Sleep disordered breathing post-ACS associated with higher incidence of CV adverse events
Impact of Sleep-Disordered Breathing on Long-Term Outcomes in Patients With Acute Coronary Syndrome Who Have Undergone Primary Percutaneous Coronary Intervention
Mazaki T, Kasai T, Yokoi H, et al.
J Am Heart Assoc. 2016;5:e003270
BackgroundSleep-disordered breathing (SDB) causes or worsens intermittent hypoxia, increased oxidative stress and sympathetic activation, endothelial dysfunction, and inflammatory response, thereby representing a risk factor for cardiovascular (CV) diseases . However, the relationship between SDB and the development of coronary artery disease (CAD), as well as between SDB and clinical outcomes in CAD patients, remains unclear [2-7].
In this study, the association between SDB and long-term clinical outcomes (median follow-up 5.6 years) following an acute coronary syndrome (ACS) was evaluated, by means of overnight cardiorespiratory monitoring of 241 patients conducted within 1 week of the index ACS event, and were treated with primary percutaneous coronary intervention (PCI). The presence of SDB was defined as the frequency of apnoeas and hypopneas (=apnoea-hypopnea index or AHI) ≥5 events per hour. Major adverse cardio-cerebrovascular events (MACCE) included death, recurrence of ACS, nonfatal stroke, and hospital admission for congestive heart failure. Overall incidence of SDB was 52%. Propensity score (PS) analysis was applied to account for possible predisposition bias due to differences in baseline characteristics between the SBD and no-SBD groups.
- The prevalence of SDB in 4 PS quartiles, and the corresponding rates of subsequent MACCE were: Quartile 1: 12.7% SDB; 15.0% MACCE, Quartile 2: 23.0% SDB; 13.3% MACCE, Quartile 3: 27.8% SDB; 13.1% MACCE, Quartile 4: 36.5% SDB; 18.3% MACCE, suggesting that if the prevalence of SDB is high, the probability of incident MACCE is high.
- The cumulative incidence of MACCE was significantly higher in patients with SDB than in those without SDB (21.4% vs. 7.8%, P=0.006).
- The cumulative event-free survival was significantly lower in de SDB group compared to the non-SDB group (Log rank p = 0.006).
- Comparing AHI quartiles revealed the greater AHI the greater the risk for MACCE (Log rank p-trend = 0.006).
- In the multivariable analysis, SDB was a significant predictor for MACCE (HR 2.28; 95% CI: 1.06-4.92, P = 0.035) along with, increase in age, decrease in left ventricular ejection fraction and mean arterial oxyhemoglobin saturation, absence of b-blocker treatment and absence of statin treatment.
- PS-matching included 88 pairs of patients and reduced the standardised difference for all variables to an absolute value of <10% (substantial balance of covariates across groups).
Among matched patients, the presence of SDB was significantly associated with an increase in MACCE (Log rank p = 0.006). Risk of developing MACCE was greater in the SDB group compared to the no-SDB group (HR 4.25, 95% CI: 1.43-12.6, p = 0.009).
ConclusionThe presence of SDB among ACS patients following primary PCI is associated with a higher incidence of MACCE. Furthermore, AHI determined by this particular cardiorespiratory monitoring device can be a predictor for long-term clinical outcomes.
Editorial comment In his editorial, Newby notes that ‘The pathophysiology of sleep disturbances and the importance of information gathered while we are sleeping are dimensions of cardiovascular risk that have been explored but not fully appreciated or integrated into risk assessment previously. He therefore emphasises the importance of the Mazaki et al findings, as well as the weaknesses of the study: ‘Because sleep-disordered breathing is potentially treatable, and given the high prevalence of sleep-disordered breathing observed among ACS patients, the findings of the study by Mazaki et al are not simply of academic interest. In this regard, however, their study did not distinguish obstructive sleep apnea from central sleep apnea, which may have different relationships with outcomes and necessitate different modes of treatment. Furthermore, the presence of clinical heart failure was not reported, but the mean left ventricular ejection fraction (LVEF) in the group with sleep-disordered breathing was 53±10%. Consequently, although the majority of patients had a normal LVEF, 15% to 20% of patients had an LVEF ≤45%; treatment with continuous positive airway pressure has not been shown to be effective in this group, and adaptive servoventilation may be harmful.’ Servoventilation has been shown to be increase all-cause mortality and CV mortality among patients with ≤45 LVEF during the SERVE-HF trial. ‘Ultimately, the effect of intervention to treat sleep‐disordered breathing to mitigate this risk of adverse outcomes after ACS would need to be demonstrated in randomized clinical trials and may depend on the subclass of sleep‐disordered breathing, comorbidities, and treatment approach.’
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