Sleep and nocturnal apneas: beyond discomfort, they increase the risk of heart attack and stroke

Editorial note: This article has been previously published and updated according to scientific and informative criteria. It is for informational purposes only and does not replace medical advice.

IN BRIEF

• Obstructive sleep apnea (OSA) interrupts breathing during the night and can cause fragmented sleep and intermittent hypoxia.
• Observational evidence links OSA to an increased risk of cardiovascular events, including stroke and heart attack, but association does not automatically prove causality.
• Plausible biological mechanisms include intermittent hypoxia, sympathetic activation, inflammation, oxidative stress, and coagulation alterations.
• Randomized studies on positive airway pressure (CPAP) therapy have not consistently shown a reduction in cardiovascular events in the populations studied so far; however, benefits for symptoms and sleep quality remain.
• For clinical and population decisions, it is important to assess individual risk, OSA severity, daytime symptoms, and co-existence of obesity or cardiovascular diseases.

Abstract: what does science say?

Obstructive sleep apnea is characterized by repeated obstructions of the upper airway during sleep, resulting in reduced oxygen flow, brief awakenings, and fragmented sleep. Observational studies on large cohorts and meta-analyses show an association between OSA and an increased likelihood of cardiovascular events (stroke, heart attack) and related risk factors (hypertension, diabetes), but the relationships appear to be influenced by severity, obesity, and comorbidities. Experimental evidence on the cardiovascular benefits of positive airway pressure (CPAP) therapy is heterogeneous: some trials have not found clear reductions in major events, suggesting that the effect depends on adherence to therapy, patient risk profile, or intervention timing. The hypothesized biological mechanisms — intermittent hypoxia, oxidative stress, inflammation, and coagulopathic alterations — offer biological plausibility but do not alone confirm a direct causal link. Open questions remain about which subgroups derive cardiovascular benefit from treatment and how to measure risk beyond the traditional apnea-hypopnea index.

Main section

Definition and clinical impact

Obstructive sleep apnea syndrome (OSA) consists of repeated partial or complete obstructions of the upper airway during sleep, each usually lasting more than 10 seconds. These episodes cause temporary drops in oxygen saturation, brief awakenings, and sleep fragmentation, leading to daytime sleepiness, reduced quality of life, and possible metabolic alterations. Prevalence increases with age and body weight; recent epidemiological studies estimate that the moderate-to-severe form is common in middle-aged adults and older [2]. Clinical impact includes daily symptoms (fatigue, poor concentration), safety risks (e.g., traffic accidents due to sleepiness), and potential systemic consequences on the cardiovascular system.

What does observational evidence show?

Population surveys and clinical cohorts have found an association between the presence and severity of OSA and an increased risk of composite cardiovascular events (heart attack, stroke, heart failure) and mortality. A large cohort study of over 10,000 adults with polysomnography showed that variables other than the apnea-hypopnea index (AHI) alone — such as time spent with saturation <90%, awakenings, and nocturnal heart rate — predict cardiovascular events during follow-up [1]. Meta-analyses of prospective studies confirm the association for stroke and cardiovascular outcomes, with a more marked effect in cases of severe OSA [4]. These results are useful for identifying risk signals but do not, by themselves, establish a certain cause-and-effect relationship.

Biological mechanisms explaining the risk

The biological plausibility of the link between OSA and cardiovascular diseases is supported by several integrated mechanisms. Nocturnal intermittent hypoxia and frequent arousals activate the sympathetic nervous system, raise blood pressure, and promote various pro-atherogenic processes. Review studies describe how these repeated fluctuations can induce systemic inflammation, endothelial dysfunction, increased oxidative stress, and metabolic alterations that promote atherosclerosis and hypertension [3].

Intermittent hypoxia and oxidative stress

Repeated exposure to cycles of desaturation and reperfusion is comparable to an ischemia-reperfusion phenomenon at the cellular level: it generates reactive oxygen species and activates inflammatory pathways. This process can damage the vascular endothelium, alter vasodilatory function, and promote atherosclerotic deposits and plaque instability [4]. Experimental data and studies on clinical biomarkers confirm increases in oxidative markers in subjects with OSA compared to controls.

