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Obstructive sleep apnea is independently associated with an increased prevalence of metabolic syndrome
Abstract
Obstructive sleep apnoea (OSA) is associated with increased cardiovascular morbidity and mortality. Although it was previously assumed that this was due to its relation with obesity, recent data suggest that OSA is independently associated with the cardiovascular risk factors that comprise metabolic syndrome, including hypertension, insulin resistance, impaired glucose tolerance, and dyslipidaemia. However, as previous studies have only considered these variables individually, it has not been possible to determine the overall association of OSA with this syndrome.
We recruited 61 male subjects with OSA and 43 controls. Glucose, insulin, lipids, and blood pressure (BP) were measured following an overnight fast. Insulin resistance was estimated using homeostasis model assessment (HOMA). Metabolic syndrome was diagnosed according to National Cholesterol Education Program (NCEP) criteria. Subjects with OSA were more obese, had higher BP and fasting insulin, were more insulin resistant, had lower HDL cholesterol, and an increased incidence of metabolic syndrome (87% vs. 35%, p<0.0001). In order to determine whether these associations were independent of obesity and other known covariates, a regression analysis adjusted for age, BMI, smoking, and alcohol consumption was performed. This demonstrated that OSA was independently associated with increased systolic and diastolic blood pressure, higher fasting insulin and triglyceride concentrations, decreased HDL cholesterol, increased cholesterol:HDL ratio, and a trend towards higher HOMA values. Metabolic syndrome was 9.1 (95% confidence interval 2.6, 31.2: p<0.0001) times more likely to be present in subjects with OSA.
OSA is independently associated with an increase in the cardiovascular risk factors that comprise the metabolic syndrome and its overall prevalence. This may help explain the increased cardiovascular morbidity and mortality associated with this condition.
... Epidemiological studies have demonstrated that sleep apnea increases risk of dyslipidemia and hyperglycemia. [7][8][9][10][11][12] This research overall indicates the importance of intervening to treat sleep apnea as a means of preventing CVD in the population [2,3,5]. ...
... These findings indicate greater risk for CVD associated with sleep apnea taken from reliable measures from random blood samples. Our results confirm prior studies showing strong associations between sleep apnea and higher levels of LDL-C and higher total cholesterol/HDL-C ratio [12,27]. However, these previous studies were conducted in samples in China and the United Kingdom, and this is the first study to show this association among Chinese and Korean Americans. ...
... High risk of sleep apnea did not have a statistically strong association with random glucose measurement. As with other studies, our current sample may have been underpowered to demonstrate strong associations between sleep apnea, diabetes, and glucose [10,12,26,29]. Previous studies have been able to demonstrate associations between sleep apnea and glucose intolerance [8,9,28,29]. ...
Study Objectives
While sleep apnea has been associated with cardiovascular disease (CVD) risk factors in white individuals in the U.S., these associations in Chinese and Korean Americans are less well-understood, particularly how these associations vary by age, gender, Asian origin, obesity, chronic conditions, and daytime sleepiness.
Methods
We used a sample of Chinese and Korean Americans ages 50-75 (n=394) from the Baltimore-Washington DC Metropolitan Area to examine the associations of high risk (HR) sleep apnea with diagnoseable hypercholesterolemia and diabetes, as well as the following biomarkers: total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol/HDL-C ratio, triglycerides, and glucose (non-fasting). Poisson models included demographic factors, socioeconomic status, and body mass index (BMI). We tested for potential effect modifiers.
Results
HR-sleep apnea was associated with higher LDL-C level (β=14.56, p<0.05) and higher total cholesterol/HDL ratio (β=0.64, p<0.01). Younger respondents had higher levels of triglycerides associated with HR-sleep apnea than older respondents. For men, HR-sleep apnea was associated with higher total cholesterol, total cholesterol/HDL-C ratio, and triglycerides. Obese and overweight respondents had positive associations between HR-sleep apnea and total cholesterol, total cholesterol/HDL ratio, and triglycerides, while underweight/normal weight individuals did not. The interactions between snoring and daytime sleepiness were associated with hypercholesterolemia and diabetes.
Conclusions
This study demonstrates associations between sleep apnea risk and dyslipidemia among Chinese and Korean Americans. Associations were particularly pronounced among younger, male, overweight/obese, and sicker individuals. Future research should examine how to improve sleep health in Asian American populations to improve CVD risk.
... En 2003 el VII Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) incluyó a este síndrome como una causa de hipertensión arterial secundaria. (18) En la cohorte de sueño de Wisconsin, se demostró una relación estadísticamente significativa entre la severidad del SAHOS y el desarrollo de HTA. Pacientes con IAH mayor a 15 eventos/ hora tuvieron más riesgo (OR = 2,89, IC 95% = 1,46 -5,64) aún después de corregir variables de confusión como obesidad, consumo de medicamentos antihipertensivos (19) . ...
... Coughlin et al. y Meslier et al. demostraron que el SAHOS se asocia a intolerancia a la glucosa, resistencia a la insulina y aumento de la actividad del sistema nervioso simpático. (18,20,21) La investigación epidemiológica poblacional de São Paulo, Brasil, evidenció que el SAHOS se asocia con alteración en el metabolismo de la glucosa y los lípidos de forma independiente a los efectos de la obesidad, género, edad y tiempo total de sueño. (21) La hipoxemia intermitente y la fragmentación del sueño activan el sistema simpático con aumento de catecolaminas, alterando el eje hipotálamo-hipófisis-adrenal, que aumenta el cortisol plasmático y el estrés oxidativo; con activación de las vías inflamatorias (22) Hay cambios en las adipoquinas con aumento de la leptina y disminución de la adiponectina, independiente del grado de obesidad. ...
Introducción:
La obesidad es una enfermedad epidémica multifactorial en constante aumento en los últimos años. Asocia el desarrollo de múltiples patologías con aumento de la morbimortalidad, entre ellas el síndrome de apneas e hipopneas obstructivas del sueño (SAHOS).
Objetivo:
Estudiar la prevalencia de SAHOS en una población de obesos pertenecientes a un Programa de Obesidad y Cirugía Bariátrica de un hospital público de Montevideo.
Metodología:
Estudio observacional descriptivo de cohorte transversal. Se incluyeron pacientes en valoración preoperatoria desde abril 2015 a marzo 2020. Se les realizó una polisomnografía. Se evaluó la prevalencia de SAHOS y la relación con otros factores de riesgo cardiovascular. El análisis estadístico se realizó con SPSS versión 25.0.
Resultados:
Se estudiaron 358 pacientes con predominio del sexo femenino (86,3%), edad media de 42,8 ± 10,7 años y un índice de masa corporal (IMC) promedio de 50,1 ± 11,4 kg/m². Se evidenció una prevalencia de SAHOS de 69%: 43,3% leve; 23,9% moderada y 32,8% severo. El Índice apnea hipopnea (IAH) se correlacionó positivamente con IMC (p ≤ 0,001). Se demostró la asociación de SAHOS con hipertensión arterial (HTA), diabetes 2 (DM2), sexo masculino e hipertrigliceridemia.
Conclusiones:
El SAHOS es altamente prevalente en la obesidad. Este estudio sugiere la realización de un screening en todos los obesos, así como su estudio con polisomnografía o poligrafía respiratoria a aquellos que vayan a someterse a una cirugía bariátrica.
... Each item was rated to 0 to 4 score. Total perceived stress score was calculated and further classified as: Low: (0-13), moderate: (14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26), high: (27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40). ...
... Persistent sleep insufficiency or deprivation raises the risk for diabetes and obesity and contributes to the aging process in addition to causing frequent mental and physical distress [33]. Similar to this, Coughlin et al. [34] have demonstrated that the prevalence of obstructive sleep apnea is independently correlated with an increase in the cardiovascular risk variables that make up the MetS. ...
Background Metabolic syndrome (MetS) is associated with an increased incidence of chronic complications and mortality of diabetes patients. Prevention and treatment of MetS is important means of lowering the risk of cardiovascular diseases and mortality. Objective This study aimed to find out metabolic syndrome and life style factors among diabetes patients. Methods A cross-sectional survey was carried out among 296 patients with type 2 diabetes mellitus attending Chitwan Medical College Teaching Hospital. Consecutive sampling technique was used to select sample. Data were collected from 15th December 2021 to 15th March, 2022 using Interview Schedule, bio-physiological measurement and record review. Obtained data were analysed in SPSS version 20 for window using descriptive and inferential statistics. Chi-square test was applied to measure the association between the variables. Logistic regression analysis was performed to identify the factors associated with metabolic syndrome. Result Findings revealed that the prevalence of MetS was 66.2% and 58.4% in patients according to International Diabetes Federation (IDF) and National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria respectively. The most common MetS parameters were raised fasting plasma glucose (94.6%) and abnormal waist circumference (78.4% in IDF criteria) while the least prevalent parameter was reduced HDL level (43.2%). Majorities of the patients were non-vegetarian (85.5%), had poor dietary compliance (poor-46.3%, very poor-32.1%), overweight/obese (65.5%), and suffered from moderate stress (90.1%). Bivariate analysis showed that MetS as per NCEP ATP criteria was significantly associated with gender (p = 0.006), occupation (p = 0.007), presence of other co-morbid condition (
... Both the reported prevalence of OSA in patients with MS and the prevalence of MS in patients with OSA are quite high (ranging from 60%-70%) [6][7][8]. MS is six to nine times more likely to be present in individuals with OSA compared with the general population [9,10]. MS and OSA share various pathophysiological mechanisms of cardiometabolic complications, highlighting the impact of obesity and related adipose tissue inflammation as the common etiological factor of both conditions [11,12]. ...
... Overall, previous evidence has consistently shown that OSA is associated with higher levels of one or more components of MS, as well as surrogate markers of cardiovascular risk. Coughlin and colleagues conducted one of the first studies to address the association between OSA and MS and its components [9]. The authors observed, from a sample of 104 patients (61 with moderate-to-severe OSA and 43 control patients), that OSA was associated with a significant increase in systolic, diastolic, and mean arterial blood pressure, fasting insulin, and triglyceride concentration; a reduction in HDL cholesterol; and an increase in the cholesterol/HDL cholesterol ratio, after adjusting for obesity. ...
Metabolic syndrome (MS) is a heterogeneous condition associated with increased cardiovascular risk. There is growing evidence from experimental, translational, and clinical investigations that has suggested that obstructive sleep apnea (OSA) is associated with prevalent and incident components of MS and MS itself. The biological plausibility is supportive, primarily related to one of the main features of OSA, namely intermittent hypoxia: increased sympathetic activation with hemodynamic repercussions, increased hepatic glucose output, insulin resistance through adipose tissue inflammation, pancreatic β‐cell dysfunction, hyperlipidemia through the worsening of fasting lipid profiles, and the reduced clearance of triglyceride‐rich lipoproteins. Although there are multiple related pathways, the clinical evidence relies mainly on cross‐sectional data preventing any causality assumptions. The overlapping presence of visceral obesity or other confounders such as medications challenges the ability to understand the independent contribution of OSA on MS. In this review, we revisit the evidence on how OSA/intermittent hypoxia could mediate adverse effects of MS parameters independent of adiposity. Particular attention is devoted to discussing recent evidence from interventional studies. This review describes the research gaps, the challenges in the field, perspectives, and the need for additional high‐quality data from interventional studies addressing the impact of not only established but promising therapies for OSA/obesity.
... Metabolic syndrome, a cluster of cardiovascular risk factors was recognized as early as in the year 1920. 1 It has been defined as a constellation of inter-related risk factors of metabolic origin including hypertension, insulin resistance, dyslipidemia and central obesity collectively called ''Syndrome X'' . 2 Obstructive sleep apnea is a condition characterized by the occurrence of repeated episodes of upper airway obstruction and airflow cessation. It is associated with fragmented sleep, disruptive snoring, nocturnal hypoxemia, and daytime symptoms most commonly excessive sleepiness. ...
... The prevalence of metabolic syndrome in patients with OSA varies from 70 to 85% and 37 to 41% among patients without OSA. 1,5 Also the prevalence of OSA is as high as 66% in patients with metabolic syndrome than in subjects without metabolic syndrome 12%. 6 Multiple pathways are involved in the interaction between OSA and metabolic syndrome including fragmented sleep nocturnal hypoxemia leading to neurohumoral changes, increased oxidative stress contributing to inflammation, a prominent phenomenon of this interaction. ...
... There is a significant evidence of relationship between OSA and metabolic syndrome. OSA is independently associated with the metabolic parameters of an individual as well as the increased prevalence of metabolic syndrome [18]. As reported in Asian [19]- [21], Caucasian [18,22,23] and Mediterranean studies [24,25] (Table 1), the association of the two conditions is very consistent. ...
... OSA is independently associated with the metabolic parameters of an individual as well as the increased prevalence of metabolic syndrome [18]. As reported in Asian [19]- [21], Caucasian [18,22,23] and Mediterranean studies [24,25] (Table 1), the association of the two conditions is very consistent. In fact, some researchers have labeled the coexistence of OSA and metabolic syndrome as "Syndrome Z" [26]. ...
Obstructive sleep apnea (OSA) is a prevalent breathing disorder with potentially adverse metabolic, cardiovascular and neurocognitive consequences. In the past few years, several studies have analyzed the potential independent contribution of OSA to the pathogenesis of metabolic abnormalities, including obesity, hypertension, type 2 diabetes/insulin resistance, and dyslipidemia. Lifestyle modification, primarily weight loss, has been assessed to improve the outcome of OSA as well as metabolic syndrome. This implies that weight loss might be one of the key approaches for the treatment of both these conditions. Numerous studies suggest that nocturnal oxygen desaturations occurring during an episode of OSA exert detrimental metabolic effects due to sympathetic stimulation. This may help explain the increasing prevalence of metabolic syndrome in the general population with OSA. This review explores the relationship between OSA and metabolic syndrome or its components and the effects of lifestyle changes on the severity of OSA.
... OSA is more common in obese patients (34). Patients with OSA are 6-9 times more likely to have MetS than the general population (35)(36)(37). The existing research on the impact of different treatments for OSA on coexisting MetS in patients has inconsistent conclusions. ...
Background
Obstructive sleep apnea (OSA) and metabolic syndrome (MetS) often coexist, and the causal relationship between them is not yet clear; treatments for OSA include continuous positive airway pressure (CPAP), mandibular advancement device (MAD), surgery, and lifestyle intervention and so on. However, the effects of different treatments on metabolic syndrome in OSA patients are still under debate.
Objectives
Review the effects of different treatments on metabolic syndrome in OSA patients by meta-analysis.
Methods
we searched articles in PubMed, Embase, Cochrane Library, CNKI, CBM, and Wanfang data from database construction to Feb. 2024.RevMan5.4 and Stata software were used to conduct a meta-analysis of 22 articles.
Results
A total of 22 articles were finally included. The results showed that CPAP treatment could reduce the prevalence of metabolic syndrome in OSA patients in randomized controlled trials (RCTs) (RR = 0.82 [95% CI, 0.75 to 0.90]; p < 0.01) and single-arm studies (RR = 0.73 [95% CI, 0.63 to 0.84]; p < 0.01). As for metabolic syndrome components, CPAP treatment reduces blood pressure, fasting glucose (FG), triglycerides (TG), and waist circumference (WC) but can’t affect high-density lipoprotein cholesterol (HDL-C) levels. Lifestyle intervention could significantly reduce the prevalence of metabolic syndrome in OSA patients (RR = 0.60 [95% CI, 0.48 to 0.74]; p < 0.01) and can lower blood pressure, fasting glucose, and waist circumference but can’t affect the lipid metabolism of OSA patients. Upper airway surgery can only reduce TG levels in OSA patients (MD = −0.74 [95% CI, −1.35 to −0.13]; p = 0.02) and does not affect other components of metabolic syndrome. There is currently no report on the impact of upper airway surgery on the prevalence of metabolic syndrome. No study has reported the effect of MAD on metabolic syndrome in OSA patients.
Conclusion
We confirmed that both CPAP and lifestyle intervention can reduce the prevalence of MetS in OSA patients. CPAP treatment can lower blood pressure, fasting glucose, waist circumference, and triglyceride levels in OSA patients. Lifestyle intervention can lower blood pressure, fasting glucose, and waist circumference in OSA patients. Upper airway surgery can only reduce TG levels in OSA patients.
Systematic review registration
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022326857.
... OSA is also an independent risk factor for hypertension, diabetes mellitus, metabolic syndrome, and other cardiovascular disease such as stroke and myocardial infarction. [1][2][3] fully explained yet, but multiple factors may contribute. Inherent differences in a) distribution of fat, b) length and collapsibility of the upper airway, c) neurochemical control mechanisms, d) arousal response, and e) sex hormones may contribute to the disparity in prevalence between the two genders. ...
Objectives
Scant data from India are available on the gender differences in presenting features of Obstructive Sleep Apnea (OSA) in India. This study aims to compare male and female patients with OSA for general characteristics and presenting symptoms.
Methodology
Retrospective study was done in OSA patients diagnosed in our sleep lab. History, biochemical reports, and polysomnography variables were retrieved from the sleep registry and were compared between males and females.
