Association between sleep disorders and sleep-wake disturbance with MACE or all-cause mortality in the post-stroke population

By Bhavana KunkalikarReviewed by Danielle Ellis, B.Sc.Feb 22 2023

In a recent study published in Sleep Medicine, researchers assessed the association between post-stroke sleep disturbances and recurrent cardiovascular events.

Background

In the US, strokes are one of the leading causes of mortality and the main causal factor of long-term disability. The one-year risk of cardiovascular disease (CVD) recurrence and mortality for survivors remains significant. Given the impact of strokes on public health, recognizing intervention targets to mitigate secondary cardiovascular disease and mortality risk among stroke survivors is an important topic of concern.

Sleep disruptions, such as poor sleep quality, abnormally long or short sleep duration, and sleep disorders, increase the risk of incident cardiovascular disease. Comparable results have been observed for stroke in particular. For instance, sleep-disordered breathing, such as obstructive sleep apnea (OSA), is an important stroke risk factor.

About the study

The present study investigated the relationship between sleep disturbances and recurring all-cause mortality or acute coronary events in post-stroke patients.

The team searched six biomedical electronic databases, namely, PubMed, Embase, The Cochrane Library, PsycINFO, CINAHL, and Allied and Complementary Medicine, between database inception and August 2021. The search techniques included subject headings as well as free-text terms pertinent to factors such as sleep, sleep length, sleep quality, sleep therapies, sleep disorders, transient ischemic attack (TIA), stroke, major adverse cardiovascular events (MACE), and recurring stroke and CVD occurrences.

The key criterion for study inclusion was that the examined study must have investigated the association between sleep and recurrent cerebrovascular or cardiovascular incidents following TIA or stroke. Individuals who had suffered a TIA or stroke were a part of the study population. The exposures of interest were disturbances in the sleep-wake pattern, sleep interventions, or sleep disorders. The outcomes included MACE recurrence and all-cause mortality.

Results

The database search yielded 5,116 references and six additional records from other sources. There were a total of 4873 references after duplicated studies were removed. After examining the abstracts and titles, 66 papers were chosen for full-text analysis. Thirty-two studies were finally involved in the systematic review. Of the 32 included studies, 10 were randomized controlled trials (RCTs), while 22 were observational studies.

The team noted that nine of 10 experiments reported randomization methods adequately. The majority of the research described allocation concealment accurately. All of the studies utilized an open-label design, posing a high potential for bias with respect to participant blinding.

Almost 15 prospective observational studies investigating the association between OSA and recurrent episodes in stroke patients were identified. Out of the 15, a total of 11 studies on OSA found a positive association of OSA and/or OSA severity with recurrent events/mortality, whereas four studies found no association. The majority of studies evaluated OSA severity using objective measurements, such as the apnea-hypopnea index (AHI), respiratory event index (REI), respiratory disturbance index (RDI), or oxygen desaturation index (ODI).

A study discovered that AHI was substantially associated with all-cause mortality throughout a two-year follow-up period in individuals who had suffered from their first-ever TIA or stroke. Another study dichotomized ischemic stroke cases into low or high-risk groups and estimated the mortalities reported for almost 60 months after the stroke. Almost 22% of those with a high AHI died, while only 9% of low AHI patients died. However, this difference did not have statistical significance.

Non-survivors were reported to have considerably higher AH than survivors. Ponsaing dichotomized high and low AHI incidences divided the sample group into two equal-sized cohorts. In the 19 to 37 months following hospitalization for stroke or TIA, a high AHI was related to all-cause mortality.

A study also compared continuous positive airway pressure (CPAP)-tolerant OSA patients to OSA patients who could not tolerate CPAP. All cases had suffered a TIA or ischemic stroke. Throughout the 18-month follow-up period, non-usage of CPAP was linked with an over five-fold increase in the risk of new vascular events compared to CPAP users. Individuals who did not tolerate CPAP had a higher risk of death than those who did use CPAP, although there were no variations in mortality between patients with no OSA, mild OSA, and those who utilized CPAP.

A later study followed the same subjects for seven years to investigate cardiovascular events. Compared to other cohorts, patients who did not utilize CPAP reported an elevated seven-year risk of both non-fatal CV events and CV death.

Conclusion

The study findings highlighted a positive association between OSA and/or OSA severity and risk of mortality and recurrent events. To reduce the risk of recurrence and death after stroke, studies should identify novel and efficacious secondary prevention targets. Future research addressing the role of sleep disruptions in the recurrence of cerebrovascular and cardiovascular events in stroke will help inform the development of novel therapies to enhance sleep among stroke survivors.