CPAP therapy in the prevention of cardiovascular risk in patients with OSA

Continuous positive airway pressure (CPAP) therapy is not always beneficial in the prevention of cardiovascular events in patients with obstructive sleep apnoea (OSA), due to low CPAP usage, the inclusion of non-sleepy patients, and the usage of wrong selection criteria. New markers, such as hypoxic burden, are showing potential in stratifying patients with OSA for cardiovascular risk. For non-sleepy patients with OSA, there is a need still for specific cardiovascular-associated markers to demonstrate the benefit of CPAP therapy on cardiovascular risk.

“We should not forget that the main target of CPAP therapy is to treat sleepiness in patients with OSA,” said Prof. Raphael Heinzer (Lausanne University Hospital, Switzerland) at the start of his presentation on the future of sleep science [1]. For this clinical outcome, CPAP has been demonstrated to be an effective therapy [2]. In addition, excessively sleepy patients with OSA are at increased risk for cardiovascular diseases [3]. However, the majority of patients with OSA do not report sleepiness [4]. “So how do we treat the non-sleepy patients? And which patients are likely to benefit from CPAP in terms of cardiovascular risk reduction?”

The SAVE study did not show a clear benefit of CPAP therapy in the secondary prevention of adverse cardiovascular events in patients with OSA [5]. “Why did we not see an effect of this intervention in these patients?” asked Prof. Heinzer. Possible explanations are the low CPAP usage (<3 hours per night) in these trials or the fact that these trials included non-sleepy patients. Irreversible cardiovascular damage and the use of the apnoea hypopnoea index (AHI) as an inadequate selection criterion are other potential explanations. “Indeed, patients with AHI <15/hour and patients with AHI >15/hour did not differ with respect to their risk for cardiovascular incidences,” stated Prof. Heinzer [6]. Fortunately, other markers that might have potential in stratifying patients with OSA for cardiovascular risk are emerging. Hypoxic burden was a significant predictor of cardiovascular death and cardiovascular events in 2 cohorts [7,8]. Next to this measure, the sleep apnoea-specific pulse-rate response as well as pulse-wave amplitude drops have been associated with the risk for cardiovascular events [4,9]. “Pulse-wave amplitude drops reflect peripheral vasoconstriction resulting from sympathetic activation,” clarified Prof. Heinzer. Interestingly, low pulse-wave amplitude drops were linked to a higher incidence of cardiovascular events. Prof. Heinzer argued that endothelial dysfunction or a blunted autonomic reactivity may be the underlying causes that explain this association.

“We need prospective primary prevention studies including patients with OSA stratified to more specific cardiovascular-associated markers, to demonstrate the benefit of CPAP therapy on cardiovascular risk in non-sleepy patients with OSA,” continued Prof. Heinzer. “However, randomised trials are not feasible in primary prevention for ethical reasons.” Follow-up of prospective clinical real-world cohorts appears to be the most suitable study design. Propensity score matching, inverse probability of treatment weighting, and other inventive techniques should be applied to gain reliable well-balanced data.

1. Heinzer R, et al. The future of sleep science: what are the correct targets, outcome parameters, innovative studies and methodologies? Session 407, Abstract 3635, ERS International Congress 2022, 4–6 September.
2. Sawyer AM, et al. Sleep Med Rev. 2011;15(6):343–356.
3. Mazotti DR, et al. Am J Respir Crit Care Med. 2019;200(4):493–506.
4. Heinzer R, et al. Lancet Respir Med. 2015;3(4):310–318.
5. McEvoy RD, et al. N Engl J Med. 2016;375:919–931.
6. Sanchez-de-la-Torre M, et al. Lancet Respi Med. 2020;8(4):359–367.
7. Azarbarzin A, et al. Eur Heart Journal. 2019;40(14):1149–1157.
8. Trzepizur W, et al. Am J Respir Crit Care Med. 2021;205(1):108–117.
9. Azarbarzin A, et al. Am J Respir Crit Care Med. 2021;203:A1103.

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Posted on 30 October 202217 May 2024