Results
Out of 514 patients of OSA (367 males; 147 females). Females were older (55.97 ± 9.73 v/s 50.2 + 12.70 years, P <0.001) and more obese (BMI 35.26 ± 7.17 v/s 29.58 ± 5.49 Kg/m ² ; P <0.001). Waist and hip circumference were significantly higher in the female patients ( P = 0.009 and <0.001 respectively). Morning headache, nocturia, fatigability ( P < 0.001), and depression ( P = 0.005) was more common in females ( P = 0.036). Hypersomnia was more commonly seen in males ( P < 0.001). Mean diastolic blood pressure was significantly higher in males, although no difference was seen in Systolic BP. Females had higher mean Fasting Blood glucose (FBS) ( P = 0.02). Apnea hypopnea index was significantly higher in females {P = 0.01}.
Conclusion
Women with OSA are more obese, elderly, and with higher fasting blood glucose than males at the time of diagnosis. Females have a higher prevalence of symptoms like fatigability, depression, nocturia and early morning headache and had more severe AHI than males.
... The current study demonstrated that OSA patients with MetS had significantly higher BMI, waist, hip, and neck circumferences than OSA without MetS, these results agreed with previous studies which proved the strong association between large waist and neck circumferences and MetS in OSA patients [7][8][9]. Previous research found that BMI was higher in OSA patients than in the control group and suggested that obesity was the primary determinant of metabolic syndrome in those patients rather than sleep apnea [10]. More recent studies have raised the possibility of a significant association between MetS and high BMI [11,12]. ...
Background
Obstructive sleep apnea (OSA) and metabolic syndrome (MetS) are two diseases associated with an increased risk of cardio-metabolic complications and both share the same risk factors such as obesity and smoking.
Objectives
To study the clinical features and predictors of MetS in OSA patients.
Methodology
A cross-sectional study was conducted in the sleep lab of the Pulmonology Department at Kasr Al-Ainy Hospital, Cairo University, during the period from September 2022 to March 2023. Eighty OSA patients were included, and each patient was subjected to history taking, body measurements, blood pressure measurements, Epworth sleepiness scale, STOP-BANG score, polysomnography, and laboratory investigations including lipid profile and (HBA1C), MetS was defined based on the International Diabetes Federation (IDF) guidelines. Then patients were classified into two groups; OSA with MetS and OSA without MetS, we compared both groups using a one-way (ANOVA) test.
Results
MetS was diagnosed in 66.3% of the study group. OSA with MetS had higher BMI (44.76 ± 9.55) with significant p values (< 0.001), lower average O2 saturation % (90.23 ± 5.5, p value = 0.013), and longer SPO2 time < 90% (37.39 ± 34.14, p value = 0.034) than the other group. BMI, waist, hip, and neck circumferences and SPO2 < 90% were predictors of MetS among OSA patients with significant p values. Females had significantly higher BMI (46.64 ± 9.58), p value = 0.015. Males had significantly higher AHI than females (32.99 ± 24.02 versus 19.83 ± 14.74 respectively), p value = 0.031.
Conclusion
MetS was diagnosed in 66.3% of OSA. BMI, neck, hip, waist circumferences, and SPO2 < 90% were predictors of MetS among OSA.
Trial registration
Retrospectively registered, date of registration is 18/09/2023, and number of registration is NCT06051097 . The link to the study on clinicaltrials.gov.
... Previous studies have shown that OSA is independently associated with cardiovascular risk factors, such as hypertension and dyslipidemia. 46 Consistent with previous studies, we observed that males, high BMI, high blood pressure, choke, sleepiness, and apnea were predictors of severe OSA. 1 Our study had some limitations. First, although the data used in the article are retrospective data, and there are confounding factors and biases in the data. ...
Purpose
Obstructive sleep apnea (OSA) is a disease with high morbidity and is associated with adverse health outcomes. Screening potential severe OSA patients will improve the quality of patient management and prognosis, while the accuracy and feasibility of existing screening tools are not so satisfactory. The purpose of this study is to develop and validate a well-feasible clinical predictive model for screening potential severe OSA patients.
Patients and Methods
We performed a retrospective cohort study including 1920 adults with overnight polysomnography among which 979 cases were diagnosed with severe OSA. Based on demography, symptoms, and hematological data, a multivariate logistic regression model was constructed and cross-validated and then a nomogram was developed to identify severe OSA. Moreover, we compared the performance of our model with the most commonly used screening tool, Stop-Bang Questionnaire (SBQ), among patients who completed the questionnaires.
Results
Severe OSA was associated with male, BMI≥ 28 kg/m², high blood pressure, choke, sleepiness, apnea, white blood cell count ≥9.5×10⁹/L, hemoglobin ≥175g/L, triglycerides ≥1.7 mmol/L. The AUC of the final model was 0.76 (95% CI: 0.74–0.78), with sensitivity and specificity under the optimal threshold selected by maximizing Youden Index of 73% and 66%. Among patients having the information of SBQ, the AUC of our model was statistically significantly greater than that of SBQ (0.78 vs 0.66, P = 0.002).
Conclusion
Based on common clinical examination of admission, we develop a novel model and a nomogram for identifying severe OSA from inpatient with suspected OSA, which provides physicians with a visual and easy-to-use tool for screening severe OSA.
... Smiley et al. reported that people with short sleep duration are more likely to develop metabolic syndrome [17]. An epidemiological study has demonstrated that the prevalence of metabolic syndrome in people with OSA is 9 times higher than that in people without OSA [18]. The poor effectiveness of upper airway surgeries for improvement of OSA, especially in obese patients, indicates the strong relationship between obesity and OSA [19,20]. ...
Purpose
Lower urinary tract symptoms (LUTS) and sleep disorders both commonly affect people’s quality of life. This study aimed to explore the associations between sleep-related disorders and LUTS through epidemiological investigations.
Methods
Data were generated from the cross-sectional study called the National Health and Nutrition Examination Survey (NHANES) 2005–2008. Multivariable logistic regression models were conducted to investigate the relationships between sleep-related disorders and LUTS.
Results
A total of 2516 men were included in the study. Participants sleeping ≤ 6 h/night had higher odds ratios of LUTS (OR: 1.38; 95% CI 1.08, 1.77), daytime LUTS (OR: 1.26; 95% CI 1.03, 1.54), and nocturia (OR: 1.23; 95% CI 1.02, 1.49) than those sleeping 7–8 h/night. Participants who required > 30 min to fall asleep had an approximately 39% higher odds ratios of nocturia than those who fell asleep within 6 to 30 min (OR: 1.39; 95% CI 1.12, 1.73). Sleep problems were positively related to LUTS (OR: 1.42; 95% CI 1.11, 1.82), daytime LUTS (OR: 1.32; 95% CI 1.08, 1.61), urinary hesitancy (OR: 1.75; 95% CI 1.31, 2.34), and nocturia (OR: 1.52; 95% CI 1.26, 1.84). Obstructive sleep apnea (OSA) symptoms were positively associated with urinary incontinence (OR: 1.52; 95% CI 1.12, 2.08). In addition, participants with daytime sleepiness were at higher prevalence of LUTS (OR: 1.66; 95% CI 1.29, 2.15), daytime LUTS (OR: 1.44; 95% CI 1.16, 1.78), urinary hesitancy (OR: 1.95; 95% CI 1.45, 2.63), and nocturia (OR: 1.66; 95% CI 1.35, 2.05).
Conclusion
The findings suggested that sleep-related disorders were associated with LUTS, daytime LUTS, urinary hesitancy, incomplete emptying, urinary incontinence, and nocturia in middle-aged and elderly males.
... The prevalence of OSA in metabolic syndrome and vice versa is high. While obesity is a major contributor of this link, metabolic syndrome is nine times more likely to be present in OSA even after adjusting for BMI [11]. Intermittent hypoxia and sleep fragmentation are both hallmarks of OSA pathophysiology that could mediate the metabolic dysfunction seen in OSA via several proposed mechanisms, including increased activation of the sympathetic nervous system and hypoathalamic-pituitary-adrenal axis, and increased oxidative stress and inflammation [12]. ...
... The term "Z syndrome" has been used to describe the association between obesity, insulin resistance, hypertension, and dyslipidemia with OSA. The OR (odds ratio) index of metabolic syndrome in OSA patients ranges from 5 to 9-fold when compared with subjects without OSA, and independent of age and BMI [97][98][99]. Due to the bidirectional association between T2DM or metabolic syndrome and OSA [75,96,[100][101][102], the personalized management of these comorbid diseases should be performed to avoid the high risk of fatal cardiovascular events. ...
... Obstructive sleep apnea is independently associated with MetS occurrence. Risk estimates are 6-9 times higher in patients with OSA compared to the general (non-OSA) population (Coughlin et al., 2004). It has been shown that CPAP reduces the risk of developing MetS in OSA patients (Phillips et al., 2011). ...
Obstructive sleep apnea (OSA) is one of the most common sleep disorders, which is characterized by recurrent apneas and/or hypopneas occurring during sleep due to upper airway obstruction. Among a variety of health consequences, OSA patients are particularly susceptible to developing metabolic complications, such as metabolic syndrome and diabetes mellitus type 2. MicroRNAs (miRNAs) as epigenetic modulators are promising particles in both understanding the pathophysiology of OSA and the prediction of OSA complications. This review describes the role of miRNAs in the development of OSA-associated metabolic complications. Moreover, it summarizes the usefulness of miRNAs as biomarkers in predicting the aforementioned OSA complications.
... Similarity, Obstructive sleep apnoea was found to decrease the level of HDL besides increase the level of glucose, body weight, insulin resistant, and cardiovascular risk. All these sequences augment the prevalence of metabolic syndrome by 87% (n = 61) compared to control group (35%, n = 43) ( Coughlin et al., 2004 ). • Stress: stressful life events relating to finance, job, relationships, health, and sheltering were self-rated in a random sample of population aged 18-78 years in Western Finland (n = 3,407). ...
Metabolic syndrome (MetS) is a bunch of metabolic defects comprising hypertension, insulin resistance, visceral obesity, fatty liver, and atherogenic cardiovascular diseases. Lifestyle modification is the first step for controlling the MetS progression. If left untreated, MetS is significantly related to a high danger of evolving type 2 diabetes and atherogenic cardiovascular diseases. Thus, MetS is a prominent cause of morbidity and mortality internationally and has been become very important to investigate novel therapies in this context to decrease the heavy burden of the disease. Though, there is no single treatment for MetS and the currently available pharmacother-apy and related comorbidities demand the continued use of multiple drugs that is challenging for patients as the polypharmacy and reduced accordance. There is increasing concern in the use of nutraceuticals in the management of MetS. This review follows MetS with an emphasis on the risk factors and how to control it, epidemiology, pathogenesis, pathophysiology, diagnosis, and treatments. Moreover, the review recaps on the health benefits of natural products in the management of the MetS to give a complete guide to other researchers for new natural products investigation. Novelty Statement MetS is significantly related to develop type 2 diabetes and car-diovascular diseases as well as MetS is considered a prominent reason of morbidity and mortality worldwide. Thus, it is critical to explore new treatments in this circumstance. However, there is no single treatment for MetS and the existing pharmacotherapy require the continuous use of numerous drugs that is challenging for patients as the polypharmacy and diminished accordance. There is rising interest in the utilization of nutraceuticals in the management of MetS. Also, the investigation of an efficient approach to manage those complications not studied well, where the authors highlighted this point in our manuscript. We presented in this review a wide information concerning the risk factors, patho
... Nuestra población pertenecía a un centro especializado y estaba compuesta mayoritariamente por sujetos de mediana edad, con sobrepeso u obesidad con una alta prevalencia de SAHOS, como lo evidencia su elevado IAH global 8 . Los estudios basados en polisomnografía (PSG) y síndrome metabólico (criterios NCEP-ATP III MS) han informado una prevalencia variable 23-87% [9][10][11][12][13] . Sin embargo, no hay datos de América Latina para esta población especí ca. ...
... Obstructive sleep apnea (OSA) comprises a group of chronic sleep-related breathing disorders characterized by the repeated occurrence of partial or complete upper airway obstruction during sleep. Te potential consequences of OSA include cardiovascular disease [1,2], metabolic syndrome [3,4], neurocognitive dysfunction [5], and diminished quality of life [6]. Tese consequences are related to higher mortality in patients and are associated with higher healthcare costs and utilization. ...
Background:
Older age is a risk factor for obstructive sleep apnea (OSA), which is associated with the development of nonalcoholic fatty liver disease (NAFLD). We aimed to investigate the correlation between OSA and liver injury among older patients. Study Design. This is a cross-sectional study.
Methods:
Consecutive older (≥60 years) snoring patients were included. Subjects were divided into no OSA, mild OSA, moderate OSA, and severe OSA groups according to the apnea-hypopnea index (AHI) and were also separated into liver injury and nonliver injury groups based on liver function. Logistic regression analysis was applied to analyze the independent risk factors for liver injury.
Results:
We studied 227 patients (155 male, 72 female). The prevalence of liver injury exhibited an increasing trend among groups with mild-to-severe OSA. In addition, body mass index, AHI, and TG showed significant differences between the liver injury and nonliver injury groups. Logistic regression analysis revealed that AHI and TG were the major contributing factors for liver injury in older patients (adjusted odds ratio [OR] = 1.055, p=0.013, and OR = 1.485, p=0.039, respectively).
Conclusions:
Older patients with OSA have an increased risk of liver injury and NAFLD, and sleep apnea and high TG are important factors in contributing to the development of liver injury.
... The latest research suggests that diabetics who are treated with insulin are at higher risk for OSA. The prevalence of OSA in patients with T2DM with obesity has been reported to be 26 to 83% [2][3][4]. There is a bidirectional relationship between OSA and T2DM [5]. ...
Objectives
To observe the efficacy and side effects of liraglutide in the treatment of type 2 diabetes mellitus (T2DM) patients with severe obstructive sleep apnea (OSA).
Methods
The study conducted in an outpatient setting was a two-center, prospective randomized controlled study. T2DM patients with severe OSA were randomized to the control group (continuous positive airway pressure [CPAP] and drug treatment without liraglutide) or the liraglutide group (CPAP and drug treatment including liraglutide). Demographic and clinical characteristics, sleep-disordered breathing indices, cardiac function indices, and side effects were evaluated and compared between the two groups before and after 3 months.
Results
Of 90 patients, 45 were randomized to the intervention arm (with liraglutide) and 45 to the control arm (without liraglutide). One patient in the liraglutide group dropped out of the study on day 8 after enrollment due to obvious gastrointestinal symptoms. No significant differences were found between the two groups in baseline demographics, clinical characteristics, cardiac function indicators, or sleep disorder respiratory indices ( P > 0.05). After 3 months, the body mass index (BMI), apnea hypopnea index (AHI), and mean systolic blood pressure in the liraglutide treatment group were significantly lower than those in the control group ( P < 0.05). The minimum oxygen saturation was significantly higher in the liraglutide group compared with that in the control group after 3 months of follow-up ( P < 0.05). No difference was found between the two groups in the summary of side effects ( P > 0.05).
Conclusions
Liraglutide combined with CPAP can effectively reduce BMI, lower mean systolic blood pressure, and improve AHI scores and hypoxia in T2DM patients with severe OSA. Liraglutide did not increase side effects.
... The term "Z syndrome" has been used to describe the association between obesity, insulin resistance, hypertension, and dyslipidemia with OSA. The OR (odds ratio) index of metabolic syndrome in OSA patients ranges from 5 to 9-fold when compared with subjects without OSA, and independent of age and BMI [97][98][99]. Due to the bidirectional association between T2DM or metabolic syndrome and OSA [75,96,[100][101][102], the personalized management of these comorbid diseases should be performed to avoid the high risk of fatal cardiovascular events. ...
Obstructive sleep apnea (OSA) is a common disease that is often under-diagnosed and under-treated in all ages. This is due to differences in morphology, diversity in clinical phenotypes, and differences in diagnosis and treatment of OSA in children and adults, even among individuals of the same age. Therefore, a personalized medicine approach to diagnosis and treatment of OSA is necessary for physicians in clinical practice. In children and adults without serious underlying medical conditions, polysomnography at sleep labs may be an inappropriate and inconvenient testing modality compared to home sleep apnea testing. In addition, the apnea–hypopnea index should not be considered as a single parameter for making treatment decisions. Thus, the treatment of OSA should be personalized and based on individual tolerance to sleep-quality-related parameters measured by the microarousal index, harmful effects of OSA on the cardiovascular system related to severe hypoxia, and patients’ comorbidities. The current treatment options for OSA include lifestyle modification, continuous positive airway pressure (CPAP) therapy, oral appliance, surgery, and other alternative treatments. CPAP therapy has been recommended as a cornerstone treatment for moderate-to-severe OSA in adults. However, not all patients can afford or tolerate CPAP therapy. This narrative review seeks to describe the current concepts and relevant approaches towards personalized management of patients with OSA, according to pathophysiology, cluster analysis of clinical characteristics, adequate combined therapy, and the consideration of patients’ expectations.
... 1,2 OSA also generates other consequences that can negatively affect an individual's quality of life, such as excessive sleepiness during the day, cognitive dysfunction, and decreased efficiency in professional activities. 2 Among the various risk factors associated with OSA, those that stand out are obesity, alcohol use, nasal congestion, nasal septum deviation, increased lymphatic tissues, tongue positioning, soft palate positioned inferiorly, maxillary and/or mandibular retrognathism, and maxillary hypoplasia. 1,3,4 Individuals who present maxillary hypoplasia commonly present nasal obstruction, and a lower positioning of the tongue below and behind the oral cavity. 5,6 Furthermore, the distance between the nasal walls and the nasal septum appears diminished, which entails greater resistance to the passage of air through this region due to the reduced volume of the airways. ...
