Don't Take Sleep Lightly: Insomnia Symptoms Tied to Stroke, MI

Damian McNamara

November 06, 2019

Insomnia symptoms are associated with an increased risk of stroke, myocardial infarction, and other cardio-cerebral vascular disease (CCVD), a large, prospective study shows. However, at least one expert urges caution in interpreting the findings, noting that the overall effect is "very small."

Researchers found early morning awakening (EMA), difficulty initiating or maintaining sleep (DIMS), and daytime dysfunction (DDF) were linked to a 7%, 9%, and 13% elevated CCVD risk, respectively.

In addition, there was a dose-dependent relationship between the number of symptoms and greater CCVD risk.

Compared with those who have no insomnia symptoms, the researchers found that one insomnia symptom was tied to a 7% increased incidence of CCVD, two symptoms to a 10% increased incidence, and three symptoms to an 18% increased incidence.

"Individual insomnia symptoms are independent risk factors for heart disease and stroke. Adults with multiple insomnia symptoms are at even higher risk of developing heart disease or stroke, which should also draw clinical attention," study investigator Liming Li, MD, Peking University Health Science Center, Beijing, China, told Medscape Medical News.

The study was published online today in Neurology.

Limited, Controversial Evidence

Previous cohort studies lack a uniform definition of insomnia, the researchers note. In some cases insomnia is defined as simply as "having difficulties initiating sleep."

They add there is "limited and controversial evidence" about whether age, sex, or other demographic differences influence an association between insomnia and CCVD.

To get a clearer picture, the researchers analyzed data from 487,200 participants in the China Kadoorie Biobank Study. The cohort included adults aged 30 to 79 years from 10 different geographic regions of China.

Participants completed a baseline survey between 2004 and 2008, including questions about presence and frequency of insomnia symptoms.

At baseline, 11% had DIMS, 10% reported EMA, and 2% of participants endorsed DDF because of poor sleep. None of the participants had CCVD at study entry.

Participants reporting insomnia symptoms were older, female, unmarried, and from a rural area compared with unaffected participants.

In addition, the symptomatic group had lower education levels, lower household incomes, and slightly lower BMI. They also were more likely to have a history of diabetes mellitus and symptoms of anxiety or depression.

The investigators assessed CCVD outcomes over a median of 9.6 years of follow-up using ICD-10 codes and data from disease registries, health insurance claims, and local residential records.

A total 130,032 CCVD cases developed during follow-up. This included 40,348 cases of ischemic heart disease and 45,316 instances of stroke.

Those with at least one insomnia symptom had "slightly increased risks" of total stroke incidence, with hazard ratios of 1.05 - 1.08, as well as ischemic stroke incidence (HRs, 1.06 -1.09). However, researchers found no such association between the three symptoms and risk of hemorrhagic stroke.

Evaluated separately, each symptom was associated with an increased risk for total CCVD incidence. DIMS at baseline, for example, was associated with a hazard ratio of 1.09 (95% confidence interval, 1.07 - 1.11) in an analysis that adjusted for potential confounders including alcohol use, smoking, and level of physical activity.

Similarly, EMA (HR, 1.07; 95% CI, 1.05 - 1.09) and DDF (HR, 1.13; 95% CI, 1.09 - 1.18) were linked to increased risk.

Interestingly, although prevalence of insomnia generally is higher among older adults, "it is indeed more detrimental for young adults in terms of CCVD risks," the researchers note.

In the study, the associations were stronger between the three symptoms and CCVD incidence in two groups — younger adults and participants without hypertension at baseline.

"Younger adults or adults without hypertension may benefit more from early detection and intervention of insomnia symptoms in terms of cardiovascular health," Li said.

The study did not address nonrestorative sleep, another common symptom of insomnia. Other possible limitations include assessment of symptoms only once, at baseline, and reliance on self-reports.

"Therefore," the researchers note, "our findings need to be interpreted with caution due to possible information bias."

Future research is needed, the authors say, to determine whether changes in lifestyle or sleep hygiene in order to improve insomnia symptoms would reduce CCVD risk.

Caveats, Clinical Implications

Commenting on the findings for Medscape Medical News, James Burke, MD, a neurologist at the University of Michigan in Ann Arbor, said the study revealed "a very small effect."

"The robustness of the statistical comparisons is due to the enormous sample size. There are an enormous number of possible explanations for that effect. I would interpret this study cautiously," said Burke, who was not associated with the study.

Burke added that the study's small effect size combined with "lots of unmeasured confounders" may make it difficult to replicate the findings.

Also commenting, Julio Fernandez-Mendoza, PhD, CBSM, DBSM, a sleep psychologist at Penn State College of Medicine in Hershey, Pennsylvania who was not involved with the research, said the study highlights the need for "better screening and early therapeutic approaches in adults aged 30 to 49 years old or in individuals who have not yet developed the more traditional cardiovascular or cerebrovascular disease risk factors such as elevated blood pressure."

"Individuals from these groups who complain of insomnia symptoms should undergo a clinical workup and not be regarded as otherwise healthy poor sleepers," Fernandez-Mendoza told Medscape Medical News.  

An "important limitation" is lack of objective measures of sleep to adjust for sleep apnea and other organic sleep disorders closely associated with cardiovascular or cerebrovascular disease, Fernandez-Mendoza said.

In addition, identifying patients with insomnia who display objective short sleep duration (ISSD) would have been useful.

"The risk estimates or hazard ratios reported in this study are only about 1.2-fold, while the ISSD phenotype has revealed risk estimates of a 2.0- to 5.0-fold magnitude for cardiovascular and brain health outcomes."

"Nevertheless, this large, longitudinal study provides further evidence that self-reported insomnia complaints occurring at least three times a week should be taken seriously by clinicians," Fernandez-Mendoza said.

Li, Fernandez-Mendoza and Burke have disclosed no relevant financial relationships. Grants from the National Key Research and Development Program of China, the Chinese Ministry of Science and Technology, and the National Natural Science Foundation of China supported the study.

Neurology. Published online November 6, 2019. Abstract

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