Oxidative stress in obstructive sleep apnea

STUDY OBJECTIVES: To investigate the relationship between the severity of obstructive sleep apnea (OSA) and oxidative stress, which plays an important role in the pathogenesis of cardiovascular disease, and to elucidate the factors contributing to this relationship. DESIGN: Cross-sectional study. PARTICIPANTS: A total of 128 consecutive subjects referred to the sleep laboratory of our hospital for screening or treatment of OSA. INTERVENTIONS: Not applicable. MEASUREMENTS: The severity of sleep-disordered breathing was evaluated by polysomnography. We measured urinary excretion of 8-hydroxy-2'-deoxyguanosine (8-OHdG) as an in vivo parameter of oxidative stress. Known risk factors for oxidative stress (age, obesity, smoking, hyperlipidemia, hypertension, and diabetes mellitus) were also investigated. RESULTS: Seventy subjects had nonsevere OSA (an apnea-hypopnea index [AHI] < 30), and 58 subjects had severe OSA (AHI >or= 30). Urinary 8-OHdG excretion was significantly higher in the severe OSA group (p = 0.03). Furthermore, urinary 8-OHdG excretion was significantly correlated with parameters of sleep-disordered breathing, including AHI, the apnea index, the oxygen desaturation index (ODI), the duration of oxygen saturation < 90%, and the respiratory arousal index. However, only ODI was significantly correlated with urinary 8-OHdG excretion after adjustment for confounding factors that are considered to be related to oxidative stress. CONCLUSIONS: The severity of OSA is independently associated with oxidative stress. Among various sleep-disordered breathing parameters, ODI is most closely related to oxidative stress.     

Familial premature coronary artery disease mortality and obstructive sleep apnea

BACKGROUND: Obstructive sleep apnea (OSA) is linked to both coronary artery disease (CAD) and sudden death, but any causal role remains unclear. A family history of premature CAD and related mortality is an independent risk factor for the development of CAD. We hypothesized that OSA is associated with a family history of premature mortality from ischemic heart disease. METHODS: We prospectively studied 588 subjects who underwent polysomnography from May 2000 to June 2004. Demographics, comorbidities, family history of cardiovascular disease, and the ages and causes of death for 10 strata of family members were recorded for all subjects. We excluded those subjects with known causes of premature cardiac death, such as hypertrophic cardiomyopathy and long-QT syndrome. OSA was defined by American Academy of Sleep Medicine criteria (ie, apnea-hypopnea index >or= 5). Premature CAD mortality was defined as death due to ischemic heart disease or sudden cardiac death before 55 years of age (men) or 65 years of age (women). RESULTS: Polysomnography confirmed OSA in 316 subjects and excluded it in 202 subjects. The unadjusted odds ratio (OR) for OSA and a family history of premature CAD mortality was 2.11 (95% confidence interval [CI], 1.10 to 4.31; p = 0.031). After adjusting for each subject's sex, body mass index, and history of CAD, there was a significant and independent association between OSA and family history of premature CAD mortality (OR, 2.13; 95% CI, 1.04 to 4.66; p = 0.046). CONCLUSIONS: Regardless of their own CAD status, people with OSA are more likely than those without OSA to have a family history of premature CAD mortality.     

Obesity hypoventilation syndrome: hypoxemia during continuous positive airway pressure