Introduction The aim of this systematic review and meta-analysis was to evaluate the effects of maxillary expansion on adults with obstructive sleep apnoea (OSA). Methods Electronic searches up to July 2021 in eight electronic databases were conducted. Study selection, data extraction, risk of bias evaluation using ROBINS-I, quality of evidence assessment using GRADE and meta-analyses were performed. Results The electronic searches yielded 1,007 studies. Following the application of the eligibility criteria, 15 articles were fully read and five studies were included. The studies evaluated the effects of surgically assisted rapid maxillary expansion in adults with OSA. The meta-analysis demonstrated an improvement in Apnoea-Hypopnea Index (AHI) (MD = -9.91, CI = -14.57 to -5.25), Oxygen Desaturation Index (ODI) (MD = -7.95, CI = -12.23 to -3.67), and Epworth Sleepiness Scale (ESS) (MD = -4.40, CI = -6.39 to -2.40). ROBINS-I indicated serious, no information and critical risk of bias for the included studies. The quality of the evidence was very low. Conclusion The findings herein suggest that maxillary expansion could improve OSA in adults in the short term.
... Dysregulation of lipid metabolism is increasingly recognized as a risk factor for many metabolic diseases, including nonalcoholic fatty liver and cardiovascular diseases. In addition, obstructive sleep apnea syndrome affects serum lipids [26][27][28][29][30] and previous studies have suggested hypoxia (See figure on next page.) Fig. 4 ANGPTL4 and PPARA are key regulators of lipid metabolism following Hypobaric Hypoxia. ...
Background
Hypoxia is a risk factor for non-alcoholic fatty liver diseases, leading to permanent imbalance of liver lipid homeostasis and steatohepatitis. However, a detailed understanding of the metabolic genes and pathways involved remains elusive.
Methods
In vivo experiments were designed to analyze body weight and lipid metabolism changes of rats under hypoxia. After this, we combined microarray analysis and gene overexpression experiments to validate the core mechanisms involved in the response to hypoxia.
Results
The hypobaric hypoxia treated rats exhibited significantly increased serum triglycerides (TG) (p < 0.05), despite no significant changes in serum alanine aminotransferase (ALT) and blood glucose (BG) were observed. In addition, serum high-density lipoprotein cholesterol (HDL-C) greatly increased after 3 days and then returned to normal level at 30 days. Interestingly, serum low-density lipoprotein cholesterol (LDL-C) showed an opposite pattern. Transcriptome analysis, qRT-PCR, ICC revealed that the genes PPARA, ANGPTL4, CPT-I, ACC and LPL play a crucial role in response to hypobaric hypoxia. IPA pathway analysis further confirmed that PPARA-mediated regulation of ANGPTL4 participated in TG clearance and lipoprotein metabolism. Finally, the PPARA-ANGPTL4 pathway was validated in rats and HL 7702 cells treated with Fenofibrate, a PPARA specific agonist.
Conclusions
Our study showed this pathway plays an important role on lipid metabolism caused by hypobaric hypoxia and the potential target genes associated with oxygen-dependent lipid homeostasis in the liver.
... In addition, OSA has also been reported to have an independent association with the Quanming Fei, Yun Tan and Minhan Yi contributed equally to this work and are co-first authors. elevated prevalence of metabolic syndrome [3]. Furthermore, OSA participates in the pathogenesis of cardiovascular disease (CVD) through multiple mechanisms including oxidative stress, inflammation, and endothelial damage [4]. ...
PurposeObstructive sleep apnea (OSA) shows a chronic inflammatory state which is often accompanied by cardiometabolic phenotypes. The aim of this study was to investigate whether or not there were differences of inflammatory proteins levels in patients with OSA with and without a certain phenotype so as to explore the associations between inflammation and additional OSA phenotypes.Methods
The literature was systematically screened and available data were collected on levels of tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), and several interleukins (ILs) in patients with OSA with and without a certain phenotype. Overall effect size of standard mean difference (SMD) was used to compare the expression of differences between the two groups. Data analysis was conducted by Review Manager 5.3, and the threshold of p value was set as < 0.05.ResultsA total of 31 articles were included, covering five traits of obesity, hypertension (HBP), metabolic syndrome (MS), heart disease, and sex. There were elevated levels of TNF-α (SMD = 0.63, p = 0.03), CRP (SMD = 0.64, p = 0.0001), and IL-6 (SMD = 0.83, p = 0.008) levels in OSA with obesity. Also, OSA with HBP showed significant increases of TNF-α (SMD = 0.36, p = 0.02), CRP (SMD = 0.98, p = 0.01), and IL-6 (SMD = 0.76, p < 0.0001) levels. A higher CRP level was also observed in OSA with MS (SMD = 0.31, p = 0.004) and female sex (SMD = 0.21, p = 0.002). There were no statistical differences for IL-1β (p = 0.22) and CRP (p = 0.14) levels of OSA with obesity and heart disease respectively compared with OSA without corresponding phenotype. TNF-α (p = 0.66) and IL-6 (p = 0.49) levels also lacked statistically significant differences between female and male patients with OSA.Conclusions
Our results revealed that inflammatory proteins TNF-α, CRP, and IL-6 levels were higher in obese and hypertensive patients with OSA and CRP levels were higher in OSA with metabolic syndrome, highlighting a link between inflammation and cardiometabolic complications in patients with OSA.
... [76] Results of epidemiological studies indicate that individuals with OSA are 6 to 9 times more likely to develop metabolic syndrome than the general population. [77,78] Additionally, the prevalence of type 2 diabetes in individuals with OSA is estimated at 15% to 30% with a higher prevalence in severe OSA. [79] Intermittent hypoxemia and sleep fragmentation, both cardinal features of OSA, are likely to be a component of the causal pathway leading to metabolic dysfunction. ...
Obstructive sleep apnea (OSA) is a chronic condition accompanied by repeated obstruction of the upper airway during sleep despite respiratory efforts, resulting in intermittent hypoxemia, altered sleep structure, and sympathetic activation. Previous studies have shown a significant association between OSA and general health issues such as cardiovascular diseases, endocrine disorders, neurocognitive function decline, and poor quality of life. Continuous positive airway pressure (CPAP) has been considered as the first line treatment for OSA. However, accumulating evidence supports the role of oral appliance (OA) therapy, including mandibular advancement devices, as an alternative option for snoring and OSA patients who do not comply with or refuse CPAP usage. Despite a generally favorable outcome of OA therapy for OSA related respiratory indices, studies focusing on the impact of systemic effects of OA therapy in OSA patients are relatively scarce compared with the extensive literature focusing on the systemic effects of CPAP. Therefore, this article aimed to provide an overview of the current evidence regarding the multisystemic effects of OA therapy for OSA.
... These can be caused by sleep apneas, for example. We know that obstructive sleep apnea (OSA) is associated with metabolic syndrome [71] and as mentioned previously, metabolic disorders are often associated with long sleep. Apneas result in intermittent hypoxia, a proinflammatory state where low levels of oxygen trigger systemic inflammation that can negatively impact cardiovascular health [72]. ...
There exists a U-shaped relationship between sleep length and mortality, with short (<7h) and long (>9h) sleep both associated with poor health. However, given that the propensity for sleep and the circadian drive for wakefulness bookend a sleep period even when further opportunity presents itself, it remains unclear whether long sleepers are indeed sleeping longer than an average sleep duration, or simply spending longer in bed. Given that self-reported long sleepers are more likely to have poor physical or mental health, preexisting health conditions may predispose these individuals to excess time in bed that is not necessarily a longer-than-average sleep duration. Depression, chronic pain, and frailty could all be likely contributors. There may be a genetic basis for long sleep, or impairments in the neural circuitry in some individuals, as well as sex differences. However, while long sleep is generally associated with elevated cardiovascular disease risk and worse mental health, some studies—particularly among older adults and cancer survivors—have suggested benefits to a longer sleep duration. More studies that incorporate objective as well as self-reported measures of sleep duration are needed.
... OSA is a risk factor for the development of metabolic syndrome independent of obesity in the general population [36,37]. In addition, OSA causes a non-dipping nocturnal blood pressure pattern, which may lead to increased cardiovascular risk [38]. ...
Narcolepsy types 1 (NT1) and 2 (NT2) and idiopathic hypersomnia (IH) are thought to be a disease continuum known as narcolepsy spectrum disorders (NSDs). This study aimed to assess the prevalence of and factors associated with metabolic-syndrome-related disorders (MRDs) among patients with NSD. Japanese patients with NSD (NT1, n = 94; NT2, n = 83; and IH, n = 57) aged ≥35 years were enrolled in this cross-sectional study. MRD was defined as having at least one of the following conditions: hypertension, diabetes, or dyslipidemia. Demographic variables and MRD incidence were compared among patients in the respective NSD categories. Multivariate logistic regression analysis was used to investigate the factors associated with MRDs. Patients with NT1 had a higher body mass index (BMI) and incidence of MRD than that had by those with NT2 or IH. Age, BMI, and the presence of OSA were significantly associated with the incidence of MRD in NSDs. Age and BMI in NT1, BMI and human leukocyte antigen (HLA)-DQB1*06:02 positivity in NT2, and only age in IH were factors associated with the incidence of MRD. Obesity should be carefully monitored in narcolepsy; however, NT2 with HLA-DQB1*06:02 positive should be followed up for the development of MRD even without obesity.
... For example, sympathetic activation, chronic intermittent hypoxia, oxidative stress, and systemic inflammation are associated with metabolic dysfunction, which may explain the lipid metabolism abnormalities in OSA. 3,4 Dyslipidemia is a well-known risk factor for the progression and development of CVDs. As a vital component of metabolic syndrome, it includes hypertension, heart failure, and coronary artery disease. ...
Background
Due to the significant role of dyslipidemia, cardiovascular diseases (CVDs) are very common in obstructive sleep apnea (OSA). Nontraditional lipid indices are considered to be a better predictive index for cardiovascular risk. Nevertheless, the association between nontraditional lipid profiles and the severity of OSA is not clear.
Methods
A retrospective study was proceeded on 635 patients. Subjects were diagnosed with OSA through polysomnography (PSG). The association between severe OSA and nontraditional lipid profiles [triglyceride (TG)/high‐density lipoprotein cholesterol (HDL‐C) ratio, total cholesterol (TC)/HDL‐C ratio, low‐density lipoprotein cholesterol (LDL‐C)/HDL‐C ratio, non‐high‐density lipoprotein cholesterol (non‐HDL‐C), atherogenic index (AI), and lipoprotein combine index (LCI)] was examined by utilizing the restricted cubic spline and multivariate logistic regression analysis.
Results
All nontraditional lipid indices had positive relationships with the severity of OSA. By multivariable adjustment, the per SD increment of the TG/HDL‐C, TC/ HDL‐C, LDL‐C/HDL‐C, non‐HDL‐C, AI, and LCI were significantly associated with 88%, 50%, 42%, 40%, 50%, and 125% higher risk for severe OSA respectively. Compared with the lowest tertiles, the adjusted ORs (95% CI) were 2.42 (1.57–3.75), 2.39 (1.53–3.73), 2.35 (1.52–3.64), 1.86 (1.21–2.86), 2.39 (1.53–3.73), and 2.23 (1.43–3.48) for the top tertiles of TG/HDL‐C, TC/ HDL‐C, LDL‐C/HDL‐C, non‐HDL‐C, AI, and LCI respectively.
Conclusion
All nontraditional lipid indices had positive relationship with the severity of OSA. In addition, TG/HDL‐C, TC/HDL‐C, and AI had better performance than the other nontraditional lipid indices for predicting severe OSA. These findings could help to determine the risk of cardiovascular diseases and improve the dyslipidemia management of OSA patients.
... A similar study by Coughlin et al. showed the prevalence of metabolic syndrome in patients with OSA to be 87% compared with 35% in normal controls. 7 The burden of metabolic syndrome in patients with OSA in India is under evaluation and research. A North-Indian-populationbased study found the prevalence to be 79 and 48% in patients with OSA and in normal controls, respectively. ...
... 58 Obesity hypoventilation syndrome, obstructive sleep apnea, and congestive heart failure are associated with the development of metabolic syndrome. [59][60][61][62][63][64] ...
... Several studies have shown that OSA is an independent risk marker and probably risk factor of coronary heart disease (BenAhmed et al., 2014;Tietjens et al., 2019). It is also a major risk factor for cardiovascular morbidity and mortality (Peker et al., 2000;Mooe et al., 2001;Coughlin et al., 2004;Bradley and Floras, 2009). In comparison with other OSA patients, coronary artery disease patients with OSA are characterized by relatively poor diurnal symptoms (Javaheri et al., 1998(Javaheri et al., , 2017Sin et al., 2002;Arzt et al., 2006). ...
Background
Obstructive sleep apnea (OSA) affects 5% of the adult population and its prevalence is up to 13 times higher in coronary artery disease (CAD) patients. However, OSA in this population is less symptomatic, leading to lower adherence to positive airway pressure (CPAP). While oropharyngeal exercise showed a significant decrease in apnea-hypopnea index (AHI) in patients with moderate OSA, there have been no studies testing the impact of specific inspiratory muscle training (IMT) for these patients. The aim of our study was to assess the effectiveness of IMT on AHI reduction in CAD patients with moderate OSA.
Methods
We included patients with CAD involved in a cardiac rehabilitation program and presenting an AHI between 15 and 30. Patients were randomized in a 1:1 allocation to a control group (CTL – classic training) or an IMT group (classic training + IMT). IMT consisted in 60 deep inspirations a day, 6 days a week, into a resistive load device set at 70% of the maximum inspiratory pressure (MIP). After 6 weeks, we compared AHI, neck circumference, Epworth Sleepiness Scale, Pittsburgh Sleep Quality index, and quality of life with the 12-item Short Form Survey before and after rehabilitation.
Results
We studied 45 patients (60 ± 9 y, BMI = 27 ± 6 kg.m ⁻² ). The IMT group ( n = 23) significantly improved MIP ( p < 0.05) and had a significant decrease in AHI by 25% (−6.5 ± 9.5, p = 0.02). In the CTL group ( n = 23), AHI decreased only by 3.5% (−0.7 ± 13.1; p = 0.29). Between groups, we found a significant improvement in MIP ( p = 0.003) and neck circumference ( p = 0.01) in favor of the IMT group. However, we did not find any significant improvement of AHI in the IMT group compared to CTL ( p = 0.09).
Conclusion
A specific IMT during cardiac rehabilitation contributes to reduce significantly AHI in CAD patients with moderate OSA. Magnitude of the decrease in OSA severity could be enhanced according to implementation of specific IMT in this population.
... Moreover, one of the most common OSA complications/comorbidities is a metabolic syndrome. Interestingly, a meta-analysis revealed that OSA predicted risk of metabolic syndrome, independently of obesity (Mesarwi et al., 2015;Qian et al., 2016); Coughlin et al. (2004) observed that metabolic syndrome was over nine times more likely to be present among OSA patients. ...
Baroreflex (BR) control is critically dependent of sympathetic and parasympathetic
modulation. It has been documented that during acute hypobaric hypoxia there is a
BR control impairment, however, the effect of a natural hypoxic environment on BR
function is limited and controversial. Therefore, the aim of this study was to determine
the effect of acute High-Altitude exposure on sympathetic/parasympathetic modulation
of BR control in normal rats. Male Sprague Dawley rats were randomly allocated into
Sea-Level (n = 7) and High-Altitude (n = 5) (3,270 m above sea level) groups. The BR
control was studied using phenylephrine (Phe) and sodium nitroprusside (SNP) through
sigmoidal analysis. The autonomic control of the heart was estimated using heart rate
variability (HRV) analysis in frequency domain. Additionally, to determine the maximum
sympathetic and parasympathetic activation of BR, spectral non-stationary method
analysis, during Phe (0.05 mg/mL) and SNP administration (0.10 mg/mL) were used.
Compared to Sea-Level condition, the High-Altitude group displayed parasympathetic
withdrawal (high frequency, 0.6–2.4 Hz) and sympathoexcitation (low frequency, 0.04–
0.6 Hz). Regarding to BR modulation, rats showed a significant decrease (p < 0.05)
of curvature and parasympathetic bradycardic responses to Phe, without significant
differences in sympathetic tachycardic responses to SNP after High-Altitude exposure.
In addition, the non-stationary analysis of HRV showed a reduction of parasympathetic
activation (Phe) in the High-Altitude group. Our results suggest that acute exposure
to High-Altitude produces an autonomic and BR control impairment, characterized by
parasympathetic withdrawal after 24 h of high-altitude exposure.
... In the present study, when assessing males at high risk for OSAS investigated through the Berlin questionnaire, we observed higher values of total cholesterol and LDL-c and lower values of HDL-c, when comparing to those men without this risk. The positive relationship between lipid profile and OSAS is also described in the literature, as in the study by Coughlin et al. (2004) 9 , who conducted case-control type research to assess the association between OSAS and metabolic syndrome. To meet this aim, they studied 61 men from the case group, who should have a polysomnographic diagnosis of OSAS, and 43 men from the control group, whose diagnosis of OSAS was discarded. ...
Objective:: This study aimed to evaluate the association between the Berlin questionnaire index and the lipid profile, according to gender.
