|Year : 2022 | Volume
| Issue : 3 | Page : 120-126
Impact of Sleep on Cardiovascular Health: A Narrative Review
Oliver Sum-Ping1, Yong-Jian Geng2
1 Department of Psychiatry and Behavioral Sciences, The Center for Sleep Sciences and Medicine, School of Medicine, Stanford University, Stanford, CA, USA
2 Department of Internal Medicine, Division of Cardiovascular Medicine, University of Texas McGovern School of Medicine, Houston, Texas, USA
|Date of Submission||26-Aug-2022|
|Date of Acceptance||05-Sep-2022|
|Date of Web Publication||30-Sep-2022|
Dr. Oliver Sum-Ping
Department of Psychiatry and Behavioral Sciences, The Center of Sleep Sciences and Medicine, Stanford University Medical School, 450 Broadway Ave., Redwood City 94063, CA
Source of Support: None, Conflict of Interest: None
Sleep is a universal biological function but remains poorly understood and a relatively new field of science and medicine. Over the past decade, there have been rapidly accumulating scientific and clinical data around sleep, including the effects of various sleep aspects on cardiovascular health. Much of the research in the field has focused on sleep-disordered breathing, particularly obstructive sleep apnea. However, other sleep pathologies including hypersomnolence disorders, sleep-related movement disorders, and parasomnia disorders have been linked with cardiovascular health. Other areas of sleep, such as sleep duration, timing, and circadian rhythms, also have a demonstrated association with heart health. In this review, we provide an updated summary of the literature connecting sleep and cardiovascular disease.
Keywords: Sleep, circadian rhythm, apnea, heart, artery, atherosclerosis, hypertension, diabetes
|How to cite this article:|
Sum-Ping O, Geng YJ. Impact of Sleep on Cardiovascular Health: A Narrative Review. Heart Mind 2022;6:120-6
| Introduction|| |
Sleep is a universal and critical biological function in all human life. However, despite being an experience that is familiar to all as a scientific and medical field, it has remained dormant until recently, and there are a number of fundamental scientific and clinical questions related to sleep or sleep disorders that remain unexplored. However, over the past several decades, a dawning of interest in the field has led to a rapid expansion in the scientific and medical sleep literature, and a much greater understanding of sleep and its functions has begun to develop. While numerous mysteries continue to surround sleep, an important theme that has emerged in the literature has been the important role of sleep in healthy life.
The health implications of sleep quality and quantity are broad, including the importance of sleep in the arena of cardiovascular health. Healthy sleep consists of cycles of alternating periods of nonrapid eye movement (NREM) and rapid eye movement (REM) sleep. During NREM sleep, parasympathetic tone dominates, which reduces heart and respiratory rates as well as blood pressure. During REM sleep, sympathetic spikes trigger a variability in heart rate and blood pressure. Many sleep disorders can disrupt these patterns, often leading to cardiovascular consequences. The third edition of the International Classification of Sleep Disorders lists over 60 distinct sleep disorders. Collectively, these disorders are highly prevalent worldwide. Estimates for the prevalence of insomnia symptoms alone are up to 30% of the general adult population. Sleep disorders are also often under-recognized, representing a significant opportunity for the improvement of cardiovascular health.
However, sleep is multidimensional, and its quality is not simply a reflection of the presence or absence of pathology. Factors such as timing and duration play a key role in the effects of sleep on cardiovascular health. In recognition of this, the American Heart Association (AHA) has newly recognized sleep duration as a component of cardiovascular health, termed “Life's Essential 8” with 7–9 h of sleep per day being recommended for most adults.
In this review, we provide a summary of literature connecting sleep and cardiovascular health.
| Sleep-Disordered Breathing and Cardiovascular Health|| |
Sleep apnea represents one of the best-researched areas of sleep medicine, with many of the most clearly established links to cardiovascular health. Central sleep apnea (CSA) is characterized by a pause in breathing associated with an absence of respiratory effort. Obstructive sleep apnea (OSA) is a more common subtype of sleep apnea characterized by the repeated collapse of the upper airway during sleep. This repeated collapse can lead to a complex cascade of downstream phenomena. Most immediately, patients with OSA may experience consequential intermittent hypoxia, recurrent arousals, and large intrathoracic pressure swings during sleep. These can provoke secondary effects, including increased sympathetic activation,, inflammation,,, endothelial dysfunction, and altered hemodynamics., In addition to the subjective symptom burden which can result from these effects, including increased sleepiness, poor cognitive function, and mood disorders, there are more insidious consequences, most notably increased risk of cardiovascular disease.