BACKGROUND: Polysomnography findings between matched groups with obstructive sleep apnea (OSA) and OSA plus obesity-hypoventilation syndrome (OHS) before and after continuous positive airway pressure (CPAP), particularly in the extremely severe obese (body mass index [BMI] >or= 50 kg/m2), are unclear. DESIGN: Prospective study of subjects (BMI >or= 50 kg/m2) undergoing diagnostic polysomnography. Subjects with an apnea-hypopnea index (AHI) >or= 15/h underwent a second polysomnography with CPAP. The effect of 1 night of CPAP on sleep architecture, AHI, arousal indexes, and nocturnal oxygenation was assessed. OHS was defined as those subjects with obesity, PaCo2 > 45 mm Hg, and PaO2 < 70 mm Hg in the absence of lung disease. RESULTS: Twenty-three subjects with moderate-to-severe OSA and 23 subjects with moderate-to-severe OSA plus OHS underwent a 1-night trial of CPAP. Both groups were matched for spirometry, BMI, and AHI, but oxygen desaturation was worse in the OSA-plus-OHS group. CPAP significantly improved rapid eye movement (REM) duration (p < 0.005), AHI (p < 0.005), arousal indexes (p < 0.005), and percentage of total sleep time (TST) with oxygen saturation (SpO2) < 90% (p < 0.005) in both groups. In subjects with OSA plus OHS, 43% continued to spend > 20% of TST with SpO2 < 90%, compared to 9% of the OSA group, despite the adequate relief of upper airway obstruction. CONCLUSIONS: Extremely severe obese subjects (BMI >or= 50 kg/m2) with moderate-to-severe OSA plus OHS exhibit severe oxygen desaturation but similar severities of AHI, arousal indexes, and sleep architecture abnormalities when compared to matched subjects without OHS. CPAP significantly improves AHI, REM duration, arousal indexes, and nocturnal oxygen desaturation. Some subjects with OHS continued to have nocturnal desaturation despite the control of upper airway obstruction; other mechanisms may contribute. Further long-term studies assessing the comparative role of CPAP and bilevel ventilatory support in such subjects with OHS is warranted.     

Elevated serum aminotransferase levels in children at risk for obstructive sleep apnea

BACKGROUND: Fatty liver disease (FLD) is a highly prevalent condition in obese (Ob) children, who are at increased risk for obstructive sleep apnea (OSA). However, the contribution of OSA to FLD remains unknown. DESIGN: Prospective study. SETTING: Polysomnographic evaluation and assessment of plasma levels of insulin, glucose, and lipids, and liver function tests. PARTICIPANTS: A total of 518 consecutive snoring children 4 to 17 years of age who were being evaluated for habitual snoring and suspected OSA. RESULTS: A total of 376 children had body mass index z score of < 1.20 (non-Ob children), 3 children (<1%) had elevated serum aminotransferase (LFT) levels, and 248 had OSA (65.9%). Among the 142 overweight/Ob children, 46 had elevated LFT levels (32.4%); of these children, 42 had OSA (91.3%). In contrast, OSA was present in only 71.8% of Ob children without elevated LFT level (p < 0.01). Insulin resistance and hyperlipidemia were more likely to occur in children with FLD. Furthermore, FLD was improved after treatment of OSA in 32 of 42 Ob children (p < 0.0001). CONCLUSION: Increased liver enzyme levels are frequently found in Ob snoring children, particularly among those with OSA and/or metabolic dysfunction. Effective treatment of OSA results in improved liver function test results in the vast majority of these patients.     

Prognosis of patients with heart failure and obstructive sleep apnea treated with continuous positive airway pressure

BACKGROUND: Therapy with continuous positive airway pressure (CPAP) provides several benefits for patients with heart failure (HF) complicated by obstructive sleep apnea (OSA). However, the effect on the prognosis of such patients remains unknown. Aims: To determine whether CPAP therapy and compliance affects the prognosis of HF patients with OSA. METHODS: We classified 88 patients with HF and moderate-to-severe OSA into a CPAP-treated group (n = 65) and an untreated group (n = 23), and then those treated with CPAP were further subclassified according to CPAP therapy compliance. The frequency of death and hospitalization was analyzed using multivariate analysis. RESULTS: During a mean (+/- SD) period of 25.3 +/- 15.3 months, 44.3% of the patients died or were hospitalized. Multivariate analysis showed that the risk for death and hospitalization was increased in the untreated group (hazard ratio [HR], 2.03; 95% confidence interval [CI], 1.07 to 3.68; p = 0.030) and in less compliant CPAP-treated patients (HR, 4.02; 95% CI, 1.33 to 12.2; p = 0.014). CONCLUSION: Therapy with CPAP significantly reduced the risk of death and hospitalization among patients with HF and OSA. However, reduced compliance with CPAP therapy was significantly associated with an increased risk of death and hospitalization.     

