyzed to elucidate the distinctive pathomechanisms of the two conditions. RESULTS: Six patients with either psRLS or psPLMS were recruited from our hospital; two patients had both conditions contemporaneously. The literature contains details on 30 cases of psRLS or psPLMS. The causative lesion was most frequently located in the pons. We found that psRLS was more often bilateral, and usually detected later in time. Lesions in both the pontine base and tegmentum (together) were associated with unilateral psPLMS, whereas lesions in the corona radiata and adjacent basal ganglia were associated with bilateral RLS. Lesions confined to the corona radiata resulted in either unilateral or bilateral RLS. CONCLUSIONS: The observed differences in the clinical and radiological features of psRLS and psPLMS suggest that the pathophysiologies of the two conditions are distinct. Further research is needed to understand the pathophysiologies of primary RLS and PLMS.

Periodic limb movements in sleep are followed by increases in EEG activity, blood pressure, and heart rate during sleep.

PURPOSE: Periodic limb movements in sleep (PLMS) are related to arousal, sympathetic activation, and increases in blood pressure (BP), but whether they are part of the arousal process or causative of it is unclear. Our objective was to assess the temporal distribution of arousal-related measures around PLMS. METHODS: Polysomnographic recordings of six patients with restless legs syndrome were analyzed. We analyzed 15 PLMS, plus three 5-s epochs before and after each movement, for every patient. Mean values per epoch of blood pressure (BP), heart rate (HR), and electroencephalographic (EEG) power were calculated. For each patient, six 5-s epochs of undisturbed sleep were analyzed as controls. RESULTS: Alpha + beta EEG power, systolic BP, and HR were significantly increased following PLMS. The EEG power and HR increases were noticed in the first epoch after PLMS, whereas that of systolic BP was observed in the second and third epochs following a PLMS. No significant changes occurred in the epochs of undisturbed sleep. CONCLUSIONS: The results suggest that PLMS are followed by arousal-related nervous system events. Given the high frequency of PLMS throughout the night, they could be a potential risk factor for nocturnal arrhythmias and hypertension, in addition to causing sleep deprivation.

Excessive Fragmentary Myoclonus: What Do We Know?

Excessive fragmentary myoclonus (EFM) is a polysomnographic finding registered by the surface electromyography (EMG) and characterized as a result of the muscle activity consisting of sudden, isolated, arrhythmic, asynchronous and asymmetric brief twitches. The EMG potentials are defined by the exact criteria in The International Classification of the Sleep Disorders, 3rd edition and they appear with high intensity in all sleep stages. Clinical significance of EFM is unclear. It was observed in combination with other diseases and features such as obstructive and central sleep apnea, narcolepsy, periodic limb movements, insomnia, neurodegenerative disorders and peripheral nerve dysfunction. Relation to such wide range of diseases supports the opinion that EFM is nor a specific sleep disorder nor a specific polysomnographic sign. The option that EFM is a normal variant has also not been ruled out so far.

Basal sympathetic predominance in periodic limb movements in sleep with obstructive sleep apnea.

Because the impact of periodic limb movements in sleep (PLMS) is controversial, no consensus has been reached on the therapeutic strategy for PLMS in obstructive sleep apnea (OSA). To verify the hypothesis that PLMS is related to a negative impact on the cardiovascular system in OSA patients, this study investigated the basal autonomic regulation by heart rate variability (HRV) analysis. Sixty patients with mild-to-moderate OSA who underwent polysomnography (PSG) and completed sleep questionnaires were analysed retrospectively and divided into the PLMS group (n = 30) and the non-PLMS group (n = 30). Epochs without any sleep events or continuous effects were evaluated using HRV analysis. No significant difference was observed in the demographic data, PSG parameters or sleep questionnaires between the PLMS and non-PLMS groups, except for age. Patients in the PLMS group had significantly lower normalized high frequency (n-HF), high frequency (HF), square root of the mean of the sum of the squares of difference between adjacent NN intervals (RMSSD) and standard deviation of all normal to normal intervals index (SDNN-I), but had a higher normalized low frequency (n-LF) and LF/HF ratio. There was no significant difference in the Epworth Sleepiness Scale, the Pittsburgh Sleep Quality Index, the Short-Form 36 and the Hospital Anxiety and Depression Scale between the two groups. After adjustment for confounding variables, PLMS remained an independent predictor of n-LF (ß = 0.0901, P = 0.0081), LF/HF ratio (ß = 0.5351, P = 0.0361), RMSSD (ß = -20.1620, P = 0.0455) and n-HF (ß = -0.0886, P = 0.0134). In conclusion, PLMS is related independently to basal sympathetic predominance and has a potentially negative impact on the cardiovascular system of OSA patients.