Endothelial dysfunction, coagulation, and sympathetic activity

Repeated arousals and sympathetic activation lead to nocturnal blood pressure spikes and greater heart rate variability. Simultaneously, alterations in coagulation and markers of inflammation are observed, which can increase the tendency for thrombus formation. These combined phenomena offer a mechanistic framework for the increased risk of ischemic events observed in populations with OSA [3][4].

Clinical evidence: observations and trials

Observational studies and meta-analyses

Analyses of large cohorts and prospective meta-analyses show an association between OSA and an increased risk of stroke, heart attack, and mortality, with an effect that increases with OSA severity. These studies also find that parameters related to nocturnal hypoxia and sleep fragmentation can predict cardiovascular events beyond simple AHI [1][4]. However, the results must be interpreted in light of potential confounders (obesity, hypertension, diabetes) and the observational nature of the studies.

Randomized studies on CPAP treatment

Randomized clinical trials that evaluated positive airway pressure (CPAP) for the secondary prevention of cardiovascular events have produced heterogeneous results. A meta-analysis of randomized trials did not find a significant reduction in cardiovascular events or mortality with PAP in aggregated data [6]. The SAVE trial (NEJM) in patients with pre-existing cardiovascular disease showed no reduction in the composite endpoint with CPAP compared to usual care; average adherence was one of the critical considerations [7]. The RICCADSA trial, conducted in coronary artery disease patients who were not excessively sleepy, showed similar results in reducing major events, highlighting its limitations in the studied populations and the importance of patient selection [8]. In summary, randomized evidence does not confirm a systematic protective effect of CPAP on cardiovascular events under the conditions and in the populations evaluated so far.

Particular populations

Obesity and shared risk

Obesity is one of the main risk factors for OSA: increased perioral and pharyngeal adipose tissue increases the likelihood of airway collapse during sleep. Furthermore, obesity, insulin resistance, and metabolic dysfunction are conditions that overlap and mutually amplify cardiovascular risk. Population studies highlight that a large proportion of patients with OSA are overweight or obese; for this reason, risk assessment must take this common determinant into account [2].

Children: development and behavior

In children, OSA often manifests with different symptoms than in adults: neurobehavioral disorders, academic difficulties, hyperactivity, and attention problems are among the most documented consequences. Pediatric clinical studies show that OSA can be associated with cognitive deficits and markers of endothelial dysfunction; some interventions (e.g., adenotonsillectomy) can improve neurocognitive aspects in younger children, but the quality and heterogeneity of the evidence require caution [5].

Practical section

What it means in practice

For the average person: snoring or noticing breathing interruptions during the night is a signal that deserves attention. The presence of marked daytime sleepiness, frequent nocturnal awakenings, observed apneas, and cardiovascular symptoms requires clinical evaluation. In a medical context, suspected OSA is addressed with screening questionnaires, assessment of symptom severity, and, when indicated, with sleep monitoring (polysomnography or home-based tests). Therapeutic decisions must balance the benefits on sleep and symptoms (which are established) with realistic expectations regarding the reduction of cardiovascular risk: CPAP therapy improves symptoms and sleep quality, but the evidence demonstrating a systematic reduction of major cardiovascular events in the studied populations is not unequivocal [6][7][8].

KEY POINTS TO REMEMBER

• OSA is common and can cause fragmented sleep, intermittent hypoxia, and daytime symptoms that reduce quality of life.
• Observational studies link OSA to an increased cardiovascular risk, but the association does not automatically imply direct causality.
• Plausible mechanisms include intermittent hypoxia, sympathetic activation, inflammation, oxidative stress, and coagulating alterations.
• CPAP is effective in reducing symptoms and improving sleep; evidence on reducing cardiovascular events is still conflicting and depends on the population, adherence, and study design.
• Assess individual risk — OSA severity, obesity, associated cardiovascular diseases — to guide clinical management.

