Effect of Continuous Positive Airway Pressure on Incident Frailty in Elderly Patients with Obstructive Sleep Apnea: A Study Based on Propensity Score Matching.

Background: The concomitant rise in the prevalence of obstructive sleep apnea (OSA) and frailty among the elderly population has been linked to an increase in mortality rates. Despite continuous positive airway pressure (CPAP) being the gold standard treatment for OSA, its impact on incident frailty remains inadequately explored. Methods: In this cohort study, we analyzed data from 1290 patients diagnosed with OSA, aged 60 years and older. A subset of 71 patients who demonstrated high adherence to CPAP therapy were categorized as the CPAP group. Propensity score matching (PSM) was employed at a 1:4 ratio, matching for variables such as age, gender, body mass index (BMI), and sleep apnea-hypopnea index (AHI), to establish a non-CPAP group for comparison. The FRAIL scale was utilized to evaluate the frailty status of participants. Logistic regression analysis examined the relationship between CPAP therapy and incident frailty, as well as its individual components, in elderly patients with OSA. Results: During a median follow-up period of 52 months, incident frailty was observed in 70 patients (19.7%). Patients with OSA receiving CPAP therapy exhibited a lower incidence of frailty compared to those not receiving CPAP (11.26% vs 21.83%, P=0.045). In the multivariate model, CPAP therapy was significantly correlated with a reduced risk of incident frailty (OR = 0.36, 95% CI, 0.15-0.88; P = 0.025). Subcomponent analyses revealed that CPAP was associated with a lower risk of fatigue (OR=0.35, 95% CI, 0.19-0.63; P < 0.001), resistance (OR = 0.32, 95% CI, 0.14-0.74; P=0.008), and weight loss (OR = 0.38, 95% CI, 0.19-0.75; P = 0.007). Conclusion: CPAP therapy was associated with a reduced risk of incident frailty among elderly patients with OSA.

Association between Serum Cystatin C levels and long-term cardiovascular outcomes and all-cause mortality in older patients with obstructive sleep apnea.

Background and Aims: To investigate the association between obstructive sleep apnea (OSA) severity and baseline serum cystatin C (Cys-C) concentration and to explore the association between baseline serum Cys-C and long-term cardiovascular outcomes and mortality in older patients with OSA. Methods: Between January 2015 and October 2017, a total of 1107 consecutive eligible older patients (≥60 years) with OSA were included in this multicenter, prospective cohort study, and baseline demographics, clinical characteristics, sleep parameters, and follow-up outcomes were collected. Participants were divided into different groups based on baseline serum Cys-C levels. The primary end point was major adverse cardiovascular events (MACE) and the secondary end point was all-cause mortality. The correlation between OSA severity and baseline serum Cys-C was evaluated by Spearman correlation analysis. Multivariate Cox regression was used to analyze the association between Cys-C and the incidence of MACE and mortality. Results: Participants included 672 men and 435 women, with a median age of 66 (range, 60-96) years. At baseline, apnea-hypopnea index (AHI) (r = 0.128, p < 0.05), oxygen desaturation index (ODI) (r = 0.116, p < 0.05), and the lowest pulse oxygen saturation (LSpO2) (r = -0.097, p < 0.05) were correlated with serum Cys-C concentration. During the median follow-up period of 42 months, 97 patients (8.8%) experienced MACE and 40 patients (3.6%) experienced death. The association between serum Cys-C levels and the risk of MACE and all-cause mortality was slow rising shaped. The multivariable Cox regression analysis showed patients with a serum Cys-C concentration of ≥1.14 mg/L had higher risks of MACE (HR = 5.30, 95% CI: 2.28-12.30, p < 0.05) and all-cause mortality (HR = 9.66, 95% CI: 2.09-44.72, p < 0.05) compared with patients with serum Cys-C of ≤0.81 mg/L in older patients with OSA. The receiver-operating characteristic curve showed baseline serum Cys-C levels exhibited moderately capable of identifying patients with a long-term risk of clinical adverse events (MACE and mortality). Conclusion: OSA severity was positively correlated with serum Cys-C concentration. High levels of Cys-C were independently associated with increased risks of MACE and all-cause mortality in older patients with OSA, suggesting that lowering Cys-C levels should be considered as a therapeutic target, and monitoring serum Cys-C may be beneficial to the favorable prognosis of older patients with OSA.

Prevalence and factors associated with atrial fibrillation in older patients with obstructive sleep apnea.

