Heart rate response to cortical arousals in patients with isolated obstructive sleep apnea and with comorbid insomnia (COMISA).

PURPOSE: Comorbid insomnia often occurs in patients with obstructive sleep apnea (OSA), referred to as COMISA. Cortical arousals manifest as a common feature in both OSA and insomnia, often accompanied by elevated heart rate (HR). Our objective was to evaluate the heart rate response to nocturnal cortical arousals in patients with COMISA and patients with OSA alone. METHODS: We analyzed data from patients with COMISA and from patients with OSA matched for apnea-hypopnea index. Sleep staging and analysis of respiratory events and cortical arousals were performed using the Philips Somnolyzer automatic scoring system. Beat-by-beat HR was analyzed from the onset of the cortical arousal to 30 heartbeats afterwards. HR responses were divided into peak and recovery phases. Cortical arousals were separately evaluated according to subtype (related to respiratory events and spontaneous) and duration (3-6 s, 6-10 s, 10-15 s). RESULTS: A total of 72 patients with COMISA and 72 patients with OSA were included in this study. There were no overall group differences in the number of cortical arousals with and without autonomic activation. No significant differences were found for spontaneous cortical arousals. The OSA group had more cortical arousals related to respiratory events (21.0 [14.8-30.0] vs 16.0 [9.0-27.0], p = 0.016). However, the COMISA group had longer cortical arousals (7.2 [6.4-7.8] vs 6.7 [6.2-7.7] s, p = 0.024) and the HR recovery phase was prolonged (52.5 [30.8-82.5] vs 40.0 [21.8-55.5] beats/min, p = 0.017). Both the peak and the recovery phase for longer cortical arousals with a duration of 10-15 s were significantly higher in patients with COMISA compared to patients with OSA (47.0 [27.0-97.5] vs 34.0 [21.0-71.0] beats/min, p = 0.032 and 87.0 [47.0-132.0] vs 71.0 [43.0-103.5] beats/min, p = 0.049, respectively). CONCLUSIONS: The HR recovery phase after cortical arousals related to respiratory events is prolonged in patients with COMISA compared to patients with OSA alone. This response could be indicative of the insomnia component in COMISA.

Sleep structure in patients with COMISA compared to OSA and insomnia.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) and insomnia frequently co-occur, making diagnosis and treatment challenging. We investigated differences in sleep structure between patients with OSA, insomnia, and comorbid insomnia and sleep apnea (COMISA) to identify characteristics that can be used to improve the diagnosis of COMISA. METHODS: We obtained polysomnography data of 326 patients from the Sleep and OSA Monitoring with Non-Invasive Applications database. The group included patients with OSA (n = 199), insomnia (n = 47), and COMISA (n = 80). We compared statistics related to sleep structure between the 3 patient groups. RESULTS: Wake after sleep onset was significantly shorter for the OSA group (median: 60.0 minutes) compared to the COMISA (median: 83.3 minutes, P < .01) and the insomnia (median: 83.5 minutes, P = .01) groups. No significant differences were found in the total number of awakenings and the number of short (up to and including 2 minutes) and medium-length awakenings (2.5 up to and including 4.5 minutes). However, the number of long awakenings (5 minutes or longer) and wake after sleep onset containing only long awakenings was significantly lower for patients with OSA (median: 2 awakenings and 25.5 minutes) compared to patients with COMISA (median: 3 awakenings, P < .01 and 43.3 minutes, P < .001) or with insomnia (median: 3 awakenings, P < .01 and 56.0 minutes, P < .001). Total sleep time was significantly longer and sleep efficiency was significantly higher for the OSA group (median: 418.5 minutes and 84.4%) compared to both the COMISA (median: 391.5 minutes, P < .001 and 77.3%, P < .001) and the insomnia (median: 381.5 minutes, P < .001 and 78.2%, P < .001) groups. The number of sleep-stage transitions during the night for patients with COMISA (median: 194.0) was lower compared to that for patients with OSA (median: 218.0, P < .01) and higher compared to that for patients with insomnia (median: 156.0, P < .001). Other sleep architectural parameters were not discriminative between the groups. CONCLUSIONS: Patients with COMISA show specific characteristics of insomnia, including prolonged awakenings. This variable is distinctive in comparison to patients with OSA. The combination of prolonged awakenings and the presence of sleep-disordered breathing leads to increased sleep disturbance compared to patients having only 1 of the sleep disorders. CITATION: Wulterkens BM, Hermans LWA, Fonseca P, et al. Sleep structure in patients with COMISA compared to OSA and insomnia. J Clin Sleep Med. 2023;19(6):1051-1059.

