Plasma homocysteine in obstructive sleep apnoea.

AIMS: Whether increased homocysteine is one mechanism linking obstructive sleep apnoea (OSA) to cardiovascular abnormalities is unclear. We hypothesised that plasma homocysteine would be higher in OSA patients than in control subjects, would increase further during sleep, and decrease after treatment with continuous positive airway pressure (CPAP). METHODS AND RESULTS: For study A, homocysteine was measured in 22 OSA patients and 20 controls first before sleep, then after 5 h of untreated OSA, and then in the morning after CPAP treatment. Homocysteine was similar in the OSA and control subjects at all three time points, and declined overnight in both groups (P=0.0017, P=0.036, respectively). To further assess this diurnal variation, we studied plasma homocysteine under a full-night protocol in 10 OSA patients and 12 controls (study B). Homocysteine was measured before sleep, in the morning after sleep, and at noon. Results in both OSA and control groups showed an overnight decline in homocysteine which was reversed by noon (repeated measures ANOVA: OSA, P=0.04; controls, P=0.02). Study C showed that disturbed sleep did not affect homocysteine levels in normal subjects. CONCLUSION: There is a significant diurnal variation in plasma homocysteine, so that homocysteine is lower in the morning after waking. Neither OSA nor disturbed sleep elicit acute or chronic changes in homocysteine.     

Baroreflex control of heart rate during sleep in severe obstructive sleep apnoea: effects of acute CPAP.

Baroreflex control of heart rate during sleep (baroreflex sensitivity; BRS) has been shown to be depressed in obstructive sleep apnoea (OSA), and improved after treatment with continuous positive airway pressure (CPAP). Whether CPAP also acutely affects BRS during sleep in uncomplicated severe OSA is still debatable. Blood pressure was monitored during nocturnal polysomnography in 18 patients at baseline and during first-time CPAP application. Spontaneous BRS was analysed by the sequence method, and estimated as the mean sequence slope. CPAP did not acutely affect mean blood pressure or heart rate but decreased cardiovascular variability during sleep. Mean BRS increased slightly during CPAP application (from 6.5+/-2.4 to 7.5+/-2.9 ms x mmHg(-1)), mostly in response to decreasing blood pressure. The change in BRS did not correlate with changes in arterial oxygen saturation or apnoea/hypopnoea index. The small change in baroreflex control of heart rate during sleep at first application of continuous positive airway pressure in severe obstructive sleep apnoea was unrelated to the acute resolution of nocturnal hypoxaemia, and might reflect autonomic adjustments to positive intrathoracic pressure, and/or improved sleep architecture. The small increase in baroreflex control of heart rate during sleep may be of clinical relevance as it was accompanied by reduced cardiovascular variability, which is acknowledged as an independent cardiovascular risk factor.     

The effect of one night of continuous positive airway pressure therapy on oxidative stress and antioxidant defense in hypertensive patients with severe obstructive sleep apnea

Purpose  

The purpose of this study was to examine the effects of one night of continuous positive airway pressure (CPAP) therapy on oxidative stress (lipid peroxidation) levels and the antioxidant activities of superoxide dismutase (SOD) in hypertensive patients with severe obstructive sleep apnea (OSA).     

Endothelin-1 plasma levels are not elevated in patients with obstructive sleep apnoea.

Endothelin-1 (ET-1), a potent vasoconstrictor, is released mainly by vascular endothelial cells under the influence of hypoxia and other stimuli. ET-1 is related to endothelial dysfunction, as well as arterial and pulmonary hypertension, all of which are thought to be associated with obstructive sleep apnoea (OSA). This study evaluated venous plasma concentrations of ET-1 and noradrenaline and 24-h systemic blood pressure in 29 patients with OSA (age=56.9+/-1.6 yrs; body mass index=29.5+/-0.7 kg x m2 (mean+/-SEM)). Blood samples were taken in the morning, evening and during sleep. In the same way, the patients were assessed during a night of continuous positive airway pressure (CPAP) and after 13.9+/-1.4 months while still on CPAP. ET-1 levels were compared to those of control subjects, who were selected from in- and outpatients and were matched to patients for age, sex, presence of arterial hypertension and coronary artery disease. ET-1 plasma levels were not elevated in the patients compared to the controls (41.6+/-2.2 and 44.9+/-1.3 pg x mL(-1), respectively, p=0.20). The ET-1 concentration did not change significantly, neither during sleep nor in the first night on CPAP therapy, nor under long-term treatment with CPAP. ET-1 neither correlated to the severity of OSA nor to that of systemic hypertension. The results suggest that endothelin-1 does not play a crucial role in the pathophysiology of obstructive sleep apnoea.     