Hypertension is a well-established cardiovascular risk factor associated with OSA. Data from the Sleep Heart Health Study, a large, multi-center community-based population study, demonstrated an increased prevalence of hypertension in participants with OSA in a dose-dependent fashion compared with controls even after adjusting for potential confounders such as Body mass index. Data from another large study, the Wisconsin Sleep Cohort Study (WSCS), demonstrated a dose-response association between OSA and presence of hypertension after 4 years, even after controlling for known confounders. While these data suggest that OSA increases the risk for developing hypertension, hypertension in those with OSA may not have the same characteristics as for those without OSA. Hypertension in the setting of OSA may also have a distinct profile, being more likely to take a refractory, form that is less responsive to anti-hypertensive medication and be nondipping, without the typically expected drop at night.
Coronary artery disease (CAD) has also been linked with OSA. Data from the WSCS demonstrated a link between severe OSA and incident CAD even after adjusting for confounding factors. Other sources have suggested that this association may be clearer with men than with women., OSA has also been identified as a risk factor for stroke through multiple prospective cohort studies independent of other vascular risk factors. This has been demonstrated to have a dose-response relationship in some studies.,, In addition to being linked to an increased risk of stroke, OSA has also been associated with worsened poststroke outcomes, including inferior functional outcomes, and increased mortality., OSA has also been associated with atrial fibrillation independent of confounding factors through multiple studies,, and respiratory events related to sleep apnea have even been suggested as an immediate triggers of paroxysms of atrial fibrillation. OSA is also frequently seen in heart failure (HF), though overlap with HF symptoms such as orthopnea, nocturnal dyspnea, and nocturia may make clinical recognition of OSA more challenging. In addition, CSA may be more commonly seen in HF patients.
While several strategies can be used to manage OSA, continuous positive airway pressure (CPAP) is the gold-standard treatment. CPAP uses the constant application of positive pressure to maintain a patent upper airway during sleep. It has been consistently shown to improve daytime sleepiness and other quality-of-life measures;,, however, evidence for its effects on cardiovascular health is a more mixed picture. Counter to the expectations of many, treatment of OSA with CPAP has not been consistently demonstrated to result in weight loss and has actually been associated with weight gain in recent studies. However, a number of intermediate endpoints and surrogate markers of cardiovascular health have been shown to improve when OSA is treated with CPAP. For example, the treatment of OSA with CPAP has been demonstrated to result in small, but statistically significant improvements in blood pressure,, decreases in markers of sympathetic activity,, improve insulin resistance in patients with impaired glucose tolerance and prediabetes,,, endothelial function,, and arterial stiffness.
Despite the above benefits of CPAP, its ability to reduce the risk of cardiovascular mortality or major adverse cardiovascular events in patients with OSA has not been supported by high-quality evidence thus far. While some observational evidence suggests that CPAP decreases risk of major cardiovascular events, no large-scale randomized control trial has demonstrated any kind of similar benefit for either primary or secondary prevention.,, The most prominent of these trials to date has been the Sleep Apnea Cardiovascular Endpoints (SAVE) which was a multicenter trial where 2717 patients with a history of CAD or cerebrovascular isease with untreated OSA were randomized to receive CPAP plus usual care or usual care alone. After a mean follow-up period of 3.7 years, no difference was reported between the groups in the primary endpoint of death resulting from cardiovascular causes, myocardial infarction, stroke, or hospitalization for unstable angina, HF, or transient ischemic attack. SAVE and other trials have had shared limitations including generally low CPAP adherence (mean duration of adherence of 3.3 h in the SAVE trial) and the necessary exclusion of the most sleepy and hypoxemic patients who may stand to benefit most from treatment.
