Sleep as a Pillar of Cardiometabolic Health

Cardiovascular disease (CVD) is the number one cause of death globally.1 One in three adults in the United States has a CVD2, depicted on the Interactive Atlas of Heart Disease and Stroke from the Centers for Disease Control and Prevention (CDC).3 It is clear that both genetic predisposition and lifestyle choices contribute to the development of CVD. Health behaviors are a key intervention target for primary care physicians and public health organizations because they allow for CVD risk modification. Health risk behaviors, such as smoking, excess alcohol, and physical inactivity, and protective health behaviors, such as healthy diet and exercise, have long been identified as CVD risk factors in longitudinal studies.4 Indeed, each are listed by the CDC on their list of Heart Disease Behaviors.5 Individual health behaviors contribute to the metabolic perturbations of obesity, dyslipidemia, and type II diabetes, further exacerbating CVD risk4,6. Sleep is a key health behavior that is known to impact numerous CVD risk factors. Recent studies have begun to clarify the mechanisms underlying the associations between sleep and CVD.

Sleep, along with diet and exercise, is a cornerstone of health. Epidemiological studies show an increased risk of obesity, diabetes, and all-cause mortality in people who report either short (<7 hours/night) or long (>9 hours/night) sleep duration^7–9. Obesity and metabolic perturbations, such as type II diabetes, are intricately linked in their dual pathophysiology to CVD.¹⁰ Laboratory studies demonstrate that the hormonal and cognitive effects of sleep restriction lead to increased appetite, decreased satiety, and impaired insulin sensitivity.¹¹ Changes in insulin sensitivity impair glucose disposal and contribute to the development of type II diabetes. Emerging evidence suggests that sleep-loss induced changes in insulin sensitivity perturb lipid metabolism .¹² These metabolic effects lead to long-term weight gain and contribute to the development of CVD. Short sleep duration in combination with excess weight and sedentary lifestyle contributes to CVD mortality.^13,14

St-Onge and colleagues describe in their AHA science advisory an extensive critical analysis of literature and review of the relationship of non-optimal sleep duration and sleep disorders on overall cardio-metabolic health. The authors identified population-level trends and meta-analyses strongly supporting an important role for sleep, net of all other covariates examined, on cardio-metabolic health. The importance of these associations is strengthened by recent controlled laboratory studies that identify mechanistic physiologic and behavioral pathways whereby sleep and sleep disorders influence cardio-metabolic health. Their analysis clearly identifies the multi-faceted and interacting effects of non-optimal sleep duration, and degraded sleep quality (e.g., sleep disorders) on cardio-metabolic risk factors and CVD.

Sleep Disorders, including sleep-disordered breathing and insomnia, have been associated with CVD risk.¹³ Insomnia is associated with risk of myocardial infarction.^15,16. Obstructive sleep apnea (OSA) is a risk factor for hypertension¹⁷ and is associated with increased risk of stroke, coronary heart disease, and heart failure.¹⁸ The evidence for associations between restless leg syndrome and CVD is mixed, however duration of exposure to symptoms may increase risk of coronary heart disease and CVD .¹⁹ Chronic exposure to sleep disorders, just like chronic exposure to poor diet, excessive alcohol use, inactive lifestyle, and other health risk behaviors, may compound CVD risk over time.

The depth and breadth of sleep phenotypes that directly and indirectly impact a large set of CVD disease markers and risk factors is extensive. Sleep impacts decision-making and lifestyle choices, adiposity, insulin and glucose control, blood pressure, and inflammation.¹³ And, consequently, non-optimal sleep is associated with myocardial infarction, stroke, coronary artery disease, and CVD all-cause mortality13. The impact of disordered, long, or short sleep on CVD is a long-term process. Sleep disorders, such as sleep disordered breathing, insomnia, and restless leg syndrome, may contribute to risk of development of CVD through their impact on sleep duration and quality, and/or their impact on other risk factors (e.g., weight gain).¹³ Insufficient sleep contributes to poor diet selection, weight gain, and the development of obesity.¹³ Short and long sleep duration are associated with development of the metabolic syndrome, a major CVD risk factor²⁰. Hypertension and diabetes risk are increased in individuals with sleep disorders and short sleep duration, particularly, as with obesity, in younger adults.¹³ Long sleep duration increases the risk of coronary heart disease, while both long and short sleep duration are associated with increased risk of stroke.¹³ Sleep restriction leads to impaired glucose tolerance and is associated with increased fasting insulin levels, elevated HbA1C, and elevated fasting blood glucose levels, all markers of type II diabetes.¹³ Additionally, acute sleep restriction leads to elevations in pro-inflammatory cytokines, further compounding cardio-metabolic perturbations.¹³ Through their effects on metabolism, decision-making, and inflammation, among many other pathways, sleep disorders and non-optimal sleep exacerbate many of the contributing factors of CVD.

A key limitation in the literature on sleep and cardio-metabolic risk is the lack of quantitative sleep measures in long-term cohort studies including appropriate contextual covariates such as sociodemographics, household, community, cultural and other factors. Future studies will likely need to more directly measure sleep variables, rather than rely on self-report, such as via actigraphy for sleep duration, quality and timing, or oximetry for hypoxemia during sleep. An emerging area of sleep and cardio-metabolic disease research is daytime napping. Habitual and long duration napping is associated with cardiovascular disease in a J- Shaped relationship.²¹ One meta-analysis demonstrated that total 24-hr sleep duration is associated with CHD and all-cause mortality in a similar u-shaped curve as nightly sleep duration.²² Future studies are needed to disentangle these differences, the role of napping in nighttime sleep quality or duration, and as a potential marker of an undiagnosed sleep disorder.

Recent evidence suggests that sleep plays a role in lipid homeostasis. A recent small study in healthy young men concluded that sleep restriction elevates overnight non-esterified fatty acid production¹² and total sleep deprivation may contribute to changes in the circulating lipid metabolome²³. Lipids act as signaling molecules throughout the body and have a role in inflammatory (and anti-inflammatory) cascades²⁴. Aberrant lipid profiles are a risk factor for CVD and are a primary clinical assessment and intervention endpoint.4 Therefore, future studies examining the effects of sleep-induced changes in lipid profiles on cardio-metabolic health are of paramount importance.

An area of sleep-health that remains to be described is the relationship between sleep, depressive symptoms and impact on CVD25. Dis-entangling of the relationship between depressive symptoms and key health behaviors such as sleep, diet, and exercise, and intervening effectively, is an important area of future research. Additionally, mental health and behavior change interventions, particularly in vulnerable populations, should be a research priority. As the relationship between health behaviors, including sleep, and CVD risk continues to be described, it is critical that replication in other cultures and cohorts be performed. Sleep and risk factors for CVD appear to impact people of various sociodemographic and ethnic backgrounds differently¹³, therefore, in order to better serve all communities it will be critical to (1) elucidate the differential risk for various populations, and (2) perform targeted interventional studies.

CDC, maps for insufficient sleep and short sleep duration demonstrate a strong spatiogeographical distribution across the US, which are notably similar to those for the “stroke belt” and the CVD risk atlas³ . In the words of Nancy Krieger, “…to the extent there is spatiotemporal and/or social variation in the age-specific patterns of any particular health outcome, it suggests modifiable causes are at play, whose mechanisms could presumably be altered by informed action.”26 At Heart.org, a simple search for “sleep” yields more than 700 articles and pages noting a role for sleep in heart health. A recent AHA report notes that sleep is one of the behavioral risk factors “reversible with lifestyle change”⁶. It’s time to add sleep to the list of important target behaviors for Heart Health.