Background: Cardiovascular disease (CVD), including coronary heart disease and cerebrovascular disease, is already amongst the leading causes of morbidity and mortality worldwide, but its burden continues to rise. Over time, relevant risk factors for CVD have been identified, many of which are modifiable. More recently, the relationship of sleep and CVD has been of interest, specifically increased rates of disrupted and disordered sleep, which have been found to be associated with CVD. Longitudinal studies have linked sleep difficulties to a predisposition of vascular risk factors, suggesting a potential role for sleep improvement in primary and secondary CVD. Summary: In the present narrative review article, we summarize the current body of research linking suboptimal sleep (e.g., short/long sleep, fragmented sleep) as well as nonbreathing-related sleep disorders (i.e., insomnia, restless legs syndrome/peripheral leg movements of sleep, narcolepsy) to modifiable CVD risk factors and CVD outcomes (morbidity and mortality).

Cardiovascular diseases (CVD) are arguably the most socioeconomically impactful and burdensome diseases globally. These diseases, which include stroke, ischemic heart disease, and heart failure, are the leading cause of global mortality and have a significant detrimental impact on quality of life [1, 2]. It has been estimated that over 2,000 Americans die of CVD daily, with over one death per minute on average [3]. Further, the burden of these diseases continues to increase, with the prevalent cases of CVD globally nearly doubling from 271 million in 1990 to over 500 million in 2019 [4].

Numerous risk factors for CVD including gender, age, and genetic contributions are non-modifiable while others, such as obesity, hypertension, diabetes mellitus, and altered blood lipid levels, are [5]. Such modifiable factors can be linked to the majority of CVD cases and deaths, which emphasizes the need for adequate measures of primary CVD prevention with a focus on vascular health. Evidence has mounted indicating that sleep may be a factor worth exploring. In the present review article, our goal was to emphasize the current evidence on the relationship between sleep and CVD and its risk factors. As recent reviews have summarized the research linking obstructive sleep apnea (OSA) and CVD [6], we have opted to focus specifically on suboptimal (e.g., shortened, fragmented) sleep as well as several of the most common nonbreathing-related sleep disorders (i.e., insomnia, restless legs syndrome [RLS]/periodic limb movements of sleep, narcolepsy).

We performed a search term-based literature review in PubMed (“sleep,” “short sleep duration,” “long sleep duration,” “fragmented sleep,” “insomnia,” “narcolepsy,” “restless legs syndrome,” “periodic limb movements of sleep,” “excessive daytime sleepiness” AND “stroke,” “hypertension,” “hypercholesterolemia,” “dyslipidemia,” “diabetes mellitus,” “weight,” “heart disease,” “cardiovascular death”). English articles from 1990 to December 2023 were considered.

Weight

Two longitudinal studies of British and US children followed from birth concluded that children sleeping less are at risk of developing obesity. In detail, in more than 8,000 British children, 3-year-olds sleeping less than ten and a half hours per night had a 45% higher chance of being obese at age 7. Additionally, 915 US infants sleeping less than 12 h a day had double the odds of being obese at age three than those sleeping longer [7, 8]. Once habituated, sleeping less may have long-term effects reaching into adulthood, as its effect on body weight has been shown up until the age of 32 [9]. Further, in a recent study investigating interactions between obesity-promoting genetic variants and behavioral factors, an irregular sleep-wake cycle was associated with high body mass index, high waist-circumference, high hip-circumference, increased waist-to-hip-ratio, and high body-fat percentage [10]. These observational data are supported by a meta-analysis by Cappuccio et al. [11] encapsulating 600,000 individuals recruited in 30 studies (12 recruited children and 18 adults). This meta-analysis concluded that the pooled odds ratio (OR) for shorter sleep duration and obesity was 1.89 (confidence interval [CI] 1.46–2.43) in children and 1.55 (CI: 1.43–1.68) in adults. Mechanistically, inadequate sleep has been linked to alterations in the regulation of appetite-controlling hormones, such as leptin and ghrelin [12‒15]. Short sleep duration (<6 h) can lead to decreased leptin levels and increased ghrelin levels, resulting in increased appetite and a preference for calorie-dense, high-carbohydrate foods. Additionally, insufficient sleep may impact energy expenditure by increasing feelings of fatigue and reducing physical activity levels. It has also been suggested that reduced sleep may affect thermoregulation and the resting metabolic rate, further contributing to weight gain [16]. A connection to gene variants promoting obesity has been declared, but these findings, detailing the link between irregular sleep-wake cycle and the obesity-associated genetic variants MC4R rs17782313, BDNF rs6265, TMEM18 rs7561317, and NEGR1 rs2815752, demonstrate an additive rather than a causative relationship in pathologic sleep patterns and obesity [10]. A recent trial showed that sleep improvement may be a useful tool in terms of obesity prevention and weight loss [17]. Specifically, participants with a body mass index between 25.0 and 29.9 and sleep durations of less than 6.5 h per night were randomized to either an individualized sleep hygiene counseling session or to maintain their normal sleep; the participants in the sleep hygiene group saw a significant increase in sleep duration and a decrease in energy intake compared to the control group.

There have been mixed results in cross-sectional studies regarding the relationship between obesity and insomnia [18, 19]. One longitudinal study of 815 participants reported that after a median of 7.5 years of follow-up, subjective and polysomnography-adjudicated sleep durations of ≤5 h and poor sleep (defined as moderate-to-severe sleep complaint) were associated with incident obesity while questionnaire-based insomnia and excessive daytime sleepiness were not [20]. Accordingly, a recent meta-analysis did not find significantly higher odds of obesity in patients with insomnia compared to individuals without (OR: 0.8; p = 0.61) [21]. A small cross-sectional association between body mass index and insomnia (r = 0.06, p = 0.03) was found.

Similarly, RLS has been associated with obesity in some but not all cross-sectional studies to-date [22‒24]. A recent meta-analysis which considered 15 observational studies found positive associations between RLS and both overweight (OR: 1.29; 95% CI: 1.22–1.36) as well as obesity (OR: 1.44; 95% CI: 1.31–1.58), though moderate heterogeneity was observed (I2: 2.3%, pheterogeneity < 0.001) [25]. Several large prospective studies have demonstrated that the presence of obesity is a risk factor for the development of RLS [26, 27], but it is less clear whether RLS predisposes to the development of obesity.

The relationship between type 1 narcolepsy and obesity was assessed in multiple observational cohorts [28‒30], and a recent meta-analysis encapsulating nine such studies [31]. As type 1 narcolepsy is characterized by deficiency in orexin (hypocretin) neurons, which are known to play a crucial role in the regulation of feeding behavior, energy metabolism, and sleep-wake cycle, a relationship to obesity seemed plausible [32, 33]. Indeed, the previously mentioned meta-analysis did reveal an increased prevalence of obesity in individuals with narcolepsy compared to those without (OR = 0.93; p < 0.001) [31].

