Paola Lanfranchi

Nocturnal blood pressure changes in patients with restless legs syndrome

Objectives: To assess heart rate (HR) and blood pressure (BP) changes associated with periodic leg movements during sleep (PLMS) with or without EEG signs of arousal in subjects with primary restless legs syndrome (RLS). Methods: Ten patients with RLS (4 women, aged 47.3 ± 13.5 years) underwent one night of polysomnography along with noninvasive beat-to-beat BP monitoring. Ten PLMS with microarousals (PLMS-MA) and 10 PLMS without microarousals (PLMS-noMA) were analyzed in each subject. Systolic and diastolic BP (SBP, DBP) were measured within a 25-beat temporal window comprising 10 beats before and 15 beats after onset of each movement. PLMS-related BP changes were assessed by repeated measures one-way analysis of variance. BP changes associated with PLMS-MA and PLMS-noMA were compared by paired t-tests. Pearson correlation coefficients were used to assess the relationship between cardiovascular changes and clinical and polysomnographic variables. Results: BP increased significantly in association with all PLMS (on average, SBP 22 mm Hg, DBP 11 mm Hg). BP changes associated with PLMS-MA were greater vs those associated with PLMS-noMA (p < 0.05). SBP and DBP changes increased with age and the duration of illness. Conclusions: Periodic leg movements–related repetitive nocturnal blood pressure fluctuations could contribute to the risk of cardiovascular diseases in patients with restless legs syndrome, especially in the elderly.

Sleep and Exertional Periodic Breathing in Chronic Heart Failure Prognostic Importance and Interdependence

Background— Sleep and exertional periodic breathing are proverbial in chronic heart failure (CHF), and each alone indicates poor prognosis. Whether these conditions are associated and whether excess risk may be attributed to respiratory disorders in general, rather than specifically during sleep or exercise, is unknown. Methods and Results— We studied 133 CHF patients with left ventricular ejection fraction (LVEF) ≤40%. During 1170±631 days of follow-up, 31 patients (23%) died. Nonsurvivors had higher New York Heart Association class, ventilatory response (&OV0312;e/&OV0312;co2 slope), and apnea-hypopnea index (AHI) and lower peak &OV0312;o2 (all P<0.01); lower LVEF and prescription of &bgr;-blockers, and shorter transmitral deceleration time (all P<0.05). Exertional oscillatory ventilation (EOV), established by cyclic fluctuations in minute ventilation that persisted for ≥60% of exercise duration with an amplitude ≥15% of the average resting value, was significantly more frequent in nonsurvivors (42% versus 15%, P<0.01). Multivariable analysis selected AHI (hazard ratio [HR] 5.66, 95% CI 2.3 to 19.9, P<0.01), peak &OV0312;o2 (HR 0.93, 95% CI 0.90 to 0.97, P<0.01), and &bgr;-blocker prescription (HR 0.34, 95% CI 0.13 to 0.87, P<0.05) as predictors of cardiac events. The best cutoff for AHI was >30/h. EOV was significantly related to AHI >30/h (&khgr;2 14.6, P<0.01): 78% of EOV patients showed AHI >30/h. Multivariable analysis, including breathing disorders alone (EOV, AHI >30/h) or in combination (EOV plus AHI >30/h), selected combined disorders as the strongest predictor of events (HR 6.65, 95% CI 2.6 to 17.1, P<0.01). Conclusions— In CHF, EOV is significantly associated with AHI >30/h. Although each breathing disorder alone is linked to total mortality, their combination has a crucial prognostic burden.

Pulmonary extravascular fluid accumulation in recreational climbers: a prospective study

BACKGROUND High altitude pulmonary oedema (HAPE) that is severe enough to require urgent medical care is infrequent. We hypothesised that subclinical HAPE is far more frequent than suspected during even modest climbs of average effort. METHODS We assessed 262 consecutive climbers of Monte Rosa (4559 m), before ascent and about 24 h later on the summit 1 h after arriving, by clinical examination, electrocardiography, oximetry, spirometry, carbon monoxide transfer, and closing volume. A chest radiograph was taken at altitude. FINDINGS Only one climber was evacuated for HAPE, but 40 (15%) of 262 climbers had chest rales or interstitial oedema on radiograph after ascent. Of 37 of these climbers, 34 (92%) showed increased closing volume. Of the 197 climbers without oedema, 146 (74%) had an increase in closing volume at altitude. With no change in vital capacity, forced expiratory volume in 1 s and forced expiratory flow at 25-75% of forced vital capacity increased slightly at altitude, without evidence of oedema. If we assume that an increased closing volume at altitude indicates increased pulmonary extravascular fluid, our data suggest that three of every four healthy, recreational climbers have mild subclinical HAPE shortly after a modest climb. INTERPRETATION The risk of HAPE might not be confined to a small group of genetically susceptible people, but likely exists for most climbers if the rate of ascent and degree of physical effort are great enough, especially if lung size is normal or low.

