Are irregular sleep patterns associated with increased mortality risk?

In a recent article posted to the medRxiv* server, researchers recruited 8,975 adults aged 40 to 69 years from the United Kingdom (UK) Biobank for a prospective analysis of their sleep regularity and risk of all-cause, cardiovascular disease (CVD), and cancer mortality.

*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Background

Sleep irregularity disrupts circadian rhythms, endogenous cycles synchronized to the 24-hour dark and light cycle. This can lead to chronic age-related diseases, such as cancer and CVDs. Scientific evidence of the adverse health impacts of irregular sleeping and waking time is still emerging. 

Exposure to artificial and blue light at night, shift work, and erratic 24/7 lifestyles have blurred the day and night distinction, exacerbating the disruption of circadian rhythm manifold and heightening the need for research in this area.

About the study

In the present study, researchers collected each participant's baseline demographics, medical history, and vitals, e.g., blood pressure (BP) and blood samples.

They used a wrist-worn device to collect accelerometry data from 106,053 randomly selected participants for seven days and nights between February 2013 and December 2015. They also estimated their sleep status (awake or asleep) at a given time using GGIR version 2.7-1. 

This software uses an algorithm to determine the time window between the onset and end of daily sleep, during which bouts of sustained inactivity are considered sleep.

The sleep regularity index (SRI) is a new metric sensitive to sleep-wake time variations on a circadian timescale. An individual with SRI=100 sleeps and wakes same time each day, whereas it is zero for someone who sleeps and wakes randomly each day. The researchers used a linear mixed effects model to average SRI measurements, which they also standardized so that all SRI results were comparable. 

The team used ICD-10 codes to define CVD and cancer mortality. They also ascertained disease status at baseline for diabetes, prevalent or past cancer, mental disorders, and nervous system disorders.

Finally, they used a Cox proportional hazards model to examine associations between the SRI and all-cause, CVD, and cancer-related mortality. They also used time hazards models depicting time-varying hazard ratios (HRs) for interaction between SRI and time aggregated into three-month intervals.

Results

The study had a 5.5% participation rate. Most respondents were older, female, and less likely to live in socioeconomically deprived areas. Accordingly, the average age of study participants was 62 years, 56% were females, and their average SRI was 60.

After accounting for all confounders, the authors noted a non-linear relationship between sleep regularity and the mortality risk among 88,975 study participants followed for an average of 7.1 years in time-to-event models.

Mortality rates were highest for people with the most irregular sleep pattern and declined almost linearly as sleep regularity attained average levels, after which this reduction began to plateau. 

Many previous studies have shown that mutations in circadian clock genes, e.g., CLOCK, influence many physiological processes, including endothelial function and glucose homeostasis. Stress to the circadian system, thus, could manifest as CVDs.

Similarly, circadian clocks are critical for cell division events. So, the slightest alterations in clock function could precipitate aberrant cell proliferation or DNA damage, materializing as cancer. Irregular sleep timing is challenging for the circadian system to put up with and typically manifests as adverse health outcomes.

Furthermore, the study results demonstrated that the SRI encompassed information about mortality risk beyond what is suggested by the standard deviation metrics of sleep onset and duration.

Hazard rates across SRI levels varied throughout the follow-up period for cancer and all-cause mortality but not for CVD mortality.

Conclusions

The study data suggested a relationship between sleep irregularity and higher mortality risk, where sleep longevity, fragmentation, quality, and duration were all important. Notably, the American Heart Association also included sleep duration as one of their Eight guidelines for CVD prevention in 2022. 

With increasing accessibility to sleep-tracking wearables, precise measurement of sleep regularity could potentially be of public and clinical use. However, the most important would be identifying the key determinants of irregular sleep that impact circadian rhythmicity and overall health. 

*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Written by

Neha Mathur

Neha is a digital marketing professional based in Gurugram, India. She has a Master’s degree from the University of Rajasthan with a specialization in Biotechnology in 2008. She has experience in pre-clinical research as part of her research project in The Department of Toxicology at the prestigious Central Drug Research Institute (CDRI), Lucknow, India. She also holds a certification in C++ programming.