Management of insomnia in sleep disordered breathing.

Both obstructive sleep apnoea (OSA) and chronic insomnia disorder are highly prevalent in the general population. Whilst both disorders may occur together by mere coincidence, it appears that they share clinical features and that they may aggravate each other as a result of reciprocally adverse pathogenetic mechanisms. Comorbidity between chronic insomnia disorder and OSA is a clinically relevant condition that may confront practitioners with serious diagnostic and therapeutic challenges. Current data, while still scarce, advocate an integrated and multidisciplinary approach that seems superior over the isolated treatment of each sleep disorder alone.

Severe Positional Central Sleep Apnea in an Asymptomatic Adult With a PHOX2B Frameshift Mutation.

ABSTRACT: We report an unusual case of an adult patient carrying a germline PHOX2B frameshift mutation and hence was diagnosed with congenital central hypoventilation syndrome. He came to medical attention after the mutation was identified in his daughter who presented with hypoventilation and a neuroblastoma. Although PHOX2B mutations are usually associated with a phenotype of congenital hypoventilation, severe autonomic dysfunction and neural crest tumors, our patient had no complaints at the time of presentation. At polysomnography we found severe positional hypercapnic central sleep apnea, partly responsive to positional therapy. Eventually, he was titrated to noninvasive ventilation with resolution of the central breathing events and, in hindsight, a more refreshing sleep than before. Clinicians working in sleep medicine need to be aware of the variable expression of this rare condition to prevent late cardiorespiratory and neurocognitive complications.

Vitamin D and muscle function: is there a threshold in the relation?

OBJECTIVES: First, to determine the association between serum 25 hydroxyvitamin D (25OHD) concentration and muscle mass, strength, and performance. Second, to explore if there is a threshold in the association. DESIGN: Cross-sectional, single-center study. SETTING: The central part of the Netherlands (52° Northern latitude). PARTICIPANTS: A total of 802 independently living men and postmenopausal women 40 to 80 years of age. MEASUREMENTS: Health-related and lifestyle factors, including physical activity, 25OHD concentration, lean mass, handgrip strength, knee extension strength, and physical performance were determined. RESULTS: Overall, higher 25OHD level was significantly associated with higher lean mass (22.6 g per nmol/L, 95% CI 7.3-37.9), handgrip strength (0.020 kg per nmol/L, 95% CI 0.001-0.038), and physical performance (0.006 points per nmol/L, 95% CI 0.001-0.012), after adjustment for various confounders. This association was most pronounced below a 25OHD level of 60 nmol/L, with lean mass increase 79.6 g per nmol/L (95% CI 40.8-118.4, P < .01), handgrip strength 0.09 kg per nmol/L (95% CI 0.045-0.141, P < .01), and physical performance 0.02 points per nmol/L (95% CI 0.005-0.032, P < .01), and these significant associations attenuated to null above this threshold. CONCLUSION: In middle-aged men and (postmenopausal) women, a higher 25OHD level was significantly associated with higher lean mass, muscle strength, and performance. These associations were most pronounced below 60 nmol/L and absent above 60 nmol/L, indicating a ceiling effect.

Muscle strength and mobility in vitamin D-insufficient female geriatric patients: a randomized controlled trial on vitamin D and calcium supplementation.