Hypertension

Large observational clinical studies have reported a U-shaped relationship between sleep duration and hypertension [34‒37]. The National Health Interview Survey evaluated more than 70,000 individuals and concluded that persons sleeping less than 6 h per night and those sleeping more than 10 h per night had a higher age-standardized prevalence of hypertension (32.4% and 32.5% respectively) [38]. However, a meta-analysis by Guo et al. [39] found that the association between longer sleep duration and hypertension was less conclusive than observational data suggest. The presented data suggest that the connection between hypertension and sleep duration seems to be confined to non-geriatric persons. As an example, the National Health and Nutrition Examination Survey, which represented a probability sample of the civilian noninstitutionalized population of the USA with a subsequent epidemiologic follow-up addendum encompassing 4,810 individuals, showed short sleeping 32–59 year olds to be 60% more likely to develop hypertension compared to same-aged 7–8 h-sleepers [35]. A similarly increased risk was not seen in persons over 60 years of age. Two subsequent studies investigating sleep duration in the elderly produced similar findings [40, 41]. Two large genome and gene variant analyses reported evidence of interactions between sleep duration and blood pressure-regulating genes. Still, even though self-reported short and long sleep were associated with genes near blood pressure regulating genes (NME7, FAM208A, MKLN1, CEP164, and RGL3/ELAVL3), the authors were unable to establish a direct connection [42]. One noteworthy association might be the variant of phosphodiesterase 11A (PDE11A) gene emphasized within the Malmö Diet and Cancer Study, which was connected to blood pressure elevation, obesity, and stroke, especially in females, as well as objective sleep duration and sleep efficiency [43]. Moreover, in addition to sleep duration, sleep architecture may also contribute to the pathogenesis of hypertension. In 784 men ≥65 years of age, reduced slow-wave sleep percentage, a restorative phase of non-Rapid-Eye-Movement (non-REM) sleep, has been associated with incident hypertension [44]. Regarding the pathophysiology underlying the above findings, studies showed that short sleep duration leads to dysregulation of stress hormones, such as cortisol, as well as elevated sympathetic nervous system activity, resulting in increased heart rate, vasoconstriction, and, consequently, higher blood pressure [45, 46]. Nevertheless, clarifying the exact pathophysiologic pathways of sleep causing hypertension remains elusive.

Shifting the focus to disordered sleep, there appears to be an association between hypertension and insomnia and/or insomnia symptoms. Cross-sectional studies have found higher odds of insomnia in patients with hypertension [47], and higher rates of chronic insomnia amongst those with high blood pressure [48]. Numerous prospective studies have yielded mixed results [49, 50], with a recent meta-analysis of prospective studies on the topic finding the pooled RR of insomnia on hypertension to be 1.21 (95% CI: 1.10–1.33); however, a high degree of heterogeneity was observed (I2 = 95.5%; p < 0.001), raising uncertainty about this result [51]. The increased risk of hypertension was confined to certain traits of insomnia (difficulty maintaining sleep and early morning awakening) as well as to individuals of European descent. In another recent meta-analysis, evidence of a bidirectional relationship was found; the authors reported an adjusted OR of 1.11 (95% CI: 1.07–1.16) in patients with insomnia having hypertension and an adjusted OR of 1.20 (95% CI: 1.08–1.32) vice versa [52]. A cohort study incorporating polysomnography in patient selection found a high risk of incident hypertension amongst individuals with chronic insomnia and polysomnographic-determined short sleep durations of <6 h compared to normal sleepers (i.e., ≥6 h of sleep) (OR = 3.8, 95% CI = 1.6–9.0) [53].

Hypertension has also been linked to RLS and periodic limb movements of sleep (PLMS). Studies have reported that individual leg movements in sleep are associated with rises in blood pressure (i.e., 20 mm in systolic and 12 mm in diastolic blood pressure) [54‒56] while another study implementing polysomnography in patients with diagnosed RLS demonstrated elevated nocturnal and sleep-time systolic blood pressure readings in these patients compared to those without RLS [57]. The association between RLS/PLMS and increased blood pressure does not appear to be limited to nighttime or to one of the sexes as associations between RLS and clinical hypertension have been seen in both women [58] and men [59]. The relationship between RLS and hypertension has also been reported in longitudinal studies. Van den Eeden et al. [60] presented retrospective data including over 12,000 RLS cases showing both primary and secondary RLS to be associated with an increased risk of incident hypertension over a mean follow-up of 3.91 years. Further, a randomized controlled trial demonstrated that RLS treatment with rotigotine significantly reduced the number of peripheral limb movement-associated elevations in systolic blood pressure compared to placebo [61].

An association between narcolepsy and hypertension has also been reported [62, 63]. This relationship has been hypothesized to be related to the role that hypocretin plays in autonomic function [64]. A recently published systematic review and meta-analysis assessing seven studies on the topic emphasizes that there is an increased prevalence of hypertension in patients with narcolepsy compared to controls, even though mean values of systolic/diastolic blood pressure are not significantly increased [31].

Diabetes

A connection between sleep duration and diabetes is debated as some observational studies suggested a U-shaped relationship [65, 66], whilst others did not [67, 68]. A meta-analysis by Shan et al. [69] from 2015 encompassing 11 studies with 18,443 diabetes cases in 482,502 individuals strengthened the U-shaped hypothesis and proclaimed that the optimal sleep duration resulting in the lowest risk of developing diabetes is 7–8 h per day. Further, the authors reported that when reducing sleep below the 7-h threshold or increasing the duration by an additional hour above the 8th hour, there was a relative additive risk of 1.09 (95% CI: 1.04–1.15) or 1.14 (1.03–1.26) per hour amounts, respectively. Additionally, changes in sleep architecture, particularly a reduction in slow wave sleep, seem to be related to diabetes. In a recent cross-sectional study of 2,026 people, those in the fourth quartile of stage N3 sleep proportion were 29% less likely to have prevalent diabetes compared to participants in the first quartile [70]. Moreover, sleep fragmentation, a common characteristic of altered sleep architecture, has been associated with increased cortisol levels, leading to insulin resistance and an elevated risk of diabetes [71]. Concerning the pathomechanisms, Smith et al. [72] have described that the effect on the daily rhythm of the hypothalamic-pituitary-adrenal axis through short sleep duration as well as the ensuing low sleep quality elevates cortisol levels, causing insulin resistance. Kadoya et al. [73] expanded on these findings, emphasizing the role of high macro thyroid stimulating hormone (TSH) levels distinct of free TSH. They found higher levels of macro-TSH in individuals with short or low-quality sleep, which in turn were associated with elevated markers for type 2 diabetes (T2D) including higher fasting glucose, glycated hemoglobin, and homeostasis model assessment for insulin resistance. Further, Morselli et al. [74] recently found that the electroencephalography spectrum power during sleep, particularly in the delta spectrum within the initial 6 h of sleep, is associated with insulin secretion.

