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. Author manuscript; available in PMC: 2023 Oct 1.
Published in final edited form as: Health Psychol. 2022 Jan 10:10.1037/hea0001143. doi: 10.1037/hea0001143

PTSD, Sleep, and Cardiovascular Disease Risk: A Mechanism-Focused Narrative Review

Corinne Meinhausen a, Aric A Prather b, Jennifer A Sumner a
PMCID: PMC9271141  NIHMSID: NIHMS1795467  PMID: 35007121

Abstract

Growing longitudinal research has demonstrated that posttraumatic stress disorder (PTSD) precedes and predicts the onset of cardiovascular disease (CVD), and a number of physiological (e.g., dysregulation of the hypothalamic-pituitary-adrenal axis and autonomic nervous system, chronic systemic inflammation) and behavioral (e.g., physical inactivity, smoking, poor diet) factors may underlie this association. In this narrative review, we focus on sleep as a modifiable risk factor linking PTSD with CVD. We summarize the evidence for sleep disturbance after trauma exposure and the potential cardiotoxic effects of poor sleep, with an emphasis on mechanisms. In addition, we review the literature that has examined sleep in the context of the PTSD-CVD risk relation. Although sleep disturbance is a hallmark symptom of PTSD and a well-established risk factor for the development of CVD, the role of sleep in the association between PTSD and CVD has been largely unexamined in the extant literature. However, such work has the potential to improve our understanding of mechanisms of risk and inform intervention efforts to offset elevated CVD risk after trauma. We outline several recommendations for future research and behavioral medicine models in order to help define and address the role of sleep behavior in the development of CVD among trauma-exposed individuals with PTSD.

Keywords: Posttraumatic stress disorder, trauma, sleep, insomnia, obstructive sleep apnea, cardiovascular, hypertension

Introduction

Cardiovascular disease (CVD) is the leading cause of global mortality, and it accounts for more deaths than all forms of cancer and chronic lower respiratory disease combined (Virani et al., 2021). The annual cost of CVD in the United States is an estimated $363.4 billion, which includes $216 billion in direct medical costs and $147.4 billion in lost future productivity as a result of premature CVD mortality (Virani et al., 2021). Yet an estimated 80% of all CVD cases could be avoided with behavioral changes, leading many CVD prevention efforts to emphasize risk factor reduction and address behavioral mediators of disease progression (Åkesson et al., 2014). Furthermore, as demonstrated in a recent Scientific Statement from the American Heart Association (Levine et al., 2021), there is a growing appreciation that an individual’s psychological health can have important consequences for cardiovascular health. A sizeable body of longitudinal research has found heightened incidence of a variety of cardiovascular events and conditions, including myocardial infarction, coronary heart disease, stroke, and heart failure, in individuals with posttraumatic stress disorder (PTSD) or elevated PTSD symptoms, suggesting that PTSD may be a potential modifiable risk factor for CVD (e.g., Gradus et al., 2015; Song et al., 2019; Sumner et al., 2015; see Edmondson & von Känel, 2017, for a review). Indeed, a recent meta-analysis of nine prospective studies indicated that PTSD was associated with a 61% greater risk of coronary heart disease or related mortality (Akosile et al., 2018).

Contingent upon trauma exposure, PTSD is the quintessential trauma-related mental disorder. Trauma exposure is highly prevalent, with 50-89% of individuals experiencing a traumatic event during their lifetime, and lifetime prevalence of PTSD is estimated at 10% for women and 5% for men (Kessler et al., 1995; Kilpatrick et al., 2013). PTSD is characterized by re-experiencing of the trauma, avoidance of trauma reminders, and alterations in cognition, mood, and arousal; symptoms last at least one month after trauma exposure and are associated with significant distress and/or functional impairment (American Psychiatric Association, 2013). Although PTSD has been linked to greater risk of a host of physical health issues, there is a particularly robust literature regarding the link between PTSD and CVD (see Edmondson & von Känel, 2017, for a review). This association has been consistently observed across populations (e.g., men, women; veterans, community-based samples), and PTSD is increasingly cited as a risk factor for subsequent CVD development (Koenen et al., 2017).

