A treatment commonly used for obstructive sleep apnoea (OSA), lowers the risk of serious cardiovascular events in some patients but not others, according to research published in the European Heart Journal [1] today.
People with OSA often snore loudly, their breathing starts and stops during the night, and they may wake up several times. Not only does this cause tiredness, but it can also increase the risk of high blood pressure, stroke and heart disease.
The treatment called a continuous positive airway pressure machine (CPAP), works by blowing air through a face mask throughout the night to prevent the user's airways from closing.
The new research was led by Dr Ali Azarbarzin from Brigham and Women's Hospital and Harvard Medical School, Boston, USA. He explained: "We know that OSA is linked to cardiovascular disease but clinical studies of treating OSA with CPAP have not shown a long-term cardiovascular benefit. This creates uncertainty about whether all people with OSA should be treated."
To address this uncertainty, the researchers brought together the results of three separate trials that have tested CPAP for people with OSA. This allowed them to study a larger group of people and to break the data down according to different groups of patients.
Altogether, this included 3,549 people with OSA and cardiovascular disease, with around half using CPAP machines and half not using CPAP. All the patients were tested at the start of the studies to confirm that they had OSA. Patients were followed up for an average of three years and any heart attacks, stokes or deaths from cardiovascular disease were recorded.
Previously, these trials studied the overall effect of CPAP without considering the fact that in some people OSA causes severe drops in the level of oxygen in the blood or large surges in heart rate, known as high-risk OSA, but in others it does not. In the new study, the researchers' analysis revealed that, in patients with high-risk OSA, CPAP lowered the risk of heart attack, stroke and death from cardiovascular disease by around 17%. This was 31% better than the effect of treatment in those without high-risk OSA', for whom CPAP may even increase the risk of serious cardiovascular events by around 22%.
When researchers looked more closely just the at patients who did not feel sleepy during the daytime, these findings were even stronger. For these patients, CPAP lowered cardiovascular risk by 24% in high-risk OSA but increased cardiovascular risks in the other patients by 30%.
Dr Azarbarzin said: "Our findings suggest that CPAP may offer long-term cardiovascular benefit in people with high-risk OSA but may have unintended harmful effects in those without high-risk OSA.
"For people with high-risk OSA, CPAP likely helps by preventing low oxygen levels and calming the overactive sympathetic nervous system during sleep. Both of these are linked to cardiovascular disease.
"But in people without these high-risk markers, who are already at very low cardiovascular risk, CPAP seems to have downsides. While we don't really know why, one possibility is that the pressure used in CPAP may stretch the lungs in a way that puts stress on the cardiovascular system. Another is that CPAP could disturb sleep for some people, and sleep disruption itself is a risk factor for cardiovascular problems. More research is needed to understand these mechanisms.
"Our findings suggest a more personalised approach to treating OSA. Instead of treating everyone the same, we should consider whether someone has high-risk features. These are the people who seem most likely to benefit from CPAP. For clinicians and policy makers, this means we may need to rethink current guidelines for treating non-sleepy patients and consider focussing treatment for cardiovascular risk reduction on those who stand to gain the most. We also need to be cautious about using CPAP in people who don't have high-risk markers, as they may not benefit and could even be harmed.
"CPAP-related harm was seen only in non-sleepy patients with existing heart disease, according to the design of the trials analysed in this study. Whether this applies to other patients remains unknown and needs further research."
To confirm their findings, Dr Azarbarzin and his colleagues are planning a new clinical trial focused on people with high-risk OSA. They are also investigating how and why CPAP could cause harm in people who do not have high-risk OSA, and they are exploring alternatives to CPAP for treating OSA and lowering cardiovascular risks.
In an accompanying editorial [2] Dr Andrea Natale from Texas Cardiac Arrhythmia Institute, Austin, USA and colleagues said: "OSA has been reported to increase the risk of heart failure by 140%, the risk of stroke by 60%, and the risk of coronary heart disease by 30%.
"Three major randomised trials (RCTs), ISAACC, RICCADSA, and SAVE, between 2016 and 2020, published their assessment on the effects of CPAP on the long-term adverse cardiovascular outcome risk in OSA patients with pre-existing cardiovascular comorbidities. […] each of these three RCTs demonstrated the failure of CPAP therapy in reducing the cardiovascular risk in minimally sleepy or non-sleepy patients with moderate to severe OSA.
"The current meta-analysis by Azarbarzin et al., published in this issue of the European Heart Journal, examined the role of CPAP in reducing CV risk in patients with vs. without high-risk OSA, defined as the presence of either a high pulse rate response or a high hypoxic burden, by pooling individual patient data from the three RCTs mentioned above.
"The current study reported two novel findings that are worth mentioning. First, the authors demonstrated a harmful impact of CPAP in 'low-risk OSA' patients that included all except those with a heart rate response >9.4 bpm or a hypoxic burden >87.1%. The possible underlying mechanism for this observation is, however, unclear. Second, they documented CPAP benefits only in high-risk individuals, especially those without excessive sleepiness and/or hypertension."