Basal cardiac autonomic tone is normal in patients with periodic leg movements during sleep.

The relationship between the autonomic nervous system and periodic leg movements during sleep (PLMS) is not completely understood. We aimed to determine whether patients with PLMS exhibit any changes in their basal heart rate variability (HRV), excluding episodes of leg movements and arousals. To investigate this, we conducted a cross-sectional study including 13 patients with PLMS (PLMS ≥ 20) and 13 matched controls, free of cardiovascular diseases and medications. Time-and frequency-domain HRV measures [mean R-R interval, low frequency (LF), high frequency (HF), LF/HF] were calculated across all sleep stages as well during wakefulness just before and after sleep during one-night polysomnography. We only took ECG segments of sleep without arousals and excluded periods of 30 s before and after the leg movements. No statistical differences between PLMS and control subjects were found in any of the time- or frequency-domain HRV measures across sleep stages. Basal cardiac autonomic modulation in patients with PLMS is similar to that of control subjects. Our results argue against a role for a basal disturbance of the cardiac autonomic nervous system in the pathogenesis of PLMS.

Intellectual disabilities and power spectra analysis during sleep: a new perspective on borderline intellectual functioning.

BACKGROUND: The role of sleep in cognitive processes has been confirmed by a growing number of reports for all ages of life. Analysing sleep electroencephalogram (EEG) spectra may be useful to study cortical organisation in individuals with Borderline Intellectual Functioning (BIF), as seen in other disturbances even if it is not considered a disease. The aim of this study was to determine if the sleep EEG power spectra in children with BIF could be different from typically developing children. METHODS: Eighteen BIF (12 males) (mean age 11.04; SD ± 1.07) and 24 typical developing children (14 men) (mean age 10.98; SD ± 1.76; P = 0.899) underwent an overnight polysomnography (PSG) recording in the Sleep Laboratory of the Clinic of Child and Adolescent Neuropsychiatry, after one adaptation night. Sleep was subdivided into 30-s epochs and sleep stages were scored according to the standard criteria and the power spectra were calculated for the Cz-A2 channel using the sleep analysis software Hypnolab 1.2 (SWS Soft, Italy) by means of the Fast Fourier Transform and the power spectrum was calculated for frequencies between 0.5 and 60 Hz with a frequency step of 1 Hz and then averaged across the following bands delta (0.5-4 Hz), theta (5-7 Hz), alpha (8-11 Hz), sigma (11-15 Hz), and beta (16-30 Hz), gamma (30-60 Hz) for S2, SWS and REM (Rapid Eye Movement) sleep stages. RESULTS: BIF have a reduced sleep duration (total sleep time; P < 0.001), and an increased rate of stage shifts (P < 0.001) and awakenings (P < 0.001) and WASO (wakefulness after sleep onset) % (P < 0.001); the stage 2% (P < 0.001), and REM% (P < 0.001) were lower and slow-wave sleep percentage was slightly higher (P < 0.001). All children with BIF had an AHI (apnoea-hypopnea index) less than 1 (mean AHI = 0.691 ± 0.236) with a mean oxygen saturation of 97.6% and a periodic leg movement index (PLMI) less than 5 (mean PLMI = 2.94 ± 1.56). All sleep stages had a significant reduction in gamma frequency (30-60 Hz) (P < 0.001) and an increased delta frequency (0.5-4.0 Hz) (P < 0.001) power in BIF subjects compared with typically developing children. CONCLUSION: Our findings shed light on the importance of sleep for cognition processes particularly in cognitive borderline dysfunction and the role of EEG spectral power analysis to recognize sleep characteristics in BIF children.

The influence of pharyngeal and esophageal pressure measurements on the parameters of polysomnography.

