Nasal continuous positive airway pressure: influence on digital volume pulse in obstructive sleep apnoea patients.

Obstructive sleep apnoea (OSA) is linked to increased cardiovascular risk. This risk can be reduced by nasal continuous positive airway pressure (nCPAP) treatment. As OSA is associated with an increase of several vasoconstrictive factors, we investigated whether nCPAP influences the digital volume pulse wave. We performed digital photoplethysmography during sleep at night in 94 consecutive patients who underwent polysomnography and 29 patients treated with nCPAP. Digital volume pulse waves were obtained independently of an investigator and were quantified using an algorithm for continuous automated analysis. In patients with OSA and an apnoea/hypopnoea index (AHI) of >10 events · h(-1), a significant vasoconstriction was observed during the night (p<0.0001 by Friedman's test). A significant positive correlation existed between vasoconstriction and AHI (Spearman correlation, r = 0.27; p<0.01; n = 94) and the arousal index (Spearman correlation, r = 0.21; p < 0.05; n = 94). After 6 months of nCPAP treatment, the AHI was significantly reduced from 27 ± 3 events · h(-1) to 4 ± 2 events · h(-1) (each n = 29; p<0.001) and vasoconstriction during the night was significantly reduced from 10 ± 3% to 3 ± 1% (p<0.01). We show changes in the reflective index during the night consistent with vasoconstriction in patients with OSA, which are significantly reduced after 6 months of nCPAP treatment.

Continuous positive airway pressure treatment of mild to moderate obstructive sleep apnea reduces cardiovascular risk.

RATIONALE: Obstructive sleep apnea (OSA) is linked to increased cardiovascular risk, but the impact of mild forms of OSA and their treatment on cardiovascular outcomes remains controversial. OBJECTIVES: To prospectively investigate cardiovascular outcomes in treated versus untreated patients with OSA. METHODS: Consecutive sleep laboratory patients with all degrees of OSA were included. Endpoints were nonfatal (myocardial infarction, stroke, and acute coronary syndrome requiring revascularization procedures) and fatal (death from myocardial infarction or stroke) cardiovascular events. MEASUREMENTS AND MAIN RESULTS: Comparison of event-free survival rates in treated versus untreated patients (Kaplan-Meier estimates, log-rank test). Of 449 patients enrolled (age, 56.0 +/- 10.5 years; body mass index, 30.8 +/- 5.4 kg/m(2)), 364 patients received OSA treatment, and 85 patients remained untreated. Median follow-up was 72.0 months (range, 1-156). Mean apnea-hypopnea index before treatment was 30.9 +/- 21.8/hour in treated and 15.3 +/- 13.0/hour in untreated patients, but there were no differences in cardiovascular comorbidities or risk factors. In patients with mild-moderate OSA (n = 288), events were more frequent in untreated patients (estimated event-free survival at 10 yr, 51.8 vs. 80.3% [P < 0.001]; absolute risk reduction, 28.5%; number needed to treat to prevent one event/10 yr, 3.5). After adjustment for age, gender, cardiovascular risk factors, and comorbidities at baseline, OSA treatment was an independent predictor for events (hazard ratio, 0.36; 95% confidence interval, 0.21-0.62; P < 0.001). CONCLUSIONS: OSA treatment was associated with a cardiovascular risk reduction of 64% independent from age and preexisting cardiovascular comorbidities. OSA treatment should be considered for primary and secondary cardiovascular prevention, even in milder OSA.

Risk factors and myocardial infarction in patients with obstructive sleep apnea: impact of beta2-adrenergic receptor polymorphisms.