Coexistence of insomnia and diabetes mellitus have been of continued interest in the literature, with many studies revealing high rates of clinical insomnia and/or symptoms of insomnia in diabetic patients [47, 75, 76]. A recent meta-analysis analyzing 78 studies calculated a prevalence of insomnia symptoms amongst patients with T2D to be 39% (95% CI: 34%, 44%) and also revealed that amongst patients with T2D, insomnia symptoms were associated with poor glycemic control [77]. Additionally, longitudinal cohort studies have showed a potential of insomnia predisposing to the development of T2D [78]. Accordingly, clinical trials have been initiated in recent years that have aimed to treat clinical insomnia in patients with comorbid T2D, in hopes of enhancing glycemic control and improving health [79‒82].

Concerning RLS, a recent study that pooled data from 42 cross-sectional, case-control and cohort studies found that one-quarter of individuals with diabetes demonstrate clinical signs of RLS, and that those with diabetes are at an increased risk of developing RLS compared to those without diabetes (OR: 1.98; 95% CI: 1.66–2.34) [83]. Still, it is worth noting that diabetic peripheral neuropathy is a common clinical RLS mimic which increases the chance of over-estimation in this patient cohort if diagnosis is solely established through clinical appraisal [84].

A relationship between narcolepsy and diabetes has been discussed in recent history, with some studies suggesting and some negating an association [85‒88]. A recent meta-analysis which encompassed six studies revealed that patients with narcolepsy had a significantly increased prevalence of unspecified diabetes mellitus compared with controls (OR = 0.64; 95% CI: 0.34–0.94) [31]. Pathomechanistic hypotheses concerning this relationship include the expression of orexin receptors in the endocrine portion of the pancreas [89].

Dyslipidemia

Overall, the evidence concerning the relationship between hyperlipidemia and hypertriglyceridemia with sleep is less robust than with other vascular risk factors. Multiple studies reported an association between short and long sleep durations and total cholesterol and triglyceride levels. Grandner et al. [90] investigated 5,649 individuals and concluded that very short sleepers (defined as less than 5 h per day) have an OR of 1.41 to have hyperlipidemia. Yet, these results could not be confirmed by Bjorvatn et al. [91] as an analysis of 8,860 persons aged between 40 and 45 years old did not show this association after adjusting for co-factors such as age, sex and co-existing risk factors. As the Zhuang et al. [92] Mendelian randomization study evaluating the potential causal effect between genetic variants associated with sleep duration and lipid levels did not find any evidence supporting a contributive aspect of sleep, the relationship has to be questioned.

Similarly, in disordered sleep, one large cross-sectional analysis found no association between having an insomnia symptom at least five times in the prior month and an elevated LDL-C or low HDL-C (in unadjusted analyses) or with high triglycerides (after adjusting for covariates) [93]. However, participants who took sleeping medication and still reported insomnia symptoms did have elevated LDL-C levels (OR: 2.18, 95% CI: 1.14–4.15). Another cross-sectional study found that self-reported frequent (≥3 times/week) insomnia was associated with an increased prevalence of dyslipidemia in women participants but not men [94].

Several analyses have assessed the relationship between blood cholesterol and RLS. One small study of idiopathic RLS patients found no difference in total cholesterol, HDL cholesterol, or triglycerides compared to those without RLS [95]. Contrarily, a prospective cohort analysis by De Vito et al. [27] revealed that elevated cholesterol was associated with an increased risk of developing RLS over the follow-up period (pooled adjusted OR was 1.33 for total serum cholesterol >240 mg/dL vs. <159 mg/dL; p trend = 0.002).

Narcolepsy has been associated with alterations in blood cholesterol with a meta-analysis of three studies by Mohammadi et al. [31] concluding that patients with narcolepsy exhibited a higher prevalence of dyslipidemia (log OR = 1.19; 0.60–1.77). There appears to be little to no research that has investigated the directionality of the relationship between narcolepsy and dyslipidemia.

Healthy sleep patterns seem to be associated with reduced risk of CVD and stroke [96]. Previous studies related the negative effect of sleep disruption and/or fragmentation to the reduced time spent in NREM sleep. Mechanistically, NREM sleep is reportedly associated to parasympathetic modulation and subsequent nocturnal non-dipping blood pressure profiles, a known risk factor for vascular events [97‒101]. Further, depending on the cause of poor sleep, multiple additional pathomechanisms are presumed to be involved in the development of CVD. These include intermittent hypoxia-reoxygenation injury, inflammation, insulin resistance, hypothalamic-pituitary-adrenal axis activation, hemodynamic swings, cardiac arrhythmia, hypercoagulability, and sympathetic dominance relating to elevated levels of catecholamines such as norepinephrine and epinephrine [102‒104]. In the short term, such changes in physiology can result in increased stress levels, reduced quality of life, mood disorders, and cognitive impairment [105]. In the long run, they are associated to risk of vascular events as detailed below.

Stroke

To date, a plethora of studies has investigated the relationship between suboptimal sleep, independent of root cause, and CVD overall. Throughout these studies, stroke risk has seldom been reported but rather encapsulated within a composite endpoint including cardiovascular events. Studies investigating stroke as an individual outcome have reported increased risks for individuals with sleep duration alteration from the predefined norm of 7–8 h of sleep per night. Still, the risk of stroke has differed according to different sleep patterns (e.g., short sleep, long sleep) and patient characteristics, such as biological sex [106‒116]. For example, in the population-based MONICA KORA Augsburg study, which investigated sleep duration and had a mean follow-up of 14 years, the HRs for stroke in those with short (≤5 h) and long (≥10 h) sleep durations were 1.44 (CI: 1.01–2.06) and 1.63 (CI: 1.16–2.29), respectively, in men, while no such association was found in women [107]. Further, in a questionnaire study investigating 31,750 individuals, long sleep duration (≥9 h/night) was associated with stroke (HR: 1.23 [CI: 1.07–1.41]) while short sleep (<6 h/night) was not [108]. These inconsistencies prompted a large recent systematic review including a dose-response meta-analysis, which concluded that, after analyzing data from 20 articles, a U-shaped relationship between sleep duration and stroke incidence (short sleep ≤6 h RR: 1.33 [CI: 1.19–1.49]; long sleep ≥8 h RR: 1.71 [CI: 1.50–1.95]) exists, which surprisingly was stronger in women [117]. Further, in another dose-response meta-analysis, if in otherwise healthy adults sleep duration was reduced by 1-h, the relative risk of stroke increased by a factor of 1.05 (CI: 1.01–1.09). If sleep duration increased by 1 h, the relative risk increased by a factor of 1.18 (CI: 1.14–1.21) [118]. In addition to these data, prospective studies have postulated that concomitant poor sleep quality in those with short sleep duration puts individuals at an even greater risk of stroke over time (OR: 6.75; CI: 2.45–14.12) [109]. Such studies support recent preclinical findings of apolipoprotein E knockout mice having an increased chance of atherosclerotic lesions if subjected to sleep deprivation and fragmentation [119]. The pathomechanism involved is believed to be reduced hypocretin levels, which, due to this hormone’s involvement in the release of colony-stimulating factor 1 in the bone marrow, regulates monocyte production and impacts inflammation [119].