Obstructive sleep apnea syndrome is associated with some components of metabolic syndrome

BACKGROUND: Obesity, hypertension, dyslipidemia, and hyperglycemia are prevalent in obstructive sleep apnea syndrome (OSAS). Metabolic syndrome, however, is defined by visceral fat obesity plus at least two of these factors. However, whether OSAS contributes to the development of metabolic syndrome has not been defined. We investigated whether the components of metabolic syndrome were associated with OSAS in nonobese patients. METHODS: We investigated the occurrence of hypertension, dyslipidemia, and hyperglycemia in 42 men with OSAS and 52 men without OSAS matched for age, body mass index (BMI), and visceral fat accumulation. RESULTS: Although serum levels of triglycerides, high-density lipoprotein cholesterol, and diastolic BP did not differ significantly between the two groups, fasting blood glucose (111 +/- 6 mg/dL vs 93 +/- 3 mg/dL) [mean +/- SE] and the percentage of hypertensive patients (45% vs 15%) were significantly higher in the group with OSAS. In addition, a significantly higher percentage of patients with OSAS (19% vs 4%) had at least two of the following: hypertension, hyperglycemia, and dyslipidemia. Logistic regression analysis showed that the apnea-hypopnea index value was the predictor of number of metabolic syndrome parameters such as hypertension, hyperglycemia, and dyslipidemia, while BMI and lowest arterial oxygen saturation during sleep did not. CONCLUSION: Independent of visceral fat obesity, OSAS was associated with hypertension, dyslipidemia, and hyperglycemia. It is possible that OSAS may predispose even nonobese patients to the development of metabolic syndrome.     

An evaluation of a titration strategy for prescription of oral appliances for obstructive sleep apnea

BACKGROUND: Oral appliances (OAs) are first-line therapy for mild-to-moderate obstructive sleep apnea (OSA) and are being used with increasing frequency. Additionally, best practice of OA titration is unknown. We describe the experience of patients treated with an OA, identify factors that predict treatment success with an OA, and offer a protocol for OA titration. METHODS: We retrospectively studied patients seen in a dental sleep clinic between 2002 and 2006. Patients selected for OA treatment underwent baseline polysomnography, were individually fit with an OA, and were instructed to titrate it at home until symptom resolution or discomfort. During follow-up polysomnography, additional titration was performed as needed. Primary outcome was successful treatment, defined as apnea-hypopnea index (AHI) <10 events per hour and AHI decrease at least 50% from baseline. Logistic regression models were created to identify associations between patient characteristics and successful treatment. Overall differences in AHI at baseline, after home titration, and after final titration were compared using Kruskal-Wallis test, and post hoc comparisons were performed with sign tests, with Bonferroni corrections. RESULTS: Of 57 subjects treated with an OA, 37 subjects (64.9%) were successfully treated with OA therapy. Of the 49 subjects for whom data were available for AHI after home titration, 27 subjects (55%) achieved successful treatment of OSA by self-titration, without need for further titration during follow-up polysomnography. CONCLUSIONS: A majority of subjects, regardless of OSA severity, are successfully treated with an OA. Men and younger patients were found to be the best responders. The titration protocol for an OA offers a beneficial initial step in the treatment of OSA.     

Independent association between obstructive sleep apnea and subclinical coronary artery disease

BACKGROUND: Obstructive sleep apnea (OSA) is associated with coronary risk factors, but it is unknown if OSA is associated with development of coronary disease. We evaluated the association between OSA and the presence of subclinical coronary disease assessed by coronary artery calcification (CAC). METHODS: Consecutive patients with no history of coronary disease who underwent electron-beam CT within 3 years of polysomnography between March 1991 and December 2003 were included. OSA was defined by an apnea-hypopnea index (AHI) > or = 5 events per hour, and patients were grouped by quartiles of AHI severity. Logistic regression modeled the association between OSA severity and presence of CAC. RESULTS: There were 202 patients (70% male; median age, 50 years; mean body mass index, 32 kg/m(2); 8% diabetic; 9% current smokers; 60% hypercholesterolemic; and 47% hypertensive). OSA was present in 76%. CAC was present in 67% of OSA patients and 31% of non-OSA patients (p < 0.001). Median CAC scores (Agatston units) were 9 in OSA patients and 0 in non-OSA patients (p < 0.001). Median CAC score was higher as OSA severity increased (p for trend by AHI quartile < 0.001). With multivariate adjustment, the odds ratio for CAC increased with OSA severity. Using the first AHI quartile as reference, the adjusted odds ratios for the second, third, and fourth quartiles were 2.1 (p = 0.12), 2.4 (p = 0.06), and 3.3 (p = 0.03), respectively. CONCLUSIONS: In patients without clinical coronary disease, the presence and severity of OSA is independently associated with the presence and extent of CAC. OSA identifies patients at risk for coronary disease and may represent a highly prevalent modifiable risk factor.     