BACKGROUND: The increased sympathetic nervous activity in patients with obstructive sleep apnea (OSA) is largely responsible for the high prevalence of arterial hypertension, and it is suggested to adversely affect triglyceride and high-density lipoprotein (HDL) cholesterol levels in these patients. The functionally relevant polymorphisms of the beta2-adrenergic receptor (Arg-47Cys/Arg16Gly and Gln27Glu) have been shown to exert modifying effects on these risk factors in previous studies, but results are inconsistent. METHODS: We investigated a group of 429 patients (55 +/- 10.7 years; 361 men, 68 women) with moderate to severe obstructive sleep apnea (apnea/hypopnea index (AHI) 29.1 +/- 23.1/h) and, on average, a high cardiovascular risk profile (body mass index 31.1 +/- 5.6, with hypertension in 60.1%, dyslipidemia in 49.2%, and diabetes in 17.2% of patients). We typed the beta2-adrenergic receptor polymorphisms and investigated the five most frequent haplotypes for their modifying effects on OSA-induced changes in blood pressure, heart rate, and lipid levels. The prevalence of cardiovascular risk factors and coronary heart disease (n = 55, 12.8%) and survived myocardial infarction (n = 27, 6.3%) were compared between the genotypes and haplotypes. RESULTS: Multivariate linear/logistic regressions revealed a significant and independent (from BMI, age, sex, presence of diabetes, use of antidiabetic, lipid-lowering, and antihypertensive medication) influence of AHI on daytime systolic and diastolic blood pressure, heart rate, prevalence of hypertension, and triglyceride and HDL levels. The beta2-adrenergic receptor genotypes and haplotypes showed no modifying effects on these relationships or on the prevalence of dyslipidemia, diabetes, and coronary heart disease, yet, for all three polymorphisms, heterozygous carriers had a significantly lower relative risk for myocardial infarction (Arg-47Cys: n = 195, odds ratio (OR) = 0.32, P = 0.012; Arg16Gly: n = 197, OR = 0.39, P = 0.031; Gln27Glu: OR = 0.37, P = 0.023). Carriers of the most frequent haplotype (n = 113) (haplotype 1; heterozygous for all three polymorphisms) showed a five-fold lower prevalence of survived myocardial infarction (OR = 0.21, P = 0.023). CONCLUSION: Our study showed no significant modifying effect of the functionally relevant beta2-adrenergic receptor polymorphisms on OSA-induced blood pressure, heart rate, or lipid changes. Nevertheless, heterozygosity of these polymorphisms is associated with a lower prevalence of survived myocardial infarction in this group with, on average, a high cardiovascular risk profile.

Modifying effects of the R389G beta1-adrenoceptor polymorphism on resting heart rate and blood pressure in patients with obstructive sleep apnoea.

OSA (obstructive sleep apnoea) stimulates sympathetic nervous activity and elevates resting HR (heart rate) and BP (blood pressure). In the present study in a cohort of 309 untreated OSA patients, the resting HR and BP during the daytime were correlated with AHI (apnoea/hypopnea index) and compared with patients with R389R (n = 162), R389G (n = 125) and G389G (n = 22) genotypes of the beta1-adrenoreceptor R389G polymorphism. We analysed the impact of the genotype on the decline of HR and BP in a subgroup of 148 patients (R389R, n = 86; R389G, n = 54; G389G, n = 8) during a 6-month follow-up period under CPAP (continuous positive airway pressure) therapy during which cardiovascular medication remained unchanged. In untreated OSA patients, we found an independent relationship between AHI and resting HR (beta = 0.096, P < 0.001), systolic BP (beta = 0.09, P = 0.021) and diastolic BP (beta = 0.059, P = 0.016). The resting HR/BP, however, did not differ among carriers with the R389R, R389G and G389G genotypes. CPAP therapy significantly reduced HR [-2.5 (-1.1 to -4.0) beats/min; values are mean difference (95% confidence intervals)] and diastolic BP [-3.2 (-1.5 to -5.0) mmHg]. The decline in HR was more significantly pronounced in the R389R group compared with the Gly(389) carriers [-4.1 (-2.3 to -5.9) beats/min (P < 0.001) compared with -0.2 (2.1 to -2.6) beats/min (P = 0.854) respectively; Student's t test between groups, P = 0.008]. Diastolic BP was decreased significantly (P < 0.001) only in Gly389 carriers (R389G or G389G) compared with R389R carriers [-5.0 (-2.3 to -7.6) mmHg compared with -2.0 (0.4 to -4.3) mmHg respectively]. ANOVA revealed a significant difference (P = 0.023) in HR reduction between the three genotypes [-4.1 (+/-8.4) beats/min for R389R, -0.5 (+/-9.3) beats/min for R389G and +1.9 (+/-7.2) beats/min for G389G]. In conclusion, although the R389G polymorphism of the beta1-adrenoceptor gene did not influence resting HR or BP in untreated OSA patients, it may modify the beneficial effects of CPAP therapy on these parameters.

Effects of glucocorticoids on generation of reactive oxygen species in platelets.