Similar to the case for suboptimal sleep, many studies assessing the relationship of CVD and specific sleep disorders apply a composite endpoint. Concerning the relationship between sleep and stroke, results have largely been inconclusive. A recent meta-analysis of prospective cohort studies determined that there were insufficient data to establish a link, despite showing that insomnia did increase the risk of nonspecific overall vascular events [120]. Still, only two of the included studies assessed insomnia and stroke individually [107, 121]. The uncertainty concerning the relationship between insomnia and stroke prompted a multidisciplinary task force in 2020 to emphasize that the effect of insomnia on stroke risk remains uncertain while treatment of insomnia with benzodiazepine and benzodiazepine-related drugs may increase the risk of stroke [122]. Since then, a large prospective cohort study found insomnia symptoms to be associated with elevated risk of stroke in a dose-response fashion [123]. The association withstood sensitivity analyses and was strongest amongst younger individuals (<50 years).

In RLS, the evidence concerning associated stroke risk is conflicting as well [124, 125]. In a meta-analysis assessing prospective studies on the topic, Katsanos et al. [126] found that patients with RLS were not at an increased risk for cerebrovascular ischemia after adjusting for confounders. Therefore, the aforementioned multidisciplinary task force declared that there is no clear evidence that RLS increases the risk for stroke, while PLMS might as one systematic review of cohort studies revealed an independent association [122, 127].

Limited research suggests that a link between narcolepsy and stroke may exist, with one large medical claims data analysis finding high rates of stroke amongst patients with narcolepsy compared to matched controls (14% vs. 7%; p < 0.0001) [63]. A similar relationship was also observed in a retrospective cohort study which reported a higher frequency of novel stroke in individuals with preexistent narcolepsy compared to matched individuals without narcolepsy (1.71; 95% CI: 1.24–2.34) [128]. The majority of individuals included in this latter study had narcolepsy type 2 (i.e., without orexin/hypocretin deficiency), suggesting that orexin is not the only factor underlying this potential relationship between narcolepsy and stroke. This study did have notable limitations, perhaps most important being that data on narcolepsy treatments, which potentially have an impact on CVD, were not collected [129].

Heart Disease

Compared to stroke, myocardial infarction (MCI) seems to be associated rather with short and disrupted sleep than long sleep duration. A prospective survey based study by Hamazaki et al. [111] reported a HR of 4.95 (CI: 1.31–18.73) if individuals slept less than 6 h per night, while Gianfagna et al. [114] found sleep disturbances to be associated with risk of MCI (HR: 1.97 [CI: 1.09–3.56]). However, these risks may be underestimated as the aforementioned studies only included men and Amagai et al. [106] emphasized that short-sleeping women are at higher risk of MCI than men. Independent of these sex-related differences, Westerlund et al. [121] found that in 41,192 individuals followed-up for more than 13 years, short sleep duration (≤5 h/night) put patients at increased risk of cardiovascular events (HR: 1.42 [CI: 1.15–1.76]). Commensurate with stroke, Yin et al. [118] reported a dose-response relationship between sleep duration and risk of coronary heart disease of 1.07 (CI: 1.03–1.12) per hour reduction below 7 h and 1.05 (CI: 1.00–1.10) per additional hour. In line with preclinical suspicions of increased risk of atherosclerosis, a recent study of more than 2,000 individuals found that sleep irregularity is associated with high coronary artery calcium burden (prevalence ratio, 1.39 [95% CI: 1.07–1.82]), a known subclinical risk factor for CVD [119, 130]. But even after MCI, poor sleep quality may put patients at risk of complications as Zhu et al. [131] demonstrated in a mouse model that 7 days of induced sleep deprivation increased values of inflammation and accompanying alterations in cardiac structure and function. Lastly, recent clinical data derived from almost 410,000 UK biobank participants emphasized that adherence to healthy sleep patterns (evaluated through a self-developed score encapsuling chronotype, sleep duration, insomnia, snoring, and excessive daytime sleepiness) is inversely associated with incident heart failure [132].

While suboptimal sleep overall may receive recognition in primary prevention guideline statements, specific sleep disorders seldomly do [133]. Despite this negligence, cross-sectional analyses have reported an association between heart disease (e.g., MI, coronary artery disease [CAD]) and insomnia [48, 134]. Several studies have assessed the directionality of this relationship, revealing insomnia as a potentially predisposing factor for the development of CAD) and/or MCI. A recent meta-analysis considering 9 studies concluded that patients with insomnia (defined according to ICD-9-CM codes as well as the criteria outlined in the DSM-5) have an increased risk of developing MCI compared to those without insomnia (RR: 1.69; 95% CI: 1.41–2.02; p < 0.00001) [135]. Significant associations with MCI were specifically observed amongst participants with difficulty initiating and maintaining sleep (and not those with non-restorative sleep and daytime dysfunction), and in those with the shortest sleep durations (5 h or less per night) compared to those who slept 7–8 h nightly. These findings led the authors to suggest that insomnia should be included in guidelines on the primary prevention of MCI. A notable limitation of this work, however, was the significant heterogeneity observed amongst included studies (I2 = 90%; p < 0.00001).

Various cross-sectional studies assessing the relationship between RLS and the risk of CAD/MCI have produced mixed results [136, 137]. A prospective study found that women who had a history of RLS of at least 3 years had an increased chance of developing coronary heart disease than matched controls [138]. Another longitudinal study did not establish an association between primary RLS and new-onset CVD or CAD but did find an association between secondary RLS and these two endpoints [60]. Accordingly, Katsanos et al. [126] reported in their meta-analysis that RLS patients did not have a higher risk of incident MCI compared to controls after adjustment for potential confounders (HR = 1.67; 95% CI: 0.62–4.47).

