The incremental role of obstructive sleep apnoea on markers of atherosclerosis in patients with metabolic syndrome

ObjectiveMetabolic syndrome (MS) is associated with subclinical atherosclerosis, but the relative role of obstructive sleep apnoea (OSA) is largely unknown. The main objective of this study is to determine the impact of OSA on markers of atherosclerosis in patients with MS.MethodsEighty-one consecutive patients with MS according to the Adult Treatment Panel III underwent a clinical evaluation, polysomnography, laboratory and vascular measurements of carotid intima media thickness (IMT), carotid-femoral pulse wave velocity (PWV) and carotid diameter (CD) in a blind fashion. OSA was defined as an apnoea-hypopnoea index (AHI) ≥15 events/hour. Multiple linear regression was performed to determine the variables that were independently associated with the vascular parameters.ResultsFifty-one patients (63%) had OSA. No significant differences existed in age, sex, MS criteria, and cholesterol levels between patients with (MS+OSA) and without OSA (MS?OSA). Compared with MS?OSA patients, MS+OSA patients had higher levels of IMT (661 ± 117 vs. 767 ± 140 μm), PWV (9.6 ± 1.0 vs. 10.6 ± 1.6 m/s), and CD (6705 ± 744 vs. 7811 ± 862 μm) (P < 0.001 for each comparison). Among patients with MS+OSA, all vascular parameters were similar in patients with and without daytime sleepiness. The independent parameters associated with IMT, PWV, and CD were AHI, abdominal circumference, and systolic blood pressure (R² = 0.42); AHI and systolic blood pressure (R² = 0.38); and AHI, age, abdominal circumference and systolic blood pressure (R² = 0.45), respectively. The R² of AHI for IMT, PWV and CD was 0.12, 0.10 and 0.20, respectively.ConclusionsOSA is very common and has an incremental role in atherosclerotic burden in consecutive patients with MS.     

Hypercapnia in obstructive sleep apnoea syndrome

BACKGROUND: The reports on the prevalence of hypercapnia in Obstructive Sleep Apnoea Syndrome (OSAS) are conflicting. We studied the prevalence of hypercapnia in a population of OSAS patients referred to a Department of Respiratory Medicine and the mechanism of the respiratory failure in OSAS associated with Obesity Hypoventilation Syndrome (OHS) or with Chronic Obstructive Pulmonary Disease (COPD) (Overlap syndrome). METHODS: We studied 219 consecutive OSAS patients during a period of 3 years. We recorded age and anthropomorphic data and performed polysomnography and pulmonary function tests. In relation to the value of PaCO(2), the patients were divided in hypercapnic (PaCO(2)>45 mmHg) patients and normocapnic patients. They were also divided into three groups in relation to the presence of "simple" or "pure" OSAS, to the presence of OSAS associated with COPD, to the presence of OSAS associated with OHS. RESULTS: Seventeen per cent of the patients were hypercapnic. They were significantly heavier, had more severe lung function test abnormalities and more severe nocturnal oxyhemoglobin desaturations than the normocapnic ones, while Forced Expiratory Volume in one second as a percentage of Forced Vital Capacity (FEV1/FVC %) and Apnoea/Hypopnoea Index (AHI) were similar. OHS patients (13%) were significantly younger and heavier, had lower PaO(2) and higher PaCO(2) than "simple" OSAS patients (77%) and Overlap patients (10%) and had more severe restrictive defect. There was no difference in terms of AHI among the three groups, but nocturnal oxyhemoglobin desaturations were more severe in OHS group. In OHS group hypercapnia was correlated to FVC% of predicted and FEV1% of predicted and to the mean nocturnal oxyhemoglobin saturation; in Overlap patients PaCO(2) was correlated to Forced Expiratory Flow rate at low Vital Capacity. CONCLUSION: Seventeen per cent of OSAS patients referred to a Department of Respiratory Medicine were hypercapnic. Hypercapnia in OHS patients correlates to the restrictive ventilatory defect whereas in Overlap patients it seems to correlate to peripheral airways obstruction. The distinction between patients with "simple" or "pure" OSAS and patients affected by OSAS associated with OHS or COPD could be important not only for clinical and prognostic implications, but also for the consequences in terms of ventilatory treatment.     