Since prednisolone and dexamethasone are known as potent anti-inflammatory agents, the effects of prednisolone and dexamethasone on production of intracellular reactive oxygen species (ROS) were investigated in human platelets. Platelet ROS were measured using the intracellular fluorescent dye dichlorofluorescein diacetate after activation of protein kinase C by phorbol-12-myristate-13-acetate (PMA) or 1-oleoyl-2-acetyl-sn-glycerol (OAG). NAD(P)H oxidase activity was measured photometrically. PMA and OAG significantly increased ROS in platelets (P<0.001). Prednisolone or dexamethasone concentration-dependently reduced the PMA-induced ROS production. The PMA-induced ROS increase was significantly reduced in the presence of 10 micromol/l prednisolone to 9+/-1% (n=31; P<0.001) or in the presence of 10 micromol/l dexamethasone to 9+/-1% (n=24; P<0.001). The inhibitory effect of prednisolone or dexamethasone could also be observed in the presence of the glucocorticoid receptor inhibitor, mifepristone (RU486). Administration of testosterone or aldosterone did not significantly reduce PMA-induced ROS increase. Prednisolone had no effect on platelet NAD(P)H oxidase activity. The inhibition of oxidative phosphorylation by sodium azide reduced platelets ROS to 8+/-1% (n=35). It is concluded that glucocorticoids, prednisolone and dexamethasone, directly inhibit production of intracellular ROS. This effect may contribute to the anti-inflammatory actions of these agents.

Sleep-related breathing disorders impair quality of life in haemodialysis recipients.

BACKGROUND: It is well known that the quality of life of haemodialysis recipients is often severely compromised. So far, the influence of sleep-related breathing disorders on the quality of life of patients receiving maintenance dialysis has not been evaluated. METHODS: Quality of life as assessed by the Medical Outcomes Study Short Form-36 (SF-36) and the Nottingham Health Profile Part 1 (NHP1) was determined in 33 patients (20 males, 13 females; median age 66 years (95% CI 22-82)) with end-stage renal disease treated with haemodialysis. Additionally, polygraphy with a validated eight-channel ambulatory recording unit was performed. RESULTS: Twenty-one patients (63.6%) had a clinically significant sleep-related breathing disorder with a median apnoea/hypopnoea index of 13.3 (6.3-78.1)/h and a median oxygen saturation during sleep of 92.5 (88-97)%. In three out of eight subjective measures of the SF-36 (vitality, social functioning and mental health) and in one out of six subjective measures of the NHP1 (emotional reactions), patients without sleep-related breathing disorders had a higher quality of life than patients with this disorder (P<0.05 each). Furthermore, the severity of the sleep-related breathing disorder as indicated by the apnoea/hypopnoea index significantly correlated with the following quality of life measures: physical functioning, social functioning, role limitation due to physical and emotional problems, general health and vitality (SF-36), and also with pain, sleep, social isolation and emotional reactions (NHP1) (P<0.05 each). CONCLUSIONS: We conclude that sleep-related breathing disorders independently influence the quality of life of patients receiving maintenance dialysis.

Effect of continuous positive airway pressure therapy on 24-hour blood pressure in patients with obstructive sleep apnea syndrome.

BACKGROUND: Patients with obstructive sleep apnea syndrome (OSAS) are subject to an increased cardiovascular morbidity including systemic hypertension. Little is known about the effects of treatment with nasal continuous positive airway pressure (CPAP) on systemic hypertension. METHODS: Automated ambulatory 24-h blood pressure (BP) monitoring was performed in 88 consecutive patients who were referred for evaluation of snoring or suspected OSAS. In addition, the long-term effects of CPAP therapy on 24-h BP were assessed. RESULTS: A total of 62 patients had OSAS and 26 habitual snoring. Patients with OSAS had significantly higher mean arterial BP values than snorers (102.7 +/- 10.7 v 94.0 +/- 10.2 mm Hg; P < .01). Multiple stepwise linear regression analysis disclosed that the degree of systemic hypertension was independently associated with the severity of OSAS as determined by the apnea/hypopnea index (R = 0.43; P < .001), but not with age, body mass index, or smoking habits. Of the 62 patients with OSAS, 52 were treated with CPAP and reevaluated after 9 months. The CPAP resulted in a significant decrease in mean arterial BP (from 103.7 +/- 10.4 to 99.1 +/- 10.8 mm Hg; P < .05). For those patients with systemic hypertension whose BP improved with CPAP therapy, 24-h mean pulse pressure at baseline (r = -0.36; P < .05) as well as average heart rate during the day (r = -0.35; P < .05) turned out as predictors. CONCLUSIONS: Obstructive sleep apnea syndrome contributes, at least in part, to the development of systemic hypertension, and CPAP may improve BP values in treated OSAS patients. Predictors of a beneficial CPAP effect on BP are a high heart rate and a high pulse pressure before treatment.