Editor's Note: Commentary based on Clark A, Lange T, Hallqvist J, Jennum P, Hulvej N. Sleep impairment and prognosis of acute myocardial infarction: a prospective cohort study. Sleep 2014;37:851-8..

Background

Sleep loss, chronic sleep deprivation, and variable sleep quality are increasing problems in modern society. While initial epidemiologic studies focused on the cardiac effects of clinical sleep disorders (i.e., sleep-disordered breathing/sleep apnea) and sleep duration, the possible effects of more common aspects of sleep quality on cardiovascular morbidity have increasingly become a topic of interest.^1,2 Studies suggest that impaired sleep may be both a risk factor for the development of primary cardiovascular disease as well as a mediator of prognosis in chronic cardiovascular disease.³ Snoring and sleep-disordered breathing have been examined in this context, while more common symptoms and excessive daytime sleepiness are less well understood. Despite evidence describing gender differences as related to the cardiovascular effects of poor quality sleep,⁴ the effects of gender differences as related to prognosis in this setting have not yet been elucidated.

The authors of a study published in Sleep hypothesize that impaired sleep could hamper restitution following an acute myocardial infarction (AMI) by suppressing slow-wave sleep with adverse effects on various body systems, including cardiovascular processes, involved in recovery. The aim of the study is to determine how disturbed sleep, impaired awakening, daytime sleepiness, and frequent nightmares affect the prognosis of AMI in terms of case fatality and subsequent AMI, stroke, and heart failure among women and men with a first-time AMI.

Methods

This is a prospective cohort study in the setting of the Stockholm Heart Epidemiology Program (SHEEP) in Sweden. SHEEP is a population-based case study of all Swedish citizens aged 45 to 70 years who developed a first-time primary AMI over a two-year period between 1992 and 1994. Criteria for AMI included the following: 1) specific symptoms, 2) specified changes in blood levels of creatine kinase and lactate dehydrogenase, 3) specified electrocardiogram changes, and 4) autopsy findings. Participants included 2,245 first-time AMI cases. Sleep impairment was assessed by the Karolina Sleep Questionnaire, which details a variety of indices of impaired sleep, including disturbed sleep, impaired awakening, daytime sleepiness, and nightmares. Symptoms were ranked on a scale of five, from (1) "never/very good" to (5) "almost every day/very bad."

Covariates included age at baseline, perceived stress, smoking status, alcohol consumption, coffee consumption, average physical activity in the decade prior to initial AMI, body mass index, diabetes, hypertension, highest achieved level of education, cohabitation, shift work, and hereditary heart problems. The prognostic outcomes analyzed included case fatality, incidence of or death from AMI, stroke, and heart failure; these events (within up to 10 years of follow-up) were identified through national registries. For statistical methods, multiple logistic regression models were used to determine the association between case fatality and measure of sleep impairment, and Cox proportional hazard models were used to determine the association with subsequent occurrence of AMI, stroke, and heart failure.

Results

The median baseline age was 60 years. About one-third of women and one-fifth of men reported disturbed sleep. Overall, a higher proportion of those patients endorsing disturbed sleep also had a more significant cardiac risk profile including diabetes, physical inactivity, smoking, drinking above sensible limits, no cohabitating, and shift work.

This large-scale prospective study revealed sex-specific effects of some aspects of impaired sleep which varied by short- and long-term prognosis, while other aspects of impaired sleep had no effect on prognosis after first AMI.

In men, a strong effect on case fatality (odds ratio = 3.27; 95% CI: 1.76–6.06) was observed in regards to impaired awakening; however, no consistent effect of impaired sleep was seen on long-term cardiovascular prognosis.

In women, disturbed sleep showed a consistently higher risk of long-term cardiovascular events: AMI (hazard ratio [HR] = 1.69; 95% confidence interval [CI] 0.95–3.00), stroke (HR = 2.61; 95% CI: 1.19–5.76), and heart failure (HR = 2.43; 95% CI: 1.18–4.97), whereas no clear effect of impaired sleep on case fatality was found in women.