Atrial overdrive pacing compared to CPAP in patients with obstructive sleep apnoea syndrome.

AIMS: Obstructive sleep apnoea (OSA) is associated with oxygen desaturation, blood pressure increase, and neurohumoral activation, resulting in possible detrimental effects on the cardiovascular system. Continuous positive airway pressure (CPAP) is the therapy of choice for OSA. In a recent study, nocturnal atrial overdrive pacing (pacing) reduced the severity of sleep apnoea in pacemaker patients. We compared the effects of CPAP with those of pacing in patients with OSA but without pacemaker indication or clinical signs of heart failure. METHODS AND RESULTS: Ten patients with OSA on CPAP therapy were studied for three nights by polysomnography. During the nights that followed a night without any treatment (baseline), the patients were treated with CPAP or pacing in a random order. Pacing was performed with a temporary pacing lead. The pacing frequency was 15 b.p.m. higher than the baseline heart rate. The apnoea-hypopnoea index was 41.0 h(-1) (12.0-66.6) at baseline and was significantly lower during CPAP [2.2 h(-1) (0.3-12.4)] compared with pacing [39.1 h(-1) (8.2-78.5)]. Furthermore, duration and quality of sleep were significantly improved during CPAP when compared with pacing. CONCLUSION: Nocturnal atrial overdrive pacing is no alternative therapeutic strategy to CPAP for the treatment of OSA in patients without clinical signs of heart failure and without conventional indication for anti-bradycardia pacing.     

Abnormal lipid peroxidation in patients with sleep apnoea.

The prevalence of cardiovascular diseases is increased in patients with the obstructive sleep apnoea syndrome (OSAS). The fall and rise of arterial oxygenation that follows each apnoea may increase lipid peroxidation and contributes to explaining this association. In the present study, the authors determined lipid peroxidation in patients with OSAS and the effect of treatment with continuous positive airway pressure (CPAP). Fourteen male patients with severe OSAS (59+/-5 apnoea x h(-1)) (+/-SEM) and 13 healthy nonsmoking, male volunteers of similar age were studied. Patients were studied at diagnosis and after treatment with CPAP for more than 1 yr (>4 h x night(-1)). A venous blood sample was obtained early in the morning after fasting all night. In patients with OSAS, a sample before and during sleep was also obtained. Low density lipoprotein (LDL) particles were isolated by sequential ultracentrifugation. Their level of oxidation was determined by the thiobarbituric acid assay (TBARs), and their susceptibility to oxidation by the lag phase measurement. Patients with OSAS showed higher TBARs (28.1+/-2.8 versus 20.0+/-1.8 nmol x malondialdehyde x mgLDL protein(-1), p=0.02) and shorter lag phase values (83.8+/-3.4 versus 99.7+/-3.4 min, p=0.005) than controls. These differences were not due to the smoking status of the patient. Likewise, these values did not change significantly throughout the night yet, the lag phase value was significantly improved by treatment with CPAP (124.9+/-8.5 min; p<0.001). These results indicate that obstructive sleep apnoea syndrome is associated with abnormal lipid peroxidation and that this is improved by chronic use of Continuous positive airway pressure. These results can contribute towards explaining the high prevalence of cardiovascular diseases seen in Obstructive sleep apnoea syndrome.     