Both physiological and behavioral pathways have been suggested as underlying the PTSD-CVD relation. PTSD has been linked to dysregulation of the physiological stress response, including the hypothalamic-pituitary-adrenal (HPA) axis and autonomic nervous system (Pitman et al., 2012). In addition, chronic systemic inflammation in those with PTSD may increase risk for a variety of chronic diseases, including CVD (Sumner et al., 2020). These physiological changes may, in turn, promote the onset of hypertension, a well-established CVD risk factor (Burg et al., 2017; Sumner et al., 2016). Numerous poor health behaviors have also been associated with PTSD, including smoking, drug and alcohol abuse, physical inactivity, poor adherence to medical regimens, and decreased health screening frequency (Hall et al., 2015; Kessler et al., 1995; Lee et al., 2018; Zen et al., 2012).

Sleep is also a key behavior with relevance to both PTSD and CVD risk, but to date it has been relatively underexamined in the PTSD-CVD literature. Sleep is complex and can be characterized in a variety of ways, including sleep duration (i.e., time spent sleeping), sleep continuity (i.e., how fragmented sleep may be across the night), sleep onset latency (i.e., how quickly or slowly one falls asleep), and the presence of sleep-related disorders, such as insomnia (i.e., perceived difficulty sleeping—despite adequate opportunity—and subsequent daytime impairment; Edinger et al., 2004) and obstructive sleep apnea (OSA; i.e., disordered breathing patterns characterized by intermittent hypoxia and repeated awakenings during sleep; Dempsey et al., 2010). In this paper, we review the evidence linking 1) PTSD with sleep and 2) sleep with CVD risk, focusing on the sleep characteristics described above. We then examine potential sleep-related mechanisms and the extent to which sleep characteristics have been examined directly in the PTSD-CVD relation. Although the current manuscript is comprehensive in considering PTSD, sleep, and CVD risk, it is not an exhaustive systematic review, and we refer the readers to additional relevant reviews throughout. We find that despite extensive research supporting each of these links (PTSD-sleep; sleep-CVD), these literatures have operated predominantly in parallel. Nevertheless, studies that bridge these lines of research have the potential to identify important targets for intervention to offset CVD risk after trauma. In an effort to support such work, we outline several recommendations for future research and behavioral medicine models to help define and address the role of sleep behavior in the development of CVD among trauma-exposed individuals with PTSD. Although the purpose of this narrative review is to explore the role of sleep in the onset of CVD following PTSD, it is worth noting that acute cardiovascular events can be potentially traumatic and trigger the development of PTSD (Edmondson & von Känel, 2017). Further, CVD-induced PTSD is associated with elevated risk of recurrent cardiac events (Edmondson et al., 2012). Thus, our examination of sleep in the context of PTSD more broadly could also have relevance for understanding the course of CVD in these patients.

PTSD and Sleep

Sleep disturbances are among the most common symptoms reported by individuals suffering from PTSD, with 70-91% of individuals with PTSD reporting some form of comorbid sleep problems (Ohayon & Shaprio, 2000). Indeed, sleep disturbance (e.g., difficulty falling or staying asleep, restless sleep) is a diagnostic criterion of PTSD, and it is often reported as the most distressing and chronic symptom of PTSD that frequently compels individuals to seek PTSD treatment (Maher et al., 2006, Nappi et al., 2012). In addition, trauma-related nightmares—a symptom within the re-experiencing domain of the PTSD diagnostic criteria—can interfere significantly with sleep. Sleep disturbance is not only a symptom of PTSD, but it is also associated with greater overall PTSD symptom severity and poorer treatment outcomes (Germain et al., 2004; Reist et al., 2017). Indeed, sleep disturbances in individuals with PTSD are often treatment-refractory and persistent, with a recent study finding 57% of individuals with PTSD continue to report sleep disturbance despite successful PTSD treatment with trauma-focused cognitive behavioral therapy that resulted in overall PTSD symptom reduction and remission (Nappi et al., 2012; Pruiksma et al., 2016).

Manifestations of Sleep Disturbance in PTSD

Sleep disturbance can manifest in a number of ways in individuals with PTSD, with nightmares and insomnia being the most frequently cited issues occurring in 50-70% and 40-90% of individuals with PTSD, respectively (Koffel et al., 2016; Spoormaker & Montgomery, 2008). PTSD-related nightmare activity may result in short or prolonged awakenings, and individuals with PTSD who report having nightmares exhibit greater vigilance while sleeping (as shown by lower arousal and startle response thresholds) compared to individuals with PTSD who do not report nightmares (Kramer & Kinney, 2003). Additionally, electroencephalographic (EEG) recordings during sleep have shown that individuals with PTSD experience lighter sleep, as indicated by more time in Stage 1 sleep and less time in Stage 3 sleep compared to those without PTSD (Kobayashi et al., 2007). This lighter sleep, in addition to the high prevalence of insomnia and nightmares, may also contribute to lower overall sleep duration. Indeed, a recent meta-analysis of 31 studies that used polysomnography—a gold-standard objective measure of sleep behavior—in individuals with and without PTSD found that PTSD was associated with lower total sleep duration, greater wake time after sleep onset, and lower sleep efficiency (i.e., the percentage of time asleep given the time spent in bed; Zhang et al., 2019).