A number of studies cited above also assessed the association between narcolepsy and heart disease, yielding positive associations [62, 63]. For instance, as reported in a recent retrospective analysis by Ben-Joseph et al. [128], elevated risks of new-onset major adverse cardiac events (defined as grouped instances of MCI, ischemic stroke, heart failure, acute coronary syndrome, coronary artery bypass grafting, or percutaneous coronary intervention) (HR: 1.45; 95% CI: 1.20–1.74) and heart failure (HR: 1.35; 95% CI: 1.03–1.76) in patients with narcolepsy compared to matched controls without were found. Unfortunately, this study was unable to differentiate between separate outcomes due to insufficient number of events.

Cardiovascular Death

Evidence points toward changes in sleep architecture/structure being associated to overall CVD-related mortality as well [106, 117, 118, 139‒144]. In detail, a Chinese population-based cohort reported that both short (≤5 h) and long sleep (≥9 h) were associated with increased stroke mortality (RR: 1.25 [CI: 1.05–1.50] and 1.54 [1.28–1.85], respectively) [145]. This seems to extend to overall cardiovascular death as Amagai et al. [106], Kim et al. [140], and Cai et al. [142] report increased CVD-related mortality both in individuals with short and long sleep. The increase in mortality in those with increased sleep duration may largely be driven by stroke mortality as Ikehara et al. [141] found that in almost 100,000 individuals followed-up for more than 14 years, long sleepers (≥10 h) had a 1.5–2-fold increase in stroke mortality, and Kawachi et al. [143] presents an increase in stroke mortality of 1.51 (CI: 1.16–1.97) in long sleep while short sleepers showed risk reduction (HR: 0.77; CI: 0.59–1.01). Sleep disruption does not seem to be associated with CVD-related mortality [139]. Of note, to combat the effect of unhealthy sleep on CVD-related mortality, Zhou et al. [146] recently created a sleep score combining five individual sleep behaviors (enveloping early chronotype, adequate sleep duration [7–8 h], free of insomnia, no snoring, and no excessive daytime sleepiness) that, if adhered to, may reduce the risk of all-cause- and CVD-mortality by 24–42%. The authors further proclaimed that there was a per point risk decrease by HR: 0.89 (CI: 0.83–0.95).

To date, a limited amount of studies exist that focus on the relationship between specific sleep disorders and CVD death. The strongest evidence relates to insomnia, with a meta-analysis incorporating 13 prospective studies which applied a random-effects model revealing that evidence of insomnia increased the risk of CVD-related death by nearly 50% compared to individuals without; of note, there was no evidence of heterogeneity amongst the studies in this analysis (I2 = 19%; p = 0.14) [147]. Another meta-analysis which included 17 cohort studies found that insomnia significantly increased risk of CVD mortality (RR: 1.33; 95% CI: 1.13–1.57; p < 0.001) [148]. The data linking RLS to CVD mortality are less robust, although one prospective study of nearly 60,000 women free of CVD at baseline found that those with RLS had a higher risk of total (adjusted HR: 1.43, 95% CI: 1.03–1.97) and CVD mortality (adjusted HR: 2.27, 95% CI: 1.21–4.28) after excluding participants with common RLS comorbidities (e.g., snoring, Parkinson disease, diabetes mellitus) [149]. However, such results are not homogenous throughout literature, as data from two large prospective studies including both women and men did not find an increased risk of any incident CVD event in those with RLS, including CVD death specifically [150]. Lastly, although there is a scarcity of studies examining CVD death in narcolepsy, excess overall mortality in these patients has been documented [151]. It is conceivable that the increased prevalence of CVD amongst these patients partially explains this increased risk of mortality, but future research must confirm this notion.

We have summarized a multitude of observational studies reporting an association of suboptimal sleep and clinical sleep disorders with CVD and its traditional and novel vascular risk factors. The body of research summarized in this article generally suggests that both suboptimal sleep and common nonbreathing-related sleep disorders may be important risk factors for CVD, conditions that predispose to CVD, and CVD-related mortality. A selection of key studies mentioned in the text is presented in Table 1.

Table 1.

Select studies from text examining the association between disrupted and/or disordered sleep and cardiovascular disease and its risk factors