Relationship between arterial stiffness and myocardial damage in patients with newly diagnosed essential hypertension

BackgroundArterial stiffness increases in hypertensive individuals. Arterial stiffness is associated with impairment of systolic and diastolic myocardial function in hypertension (HT). However, the relationship between arterial stiffness and serum heart-type fatty acid-binding protein (H-FABP) levels, a sensitive marker of myocardial damage, has not been previously examined in patients with HT. We investigate the relationship between serum H-FABP levels and arterial stiffness in patients with newly diagnosed HT.MethodsWe studied 46 (48.5 +/- 10.6, years) never-treated patients with HT and age-matched control group of 40 (47 +/- 8.6, years) normotensive individuals. H-FABP levels were determined in all subjects. We evaluated arterial stiffness and wave reflections of study population, using applanation tonometry (Sphygmocor). Carotid-femoral pulse wave velocity (PWV) was measured as indices of elastic-type, aortic stiffness. The heart rate-corrected augmentation index (AIx@75) was estimated as a marker of wave reflections.ResultsCarotid-femoral PWV (10.5 +/- 2.2 vs. 8.7 +/- 1.6, m/s, P = 0.0001) and AIx@75 (22.7 +/- 9.5 vs. 15 +/- 11, %, P = 0.001) were significantly higher in patients with HT than control group. H-FABP levels were increased in hypertensive patients compared with control group (21.1 +/- 14.8 vs. 12.9 +/- 8.5, ng/ml, P = 0.002). In multiple linear regression analysis, we found that the body mass index (beta = 0.42, P = 0.0001) and carotid-femoral PWV (beta = 0.23, P = 0.03) were significant determinants of H-FABP levels.ConclusionArterial stiffness is associated with serum H-FABP levels, a sensitive marker of myocardial damage, in patients with newly diagnosed HT.American Journal of Hypertension (2008). doi 10.1038/ajh.2008.235American Journal of Hypertension (2008); 21, 9, 989-993. doi 10.1038/ajh.2008.235.     

The effect of continuous positive airway pressure therapy on blood pressure and arterial stiffness in hypertensive patients with obstructive sleep apnea

Aim

We aimed to evaluate the effect of continuous positive airway pressure (CPAP) therapy on blood pressure (BP) and arterial stiffness in hypertensive patients with obstructive sleep apnea (OSA).

Patients and methods

We studied 38 hypertensive patients who suffered from severe OSA. Ambulatory BP measurement was performed at baseline and after at least 3 months of uninterrupted CPAP therapy. In 19 of these patients, we also measured pulse wave velocity (PWV) at baseline, after the first night of CPAP therapy and at 3 months. Fifteen normotensive subjects without OSA comprised the control group.

Results

CPAP therapy reduced systolic BP from 141.5?±?12.1 to 133.5?±?9.7 mmHg (p?=?0.007) and diastolic BP from 87.8?±?6.8 to 83?±?5.4 mmHg (p?=?0.004). CPAP also reduced the PWV from 8.81?±?1.4 to 8.18?±?1 m/s after the first night of CPAP therapy (p?=?0.003) and to 7.37?±?1 m/s at 3 months (p?=?0.007).

Conclusions

To the best of our knowledge, this is the first study demonstrating that CPAP therapy in hypertensive patients with OSA improves arterial stiffness from the first night and that this favorable effect is maintained for at least 3 months of CPAP use. A reduction in BP was also observed, even though BP control was not always achieved.     