Sleep bruxism is associated to micro-arousals and an increase in cardiac sympathetic activity

Sleep bruxism (SB) subjects show a higher incidence of rhythmic masticatory muscle activity (RMMA) than control subjects. RMMA is associated with sleep micro‐arousals. This study aims to: (i) assess RMMA/SB episodes in relation to sleep cycles; (ii) establish if RMMA/SB and micro‐arousals occur in relation to the slow wave activity (SWA) dynamics; (iii) analyze the association between RMMA/SB and autonomic cardiac activity across sleep cycles. Two nights of polygraphic recordings were made in three study groups (20 subjects each): moderate to high SB, low SB and control. RMMA episodes were considered to occur in clusters when several groups of RMMA or non‐specific oromotor episodes were separated by less than 100 s. Correlations between sleep, RMMA/SB index and heart rate variability variables were assessed for the first four sleep cycles of each study group. Statistical analyses were done with SYSTAT and SPSS. It was observed that 75.8% of all RMMA/SB episodes occurred in clusters. Micro‐arousal and SB indexes were highest during sleep cycles 2 and 3 (P < 0.001). Within each cycle, micro‐arousal and RMMA/SB indexes showed an increase before each REM sleep (P ≤ 0.02). The cross‐correlation plot for micro‐arousal index showed positive association from 4 min preceding SB onset in the moderate to high SB subjects (P ≤ 0.06). The cross‐correlation plot revealed that SWA decreases following SB onset (P ≤ 0.05). Further cross‐correlation analysis revealed that a shift in sympatho‐vagal balance towards increased sympathetic activity started 8 min preceding SB onset (P ≤ 0.03). In moderate to severe SB subjects, a clear increase in sympathetic activity precedes SB onset.

Cardiac autonomic dysfunction in idiopathic REM sleep behavior disorder

More than 50% of persons with idiopathic REM sleep behavior disorder (RBD) will develop Parkinsons disease or Lewy body dementia. Symptom screens and metaiodobenzylguanine (MIBG)‐scintigraphy suggest autonomic abnormalities in idiopathic RBD, but it is unclear whether autonomic abnormalities can predict neurodegenerative disease. From a cohort of 99 patients with idiopathic RBD, we selected those who developed parkinsonism or dementia. These were matched by age, sex, and follow‐up duration to patients with RBD who remained disease free and to matched controls. From the polysomnographic trace performed at baseline evaluation, measures of beat‐to‐beat RR variability including time domains (mean RR‐interval and RR‐standard deviation) and frequency domains (low and high frequency components) were retrospectively assessed. Twenty‐one patients with idiopathic RBD who developed neurodegenerative disease were included (Parkinsons disease‐11, multiple system atrophy‐1, and dementia‐9). Age at PSG was 66 years, and 86% were male. PSG was performed on average 6.7 years before defined neurodegenerative disease. Comparing all patients with idiopathic RBD to controls, there were significant reductions in RR‐standard deviation (24.6 ± 2.2 ms vs. 35.2 ± 3.5 ms, P = 0.006), very low frequency components (238.6 ± 99.6 ms2 vs. 840.1 ± 188.3 ms2, P < 0.001), and low frequency components (127.8 ± 26.3 ms2 vs. 288.7 ± 66.2 ms2, P = 0.032). However, despite clear differences between patients with idiopathic RBD and controls, there were no differences in any measure between those who did or did not develop disease. RR‐variability analysis demonstrates substantial autonomic dysfunction in idiopathic RBD. However, this dysfunction is identical in patients who will or will not develop defined neurodegenerative disease. This suggests that autonomic dysfunction is linked with RBD independent of associated Parkinsons disease or Lewy body dementia.

Comparison between spectral analysis and the phenylephrine method for the assessment of baroreflex sensitivity in chronic heart failure

Baroreflex sensitivity assessed by means of the phenylephrine test plays a prognostic role in patients with previous myocardial infarction, but the need for drug injection limits the use of this technique. Recently, several non-invasive methods based on spectral analysis of systolic arterial pressure and heart period have been proposed, but their agreement with the phenylephrine test has not been investigated in patients with heart failure. The two methods (phenylephrine test and spectral analysis) were compared in a group of 49 patients with chronic congestive heart failure both at rest and during controlled breathing. The linear correlation and the limits of agreement between the phenylephrine test slope and the alpha-index [alpha(c); corrected by the coherence function between the interbeat interval (RR interval) and systolic arterial pressure] were evaluated. Only 16 patients had a measurable alpha-index at rest in both the low-frequency (LF) and high-frequency (HF) bands; the alpha(c)-index allowed measurements in all patients. It correlated moderately with the phenylephrine test slope at rest (r=0. 71 and P<0.001 in LF; r=0.57 and P<0.001 in HF) and during controlled breathing (r=0.51 and P<0.001 in LF; r=0.63 and P<0.001 in HF). Multivariate regression analysis showed that only alpha(c)LF during rest and alpha(c)HF during controlled breathing contributed significantly to baroreflex gain estimation. However, the agreement between methods was weak; the normalized limits of agreement and bias were -162 to 243% (0.46 ms/mmHg) for alpha(c)LF and -185 to 151% (-0.99 ms/mmHg) for alpha(c)HF. Thus the comparison between baroreflex sensitivity measurements obtained by the phenylephrine test and spectral analysis showed a moderate correlation between the two methods; however, despite the linear association, a consistent lack of agreement between the two techniques was found. Because both systematic and random factors contribute to the difference, these two techniques cannot be considered as alternatives for the assessment of heart failure.