StudyaDesignParticipantsSummary of findings
Disrupted sleep 
 Landhuis et al. [9], 2008 Observational cohort study General-population birth cohort (n = 1,037), parental reports of sleep duration at ages 5, 7, 9, and 11 years. BMI at 32 years of age Shorter childhood sleep times were significantly associated with higher adult BMI values even after adjusting for adult sleep time and early childhood confounders (BMI, socioeconomic status, parental BMI, television viewing, and adult physical activity 
 Tasali et al. [17], 2022 Randomized controlled trial 80 adults, 21–40 years old, with BMI between 25.0 and 29.9 and habitual sleep duration less than 6.5 h per night Intervention group underwent individualized sleep hygiene counseling intended to extend sleep duration to 8.5 h while the others were considered controls. Intervention group had a significant decrease in energy intake (−270 kcal/day; 95% CI: −393 to −147 kcal/day; p< 0.001). Further, sleep duration was inversely correlated with change in energy intake. No effect on weight (short follow-up, 2 weeks) 
 Gangwisch et al. [35], 2006 Prospective cohort study Probability sample of the civilian noninstitutionalized population of the USA, questionnaire study (n = 4,810) Short sleep duration (≤5 h) associated with 60% increase in likelihood of developing hypertension in 32–59-year-olds but not in individuals over 60 years of age 
 Fung et al. [44], 2011 Prospective cohort study Community-dwelling men aged 65 or older undergoing polysomnography (n = 784) After adjustment for confounders, slow-wave-sleep percentage remained significantly associated with incident hypertension (OR 1.83; 95% CI: 1.18–2.85) emphasizing on the importance of sleep architecture 
 Kianersi et al. [70], 2023 Cross-sectional prospective study Community-based prospective cohort study of individuals free of clinically apparent cardiovascular disease undergoing polysomnography (n = 2,026) 6,346 person-years of follow-up of 1,251 participants. Individuals in Q4 of N3 stage sleep (i.e., slow-wave sleep) proportion were 29% less likely to have prevalent diabetes compared to those in Q1 (95% CI: 0.58–0.87) 
 Helbig et al. [107], 2015 Prospective cohort study Population-based cohort of 17,604 men and women (aged 25–74 years) After mean follow-up of 14 years, risk of stroke was increased in men with short (≤5 h; HR: 1.44; 95% CI: 1.01–2.06) and long sleep duration (≥10 h; HR: 1.63; 95% CI: 1.16–2.29). No such association was seen in women 
 Ji et al. [109], 2020 Prospective cohort study Chance sample of 41,786 adults in China. Mean age 45.7±15.1 years and average sleep duration 7.16±1.07 h Median follow-up of 7 years, both short sleep (<6 h; RR 1.63; 95% CI: 1.23–2.11) and poor sleep quality (RR: 2.37; 95% CI: 1.52–3.41) associated with increased risk of stroke. Combination of both accentuates stroke risk over time (OR: 6.75; 95% CI: 2.45–14.12) 
 Westerlund et al. [121], 2013 Prospective cohort study Population-based chance sample of 41,192 adults Short sleep duration (≤5 h/night) put patients at increased risk of cardiovascular events (HR: 1.42; 95% CI: 1.15–1.76) during a follow-up time of 13 years 
 Gianfagna et al. [114], 2016 Prospective cohort study Population-based sample of 2,277 men aged 35–74 years and CVD free at baseline Evidence of sleep disturbances (based on the Jenkins Sleep Questionnaire) was associated with risk of MCI (HR: 1.97; 95% CI: 1.09–3.56) during a median follow-up of 17 years 
 Ikehara et al. [141], 2009 Prospective cohort study 98,634 subjects (41,489 men and 57,145 women) aged 40–79 years During a median follow-up of 14.3 years, short sleep duration (≤4 h) was associated with increased mortality from coronary heart disease for women (HR: 2.32; 95% CI: 1.19–4.50). Individuals with long sleep duration (≥10 h) had a 1.5–2-fold increase in stroke mortality 
Disordered sleep 
 Budhiraja et al. [47], 2011 Prospective cross-sectional study Community-based sample of 3,282 adults aged 18–65 years old (mean age = 41.7 years; 50.8% female) Odds of insomnia (as assessed by DSM-IV criteria) were higher in patients with numerous different conditions including heart disease (adjusted OR: 1.6; 95% CI: 1.2–2.3), hypertension (adjusted OR: 1.5; 95% CI: 1.2–1.8), and diabetes (adjusted OR: 1.4; 95% CI: 1.05–2.0) 
 Garfinkel et al. [79], 2011 Randomized crossover study 36 adult patients with type 2 diabetes and insomnia (mean age = 63; 69% women) Short-term (i.e., 3-week) use of nightly prolonged melatonin improved several metrics of wrist actigraphy-measured sleep (sleep efficiency, wake after sleep onset, number of awakenings; only measured in a subgroup of 22 participants) as compared to placebo. After a 5-month open-label extension period where all patients received nightly prolonged-release melatonin, HbA1c was lower than at baseline (9.13% vs. 8.47%; p = 0.005) 
 Sawadogo et al. [123], 2023 Prospective cohort study American adults older than 50 years old and their spouses of any age (n = 31,126; mean age = 61; 57% female) Insomnia symptoms were associated with an elevated risk of stroke over a mean follow-up period of 9 years in a dose-response manner (HR: 1.51 in participants with more severe insomnia symptoms, 95% CI: 1.29–1.77). An especially strong association was observed amongst participants under 50 years old (HR: 3.84, 95% CI: 1.50–9.85) compared to older participants 
 Van Den Eeden et al. [60], 2015 Retrospective cohort study 7,621 individuals with primary RLS (mean age = 58.1; 69.2% female) and 4,507 with secondary RLS (mean age = 66.5; 67.7% female) Participants with primary RLS had an elevated risk of incident hypertension (HR: 1.19; 95% CI: 1.12–1.25) compared to the comparison group, though similar risks of incident CVD and CAD. Participants with secondary RLS saw an elevated risk of incident hypertension (HR: 1.28; 95% CI: 1.18–1.40), CVD (HR: 1.33; 95% CI: 1.21–1.46), and CAD (HR: 1.40; 95% CI: 1.25–1.56) 
 Bauer et al. [61], 2016 Randomized controlled trial Safety set included 80 adults with moderate to severe RLS (mean age = 57.5; 64% female), 66 which were included in efficacy assessments Patients taking rotigotine (a US Food and Drug Administration-approved RLS treatment) saw improvements in several metrics including PLM-associated systolic BP elevations (LSMTD: −160.34; 95% CI: −213.23 to −107.45; p< 0.0001), total systolic BP elevations (LSMTD: −161.13; 95% CI: −264.47 to −57.79; p = 0.0028), and total diastolic BP elevations (LSMTD: −93.81; 95% CI: −168.45 to −19.16; p = 0.0146) compared with those taking placebo 
 Winkelman et al. [124], 2017 Prospective cohort study 2,823 community-dwelling men 65 years or older (mean age = 76.3) Over a follow-up period of 8.7±2.6 years, both physician-diagnosed RLS (HR: 2.02, 95% CI: 1.04–3.91) and polysomnography-measured PLM of sleep (HR: 1.14, 95% CI: 1.00–1.30) were each independently associated with incident MCI. However, neither RLS nor PLM of sleep were significantly associated with incident overall CVD, stroke/transient ischemic attack, nor mechanical coronary revascularization 
 Black et al. [63], 2017 Retrospective medical claims data analysis 9,312 subjects with narcolepsy and 46,559 matched controls (mean age = 46.1; 59.2% female) A diagnosis of narcolepsy was associated with numerous comorbid claims compared to matched controls, including diseases of the circulatory system (OR: 2.6; 95% CI: 2.5–2.8), obesity (OR: 2.3; 95% CI: 2.2–2.5), diabetes (OR: 1.8; 95% CI: 1.7–1.8), stroke (OR: 2.5; 95% CI: 2.3–2.7), MCI (OR 1.6; 95% CI: 1.3–1.8), cardiac arrest (OR: 1.6; 95% CI: 1.1–2.3), and heart failure (OR: 2.6; 95% CI: 2.3–2.9) 
 Ben-Joseph et al. [128], 2023 Retrospective cohort study 12,816 adults diagnosed with narcolepsy (mean age = 38.1) and 38,441 matched controls without narcolepsy (mean age = 38.5) (67.1% female) Patients with a narcolepsy diagnosis had a higher risk of several types of incident cardiovascular events including any stroke (adjusted HR: 1.71; 95% CI: 1.24–2.34), ischemic stroke (adjusted HR: 1.67; 95% CI: 1.19–2.34), heart failure (adjusted HR: 1.35; 95% CI: 1.03–1.76), and major adverse cardiac events (adjusted HR: 1.45; 95% CI: 1.20–1.74), even after adjustment 
