Waking up to the importance of sleeping well for cardiovascular health

The potentially adverse impact of poor sleep quality, insomnia, and other sleep disorders on cardiovascular disease (CVD) risk has been the subject of increasing exploration over the past decade. Obstructive sleep apnea has been the most extensively studied sleep disorder in relation to hypertension, and is thought to be causally related through mechanisms including heightened sympathetic nervous system activity and vascular endothelial dysfunction that are triggered by sleep‐disordered breathing.1 A growing body of research evidence has also revealed relationships between insomnia and CVD. Insomnia is the most common sleep disorder and is defined by subjective reports of difficulty in falling asleep, maintaining sleep, or waking too early.2 With insomnia, both sleep quality and duration are often impaired. Although a diagnosis of insomnia disorder may be based on self‐report alone, objectively assessed insomnia features using polysomnography reveals longer sleep onset latency, more frequent nocturnal awakenings, and prolonged periods of wakefulness during the sleep period relative to normal sleepers.3 Observational studies employing objective sleep measures show that individuals with insomnia are more likely to have CVD, even after controlling for comorbid sleep disorders, and other potentially confounding comorbidities.4 Short sleep duration has also been associated with an increased risk of heart disease, higher blood pressure (BP), metabolic syndrome, greater coronary calcification, and higher levels of stress hormones.5 An important pathway through which sleep may affect CVD risk is through its relationship with BP, with substantial support for an association between insomnia and incident hypertension.6, 7 For example, in a prospective study of 786 men and women from the Penn State Cohort, those with chronic insomnia, determined by polysomnographic study and subjective reports of sleep problems persisting for over a year, were at over twice the risk of developing hypertension over a 7.5‐year follow‐up period. Furthermore, chronic insomnia coupled with short sleep duration (<6 hours) was associated with a fourfold increased risk of developing hypertension.8 Other studies, including the National Health and Nutrition Examination Survey, have reported similar observations, reinforcing the perspective that insomnia, when coupled with short sleep duration, may be especially hazardous in terms of its association with hypertension and CVD.9, 10, 11

Poor sleep quality is a widespread problem, commonly reported by patients with a variety of medical and mental health conditions,12, 13 as well as among those with diagnosed sleep disorders. However, the potentially broad impact of poor self‐reported sleep quality on CVD risk has received relatively little attention. In the current issue of the Journal of Clinical Hypertension, Lo and colleagues report14 an informative meta‐analysis examining the association between subjective sleep quality and BP. The authors include data from studies based on over 45 000 participants spanning five continents and provide formal analyses of studies that assessed subjective sleep quality using the well‐established and validated Pittsburgh Sleep Quality Index.15, 16 Their analyses showed that poor subjective sleep quality was associated with higher BP and an increased likelihood of hypertension. The impact of poor sleep quality is perhaps likely to be most conspicuously reflected in BP during the nighttime sleep period. Ambulatory BP monitoring studies have established that BP typically exhibits a circadian rhythm characterized by a fall in pressure during the nighttime sleep period. Relative to daytime pressure, a nighttime dip in BP of ≥10% is considered normal and individuals with this level of BP dipping are referred to as BP dippers, whereas a nighttime BP dip of <10% describes nondippers.17 Lo and colleagues found that in the subset of studies in their meta‐analysis, which used both the Pittsburgh Sleep Quality Index and ambulatory BP monitoring, BP dippers were characterized by better sleep quality than nondippers. Other studies, using subjective as well as objective measures of sleep quality derived from polysomnography and actigraphy, also have shown poor sleep quality to be associated with a blunting of the normal nighttime dip in BP.18, 19, 20, 21, 22

The nondipping circadian BP profile is associated with target organ damage, including cardiac left ventricular hypertrophy and chronic kidney disease23, 24 and is a strong prognostic indicator of cardiovascular morbidity and mortality for both patients with and those without hypertension.23, 25, 26, 27, 28 This evidence underscores the importance of BP measured during the nighttime sleep period, reflecting its greater prognostic significance than clinic BP, or ambulatory BP assessed during the daytime.29 Nonetheless, the physiological mechanisms accounting for blunted nighttime BP dipping and elevated nighttime BP are not well understood.30 Sympathetic nervous system activity normally shows a substantial decline from daytime waking activities to nighttime sleep, but the magnitude of this decline is attenuated in the context of a nondipping nighttime BP profile.21, 31, 32 Heightened nighttime sympathetic nervous system activity would favor peripheral vascular constriction, resulting in abnormally elevated systemic vascular resistance during the sleep period.33 The contribution of vascular disease to a blunted nighttime BP dip is supported by observations that a nondipping circadian BP profile is approximately twice as common in patients with coronary heart disease compared with age‐matched healthy controls.34, 35 Blunted BP dipping has also been associated with impaired vascular endothelial function in women with untreated hypertension.35 As might be anticipated, in a study of men and women with hypertension, the hemodynamic mechanism related to a nondipping BP profile was a failure for systemic vascular resistance to show a normal decline during the nighttime sleep period.37 In view of the well‐established pathophysiologic significance of elevated systemic vascular resistance in the development of left ventricular hypertrophy in hypertension,38 coupled with the prognostic significance of elevated nighttime BP, it is not difficult to appreciate the potential importance that sleep quality may have in the pathogenesis of hypertensive heart disease.

The available evidence therefore clearly implicates poor sleep quality and insomnia as risk factors in the cause of hypertension. It also suggests that in the context of high BP and hypertension, poor sleep quality may exacerbate hypertension by promoting target organ damage and increasing the likelihood of adverse cardiovascular events. However, the critical question of whether poor sleep quality is a modifiable risk factor for hypertension and CVD remains unanswered. In 2016, the American Heart Association published a scientific statement calling for research aimed at better understanding the association between sleep duration, sleep quality, and insomnia with CVD.39 Despite the wealth of available evidence, it is almost all observational, and the existence of a causal relationship between insomnia and CVD remains conjecture rather than inference. However, there is some preliminary evidence suggesting that sleep may be a modifiable risk factor for hypertension. In a pilot study of 22 adults with high BP, who slept <7 h/d, 13 were randomized to a 6‐week intervention designed to extend the sleep period and 9 to a control condition.40 Those in the sleep‐extension group showed a postintervention increase in sleep duration of 35 minutes following the intervention, which was accompanied by a significant decrease in 24‐hour BP, whereas no significant changes occurred in the control group. We now need more well‐designed randomized controlled trials to test the broad hypothesis that improving sleep quality in individuals with insomnia or subjectively reported sleep problems will reduce the risk of developing hypertension, as well as help control BP in those with hypertension, ultimately reducing the risk of adverse clinical events. Examining the effects of pharmacological treatments to improve sleep would be of interest, but interventions using cognitive behavior therapy for insomnia may be especially informative. Cognitive behavior therapy for insomnia is safe and effective and is the current gold standard for insomnia treatment.41 Therefore, it is ideally suited for intervention trials in healthy individuals and in patients with hypertension and/or other medical and psychiatric comorbidities.

CONFLICT OF INTEREST

The authors have no conflicts of interest to disclose.

Sherwood A, Ulmer CS, Beckham JC. Waking up to the importance of sleeping well for cardiovascular health. J Clin Hypertens. 2018;20:606–608. 10.1111/jch.13243