Fixed and autoadjusting continuous positive airway pressure treatments are not similar in reducing cardiovascular risk factors in patients with obstructive sleep apnea

BACKGROUND: A strong association between obstructive sleep apnea (OSA) and the risk for cardiovascular and cerebrovascular diseases has been reported. Continuous positive airway pressure (CPAP) is the first-line therapy for OSA, able not only to reduce daytime sleepiness but also to improve cardiovascular and metabolic outcomes. Autoadjusting CPAP (APAP), an alternative treatment to CPAP, can reduce OSA symptoms while increasing long-term CPAP compliance without the high costs of CPAP titration. However, no data are available on the effects of APAP on cardiovascular risk factors METHODS: We performed standard full polysomnography; obtained plasma levels of glucose, insulin, and C-reactive protein (CRP); and measured systolic BP (SBP) and diastolic BP (DBP) in 31 patients with newly diagnosed, severe OSA. After standard CPAP titration, all subjects were randomized to CPAP or APAP treatment. Measurements were obtained at baseline and after 3 months of treatment. RESULTS: The two groups were similar in terms of age, sex, body mass index (BMI), and severity of OSA. SBP, DBP, heart rate (HR), homeostasis model assessment index (HOMA-IR), and CRP were similar in the two groups. After 3 months of treatment, BMI, HR, and compliance to therapy were also comparable. OSA indexes were significantly reduced in both groups. Significant reductions in SBP, DBP, and HOMA-IR were observed in the CPAP group but not in the APAP group, while CRP plasma levels were similarly reduced. CONCLUSIONS: Our results suggest that CPAP and APAP, despite significant effects on OSA indexes and symptoms, do not improve cardiovascular risk factors in the same fashion.     

Timing of nocturnal ventricular ectopy in heart failure patients with sleep apnea

BACKGROUND: Ventricular ectopy is frequent in heart failure (HF) patients with sleep apnea. A previous report indicated that in HF patients, ventricular premature beats (VPB) occurred more frequently during episodes of recurrent central sleep apnea (CSA) than during normal breathing, and their frequency was greater during hyperpnea than during apnea. We hypothesized that, because respiratory stimuli that might provoke ventricular ectopy are stronger during obstructive apneas than during central apneas, in contrast to CSA, VPBs would be more frequent during apnea than hyperpnea in HF patients with obstructive sleep apnea (OSA). METHODS: HF patients in sinus rhythm who have OSA or CSA (apnea-hypopnea index, > or = 15 events per hour) and with > 30 VPBs per hour were matched for severity of cardiac dysfunction and sleep apnea. The frequency of VPBs was then assessed during stage 2 sleep during the apneic and the hyperpneic phases of recurrent obstructive or central apneas. RESULTS: VPBs occurred more frequently during the apneic phase than during the hyperpneic phase in patients with OSA. In contrast, VPBs occurred more frequently during the hyperpneic phase than the apneic phase in patients with CSA. There was no difference in the degree of apnea-related oxygen desaturation between central and obstructive apneas. CONCLUSIONS: In patients with HF, nocturnal ventricular ectopy oscillates in time with oscillations in ventilation, with VPBs occurring predominantly during apneas in patients with OSA, but during hyperpneas in patients with CSA. This difference in VPB timing between OSA and CSA may be attributable to the differences in timing of arrhythmic stresses in these patients.     

A case-control study of obstructive sleep apnea-hypopnea syndrome in obese and nonobese chinese children