QT dispersion in childhood obstructive sleep apnoea syndrome

The difference between maximal and minimal QT interval and corrected QT interval defined as QT dispersion and corrected QT dispersion may represent arrhythmogenic risks. This study sought to evaluate QT dispersion and corrected QT dispersion in childhood obstructive sleep apnoea syndrome. Forty-four children (34 male) with obstructive sleep apnoea syndrome, aged 6.2 plus or minus 3.5 years along with 38 healthy children (25 male), 6.6 plus or minus 2.1 years underwent electrocardiography to measure QT and RR intervals. Means QT dispersion and corrected QT dispersion were significantly higher in obstructive sleep apnoea syndrome than controls, 52 plus or minus 27 compared to 40 plus or minus 14 milliseconds (p equal to 0.014), and 71 plus or minus 29 compared to 57 plus or minus 19 milliseconds (p equal to 0.010), respectively. Interestingly, QT dispersion and corrected QT dispersion in obstructive sleep apnoea syndrome with obesity, 57 plus or minus 30 and 73 plus or minus 31 milliseconds, were significantly higher than in control, 40 plus or minus 14 and 57 plus or minus 19 milliseconds (p equal to 0.009 and 0.043, respectively). However, QT dispersion and corrected QT dispersion in obstructive sleep apnoea syndrome without obesity, 43 plus or minus 20 and 68 plus or minus 26 milliseconds, were not significantly different. In conclusion, QT dispersion and corrected QT dispersion were significantly increased only in childhood obstructive sleep apnoea syndrome with obesity. Obesity may be the factor affecting the increased QT dispersion and corrected QT dispersion.     

Treatment of obstructive sleep apnea reduces arterial stiffness

Purpose  

A close relationship between obstructive sleep apnea (OSA) and atherosclerosis has been reported, but it is still discussed controversially whether OSA affects vascular function and structure independently. Therefore, we prospectively investigated the independent impact of OSA and its treatment on arterial stiffness.     

Progression of obstructive sleep apnoea syndrome in Japanese patients

Sleep and Breathing - The aggravation of obstructive sleep apnoea syndrome (OSAS) is reportedly associated with weight gain. The present study investigated the factors associated with worsening of...     

The genetics of obstructive sleep apnoea

Obstructive sleep apnoea (OSA) is a common chronic disease and is associated with high social and economic costs. OSA is heritable, and there is evidence of both direct genetic contributions to OSA susceptibility and indirect contributions via ‘intermediate’ phenotypes such as obesity, craniofacial structure, neurological control of upper airway muscles and of sleep and circadian rhythm. Investigation of the genetics of OSA is an important research area and may lead to improved understanding of disease aetiology, pathogenesis, adverse health consequences and new preventive strategies and treatments. Genetic studies of OSA have lagged behind other chronic diseases; however recent gene discovery efforts have been successful in finding genetic loci contributing to OSA‐associated intermediate phenotypes. Nevertheless, many of the seminal questions relating to the genetic epidemiology of OSA and associated factors remain unanswered. This paper reviews the current state of knowledge of the genetics of OSA, with a focus on genomic approaches to understanding sleep apnoea.     

Structural and functional arterial properties in patients with obstructive sleep apnoea syndrome and cardiovascular comorbidities

The increased severity of obstructive sleep apnoea syndrome (OSAS) is associated with a parallel increase in the incidence of cardiovascular events. Whether the increased severity of OSAS is in fact associated with impaired arterial properties has never been thoroughly studied. In patients with OSAS who carry a high burden of cardiovascular risk factors, we investigated whether the severity of OSAS is associated with deterioration in the arterial properties, independent of classical cardiovascular risk factors. In 74 consecutive patients with OSAS, we non-invasively assessed, by means of tonometry and high-resolution ultrasound: carotid intima-media thickness (IMT), carotid diameter and plaques, carotid-femoral pulse wave velocity (PWV), central augmentation index (AI) and central blood pressures. The respiratory disturbance index was an independent predictor of IMT and PWV but not of carotid plaques, carotid diameter, AI or central blood pressures. Several parameters of nocturnal hypoxaemia were independently correlated with carotid IMT and PWV. In conclusion, arterial stiffening and thickening are modulated by the severity of OSAS, independently from age and cardiovascular risk factors.     