Method:: This is a cross-sectional study. The group investigated was composed of the Bahiana School of Medicine and Public Health (EBMSP) employees by a sequential non-probabilistic sampling. Study design: The data were obtained by applying a validated questionnaire and collecting laboratory blood samples at the Outpatient Clinics of EBMSP.
Results:: The total sample consisted of 94 employees, 21 of whom were excluded because they had not been submitted to blood collection. The sample profile evaluation had a total of 73 employees and obtained the following results in the study: the female was the most prevalent with (54.8%); the age ranged from 18 to 65 years, with a mean 38 ± 10.6 years; in men with positive Berlin (with respiratory sleep disorder), higher values of total cholesterol and LDL-c, and lower HDL-c were observed when compared to men without respiratory sleep disorder, as follows: total cholesterol (202 ± 19 vs. 180±40; p=0.040); LDL-c (137± 17 vs. 113 ± 34; p=0.048); lower HDL-c (37 ± 6 vs. 42,5 ±8; p=0.047). While in women, no significant change was observed among those with positive Berlin when compared with those with negative Berlin.
Conclusion:: The findings of this study showed that men with positive Berlin (with a respiratory sleep disorder) had higher values of total cholesterol, LDL-c, and lower HDL-c when compared to men without a respiratory sleep disorder.
Obstructive sleep apnea is a common comorbidity that occurs in individuals with obesity. It classically manifests with excessive daytime sleepiness, resulting in reduced quality of life, workplace productivity, and an increased risk of motor vehicle accidents. Weight gain plays an important role in its pathogenesis through worsening upper airway collapsibility, and current treatment options are targeted towards mechanically overcoming upper airway obstruction and weight loss. Continuous positive airway pressure therapy remains the most widely prescribed treatment for obstructive sleep apnea but poor tolerance is a common barrier to effective treatment. Sustainable weight loss is an important treatment option but can be difficult to achieve without bariatric surgery. The recent advances in incretin-based pharmacotherapies represent a promising avenue not only in achieving long-term weight loss but also in treating obstructive sleep apnoea and alleviating the burden of its symptoms and comorbidities.
Objectives
Obstructive sleep apnea (OSA) patients increasingly require shoulder surgery. Their management can be complex for anesthetists and surgeons. Interscalene nerve blocks are used routinely in shoulder surgery, providing adequate analgesia. This study aimed to investigate whether using an interscalene block in patients with OSA is associated with increased postoperative complications and morbidity when undergoing elective musculoskeletal shoulder surgery.
Methods
Patients undergoing elective musculoskeletal shoulder operations with OSA were recruited for the study. They received an interscalene brachial plexus nerve block, with or without general anesthesia. Continuous positive airway pressure (CPAP) was used routinely in the perioperative period. Patients were followed up at 24 h and 30 days postoperatively. Patients were reviewed for complications, recovery time, and length of hospital stay.
Results
Thirty-one patients were included in the study: 20 arthroscopic and 11 open shoulder procedures. No patients suffered any perioperative morbidity or mortality in the first 24 h or 30-day follow-up periods. There were no complications nor high dependency unit admissions.
Conclusion
This study indicates that OSA patients may safely undergo musculoskeletal shoulder surgery with an interscalene nerve block without an increase in perioperative morbidity and mortality. The use of an interscalene nerve block is important as it reduces or eliminates the use of opioids. Furthermore, CPAP use assists in preventing common complications related to the OSA cohort, facilitating day-case surgery.
Cardiovascular-kidney-metabolic health reflects the interplay among metabolic risk factors, chronic kidney disease, and the cardiovascular system and has profound impacts on morbidity and mortality. There are multisystem consequences of poor cardiovascular-kidney-metabolic health, with the most significant clinical impact being the high associated incidence of cardiovascular disease events and cardiovascular mortality. There is a high prevalence of poor cardiovascular-kidney-metabolic health in the population, with a disproportionate burden seen among those with adverse social determinants of health. However, there is also a growing number of therapeutic options that favorably affect metabolic risk factors, kidney function, or both that also have cardioprotective effects. To improve cardiovascular-kidney-metabolic health and related outcomes in the population, there is a critical need for (1) more clarity on the definition of cardiovascular-kidney-metabolic syndrome; (2) an approach to cardiovascular-kidney-metabolic staging that promotes prevention across the life course; (3) prediction algorithms that include the exposures and outcomes most relevant to cardiovascular-kidney-metabolic health; and (4) strategies for the prevention and management of cardiovascular disease in relation to cardiovascular-kidney-metabolic health that reflect harmonization across major subspecialty guidelines and emerging scientific evidence. It is also critical to incorporate considerations of social determinants of health into care models for cardiovascular-kidney-metabolic syndrome and to reduce care fragmentation by facilitating approaches for patient-centered interdisciplinary care. This presidential advisory provides guidance on the definition, staging, prediction paradigms, and holistic approaches to care for patients with cardiovascular-kidney-metabolic syndrome and details a multicomponent vision for effectively and equitably enhancing cardiovascular-kidney-metabolic health in the population.
Rationale:
Positive airway pressure (PAP) is standard treatment for obstructive sleep apnea (OSA). Telemedicine has been introduced for improved PAP follow-up.
Objective:
Our study aim was to evaluate clinical utility and patient satisfaction of PAP follow-up with an early intervention telemedical protocol.
Methods:
Randomized, controlled trial conducted at four sleep clinics of the same county. Treatment naive OSA patients were randomized to standard PAP follow-up (203 patients, fixed follow-up procedures) or early intervention telemedical follow-up (Air View, ResMed; 206 patients, continuous follow-up) for 3 months. Evaluated variables included PAP adherence at 3 months, patient-related outcome measures (Epworth Sleepiness Scale, Short Form 36, Insomnia Severity Scale, Hospital Anxiety and Depression Scale), and staff time. Group differences were analyzed with linear mixed regression models adjusted for age, Body Mass Index (BMI) and Apnea Hypopnea Index, and study center.
Results:
The study groups were comparable at baseline (N=409, mean age 59±12 years, BMI 31.9±6 kg/m2, AHI 41.5±21 n/h). PAP adherence was higher in the proactive telemedicine compared with the control group (4.3±2.4 and 4.1±2.6 hours/night, P=0.01, respectively) and mean mask pressure at follow-up was significantly lower in the telemedicine group, 8.7 ±2.1 cm/H20 compared to 9.2cm±2.5 cm/H20 in the control group (p=0.028). In post-hoc analysis the difference was most pronounced in patients with depression (4.8±2.6 vs 2.7±2.3 hours/night, p=0.03). Relevant mask leakage (>24 l/min) was lower in the telemedicine group (N=5.4% versus N=12.1%, P=0.024, respectively). Improvement of patient related outcome measures and patient satisfaction were equivalent between groups.
Conclusions:
Proactive telemedical management of the initial follow-up of PAP treatment compared favorably to conventional follow-up in terms of adherence, pressure level, and mask leakage. Patients with depression may particularly benefit from telemedical follow-up. Specific clinical routines are required to establish this practice in sleep clinics.
Clinicaltrials:
gov NCT03446560.
Objective
To evaluate the effect of surgical intervention on serum insulin-like growth factor 1 levels in patients with obstructive sleep apnoea.
Methods
A prospective study was conducted in a tertiary care hospital of adult patients with obstructive sleep apnoea for whom continuous positive airway pressure therapy failed or was refused. All patients underwent polysomnography and serum insulin-like growth factor 1 evaluation pre-operatively and at three months post-operatively. The site of surgery was determined using Müller's manoeuvre and ApneaGraph AG 200.
Results
Fifteen patients were included with a mean age of 38 years: 11 males and 4 females. The mean pre-operative Apnoea–Hypopnoea Index using polysomnography was 53.7 events per hour, and the mean post-operative Apnoea–Hypopnoea Index at three months was 15.3 events per hour ( p = 0.0001). The mean pre-operative serum insulin-like growth factor 1 was 160.2 μg/l, while the mean post-operative value was 236.98 μg/l ( p = 0.005).
Conclusion
In adult patients with obstructive sleep apnoea for whom continuous positive airway pressure therapy fails, site-specific surgical intervention to treat the obstruction leads to an increase in serum insulin-like growth factor 1 levels.
Arterial hypertension, the most prevalent cardiovascular disease, affects approximately 1 billion individuals worldwide. As the population ages it is expected that the number of affected subjects will further increase; therefore broad and effective preventive measures are needed. There is a growing body of evidence that sleep disruption may increase the risk of incident hypertension and cardiovascular morbidity. Sleep deprivation alone may result in higher blood pressure and higher prevalence of hypertension. One of the commonest sleep disorders, obstructive sleep apnea, may compromise cardiovascular control beyond the effects of sleep disruption per se. Sleep apnea has also been linked independently to target organ damage, usually ascribed to hypertension alone.
Proper sleep is necessary for the body to maintain homeostasis. Sleep disorders are associated with physiological and psychological medical conditions, classified by the International Classification of Sleep Disorders (ICSD). In the third edition of the ICSD, Obstructive Sleep Apnea (OSA) is classified under Sleep-Related Disorder Breathing (SRDB) and is subcategorized as adult and pediatric OSA.OSA is a sleep-related breathing disorder characterized by episodes of breathing cessation (apnea) or reduction in airflow (hypopnea) that lasts more than 10 seconds, occurring more than five times per hour of sleep. Approximately 1 billion of the world’s population, between 30 and 69 years, are estimated to have OSA. ROSA risk factors of OSA include obesity, gender, age, genetics, and craniofacial as well as orofacial abnormalities. Common symptoms include fatigue, tiredness, lack of energy, chronic snoring, witnessed apneas during sleep, and nocturnal gasping/choking isbeing the most reliable indicator of OSA.Other symptoms may include chronic morning headaches, nocturnal gastroesophageal reflux, nocturnal sweating, and decreased libido.OSA is associated with an increased risk of medical conditions and comorbidities, such as hypertension, arrhythmias, stroke, chronic renal failure, metabolic syndrome, irritable bowel syndrome, diabetes, obesity, enlarged upper airway soft tissue, headache, mood disorders, and cognitive impairment such as deficit in attention, executive functions, and memory. This chapter offers an overview of OSA and its medical comorbidities.KeywordsObstructive sleep apneaCentral sleep apneaDental sleep applianceApnea-hypopnea indexSleep bruxismSleep apnea headacheTension-type headacheGastroesophageal refluxTemporomandibular joint disorderDepression
Background
Obstructive sleep apnea hypopnea syndrome (OSAHS) is a common disease that has serious cardiovascular and metabolic effects. Insulin-like growth factor 1 (IGF-1) levels are reportedly reduced in patients with OSAHS; however, this is still a matter of debate. Therefore, we investigated the association between serum/plasma IGF-1 levels and OSAHS in this meta-analysis.
Methods
Wan Fang, Excerpta Medica dataBASE, Web of Science, China National Knowledge Infrastructure, VIP, PubMed, and other databases were searched for materials published in any language before April 2, 2022. Two researchers analyzed the studies for quality according to the Newcastle-Ottawa Scale. The acquired data were analyzed using Stata 11.0 and R 3.6.1 software. The effect size was estimated and calculated using standard mean differences and correlation coefficients. Moreover, a combined analysis was conducted using either a random- or fixed-effects model.
Results
Ultimately, 34 studies met our inclusion criteria. Our findings revealed that the plasma/serum IGF-1 concentrations in patients with OSAHS was significantly reduced compared with those in healthy subjects. Subgroup analyses were performed according to OSAHS severity, ethnicity, age, body mass index, specimen testing method, and study design. The outcomes suggested that nearly all subgroups of patients with OSAHS had reduced serum IGF-1 levels. Disease severity and differences in ethnicity were identified as possible influencing factors of serum IGF-1 levels in patients with OSAHS in the meta-regression analysis, and no other factors were found to alter plasma/serum IGF-1 concentrations. Moreover, plasma/serum IGF-1 concentrations were negatively correlated with apnea-hypopnea index and oxygen desaturation index scores and positively associated with minimum oxygen saturation.
Conclusion
Serum/plasma IGF-1 concentrations in patients with OSAHS were greatly reduced compared with those of patients in the control group, and were negatively correlated with apnea-hypopnea index and oxygen desaturation index scores and positively correlated with minimum oxygen saturation.
Systematic Review Registration
https://www.crd.york.ac.uk/PROSPERO/ , identifier CRD42022322738.
Background: To explore the prognostic and therapeutic value of the age-adjusted Charlson Comorbidity Index (ACCI) for patients with obstructive sleep apnea (OSA) aged 60 years and older.
Methods: Between January 2015 and October 2017, this multicenter, prospective, observational cohort study continuously enrolled 1183 older patients (age ≥60 years) with clinician-diagnosed OSA (sleep-laboratory-based overnight polysomnography) from sleep centers of six hospitals. Baseline demographics, clinical characteristics, sleep parameters, and medical history were obtained from electronic patient records, the ACCI was calculated, and participants were followed up prospectively to determine the primary outcome of all-cause mortality. Based on an ACCI cutoff of 4.5, participants were classified into the low-ACCI and high-ACCI groups and the receiver operating characteristic (ROC) curves were plotted. Kaplan–Meier survival analysis with log-rank test and Cox proportional hazards regression modeling was performed.
Results: During a median 43-month follow-up, 63 (5.3%) patients died. ROC curves revealed an optimal ACCI cutoff of 4.5, and the area under the curve (AUC) of 0.70 [95% confidence interval (CI): 0.63–0.77] reached statistical significance (P<0.001). Kaplan–Meier survival analysis revealed 6-year survival rate of 56.04% and 92.17% for the high-ACCI and low-ACCI (ACCI ≥5 and <5; n=336 and n=847) groups, respectively. Regardless of sex or OSA severity, the ACCI was associated with the all-cause mortality risk of older OSA patients (log-rank, both P<0.001). After controlling for confounding variables, the mortality risk was 3.32 times (95% CI: 1.91–5.77) higher in the high-ACCI group than in the low-ACCI group. Multivariate Cox stepwise regression analyses indicated that total sleep time (TST), Mean Corpuscular Volume (MCV), and ACCI (aHR [95% CI]=1.258 [1.053–1.503], 1.047 [1.007–1.087], and 1.583 [1.384–1.815]; P=0.011, 0.019, and 0.000, respectively) were significant independent predictors of all-cause mortality.
Conclusion: The ACCI is a predictor of all-cause mortality in older OSA patients (age≥60 years), with a higher ACCI indicating a higher mortality risk. The ACCI can guide clinical treatment selection for older OSA patients.
Introduction:
Sleep disturbance and clinical sleep conditions disrupt endocrine signals, energy expenditure and nutritional intake. Women with polycystic ovary syndrome (PCOS) are at higher risk of sleep disturbances and clinical conditions. It is possible that sleep may contribute to the exacerbation of PCOS. This review aims to explore the relationship between sleep and chronic disease, particularly in women with PCOS.
Areas covered:
This review narratively explores what sleep is, how to measure sleep and the possible mechanisms that support the link between sleep in adipose tissue deposition, insulin resistance and the presentation of PCOS.
Expert opinion:
Research shows that disturbed sleep and clinical sleep conditions disrupt energy expenditure. This may increase adipose tissue deposition and exacerbate insulin resistance which are known to worsen the presentation of PCOS. Further, sleep disturbance in women with PCOS may ameliorate any positive lifestyle changes made after diagnosis. Cognitive behavioural therapy interventions for sleep are a successful strategy for the management of sleep disturbances in the general population. However, such interventions are yet to be trialled in women with PCOS. Given the proposed implications, interventions to improve sleep could provide additional support for women with PCOS to successfully implement lifestyle strategies and should be further investigated.
Study objectives:
Supine predominant obstructive sleep apnea (OSA) is highly prevalent. The proportion of time spent in the supine position may be overrepresented during polysomnography, which would impact on the apnea-hypopnea index (AHI) and have important clinical implications. We aimed to investigate the difference in body position during laboratory or home polysomnography compared to habitual sleep and estimate its effect on OSA severity. Secondary aims were to evaluate the consistency of habitual sleeping position and accuracy of self-reported sleeping position.
Methods:
Patients undergoing diagnostic laboratory or home polysomnography were recruited. Body position was recorded using a neck-worn device. Habitual sleeping position was the average time spent supine over three consecutive nights at home. Primary outcomes were the proportion of sleep time spent supine (%time supine) and AHI adjusted for habitual sleeping position.
Results:
Fifty-seven patients who underwent laboratory polysomnography and 56 who had home polysomnography were included. Compared to habitual sleep, %time supine was higher during laboratory polysomnography (mean difference 14.1% [95%CI: 7.2-21.1]; p=0.0002) and home polysomnography (7.1% [95%CI 0.9-13.3]; p=0.03). Among those with supine predominant OSA, there was a trend towards lower adjusted AHI than polysomnography-derived AHI (p=0.07), changing OSA severity in 31.6%. There was no significant between-night difference in % time supine during habitual sleep (p=0.4). Self-reported % time supine was inaccurate (95% limits of agreement -49.2% to 53.9%).
Conclusions:
More time was spent in the supine position during polysomnography compared to habitual sleep, which may overestimate OSA severity for almost one-third of patients with supine predominant OSA.
Clinical trial registration:
Registry: Australia and New Zealand Clinical Trials Registry (ANZCTR); Title: Sleeping position during sleep tests and at home; Identifier: ACTRN12618000628246; URL: anzctr.org.au.