BACKGROUND: Obesity is a risk factor for obstructive sleep apnea-hypopnea syndrome (OSAHS) in adults. However, the prevalence of OSAHS in children is not clear, and the relationship between obesity and OSAHS remains controversial. METHODS: Obese children were recruited from the endocrinology, respiratory, and ear, nose, and throat clinics. Weight-matched, age-matched, and sex-matched children were recruited as control subjects. Standard questionnaires were administered, and a standardized physical examination was carried out. Lateral neck roentgenography, sleep polysomnography, full blood count, and arterial blood gas analysis were also performed. Children with body mass index z-scores of > 1.96 were considered to be obese. An adenoidal/nasopharygeal ratio of > 0.67 was considered to constitute adenotonsillar hypertrophy (ATH). OSAHS was defined as an apnea-hypopnea index (AHI) score of > 5 or obstructive apnea index (OAI) score of > 1. RESULTS: Ninety-nine obese children and 99 control subjects were recruited into the study. Obese patients had significantly higher AHI and OAI scores, and lower sleep efficiency and minimum arterial oxygen saturation (MinSao(2)) than control subjects. The prevalence of OSAHS was significantly higher in obese children with or without the ATH groups than their nonobese counterparts (odds ratio, 1.9 vs 108, respectively; 95% confidence interval, 1.21 to 4.7 vs 6.2 to 191, respectively). Obesity, tonsillar hypertrophy, and adenoid hypertrophy were independent risk factors for OSAHS (p < 0.001, p = 0.042, and p = 0.004, respectively). There was a positive correlation between the degree of obesity and AHI (r = 0.535; p < 0.001), and an inverse correlation between obesity and MinSao(2) (r = -0.507; p < 0.001). End-tidal CO(2), Paco(2), and bicarbonate levels were within the normal range. CONCLUSIONS: Obesity is a risk factor for OSAHS, and the degree of obesity is positively correlated with the severity of OSAHS.     

Plasma aldosterone is related to severity of obstructive sleep apnea in subjects with resistant hypertension

OBJECTIVE: Obstructive sleep apnea (OSA) and primary aldosteronism are common in subjects with resistant hypertension; it is unknown, however, if the two disorders are causally related. This study relates plasma aldosterone and renin levels to OSA severity in subjects with resistant hypertension, and in those with equally severe OSA but without resistant hypertension serving as control subjects. METHODS: Seventy-one consecutive subjects referred to the University of Alabama at Birmingham (UAB) for resistant hypertension (BP uncontrolled on three medications) and 29 control subjects referred to UAB Sleep Disorders Center for suspected OSA were prospectively evaluated by an early morning plasma aldosterone concentration (PAC) and renin level, and by overnight, attended polysomnography. RESULTS: OSA (apnea-hypopnea index [AHI] > or = 5/h) was present in 85% of subjects with resistant hypertension. In these subjects, PAC correlated with AHI (rho = 0.44, p = 0.0002) but not renin concentration. Median PAC was significantly lower in control subjects compared to subjects with resistant hypertension (5.5 ng/dL vs 11.0 ng/dL, p < 0.05) and not related to AHI. In male subjects compared to female subjects with resistant hypertension, OSA was more common (90% vs 77%) and more severe (median AHI, 20.8/h vs 10.8/h; p = 0.01), and median PAC was significantly higher (12.0 ng/dL vs 8.8 ng/dL, p = 0.006). CONCLUSION: OSA is extremely common in subjects with resistant hypertension. A significant correlation between PAC and OSA severity is observed in subjects with resistant hypertension but not in control subjects. While cause and effect cannot be inferred, the data suggest that aldosterone excess may contribute to OSA severity.     

The effects of 1-year treatment with a herbst mandibular advancement splint on obstructive sleep apnea, oxidative stress, and endothelial function