CSA often occurs in the setting of other medical conditions, and CSA with Cheyne–Stokes respiration (CSR) is a CSA subtype particularly closely entwined with cardiovascular health. CSA-CSR is defined by periodic breathing with a crescendo-decrescendo pattern of tidal volume alternating with a central apnea or hypopnea. The presence CSR has been identified as a predictor of mortality in patients with HF. Efforts to target CSR with PAP, however, have failed to demonstrate a mortality benefit. The Canadian Continuous Positive Airway Pressure for Patients with Central Sleep Apnea and HF study investigated the effect of CPAP on mortality for patients with chronic HF. While the CPAP group demonstrated improvement in markers such as CSA events and oxygenation, no mortality benefit was seen compared to the control group. Adaptive servo-ventilation (ASV) is a form of noninvasive ventilation utilizing a dynamic inspiratory pressure support, responding to breath-by-breath changes in ventilation in a manner to create a cyclical pattern that is counter to the patient's periodic breathing. The treatment of sleep-disordered breathing with predominant CSA by Adaptive Servo-Ventilation in Patients with HF (SERVE-HF) trial tested the hypothesis that ASV may provide mortality benefit to patients with CSR in the context of chronic HF. However, there was an unexpected increase in all-cause and cardiovascular mortality in participants treated with ASV leading to the early termination of the study.
| Other Sleep Disorders and Cardiovascular Health|| |
While sleep-disordered breathing is the branch of sleep pathology most commonly considered in the context of cardiovascular health, there is evidence that links other sleep disorders to cardiovascular pathology.
Narcolepsy, a disorder of hypersomnolence, has been connected with a variety of other medical comorbidities. A retrospective medical claims analysis comparing patients with narcolepsy and healthy controls revealed a broad range of pathology with higher rates among patients with narcolepsy, including several cardiovascular diseases such as stroke, myocardial infarction, and cardiac arrest. Similar findings were reported in a questionnaire-based epidemiological study where statistically significant findings included a higher prevalence of heart disease, hypertension, and hypercholesterolemia among those with narcolepsy. However, there has not been complete agreement in the literature on these conclusions. The analysis of the Danish National Patient Registry revealed that patients with narcolepsy experienced higher rates of morbidity in several disease categories, including endocrine, neurologic, and musculoskeletal disorders, but there was no significant difference in the rates of cardiovascular disease between cases and controls observed. One of the more consistent findings in the literature has been increased rates of obesity among patients with narcolepsy, possibly as a consequence of hypocretin deficiency, with many children, in particular, experiencing rapid weight gain at disease onset,, and it has been speculated that this could be a contributing link between narcolepsy and potential cardiovascular morbidity. Even in Kleine–Levin syndrome, a rare disorder of hypersomnolence characterized by recurrent episodes of extreme sleepiness associated with cognitive and behavioral changes which can include megaphagia alternating with periods of normalcy, there is a reported case of cardiopulmonary arrest occurring during a period of autonomic instability in the setting excessive eating.,
Restless legs syndrome (RLS) is a sleep-related movement disorder characterized by an uncomfortable urge to move the legs, typically during the evening and sometimes interfering with attempts to sleep. Periodic limb movements of sleep (PLMS) describe the leg movements commonly seen during sleep in most patients with RLS. Analyses of RLS and PLMS in relation to cardiovascular disease and risk factors have produced mixed findings. Some data suggest that RLS is associated with a higher prevalence of CAD and cardiovascular disease. A proposed mechanism for this association has been that frequent periodic limb movements (PLMs) associated with more frequent sympathetic activation during sleep could result in a higher risk for cardiovascular pathology. However, some data suggest a degree of risk with RLS independent of PLMS. Little consensus exists on the matter, however, as some studies have not shown any association between primary RLS and cardiovascular disease after controlling for confounding factors.,,
There are fewer established connections between parasomnias and cardiovascular risk. REM sleep behavior disorder, a REM-related parasomnia marked by dream enactment behavior and frequently associated with synucleinopathies, has been linked to greater stroke risk, perhaps mediated by autonomic dysfunction.