Dysregulation of rapid eye movement (REM) sleep, specifically alterations in REM density (i.e., frequency of eye movements) and REM fragmentation (i.e., shorter duration of REM sleep and greater number of REM sleep periods), has also been observed at greater rates among individuals with PTSD compared to those without PTSD (Kobayashi et al., 2007; Mellman et al., 2002; van Boxtel et al., 2018; Walker & van der Helm, 2009). Sleep is essential for learning and memory function, and key memory consolidation processes related to PTSD pathology are thought to occur during REM sleep (Pace-Schott et al., 2015; Smith & Lapp, 1991). Learning and memory processes are particularly relevant to PTSD, as the disorder is characterized by dysregulated fear extinction processes and difficulties with discriminating between danger and safety signals (Briscione et al., 2014; Foa & Kozak, 1986). Generalization of fear extinction and fear inhibition is thought to be heavily reliant on memory consolidation processes that occur during REM sleep (Pace-Schott et al., 2015). Additionally, greater sympathetic activation and physiological arousal have been observed during periods of REM sleep in individuals with PTSD (van Boxtel et al., 2018), and these periods of sympathetic hyperarousal during REM may be a potential mechanism of maladaptive fear generalization and maintenance of PTSD symptoms (Pace-Schott et al., 2015).

Furthermore, there is some evidence that a pharmacologic therapy often used for PTSD may influence REM sleep. Specifically, the antihypertensive medication prazosin has been used in the treatment of PTSD-related nightmares. Prazosin, an α1-adrenoreceptor antagonist, has been found to reduce noradrenergic activation of α1-adrenoreceptors in the brain even when administered peripherally (Menkes et al., 1981), and heightened central nervous system noradrenergic activity has been linked to sleep disturbances in PTSD (Mellman et al., 1995). Research suggests that treatment with prazosin increases the amount of time spent in REM and overall sleep duration in individuals with PTSD (Taylor et al., 2008). Additionally, there is initial evidence that prazosin may be efficacious for treating not only sleep-related symptoms of PTSD (distressing dreams, difficulty falling or staying asleep) but also a number of hyperarousal symptoms (e.g., hypervigilance, difficulty concentrating), which have been linked to noradrenergic signaling (Hendrickson et al., 2021). Further support for noradrenergic mechanisms underlying benefits of prazosin for individuals with PTSD comes from research indicating that those with an underlying noradrenergic-related pathophysiology may be most likely to respond to prazosin (Raskind et al., 2016). However, despite these treatment-related changes—particularly with respect to sleep characteristics—a recent meta-analysis found that prazosin did not improve overall PTSD symptoms significantly more than placebo (Zhang et al., 2020). Moreover, even though altered REM sleep is considered a hallmark of PTSD-related sleep disturbance and is also the period in which nightmares typically occur, nightmare activity and general sleep disturbances have been observed in both REM and non-REM sleep in individuals with PTSD (Germain, 2013; Phelps et al., 2018).

OSA is a sleep-related disorder that may contribute to sleep disturbance in individuals with PTSD. OSA is up to three times more prevalent in individuals with PTSD compared to the general population, and a recent meta-analysis found diagnosable OSA in 43-75% of individuals with PTSD (Sharafkhaneh et al., 2005; Zhang et al., 2017). Individuals with PTSD and OSA were also found to have significantly lower adherence to continuous positive airway pressure (CPAP)—the primary treatment for OSA—than individuals with OSA alone (Zhang et al., 2017). The presence of OSA is also related to greater PTSD symptom severity (van Liempt et al., 2011), and elevated respiratory event index during sleep (a measure of sleep-disordered breathing characteristic of OSA) has been associated with reports of nightmares the next morning among veterans with PTSD (Miller et al., 2018). However, research suggests that successfully treating OSA not only diminishes symptoms of sleep disturbance but can impact PTSD symptoms and key memory and learning processes related to PTSD. For example, in a prospective cohort of veterans with PTSD and OSA, CPAP usage was associated with PTSD symptom improvement, including the frequency of nightmares (El-Solh et al., 2017). A recent study also found that CPAP treatment enhanced generalization of fear extinction learning in veterans with OSA, yet dysregulation of fear extinction and inhibition processes were still observed in veterans with PTSD when compared to veterans without PTSD (Reist et al., 2021).

