Yüksel Peker

Increased incidence of coronary artery disease in sleep apnoea: a long-term follow-up.

An increased incidence of cardiovascular disease has previously been reported in middle-aged males during a follow-up period of 7 yrs. The aim of the present study was to address the incidence of coronary artery disease (CAD) in a larger sample without any heart disease at baseline. The population comprised 308 snorers (245 males and 63 females) with a mean±sd age of 49.0±9.9 yrs in 1991. Data were collected via the Swedish Hospital Discharge Register, National Cause of Death Registry, clinical charts and questionnaires. Over 7 yrs, CAD was observed in 17 (16.2%) of 105 patients with obstructive sleep apnoea (OSA; overnight (6 h) oxygen desaturations ≥30 events) compared with 11 (5.4%) of 203 snorers without OSA. OSA diagnosis at baseline was associated with an increased risk of development of CAD in a multivariate model. In the OSA group, CAD was confirmed in 16 (24.6%) of 65 incompletely treated patients compared with one (3.9%) of 26 efficiently treated subjects. Efficient treatment of OSA reduced this risk. It is concluded that middle-aged sleep apnoeics are at high risk of developing coronary artery disease if they are not treated efficiently, which should be considered in cardiovascular disease prevention models.

Effect of Positive Airway Pressure on Cardiovascular Outcomes in Coronary Artery Disease Patients with Nonsleepy Obstructive Sleep Apnea. The RICCADSA Randomized Controlled Trial

RATIONALE Obstructive sleep apnea (OSA) is common in patients with coronary artery disease (CAD), many of whom do not report daytime sleepiness. First-line treatment for symptomatic OSA is continuous positive airway pressure (CPAP), but its value in patients without daytime sleepiness is uncertain. OBJECTIVES To determine the effects of CPAP on long-term adverse cardiovascular outcome risk in patients with CAD with nonsleepy OSA. METHODS This single-center, prospective, randomized, controlled, open-label, blinded evaluation trial was conducted between December 2005 and November 2010. Consecutive patients with newly revascularized CAD and OSA (apnea-hypopnea index ≥15/h) without daytime sleepiness (Epworth Sleepiness Scale score <10) were randomized to auto-titrating CPAP (n = 122) or no positive airway pressure (n = 122). MEASUREMENTS AND MAIN RESULTS The primary endpoint was the first event of repeat revascularization, myocardial infarction, stroke, or cardiovascular mortality. Median follow-up was 57 months. The incidence of the primary endpoint did not differ significantly in patients who did versus did not receive CPAP (18.1% vs. 22.1%; hazard ratio, 0.80; 95% confidence interval, 0.46-1.41; P = 0.449). Adjusted on-treatment analysis showed a significant cardiovascular risk reduction in those who used CPAP for ≥4 versus <4 hours per night or did not receive treatment (hazard ratio, 0.29; 95% confidence interval, 0.10-0.86; P = 0.026). CONCLUSIONS Routine prescription of CPAP to patients with CAD with nonsleepy OSA did not significantly reduce long-term adverse cardiovascular outcomes in the intention-to-treat population. There was a significant reduction after adjustment for baseline comorbidities and compliance with the treatment. Clinical trial registered with www.clinicaltrials.gov (NCT 00519597).

Hypertension prevalence in obstructive sleep apnoea and sex: a population-based case–control study

Obstructive sleep apnoea (OSA) is a recognised risk factor for hypertension (HT). The current authors investigated confounders of this association in a sex-balanced community-based sample of patients with HT (n = 161) from the Skaraborg Hypertension and Diabetes Project (n = 1,149) and normotensive controls (n = 183) from an age and sex stratified community-based population sample (n = 1,109). All participants underwent ambulatory home polysomnography. Severe OSA (apnoea-plus-hypopnoea index (AHI) ≥30 events·h−1) was found in 47 and 25% of hypertensive and normotensive males, respectively. The corresponding numbers in females were 26 and 24%, respectively. The odds ratio (OR) for HT increased across AHI tertiles from 1.0 to 2.1 (95% confidence interval: 0.9–4.5) and 1.0 to 3.7 (95% CI: 1.7–8.2) in males, but not in females where the OR increased from 1.0 to 1.8 (95% CI: 0.8–3.9) and 1.0 to 1.6 (95% CI: 0.7–3.5). Regression analysis correcting for age, body mass index (or waist–hip ratio) and smoking did not eliminate the association between OSA and HT in males. The present data suggest that obstructive sleep apnoea is highly prevalent in both the general population and in patients with known hypertension. The contribution of obstructive sleep apnoea to hypertension risk may be sex dependent and higher in males than in females.