| Sleep Duration, Circadian Rhythms, and Cardiovascular Health|| |
An early observation regarding sleep duration and mortality was Hammond's 1964 finding that subjects from the American Cancer Society I study who self-reported 7 h of sleep had lower mortality than those reporting either more or <7 h of sleep. Over the ensuing decades, additional studies and meta-analyses, have reached similar conclusions, describing a U-shaped relationship between sleep duration and mortality where too short or too long of sleep duration is associated with increased all-cause mortality. Professional health organizations such as the American Academy of Sleep Medicine, Sleep Research Society, and the National Sleep Foundation have recommended a sleep duration of 7–9 h for most adults as well as the aforementioned AHA more recently.,, While our understanding of the exact mechanisms for this link between sleep mortality is not complete, it is likely multifactorial with cardiovascular health serving as an important mediator. Multiple analyses have demonstrated an increase in mortality and cardiovascular events with either short or long sleep. More recent work has been able to more clearly establish short sleep as a causal risk factor for CAD and HF. However, in the same analysis, no causal association between long sleep time and CAD or stroke was not clearly established. In addition to data connecting sleep duration and risk of cardiovascular events and CAD directly, sleep duration has been linked to a number of other risk factors for cardiovascular disease, including obesity, diabetes, and hypertension.,
Short sleep duration and insomnia are two distinct but overlapping conditions. Chronic insomnia is often associated with a state of constant hypervigilance, which may lead to changes in sympathetic activity and alterations of endocrine function such as cortisol suggesting important connections with the hypothalamic–pituitary–adrenal axis.,,, Elevated inflammatory markers have also been reported in patients with insomnia and short sleep duration, as have changes in endothelial function. These factors may contribute to the high rates of comorbidity of insomnia with hypertension,,,, other cardiovascular diseases,, and mortality.,, Long sleep times have also been associated with increased risk for cardiovascular events such as stroke., While the mechanism of this connection is incompletely understood, it has been hypothesized that metabolic dysregulation and inflammation may play a role.
While it is clear that sleep duration plays an important role in cardiovascular health, timing of sleep and other circadian factors are also valuable in the assessment of cardiovascular risk. Circadian clocks are ubiquitous within the human body and play a role in regulating a diverse array of biological processes, including many aspects of cardiovascular function. The importance of circadian rhythms in cardiovascular health is reflected in the fact that all cell types of major blood vessel layers, cardiomyocytes, myocardial stromal fibroblasts, and cardiac progenitor-like cells all have functional circadian clocks. In addition, certain cardiovascular functions such as blood pressure and heart rate have unique circadian patterns. Similarly, the timing of acute cardiovascular events such as stroke, and myocardial infarction, and sudden cardiac death has a circadian pattern as they all occur more frequently in the morning. Chronic disruptions to circadian rhythms can lead to increased risk of hypertension and atherosclerosis. This type of chronic circadian disruption is exemplified by shift workers who often experience repeated circadian disruptions which have been linked to cardiovascular disease.,
| Conclusion|| |
Sleep and cardiovascular health are closely intertwined, and data continue to emerge demonstrating the many facets of this relationship, ranging from sleep-disordered breathing to parasomnias to sleep-related movement disorders and beyond. As a result, sleep has become increasingly recognized as a potential therapeutic target for reducing cardiovascular risk. One potential treatment that has captured significant attention has been CPAP for sleep-disordered breathing. However, while the literature demonstrates the existence of many benefits with CPAP use, the role of CPAP in reducing cardiovascular mortality has not been supported by results from randomized-controlled trials. Continued research in this area, including projects such as the ongoing Sleep Stroke Management and Recovery Trial investigating the use of CPAP in preventing vascular events after a stroke and the ADVENT-HF trial to evaluate the use of ASV in patients with HF, is of critical importance. However, efforts to improve sleep and heart health do not have to be limited to large, high-profile projects such as these. Greater recognition of the importance of sleep and simple clinical interventions such as counseling patients to get sufficient sleep and implementing good sleep hygiene could carry great benefits toward improved cardiovascular health.
The dawning of sleep as a scientific and medical field has been relatively recent. There remains fertile grounds for additional discovery in the realm of sleep. This represents a significant opportunity not just for sleep itself but also for the dream of improving cardiovascular health.
Ethical statement is not applicable for this article.
The authors thank Drs. Michael Smolensky, Ramon Herminda, and Richard Castriotta for discussion and suggestions.
Financial support and sponsorship
The work of Dr. Yong-Jian Geng is supported in part by the Memorial-Hermann Foundation.
Conflicts of interest
There are no conflicts of interest.
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