Sleep Disturbance as a PTSD Risk Factor

In addition to being a common symptom of PTSD, sleep disturbance is a proposed risk factor for the development of PTSD after trauma. Sleep disturbances before a traumatic event have been found to contribute to elevated risk of new-onset PTSD (Koffel et al., 2013). Indeed, insomnia in veterans prior to deployment was nearly as strong a predictor of post-deployment PTSD development as the degree of combat exposure (Gehrman et al., 2013). A prospective cohort study of veterans also found that self-reported nightmares prior to deployment predicted greater risk of PTSD at a 6-month follow up (van Liempt et al., 2013). In addition, sleep disruption in the acute aftermath of trauma has been linked to greater risk of developing PTSD in response to the traumatic event. For example, sleep fragmentation, greater REM fragmentation, and nightmares in the period following trauma exposure have been associated with greater risk of PTSD onset and/or persistence of PTSD symptoms (Kobayashi et al., 2007; Mellman et al., 2002; Mellman et al., 2007). The links between sleep disturbances and impairments in fear learning and memory may be particularly relevant for understanding risk for PTSD after trauma. For example, research in rodent models of PTSD has documented REM sleep patterns during pre-trauma and acute post-trauma periods that predict PTSD-like phenotypes, and these changes in sleep behavior were associated with poorer fear extinction, which mirrors impairments in generalization of fear extinction memory seen in human studies of PTSD (Polta et al., 2013; Vanderheyden et al., 2015). Together, these findings suggest that sleep disturbance is more than a symptom of the disorder. Rather, sleep may be involved in the etiology and persistence of PTSD (Germain, 2013; Walker & van der Helm, 2009).

In sum, research has linked PTSD to various manifestations of sleep disturbance, including nightmares, shorter sleep duration, poor sleep quality, greater prevalence of OSA and insomnia, and dysregulated REM sleep. Furthermore, poor sleep before trauma and in the acute posttraumatic period may confer risk for the onset of PTSD, presenting a potential period for early interventions targeting sleep to offset risk of PTSD. For example, sleep-related interventions aimed at preventing PTSD have been suggested, including sleep restriction in the hours following trauma exposure to alter emotional memory consolidation during REM sleep, but empirical work is needed (Repantis et al., 2020). Figure 1 outlines ways in which sleep disturbance may manifest before and after trauma exposure and contribute to PTSD onset and maintenance. These findings have prompted researchers to no longer regard sleep as merely a symptom of PTSD and instead consider sleep as playing a role in the development and/or persistence of the disorder via mechanisms such as sympathetic hyperarousal and disrupted fear learning and memory. However, the impact of disturbed sleep does not end with psychological consequences of trauma but also extends to the cardiovascular system.

Figure 1. Potential Pathways by which Sleep Disturbance May Contribute to PTSD and Elevated CVD Risk in Individuals Exposed to Trauma.

Figure 1

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Note. Text boxes with dotted lines denote windows of opportunity for screening and sleep behavior intervention before and after trauma and PTSD onset. Recursive arrows indicate factors that may maintain PTSD. CVD=cardiovascular disease; OSA=obstructive sleep apnea; PTSD=posttraumatic stress disorder; REM=rapid eye movement.

Sleep and CVD Risk

A substantial body of evidence demonstrates that poor sleep quality and short sleep duration, as well as the presence of sleep disorders like insomnia and OSA, have deleterious consequences for cardiovascular health (Virani et al., 2021). A review of cross-sectional studies found that shorter sleep duration was associated with greater risk of CVD, with elevations in risk particularly pronounced for those sleeping ≤5 hours (vs. 7 hours) per night (Sabanayagam & Shankar, 2010). In addition, a large prospective cohort study of men and women found that individuals with short sleep duration and poor subjective sleep quality were at the greatest risk of incident CVD during a 10-15-year follow-up period (Hoevenaar-Blom et al., 2011). When compared to those who slept 7 hours per night and reported good sleep quality, individuals with both short sleep duration (≤ 6 hours) and poor sleep quality had a 63% higher risk of incident CVD and 79% higher risk of incident coronary heart disease, after adjusting for relevant confounders. Furthermore, longitudinal research has documented a link between sleep disturbance and elevated cardiovascular risk factors and conditions, including hypertension and dyslipidemia (Clark et al., 2016). A meta-analysis of prospective cohort studies of incident hypertension found that short sleep duration and insomnia symptoms predicted the development of hypertension (Meng et al., 2013).