Blood pressure changes associated with periodic leg movements during sleep in healthy subjects

BACKGROUND AND OBJECTIVES Periodic leg movements during sleep (PLMS) are associated with important blood pressure (BP) increases in restless legs syndrome (RLS) patients. These movements also are highly prevalent in the healthy elderly population. The aims of our study were to evaluate if heart rate (HR) and BP changes associated with PLMS are present in healthy subjects with no report of health concerns and to compare the amplitude of cardiovascular changes in healthy subjects to that of RLS subjects. METHODS Fourteen healthy subjects (six men, eight women; 46.6±9.7 y) and 14 RLS subjects (six men, eight women; 47.6±11.8 y) matched for age and gender participated in our study. Beat-to-beat noninvasive BP was continuously recorded during one night of polysomnography. HR, systolic BP (SBP) and diastolic BP (DBP) were measured for 10 beats before and 15 beats after onset of PLMS with and without microarousals (MA). RESULTS PLMS were associated with sudden and significant increases of HR, SBP and DBP in both groups; however, cardiovascular increases were more pronounced in RLS subjects than in healthy subjects. CONCLUSIONS Because PLMS index increases with age in healthy subjects and aging is associated with higher cardiovascular risk, further studies should investigate the impact of PLMS-related BP changes on the development of cardiovascular diseases in healthy elderly populations.

Cardiac Autonomic Denervation in Parkinson's Disease Is Linked to REM Sleep Behavior Disorder

Recent studies have suggested a close connection between autonomic dysfunction and rapid eye movement sleep behavior disorder, which differs in nature from other early‐stage markers of Parkinsons disease. In this study we examined the relationship between rapid eye movement sleep behavior disorder and autonomic dysfunction in Parkinsons disease as measured by cardiac beat‐to‐beat variability.

Sleep-disordered breathing in heart failure: characteristics and implications

Sleep-disordered breathing, namely obstructive sleep apnea (OSA) and central sleep apnea (CSA), are both often encountered in the setting of heart failure (HF), and have distinct differences in terms of prevalence, pathophysiology and consequences. OSA is independently associated with an increased risk for cardiovascular disease and for congestive HF in the general population. It is conceivable that this breathing disorder may have particularly deleterious effects in patients with coexisting heart disease, especially in those with a failing heart. There are considerable data addressing the interaction between OSA and the cardiovascular system, which underscore the importance of an early detection of this breathing disorder, especially in patients with HF. CSA is generally considered a consequence rather than a cause of HF, and is correlated with the severity of hemodynamic impairment. However, when present, it is associated with increased arrhythmic risk and higher cardiac mortality. Potential mechanisms implicated in the genesis of this breathing pattern and the possible therapeutic options, which have been proven to be effective in the clinical setting, are discussed.

Gender specificity of the slow wave sleep lost in chronic widespread musculoskeletal pain

OBJECTIVES The majority of patients suffering from musculoskeletal chronic widespread pain (CWP) are females, and they tend to report poor sleep. We tested the hypothesis that the poor sleep of female patients reporting CWP is gender specific for changes in (1) electroencephalograph (EEG) features and (2) heart rate variability (HRV). METHODS Twenty-four normal sleepers were compared to 24 patients with CWP who complained of poor sleep. Patients were referred from general practice and were matched for age (41-47 years) and gender (25 W, 23 M). Sleep variables and spectral EEG activity analyses were performed during 1 night of sleep recording. Time-domain cardiac RR interval and spectral autoregressive analyses were also performed from the same data set. RESULTS Compared to normal females, female patients with CWP had significantly shorter sleep duration (-68 min), lower sleep efficiency (-9.9%), twice the awakenings and a trend for more periodic limb movements per hour of sleep. Daytime napping was reported by 78% of CWPs. Compared to all controls, females with CWP had significantly less power in the EEG delta band in the first and second non-REM sleep cycle. Although RR interval analysis revealed that CWP patients had a faster heart rate, neither the sympathetic nor sympathovagal analysis reached statistical significance for gender or pain status comparisons. CONCLUSIONS Female CWP patients have shorter sleep duration with many awakenings and lower sleep EEG delta activity without gender difference in HRV.