Sleep-disordered breathing (SDB) is highly prevalent and accompanied by a considerable reduction in quality of life and an increase in cardiovascular morbidity and mortality. To diagnose SDB and to assess the localization of an airway obstruction, multichannel pressure measurements in the pharynx and esophagus have been used but are still under debate. Specifically, these devices are often labeled to be uncomfortable for patients and to influence the parameters of sleep recordings. The aims of the current study were to determine the tolerability of multilevel pressure measurement and to assess their impact on the parameters of polysomnography (PSG). Patients who were referred for two nights of standard PSG for diagnostic purposes were included. The device for multilevel pressure recordings was applied in addition to PSG on one of the two nights according to a randomization protocol. Tolerability of the device was assessed and the most relevant outcome measures of PSG were compared between the nights with and without the pressure sensor. All polysomnographic data were analyzed by the same trained observer who was blinded to the presence of the pressure catheter. Fifty-one patients were included in the trial. Ten of the patients tolerated insertion of the pressure catheter but complained about persisting discomfort during the night, requiring removal of the device. Forty-one patients tolerated the multilevel pressure transducer, which is equivalent to a tolerability of 80%. The results of the sleep parameters are based on the data of 31 patients. The pressure device minimally influenced the outcome data of the PSG. None of the recorded differences however were clinically relevant or statistically significant. Pressure measurements with devices of small diameter (≈2 mm) are well accepted by patients and have a tolerability of at least 80%. The impact of multilevel pressure recordings on objective sleep parameters is negligible. The study strongly supports the use of multilevel pressure recordings and disproves the most relevant objections against their use.

Manual scoring of periodic limb movements in children: is it still necessary?

OBJECTIVE: Although manual scoring has been classically considered the gold standard to identify periodic leg movements (PLM), it is a very time consuming and expensive process, also subject to variability in interpretation. In the last decades, different authors have observed reasonably good agreement between automated PSG scoring algorithms and manual scoring in adults, according to established criteria. We aim to compare the automatic software analysis of our polysomnogram with the manual staging in children with sleep-disordered breathing. METHODS: We performed a semiautomatic method, in which an experienced technician watched the video recording and removed from the automatic analysis those movements that did not correspond to true candidate leg movement (LM). RESULTS: A total of 131 PSGs were studied; applying the established criteria, 65 children were diagnosed of obstructive sleep apnea, and 66 presented snoring but with no sleep apnea. The mean age was 6.7 years (±1.7) and twenty-five children (19.08 %) had a PLMI >5/h. Statistical differences were found not only for PLMI (manual: 2.20 (0.7, 4.1) vs automatic (6.4 (3.85,9.5); p < 0.001), but for almost of all indexes assessed between the automatic and the manual scoring analysis. The level of concordance was only moderate for PLM index (0.63 [0.51-0.72]); showing that, unlike the articles published in the adult population, automatic analysis is not accurate in children and, manually or semi-automatically analysis as ours need to be done. CONCLUSION: It seems that PLM detection algorithm might work accurately but, the real need would be a true LM detection algorithm.

Sleep stage sequence analysis of sleep onset REM periods in the hypersomnias.

BACKGROUND: The Multiple Sleep Latency Test (MSLT) remains an important diagnostic tool in the diagnosis of hypersomnias. However, a positive MSLT may be found in other sleep disorders, such as behaviourally induced inadequate sleep syndrome (BIISS). It has been demonstrated that in sleep onset rapid eye movement (SOREM) periods in BIISS, REM sleep tends to arise from stage 2 sleep (non-REM (NREM) 2), rather than stage 1 sleep (NREM1), as in narcolepsy. METHODS: We performed sleep stage sequence analysis on 127 patients with nocturnal polysomnography and MSLT, including 25 with narcolepsy with cataplexy (N+C), 41 with narcolepsy without cataplexy (N-C), 21 with idiopathic hypersomnia with long sleep time (IHL), 20 with BIISS and 20 with periodic limb movement disorder (PLMD). 537 naps were recorded, containing 176 SOREM periods. RESULTS: All SOREM periods in the IHL, BIISS and PLMD groups arose from NREM2 sleep, 75% of those in N+C arose from NREM1 and in N-C only 52% arose from NREM1. Within the N-C group, those with SOREM periods all arising from stage 1 had a shorter MSL (p=0.02). CONCLUSIONS: These results suggest that SOREM periods arising from NREM1 have high sensitivity for the diagnosis of narcolepsy and that SOREM periods from NREM1 are a marker of severity, either of sleepiness or REM instability. Sleep stage sequence analysis of SOREM periods may also aid more accurate phenotyping of the hypersomnias and in particular clarify heterogeneity among patients with narcolepsy without cataplexy.