Short sleep duration can occur as a result of sleep disorders including insomnia and OSA, and it can have adverse downstream consequences for cardiovascular health (Institute of Medicine Committee on Sleep & Research, 2006). Individuals with habitual short sleep duration measured by actigraphy showed exaggerated coronary responses to laboratory stressors, including prolonged elevated heart rate and diastolic blood pressure (Meznick et al., 2014), and similar findings have been reported in short-term laboratory sleep deprivation studies (Franzen et al., 2011; Tochikubo et al., 1996). In addition, a number of studies have found increased proinflammatory biomarkers in experimental studies of sleep deprivation and in individuals with habitual short sleep duration (Irwin et al., 2016). These proinflammatory processes contribute to all stages of CVD, from endothelial dysfunction and the development of atherosclerotic plaques to acute events including myocardial infarction and stroke (Libby et al., 2019).

Hypertension is a major CVD risk factor that is highly prevalent in the general population, occurring in approximately 40% of adults in the United States (Virani et al., 2021), and it represents an important pathway linking poor sleep with CVD. Proposed physiological mechanisms of the relation between sleep disturbance and hypertension include increased sympathetic nervous system activity and increased inflammation (Javaheri & Redline, 2017). Furthermore, insomnia has been characterized as a disorder of cognitive and physiological hyperarousal (Bonnet & Arand, 2010). Individuals with insomnia have been found to have elevated resting heart rates, sympathetic nervous system activity, and HPA axis activity compared to those without insomnia, all indicative of physiological hyperarousal (Hauan et al., 2018; Vgontzas et al., 2001).

In 2003, sleep apneas were recognized as a common cause of hypertension in the seventh report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure (Chobanian et al., 2003). Intermittent hypoxia that occurs with apneic events results in sustained activation of the sympathetic nervous system, which promotes vasoconstriction and increased blood pressure, and sympathetic overactivity is a frequently cited mechanism of the OSA and hypertension relation, in addition to endothelial dysfunction (Fletcher, 2003; Prabhakar & Kumar, 2010). A recent longitudinal study of individuals without hypertension found that mild or moderate OSA predicted greater rates of incident hypertension over an approximately 9-year follow-up (Vgontzas et al., 2019). Treatment of OSA with CPAP was found to decrease systolic and diastolic blood pressure and mean arterial pressure, another blood pressure-related CVD risk factor (Bazzano et al., 2007). OSA is also related to several adverse CVD outcomes. A recent meta-analysis found that the presence of OSA in adults significantly increased the risk of cerebrovascular disease (Wu et al., 2018). In addition, treatment with CPAP was found to reduce the elevated risk of stroke associated with OSA (Catalan-Serra et al., 2019). Identification and treatment of OSA is thus increasingly considered an important factor in the management of CVD risk.

In sum, substantial research has linked manifestations of sleep disturbance, including short sleep duration, insomnia, and OSA, with poor cardiovascular health. As shown in Figure 1, sleep disruption may trigger a cascade of physiological processes that, in turn, have deleterious effects for cardiovascular health. For example, hypertension, sympathetic hyperarousal, and inflammation are sensitive to sleep disturbance and may contribute to CVD risk.

Research Examining the Role of Sleep in the PTSD-CVD Risk Relation

Given the evidence linking PTSD with sleep disturbance and sleep disturbance with incident CVD, research investigating sleep as a potential modifiable behavioral factor in the PTSD-CVD relation is a natural extension of the literature. However, although studies have explored behavioral pathways underlying the association of PTSD with CVD (e.g., Scherrer et al., 2019; Sumner et al., 2015) or considered the role of sleep in the relation between PTSD and physical inactivity (a CVD risk factor; Talbot et al., 2014a), there is little published research testing the effects of sleep disturbance with respect to the PTSD-CVD association (Edmondson & von Känel, 2017). Nevertheless, sleep disturbance may contribute to a number of downstream physiological consequences that may be plausible mechanisms in the PTSD-CVD risk relation (e.g., autonomic nervous system dysregulation, elevated inflammation; see Figure 1), and studies have begun to investigate these processes in the context of PTSD. We highlight some of these studies below, as they may help guide research on PTSD, sleep, and CVD risk.