BACKGROUND AND AIMS: Insufficient vitamin D status, commonly found in older people, has been associated with muscle weakness which, in old age, impairs mobility and is a risk factor for falling. In a randomized, double-blind placebo-controlled trial, we tested the hypothesis that vitamin D + calcium supplementation improves muscle strength and mobility, compared with calcium mono-therapy in vitamin D-insufficient female geriatric patients. METHODS: Seventy female geriatric patients >65 years of age with serum 25-hydroxyvitamin D3 (25OHD) concentrations between 20 and 50 nmol/L, visiting an outpatient geriatric department, were included. Participants received either cholecalciferol 400 IU/day + calcium 500 mg/day (D/Cal group) or a placebo + calcium 500 mg/day (Plac/Cal group) for 6 months. At baseline and 6 months, muscle strength, power and functional mobility were tested. RESULTS: At baseline, 25OHD was significantly (p<0.05) associated with knee extension strength (r=0.42), handgrip strength (r=0.28), leg extension power (r=0.34), Timed Get Up and Go (r=-0.31) and Modified Cooper test (r=0.44). At 6 months, a significant difference in 25OHD (77.2 vs 41.6 nmol/L, p<0.001) and 1,25OHD was found between the two groups. Significantly improving vitamin D status in the D/Cal group compared with the Plac/Cal group did not result in a significant difference in strength or functional mobility between the two groups. CONCLUSIONS: Daily 400 IU vitamin D + 500 mg calcium supplementation is not enough to significantly improve strength or mobility in vitamin D-insufficient female geriatric patients.

Strength, mobility and falling in women referred to a geriatric outpatient clinic.

BACKGROUND AND AIMS: Mobility impairment and falling have a multifactorial etiology in frail older people. Muscle weakness is one of the risk factors and is accessible to intervention. The aim of this study was to determine the most important contributors of mobility and indicators of fall occurrence in women referred to a geriatric outpatient clinic. METHODS: Mobility was assessed using the Timed 'Get-Up-and-Go' test (TGUG) and the modified Coopertest (COOP). Falling was assessed retrospectively and isometric knee extension force was measured using fixed dynamometry. Habitual physical activity was quantified using a questionnaire for the elderly. Height, weight, medical conditions and current medication were recorded. RESULTS: Isometric knee extension strength and habitual physical activity, which consisted predominantly of household work, were independent variables of performance on TGUG and COOP and together explained 57% of the variance in TGUG (r=0.75, p<0.001), and 64% of that in COOP, (r=0.80, p<0.001). Age, total number of medical conditions, and presence of cardiovascular disease were not significant in the model. Women in the lowest tertile of knee extension strength had a significantly higher probability of falling (0.75, 95% CI 0.56-0.91) compared with women in the highest tertile (0.27, 95% CI 0.14-0.50). CONCLUSIONS: Knee extension strength remains a strong determinant of mobility and fall occurrence in women referred to a geriatric outpatient clinic. Performing light to moderate household work remains independently associated with functional mobility.

Vitamin D deficiency, muscle function, and falls in elderly people.

An inadequate serum vitamin D status is commonly seen in elderly people as the result of various risk factors interacting in this population. Apart from the well-known effects on bone metabolism, this condition is also associated with muscle weakness, predominantly of the proximal muscle groups. Muscle weakness below a certain threshold affects functional ability and mobility, which puts an elderly person at increased risk of falling and fractures. Therefore, we wanted to determine the rationale behind vitamin D supplementation in elderly people to preserve and possibly improve muscle strength and subsequently functional ability. From experimental studies it was found that vitamin D metabolites directly influence muscle cell maturation and functioning through a vitamin D receptor. Vitamin D supplementation in vitamin D-deficient, elderly people improved muscle strength, walking distance, and functional ability and resulted in a reduction in falls and non-vertebral fractures. In healthy elderly people, muscle strength declined with age and was not prevented by vitamin D supplementation. In contrast,severe comorbidity might affect muscle strength in such a way that restoration of a good vitamin D status has a limited effect on functional ability. Additional research is needed to further clarify to what extent vitamin D supplementation can preserve muscle strength and prevent falls and fractures in elderly people.