BACKGROUND: Obstructive sleep apnea (OSA) is associated with endothelial dysfunction. In the current study, we assessed the effect of long-term modified Herbst mandibular advancement splint (MAS) treatment on OSA, oxidative stress markers, and on endothelial function (EF). METHODS: A total of 16 subjects participated (11 men and 5 women; mean [+/- SD] age, 54.0 +/- 8.3 years; mean body mass index, 28.0 +/- 3.1 kg/m(2)), 12 of whom completed the 1-year evaluation. Apnea severity, levels of oxidative stress markers, and EF were assessed after 3 months and 1 year of receiving treatment. For comparison, 6 untreated patients underwent two evaluations 9 months apart, and 10 non-OSA individuals were assessed once as a reference group. The results are presented as the mean +/- SD. RESULTS: The mean apnea-hypopnea index (AHI) decreased significantly from 29.7 +/- 18.5 events/h before treatment to 17.7 +/- 11.1 events/h after 3 months of treatment and 19.6 +/- 11.5 events/h after 1 year of treatment (p < 0.005 for both). The mean Epworth sleepiness scale score decreased significantly from 12.4 +/- 6.0 before treatment to 10.2 +/- 6.6 after 3 months of treatment and 7.8 +/- 3.8 after 1 year of treatment (p < 0.001 for both). The mean EF improved significantly from 1.77 +/- 0.4 before treatment to 2.1 +/- 0.4 after 3 months of treatment (p < 0.05) and 2.0 +/- 0.3 after 1 year of treatment (p = 0.055), which were similar to the values of the reference group. Thiobarbituric acid-reactive substance (TBARS) levels decreased from 18.8 +/- 6.2 nmol malondialdehyde (MDA)/mL before treatment to 15.8 +/- 3.9 MDA/mL after 3 months of treatment (p = 0.09) and 15.5 +/- 3.2 nmol MDA/mL after 1 year of treatment (p < 0.05). There was a correlation between the improvement in AHI and in EF or TBARS levels (r = 0.55; p = 0.05). The untreated control group remained unchanged. CONCLUSIONS: The Herbst MAS may be a moderately effective long-term treatment for patients with OSA. EF improved to levels that were not significantly different than reference levels, even though apneic events were not completely eliminated. We think that these data are encouraging and that they justify the performance of larger randomized controlled studies.     

Sympathetic chemoreflex responses in obstructive sleep apnea and effects of continuous positive airway pressure therapy

BACKGROUND: Sympathetic nerve activity is increased in awake and regularly breathing patients with obstructive sleep apnea (OSA). Over time, repetitive hypoxic stress could alter sympathetic chemoreflex function in OSA. METHODS: We determined the responses to acute hypoxia (fraction of inspired oxygen of 0.1, for 5 min), static handgrip exercise, and the cold pressor test (CPT) in 24 patients with OSA (age, 50 +/- 3 years [mean +/- SEM]; apnea-hypopnea index, 47 +/- 6 events per hour) and in 14 age- and weight-matched nonapneic control subjects. Muscle sympathetic nerve activity (MSNA) [peroneal microneurography], BP, and ventilation were monitored. RESULTS: Basal MSNA was higher in OSA patients compared to control subjects (45 +/- 4 bursts per minute vs 33 +/- 4 bursts per minute, respectively; p < 0.05). Furthermore, compared to control subjects, the MSNA responses to hypoxia were markedly enhanced in OSA (p < 0.001). Whereas the ventilatory responses to hypoxia tended to be increased in OSA (p = 0.06), the BP responses did not differ between the groups (p = 0.45). The neurocirculatory reflex responses to handgrip exercise and to the CPT were similar in the two groups (p = not significant). In OSA patients who were retested after 1 to 24 months of continuous positive airway pressure (CPAP) therapy (n = 11), basal MSNA (p < 0.01) and the responses of MSNA to hypoxia (p < 0.01) decreased significantly, whereas the ventilatory responses remained unchanged (p = 0.82). CONCLUSION: These data suggest that the sympathetic responses to hypoxic chemoreflex stimulation are enhanced in OSA and may normalize in part following CPAP therapy.     

Impact of body mass index and metabolic phenotypes on coronary artery disease according to glucose tolerance status

ObjectiveThis study aimed to examine the impact of obesity, as defined by body mass index (BMI), and a metabolically unhealthy phenotype on the development of coronary artery disease (CAD) according to glucose tolerance status.MethodsThis population-based retrospective cohort study included 123,746 Japanese men aged 18–72 years (normal glucose tolerance: 72,047; prediabetes: 39,633; diabetes: 12,066). Obesity was defined as a BMI ≥ 25 kg/m². Metabolically unhealthy individuals were defined as those with one or more of the following conditions: hypertension, hypertriglyceridaemia and/or low HDL cholesterol. A Cox proportional hazards regression model identified variables related to CAD incidence.ResultsThe prevalences of obese subjects with normal glucose tolerance, prediabetes and diabetes were 21%, 34% and 53%, whereas those for metabolically unhealthy people were 43%, 60% and 79%, respectively. Multivariate analysis showed that a metabolically unhealthy phenotype increases hazard ratios (HRs) for CAD compared with a metabolically healthy phenotype, regardless of glucose tolerance status (normal glucose tolerance: 1.98, 95% CI: 1.32–2.95; prediabetes: 2.91, 95% CI: 1.85–4.55; diabetes: 1.90, 95% CI: 1.18–3.06). HRs for CAD among metabolically unhealthy non-obese diabetes patients and obese diabetes patients with a metabolically unhealthy status were 6.14 (95% CI: 3.94–9.56) and 7.86 (95% CI: 5.21–11.9), respectively, compared with non-obese subjects with normal glucose tolerance and without a metabolically unhealthy status.ConclusionA metabolically unhealthy state can associate with CAD independently of obesity across all glucose tolerance stages. Clinicians may need to consider those with at least one or more conditions indicating a metabolically unhealthy state as being at high risk for CAD regardless of glucose tolerance status.     