PURPOSE: This study sought to identify the prevalence and factors associated with atrial fibrillation (AF) in older patients with obstructive sleep apnea (OSA) in China.  METHODS: This was an explorative cross-sectional study. Between January 2015 and October 2017, we continuously recruited 1285 older patients with OSA who underwent overnight polysomnography from sleep centers of multiple hospitals. They were assessed using 12-lead ECG or 24-h dynamic ECG, and their baseline demographics, clinical characteristics, sleep parameters, and medical history were determined. Multivariate binary logistic regression analysis was used to investigate the factors related to AF in these older patients with OSA. RESULTS: The clinician classified 122 (9.5%) patients as having AF. The prevalence of AF significantly increased with age (P < 0.05) but did not significantly differ between the mild, moderate, and severe OSA groups. Additionally, the prevalence of paroxysmal AF was 7.2% among the overall study population, and it increased with OSA severity or advanced age (P < 0.05). Persistent AF was noted in 2.3% participants, and the prevalence also increased with age. The logistic regression analysis showed that age (OR = 1.054, 95%CI: 1.027-1.018, P < 0.001), history of drinking (OR = 1.752, 95%CI: 1.070-2.867, P < 0.05), chronic heart disease (OR = 1.778, 95%CI: 1.156-2.736, P < 0.01), diabetes mellitus (OR = 1.792, 95%CI: 1.183-2.713, P < 0.01), and reduced diastolic function (OR = 2.373, 95%CI = 1.298-4.337, P < 0.01) were relevant to AF among participants with OSA. CONCLUSION: The prevalence of AF is significantly common in older patients with OSA. Age, history of drinking, chronic heart disease, diabetes mellitus, and reduced diastolic function are independently related to AF in these patients.

Impact of obstructive sleep apnea complicated with type 2 diabetes on long-term cardiovascular risks and all-cause mortality in elderly patients.

BACKGROUND: The prognostic significance of obstructive sleep apnea (OSA) in elderly patients with type 2 diabetes is unclear. The aim of this study was to determine the risk of cardiovascular disease (CVD) and mortality in elderly patients with OSA complicated with type 2 diabetes compared to patients with OSA without type 2 diabetes. METHODS: From January 2015 to October 2017, 1113 eligible elderly patients with OSA, no history of cardiovascular, ≥60 years of age, and complete follow-up records were enrolled in this consecutive multicentre prospective cohort study. All patients had completed polysomnography (PSG) examinations. An apnoea-hypopnoea index of ≥5 events per hour recorded by polysomnography was defined as the diagnostic criterion for OSA. We collected baseline demographics, clinical characteristics, sleep parameters and follow-up outcomes. The primary aim of this study was to identify the risk of incident major adverse cardiovascular events (MACE). Secondary outcomes were all-cause mortality, components of MACE and a composite of all events. Kaplan-Meier survival analysis and Cox proportional hazards models were used to evaluate whether type 2 diabetes was associated with incident events. RESULTS: A total of 266 (23.9%) patients had OSA complicated with type 2 diabetes. MACE occurred in 97 patients during the median 42-month follow-up. Kaplan-Meier survival curves indicated a significant relationship between type 2 diabetes and MACE (log-rank P = 0.003). Multivariable Cox regression analysis showed that type 2 diabetes increased the risk of MACE (HR = 1.64, 95% CI:1.08-2.47, P = 0.019), hospitalisation for unstable angina (HR = 2.11, 95% CI:1.23-3.64, P = 0.007) and a composite of all events in elderly patients with OSA (HR = 1.70, 95% CI:1.17-2.49, P = 0.007). However, there were no significant differences in the incidence of cardiovascular death, all-cause mortality, MI and hospitalisation for heart failure between patients with and without diabetes (P > 0.05). The subgroup analysis demonstrated that females (AHR = 2.46, 95% CI:1.17-5.19, P = 0.018), ≥ 70 years (AHR = 1.95, 95% CI:1.08-3.52, P = 0.027), overweight and obese (AHR = 2.04, 95% CI:1.29-3.33, P = 0.002) with mild OSA (AHR = 2.42, 95% CI: 1.03-5.71, P = 0.044) were at a higher risk for MACE by diabetes. CONCLUSION: OSA and type 2 diabetes are interrelated and synergistic with MACE, hospitalisation for unstable angina and a composite of all events development. Overweight and obese females, ≥ 70 years with mild OSA combined with type 2 diabetes presented a significantly high MACE risk.

Association Cystatin C and Risk of Stroke in Elderly Patients With Obstructive Sleep Apnea: A Prospective Cohort Study.