Effect of CPAP therapy on endothelial function in obstructive sleep apnoea: A systematic review and meta‐analysis

Obstructive sleep apnoea (OSA) is a prevalent sleep‐related breathing disorder associated with adverse cardiovascular outcome. Endothelial dysfunction is one of the proposed mechanistic links between OSA and the increased cardiovascular risk. Treatment with continuous positive airway pressure (CPAP) may reverse this detrimental pathophysiological consequence of OSA. Most studies on the effect of CPAP on endothelial function in OSA are limited by their low sample size. The objective of this systematic review was to assess the effect CPAP therapy on endothelial function in patients with OSA. We conducted a systematic review and meta‐analysis searching literature databases up to August 2013 for randomized controlled trials (RCTs) on the effect of CPAP on endothelial function in OSA, assessed by flow‐mediated dilatation (FMD) and other validated techniques. The primary outcome for the meta‐analysis (DerSimonian/Laird random‐effects method) was the treatment effect on FMD. Eight RCTs comparing the effects of therapeutic CPAP versus subtherapeutic CPAP (or no intervention) on endothelial function involving 245 OSA patients were included in the systematic review. The studies are consistent in effect direction, showing an improvement of endothelial function by CPAP. Four RCTs involving 150 patients could be used for the meta‐analysis. Compared to the control group, CPAP therapy (range 2–24 weeks) significantly increased absolute % FMD by 3.87% (95% confidence interval: 1.93–5.80, P < 0.001). In patients with OSA, CPAP therapy improves endothelial function significantly and to a clinically important extent.     

Effect of Continuous Positive Airway Pressure on Glucose and Lipid Profiles in Patients With Obstructive Sleep Apnoea: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background and aimContinuous Positive Airway Pressure (CPAP) is the most effective therapy for symptomatic obstructive sleep apnoea (OSA). However, uncertainty remains about the effectiveness of CPAP in improving OSA-related metabolic dysregulation. This meta-analysis of randomized controlled trials (RCTs) aimed to investigate whether CPAP, compared to other control treatments, could improve glucose or lipid metabolism in OSA patients.MethodsRelevant articles were searched in three different databases (MEDLINE, EMBASE and Web of Science) from inception to 6th Feb 2022 through specific search terms and selection criteria.ResultsFrom a total of 5553 articles, 31 RCTs were included. CPAP modestly improved insulin sensitivity as determined by mean fasting plasma insulin and Homeostasis Model Assessment of Insulin Resistance reduction of 1.33 mU/L and 0.287, respectively. In subgroup analyses pre-diabetic/type 2 diabetic patients as well as those with sleepy OSA showed a greater response to CPAP. Regarding lipid metabolism, CPAP was associated with a mean total cholesterol reduction of 0.064 mmol/L. In subgroup analyses, the benefit was higher in patients that showed more severe OSA and oxygen desaturations at the baseline sleep study as well as in younger and obese subjects. Neither glycated haemoglobin nor triglycerides, HDL- and LDL-cholesterol were reduced by CPAP.ConclusionCPAP treatment may improve insulin sensitivity and total cholesterol levels in OSA patients but with low effect size. Our results suggest that CPAP does not substantially improve metabolic derangements in an unselected OSA population, but the effect may be higher in specific subgroups of OSA patients.     

Association between lipid peroxidation and inflammation in obstructive sleep apnoea.

In the present study, the authors examined the relationship between lipid peroxidation and inflammation in patients with obstructive sleep apnoea (OSA). A total of 40 obese patients with OSA were studied, along with 18 obese and 12 lean subjects without OSA. Overnight excretion of 8-isoprostane in urine and serum levels of high-sensitivity C-reactive protein (hsCRP) were measured. In addition, the effects of 3 months' treatment with nasal continuous positive airway pressure (nCPAP) were studied in 20 obese patients with moderate-to-severe OSA. Overnight urinary excretion of 8-isoprostane and serum levels of hsCRP were significantly higher in patients with moderate-to-severe OSA compared with patients with mild OSA and obese or lean subjects without OSA. Overnight urinary excretion of 8-isoprostane significantly correlated with apnoea-hypopnoea index, duration of hypoxia during sleep, body mass index, and serum levels of hsCRP in patients with OSA. The severity of OSA was an independent factor predicting the urinary excretion of 8-isoprostane. nCPAP significantly decreased urinary excretion of 8-isoprostane and serum levels of hsCRP. In conclusion, these results suggest that both obstructive sleep apnoea severity and obesity can independently contribute to elevations in urinary excretion of 8-isoprostane. Therefore, obstructive sleep apnoea may increase the risks of cardiovascular morbidity in obese patients.     