Obstructive sleep apnea, hypertension, and their interaction on arterial stiffness and heart remodeling

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) and hypertension are independently associated with increased stiffness of large arteries that may contribute to left ventricular (LV) remodeling. We sought to investigate the impact of OSA, hypertension, and their association with arterial stiffness and heart structure. DESIGN: We studied 60 middle-aged subjects classified into four groups according to the absence or presence of severe OSA with and without hypertension. All participants were free of other comorbidities. The groups were matched for age, sex, and body mass index. MEASUREMENTS AND RESULTS: Full polysomnography, pulse-wave velocity (PWV), and transthoracic echocardiography were performed in all participants. Compared with normotensive subjects without OSA, PWV, left atrial diameter, interventricular septal thickness, LV posterior wall thickness, LV mass index, and percentage of LV hypertrophy had similar increases in normotensive OSA and patients with hypertension and no OSA (p < 0.05 for all comparisons), with a significant further increase in PWV, LV mass index, and percentage of LV hypertrophy in subjects with OSA and hypertension. Multivariate regression analysis showed that PWV was associated with systolic BP (p < 0.001) and apnea-hypopnea index (p = 0.002). The only independent variable associated with LV mass index was PWV (p < 0.0001). CONCLUSIONS: Severe OSA and hypertension are associated with arterial stiffness and heart structure abnormalities of similar magnitude, with additive effects when both conditions coexist. Increased large arterial stiffness contributes to ventricular afterload and may help to explain heart remodeling in both OSA and hypertension.     

Central sleep apnea induced by acute ingestion of opioids

OBJECTIVES: Three cases are presented in which patients were using opioids as required for nonmalignant pain management and significant central sleep apnea developed. Patients in the first two cases had no evidence of sleep-related breathing disorders on polysomnography until they ingested an opioid for treatment of chronic pain during the night and severe central sleep apnea developed. The patient in our third case had established obstructive sleep apnea but experienced a significant number of central events after the ingestion of an opioid analgesic, leading to worsening severity of his underlying sleep-related breathing disorder. CONCLUSION: The short-term ingestion of opioid analgesics can precipitate central sleep apnea in patients with chronic pain receiving long-term opiate therapy who otherwise show no evidence of central sleep apnea and have no cardiac or neurologic disease that would predispose them to central sleep apnea.     

A whole-grain cereal-based diet lowers postprandial plasma insulin and triglyceride levels in individuals with metabolic syndrome

Background and aimUntil recently, very few intervention studies have investigated the effects of whole-grain cereals on postprandial glucose, insulin and lipid metabolism, and the existing studies have provided mixed results. The objective of this study was to evaluate the effects of a 12-week intervention with either a whole-grain-based or a refined cereal-based diet on postprandial glucose, insulin and lipid metabolism in individuals with metabolic syndrome.Methods and resultsSixty-one men and women age range 40–65 years, with the metabolic syndrome were recruited to participate in this study using a parallel group design. After a 4-week run-in period, participants were randomly assigned to a 12-week diet based on whole-grain products (whole-grain group) or refined cereal products (control group). Blood samples were taken at the beginning and end of the intervention, both fasting and 3 h after a lunch, to measure biochemical parameters. Generalized linear model (GLM) was used for between-group comparisons. Overall, 26 participants in the control group and 28 in the whole-grain group completed the dietary intervention. Drop-outs (five in the control and two in the whole-grain group) did not affect randomization. After 12 weeks, postprandial insulin and triglyceride responses (evaluated as average change 2 and 3 h after the meal, respectively) decreased by 29% and 43%, respectively, in the whole-grain group compared to the run-in period. Postprandial insulin and triglyceride responses were significantly lower at the end of the intervention in the whole-grain group compared to the control group (p = 0.04 and p = 0.05; respectively) whereas there was no change in postprandial response of glucose and other parameters evaluated.ConclusionsA twelve week whole-grain cereal-based diet, compared to refined cereals, reduced postprandial insulin and triglycerides responses. This finding may have implications for type 2 diabetes risk and cardiovascular disease.     