Background: Few prospective cohort studies have assessed the relationship between Cystatin C (Cys-C) and risk of stroke in elderly patients with obstructive sleep apnea (OSA). The study sought to examine the association between baseline serum Cys-C and long-term risk of stroke among elderly OSA patients. Methods: A total of 932 patients with OSA, no history of stroke, ≥60 years of age, and complete serum Cys-C records were included in this study. All patients had completed polysomnography (PSG). OSA was defined as an apnea-hypopnea index (AHI) of ≥5 events per hour. Participants were categorized into four groups according to baseline serum Cys-C concentration, split into quartiles. Multivariate Cox regression were used to evaluate the association between Cys-C and the incidence of new-onset stroke. Results: Stroke occurred in 61 patients during the median 42-month follow-up period. The cumulative incidence rate of stroke was 6.5%, which included 54 patients with ischemic stroke and 7 patients with hemorrhagic stroke. The cumulative incidence of stroke was higher among patients with baseline serum Cys-C concentration of ≥1.15 mg/L when compared with other groups (P Log-rank < 0.001). After adjusting for potential confounding factors in the Cox regression model, patients with a serum Cys-C concentration of ≥1.15 mg/L had a 2.16-fold higher risk of developing stroke compared with patients with serum Cys-C ≤ 0.81 mg/L (HR, 2.16, 95%CI, 1.09-6.60; P = 0.017). Additionally, there was a higher risk in those of age ≥70 years (HR, 3.23, 95%CI, 1.05-9.24; P = 0.010). The receiver-operating characteristic curves showed that the capability of Cys-C to identify elderly patients with OSA who had a long-time risk of stroke was moderate (AUC = 0.731, 95% CI: 0.683-0.779, P = 0.001). Conclusion: Increased Cys-C concentration was identified as a risk factor in the incidence of stroke in elderly patients with OSA, independent of gender, BMI, hypertension and other risk factors. Additionally, it conferred a higher risk in patients of age ≥70 years.

[Cardiac functional alterations and its risk factors in elderly patients with obstructive sleep apnea syndrome free of cardiovascular disease].

OBJECTIVE: To evaluate the changes of cardiac structure and function and their risk factors in elderly patients with obstructive sleep apnea syndrome (OSA) without cardiovascular complications. METHODS: Eighty-two elderly OSA patients without cardiovascular disease admitted between January, 2015 and October, 2016 were enrolled in this study. According to their apnea-hypopnea index (AHI, calculated as the average number of episodes of apnoea and hypopnoea per hour of sleep), the patients were divided into mild OSA group (AHI < 15) and moderate to severe OSA group (AHI ≥ 15). The demographic data and the general clinical data were recorded and fasting blood samples were collected from the patients on the next morning following polysomnographic monitoring for blood cell analysis and biochemical examination. Echocardiography was performed within one week after overnight polysomnography, and the cardiac structure, cardiac function and biochemical indexes were compared between the two groups. RESULTS: Compared with those with mild OSA group, the patients with moderate to severe OSA had significantly higher hematocrit (0.22±0.08 vs 0.17±0.04, P=0.032) and serum creatinine level (70.94± 27.88 vs 54.49±34.22 µmol/L, P=0.022). The left ventricular ejection fraction, interventricular septal thickness, left ventricular posterior wall thickness, left atrial diameter and left ventricular end-diastolic diameter were all similar between the two groups. With a similar early diastolic mitral flow velocity (E) between the two groups, the patients with moderate to severe OSA had a significantly higher late diastolic mitral flow velocity (A) (70.35±6.87 vs 64.09±8.31, P=0.0001) and a significantly lower E/A ratio (0.98±0.06 vs 1.08±0.05, P=0.0001) than the patients with mild OSA. Multiple linear regression showed that the E/A ratio was negatively correlated with AHI (ß =- 0.645, P=0.0001). CONCLUSIONS: Cardiac diastolic function impairment may occur in elderly patients with moderate or severe OSA who do not have hypertension or other cardiovascular diseases, and the severity of the impairment is positively correlated with AHI.

[Correlation between severity of obstructive sleep apnea syndrome and red cell distribution width in elderly patients].