StudyaDesignParticipantsSummary of findings
Disrupted sleep 
 Landhuis et al. [9], 2008 Observational cohort study General-population birth cohort (n = 1,037), parental reports of sleep duration at ages 5, 7, 9, and 11 years. BMI at 32 years of age Shorter childhood sleep times were significantly associated with higher adult BMI values even after adjusting for adult sleep time and early childhood confounders (BMI, socioeconomic status, parental BMI, television viewing, and adult physical activity 
 Tasali et al. [17], 2022 Randomized controlled trial 80 adults, 21–40 years old, with BMI between 25.0 and 29.9 and habitual sleep duration less than 6.5 h per night Intervention group underwent individualized sleep hygiene counseling intended to extend sleep duration to 8.5 h while the others were considered controls. Intervention group had a significant decrease in energy intake (−270 kcal/day; 95% CI: −393 to −147 kcal/day; p< 0.001). Further, sleep duration was inversely correlated with change in energy intake. No effect on weight (short follow-up, 2 weeks) 
 Gangwisch et al. [35], 2006 Prospective cohort study Probability sample of the civilian noninstitutionalized population of the USA, questionnaire study (n = 4,810) Short sleep duration (≤5 h) associated with 60% increase in likelihood of developing hypertension in 32–59-year-olds but not in individuals over 60 years of age 
 Fung et al. [44], 2011 Prospective cohort study Community-dwelling men aged 65 or older undergoing polysomnography (n = 784) After adjustment for confounders, slow-wave-sleep percentage remained significantly associated with incident hypertension (OR 1.83; 95% CI: 1.18–2.85) emphasizing on the importance of sleep architecture 
 Kianersi et al. [70], 2023 Cross-sectional prospective study Community-based prospective cohort study of individuals free of clinically apparent cardiovascular disease undergoing polysomnography (n = 2,026) 6,346 person-years of follow-up of 1,251 participants. Individuals in Q4 of N3 stage sleep (i.e., slow-wave sleep) proportion were 29% less likely to have prevalent diabetes compared to those in Q1 (95% CI: 0.58–0.87) 
 Helbig et al. [107], 2015 Prospective cohort study Population-based cohort of 17,604 men and women (aged 25–74 years) After mean follow-up of 14 years, risk of stroke was increased in men with short (≤5 h; HR: 1.44; 95% CI: 1.01–2.06) and long sleep duration (≥10 h; HR: 1.63; 95% CI: 1.16–2.29). No such association was seen in women 
 Ji et al. [109], 2020 Prospective cohort study Chance sample of 41,786 adults in China. Mean age 45.7±15.1 years and average sleep duration 7.16±1.07 h Median follow-up of 7 years, both short sleep (<6 h; RR 1.63; 95% CI: 1.23–2.11) and poor sleep quality (RR: 2.37; 95% CI: 1.52–3.41) associated with increased risk of stroke. Combination of both accentuates stroke risk over time (OR: 6.75; 95% CI: 2.45–14.12) 
 Westerlund et al. [121], 2013 Prospective cohort study Population-based chance sample of 41,192 adults Short sleep duration (≤5 h/night) put patients at increased risk of cardiovascular events (HR: 1.42; 95% CI: 1.15–1.76) during a follow-up time of 13 years 
 Gianfagna et al. [114], 2016 Prospective cohort study Population-based sample of 2,277 men aged 35–74 years and CVD free at baseline Evidence of sleep disturbances (based on the Jenkins Sleep Questionnaire) was associated with risk of MCI (HR: 1.97; 95% CI: 1.09–3.56) during a median follow-up of 17 years 
 Ikehara et al. [141], 2009 Prospective cohort study 98,634 subjects (41,489 men and 57,145 women) aged 40–79 years During a median follow-up of 14.3 years, short sleep duration (≤4 h) was associated with increased mortality from coronary heart disease for women (HR: 2.32; 95% CI: 1.19–4.50). Individuals with long sleep duration (≥10 h) had a 1.5–2-fold increase in stroke mortality 
Disordered sleep 
 Budhiraja et al. [47], 2011 Prospective cross-sectional study Community-based sample of 3,282 adults aged 18–65 years old (mean age = 41.7 years; 50.8% female) Odds of insomnia (as assessed by DSM-IV criteria) were higher in patients with numerous different conditions including heart disease (adjusted OR: 1.6; 95% CI: 1.2–2.3), hypertension (adjusted OR: 1.5; 95% CI: 1.2–1.8), and diabetes (adjusted OR: 1.4; 95% CI: 1.05–2.0) 
 Garfinkel et al. [79], 2011 Randomized crossover study 36 adult patients with type 2 diabetes and insomnia (mean age = 63; 69% women) Short-term (i.e., 3-week) use of nightly prolonged melatonin improved several metrics of wrist actigraphy-measured sleep (sleep efficiency, wake after sleep onset, number of awakenings; only measured in a subgroup of 22 participants) as compared to placebo. After a 5-month open-label extension period where all patients received nightly prolonged-release melatonin, HbA1c was lower than at baseline (9.13% vs. 8.47%; p = 0.005) 
 Sawadogo et al. [123], 2023 Prospective cohort study American adults older than 50 years old and their spouses of any age (n = 31,126; mean age = 61; 57% female) Insomnia symptoms were associated with an elevated risk of stroke over a mean follow-up period of 9 years in a dose-response manner (HR: 1.51 in participants with more severe insomnia symptoms, 95% CI: 1.29–1.77). An especially strong association was observed amongst participants under 50 years old (HR: 3.84, 95% CI: 1.50–9.85) compared to older participants 
 Van Den Eeden et al. [60], 2015 Retrospective cohort study 7,621 individuals with primary RLS (mean age = 58.1; 69.2% female) and 4,507 with secondary RLS (mean age = 66.5; 67.7% female) Participants with primary RLS had an elevated risk of incident hypertension (HR: 1.19; 95% CI: 1.12–1.25) compared to the comparison group, though similar risks of incident CVD and CAD. Participants with secondary RLS saw an elevated risk of incident hypertension (HR: 1.28; 95% CI: 1.18–1.40), CVD (HR: 1.33; 95% CI: 1.21–1.46), and CAD (HR: 1.40; 95% CI: 1.25–1.56) 
 Bauer et al. [61], 2016 Randomized controlled trial Safety set included 80 adults with moderate to severe RLS (mean age = 57.5; 64% female), 66 which were included in efficacy assessments Patients taking rotigotine (a US Food and Drug Administration-approved RLS treatment) saw improvements in several metrics including PLM-associated systolic BP elevations (LSMTD: −160.34; 95% CI: −213.23 to −107.45; p< 0.0001), total systolic BP elevations (LSMTD: −161.13; 95% CI: −264.47 to −57.79; p = 0.0028), and total diastolic BP elevations (LSMTD: −93.81; 95% CI: −168.45 to −19.16; p = 0.0146) compared with those taking placebo 
 Winkelman et al. [124], 2017 Prospective cohort study 2,823 community-dwelling men 65 years or older (mean age = 76.3) Over a follow-up period of 8.7±2.6 years, both physician-diagnosed RLS (HR: 2.02, 95% CI: 1.04–3.91) and polysomnography-measured PLM of sleep (HR: 1.14, 95% CI: 1.00–1.30) were each independently associated with incident MCI. However, neither RLS nor PLM of sleep were significantly associated with incident overall CVD, stroke/transient ischemic attack, nor mechanical coronary revascularization 
 Black et al. [63], 2017 Retrospective medical claims data analysis 9,312 subjects with narcolepsy and 46,559 matched controls (mean age = 46.1; 59.2% female) A diagnosis of narcolepsy was associated with numerous comorbid claims compared to matched controls, including diseases of the circulatory system (OR: 2.6; 95% CI: 2.5–2.8), obesity (OR: 2.3; 95% CI: 2.2–2.5), diabetes (OR: 1.8; 95% CI: 1.7–1.8), stroke (OR: 2.5; 95% CI: 2.3–2.7), MCI (OR 1.6; 95% CI: 1.3–1.8), cardiac arrest (OR: 1.6; 95% CI: 1.1–2.3), and heart failure (OR: 2.6; 95% CI: 2.3–2.9) 
 Ben-Joseph et al. [128], 2023 Retrospective cohort study 12,816 adults diagnosed with narcolepsy (mean age = 38.1) and 38,441 matched controls without narcolepsy (mean age = 38.5) (67.1% female) Patients with a narcolepsy diagnosis had a higher risk of several types of incident cardiovascular events including any stroke (adjusted HR: 1.71; 95% CI: 1.24–2.34), ischemic stroke (adjusted HR: 1.67; 95% CI: 1.19–2.34), heart failure (adjusted HR: 1.35; 95% CI: 1.03–1.76), and major adverse cardiac events (adjusted HR: 1.45; 95% CI: 1.20–1.74), even after adjustment 