Limitations of the evidence

It is useful to distinguish between different types of evidence. Observational studies (cohorts, case-control) report robust associations between OSA and cardiovascular disease, but remain subject to residual confounding (e.g., obesity, lifestyle) and selection bias. Causal evidence requires randomized controlled interventions: available RCT trials have not shown a clear reduction in cardiovascular events with CPAP in most analyzed contexts, but they have limitations — insufficient adherence, populations with already advanced or selected disease, limited follow-up — which complicate interpretation [6][7][8]. Furthermore, the conventional measure of severity (AHI) may not capture relevant aspects such as the duration of hypoxia or sleep fragmentation, which have been predictive in some studies [1]. Biological variability, differences in design, and population heterogeneity require caution in clinical conclusions and public health recommendations.

Editorial conclusion

Obstructive sleep apnea represents a medical condition with broad implications for sleep quality and systemic implications affecting metabolism and the cardiovascular system. Observational literature indicates a consistent association with stroke, heart attack, and other vascular complications, and the described biological mechanisms are plausible. However, the results of randomized studies on the prevention of cardiovascular events remain inconclusive: this suggests that the relationship is complex and that the benefit of therapy depends on specific patient factors, adherence to treatment, and the timing of the intervention. For the general public and clinicians, the prudent approach combines symptom assessment, severity measurement, control of modifiable risk factors (weight, blood pressure, glycemic control), and a personalized diagnostic-therapeutic pathway. Further studies are needed to identify subgroups that derive real cardiovascular benefit from treatment and to improve diagnostic tools that go beyond AHI alone.

Editorial note

This article has been updated to reflect available scientific evidence and to improve clarity and transparency. The information provided is for informational purposes only and does not replace medical advice. Anyone who suspects they have sleep apnea or has cardiovascular conditions should consult their doctor or a sleep specialist.

SCIENTIFIC RESEARCH

1. Kendzerska T, Gershon AS, Hawker G, Leung RS, Tomlinson G. Obstructive sleep apnea and risk of cardiovascular events and all-cause mortality: a decade-long historical cohort study. PLoS Med. 2014;11(2):e1001599. https://doi.org/10.1371/journal.pmed.1001599
2. Peppard PE, Young T, Barnet JH, Palta M, Hagen EW, Hla KM. Increased prevalence of sleep-disordered breathing in adults. Am J Epidemiol. 2013;177(9):1006–1014. https://doi.org/10.1093/aje/kws342
3. Kohler M, Stradling JR. Mechanisms of vascular damage in obstructive sleep apnea. Nat Rev Cardiol. 2010;7(12):677–685. https://doi.org/10.1038/nrcardio.2010.145
4. Lavie L. Obstructive sleep apnoea syndrome—an oxidative stress disorder. Sleep Med Rev. 2003;7(1):35–51. https://doi.org/10.1053/smrv.2002.0261
5. Gozal D, Kheirandish-Gozal L, Bhattacharjee R, Spruyt K. Neurocognitive and endothelial dysfunction in children with obstructive sleep apnea. Pediatrics. 2010;126(2):e233–e239. https://doi.org/10.1542/peds.2010-0688
6. Yu J, Zhou Z, McEvoy RD, et al. Association of Positive Airway Pressure With Cardiovascular Events and Death in Adults With Sleep Apnea: A Systematic Review and Meta-analysis. JAMA. 2017;318(2):156–166. https://doi.org/10.1001/jama.2017.7967
7. McEvoy RD, Antic NA, Heeley E, et al. CPAP for Prevention of Cardiovascular Events in Obstructive Sleep Apnea. N Engl J Med. 2016;375(10):919–931. https://doi.org/10.1056/NEJMoa1606599
8. Rosenberg R, (RICCADSA investigators) et al. Effect of Positive Airway Pressure on Cardiovascular Outcomes in Coronary Artery Disease Patients with Nonsleepy Obstructive Sleep Apnea: The RICCADSA Randomized Controlled Trial. Am J Respir Crit Care Med. 2016; (see DOI below). https://doi.org/10.1164/rccm.201601-0088OC

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