Orexin Receptor Antagonism, a New Sleep-Enabling Paradigm: A Proof-of-Concept Clinical Trial

The orexin system is a key regulator of sleep and wakefulness. In a multicenter, double‐blind, randomized, placebo‐controlled, two‐way crossover study, 161 primary insomnia patients received either the dual orexin receptor antagonist almorexant, at 400, 200, 100, or 50 mg in consecutive stages, or placebo on treatment nights at 1‐week intervals. The primary end point was sleep efficiency (SE) measured by polysomnography; secondary end points were objective latency to persistent sleep (LPS), wake after sleep onset (WASO), safety, and tolerability. Dose‐dependent almorexant effects were observed on SE, LPS, and WASO. SE improved significantly after almorexant 400 mg vs. placebo (mean treatment effect 14.4%; P < 0.001). LPS (–18 min (P = 0.02)) and WASO (–54 min (P < 0.001)) decreased significantly at 400 mg vs. placebo. Adverse‐event incidence was dose‐related. Almorexant consistently and dose‐dependently improved sleep variables. The orexin system may offer a new treatment approach for primary insomnia.

Blood pressure, cardiac structure and severity of obstructive sleep apnea in a sleep clinic population.

Objectives We investigated whether the severity of obstructive sleep apnea (OSA) predicts blood pressure or cardiac left ventricular thickness in a clinical population of OSA patients, if adjustments are made for age, gender, use of antihypertensive agents, smoking, body mass index, history of coronary artery disease, hypercholesterolemia and circulating C-peptide concentrations. Design Relationships in this cross-sectional study were investigated with correlation analysis and multiple regression procedures. Patients and methods Apnea–hypopnea index (AHI, polysomnography) and office systolic and diastolic blood pressures (SBP and DBP) were measured in 81 subjects referred to a university hospital sleep laboratory. Ambulatory blood pressures were recorded during one 24 h cycle. Left ventricular (LV) muscle size was quantified as two-dimensionally directed M-mode-derived end-diastolic thickness of interventricular septum and posterior chamber wall. Results After adjustment for separate or the entire set of covariates, AHI predicted office SBP and DBP as well as daytime ambulatory DBP and night-time ambulatory SBP and DBP, but not daytime ambulatory SBP. In contrast, associations between AHI and LV muscle thickness reflected complex inter-relationships with confounding variables. Smoking and age suppressed, whereas body mass index (BMI) and hypertension inflated the relationship between OSA severity and LV muscle thickness in this study. Conclusions AHI is an independent predictor of several measures of blood pressure. OSA severity and LV muscle thickness appear to be primarily linked via increased blood pressure.

The influence of patent foramen ovale on oxygen desaturation in obstructive sleep apnoea

Obstructive sleep apnoea (OSA) is associated with oxygen desaturation to a varying degree. A patent foramen ovale (PFO) may allow interatrial right-to-left shunting. The hypothesis of the current study was that oxygen desaturation will occur more often, in proportion to the frequency of respiratory disturbances, in OSA subjects with PFO than in those without. In a group of 209 subjects diagnosed with OSA, the proportion of desaturation to respiratory events was calculated as the ratio of oxygen desaturation index (ODI)/apnoea–hypopnoea index (AHI). A total of 15 cases with high proportional desaturation (ODI/AHI ≥0.66) were individually matched with 15 controls with low proportional desaturation (ODI/AHI ≤0.33), all without pulmonary disease. PFO was assessed with contrast transoesophageal echocardiography and considered large when ≥20 bubbles passed over from the right to the left atrium after a single injection. The prevalence of large PFO was nine out of 15 (60%) in the high proportional desaturation group versus two out of 15 (13%) in the low proportional desaturation group. The median number of passing bubbles was positively correlated to minimum oxygen saturation among those with PFO. In conclusion, oxygen desaturation occurs more often, in proportion to the frequency of respiratory disturbances, in obstructive sleep apnoea subjects with a patent foramen ovale than in those without.