Obstructive Sleep Apnea as a Cardiovascular Risk Factor—Beyond CPAP

Patients with obstructive sleep apnea (OSA) experience repetitive partial or complete airway collapse during sleep resulting in nocturnal hypoxia-normoxia cycling, and are at increased cardiovascular risk. The number of apneas and hypopneas indexed per hour of sleep (apnea-hypopnea index) along with the associated intermittent hypoxia predict the increased cardiovascular risk; thus, their attenuation or prevention are objectives of OSA therapy. Continuous positive airway pressure (CPAP) is the gold standard treatment for OSA and, when effective, mitigates the apnea-hypopnea index and hypoxemia. As such, it is reasonable to expect CPAP would decrease cardiovascular risk. However, 3 recent randomized clinical trials of CPAP vs usual care did not show any significant effects of CPAP in attenuating incident cardiovascular events in patients with OSA. In this review, we discuss these studies in addition to potential complementary therapeutic options to CPAP (eg, neurostimulation) and conclude with suggested therapeutic targets for future interventional studies (eg, the autonomic nervous system). Although these areas of research are exciting, they have yet to be tested to any similar degree of rigour as CPAP.     

Obstructive sleep apnea and cardiovascular disease - time to act!

Sleep related breathing disorders are common and their potential to disrupt sleep leading to daytime fatigue and hypersomnolence is widely acknowledged. In the future, obstructive sleep apnoea (OSA) may become even more important because obesity as a main risk factor is increasingly prevalent. Apart from disturbing sleep, OSA has also been recognised as a risk factor for hypertension, acute cardiovascular events and metabolic disturbance such as insulin resistance. Several randomised controlled trials demonstrated a positive effect of nasal continuous positive airway pressure (CPAP) treatment on arterial blood pressure, leading the "Joint National Council on High Blood Pressure" to list obstructive sleep apnoea as the first identifiable cause of arterial hypertension. Recently, a growing body of evidence demonstrated also a risk reduction of fatal and non-fatal cardiovascular events by treatment of obstructive sleep apnoea. A beneficial effect of treatment of OSA was also shown for patients with heart failure, or heart rhythm disturbance. Obstructive sleep apnoea may no longer be seen as a cause for daytime sleepiness and impaired quality of life only, but also as an independent risk factor, at least for the occurrence of hypertension but probably for any cardiovascular and cerebrovascular disease. While prospective controlled trials to document a reduction of cardiovascular morbidity and mortality are awaited, therapeutic nihilism seems no longer appropriate. With effective treatment available, subgroups that may profit best remain to be identified.     

Lipid peroxides,superoxide dismutase and circulating IL-8 and GCP-2 in patients with severe obstructive sleep apnea: a pilot study

Obstructive sleep apnea (OSA) is associated with cardiovascular morbidity and mortality and many other physiological and immunological disorders. An increase in hypoxia due to OSA may cause generation of reactive oxygen species (ROS). ROS are toxic to biomembranes and may lead to peroxidation of lipids. An increase in systemic biomarkers of inflammation and oxidative stress has been found in patients with OSA. The first aim of this study was to test the hypothesis that OSA is linked to increased oxidative stress (lipid peroxidation) and decreased antioxidant defense [superoxide dismutase (SOD)]. The second aim was to measure the serum levels of neutrophil chemokines [interleukin-8 (IL-8)], and granulocyte chemotactic protein-2 (GCP-2) in OSA patients. Twenty five patients with severe OSA and 17 healthy subjects were recruited. IL-8 and GCP-2 were measured in the serum by a specific enzyme immunoassay kit. Oxidative stress level was quantitated by measurement of thiobarbituric acid reactive substances. SOD enzymatic activity was measured by purely chemical system based on NAD(P)H oxidation. Mean SOD and lipid peroxidation concentrations of patients were not significantly different from those of control subjects (0.29±0.015 vs 0.31±0.01 U/ml and 4.64±0.57 vs 4.62±0.54 mmol/ml, respectively). Higher concentrations of IL-8 and GCP-2 were found in OSA patients (198.8±4.76 vs 180.83±3.38 and 383.34±46.19 vs 218±13.16 pg/ml, respectively, p<0.005). The present study does not support the hypothesis that OSA is linked to increased oxidative stress and decreased antioxidant defense. On the other hand, it suggests that systemic inflammation characterizes OSA patients.     

