Insomnia and risk of mortality from all-cause, cardiovascular disease, and cancer: Systematic review and meta-analysis of prospective cohort studies

Summary

Growing evidence indicates that insomnia may be associated with mortality. However, these findings have been inconsistent. We systematically searched MEDLINE and EMBASE to identify prospective cohort studies that assessed the association between insomnia disorder/individual insomnia symptoms and the risk of mortality among adults aged ≥18 yrs. We addressed this association using summary hazard ratios (HRs) and 95% confidence intervals (CIs) calculated using random-effects meta-analysis, and the GRADE approach to rate the certainty of evidence. Twenty-nine cohorts including 1,598,628 individuals (55.3% men; mean age 63.7 yrs old) with a median follow-up duration of 10.5 yrs proved eligible. Difficulty falling asleep (DFA) and non-restorative sleep (NRS) were associated with an increased risk of all-cause mortality (DFA: HR = 1.13, 95%CI 1.03 to 1.23, p = 0.009, moderate certainty; NRS: HR = 1.23, 95%CI 1.07 to 1.42, p = 0.003, high certainty) and cardiovascular disease mortality (DFA: 1.20, 95%CI: 1.01, 1.43; p = 0.04, moderate certainty; NRS: HR = 1.48, 95%CI 1.06 to 2.06, p = 0.02, moderate certainty). Convincing associations between DFA and all-cause mortality were restricted to the mid to older-aged population (moderate credibility). Insomnia disorder, difficulty maintaining sleep, and early morning awakening proved to be unassociated with all-cause and cardiovascular disease mortality. No insomnia symptoms proved to be associated with cancer-related mortality.

Introduction

Insomnia, most commonly characterized by difficulty falling asleep, difficulty maintaining sleep, or early morning awakening, is an important public health problem with substantial medical, psychiatric, and financial ramifications [1]. Epidemiological surveys have reported a prevalence of insomnia symptoms in between 35% and 70% of the general adult population [2]. The total costs associated with insomnia exceed $100 billion annually in the United States of America [3]. Systematic reviews have established the association between insomnia and an increased risk of mental or medical disorders including depression [4], dementia [5], nonalcoholic fatty liver disease [6], hypertension [7], cardiovascular disease [8], [9], [10], and perinatal depressive symptoms [11].

Increasing evidence has also suggested that sleep disorders may be associated with mortality. Several meta-analyses have presented evidence that longer or shorter sleep duration is associated with a higher risk of mortality [12], [13], [14], ∗[15]. Published cohort studies have reported that some insomnia symptoms may be independently associated with mortality; these findings have, however, proved inconsistent [16], ∗[17], [18], [19], ∗[20], [21], ∗[22], [23], [24]. For example, although several studies have reported associations between insomnia symptoms and mortality [16], ∗[17], [18], [19], [21], others have not ∗[20], ∗[22], [23], [24]. Varying assessment methods of insomnia symptoms, and approaches to adjusted analysis may, at least in part, explain these inconsistencies.

To clarify this issue, we performed a systematic review and meta-analysis of prospective cohort studies from the general population. The aim of this was to comprehensively assess the association between mortality from all-cause, cardiovascular, and cancer and both insomnia disorder and individual insomnia symptoms (difficulty falling asleep, difficulty maintaining sleep, early morning awakening, and non-restorative sleep).