Occurrence and Predictors of Obstructive Sleep Apnea in a Revascularized Coronary Artery Disease Cohort

BACKGROUND Knowledge about the prevalence of obstructive sleep apnea (OSA) in coronary artery disease (CAD) is insufficient. The aim of the current report was to evaluate the occurrence and predictors of OSA among revascularized patients with CAD within the framework of a randomized controlled trial (Randomized Intervention with CPAP in Coronary Artery Disease and Sleep Apnea [RICCADSA]), evaluating the impact of continuous positive airway pressure on cardiovascular outcomes in CAD patients with OSA. MATERIAL AND METHODS All patients undergoing percutaneous coronary intervention or coronary artery bypass grafting between September 2005 and November 2010 (n = 1,291) were invited to participate. Anthropometrics and medical history were obtained, ambulatory sleep recording was performed, and all subjects completed the Epworth Sleepiness Scale (ESS) questionnaire. RESULTS In total, 662 patients participated in the sleep study. OSA, defined as an apnea-hypopnea index equal to or greater than 15/hour, was found among 422 (63.7%). The prevalence of hypertension was 55.9%; obesity (body mass index ≥ 30 kg/m²), 25.2%; diabetes mellitus, 22.1%; and current smoking, 18.9%. The patients with CAD who did not participate in the study demonstrated an almost similar anthropometric and clinical profile compared with the studied group. The majority (61.8%) of the patients with OSA were nonsleepy (ESS score < 10). Patients with OSA had a higher prevalence of obesity, hypertension, diabetes mellitus, and history of atrial fibrillation, whereas current smoking was more common in the non-OSA group. Age, male sex, body mass index, and ESS score, but not comorbidities, were independent predictors of OSA. CONCLUSIONS The occurrence of unrecognized OSA in this revascularized CAD cohort was higher than previously reported. We suggest that OSA should be considered in the secondary prevention protocols in CAD.

Rationale and design of the Randomized Intervention with CPAP in Coronary Artery Disease and Sleep Apnoea RICCADSA trial

Rationale. Obstructive sleep apnoea (OSA) is common in coronary artery disease (CAD) and a possible cause of increased mortality. To date, there is a lack of randomized controlled trials to draw the conclusion that all CAD patients should be investigated for OSA and subsequently be treated with continuous positive airway pressure (CPAP). Objective. The Randomized Intervention with CPAP in CAD and OSA (RICCADSA) trial is designed to address if CPAP treatment reduces the combined rate of new revascularization, myocardial infarction, stroke and cardiovascular mortality over a 3-year period in CAD patients with OSA. Secondary outcomes include cardiovascular biomarkers, cardiac function and maximal exercise capacity at 3-month- and 1-year follow-ups. Patients and methods. A sample of 400 CAD patients (100 non-sleepy OSA patients randomized to CPAP, 100 to non-CPAP; 100 sleepy OSA patients on CPAP, and 100 CAD patients without OSA) will be included. So far, 240 patients have been enrolled in the trial since December 31, 2005. Conclusion. The RICCADSA trial will contribute to defining the impact of CPAP on prognosis of CAD patients with OSA.

Blood Pressure Response to Losartan and Continuous Positive Airway Pressure in Hypertension and Obstructive Sleep Apnea

RATIONALE Obstructive sleep apnea (OSA) is common in people with hypertension, particularly resistant hypertension. Treatment with an antihypertensive agent alone is often insufficient to control hypertension in patients with OSA. OBJECTIVES To determine whether continuous positive airway pressure (CPAP) added to treatment with an antihypertensive agent has an impact on blood pressure (BP) levels. METHODS During the initial 6-week, two-center, open, prospective, case-control, parallel-design study (2:1; OSA/no-OSA), all patients began treatment with an angiotensin II receptor antagonist, losartan, 50 mg daily. In the second 6-week, sex-stratified, open, randomized, parallel-design study of the OSA group, all subjects continued to receive losartan and were randomly assigned to either nightly CPAP as add-on therapy or no CPAP. MEASUREMENTS AND MAIN RESULTS Twenty-four-hour BP monitoring included assessment every 15 minutes during daytime hours and every 20 minutes during the night. Ninety-one patients with untreated hypertension underwent a home sleep study (55 were found to have OSA; 36 were not). Losartan significantly reduced systolic, diastolic, and mean arterial BP in both groups (without OSA: 12.6, 7.2, and 9.0 mm Hg; with OSA: 9.8, 5.7, and 6.1 mm Hg). Add-on CPAP treatment had no significant changes in 24-hour BP values but did reduce nighttime systolic BP by 4.7 mm Hg. All 24-hour BP values were reduced significantly in the 13 patients with OSA who used CPAP at least 4 hours per night. CONCLUSIONS Losartan reduced BP in OSA, but the reductions were less than in no-OSA. Add-on CPAP therapy resulted in no significant changes in 24-hour BP measures except in patients using CPAP efficiently. Clinical trial registered with www.clinicaltrials.gov (NCT00701428).​

Sleep apnoea and quality of life in growth hormone (GH)-deficient adults before and after 6 months of GH replacement therapy.

Objective  To investigate the sleep architecture and breathing as well as quality of life (QoL) in adults with GH deficiency (GHD) before and 6 months after GH replacement therapy.