Continuous positive airway pressure does not reduce blood pressure in nonsleepy hypertensive OSA patients.

Obstructive sleep apnoea (OSA) is associated with high cardiovascular morbidity and mortality. Several randomised controlled trials have shown that continuous positive airway pressure (CPAP) treatment of OSA reduces blood pressure (BP). This randomised, sham-placebo controlled crossover trial assesses whether CPAP produces a similar clinically significant fall in BP in hypertensive OSA patients, but without hypersomnolence. Thirty-five, nonsleepy, hypertensive patients with OSA were treated with CPAP for 1 month, randomised first to either therapeutic or sham-placebo (subtherapeutic CPAP, about 1 cmH(2)O pressure). The second months' alternative treatment followed a 2-week washout period. BP was measured over 24 h, before and at the end of the two treatment periods: mean 24-h BP was the primary outcome variable. There was no overall significant difference in mean 24-h BP: the change in mean 24-h BP on therapeutic CPAP was -2.1 mmHg (sd 8.1), and -1.1 mmHg (sd 8.1) on subtherapeutic CPAP, with a difference of 0.7 mmHg (95% confidence interval (CI) +2.9- -4.4). There was a small significant fall in Epworth Sleepiness Score, therapeutic (-1.4) versus sham (-0.3), and difference -1.2 (95% CI -2.0- -0.4), but no change in objective sleepiness. In nonhypersomnolent hypertensive patients with obstructive sleep apnoea, there is no significant fall in mean 24-h blood pressure with continuous positive airway pressure, in contrast to the fall seen in hypersomnolent patients with obstructive sleep apnoea.     

Prevalence and treatment of central sleep apnoea emerging after initiation of continuous positive airway pressure in patients with obstructive sleep apnoea without evidence of heart failure

Background  

This study aimed to assess the prevalence of complex sleep apnoea (CompSA), defined as central sleep apnoea (CSA) emerging after the initiation of continuous positive airway pressure (CPAP) therapy for obstructive sleep apnoea (OSA), in patients with normal brain natriuretic peptide (BNP) levels, along with assessing the prevalence of CSA persisting in such patients after the onset of CPAP therapy. We hypothesised that the prevalence of CompSA and persistent CSA after CPAP initiation would be low in patients with OSA and normal BNP levels.     

Restless legs syndrome: Impact on sleep‐related breathing disorders

Restless legs syndrome (RLS) is a common chronic sensory‐motor neurological disorder that remains a clinical diagnosis. Most RLS patients present with sleep complaints in the form of initiation and/or maintenance insomnia as RLS has a circadian rhythmicity. An increased number of periodic leg movements during sleep (PLMS) is a supportive criterion in the diagnosis of RLS. Abnormalities in the central dopaminergic and iron systems are involved in the physiopathology of RLS. There is a higher prevalence of RLS and PLMS in sleep‐disordered breathing patients, particularly those with obstructive sleep apnoea (OSA), the most common sleep disorder in western societies. The complex mechanisms underlying the association between OSA, RLS and PLMS remain unclear. Untreated OSA can lead to adverse cardiovascular consequences due to cardio‐metabolic dysfunction. It remains controversial whether RLS could further adversely impact the cardiovascular consequences of OSA. The PLMS do not have an additive effect on the hypersomnia experienced by some sleep‐disordered breathing patients. Continuous positive airway pressure (CPAP) therapy is the most effective therapy for OSA. The presence of PLMS during CPAP treatment could be a marker of an incomplete resolution of sleep‐disordered breathing in the form of increased upper airway resistance syndrome, despite treatment. Dopaminergic agonists are the preferred agent for the treatment of RLS, and are indicated when RLS symptoms are frequent and affect quality of life. PLMS and RLS do not seem to contribute to the residual hypersomnia that can be observed in some sleep‐disordered breathing patients despite adequate compliance and effective CPAP therapy.     

