Insomnia’s toll on the heart: study highlights cardiovascular event risks

In a recent study published in PLoS ONE, researchers performed a meta-analysis to evaluate the incidence of cardiovascular (CV) events among individuals with insomnia.

Insomnia, a common sleep disorder and the second most prevalent psychiatric disorder worldwide, is associated with cardiovascular disease and increased morbidity and mortality. It is characterized by difficulty in sleep quality, often accompanied by daytime dysfunction. Risk factors include hypertension, metabolic disorders, and diabetes mellitus. Recent studies on insomnia patients evaluating cardiovascular outcomes are scarce, necessitating an updated meta-analysis to assess its impact on cardiovascular disease.

About the study

In the present meta-analysis of real-world data, researchers investigated the link between insomnia and cardiovascular disease-related deaths, myocardial infarction (MI), any-cause deaths, and the incidence of cardiovascular disease.

Databases such as PubMed/MEDLINE, Cochrane Library, and Google Scholar were searched through August 2022 for studies comparing predefined CV outcomes among insomniac individuals. The primary study outcomes were MI and CV mortality, whereas secondary study outcomes included any-cause deaths and cardiovascular disease incidence. 

Reverse-type snowballing of previously published meta-analytic studies was performed by screening references of the included records without any language or publication time restrictions. The team also searched other sources of data, including editorial bibliographies, literature reviews from main scientific journals, databases of unpublished/grey literature, and conference proceedings. Two researchers independently screened the data, and discrepancies were resolved by discussion or consulting another researcher.

Inverse variance-weighted-type random effects modeling was performed to pool data and calculate the risk ratios (RRs). Only records, including adults, observational studies, and secondary evaluations of original research reporting only insomnia and related symptoms, including difficulties in sleep initiation, difficulties in sleep maintenance, early morning awakening (EMA), and non-restorative-type sleep, were included.

Studies conducted on animals and children, records such as case-control studies, case reports, and case series, and studies lacking comparators or controls were excluded from the analysis. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of evidence. The researchers performed a sub-group analysis to evaluate the associations of CVD outcomes by follow-up duration. In addition, sensitivity analyses were performed for records with I2 values exceeding 50.

Results

In the initial search, 12,250 records were identified, of which 9,980 remained after duplicate removal. However, after the title-abstract screening and full-text screening, only 21 records were analyzed, including 388,906 insomniac individuals and 2,194,211 disease-free individuals, with a mean participant age of 59 years. The duration of follow-up ranged between three and 20 years.

Risks for cardiovascular mortality (RR, 1.5) and myocardial infarction (RR, 1.5) were significantly greater among individuals with insomnia. In addition, all-cause death risks and cardiovascular disease incidence rates were significantly greater among individuals with insomnia, with RR values of 1.1 and 1.3, respectively. Insomnia patients experienced an increased risk of long-term deaths, myocardial infarction, and cardiovascular illness incidence.

In the sub-group analysis, analyzing for 10 to 20 years of follow-up, any-cause deaths were significantly higher among individuals with insomnia versus those without (RR, 1.2). Consistent trends were observed with the overall results at 10 to 20 years, revealing significantly greater incidences of cardiovascular events among insomniacs versus non-insomniacs (RR, 1.3).

In the sensitivity analysis, excluding studies underpowered for confounding variables (smoking, physical exercise, body mass index (BMI), caffeine and alcohol intake, family history, and dietary factors) with particular study populations such as Caucasians and those with chronic renal disease reduced heterogeneity. There was no evidence of publication bias in the included studies.

The renin-angiotensinogen-aldosterone system, an activated renin-angiotensinogen-aldosterone system, has been hypothesized to increase the risk of mortality in insomniac patients. This is due to the comorbidity of psychological disorders, such as depression and anxiety, and the higher rates of self-harm and suicide associated with these illnesses. The hypothalamic-pituitary (HPA) axis, abnormal modulation of the autonomic nervous system, increased sympathetic nervous system activity, systemic inflammation, and atherogenesis are hypothesized to contribute to this association.

Conclusions

Overall, the study findings showed that individuals presenting with insomnia symptoms had significantly greater risks of myocardial infarction (48%), cardiovascular mortality (53%), cardiovascular illness incidence (14%), as well as all-cause deaths (31%), in comparison to healthy individuals. In addition, there was a significant increase in mortality rates linked to longer follow-ups.

Clinicians should evaluate cardiovascular risks and tailor interventions, considering coexisting risks like coronary artery disease and smoking. Adequately powered observational studies, controlled for confounding risk factors and sleep disorders, are needed to understand pathophysiological mechanisms better and improve treatment for insomnia and related conditions.