Autonomic dysregulation is well-established in individuals with PTSD (Pitman et al., 2012). Heart rate variability (HRV) is a noninvasive measure of autonomic balance, and meta-analytic evidence suggests PTSD is associated with lower HRV, indicating sympathetic predominance and/or parasympathetic withdrawal (Schneider & Schwerdtfeger, 2020). Further, individuals with lower HRV have a higher lifetime incidence of CVD (Dekker et al., 2000). Sleep disturbances may also contribute to autonomic dysregulation. For example, short sleep duration that may occur as a result of sleep disorders like insomnia and OSA has been consistently associated with daytime and overnight sympathetic overactivity and parasympathetic withdrawal (Tobaldini et al., 2019), with convergent evidence observed in longitudinal studies of individuals with habitual short sleep duration (Takase et al., 2004) and in laboratory studies of acute sleep deprivation (Tobaldini et al., 2013, Grimaldi et al., 2016). Individuals with PTSD have been shown to exhibit physiological markers of parasympathetic withdrawal during sleep (Woodward et al., 2009), and trauma-related nightmares in particular have been linked to lower parasympathetic activity in individuals with PTSD when sleeping and awake (Miller et al., 2018; Tanev et al., 2017). Additionally, research has shown that although greater PTSD symptoms are associated with lower HRV, this association was no longer significant when adjusting for sleep disturbance, suggesting that sleep disturbance may account for much of the association between PTSD symptoms and autonomic dysregulation (Dennis et al., 2014).

Elevated inflammation can also result from poor sleep (Irwin et al., 2016) and is another hypothesized pathway linking PTSD, sleep, and CVD risk. Experimental studies have shown that acute induction of partial sleep deprivation results in subsequent elevation of inflammatory cytokines implicated in atherogenesis (Meier-Ewert et al., 2004, van Leeuwen et al., 2009). Meta-analytic evidence indicates that PTSD is associated with elevated levels of several inflammatory markers (Passos et al., 2015), and there is also some evidence that overnight trajectories of pro-inflammatory cytokines differ in individuals with and without PTSD (Küffer et al., 2019). Additionally, sleep improvements over 3 months in previously deployed military personnel were associated with reductions in C-reactive protein over the 3-month period (Heinzelmann et al., 2014), suggesting that remedying sleep disturbance after trauma might decrease inflammation. Together, these studies provide some examples of how to investigate CVD risk pathways that may result from poor sleep in the context of PTSD. Additional mechanism-focused research—particularly studies that use longitudinal and/or experimental designs—will extend our understanding of key downstream physiological processes associated with sleep disturbance that may contribute to cardiovascular risk in individuals with PTSD.

Although published research addressing the link between sleep disturbance in the context of PTSD and subsequent CVD risk is minimal, there are, however, a number of National Institutes of Health-funded studies underway that directly test these associations, and many include measures of potential mechanisms. For example, in a study of twins with and without PTSD, Vaccarino and colleagues (R01HL136205) are using polysomnography- and actigraphy-based measures of sleep characteristics to examine whether disturbed sleep is related to autonomic dysregulation and increased cardiovascular risk in individuals with PTSD. Additionally, our lab is examining whether self-reported sleep disturbance may underlie, in part, associations of PTSD symptoms with endothelial dysfunction (R01HL139614, PI: Sumner). Furthermore, research by Burg and colleagues (R01HL125587) is testing whether objectively measured poor sleep is related to elevated ambulatory blood pressure in individuals with PTSD and whether successful PTSD treatment improves sleep while also reducing blood pressure and incident CVD risk. An ongoing study by Beckham and Sherwood (R01HL148327) is also evaluating whether decreased insomnia symptoms following 8 weeks of Cognitive Behavioral Therapy for Insomnia (CBT-I)—the leading treatment for addressing insomnia in non-psychiatric and psychiatric populations (Edinger et al., 2021)—will result in improved markers of CVD risk (specifically endothelial function) among individuals with PTSD. The results of these observational and experimental studies have yet to be published, but they may further our understanding of the impact of sleep on CVD risk in individuals with PTSD and inform the development and refinement of sleep-based interventions aimed at offsetting CVD risk.