Sleep disorders that range from an inadequate number of hours of sleep to disrupted and fragmented sleep to insomnia or sleep‐related breathing disorders (SRBDs), are often times related to many medical and health problems. The most common association between sleep disorders and our health are related to cardiovascular disease, hypertension, diabetes type 2, dementia including Alzheimer's disease, to some types of cancer and even periodontal disease. It is important for the astute clinician to be vigilant regarding these associations and be able to advise patients accordingly. Management of the sleep disorder may result in improved management of any health‐related issue and thus lead to an improvement in one's quality of life.
Objective:
To investigate the relationship between obstructive sleep apnea (OSA) and components of metabolic syndrome (MetS) in the elderly and the implications for long-term risk for major adverse cardiovascular events (MACE).
Methods:
This multicenter prospective cohort study was conducted among 1157 consecutive patients with OSA [defined as an apnea-hypopnea index (AHI) ≥5 times/h recorded by overnight polysomnography] aged ≥60 years enrolled from January, 2015 to October, 2017. All the patients did not have a history of MACE at baseline and had complete documentations of MetS indicators. The baseline demographic data, clinical characteristics, biochemical markers, and sleep parameters were collected from all the patients, who were divided into 4 groups according to the quartile level of AHI and followed up for a median of 42 months for MACE and its component events (cardiovascular death, myocardial infarction, and hospitalization for unstable angina or heart failure). Multivariate linear regression and Cox proportional risk regression models were used to analyze the correlation of MetS components with major objective predictors of OSA, AHI and LSpO2 and the long- term risk of MACE.
Results:
AHI and LSpO2 quartiles group showed a positive dose-response relationship with MetS components [fasting blood glucose, waist circumference, systolic blood pressure, and triglycerides] and a negative dose-response relationship with high-density lipoprotein level. MACE occurred in 119 (10.3%) patients with OSA during the follow-up. Multivariate Cox regression analysis showed that a high triglycerides, a high systolic blood pressure, and an increased waist circumference were independent risk factors for MACE and its component events (P < 0.05 or 0.01); a high HDL was a protective factor against MACE and myocardial infarction (P < 0.05 or 0.01) independent of the AHI. MetS components independent of LSpO2 showed no significant correlations with the risk of MACE or its component events.
Conclusion:
The major diagnostic indexes AHI and LSPO2 in elderly patients with OSA have a dose-response relationship with MetS components, and the interaction between the components of MetS and AHI can increase the risk of MACE and its component events.
The development and use of a new scale, the Epworth sleepiness scale (ESS), is described. This is a simple, self-administered questionnaire which is shown to provide a measurement of the subject's general level of daytime sleepiness. One hundred and eighty adults answered the ESS, including 30 normal men and women as controls and 150 patients with a range of sleep disorders. They rated the chances that they would doze off or fall asleep when in eight different situations commonly encountered in daily life. Total ESS scores significantly distinguished normal subjects from patients in various diagnostic groups including obstructive sleep apnea syndrome, narcolepsy and idiopathic hypersomnia. ESS scores were significantly correlated with sleep latency measured during the multiple sleep latency test and during overnight polysomnography. In patients with obstructive sleep apnea syndrome ESS scores were significantly correlated with the respiratory disturbance index and the minimum SaO2 recorded overnight. ESS scores of patients who simply snored did not differ from controls.
Ambulatory blood pressure (BP) was measured noninvasively (Oxford Medilog ABP) at 15-minute intervals for 24 hours before and after 8 weeks of treatment with nasal continuous positive airway pressure (nCPAP) in 19 men with obstructive sleep apnea (OSA). We included both normotensive and hypertensive patients, but hypertensives were studied after withdrawal of antihypertensive drugs. Ambulatory BP before and after treatment was compared using patients as their own controls. Treatment with nCPAP was successfully established in 14 of the 19 patients (74%). Blood pressure fell significantly in patients who were successfully treated: 24-hour mean BP (systolic/diastolic) decreased from 141 +/- 18/89 +/- 11 mm Hg to 134 +/- 19/85 +/- 13 mm Hg (p < 0.05). The reduction in 24-hour mean systolic BP occurred during both day and night, but a significant fall in mean diastolic BP was only observed during the day. The mean blood pressure fell in both normotensive and hypertensive patients. Patients who were inadequately treated with nCPAP had no reduction in mean 24-hour BP. Effective treatment of sleep apnea with nCPAP was associated with a significant fall in both systolic and diastolic BP independent of changes in body weight or alcohol consumption, suggesting that sleep apnea was an independent factor contributing to elevated nighttime and daytime BP in these patients.
Sleep apnea and associated daytime sleepiness and fatigue are common manifestations of mainly obese middle-aged men. The onset of sleep apnea peaks in middle age, and its morbid and mortal sequelae include complications from accidents and cardiovascular events. The pathophysiology of sleep apnea remains obscure. The purpose of this study was to test three separate, albeit closely related, hypotheses. 1) Does sleep apnea contribute to the previously reported changes of plasma cytokine (tumor necrosis factor-alpha and interleukin-6) and leptin levels independently of obesity? 2) Among obese patients, is it generalized or visceral obesity that predisposes to sleep apnea? 3) Is apnea a factor independent from obesity in the development of insulin resistance? Obese middle-aged men with sleep apnea were first compared with nonapneic age- and body mass index (BMI)-matched obese and age-matched lean men. All subjects were monitored in the sleep laboratory for 4 consecutive nights. We obtained simultaneous indexes of sleep, sleep stages, and sleep apnea, including apnea/hypopnea index and percent minimum oxygen saturation. The sleep apneic men had higher plasma concentrations of the adipose tissue-derived hormone, leptin, and of the inflammatory, fatigue-causing, and insulin resistance-producing cytokines tumor necrosis factor-alpha and interleukin-6 than nonapneic obese men, who had intermediate values, or lean men, who had the lowest values. Because these findings suggested that sleep apneics might have a higher degree of insulin resistance than the BMI-matched controls, we studied groups of sleep-apneic obese and age- and BMI-matched nonapneic controls in whom we obtained computed tomographic scan measures of total, sc, and visceral abdominal fat, and additional biochemical indexes of insulin resistance, including fasting plasma glucose and insulin. The sleep apnea patients had a significantly greater amount of visceral fat compared to obese controls (<0.05) and indexes of sleep disordered breathing were positively correlated with visceral fat, but not with BMI or total or sc fat. Furthermore, the biochemical data confirmed a higher degree of insulin resistance in the group of apneics than in BMI-matched nonapneic controls. We conclude that there is a strong independent association among sleep apnea, visceral obesity, insulin resistance and hypercytokinemia, which may contribute to the pathological manifestations and somatic sequelae of this condition.
The Tanita body-fat analyser is a novel device to estimate body fat, based on the principles of bioelectrical impedance. It differs from other impedance systems which use surface electrodes in that the subjects stand bare-footed on a metal sole-plate which incorporates the electrodes, hence impedance is measured through the legs and lower trunk. In 104 men and 101 women (16-78 years and BMI 16-41 kg/m2) the mean bias in body-fat mass measured using the Tanita body-fat analyser was 0.8 (2SD 7.9) kg relative to a four-compartment model. This is comparable to the other prediction techniques tested (conventional tetrapolar impedance -1.3 (2SD 6.9) kg, skinfold thicknesses 0.3 (2SD 7.4) kg, and BMI-based formulas -0.2 (2SD 9.0) kg and -0.6 (2SD 8.5) kg), but the agreement was poorer than for 'reference' methods to measure body fat (density 0.2 (2SD 3.7) kg, total body water -0.9 (2SD 3.4) kg and dual-energy X-ray absorptiometry 0.1 (2SD 5.0) kg). The present paper also describes the derivation of a new prediction equation for the calculation of body composition from the Tanita body-fat analyser. The equation incorporates sex, age, and a log-transformation of height, weight and the measured impedance to predict body fat measured by a four-compartment model. This approach is recommended in the derivation of other prediction equations in body composition analysis. Using this novel prediction equation the residual standard deviations were 4.8% for men and 3.3% for women. A similar analysis using data collected with a conventional tetrapolar system yielded residual standard deviations of 4.3% for men and 3.1% for women. This demonstrates that the practical simplicity of the novel Tanita method is not associated with a clinically significant decrement in performance relative to a traditional impedance device.
Sleep-disordered breathing is prevalent in the general population and has been linked to chronically elevated blood pressure in cross-sectional epidemiologic studies. We performed a prospective, population-based study of the association between objectively measured sleep-disordered breathing and hypertension (defined as a laboratory-measured blood pressure of at least 140/90 mm Hg or the use of antihypertensive medications).
We analyzed data on sleep-disordered breathing, blood pressure, habitus, and health history at base line and after four years of follow-up in 709 participants of the Wisconsin Sleep Cohort Study (and after eight years of follow-up in the case of 184 of these participants). Participants were assessed overnight by 18-channel polysomnography for sleep-disordered breathing, as defined by the apnea-hypopnea index (the number of episodes of apnea and hypopnea per hour of sleep). The odds ratios for the presence of hypertension at the four-year follow-up study according to the apnea-hypopnea index at base line were estimated after adjustment for base-line hypertension status, body-mass index, neck and waist circumference, age, sex, and weekly use of alcohol and cigarettes.
Relative to the reference category of an apnea-hypopnea index of 0 events per hour at base line, the odds ratios for the presence of hypertension at follow-up were 1.42 (95 percent confidence interval, 1.13 to 1.78) with an apnea-hypopnea index of 0.1 to 4.9 events per hour at base line as compared with none, 2.03 (95 percent confidence interval, 1.29 to 3.17) with an apnea-hypopnea index of 5.0 to 14.9 events per hour, and 2.89 (95 percent confidence interval, 1.46 to 5.64) with an apnea-hypopnea index of 15.0 or more events per hour.
We found a dose-response association between sleep-disordered breathing at base line and the presence of hypertension four years later that was independent of known confounding factors. The findings suggest that sleep-disordered breathing is likely to be a risk factor for hypertension and consequent cardiovascular morbidity in the general population.
There is considerable debate regarding the relationship between obstructive sleep apnoea (OSA) and hypertension. It is unclear whether OSA is an independent vascular risk factor as studies attempting to assess this association have produced conflicting results because of confounding variables such as upper body obesity, alcohol, and smoking. A case-control study of 24 hour ambulatory blood pressure was undertaken in patients with OSA and matched controls to assess whether OSA is an independent correlate of diurnal hypertension.
Forty five patients with moderate to severe OSA and excessive daytime sleepiness were matched with 45 controls without OSA in a sleep study. Matched variables included age, body mass index (BMI), alcohol, cigarette usage, treated hypertension, and ischaemic heart disease. Upper body obesity was compared by waist:hip and waist:height ratios; 24 hour ambulatory blood pressure recordings were performed (before treatment for OSA) in all subjects.
Patients with OSA had significantly increased mean (SD) diastolic blood pressure (mm Hg) during both daytime (87.4 (10.2) versus 82.8 (9.1); p=0.03, mean difference 4.6 (95% CI 0.7 to 8.6) and night time (78.6 (9.3) versus 71.4 (8.0); p<0.001, mean difference 7.2 (95% CI 3.7 to 10.6)), and higher systolic blood pressure at night (119.4 (20.7) versus 110.2 (13.9); p=0.01, mean difference 9.2 (95% CI 2.3 to 16.1)). The nocturnal reduction in blood pressure ("dipping") was smaller in patients with OSA than in control subjects.
Compared with closely matched control subjects, patients with OSA have increased ambulatory diastolic blood pressure during both day and night, and increased systolic blood pressure at night. The magnitude of these differences is sufficient to carry an increased risk of cardiovascular morbidity. The slight excess of upper body fat deposition in the controls may make these results conservative.
BACKGROUND
There is considerable debate regarding the relationship between obstructive sleep apnoea (OSA) and hypertension. It is unclear whether OSA is an independent vascular risk factor as studies attempting to assess this association have produced conflicting results because of confounding variables such as upper body obesity, alcohol, and smoking. A case-control study of 24 hour ambulatory blood pressure was undertaken in patients with OSA and matched controls to assess whether OSA is an independent correlate of diurnal hypertension.
METHODS
Forty five patients with moderate to severe OSA and excessive daytime sleepiness were matched with 45 controls without OSA in a sleep study. Matched variables included age, body mass index (BMI), alcohol, cigarette usage, treated hypertension, and ischaemic heart disease. Upper body obesity was compared by waist:hip and waist:height ratios; 24 hour ambulatory blood pressure recordings were performed (before treatment for OSA) in all subjects.
RESULTS
Patients with OSA had significantly increased mean (SD) diastolic blood pressure (mm Hg) during both daytime (87.4 (10.2) versus 82.8 (9.1); p=0.03, mean difference 4.6 (95% CI 0.7 to 8.6) and night time (78.6 (9.3) versus 71.4 (8.0); p<0.001, mean difference 7.2 (95% CI 3.7 to 10.6)), and higher systolic blood pressure at night (119.4 (20.7) versus 110.2 (13.9); p=0.01, mean difference 9.2 (95% CI 2.3 to 16.1)). The nocturnal reduction in blood pressure (“dipping”) was smaller in patients with OSA than in control subjects.
CONCLUSIONS
Compared with closely matched control subjects, patients with OSA have increased ambulatory diastolic blood pressure during both day and night, and increased systolic blood pressure at night. The magnitude of these differences is sufficient to carry an increased risk of cardiovascular morbidity. The slight excess of upper body fat deposition in the controls may make these results conservative.
Epidemiologic studies have shown an association between higher insulin levels and coronary artery disease, and metabolic studies have associated insulin resistance and compensatory hyperinsulinemia with hypertension, obesity, and lipid disorders. This review focuses on the clinical implications (rather than the metabolic pathogeneses) of these associations and how practicing physicians should manage patients with insulin resistance.
Background: Primary as well as secondary prevention trials have shown the relevance of lowering LDL-cholesterol to reduce coronary heart disease (CHD) risk. However, although the association between LDL-cholesterol and CHD is well recognized, there is a considerable overlap in the distribution of plasma LDL-cholesterol levels between CHD patients and healthy subjects. The objective of the present review article is to use data from the Quebec cardiovascular study to demonstrate that in men, a low HDL-cholesterol may be even more of a risk factor and a target for therapy than a high LDL-cholesterol. Methods and results: Results of the Quebec cardiovascular study, a prospective study of 2103 middle-aged men followed for a period of 5 years, have confirmed results of previous studies in showing that plasma HDL-cholesterol concentration was an independent predictor of a first ischemic heart disease (IHD) event which included typical effort angina, coronary insufficiency, nonfatal myocardial infarction and coronary death. In addition, a reduced plasma HDL-cholesterol concentration was found to have a greater impact than raised LDL-cholesterol on the atherogenic index (total cholesterol:HDL-cholesterol ratio), this ratio being the best variable of the traditional lipid profile for the prediction of IHD events in the Quebec cardiovascular study. However, a low HDL-cholesterol concentration is not often observed as an isolated disorder but also includes hypertriglyceridemia, elevated apo B concentration, and an increased proportion of small, dense LDL particles. These abnormalities are features of an insulin resistant-hyperinsulinemic state resulting from abdominal obesity. Conclusions: It is therefore recommended that we need to go beyond LDL-cholesterol measurement lowering therapy for the optimal management of CHD risk. Raising plasma HDL-choles- terol through weight loss and a healthy diet, by an increased physical activity and, if required, by proper pharmacotherapy is therefore a legitimate therapeutic target for the optimal prevention of CHD in a large proportion of high risk patients. © 2000
Context
Sleep-disordered breathing (SDB) and sleep apnea have been linked to
hypertension in previous studies, but most of these studies used surrogate
information to define SDB (eg, snoring) and were based on small clinic populations,
or both.Objective
To assess the association between SDB and hypertension in a large cohort
of middle-aged and older persons.Design and Setting
Cross-sectional analyses of participants in the Sleep Heart Health Study,
a community-based multicenter study conducted between November 1995 and January
1998.Participants
A total of 6132 subjects recruited from ongoing population-based studies
(aged ≥40 years; 52.8% female).Main Outcome Measures
Apnea-hypopnea index (AHI, the average number of apneas plus hypopneas
per hour of sleep, with apnea defined as a cessation of airflow and
hypopnea defined as a ≥30% reduction in airflow
or thoracoabdominal excursion both of which are accompanied by a ≥4% drop in oxyhemoglobin
saturation), obtained by unattended home polysomnography. Other measures include
arousal index; percentage of sleep time below 90% oxygen saturation; history
of snoring; and presence of hypertension, defined as resting blood pressure
of at least 140/90 mm Hg or use of antihypertensive medication.Results
Mean systolic and diastolic blood pressure and prevalence of hypertension
increased significantly with increasing SDB measures, although some of this
association was explained by body mass index (BMI). After adjusting for demographics
and anthropometric variables (including BMI, neck circumference, and waist-to-hip
ratio), as well as for alcohol intake and smoking, the odds ratio for hypertension,
comparing the highest category of AHI (≥30 per hour) with the lowest category
(<1.5 per hour), was 1.37 (95% confidence interval [CI], 1.03-1.83; P for trend=.005). The corresponding estimate comparing
the highest and lowest categories of percentage of sleep time below 90% oxygen
saturation (≥12% vs <0.05%) was 1.46 (95% CI, 1.12-1.88; P for trend <.001). In stratified analyses, associations of hypertension
with either measure of SDB were seen in both sexes, older and younger ages,
all ethnic groups, and among normal-weight and overweight individuals. Weaker
and nonsignificant associations were observed for the arousal index or self-reported
history of habitual snoring.Conclusion
Our findings from the largest cross-sectional study to date indicate
that SDB is associated with systemic hypertension in middle-aged and older
individuals of different sexes and ethnic backgrounds.