Polysomnographic study of nocturnal sleep in idiopathic hypersomnia without long sleep time.

We investigated nocturnal sleep abnormalities in 19 patients with idiopathic hypersomnia without long sleep time (IH) in comparison with two age- and sex- matched control groups of 13 normal subjects (C) and of 17 patients with narcolepsy with cataplexy (NC), the latter considered as the extreme of excessive daytime sleepiness (EDS). Sleep macro- and micro- (i.e. cyclic alternating pattern, CAP) structure as well as quantitative analysis of EEG, of periodic leg movements during sleep (PLMS), and of muscle tone during REM sleep were compared across groups. IH and NC patients slept more than C subjects, but IH showed the highest levels of sleep fragmentation (e.g. awakenings), associated with a CAP rate higher than NC during lighter sleep stages and lower than C during slow wave sleep respectively, and with the highest relative amount of A3 and the lowest of A1 subtypes. IH showed a delta power in between C and NC groups, whereas muscle tone and PLMS had normal characteristics. A peculiar profile of microstructural sleep abnormalities may contribute to sleep fragmentation and, possibly, EDS in IH.

Change in heart rate variability precedes the occurrence of periodic leg movements during sleep: an observational study.

BACKGROUND: Several reports have described that individual periodic leg movements during sleep (PLMS) activities are associated with autonomic nervous system activity occurring shortly before each PLMS activity. Nevertheless, no study has investigated dynamic changes of autonomic nervous system activity before the onset of PLMS. This study detected changes in heart rate variability (HRV) at the onset of the period with PLMS using complex demodulation method. METHODS: This study enrolled 14 patients diagnosed as having idiopathic PLMS disorder (PLMD). In periods with and without PLMS during sleep stage 2, HRV-related variables and the spectral power of fluctuation of a high frequency (HF) band (FHFB) were analyzed and compared. The changes of those parameters during transition from the period without PLMS to that with PLMS were explored. RESULTS: Spectral power in the low frequency (LF) band and very low frequency (VLF) band were higher in the period with PLMS. Additionally, the average frequency in FHFB was higher. The frequency in this band fluctuated during the period with PLMS with remarkable elevation of FHFB. Moreover, spectral powers in FHFB, LF, and VLF were remarkably elevated shortly before the beginning of the period with PLMS (FHFB, -65 s; LF, -53 s; and VLF, -45 s). CONCLUSIONS: Elevation of sympathetic nervous system activity and mean frequency fluctuation in an HF band can occur several tens of seconds before the period with PLMS. Dynamic changes in the autonomic nervous system activity might be related to the vulnerability to PLMS occurrence during the night.

Restless legs syndrome: impact on sleep-related breathing disorders.

Restless legs syndrome (RLS) is a common chronic sensory-motor neurological disorder that remains a clinical diagnosis. Most RLS patients present with sleep complaints in the form of initiation and/or maintenance insomnia as RLS has a circadian rhythmicity. An increased number of periodic leg movements during sleep (PLMS) is a supportive criterion in the diagnosis of RLS. Abnormalities in the central dopaminergic and iron systems are involved in the physiopathology of RLS. There is a higher prevalence of RLS and PLMS in sleep-disordered breathing patients, particularly those with obstructive sleep apnoea (OSA), the most common sleep disorder in western societies. The complex mechanisms underlying the association between OSA, RLS and PLMS remain unclear. Untreated OSA can lead to adverse cardiovascular consequences due to cardio-metabolic dysfunction. It remains controversial whether RLS could further adversely impact the cardiovascular consequences of OSA. The PLMS do not have an additive effect on the hypersomnia experienced by some sleep-disordered breathing patients. Continuous positive airway pressure (CPAP) therapy is the most effective therapy for OSA. The presence of PLMS during CPAP treatment could be a marker of an incomplete resolution of sleep-disordered breathing in the form of increased upper airway resistance syndrome, despite treatment. Dopaminergic agonists are the preferred agent for the treatment of RLS, and are indicated when RLS symptoms are frequent and affect quality of life. PLMS and RLS do not seem to contribute to the residual hypersomnia that can be observed in some sleep-disordered breathing patients despite adequate compliance and effective CPAP therapy.