Future Directions for Research and Implications for Clinical Practice

More research is needed to better understand pathological processes in sleep and their role in the PTSD-CVD relationship and inform screening and intervention efforts. Key questions remain unanswered, including whether disrupted sleep accounts, in part, for the link between PTSD and CVD; whether pre-existing sleep disturbances and related disorders (i.e., prior to trauma exposure) contribute to poor sleep in individuals with PTSD and, in turn, relate to CVD risk; and whether treating disrupted sleep and related disorders with gold-standard interventions may reduce cardiovascular risk markers in individuals with PTSD. Here, we outline several directions for such research, highlighting ways in which commonly used study designs and research paradigms can be harnessed to address these questions in feasible ways.

One avenue for examining the role of sleep in the PTSD-CVD relation is leveraging existing longitudinal cohort studies. For example, a number of cohorts focused on understanding risk for CVD include measures of sleep, such as the Multi-Ethnic Study of Atherosclerosis and the Atherosclerosis Risk in Communities study (Full et al., 2020; Lutsey et al., 2015). Many of these studies also measure psychosocial factors, although trauma exposure and PTSD symptoms may not always be included in these assessments. Nevertheless, brief measures of these constructs exist and have been incorporated successfully into longitudinal observational cohorts (e.g., the Nurses’ Health Study II; Koenen et al., 2009). With their rich data on cardiovascular risk factors and outcomes, these cohorts could thereby permit examinations of disrupted sleep and downstream physiological consequences as pathways linking PTSD with CVD events that account for a range of covariates.

Another potential approach is to harness electronic medical record data that include information on PTSD, sleep, and CVD. For example, the Veterans Health Administration electronic medical record contains diagnostic data on sleep-related disorders such as insomnia and OSA (Alexander et al., 2016), in addition to PTSD and CVD. Although retrospective database analyses are characterized by certain limitations (e.g., selection bias, possible misclassification, issues with representativeness, missing data) and administrative data are restricted in terms of the aspects of sleep that are captured, these data resources permit an examination of the links between PTSD, disrupted sleep, and CVD in veterans, a population for whom trauma and PTSD are a major public health concern.

To better understand how sleep-related risk processes unfold after trauma and how they may relate to subsequent PTSD and cardiovascular health, particular study designs that have been employed to examine risk for developing PTSD may hold promise. Specifically, longitudinal studies of populations with a high risk of trauma exposure (e.g., first responders, military personnel before deployment) have been assessed prior to and after trauma (e.g., Bryant & Guthrie, 2005; Yuan et al., 2011). Incorporating repeated measures of sleep and cardiovascular risk markers can shed light on manifestations of sleep before and after trauma and how they relate to PTSD and cardiovascular risk over time. In addition, research frameworks exist for studying individuals admitted to the hospital following acute trauma exposure in order to understand risk for PTSD (e.g., the AURORA Study; McLean et al., 2020). Incorporating repeated measures of sleep into these designs can help to elucidate the temporal factors of sleep disturbance that manifest after trauma and that influence both PTSD development and future cardiovascular risk. In these studies, sleep disturbance can be measured with various validated techniques, including self-report (e.g., questionnaires, sleep diaries) and objective (e.g., actigraphy, electroencephalography) measurements. In addition, including repeated measures of predeterminants of CVD that exhibit variability even in relatively healthy populations, such as blood pressure and endothelial function, may hold promise for understanding mechanisms in samples that are not powered for predicting CVD events.

Future research that examines circadian influences in individuals with PTSD may also provide a more nuanced understanding of PTSD-related sleep disturbance and CVD risk. Circadian influence provides temporal organization to homeostatic mechanisms and, in addition to being highly related to sleep, is sensitive to overactivity in the stress response system (Agorastos et al., 2020). Both the autonomic nervous system and the HPA axis follow consistent circadian patterns that, when disrupted by exaggerated or sustained stress response, may set the stage for elevated CVD risk. For example, when combat-exposed men with and without PTSD were compared, those with PTSD exhibit blunted autonomic variation between day and night measures and higher baseline heart rate over the 24-hour recording period (Agorastos et al., 2013). Circadian HRV has also been shown to differ in relation to PTSD symptom severity, with greater symptom severity linked to decreased parasympathetic activity (Rissling et al., 2016). Additionally, blood pressure is sensitive to circadian influence, and CVD risk increases dramatically with disturbances in the natural tendency of blood pressure to decrease during sleep. Indeed, each 5% deficiency in the normal decline in nocturnal blood pressure (i.e., non-dipping) is associated with an approximately 20% greater risk in cardiovascular mortality (Ohkubo et al., 2002), and some evidence suggests that PTSD may be associated with non-dipping (Mellman et al., 2009). Research examining within-day differences in heart rate, ambulatory and overnight blood pressure, and HRV may help us better understand specific characteristics of PTSD-related sleep disturbance that influence these CVD risk factors and may serve in the development of targeted chronotherapeutic interventions.