Figures in this Article
Sleep-disordered breathing (SDB) and the related clinical syndrome,
sleep apnea, have been associated with hypertension in clinical reports since
the early 1980s.1- 4
Earlier studies of this association used self-reported history of "snoring"
as a surrogate for the presence of sleep apnea. Although some of these studies
showed an independent association between snoring and hypertension,5- 7 others found that this
relationship may be explained by confounding effects of age, sex, or obesity.8- 11 Two
recent studies have demonstrated that self-reported history of snoring is
associated with increased incidence of self-reported hypertension in middle-aged
men12 and women.13
Other studies have used polysomnography (PSG), a more objective measure of
SDB. Most of these studies,14- 19
but not all,20- 21 found an association
between sleep apnea and hypertension, independent of age, sex, body weight,
and other potential confounders. With the exception of the reports from the
Wisconsin Sleep Cohort Study of middle-aged employed persons,15,18
most previous studies were based on a small number of patients in clinical
settings.22
Given the strong association between SDB and obesity and adiposity measures,23 some researchers have cautioned that even in studies
controlling for body mass index (BMI), there is a potential for residual confounding,
since fat distribution may be the strongest confounding component of obesity.24
This study is based on baseline cross-sectional data from the Sleep
Heart Health Study (SHHS), a multicenter study of the cardiovascular consequences
of sleep apnea in participants recruited from ongoing population-based cohort
studies.25 Our results represent the largest
cross-sectional study to date of the association between SDB and hypertension
in apparently healthy middle-aged and older adults. We assessed SDB in the
subjects' homes using a portable PSG monitor. Its association with blood pressure
and hypertension is examined while controlling for the potential confounding
effects of demographic variables, body weight, and measures of body fat distribution.
Resistance to insulin-stimulated glucose uptake is present in the majority of patients with impaired glucose tolerance (IGT) or non-insulin-dependent diabetes mellitus (NIDDM) and in ∼25% of nonobese individuals with normal oral glucose tolerance. In these conditions, deterioration of glucose tolerance can only be prevented if the β-cell is able to increase its insulin secretory response and maintain a state of chronic hyperinsulinemia. When this goal cannot be achieved, gross decompensation of glucose homeostasis occurs. The relationship between insulin resistance, plasma insulin level, and glucose intolerance is mediated to a significant degree by changes in ambient plasma free-fatty acid (FFA) concentration. Patients with NIDDM are also resistant to insulin suppression of plasma FFA concentration, but plasma FFA concentrations can be reduced by relatively small increments in insulin concentration.Consequently, elevations of circulating plasma FFA concentration can be prevented if large amounts of insulin can be secreted. If hyperinsulinemia cannot be maintained, plasma FFA concentration will not be suppressed normally, and the resulting increase in plasma FFA concentration will lead to increased hepatic glucose production. Because these events take place in individuals who are quite resistant to insulinstimulated glucose uptake, it is apparent that even small increases in hepatic glucose production are likely to lead to significant fasting hyperglycemia under these conditions. Although hyperinsulinemia may prevent frank decompensation of glucose homeostasis in insulin-resistant individuals, this compensatory response of the endocrine pancreas is not without its price. Patients with hypertension, treated or untreated, are insulin resistant, hyperglycemic, and hyperinsulinemic. In addition, a direct relationship between plasma insulin concentration and blood pressure has been noted. Hypertension can also be produced in normal rats when they are fed a fructose-enriched diet, an intervention that also leads to the development of insulin resistance and hyperinsulinemia. The development of hypertension in normal rats by an experimental manipulation known to induce insulin resistance and hyperinsulinemia provides further support for the view that the relationship between the three variables may be a causal one. However, even if insulin resistance and hyperinsulinemia are not involved in the etiology of hypertension, it is likely that the increased risk of coronary artery disease (CAD) in patients with hypertension and the fact that this risk if not reduced with antihypertensive treatment are due to the clustering of risk factors for CAD, in addition to high blood pressure, associated with insulin resistance. These include hyperinsulinemia, IGT, increased plasma triglyceride concentration, and decreased high-density lipoprotein cholesterol concentration, all of which are associated with increased risk for CAD. It is likely that the same risk factors play a significant role in the genesis of CAD in the population as a whole. Based on these considerations the possibility is raised that resistance to insulin-stimulated glucose uptake and hyperinsulinemia are involved in the etiology and clinical course of three major related diseases— NIDDM, hypertension, and CAD.
To estimate the prevalence of and the cardiovascular risk associated with the metabolic syndrome using the new definition proposed by the World Health Organization
A total of 4,483 subjects aged 35-70 years participating in a large family study of type 2 diabetes in Finland and Sweden (the Botnia study) were included in the analysis of cardiovascular risk associated with the metabolic syndrome. In subjects who had type 2 diabetes (n = 1,697), impaired fasting glucose (IFG)/impaired glucose tolerance (IGT) (n = 798) or insulin-resistance with normal glucose tolerance (NGT) (n = 1,988), the metabolic syndrome was defined as presence of at least two of the following risk factors: obesity, hypertension, dyslipidemia, or microalbuminuria. Cardiovascular mortality was assessed in 3,606 subjects with a median follow-up of 6.9 years.
In women and men, respectively, the metabolic syndrome was seen in 10 and 15% of subjects with NGT, 42 and 64% of those with IFG/IGT, and 78 and 84% of those with type 2 diabetes. The risk for coronary heart disease and stroke was increased threefold in subjects with the syndrome (P < 0.001). Cardiovascular mortality was markedly increased in subjects with the metabolic syndrome (12.0 vs. 2.2%, P < 0.001). Of the individual components of the metabolic syndrome, microalbuminuria conferred the strongest risk of cardiovascular death (RR 2.80; P = 0.002).
The WHO definition of the metabolic syndrome identifies subjects with increased cardiovascular morbidity and mortality and offers a tool for comparison of results from diferent studies.
LR: 20061115; JID: 7501160; 0 (Antilipemic Agents); 0 (Cholesterol, HDL); 0 (Cholesterol, LDL); 57-88-5 (Cholesterol); CIN: JAMA. 2001 Nov 21;286(19):2401; author reply 2401-2. PMID: 11712930; CIN: JAMA. 2001 Nov 21;286(19):2400-1; author reply 2401-2. PMID: 11712929; CIN: JAMA. 2001 Nov 21;286(19):2400; author reply 2401-2. PMID: 11712928; CIN: JAMA. 2001 Nov 21;286(19):2400; author reply 2401-2. PMID: 11712927; CIN: JAMA. 2001 May 16;285(19):2508-9. PMID: 11368705; CIN: JAMA. 2003 Apr 16;289(15):1928; author reply 1929. PMID: 12697793; CIN: JAMA. 2001 Aug 1;286(5):533-5. PMID: 11476650; CIN: JAMA. 2001 Nov 21;286(19):2401-2. PMID: 11712931; ppublish
This paper presents a simple and widely ap- plicable multiple test procedure of the sequentially rejective type, i.e. hypotheses are rejected one at a tine until no further rejections can be done. It is shown that the test has a prescribed level of significance protection against error of the first kind for any combination of true hypotheses. The power properties of the test and a number of possible applications are also discussed.
Our understanding of obstructive sleep apnoea (OSA) has advanced much beyond that of the condition being a noisy breathing abnormality during sleep which classically presents with daytime sleepiness, to a condition with numerous potentially significant downstream sequelae and multisystem manifestations. The relationship between OSA and metabolic dysfunction is a moving target. Cross sectional studies have provided suggestive evidence for an independent relationship between OSA and adverse glucose metabolism, while supportive longitudinal data and interventional data from randomised controlled trials are still lacking.1 Recently, data from the Sleep Heart Health Study again confirmed the independent association between sleep disordered breathing and impaired glucose metabolism in normal weight and overweight/obese individuals.2 In this issue of Thorax , the study of Barcelo and colleagues3 suggested that the presence/absence of daytime sleepiness determined the presence/absence of increased insulin resistance in OSA, and that continuous positive airway pressure (CPAP) treatment decreased insulin resistance in sleepy subjects but had no effect in non-sleepy subjects (see page 946) . Their findings showed a pattern analogous to the previously reported phenomenon regarding OSA and elevated blood pressure, whereby the severity of daytime sleepiness in OSA predicted a blood pressure lowering response to CPAP treatment.4 5
Excessive daytime sleepiness has always been considered as one of the cardinal symptoms of OSA, and it is usually improved by effective treatment of OSA. However, it has also been well recognised that excessive daytime sleepiness is not universally present in OSA …
The relationship of future clinical coronary heart-disease (C.H.D.) to the plasma-high-density-lipoprotein (H.D.L.)-cholesterol concentration has been examined in a 2-year case-control follow-up study of 6595 men aged 20-49 years living in the municipality of Tromsø, Norway. Measurements were also made of the cholesterol concentration in lower-density (i.e., density less than 1-603 g/ml) lipoproteins, plasma-triglycerides, systolic and diastolic blood-pressures, relative body-weight, and cigarette consumption. Discriminant-function analysis showed that coronary risk was inversely related to H.D.L.-cholesterol concentration and directly related to density less than 1-063 cholesterol. These relationships were independent of each other and of the other measured variables, which showed no significant differences between the cases and controls. H.D.L. cholesterol made a three-fold greater contribution to the prediction of future C.H.D. than did density less than 1-063 cholesterol in this cohort of young men. These findings support the proposal that a low H.D.L. concentration is a common antecedent of clinical C.H.D. and is important in accelerating the progression of coronary atherosclerosis.
The relation between coronary heart disease (CHD) prevalence and fasting lipid levels was assessed by a case-control study in five populations with a total of 6859 men and women of black, Japanese and white ancestry drawn from subjects aged 40 years and older from populations in Albany, Framingham, Evans County, Honolulu and San Francisco. In each major study group mean levels of high density lipoprotein (HDL) cholesterol were lower in persons with CHD than in those without the disease. The average difference was small -- typically 3-4 mg/dl -- but statistically significant. It was found in most age-race-sex specific groups. The inverse HDL cholesterol-CHD association was not appreciably diminished when adjusted for levels of low density lipoprotein (LDL) cholesterol and triglyceride. LDL, totoal cholesterol and triglycerides were directly related to CHD prevalence; surprisingly, these findings were less uniformly present in the various study groups than the inverse HDL cholesterol-CHD association.
Lipid and lipoprotein values, including fasting triglycerides and high density lipoproteins (HDL), low density lipoproteins (LDL) and total cholesterol levels, were obtained on 2,815 men and women aged 49 to 82 years chiefly between 1969 and 1971 at Framingham. In the approximately four years following the characterization of lipids, coronary heart disease developed in 79 of the 1,025 men and 63 of the 1,445 women free of coronary heart diseases. At these older ages the major potent lipid risk factor was HDL cholesterol, which had an inverse association with the incidence of coronary heart disease (p less than 0.001) in either men or women. This lipid was associated with each major manifestation of coronary heart disease. These associations were equally significant even when other lipids and other standard risk factors for coronary heart disease were taken into consideration. A weaker association with the incidence of coronary heart disease (p less than 0.05) was observed for LDL cholesterol. Triglycerides were associated with the incidence of coronary heart disease only in women and then only when the level of other lipids was not taken into account. At these ages total cholesterol was not associated with the risk of coronary heart disease.
To assess the combined influence of blood pressure (BP), serum cholesterol level, and cigarette smoking on death from coronary heart disease (CHD) and to describe how these associations vary with age, data on those factors and on mortality for 316,099 men screened for the Multiple Risk Factor Intervention Trial (MRFIT) were examined. Vital status of participants has been determined after an average follow-up of 12 years; 6327 deaths from CHD have been identified. Strong graded relationships between serum cholesterol levels above 4.65 mmol/L (180 mg/dL), systolic BP above 110 mm Hg, and diastolic BP above 70 mm Hg and mortality due to CHD were evident. Smokers with serum cholesterol and systolic BP levels in the highest quintiles had CHD death rates that were approximately 20 times greater than nonsmoking men with systolic BP and cholesterol levels in the lowest quintile. Systolic and diastolic BP, serum cholesterol level, and cigarettes per day were significant predictors of death due to CHD in all age groups. Systolic BP was a stronger predictor than diastolic BP. These results, together with the findings of clinical trials, offer strong support for intensified preventive efforts in all age groups.
The associations of diastolic blood pressure (DBP) with stroke and with coronary heart disease (CHD) were investigated in nine major prospective observational studies: total 420,000 individuals, 843 strokes, and 4856 CHD events, 6-25 (mean 10) years of follow-up. The combined results demonstrate positive, continuous, and apparently independent associations, with no significant heterogeneity of effect among different studies. Within the range of DBP studied (about 70-110 mm Hg), there was no evidence of any "threshold" below which lower levels of DBP were not associated with lower risks of stroke and of CHD. Previous analyses have described the uncorrected associations of DBP measured just at "baseline" with subsequent disease rates. But, because of the diluting effects of random fluctuations in DBP, these substantially underestimate the true associations of the usual DBP (ie, an individual's long-term average DBP) with disease. After correction for this "regression dilution" bias, prolonged differences in usual DBP of 5, 7.5, and 10 mm Hg were respectively associated with at least 34%, 46%, and 56% less stroke and at least 21%, 29%, and 37% less CHD. These associations are about 60% greater than in previous uncorrected analyses. (This regression dilution bias is quite general, so analogous corrections to the relations of cholesterol to CHD or of various other risk factors to CHD or to other diseases would likewise increase their estimated strengths.) The DBP results suggest that for the large majority of individuals, whether conventionally "hypertensive" or "normotensive", a lower blood pressure should eventually confer a lower risk of vascular disease.
Although the literature on epidemiological associations between plasma triglyceride and CHD is not completely consistent, trends do emerge from the studies described here. First, the majority of observational studies demonstrate a significant univariate relation, although the results of case-control and cross-sectional studies are more uniform than those from prospective study designs. In many but not all studies, triglyceride remains a significant predictor of CHD in multivariate statistical analyses after controlling for TC or LDL-C. Perhaps the least consistent result is that the triglyceride association does not persist in some analyses controlling for HDL-C, while in other studies, the association remains significant. Although most studies have been conducted in men, the studies providing data on women, normocholesterolemic subjects, and diabetic subjects have generally found triglyceride to be, at the very least, a univariate risk factor. The results of intervention trials differ considerably, but no such study to date has been specifically designed to evaluate triglyceride-lowering effects on primary prevention of CHD. Important statistical properties must be taken into consideration in evaluating triglyceride as a risk factor for CHD. The large variability of triglyceride measurements and the correlation of triglyceride values with other lipid measures appears to result in the underestimation of the association between triglyceride and disease in multivariate analyses. Finally, individual genetic susceptibility may play an important role in the relation between plasma triglyceride levels and CHD. For example, risk of CHD clearly varies among the well-established familial forms of hypertriglyceridemia. A predominance of small, dense, LDL particles (LDL subclass pattern B) also appears to be a genetic trait associated with both increased risk of MI and increases in plasma triglyceride levels.
The contribution of obesity to cardiovascular risk has not been adequately appreciated because of a failure to recognize the involvement of upper-body predominance of body weight with hypertension, diabetes, and hypertriglyceridemia even in the absence of significant overall obesity. This article examines the evidence that upper-body obesity, as usually induced by caloric excess in the presence of androgens, mediates these problems by way of hyperinsulinemia. Because of these interrelationships, there is a need to identify and prevent upper-body obesity or, failing that, to provide therapies that will control the associated problems without aggravating hyperinsulinemia.
The ability of insulin to stimulate glucose uptake can vary substantially in non-obese individuals with no apparent disease (10). In addition, differences in either degree of obesity or level of habitual physical activity can also modulate in vivo insulin action (18,24). In an apparent attempt to maintain glucose homeostasis, the compensatory response to a decrease in insulin-stimulated glucose up take is an increase in plasma insulin concentration. A defect in the ability of insulin-stimulated glucose uptake has also been demonstrated (21) in patients with either impaired glucose tolerance (IGT) or non-insulin dependent diabetes mellitus (NIDDM). It has been suggested that the degree to which glucose tolerance deteriorates in these individuals is a function of the level of compensatory hyperinsulinemia that they can maintain, and the appearance of severe fasting hyperglycemia marks the failure of the pancreatic beta cell to sustain the necessary increase in insulin secretory response (21).