Predictors of heartburn during sleep in a large prospective cohort study

BACKGROUND AND AIMS: Nocturnal gastroesophageal reflux, which may result in nocturnal heartburn, has been demonstrated to be associated with a more severe form of gastroesophageal reflux disease (GERD). The aim of this study was to determine the clinical predictors of heartburn during sleep in a large prospective cohort study. METHODS: Study subjects were members of the parent cohorts from which the Sleep Heart Health Study (SHHS) recruited participants. SHHS is a multicenter, longitudinal, cohort study of the cardiovascular consequences of sleep-disordered breathing. As part of the recruitment process, parent cohort members completed a questionnaire that permitted an assessment of the relationships between heartburn during sleep, and patient demographics, sleep abnormalities, medical history, and social habits in nine community-based parent cohorts across the United States. All variables, significant at the p < 0.05 level, were included as independent variables in multivariate logistic regression models with heartburn during sleep status included as the dependent variable RESULTS: A total of 15,314 subjects completed the questions about heartburn during sleep, and of these, 3,806 subjects (24.9%) reported having this symptom. In four increasingly comprehensive multivariate models, increased body mass index (BMI), carbonated soft drink consumption, snoring and daytime sleepiness (Epworth sleepiness scale score), insomnia, hypertension, asthma, and usage of benzodiazepines were strong predictors of heartburn during sleep. In contrast, college education decreased the risk of reporting heartburn during sleep. CONCLUSIONS: Heartburn during sleep is very common in the general population. Reports of this type of symptom of GERD are strongly associated with increased BMI, carbonated soft drink consumption, snoring and daytime sleepiness, insomnia, hypertension, asthma, and usage of benzodiazepines. Overall, heartburn during sleep may be associated with sleep complaints and excessive daytime sleepiness.     

Association between polysomnographic measures of disrupted sleep and prothrombotic factors

BACKGROUND: Subjective sleep disturbances have been associated with increased risk of coronary artery disease (CAD). We hypothesized that disrupted sleep as verified by polysomnography is associated with increased levels of prothrombotic hemostasis factors previously shown to predict CAD risk. METHODS: Full-night polysomnography was performed in 135 unmedicated men and women (mean age +/- SD, 36.8 +/- 7.8 years) without a history of sleep disorders. Morning fasting plasma levels of von Willebrand Factor (VWF) antigen, soluble tissue factor (sTF) antigen, d-dimer, and plasminogen activator inhibitor (PAI)-1 antigen were determined. Statistical analyses were adjusted for age, gender, ethnicity, body mass index, BP, and smoking history. RESULTS: Higher total arousal index (ArI) was associated with higher levels of VWF (beta = 0.25, p = 0.011, DeltaR(2) = 0.045), and longer wake after sleep onset was associated with higher levels of sTF (beta = 0.23, p = 0.023, DeltaR(2) = 0.038). More nighttime spent at mean oxygen saturation < 90% (beta = 0.20, p = 0.020, DeltaR(2) = 0.029) and higher apnea-hypopnea index (AHI) [beta = 0.19, p = 0.034, DeltaR(2) = 0.024] were associated with higher PAI-1. There was a trend for a relationship between mean oxygen desaturation < 90% and PAI-1 (p = 0.053), even after controlling for AHI. Total ArI (beta = 0.28, p = 0.005, DeltaR(2) = 0.056) and WASO (beta = 0.25, p = 0.017, DeltaR(2) = 0.042) continued to predict VWF and sTF, respectively, even after controlling for AHI. CONCLUSIONS: Polysomnographically verified sleep disruptions were associated with prothrombotic changes. Measures of sleep fragmentation and sleep efficiency were related to VWF and sTF, respectively. Apnea-related measures were related to PAI-1. Our findings suggest that sleep disruptions, even in a relatively healthy population, are associated with potential markers of prothrombotic cardiovascular risk.