OBJECTIVE: To investigate the correlation between the severity of obstructive sleep apnea syndrome (OSAS) and red cell distribution width (RDW) in elderly patients. METHODS: A cross-sectional study was conducted among 311 elderly patients diagnosed with OSAS in the snoring clinic between January, 2015 and October, 2016 and 120 healthy controls without OSAS from physical examination populations in the General Hospital of PLA. The subjects were divided into control group with apnea-hypopnea index (AHI) <5 (n=120), mild OSAS group (AHI of 5.0-14.9; n=90), moderate OSAS group (AHI of 15.0-29.9; n=113) and severe OSAS group (AHI ≥ 30; n=108). The clinical characteristics and the results of polysomnography, routine blood tests and biochemical tests of the subjects were collected. Multiple linear regression analysis was used to examine the correlation between OSAS severity and RDW. RESULTS: The levels of RDW and triglyceride were significantly higher in severe OSAS group than in the other groups (P < 0.01). The levels of fasting blood glucose and body mass index were significantly higher in severe and moderate OSAS groups than in mild OSAS group and control group (P < 0.05 or P < 0.01). Multiple linear regression analysis showed that AHI was positively correlated with body mass index (ß=0.111, P=0.032) and RDW (ß=0.106, P=0.029). The area under ROC curve of RDW for predicting the severity of OSAS was 0.687 (P=0.0001). CONCLUSIONS: The RDW increases as OSAS worsens and may serve as a potential marker for evaluating the severity of OSAS.

The association between migraine and restless legs syndrome: an updated systematic review and meta-analysis.

OBJECTIVE: This study aims to gain further insight into the association between migraine and restless legs syndrome (RLS). METHODS: A literature search of PubMed, Embase, and Web of Science was performed for studies investigating the association between any migraine and RLS; a meta-analysis of eligible studies was conducted to determine a pooled effect estimate for the association. RESULTS: Fifteen studies were included in this meta-analysis. The studies differed in methodology, but all investigated the association between migraine and RLS. Pooled RLS prevalence was 17.0% [95% confidence interval (CI) 15.0%-20.0%] among migraineurs, and 7.0% (95% CI 5.0%-8.0%) among no migraine individuals. Pooled analyses showed that migraine was associated with RLS, but effect estimates were substantially higher in case-control studies [pooled odds ratio (OR) = 3.77, 95% CI 2.73-5.21; I2 = 50.1%] than in cross-sectional studies (pooled OR = 1.25, 95% CI 1.11-1.41; I2 = 34.2%). Subgroup analyses were not conducted to find potential factors that affect this association because of too few available studies. CONCLUSIONS: This updated meta-analysis confirms the association between migraine and RLS. Future studies should specifically investigate the potential effects of gender, age, aura status, and type (episodic or chronic) of migraine on the association between the two disorders.

Role of the lung in the progression of multiple organ dysfunction syndrome in ageing rat model.

BACKGROUND: Multiple organ dysfunction syndrome in the elderly (MODSE) is a problem with high mortality in the critical care of elderly patients. The pathogenesis of MODSE remains elusive. This study aimed to establish rat models of MODSE and to investigate the pathogenetic mechanism responsible for the development of MODSE in the rat models. METHODS: Twenty-four-month old rats (elderly) received intravenous injection of lipopolysaccharide (LPS) to induce rat model of MODSE. In the model, we observed the physical responses, biochemical indices changes, histopathological features of vital organs, including lung, liver, heart, and kidney. We also investigated the sequence of individual organ dysfunction and changes of proinflammatory factors. Three-month-old rats, serving as young rat controls, received parallel procedures. Besides, normal saline injection was also performed on elderly and young control rats. RESULTS: All rats displayed different degree of physical response after LPS injection, preceded by deterioration of respiratory status. At 6 hours, lung injury was observed, which started earlier than other organ injury that was observed in about 24 hours. Furthermore, all vital organ injury was more severe in elderly rats than in young rats at the same time points. After LPS injection, pulmonary alveolar macrophages apoptosis rate increased obviously, and was more significant in elderly rats ((43.4 ± 8.4)%) than in young rats ((24.2 ± 3.0)%). LPS injection also enhanced tumor necrosis factor a (TNF-a) concentration significantly in these organs. Its peak concentration appeared at 6 hours in lung tissue and at 24 hours in other organs after LPS injection. TNF-a level was higher in elderly rats than in young rats at the same time points. The increase was most significant in lung tissue. After intravenous administration of LPS, toll-like receptor 4 (TLR4) expression in lung tissue was upregulated markedly, and peaked at 6 hours. In contrast, upregulation of TLR4 expression in liver peaked at 24 hours, lagging behind that in the lung. CONCLUSION: Lung is the first and most seriously injured organ in rat model of MODSE and it may play an "initiating" role in the development of MODSE.

High levels of inflammation and insulin resistance in obstructive sleep apnea patients with hypertension.