The steady-state basal plasma glucose and insulin concentrations are determined by their interaction in a feedback loop. A computer-solved model has been used to predict the homeostatic concentrations which arise from varying degrees beta-cell deficiency and insulin resistance. Comparison of a patient's fasting values with the model's predictions allows a quantitative assessment of the contributions of insulin resistance and deficient beta-cell function to the fasting hyperglycaemia (homeostasis model assessment, HOMA). The accuracy and precision of the estimate have been determined by comparison with independent measures of insulin resistance and beta-cell function using hyperglycaemic and euglycaemic clamps and an intravenous glucose tolerance test. The estimate of insulin resistance obtained by homeostasis model assessment correlated with estimates obtained by use of the euglycaemic clamp (Rs = 0.88, p less than 0.0001), the fasting insulin concentration (Rs = 0.81, p less than 0.0001), and the hyperglycaemic clamp, (Rs = 0.69, p less than 0.01). There was no correlation with any aspect of insulin-receptor binding. The estimate of deficient beta-cell function obtained by homeostasis model assessment correlated with that derived using the hyperglycaemic clamp (Rs = 0.61, p less than 0.01) and with the estimate from the intravenous glucose tolerance test (Rs = 0.64, p less than 0.05). The low precision of the estimates from the model (coefficients of variation: 31% for insulin resistance and 32% for beta-cell deficit) limits its use, but the correlation of the model's estimates with patient data accords with the hypothesis that basal glucose and insulin interactions are largely determined by a simple feed back loop.
• Based on six years of follow-up evaluations of the Framingham, Mass, men and women aged 49 to 82 years, it was found that a low-density lipoprotein (LDL) cholesterol concentration was associated with a low incidence of coronary heart disease (CHD) risk but with a statistically significant excess of stroke incidence in women and of deaths from non-CHD causes in both sexes. There was no suggestion that an elevated HDL cholesterol level was associated with an excess incidence of any of the cardiovascular end points considered or of death. An inverse relation of high-density lipoprotein (HDL) cholesterol level with CHD and its major consequences, CHD death and congestive heart failure, was observed. Triglyceride determinations seem to add little information respecting cardiovascular risk to that elicited from HDL and LDL cholesterol and other known cardiovascular risk factors. While the relation of HDL and LDL cholesterol with CHD is paralleled by findings from a variety of sources, the inverse relation of LDL cholesterol with stroke in women and with death from non-CHD causes requires additional confirmation and exploration.
(Arch Intern Med 1981;141:1128-1131)
Patients with isolated systolic hypertension are at increased risk for cardiovascular disorders. We attempted to determine whether those with borderline isolated systolic hypertension (defined as a systolic blood pressure of 140 to 159 mm Hg and a diastolic blood pressure below 90 mm Hg) have a greater risk of progression to definite (more severe) hypertension and of major morbid or fatal events than people with normal blood pressure (< 140/90 mm Hg).
A total of 2767 of the original participants in the Framingham Heart Study were monitored with biennial examinations for up to 34 years for the development of definite hypertension (defined as a systolic blood pressure of > or = 160 mm Hg, a diastolic blood pressure of > or = 90 mm Hg, or the initiation of antihypertensive therapy) and for major cardiovascular events.
Borderline isolated systolic hypertension was the most common type of untreated hypertension among adults over the age of 60. After 20 years of follow-up, 80 percent of those with borderline isolated systolic hypertension had progression to definite hypertension, as compared with 45 percent of the normotensive participants (P < 0.001). After adjustment for age, sex, and risk factors for cardiovascular disease, participants with borderline isolated systolic hypertension had an excess long-term risk of cardiovascular disease (hazard ratio, 1.47; 95 percent confidence interval, 1.24 to 1.74) and death from cardiovascular disease (hazard ratio, 1.57; 95 percent confidence interval, 1.24 to 2.00), as compared with normotensive participants. In an analysis of pooled data from biennial examinations to study short-term sequelae, subjects with borderline isolated systolic hypertension had an increased risk of progression to definite hypertension (odds ratio, 3.84; 95 percent confidence interval, 3.35 to 4.41) and of cardiovascular disease (odds ratio, 1.39; 95 percent confidence interval, 1.06 to 1.82).
In both the short term and the long term, subjects with borderline isolated systolic hypertension are at increased risk of progression to definite hypertension and the development of cardiovascular disease.
The National High Blood Pressure Education Program (NHBPEP) was launched 20 years ago based on data from population studies and clinical trials that showed high blood pressure (HBP) was a major unsolved--but soluble--mass public health problem. The present review summarizes recent data from US prospective population studies on blood pressure--systolic (SBP), diastolic (DBP)--and cardiovascular risk. The outcome variables include blood pressure-related risks, primarily incidence and mortality from coronary heart disease, stroke, other and all cardiovascular diseases (CVD); also cardiac abnormalities (roentgenographic, electrocardiographic, echocardiographic); also, all-cause mortality and life expectancy. Data accrued during the past 20 years confirm that SBP and DBP have continuous, graded, strong, independent, etiologically significant relationships to the outcome variables. These relationships are documented for young, middle-aged, and older men and for middle-aged and older women of varying socioeconomic backgrounds and ethnicity. Among persons aged 35 years or more, most have SBP/DBP above optimal (< 120/< 80 mm Hg); hence, they are at increased CVD risk, ie, the blood pressure problem involves most of the population, not only the substantial minority with clinical HBP. For middle-aged and older persons, SBP relates even more strongly to risk than DBP; at every DBP level, higher SBP results in greater CVD risk and curtailment of life expectancy. A great potential exists for improved health and increased longevity through control of the blood pressure problem. Its realization requires a strategy combining population wide and high-risk approaches, the former to prevent rise of blood pressure with age and to achieve primary prevention of HBP by nutritional-hygienic means; the latter to enhance detection, treatment, and control of HBP. The newly expanded goals of the NHBPEP, aimed at implementing this broader strategy for the solution of the blood pressure problem, merit active support from physicians and all health professionals.
Limited data have suggested that sleep-disordered breathing, a condition of repeated episodes of apnea and hypopnea during sleep, is prevalent among adults. Data from the Wisconsin Sleep Cohort Study, a longitudinal study of the natural history of cardiopulmonary disorders of sleep, were used to estimate the prevalence of undiagnosed sleep-disordered breathing among adults and address its importance to the public health.
A random sample of 602 employed men and women 30 to 60 years old were studied by overnight polysomnography to determine the frequency of episodes of apnea and hypopnea per hour of sleep (the apnea-hypopnea score). We measured the age- and sex-specific prevalence of sleep-disordered breathing in this group using three cutoff points for the apnea-hypopnea score (> or = 5, > or = 10, and > or = 15); we used logistic regression to investigate risk factors.
The estimated prevalence of sleep-disordered breathing, defined as an apnea-hypopnea score of 5 or higher, was 9 percent for women and 24 percent for men. We estimated that 2 percent of women and 4 percent of men in the middle-aged work force meet the minimal diagnostic criteria for the sleep apnea syndrome (an apnea-hypopnea score of 5 or higher and daytime hypersomnolence). Male sex and obesity were strongly associated with the presence of sleep-disordered breathing. Habitual snorers, both men and women, tended to have a higher prevalence of apnea-hypopnea scores of 15 or higher.
The prevalence of undiagnosed sleep-disordered breathing is high among men and is much higher than previously suspected among women. Undiagnosed sleep-disordered breathing is associated with daytime hypersomnolence.
- To examine the prevalence, incidence, predisposing factors for hypertension, its hazards as an ingredient of the cardiovascular risk profile, and the implications of this information for prevention and treatment.
- Prospective longitudinal analysis of 36-year follow-up data from the Framingham Study of the relation of antecedent blood pressure to occurrence of subsequent cardiovascular morbidity and mortality depending on the metabolically linked burden of associated risk factors.
- Hypertension is one of the most prevalent and powerful contributors to cardiovascular diseases, the leading cause of death in the United States. There is, on average, a 20 mm Hg systolic and 10 mm Hg diastolic increment increase in blood pressure from age 30 to 65 years. Isolated systolic hypertension is the dominant variety. There is no evidence of a decline in the prevalence of hypertension over 4 decades despite improvements in its detection and treatment. Hypertension contributes to all of the major atherosclerotic cardiovascular disease outcomes increasing risk, on average, 2- to 3-fold. Coronary disease, the most lethal and common sequela, deserves highest priority. Hypertension clusters with dyslipidemia, insulin resistance, glucose intolerance, and obesity, occurring in isolation in less than 20%. The hazard depends on the number of these associated metabolically linked risk factors present. Coexistent overt cardiovascular disease also influences the hazard and choice of therapy.
- The absence of a decline in the prevalence of hypertension indicates an urgent need for primary prevention by weight control, exercise, and reduced salt and alcohol intake. The urgency and choice of therapy of existing hypertension should be based on the multivariate cardiovascular risk profile that more appropriately targets hypertensive persons for treatment and prevention of cardiovascular sequelae.
We retrospectively analyzed night-to-night variability in the indices of sleep apnea in a group of men who underwent consecutive polysomnograms (PSGs) in the evaluation of impotence. The study group consisted of 37 subjects. Fifty-seven percent of the subjects had an apnea/hypopnea index (AHI) of 5 or more on the first PSG, whereas 70% met this criterion on the second study. On both PSGs, 49% of the subjects exhibited an AHI of 10 or more. The AHI varied by 10 or more between the two PSGs in 32% of the cases. Using a threshold AHI of 5 or more to establish a diagnosis of sleep apnea, 22% of the subjects would not have been diagnosed by the first PSG, and the negative rate for the first PSG was 50%. The variability observed in the AHI could not be explained by differences in total sleep time; sleep stages [1 through 4 and rapid eye movement (REM) sleep]; the amount of time sleeping supine, or a combination of sleep stage and position. The mean AHI, the apnea/hypopnea-related nadir, and the mean oxyhemoglobin saturation did not differ among the two PSGs. Our observations support the notion that for groups of subjects the mean AHI is relatively constant across 2 nights of study in the sleep laboratory. However, when an AHI of 5 or 10 or more is the sole criterion used to establish the diagnosis of sleep apnea, a single PSG may not be sufficient to rule out the presence of a sleep apnea syndrome.
To examine the research evidence for the health consequences of obstructive sleep apnoea and the effectiveness of continuous positive airways pressure.
A systematic review of published research, studies being identified by searching Medline (1966-96), Embase (1974-96), and CINAHL (Cumulative Index to Nursing and Allied Health Literature) (1982-95); scanning citations; and consulting experts. Studies in all languages were considered which either investigated the association between obstructive sleep apnoea in adults and key health outcomes or evaluated the effectiveness of treatment of obstructive sleep apnoea with continuous positive airways pressure in adults.
Mortality, systematic hypertension, cardiac arrhythmias, ischaemic heart disease, left ventricular hypertrophy, pulmonary hypertension, stroke, vehicle accidents, measures of daytime sleepiness, and quality of life.
54 epidemiological studies examined the association between sleep apnoea and health related outcomes. Most were poorly designed and only weak or contradictory evidence was found of an association with cardiac arrhythmias, ischaemic heart disease, cardiac failure, systemic or pulmonary hypertension, and stroke. Evidence of a link with sleepiness and road traffic accidents was stronger but inconclusive. Only one small randomised controlled trial evaluated continuous positive airways pressure. Five non-randomised controlled trials and 38 uncontrolled trials were identified. Small changes in objectively measured daytime sleepiness were consistently found, but improvements in morbidity, mortality, and quality of life indicators were not adequately assessed.
The relevance of sleep apnoea to public health has been exaggerated. The effectiveness of continuous positive airways pressure in improving health outcomes has been poorly evaluated. There is enough evidence suggesting benefit in reducing daytime sleepiness in some patients to warrant large randomised placebo controlled trials of continuous positive airways pressure versus an effective weight reduction programme and other interventions.
A study was undertaken to test the hypothesis that unsupervised domiciliary limited sleep studies do not impair the accuracy of diagnosis when used to investigate the sleep apnoea/hypopnoea syndrome (SAHS) and can be cheaper than laboratory polysomnography.
For validation, 23 subjects with suspected SAHS underwent laboratory polysomnography and a home study (EdenTec 3711) on successive nights. All subjects with > 15 apnoeas + hypopnoeas (A + H)/hour on polysomnography showed > 30 A + H/hour on their home study. Thereafter, in a prospective trial 150 subjects had a home study as the initial investigation and studies showing > 30 events/hour were regarded as diagnostic of SAHS. Those showing fewer events were investigated with polysomnography if necessary. Time to treatment, outcome, and costs of this protocol were compared with those of 75 patients investigated initially with polysomnography.
Of the prospective trial subjects, 29% had > 30 A + H/hour and proceeded directly from home study to treatment; 15% without daytime sleepiness were not investigated further. Polysomnography was undertaken to establish a diagnosis in 56% of cases, including 18% whose home studies were unsuccessful. Compared with the 75 control patients, this protocol gave a diagnosis faster (median 18 (range 0-221) versus 47 (0-227) days, p < 0.001) and more cheaply (mean (SD) 164 pounds (104) versus 210 pounds (0), p < 0.001). The proportions offered CPAP (61% versus 67%) and subsequent objective CPAP usage (mean 4.7 (2.4) versus 5.0 (2.4) hours/night) were not different.
Use of home sleep studies has benefits in time and cost. For diagnostic reliability a further sleep study was required in 56% of cases.
The classification of diabetes mellitus and the tests used for its diagnosis were brought into order by the National Diabetes Data Group of the USA and the second World Health Organization Expert Committee on Diabetes Mellitus in 1979 and 1980. Apart from minor modifications by WHO in 1985, little has been changed since that time. There is however considerable new knowledge regarding the aetiology of different forms of diabetes as well as more information on the predictive value of different blood glucose values for the complications of diabetes. A WHO Consultation has therefore taken place in parallel with a report by an American Diabetes Association Expert Committee to re-examine diagnostic criteria and classification. The present document includes the conclusions of the former and is intended for wide distribution and discussion before final proposals are submitted to WHO for approval. The main changes proposed are as follows. The diagnostic fasting plasma (blood) glucose value has been lowered to > or =7.0 mmol l(-1) (6.1 mmol l(-1)). Impaired Glucose Tolerance (IGT) is changed to allow for the new fasting level. A new category of Impaired Fasting Glycaemia (IFG) is proposed to encompass values which are above normal but below the diagnostic cut-off for diabetes (plasma > or =6.1 to <7.0 mmol l(-1); whole blood > or =5.6 to <6.1 mmol l(-1)). Gestational Diabetes Mellitus (GDM) now includes gestational impaired glucose tolerance as well as the previous GDM. The classification defines both process and stage of the disease. The processes include Type 1, autoimmune and non-autoimmune, with beta-cell destruction; Type 2 with varying degrees of insulin resistance and insulin hyposecretion; Gestational Diabetes Mellitus; and Other Types where the cause is known (e.g. MODY, endocrinopathies). It is anticipated that this group will expand as causes of Type 2 become known. Stages range from normoglycaemia to insulin required for survival. It is hoped that the new classification will allow better classification of individuals and lead to fewer therapeutic misjudgements.
Chronic sleep debt is becoming increasingly common and affects millions of people in more-developed countries. Sleep debt is currently believed to have no adverse effect on health. We investigated the effect of sleep debt on metabolic and endocrine functions.
We assessed carbohydrate metabolism, thyrotropic function, activity of the hypothalamo-pituitary-adrenal axis, and sympathovagal balance in 11 young men after time in bed had been restricted to 4 h per night for 6 nights. We compared the sleep-debt condition with measurements taken at the end of a sleep-recovery period when participants were allowed 12 h in bed per night for 6 nights.
Glucose tolerance was lower in the sleep-debt condition than in the fully rested condition (p<0.02), as were thyrotropin concentrations (p<0.01). Evening cortisol concentrations were raised (p=0.0001) and activity of the sympathetic nervous system was increased in the sleep-debt condition (p<0.02).
Sleep debt has a harmful impact on carbohydrate metabolism and endocrine function. The effects are similar to those seen in normal ageing and, therefore, sleep debt may increase the severity of age-related chronic disorders.
Elevated blood pressure is known to be a risk factor for death from coronary heart disease (CHD). However, it is unclear whether the risk of death from CHD in relation to blood pressure varies among populations.
In six populations in different parts of the world, we examined systolic and diastolic blood pressures and hypertension in relation to long-term mortality from CHD, both with and without adjustment for variability in blood pressure within individual subjects. Blood pressure was measured at base-line in 12,031 men (age range, 40 to 59 years) who were free of CHD. During 25 years of follow-up, 1291 men died from CHD.
At systolic and diastolic blood pressures of about 140 and 85 mm Hg, respectively, 25-year rates of mortality from CHD (standardized for age) varied by a factor of more than three among the populations. Rates in the United States and northern Europe were high (approximately 70 deaths per 10,000 person-years), but rates in Japan and Mediterranean southern Europe were low (approximately 20 deaths per 10,000 person-years). However, the relative increase in 25-year mortality from CHD for a given increase in blood pressure was similar among the populations. The overall unadjusted relative risk of death due to CHD was 1.17 (95 percent confidence interval, 1.14 to 1.20) per 10 mm Hg increase in systolic pressure and 1.13 (95 percent confidence interval, 1.10 to 1.15) per 5 mm Hg increase in diastolic pressure, and it was 1.28 for each of these increments after adjustment for within-subject variability in blood pressure.
Among the six populations we studied, the relative increase in long-term mortality due to CHD for a given increase in blood pressure is similar, whereas the absolute risk at the same level of blood pressure varies substantially. If the absolute risk of CHD is used as an indication for antihypertensive therapy, these findings will have major implications for treatment in different parts of the world.