Dysfunctional breathing treated with continuous positive airway pressure in newly diagnosed obstructive sleep apnoea: a prospective cohort study

A prospective cohort study investigating patients with obstructive sleep apnoea (OSA) was conducted to determine the prevalence of dysfunctional breathing and if continuous positive airway pressure (CPAP) therapy improves associated symptoms. Almost half of newly diagnosed patients with OSA had dysfunctional breathing and CPAP was not an effective treatment. Dysfunctional breathing is common in patients with OSA.     

Visceral fat accumulation as an important risk factor for obstructive sleep apnoea syndrome in obese subjects

Objectives. It is well known that obstructive sleep apnoea (OSA) is frequently associated with obesity. In the current study, we investigated the correlation between abdominal visceral fat accumulation and the presence of OSA in obese subjects.
Subjects. A consecutive series of 37 patients (17 men and 20 women) with primary obesity who were admitted to the Second Department of Internal Medicine, Osaka University Hospital, were investigated. Patients with OSA were designated as those whose apnoea index (number of apnoea h⁻¹ of sleep) was more than 5.
Main outcome measures. The distribution of body fat was determined using computed tomographic sections. The upper airway dimensions were evaluated with indices obtained by cephalometry in both inspiratory and expiratory phases.
Results. Visceral adipose tissue (AT) area which was measured at the level of the umbilicus, and its ratio to total AT area were both significantly greater in OSA patients as compared with those in non-OSA patients. All subjects whose visceral AT area measured more than 220 cm² manifested OSA. These two parameters also closely correlated with an increase in apnoea index. A multiple linear regression analysis revealed that the visceral AT area significantly correlated to apnoea index when age, AT mass and lean body mass were taken into account. The fluctuations of the upper airway were significantly greater in the large visceral fat group than in the small visceral fat group.
Conclusions. These results suggest that visceral fat accumulation is an important risk indicator for OSA in obese subjects.     

Platelet function in patients with obstructive sleep apnoea syndrome.

Patients with obstructive sleep apnoea syndrome (OSAS) are subject to an increased cardiovascular morbidity including myocardial infarction and stroke. Platelets play an important role in the pathogenesis and triggering of acute cardiovascular syndromes. So far, the influence of OSAS on platelet function is not fully understood. Platelet aggregability to epinephrine, collagen, arachidonic acid, and adenosine diphosphate in vitro was measured in 17 consecutive male patients (53.0+/-2.1 yrs) with polysomnographically verified OSAS and compared with that of 15 male controls (50.1+/-3.6 yrs) at 20:00 h, 24:00 h, and 06:00 h. In addition, the long-term effects of continuous positive airway pressure (CPAP) therapy on platelet aggregability was assessed after 6 months. Platelet aggregation in vitro induced by epinephrine showed a slight increase overnight in the untreated OSAS patients (NS) whereas it decreased slightly (NS) in the controls and in the treated OSAS patients. Pretherapeutic platelet aggregability was significantly lowered by CPAP therapy both at 24:00 h (64.0+/-6.5 versus 55.3+/-6.7%, p<0.05) and at 06:00 h (64.1+/-6.5 versus 45.8+/-7.6%; p=0.01). Platelet aggregability during sleep in the controls resembled that found in patients with OSAS during CPAP therapy. The results suggest that obstructive sleep apnoea syndrome contributes, at least in part, to platelet dysfunction and that long-term continuous positive airway pressure treatment may reduce platelet aggregability.     