Hypertension induced by obstructive sleep apnea (OSA) may be multifactorial in origin, and systemic inflammation is one of the major factors. However, OSA patients do not always have the identical probability with hypertension even in patients with the same history and degree of OSA. The aim of this study was to compare the levels of inflammation and insulin resistance in two groups of patients who had the same degree as well as the same long history of OSA, but with/without hypertension. OSA patients (Apnea Hyponea Index, AHI ≥ 40/h, n = 70) were examined by polysomnography and blood analysis for the measurements of fasting plasma glucose, serum insulin (FINS), high-sensitivity C-reactive protein (CRP), peptide C,TNF-α, IL-6, and IL-10. Patients with hypertension (n = 40) had higher level of LDL-C and lower HDL-C levels than patients without hypertension. Almost half (16/40) of OSA patients with hypertension had family history of hypertension. Moreover in OSA patients with hypertension, the levels of TNF-α, IL-6, and CRP were higher, but IL-10 was lower than those without hypertension. FINS, peptide C, HOMA-IR, and HOMA-islet were also higher in OSA patients with hypertension. OSA patients with hypertension have higher level of inflammation and insulin resistance. Systemic inflammation and insulin resistance are both important factors for the development of hypertension in OSA patients.

A comparison of elderly and adult multiple organ dysfunction syndrome in the rat model.

Multiple organ dysfunction syndrome (MODS) in the elderly is the most common cause of mortality in critically ill elderly patients, and it is different from MODS in the adult in clinic. Rare studies have been done on its pathogenesis and the comparison between adult and elderly MODS animal models. This work aimed at exploring the mechanisms mediating elderly MODS and compared this with adult MODS. Male Sprague-Dawley aged and adult rats were intraperitoneally injected with zymosan for incitement of MODS. Aged rats receiving zymosan showed severer pulmonary, cardiac and renal dysfunctions than adult rats. Likewise, the tissue lesions under light microscope in major organs of zymosan treated aged rats were much worse than those of zymosan treated adult rats. Moreover, zymosan treated aged rats showed 142% and 64% greater increase in pulmonary alveolar macrophages (AMs) apoptotic rate and serum TNF-alpha level, respectively, whereas 43% smaller increase in serum IL-10 level compared to zymosan treated adult rats. Furthermore, lung injury was much worse than that in other organs in zymosan treated aged rats. Overall, these results suggest that zymosan can be used in aged rats to incite MODS in the elderly. In the animal model of elderly MODS, there are (1) severer injury in lung, heart and kidney vs adult; (2) easier to develop severe systemic inflammatory response syndrome (SIRS) instead of compensatory anti-inflammatory response syndrome (CARS) compared to the adult; and (3) severer inflammation in lung than other organs indicative of the possible roles of lung in triggering MODS in the elderly.

[Apoptosis of pulmonary alveolar macrophages in aged and adult rats: a comparative study].

OBJECTIVE: To investigate the role of alveolar macrophages (AM) in the initiation of multiple organ failure in the elderly (MOFE). METHODS: Three-month-old (adult) and 24-month-old (aged) males SD rats were used as experimental animals. Zymosan 0.5 g/kg was used to establish animal model of MOFE, normal saline were used among the control rats. The rats were divided into 4 groups: aged model group, aged control group, adult model group, and adult control group. Twenty-four hours after the establishment of model, 6 surviving rats from each group were killed. The trachea, bronthi, and lungs were isolated and lavaged with normal saline. One minute later the bronchi-alveolar lavage fluid (BALF) was re-extracted. Cells were collected from the fluid and put into 24-well cell culture plate. The alveolar macrophages (AMs) adhered to the wall were collected, suspended again, cultured, re-collected, centrifuged, and isolated. Apoptosis of the enriched AM was measured by propidium staining and flow cytometry. Fluo-3.AM staining and flow cytometry were used to detect the intracellular free calcium. Mitochondrial membrane electric potential was detected by rhodamine 123 staining with flow cytometry. RESULTS: The apoptotic rate (APO) of AM in the aged rat models was 43.4% +/- 8.4%, significantly higher than that of adult model rats (24.2% +/- 3.0%, P < 0.01). Compared with the controls, the intracellular calcium increased, but mitochondrial Dgr;Psim decreased in the 2 model groups. CONCLUSION: The AM APO% of aged MOFE model increases. It may be one of the causes of difficulty to control the inflammation in the lung with MOFE and easiness to induce MOFE in elderly when their lungs are infected or injured. Changes of intracellular calcium and mitochondrial Dgr;Psim may play pivotal roles in apoptosis of AM.