This article is a critical review of the available evidence on the prognostic value of ambulatory blood pressure (ABP). Several event-based cohort studies have shown that ABP improves cardiovascular risk stratification over and beyond traditional risk factors, including office BP. Most of these studies have been conducted in subjects with essential hypertension who were untreated at the time of execution of ABP monitoring; other studies have been conducted in subjects who were poorly controlled with treatment or in the general population. In these studies, ABP was examined as a continuous variable or with operational risk categories. Cardiovascular risk showed a direct and independent association with the observed ABP (systolic, diastolic, and pulse) and an inverse association with the degree of BP reduction from day to night. Cardiovascular risk was also directly associated with the difference between the observed value of ABP and that predicted from the office BP. White-coat hypertension versus ambulatory hypertension and dippers versus nondippers are 2 classifications based on arbitrary operational risk categories. A blunted or absent BP reduction from day to night, defined with ABP as a continuous variable or with operational thresholds, was also associated with a worse outcome regardless of the average value of ABP during the 24 hours. Overall, these studies indicate that ABP monitoring is particularly valuable to refine cardiovascular risk stratification in untreated subjects with office hypertension and in those with resistant hypertension. Intervention studies targeted at ABP are now needed.
Sleep-disordered breathing (SDB) and sleep apnea have been linked to hypertension in previous studies, but most of these studies used surrogate information to define SDB (eg, snoring) and were based on small clinic populations, or both.
To assess the association between SDB and hypertension in a large cohort of middle-aged and older persons.
Cross-sectional analyses of participants in the Sleep Heart Health Study, a community-based multicenter study conducted between November 1995 and January 1998.
A total of 6132 subjects recruited from ongoing population-based studies (aged > or = 40 years; 52.8% female).
Apnea-hypopnea index (AHI, the average number of apneas plus hypopneas per hour of sleep, with apnea defined as a cessation of airflow and hypopnea defined as a > or = 30% reduction in airflow or thoracoabdominal excursion both of which are accompanied by a > or = 4% drop in oxyhemoglobin saturation) [corrected], obtained by unattended home polysomnography. Other measures include arousal index; percentage of sleep time below 90% oxygen saturation; history of snoring; and presence of hypertension, defined as resting blood pressure of at least 140/90 mm Hg or use of antihypertensive medication.
Mean systolic and diastolic blood pressure and prevalence of hypertension increased significantly with increasing SDB measures, although some of this association was explained by body mass index (BMI). After adjusting for demographics and anthropometric variables (including BMI, neck circumference, and waist-to-hip ratio), as well as for alcohol intake and smoking, the odds ratio for hypertension, comparing the highest category of AHI (> or = 30 per hour) with the lowest category (< 1.5 per hour), was 1.37 (95% confidence interval [CI], 1.03-1.83; P for trend = .005). The corresponding estimate comparing the highest and lowest categories of percentage of sleep time below 90% oxygen saturation (> or = 12% vs < 0.05%) was 1.46 (95% CI, 1.12-1.88; P for trend <.001). In stratified analyses, associations of hypertension with either measure of SDB were seen in both sexes, older and younger ages, all ethnic groups, and among normal-weight and overweight individuals. Weaker and nonsignificant associations were observed for the arousal index or self-reported history of habitual snoring.
Our findings from the largest cross-sectional study to date indicate that SDB is associated with systemic hypertension in middle-aged and older individuals of different sexes and ethnic backgrounds.
Cardiovascular disorders are common in patients with obstructive sleep apnoea syndrome (OSAS) but there is debate as to whether OSAS is an independent risk factor for their development, since OSAS may be associated with other disorders and risk factors that predispose to cardiovascular disease. In an effort to quantify the risk of OSAS patients for cardiovascular disease arising from these other factors, the authors assessed the future risk for cardiovascular disease among a group of 114 consecutive patients with established OSAS prior to nasal continuous positive airway pressure therapy, using an established method of risk prediction employed in the Framingham studies. Patients were 100 males, aged (mean+/-SD) 52+/-9.0 yrs, and 14 females, aged 51+/-10.4 yrs, with an apnoea/hypopnoea index of 45+/-22 x h(-1). Based on either a prior diagnosis, or a mean of three resting blood pressure recordings >140 mmHg systolic and/or 90 diastolic, 68% of patients were hypertensive. Only 18% were current smokers, while 16% had either diabetes mellitus or impaired glucose tolerance, and 63% had elevated fasting cholesterol and/or triglyceride levels. The estimated 10-yr risk of a coronary heart disease (CHD) event in males was (mean+/-SEM) 13.9+/-0.9%, 95% confidence interval (95% CI) 12.1-16.0, and for a stroke was 12.3+/-1.4%; 95% CI 9.4-15.1, with a combined 10 yr risk for stroke and CHD events of 32.9+/-2.7%; 95% CI 27.8-38.5 in males aged >53 yrs. These findings indicate that obstructive sleep apnoea syndrome patients are at high risk of future cardiovascular disease from factors other than obstructive sleep apnoea syndrome, and may help explain the difficulties in identifying a potential independent risk from obstructive sleep apnoea syndrome.
To define the metabolic profile relevant to vascular risks in obstructive sleep apnea (OSA) and the role of leptin resistance in this risk profile.
Case control study.
Sleep Laboratory, Queen Mary Hospital, University of Hong Kong, China.
Thirty OSA subjects were matched with 30 non-OSA subjects for body mass index (BMI), age, sex, and menopausal status. Neck, waist, and hip girth, skinfold thickness, and fasting serum levels of lipids, glucose, insulin, and leptin were compared between these two groups.
Compared with control subjects with a similar BMI but without OSA, the OSA group had a significantly more adverse vascular risk factor profile, including dyslipidemia, higher diastolic BP, insulin resistance, and greater adiposity reflected by skinfold thickness. OSA subjects also had higher circulating leptin levels (9.18+/-4.24 ng/mL vs 6.54+/-3.81 ng/mL, mean +/- SD, p = 0.001). Serum leptin levels correlated positively with BMI, skinfold thickness, serum cholesterol, low-density lipoprotein cholesterol, insulin, insulin/glucose ratio, apnea-hypopnea index, and oxygen desaturation time; multiple stepwise regression analysis identified skinfold thickness, waist/hip ratio, serum low-density lipoprotein cholesterol, and diastolic BP as independent correlates, while only serum insulin and diastolic BP were independent correlates in OSA subjects. After treatment with nasal continuous positive airway pressure for 6 months, there was a significant decrease in circulating leptin (p = 0.01) and triglyceride levels (p = 0.02) without change in other parameters.
Despite controlling for BMI, OSA subjects showed distinct profiles with clustering of vascular risk factors. Hyperleptinemia was present in the OSA subjects, but it can be normalized by treatment with nasal continuous positive airway pressure, suggesting that increased leptin resistance was not the cause of OSA or its associated vascular risks.
Obstructive sleep apnoea (OSA) is strongly associated with obesity, especially abdominal obesity. Obesity in turn is a well-known risk factor for coronary artery disease (CAD). The aim of our study was to evaluate the relationship between OSA severity and CAD risk factors.
The sample consisted of 73 subjects (mean age +/- SE, 46.7 +/- 1 years) referred to a sleep laboratory. Subjects were either: 1. obese with OSA (O-OSA group n = 35; body mass index, BMI ł 30 kg/m2; apnoea/hypopnoea index, AHI > 35), 2. non-obese with OSA (BO-OSA group n = 14; BMI < 27 kg/m2; AHI > 35), or 3. obese without OSA (O-Z group n = 24; BMI ł 30 kg/m2; AHI < 5). All subjects underwent full overnight polysomnography. Blood samples were taken from all subject, for fasting levels of insulin (INS), glucose (GLU), total, HDL and LDL cholesterol, triglyceride (TG) and uric acid (UA).
O-OSA had significantly higher INS and UA levels (p < 0.05) compared to BO-OSA and O-Z. GLU and lipid levels were comparable in the studied groups. GLU level correlated (p < 0.05) negatively to minimum oxyhemoglobin saturation (SAT-MIN) and positively to neck circumference. TG and UA levels were correlated (p < 0.05) positively to AHI and negatively to SAT-MIN. UA level was also positively correlated (p < 0.05) to BMI, waist/hip circumference ratio (WHR), and INS level. INS level correlated (p < 0.05) positively to AHI, T90, WHR and UA, and negatively to SAT-MIN and mean oxyhemoglobin saturation. After adjusting for the influence of OSA and obesity (multiple regression analysis), we found independent negative correlations (p < 0.05) between: GLU level and SAT-MIN, UA level and SAT-MIN, and INS level and SAT-MIN. An independent, positive correlation (p < 0.05) was found between TG level and AHI.
Results of our study suggest that OSA increases the risk of coronary artery disease by increasing plasma levels of glucose, triglyceride and insulin, independent of obesity.
Factor analysis has emerged as a useful method for understanding patterns underlying the co-occurrence of metabolic risk factors for both type 2 diabetes and atherosclerosis--often referred to as "insulin resistance syndrome." In factor analysis of data on 322 healthy elderly people from the Cardiovascular Health Study, Sakkinen et al. (Am J Epidemiol 2000;152:897-907) confirmed findings from a dozen prior studies that as many as four distinct physiologic domains comprise the syndrome, with a unifying role for markers of insulin resistance. With the addition of markers of hemostasis and inflammation, they also found that impaired fibrinolysis and endothelial dysfunction are central features of the syndrome, while inflammation is only weakly linked to insulin resistance through associations with obesity.
Primary as well as secondary prevention trials have shown the relevance of lowering LDL-cholesterol to reduce coronary heart disease (CHD) risk. However, although the association between LDL-cholesterol and CHD is well recognized, there is a considerable overlap in the distribution of plasma LDL-cholesterol levels between CHD patients and healthy subjects. The objective of the present review article is to use data from the Quebec cardiovascular study to demonstrate that in men, a low HDL-cholesterol may be even more of a risk factor and a target for therapy than a high LDL-cholesterol.
Results of the Quebec cardiovascular study, a prospective study of 2103 middle-aged men followed for a period of 5 years, have confirmed results of previous studies in showing that plasma HDL-cholesterol concentration was an independent predictor of a first ischemic heart disease (IHD) event which included typical effort angina, coronary insufficiency, nonfatal myocardial infarction and coronary death. In addition, a reduced plasma HDL-cholesterol concentration was found to have a greater impact than raised LDL-cholesterol on the atherogenic index (total cholesterol/HDL-cholesterol ratio), this ratio being the best variable of the traditional lipid profile for the prediction of IHD events in the Quebec cardiovascular study. However, a low HDL-cholesterol concentration is not often observed as an isolated disorder but also includes hypertriglyceridemia, elevated apo B concentration, and an increased proportion of small, dense LDL particles. These abnormalities are features of an insulin resistant-hyperinsulinemic state resulting from abdominal obesity.
It is therefore recommended that we need to go beyond LDL-cholesterol measurement lowering therapy for the optimal management of CHD risk. Raising plasma HDL-cholesterol through weight loss and a healthy diet, by an increased physical activity and, if required, by proper pharmacotherapy is therefore a legitimate therapeutic target for the optimal prevention of CHD in a large proportion of high risk patients.
Disordered breathing during sleep is associated with acute, unfavorable effects on cardiovascular physiology, but few studies have examined its postulated association with cardiovascular disease (CVD). We examined the cross-sectional association between sleep- disordered breathing and self-reported CVD in 6,424 free-living individuals who underwent overnight, unattended polysomnography at home. Sleep-disordered breathing was quantified by the apnea-hypopnea index (AHI)-the average number of apneas and hypopneas per hour of sleep. Mild to moderate disordered breathing during sleep was highly prevalent in the sample (median AHI: 4.4; interquartile range: 1.3 to 11.0). A total of 1,023 participants (16%) reported at least one manifestation of CVD (myocardial infarction, angina, coronary revascularization procedure, heart failure, or stroke). The multivariable-adjusted relative odds (95% CI) of prevalent CVD for the second, third, and fourth quartiles of the AHI (versus the first) were 0.98 (0.77-1.24), 1.28 (1.02-1.61), and 1.42 (1.13-1.78), respectively. Sleep-disordered breathing was associated more strongly with self-reported heart failure and stroke than with self-reported coronary heart disease: the relative odds (95% CI) of heart failure, stroke, and coronary heart disease (upper versus lower AHI quartile) were 2.38 (1.22-4.62), 1.58 (1.02- 2.46), and 1.27 (0.99-1.62), respectively. These findings are compatible with modest to moderate effects of sleep-disordered breathing on heterogeneous manifestations of CVD within a range of AHI values that are considered normal or only mildly elevated.
Sleep-disordered breathing is a prevalent condition associated with impairment of daytime function and may predispose individuals to metabolic abnormalities independent of obesity. The primary objective of this study was to determine the metabolic consequences and community prevalence of sleep-disordered breathing in mildly obese, but otherwise healthy, individuals. One hundred and fifty healthy men, without diabetes or cardiopulmonary disease, were recruited from the community. Measurements included polysomnography, a multiple sleep latency test, an oral glucose tolerance test, determination of body fat by hydrodensitometry, and fasting insulin and lipids. The prevalence of sleep-disordered breathing, depending on the apnea-hypopnea index (AHI) cutoff, ranged from 40 to 60%. After adjusting for body mass index (BMI) and percent body fat, an AHI gt-or-equal, slanted 5 events/h was associated with an increased risk of having impaired or diabetic glucose tolerance (odds ratio, 2.15; 95% CI, 1.05-4.38). The impairment in glucose tolerance was related to the severity of oxygen desaturation (DeltaSa(O(2))) associated with sleep-disordered breathing. For a 4% decrease in oxygen saturation, the associated odds ratio for worsening glucose tolerance was 1.99 (95% CI, 1.11 to 3.56) after adjusting for percent body fat, BMI, and AHI. Multivariable linear regression analyses revealed that increasing AHI was associated with worsening insulin resistance independent of obesity. Thus, sleep-disordered breathing is a prevalent condition in mildly obese men and is independently associated with glucose intolerance and insulin resistance.
Epidemiological studies have implicated obstructive sleep apnea (OSA) as an independent comorbid factor in cardiovascular and cerebrovascular diseases. It is postulated that recurrent episodes of occlusion of upper airways during sleep result in pathophysiological changes that may predispose to vascular diseases. Insulin resistance is a known risk factor for atherosclerosis, and we postulate that OSA represents a stress that promotes insulin resistance, hence atherogenesis. This study investigated the relationship between sleep-disordered breathing and insulin resistance, indicated by fasting serum insulin level and insulin resistance index based on the homeostasis model assessment method (HOMA-IR). A total of 270 consecutive subjects (197 male) who were referred for polysomnography and who did not have known diabetes mellitus were included, and 185 were documented to have OSA defined as an apnea-hypopnea index (AHI) > or =5. OSA subjects were more insulin resistant, as indicated by higher levels of fasting serum insulin (p = 0.001) and HOMA-IR (p < 0.001); they were also older and more obese. Stepwise multiple linear regression analysis showed that obesity was the major determinant of insulin resistance but sleep-disordered breathing parameters (AHI and minimum oxygen saturation) were also independent determinants of insulin resistance (fasting insulin: AHI, p = 0.02, minimum O(2), p = 0.041; HOMA-IR: AHI, p = 0.044, minimum O(2), p = 0.022); this association between OSA and insulin resistance was seen in both obese and nonobese subjects. Each additional apnea or hypopnea per sleep hour increased the fasting insulin level and HOMA-IR by about 0.5%. Further analysis of the relationship of insulin resistance and hypertension confirmed that insulin resistance was a significant factor for hypertension in this cohort. Our findings suggest that OSA is independently associated with insulin resistance, and its role in the atherogenic potential of sleep disordered breathing is worthy of further exploration.
The prospective association between insulin levels and risk of cardiovascular disease (CVD) is controversial. The objective of the present study was to investigate the relationship of the homeostasis model assessment of insulin resistance (HOMA-IR), as well as insulin levels, with risk of nonfatal and fatal CVD over the 8-year follow-up of the San Antonio Heart Study.
Between 1984 and 1988, randomly selected Mexican-American and non-Hispanic white residents of San Antonio participated in baseline examinations that included fasting blood samples for glucose, insulin, and lipids, a glucose tolerance test, anthropometric measurements, and a lifestyle questionnaire. Between 1991 and 1996, 2,569 subjects who were free of diabetes at baseline were reexamined using the same protocol.
Over the follow-up period, 187 subjects experienced an incident cardiovascular event (heart attack, stroke, heart surgery, angina, or CVD death). Logistic regression analysis indicated that risk of a CVD event increased across quintiles of HOMA-IR after adjustment for age, sex, and ethnicity (P for trend <0.0001; quintile 5 vs. quintile 1, odds ratio [OR] 2.52, 95% CI 1.46-4.36). Additional adjustment for LDL, triglyceride, HDL, systolic blood pressure, smoking, alcohol consumption, exercise, and waist circumference only modestly reduced the magnitude of these associations (P for trend 0.02; quintile 5 vs. quintile 1, OR 1.94, 95% CI 1.05-3.59). Furthermore, there were no significant interactions between HOMA-IR and ethnicity, sex, hypertension, dyslipidemia, glucose tolerance (impaired glucose tolerance versus normal glucose tolerance), or obesity. The magnitude and direction of the relationship between insulin concentration and incident CVD were similar.
We found a significant association between HOMA-IR and risk of CVD after adjustment for multiple covariates. The topic remains controversial, however, and additional studies are required, particularly among women and minority populations.