BMI, body mass index; CI, confidence interval; OR, odds ratio; Q4, fourth quartile; Q1, first quartile; HR, hazard ratio; RR, relative risk; CVD, cardiovascular disease; DSM-IV, Diagnostic and Statistical Manual of Mental Disorders, 4th Edition; HbA1c, glycated hemoglobin; RLS, restless legs syndrome; CAD, coronary artery disease; PLM, periodic limb movements; BP, blood pressure; LSMTD, least squares mean treatment difference.

aReference in text shown in square brackets.

Still, these findings linking sleep and CVD, and subsequently the summary of content presented in our review, have to be put into perspective. First, limitations exist concerning the currently available evidence. A number of the studies described have shortcomings which are highlighted above. Most analyses to date are observational, predominantly questionnaire-based studies, and importantly, such results suggesting a relationship between non-respiratory sleep disorders/suboptimal sleep and CVD may be considerably confounded by factors such as coexistent, non-reported OSA, which numerous studies above did not account for. Though not the focus of this current review, OSA is highly prevalent in the general public (∼20%), often coexists with other sleep disorders including insomnia, and is known to be strongly associated with various forms of CVD [6, 152‒154]. This clearly emphasizes a potential overlap limiting the quality of data currently available, which in turn, may hamper the quality of evidence presented within our narrative review. A particularly strong link may exist between sleep-related breathing disorders and stroke: sleep apnea may be present in over half of stroke survivors, and contingent on sleep apnea severity and patient age, OSA can up to double the risk of stroke as highlighted in a recent joint statement by the EAN/ERS/ESO/ESRS [122, 153, 155‒157]. Bassetti et al. [122] further elaborate that after a stroke, OSA is a recognized risk factor for stroke recurrence, and may additionally be associated with all-cause mortality. These key facts, as well as other traits emphasized in recent high quality reviews, highlight the necessity to definitively account for OSA when assessing the potential relationship between nonbreathing-related sleep disorders and stroke [122, 153]. Another major point of emphasis should be the harmonization of definitions of sleep disorders and sleep disruption applied in future research. The included studies within our review show considerable heterogeneity in terms of definitions used, for instance, of short and long sleep duration, insomnia, or fragmented sleep. Lastly, due to its narrative style, our review lacks quantitative assessment of the current data. Such analyses would be rewarding, but the evidence generated would still be confounded by the abovementioned limitations of present studies. Therefore, there is a continued need for methodologically sound and consistent studies in this area.

There is a growing understanding of the factors underlying the association between sleep and CVD, and Figure 1 schematically outlines several pathomechanisms which are described above. There is still much to be understood in this regard, however. One may argue that the relative paucity of knowledge in this area is at least partially related to abovementioned issues in methodology hindering the attribution of sleep characteristics, such as sleep duration and quality, to definitive non-respiratory sleep disorders. More basic science studies investigating the pathomechanisms underlying these relationships would be helpful as well.

Fig. 1.

Select pathomechanisms underlying the association between suboptimal/disordered sleep and cardiovascular disease and its risk factors. The dotted line represents the speculative link between sleep and dyslipidemia. TSH, thyroid stimulating hormone; EEG, electroencephalography; CVD, cardiovascular disease.

Fig. 1.

Select pathomechanisms underlying the association between suboptimal/disordered sleep and cardiovascular disease and its risk factors. The dotted line represents the speculative link between sleep and dyslipidemia. TSH, thyroid stimulating hormone; EEG, electroencephalography; CVD, cardiovascular disease.

Close modal

Historically, it took time to establish the positive effect of other modifiable factors of daily living nowadays considered beneficial for cardiovascular health (e.g., regular exercise, smoking cessation, limiting excessive caloric intake). These findings linking sleep and CVD suggest that enhancement of suboptimal and disordered sleep is another similar practice that can improve CVD risk factors and alleviate CVD morbidity and mortality. As described above, some interventional studies seeking to improve sleep and subsequently elements of CVD risk in different populations have already been conducted [17, 79, 80]. However, there is much more work that needs to be done in this domain.

JWW receives royalties from UpToDate; consultation fees from American Regent, Azurity, Avadel, Emalex, Idorsia, Noctrix, and Disc Medicine; and research support from Merck, NIDA, the RLS Foundation, and the Baszucki Brain Research Fund. All other authors report no conflicts of interest.

S.K. is supported by VASCage – Research Centre on Clinical Stroke Research. VASCage is a COMET Centre within the Competence Centers for Excellent Technologies (COMET) programme and funded by the Federal Ministry for Climate Action, Environment, Energy, Mobility, Innovation and Technology, the Federal Ministry of Labour and Economy, and the federal states of Tyrol, Salzburg and Vienna. COMET is managed by the Austrian Research Promotion Agency (Österreichische Forschungsförderungsgesellschaft). FFG Project number: 898252.

B.W. and L.M.S. contributed equally in terms of initial conception and drafting, as well as final editing of the article. M.C., A.I., J.W., and S.K. all critically revised the work for important intellectual content. All authors approved the final version of the manuscript.

Additional Information

Benjamin Wipper and Lukas Mayer-Suess contributed equally to this work.

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