Helena Glantz

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).

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.

Increased inflammatory activity in nonobese patients with coronary artery disease and obstructive sleep apnea.

STUDY OBJECTIVES Obstructive sleep apnea (OSA) is common in patients with coronary artery disease (CAD). Enhanced vascular inflammation is implicated as a pathophysiologic mechanism but obesity is confounding. We aimed to address the association of OSA with inflammatory biomarkers in a nonobese cohort of revascularized patients with CAD and preserved left ventricular ejection fraction. DESIGN Cross-sectional analysis of baseline investigations of a randomized controlled trial. SETTING Clinic-based. PARTICIPANTS There were 303 nonobese patients with CAD, of whom 213 with OSA (apnea-hypopnea index [AHI] ≥15 events/h) and 90 without OSA (AHI < 5 events/h). Obese patients with CAD and OSA (N = 105) were chosen as an additional control group. INTERVENTIONS None. MEASUREMENTS Circulating levels of high-sensitivity C-reactive protein (hs-CRP), interleukin (IL)-6, IL-8, and tumor necrosis factor-α were assessed in relation to OSA diagnosis based on AHI ≥ 15 events/h as well as oxygen desaturation index (ODI) ≥ 5 events/h. RESULTS Nonobese patients with OSA had significantly higher levels of hs-CRP and IL-6 than those without OSA. The values did not differ significantly between obese and nonobese patients with OSA. In bivariate regression analysis, AHI ≥ 15 events/h was associated with all four biomarkers but not so in the multivariate model after adjustment for confounders. ODI ≥ 5 events/h was associated with hs-CRP (odds ratio [OR] 1.49, 95% confidence interval [CI] 1.13-1.99) and IL-6 (OR 1.30; 95% CI 1.05-1.60) in multivariate analysis. CONCLUSIONS OSA with ODI ≥ 5 was independently associated with increased inflammatory activity in this nonobese CAD cohort. The intermittent hypoxemia, rather than the number of apneas and hypopneas, appears to be primarily associated with enhanced inflammation.

Obstructive sleep apnea is independently associated with worse diastolic function in coronary artery disease

BACKGROUND Diastolic dysfunction is common in patients with coronary artery disease (CAD). We hypothesize that patients with CAD and preserved left ventricular ejection fraction (LVEF) and obstructive sleep apnea (OSA) will have worse diastolic function than similar patients without OSA. MATERIAL AND METHODS We analyzed sleep-study recordings and echocardiographic measurements obtained at baseline in a randomized controlled trial (RICCADSA) of revascularized patients with CAD who had LVEF of at least 50%. OSA was defined as an apnea-hypopnea-index (AHI) ≥15 events/h, and, no OSA, as an AHI <5. Worse diastolic function was defined as assumed elevated left ventricular filling pressure based on peak flow velocity in early diastole/Tissue Doppler of early diastolic ventricular filling (E/é) of >13 (or >9 in patients with an enlarged left atrial diameter [≥39 mm for women and ≥40 mm for men]). RESULTS Data from 431 patients were evaluated (mean age: 63.7 ± 8.8 y; men: 82.5%; OSA: n = 331). Worse diastolic function was more common among the patients with OSA than those without (54.4% vs 41.0%, p = 0.019). In multivariate analysis, OSA was associated with worse diastolic function (odds ratio [OR] 1.90, 95% confidence interval [CI] 1.13; 3.18) adjusted for female sex (OR 2.28, 95% CI 1.28; 4.07), hypertension (OR 1.84, 95% CI 1.20; 2.82), and diabetes mellitus (OR 2.45, 95% CI 1.42; 4.23). Age ≥60 years, obesity, and current smoking were nonsignificant. CONCLUSIONS In this cohort with CAD and preserved LVEF, OSA was associated with worse diastolic function independent of the traditionally recognized risk indicators.

CPAP Does Not Reduce Inflammatory Biomarkers in Patients With Coronary Artery Disease and Nonsleepy Obstructive Sleep Apnea: A Randomized Controlled Trial

Objectives Obstructive sleep apnea (OSA) and enhanced vascular inflammation coexist in patients with coronary artery disease (CAD). Continuous positive airway pressure (CPAP) is first-line treatment for OSA with daytime sleepiness. This analysis of data from the RICCADSA (Randomized Intervention with CPAP in Coronary Artery Disease and Sleep Apnea) trial investigated the effects of CPAP on inflammatory markers in patients with CAD and nonsleepy OSA. Methods This single-center, randomized, controlled, open-label trial enrolled consecutive revascularized patients with nonsleepy OSA (apnea-hypopnea index >15/h; Epworth Sleepiness Scale score <10). Levels of high-sensitivity C-reactive protein (hs-CRP), interleukin (IL)-6, IL-8, and tumor necrosis factor-α (TNF-α) were measured in blood samples taken at baseline (median 94 days after revascularization) and after 1 year of follow-up in patients randomized to CPAP or no-CPAP. Results A total of 220 patients with analyzable blood samples at baseline and 1 year were included. Baseline IL-6 levels were significantly lower in the CPAP versus no-CPAP group (median 3.1 pmol/L [interquartile range 1.3-5.7] vs. 4.2 pmol/L [2.0-8.9], respectively; p = .005). At 1-year follow-up, median IL-6 levels were significantly reduced in both groups (to 2.2 pmol/L [1.2-3.9] in the CPAP group and to 2.2 [1.2-4.7] in no-CPAP group; both p < .001 vs. baseline). IL-8, hs-CRP, and TNF-α did not change significantly from baseline. There was no association between CPAP adherence and changes in inflammatory marker levels. Conclusions In patients with stable CAD and nonsleepy OSA, inflammatory biomarkers did not change significantly over time except for IL-6 levels, which reduced to the same extent in the CPAP and no-CPAP groups. Clinical Trial Registration ClinicalTrials.gov, ID: NCT00519597; researchweb.org, VGSKAS-4731.

Outcomes in coronary artery disease patients with sleepy obstructive sleep apnoea on CPAP

Coronary artery disease (CAD) patients with obstructive sleep apnoea (OSA) have increased risk for major adverse cardiovascular and cerebrovascular events (MACCEs) compared with CAD patients without OSA. We aimed to address if the risk is similar in both groups when OSA patients are treated. This study was a parallel observational arm of the RICCADSA randomised controlled trial, conducted in Sweden between 2005 and 2013. Patients with revascularised CAD and OSA (apnoea–hypopnoea index (AHI) ≥15 events·h−1) with daytime sleepiness (Epworth Sleepiness Scale score ≥10) were offered continuous positive airway pressure (CPAP) (n=155); CAD patients with no OSA (AHI <5 events·h−1) acted as controls (n=112), as a randomisation of sleepy OSA patients to no treatment would not be ethically feasible. The primary end-point was the first event of MACCEs. Median follow-up was 57 months. The incidence of MACCEs was 23.2% in OSA patients versus 16.1% in those with no OSA (adjusted hazard ratio 0.96, 95% CI 0.40–2.31; p=0.923). Age and previous revascularisation were associated with increased risk for MACCEs, whereas coronary artery bypass grafting at baseline was associated with reduced risk. We conclude that the risk for MACCEs was not increased in CAD patients with sleepy OSA on CPAP compared with patients without OSA. Cardiovascular risk in coronary artery disease patients with OSA on CPAP treatment is similar to those without OSA http://ow.ly/hB1z30eXxFx