The effect of sibutramine-assisted weight loss in men with obstructive sleep apnoea

OBJECTIVE: Obstructive sleep apnoea (OSA) occurs frequently in obese patients and may be reversible with weight loss. Obstructive sleep apnoea and obesity are both independent risk factors for hypertension and increased sympathetic activity. Sibutramine has been increasingly used in the management of obesity, but is relatively contraindicated in patients with hypertension. No studies have investigated the effect of sibutramine on OSA, blood pressure and heart rate. We aimed to assess the changes in OSA and cardiovascular parameters in obese men with OSA enrolled in a sibutramine-assisted weight loss programme (SIB-WL). DESIGN: Open uncontrolled cohort study of obese male subjects with OSA in an SIB-WL. SUBJECTS: Eighty-seven obese (body mass index =34.2+/-2.8 kg/m(2)) middle-aged (46.3+/-9.3 years) male subjects with symptomatic OSA (Epworth score 13.4+/-3.6; respiratory disturbance index (RDI) 46.0+/-23.1 events/h) completed the study. RESULTS: At 6 months, there was significant weight loss (8.3+/-4.7 kg, P<0.0001), as well as a reduction in waist and neck circumference and sagittal height (all P<0.0001). These changes were accompanied by a reduction in OSA severity (RDI fell by 16.3+/-19.4 events/h and Epworth score by 4.5+/-4.6), both P<0.0001). There was no significant change to systolic (P=0.07) or diastolic blood pressure (P=0.87); however, there was a mild rise in resting heart rate (P<0.0001). CONCLUSION: Moderate (approximately 10%) weight loss with SIB-WL results in improvement in OSA severity without increase in blood pressure in closely monitored OSA subjects.     

Skeletal muscle changes in patients with obstructive sleep apnoea syndrome

Previous studies have shown that chronic hypoxia leads to changes in skeletal muscle structure (fibre size and type) and activities of several bioenergetic enzymes. Whether this occurs also in conditions characterised by intermittent hypoxia, such as the obstructive sleep apnoea syndrome (OSAS), is unknown. To explore this possibility, we obtained a needle biopsy of the quadriceps femoris in 12 consecutive stable outpatients with severe OSAS (52 +/- 9 year, apnoea-hypopnoea index 70 +/- 14 h(-1)) (x +/- SD) and in six healthy volunteers (49 +/- 8 year), where we quantified fibre type, size and protein content, as well as phosphofructo-kinase (PFK) and cytochrome oxidase (CytOx) activities. We found that fibre-type distribution was similar in patients and controls. In contrast, the diameter of type II fibres (74 +/- 10 microm vs. 56 +/- 11 microm, P < 0.05) and protein content (100 +/- 14 vs. 88 +/- 8 microg/mg) was higher in patients with OSAS. Likewise, we observed upregulation of CytOx (0.93 +/- 0.38 vs. 0.40 +/- 0.22 microkat/mg protein, P < 0.01) and PFK activities (5.35 +/- 4.8 vs. 1.3 +/- 1.3 microkat/ mg protein, P < 0.05) in patients with OSAS. These results show that, paralleling which occurs in conditions characterised by continuous hypoxia, patients with OSAS (and intermittent hypoxia) also show structural and bioenergetic changes in their skeletal muscle.     

高血压病患者动脉硬化指数增高的相关因素分析

目的观察动脉硬化指数(ASI)增高的高血压病患者,探讨其临床一般情况、血液生化指标等特点,分析临床意义。方法随机检测156例高血压病患者的动脉硬化指数、血压、脉压,并检测患者的血尿酸、血糖、血脂、肌酐、尿素氮等血液生化指标。按照患者的ASI分为两组。ASI正常组:127例,ASI值在0~70之间;ASI增高组:29例,ASI值为71或以上。结果(1)ASI增高组患者的年龄、病史、收缩压和脉压显著高于ASI正常组,其舒张压显著低于ASI正常组(均P<0.01)。(2)ASI增高组患者的血尿酸(P<0.01),尿素氮(P<0.05)水平也显著增高。结论年龄大、病史时间长、收缩压升高、舒张压降低、脉压增大、血尿酸和尿素氮水平升高均可能与ASI异常增高相关联。