Pharmacologic approaches for the management of symptoms and cardiovascular consequences of obstructive sleep apnea in adults

Introduction

Obstructive sleep apnea (OSA) is characterized by intermittent hypoxemia, arousals from sleep, and daytime sleepiness. Accumulating evidence indicates that hypoxemia and sleep disruption contribute to the development of cardiovascular abnormalities in OSA. OSA is effectively treated with continuous positive airway pressure (CPAP) therapy that splints open the airway during sleep. Studies have shown that CPAP therapy improves daytime sleepiness and attenuates cardiovascular abnormalities in patients with OSA. However, not all patients with OSA tolerate or adhere to CPAP therapy. Even patients who regularly use CPAP therapy may have a few hours each night exposed to the negative effects of untreated OSA. As a result, complementary pharmacologic therapies that can be used with CPAP therapy have the potential to reduce symptoms and consequences of OSA.

Discussion

The wake-promoting medications modafinil and armodafinil effectively improve residual sleepiness in patients treated with CPAP therapy. Although results are equivocal so far, modafinil and armodafinil may also improve quality of life and global clinical condition in patients with OSA and residual sleepiness treated with CPAP therapy. Pharmacologic therapies also have the potential to be used with CPAP therapy to minimize cardiovascular perturbations and risk of cardiovascular disease. Preliminary studies suggest that inhibition of the enzyme xanthine oxidase and inhibition of sympathetic nervous system overactivity may have therapeutic potential to reduce cardiovascular harm in patients with OSA.

Conclusion

Future studies of pharmacologic therapies to reduce symptoms and cardiovascular consequences of OSA should be increasingly performed as our understanding of the mechanisms mediating the adverse effects of OSA continues to evolve.     

Endocrine disorders in obstructive sleep apnoea syndrome: A bidirectional relationship

Obstructive sleep apnoea (OSA) is a common disorder characterized by recurrent episodes of apnoea or hypopnea due to total or partial pharyngeal collapse and temporary upper airway obstruction during sleep. The prevalence of OSA is increasing and currently affects about 30% of men and 13% of women in Europe. Intermittent hypoxia, oxidative stress, systemic inflammation, and sleep fragmentation resulting from OSA can provoke subsequent cardiometabolic disorders. The relationships between endocrine disorders and OSA are complex and bidirectional. Indeed, several endocrine disorders are risk factors for OSA. Compared with the general population, the prevalence of OSA is increased in patients with obesity, hypothyroidism, acromegaly, Cushing syndrome, and type 1 and 2 diabetes. In some cases, treatment of the underlying endocrine disorder can improve, and occasionally cure, OSA. On the other hand, OSA can also induce endocrine disorders, particularly glucose metabolism abnormalities. Whether continuous positive airway pressure (CPAP) treatment for OSA can improve these endocrine disturbances remains unclear due to the presence of several confounding factors. In this review, we discuss the current state-of-the-art based on the review of the current medical literature for key articles focusing on the bidirectional relationship between endocrine disorders and OSA and the effects of treatment. Screening of OSA in endocrine patients is also discussed, as it remains a subject of debate.     

Increased incidence of nonfatal cardiovascular events in stroke patients with sleep apnoea: effect of CPAP treatment