Another promising research direction involves testing whether the treatment of PTSD-related sleep disturbance leads to decreased CVD risk. A number of interventions for sleep disturbance have been explored in individuals with PTSD-related sleep disturbances, including CBT-I. Compared to a waitlist control condition, CBT-I has been shown to lead to improvements in a number of sleep characteristics, including sleep onset latency, subjective sleep quality, and insomnia severity (Talbot et al., 2014b). Including measures of cardiovascular risk factors such as those mentioned above in randomized controlled trials of CBT-I has the potential to provide insights into whether gold-standard treatments for disrupted sleep may bring about improvement in cardiovascular risk markers in those with PTSD.

Although CBT-I has promising results, it has been found to have limited success with increasing sleep duration—a well-documented harmful dimension of sleep disturbance in terms of CVD risk (van Straten et al., 2018). Preliminary work in a small sample of individuals with hypertension using a behavioral intervention aimed at extending sleep duration by assigning sleep schedules that increased time spent in bed found greater daily sleep duration and lower ambulatory blood pressure in individuals who received the sleep extension intervention (Haack et al., 2013). Reduced blood pressure and increased total sleep time were also found following a sleep extension intervention that consisted of a smartphone application, weekly didactic lessons, and brief telephone coaching (Baron et al., 2019), thereby suggesting that future intervention-focused research may also benefit from emphasizing sleep extension.

Although the above research frameworks focus on human participants, translational preclinical research that offers insights into potential pathways underlying the behavioral mechanisms of cardiovascular pathology and disease risk after trauma are also recommended. A notable recent review by Schloss et al. (2020) summarizes animal and human research exploring modifiable factors of CVD risk and progression, including sleep, and it provides a model for how preclinical and clinical research can inform each other. Although we focused on human studies in this review, animal models of PTSD (e.g., single prolonged stressor and fear conditioning and extinction paradigms) are relevant to the identification of sleep characteristics predictive of PTSD, as they allow researchers to observe changes in sleep behavior that are evident from baseline to following traumatic stress exposure (i.e., both before and after PTSD-like phenotypes emerge). These models also offer an experimental framework for testing the hypothesis that disrupted consolidation of fear extinction memory during sleep plays a role in the onset and maintenance of PTSD symptoms and can be adapted to include CVD risk markers associated with specific dimensions of sleep disturbance.

Despite the current lack of conclusive evidence of the role of sleep disturbance in the development of CVD in individuals with PTSD, the research directions described above may have important implications for CVD prevention and enhanced behavioral medicine models of the cardiovascular impact of psychological health after trauma. Indeed, as shown in Figure 1, there are multiple windows of opportunity for screening and sleep behavior intervention before and after trauma and PTSD onset.

Conclusions

If research indicates that disrupted sleep explains, at least in part, the onset of CVD in individuals with PTSD and that behavioral sleep interventions can reduce this elevated CVD risk, then mental health care providers and physicians on either side of the PTSD-CVD equation in the future may screen for sleep disruptions and cardiovascular risk in those with PTSD and provide behavioral recommendations or referrals for sleep interventions to improve cardiovascular health outcomes. Research findings could be incorporated into a number of clinical settings, including mental health, primary care, and cardiovascular clinics, and they have the potential to offer an enhanced framework for the evaluation, screening, and management of trauma-exposed individuals at risk of CVD. Implementation of this model of care would exemplify the power of incorporating the psychological and behavioral evidence base to directly address the mind-heart-body connection (Levine et al., 2021) in order to promote cardiovascular health.

Acknowledgments

This work was supported by the National Heart, Lung, and Blood Institute (R01HL139614 to J.A.S.). There are no conflicts of interest to report.

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