Discussion
The present study showed that OSA was associated with an increased risk of MACCE in patients with hypertension, although no significant hypertension by OSA interaction was noted. This risk is particularly pronounced among patients who already have severe hypertension. Conversely, among patients who do not have hypertension, there was no significant difference in the incidence of MACCE between those with and without OSA.
Previous observational studies and meta-analyses have consistently demonstrated a robust association between moderate-to-severe OSA and an increased risk of cardiac events following ACS.23 24 Yet recent randomised controlled studies have found no benefit from CPAP for secondary cardiovascular prevention. Building on this existing research, our study sought to explore the effect of moderate-to-severe OSA on MACCE, specifically in the high-risk subgroup of patients with hypertension following ACS onset. This study was motivated by epidemiological data, indicating that hypertension is present in approximately half of OSA patients, and that the incidence of OSA is elevated in hypertensive patients.25 Both of these conditions are known to contribute to endothelial dysfunction and accelerate the progression of atherosclerotic plaque,24 thereby increasing the likelihood of recurrent cardiovascular events after ACS. Our study findings align with this body of knowledge, 1247 (64.7%) patients had hypertension and 1014 (52.6%) patients had OSA, revealing that OSA is significantly associated with recurrent cardiovascular events among hypertensive patients, but not among those without hypertension. Moreover, we found that patients with preexisting severe hypertension who also had OSA were at particularly high risk for MACCE, while this relationship was not observed in patients with grade 1 or 2 hypertension. No significant signal of interaction was observed between OSA and hypertension for cardiovascular events. This could be due to the limited statistical power, resulting from the relatively small sample size and the low event rates during the relatively short follow-up period. Therefore, the results should be interpreted with caution and require further verification with larger cohorts.
A growing body of evidence suggests a close association between OSA and hypertension, with OSA potentially playing an active role in the development of hypertension.26 27 The underlying mechanism may involve OSA-mediated intermittent hypoxemia and sympathetic nervous system activation, which can contribute to the development of hypertension. Moreover, the cyclical hypoxemia-reoxygenation associated with OSA can promote oxidative stress, systemic vascular inflammation and endothelial dysfunction, all of which can further contribute to the development of hypertension.28 29 Notably, OSA and hypertension exhibit a bidirectional relationship, and together, they may synergistically accelerate the progression of atherosclerosis and increase the risk of adverse cardiovascular events. Our study found that the presence of OSA and hypertension was associated with a higher rate of PCI due to severe coronary lesions. Furthermore, we observed a greater incidence of ischaemia-driven revascularisation in patients with OSA and hypertension, compared with those without OSA. This association was only observed in patients with hypertension and not in those without hypertension.
Current evidence suggests that CPAP has a neutral effect on secondary cardiovascular prevention.4 5 In the ISAACC trial, non-sleepy patients with ACS and OSA were randomly assigned to receive either CPAP treatment plus usual care or usual care alone. Over an average follow-up of 3.35 years, no significant difference was observed in the composite endpoint of cardiovascular death or non-fatal events. However, adherence to CPAP treatment was poor, with an average use of only 2.78 hours per night.4 Subgroup analyses showed no significant difference in primary outcomes between CPAP treatment and usual care in patients with OSA after ACS (with or without hypertension). Nonetheless, the number of adverse events was numerically lower in patients with hypertension who received CPAP treatment (18.86% vs 22.41%).4 Our study found that only patients with both OSA and hypertension had a greater risk of adverse events after suffering ACS, indicating that this high-risk subgroup is likely to benefit from treatment. Conversely, the prognosis of patients with hypertension but without OSA was similar to those without hypertension (with or without OSA). OSA appears to be a crucial modifiable factor responsible for the adverse impact of hypertension on ACS. Therefore, screening for OSA in patients with hypertension and ACS is essential, and a modest intervention may be required. Further trials are needed to prove the efficacy of such interventions in this high-risk subgroup.
Limitations
First, the diagnosis of OSA was based on portable cardiorespiratory polygraphy, which may underestimate AHI compared with full polysomnography. However, this method is a safe and straightforward way to monitor OSA in high-risk patients, and there is evidence of its validity.30 Second, the severity of OSA could potentially change in the weeks after ACS,31 32 suggesting that OSA identified after ACS may be a temporary phenomenon. Nevertheless, this is true for OSA evaluation in the setting of any acute disease, including heart failure. Also, sleep studies were conducted after clinical stabilisation in this study to minimise potential bias. Third, although we excluded patients with diagnosed secondary hypertension, it is possible that there are patients with unidentified secondary hypertension, which may affect the accuracy of the results to some extent. Fourthmore, it is unknown whether our results can be extrapolated to the women or obese population as the majority of participants were men and non-obese. Last but not least, this study primarily recruited East-Asian patients, and our findings cannot be generalised to patients from other ethnicities.