Obstructive sleep apnoea (OSA) is a risk factor for stroke, but little is known about the effect of OSA and continuous positive airway pressure (CPAP) on the incidence of long-term, nonfatal cardiovascular events (CVE) in stroke patients. A prospective observational study was made in 223 patients consecutively admitted for stroke. A sleep study was performed on 166 of them. 31 had an apnoea/hypopnoea index (AHI) <10 events · h(-1); 39 had an AHI between 10 and 19 events · h(-1) and 96 had an AHI ≥ 20 events · h(-1). CPAP treatment was offered when AHI was ≥ 20 events · h(-1). Patients were followed up for 7 yrs and incident CVE data were recorded. The mean ± SD age of the subjects was 73.3 ± 11 yrs; mean AHI was 26 ± 16.7 events · h(-1). Patients with moderate-to-severe OSA who could not tolerate CPAP (AHI ≥ 20 events · h(-1); n = 68) showed an increased adjusted incidence of nonfatal CVE, especially new ischaemic strokes (hazard ratio 2.87, 95% CI 1.11-7.71; p = 0.03), compared with patients with moderate-to-severe OSA who tolerated CPAP (n = 28), patients with mild disease (AHI 10-19 events · h(-1); n = 36) and patients without OSA (AHI <10 events · h(-1); n = 31). Our results suggest that the presence of moderate-to-severe OSA is associated with an increased long-term incidence of nonfatal CVE in stroke patients and that CPAP reduces the excess of incidence seen in these patients.     

Sleep‐disordered breathing in heart failure

Sleep‐disordered breathing—comprising obstructive sleep apnoea (OSA), central sleep apnoea (CSA), or a combination of the two—is found in over half of heart failure (HF) patients and may have harmful effects on cardiac function, with swings in intrathoracic pressure (and therefore preload and afterload), blood pressure, sympathetic activity, and repetitive hypoxaemia. It is associated with reduced health‐related quality of life, higher healthcare utilization, and a poor prognosis. Whilst continuous positive airway pressure (CPAP) is the treatment of choice for patients with daytime sleepiness due to OSA, the optimal management of CSA remains uncertain. There is much circumstantial evidence that the treatment of OSA in HF patients with CPAP can improve symptoms, cardiac function, biomarkers of cardiovascular disease, and quality of life, but the quality of evidence for an improvement in mortality is weak. For systolic HF patients with CSA, the CANPAP trial did not demonstrate an overall survival or hospitalization advantage for CPAP. A minute ventilation‐targeted positive airway therapy, adaptive servoventilation (ASV), can control CSA and improves several surrogate markers of cardiovascular outcome, but in the recently published SERVE‐HF randomized trial, ASV was associated with significantly increased mortality and no improvement in HF hospitalization or quality of life. Further research is needed to clarify the therapeutic rationale for the treatment of CSA in HF. Cardiologists should have a high index of suspicion for sleep‐disordered breathing in those with HF, and work closely with sleep physicians to optimize patient management.     

Systemic levels of lipid peroxidation and its metabolic and dietary correlates in patients with nonalcoholic steatohepatitis

BACKGROUND AND AIM: Products of systemic lipid peroxidation are important in the pathogenesis of cardiovascular disease. Subjects with NASH have increased hepatic lipid peroxidation, but it is unknown if they have increased oxidative stress and lipid peroxidation systemically. Therefore, we conducted a study to measure the circulating levels of lipid peroxidation products and their metabolic and nutritional correlates in patients with NASH and controls. METHODS: Systemic lipid peroxidation was assessed by measuring the levels of oxidized LDL (ox-LDL) and thiobarbituric acid-reacting substances (TBARS) in 21 subjects with NASH and 19 controls. Correlations were made between serum lipid peroxidation and nutritional determinants of oxidative stress and defense, serum lipids, insulin resistance, transaminases, and liver histology. The short-term nutrient intake was analyzed by maintaining a 3-wk dietary diary. RESULTS: The serum levels of ox-LDL were significantly higher in NASH patients compared to controls (56 +/- 16 U/L vs 40 +/- 12 U/L, respectively, p < 0.001). Similarly, serum TBARS were significantly higher in NASH patients compared to controls (3.4 +/- 1.3 vs 1.8 +/- 0.9 nmols/ml, respectively, p= 0.0001). Insulin resistance was independently associated with ox-LDL (p= 0.01) and TBARS levels (p= 0.01). We found no differences in the intake of various macro- and micronutrients between the two groups and there was no association between nutrient intake and ox-LDL or TBARS. CONCLUSION: Subjects with NASH have significantly higher systemic levels of lipid peroxidation products and this could indicate an increased risk of cardiovascular disease. More studies are needed to evaluate this possibility.