The authors admit that it is unclear why women are more prone to the consequences of disturbed sleep over time, whereas men are more susceptible to the consequences of impaired awakening in the sub-acute time period immediately following AMI.

Conclusion

This study suggests that disturbed sleep in women and impaired sleep in men might be related to a moderately higher risk of poor cardiac prognosis after first AMI – regardless of demographic, behavioral, or cardiac risk factors affecting prognosis. Evaluation of sleep complaints may have a role in secondary cardiovascular prevention even if, as the authors note, these sleep complaints represent prognostic risk markers rather than risk factors.

Commentary/Perspective

This study should be commended for being the first prospective cohort study that addresses how common aspects of impaired sleep affect short- and long-term cardiovascular prognosis following AMI. Various aspects of impaired sleep were detailed and correlated with possible confounders and established cardiovascular biomarkers. In addition, the analysis of gender differences is an important aspect of this study that revealed interesting results, as noted above.

The authors concede the potential drawbacks of using subjective questionnaire-based data compared to more objective data (i.e., polysomnography). However given the size of the data set, performing a polysomnogram on every patient would not be feasible. As the data collected for the patients reflected a one-time questionnaire focusing on quality of sleep within one year prior to the initial AMI, it was not possible to analyze change of symptoms over time or symptoms post-AMI.

About 20% of patients in the study failed to complete the questionnaire, and these patients often had a worse cardiovascular prognosis. If, as the authors point out, patients with impaired sleep were more likely to be non-responders, this could imply an underestimation of the observed associations. Of course, this scenario is impossible to assume.

Modern sleep medicine practice often puts sleep-disordered breathing and sleep apnea as "first on the list" of conditions that require diagnosis and treatment, with the assumption that focusing on treating specific sleep-related symptoms such as excessive daytime sleepiness and snoring is a futile effort without treating underlying sleep-disordered breathing first. In addition, the treatment of sleep-disordered breathing has been shown to decrease the risk of certain cardiovascular outcomes.⁵ The authors note that this patient population was not routinely screened or treated for sleep-disordered breathing and that this may affect data analysis.

Clearly the management of acute coronary syndrome has also advanced dramatically in the over twenty years since this study population was analyzed. Indeed, troponin levels were not analyzed in this study, presumably because they were not part of routine clinical practice at the time. Therefore the results of this study may not be entirely applicable to cardiovascular and sleep medicine practices and patient populations of today.

Finally, and as noted by the authors, the study population consisted of older, mostly male Swedish adults, which makes generalizability to other populations a challenge.

Despite these limitations, however, this study demonstrates a fascinating analysis of the effect of impaired sleep on cardiovascular outcomes after first AMI. The treatment of impaired sleep patterns focuses primarily on behavioral/lifestyle modifications, which, if effective, certainly costs less than many treatments in both cardiovascular and sleep medicine. This could potentially have clinical, economic, and societal implications regarding optimal management in preventive cardiovascular medicine. Hopefully this study will provide a foundation for future investigation into the effects of disturbed sleep on cardiovascular outcomes.

References

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1. Laugsand LE, Vatten LJ, Platou C, Janszky I. Insomnia and the risk of acute myocardial infarction: a population study. Circulation 2011;124:2073-81.
2. Meisinger C, Heier M, Lowel H, Schneider A, Doring A. Sleep duration and sleep complaints and risk of myocardial infarction in middle-aged men and women from the general population: the MONICA/KORA Augsburg cohort study. Sleep 2007;30:1121-7.
3. Janszky I, Ljung R, Rohani M, Hallqvist J. Heavy snoring is a risk factor for case fatality and poor short-term prognosis after a first acute myocardial infarction. Sleep 2008;31:801-7.
4. Cappuccio FP, Miller MA. The epidemiology of sleep and cardiovascular risk and disease. In: Cappuccio FP, Miller MA, Lockley SW, eds. Sleep, Health, and Society - from Aetiology to Public Health. New York: Oxford Universty Press, 2010:83-110.
5. Bradley TD, Floras JS. Obstructive sleep apnoea and its cardiovascular consequences. Lancet 2009;373:82–93.

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