Association of incident cardiovascular disease with periodic limb movements during sleep in older men: outcomes of sleep disorders in older men (MrOS) study.

BACKGROUND: Periodic limb movements during sleep (PLMS) cause repetitive sympathetic activation and may be associated with increased cardiovascular risk. We hypothesized that PLMS frequency (periodic limb movement index [PLMI]) and PLMS arousal frequency (periodic limb movement arousal index [PLMAI]) are predictive of incident cardiovascular disease, including coronary heart disease, peripheral arterial disease, and cerebrovascular disease, in an elderly male cohort. METHODS AND RESULTS: A total of 2911 men in the observational Outcomes of Sleep Disorders in Older Men (MrOS) Sleep Study cohort underwent in-home polysomnography with PLMS measurement and were followed up for 4 years for the outcomes coronary heart disease, cerebrovascular disease, peripheral arterial disease, and all-cause cardiovascular disease, which included coronary heart disease, cerebrovascular disease, and peripheral arterial disease. Cox proportional hazards regression assessed the association between PLMI, PLMAI, and these outcomes. Models were minimally adjusted for age, clinic, and body mass index and then fully adjusted for conventional cardiovascular risk factors. During follow-up, 500 men experienced all-cause cardiovascular disease: 345 coronary heart disease, 117 cerebrovascular disease, and 98 peripheral arterial disease events. In fully adjusted models, men with PLMAI ≥5 compared with the referent PLMA <1 group had a 1.26-fold increased relative hazard for all-cause cardiovascular disease. Similar findings were observed for PLMI and all-cause cardiovascular disease. For peripheral arterial disease, men with PLMI ≥30 compared with the referent PLMI <5 group had a 2-fold increased relative hazard (95% confidence interval, 1.14 to 3.49; P=0.025). Compared with the referent group, men with PLMI ≥30 had an increased risk of coronary heart disease (relative hazard, 1.31; 95% confidence interval, 1.01 to 1.70; P=0.045) after minimal adjustment, but this association was attenuated after further adjustments. After stratification, risk of incident all-cause cardiovascular disease among high-PLMI and high-PLMAI groups was significantly elevated only for men without prevalent hypertension (P for interactions <0.10). CONCLUSION: These findings provide evidence that PLMS frequency is associated with incident cardiovascular disease in community-dwelling elderly men.

Periodic limb movements in sleep are associated with stroke and cardiovascular risk factors in patients with renal failure.

Periodic limb movements in sleep (PLMS) is prevalent among dialysed patients and is associated with increased risk of mortality. Our study aimed to determine the prevalence of this disease in a sample of transplanted and waiting-list haemodialysed patients. One hundred transplanted and 50 waiting-list patients underwent polysomnography. Moderate and severe diseases were defined as periodic limb movements in sleep index (PLMSI) higher than 15 and 25 events h(-1), respectively. The 10-year coronary heart disease risk was estimated for all patients using the Framingham Score. Moreover, the 10-year estimated risk of stroke was calculated according to the modified version of the Framingham Stroke Risk Profile. PLMS was present in 27% of the transplanted and 42% of the waiting-list group (P = 0.094); the proportion of severe disease was twice as high in waiting-list versus transplanted patients (32 versus 16%, P = 0.024). Patients with severe disease had a higher 10-year estimated risk of stroke in the transplanted group [10 (7-17) versus 5 (4-10); P = 0.002] and a higher 10-year coronary heart disease risk in both the transplanted [18 (8-22) versus 7 (4-14); P = 0.002], and the waiting-list groups [11 (5-18) versus 4 (1-9); P = 0.032]. In multivariable linear regression models the PLMSI was associated independently with the Framingham cardiovascular and cerebrovascular scores after adjusting for important covariables. Higher PLMSI is an independent predictor of higher cardiovascular and cerebrovascular risk score in patients with chronic kidney disease. Severe PLMS is less frequent in kidney transplant recipients compared to waiting-list dialysis patients.