Poor Sleep Quality Linked to CVD Events and Mortality

Reduced sleep quality, defined as low delta entropy as measured by electroencephalogram (EEG), is associated with a greater long-term risk of cardiovascular disease events and mortality, according to new observational data.

The study offers the tantalizing prospect of having objective sleep metrics that could be used for assessing sleep quality and making positive changes for patients.

“Our findings suggested that disrupted delta wave activity during non-rapid eye movement sleep may have an impact on cardiovascular health,” lead author Sizhi Ai, MD, PhD (The Affiliated Brain Hospital of Guangzhou Medical University, Guangdong, China), told TCTMD in an email. “This extends our understanding of the memory function of delta wave activity during sleep.”

Additionally, the findings should encourage clinicians to address sleep quality with their patients, especially for those at risk for or with diagnosed CVD, he suggested. “Healthcare providers should consider incorporating sleep evaluation and interventions as part of CVD prevention and management strategies,” Ai said. “Promoting healthy sleep habits and addressing sleep disorders may help reduce the burden of CVD and improve long-term outcomes for patients.”

Promoting healthy sleep habits and addressing sleep disorders may help reduce the burden of CVD and improve long-term outcomes for patients. Sizhi Ai

Sleep was incorporated into the American Heart Association’s Life’s Essential 8 tool in 2022 to stress its important role in cardiovascular health and is an emerging target for preventive cardiology. Specific disorders like sleep apnea have been linked to worse outcomes in patients with CVD, and sleep duration was recently shown to be associated with hypertension.

Measuring quality of sleep has proven trickier, with traditional sleep studies using overnight polysomnography (PSG) using scoring metrics that some argue are subjective. EEG signals, however, measure deep sleep by analyzing delta wave activity during NREM sleep that has been shown to affect metabolism by regulating leptin and appetite.

The concept of using these kinds of measurements is not new, Michael A. Grandner, PhD (University of Arizona College of Medicine, Tucson), who was not involved in the study, told TCTMD, but they were previously only seen in a controlled laboratory setting. Now, studies like this are suggesting that “slow wave activity seems to be an important marker for sleep being able to do its job,” he said. “What this study helps show is that it actually does matter and that it's something worth paying attention to.”

Delta Entropy a Successful Predictor

For the study, published in the April 30, 2024, issue of the Journal of the American College of Cardiology, Ai and colleagues included groups from both the Sleep Heart Health Study (SHHS; n = 4,058) and the Osteoporotic Fractures in Men Study (MrOS; n = 2,193) who all underwent in-home sleep evaluations for 1 night. Participants were on average younger in the SHHS compared with MrOS (62.4 vs 72.6 years) and less likely to smoke and drink or have histories of diabetes and hypertension.

Delta entropy is an objective measurement of sleep quality describing the irregularity of delta power signal on EEG in a single night. Someone with low entropy during sleep, for example, may show either no periodic delta wave activity or no delta waves over a certain length of time.

Over a mean follow-up period of 11.0 years in SHHS and 15.5 years in MrOS, those with the lowest delta wave entropy during sleep (≤ 5th percentile: ≤ 5.8 in SHHS and ≤ 5.8 in MrOS) had the highest rates of coronary heart disease, CVD events (fatal and nonfatal), and CVD mortality.

Multivariate analysis confirmed an independent association of low delta wave entropy with higher risks of coronary heart disease, CVD events, and CVD mortality compared with those with delta wave entropies in the fifth to 95th percentiles.

Risk With Low vs Mid Delta Wave Entropy

Additionally, lower delta entropy was associated with increased risks of stroke in the SHHS population (HR 2.34; 95% CI 1.43-3.85) and all-cause mortality in MrOS (HR 1.58; 95% CI 1.25-1.99). Notably, there were no decreases in any of these risks seen among those with high (≥ 95th percentile) delta wave entropy.

All results were maintained in sensitivity analyses. Sex-based analyses showed no differences in outcomes between men and women, but age-based analyses showed a trend toward stronger associations between low delta entropy and worse CV outcomes among older individuals.

Finally, machine-learning models indicated that delta entropy could more robustly predict coronary heart disease, CVD events, and CVD mortality than conventional PSG-obtained sleep parameters like total sleep time, wake after sleep onset, and overnight oxygen desaturation.

Mechanisms Unclear

Ai told TCTMD he expected to find a link between low delta entropy and outcomes but was surprised by its scale. “While previous studies had hinted at a potential link, the magnitude of the effect observed in our study exceeded our expectations,” he said. “This finding underscores the importance of prioritizing deep sleep for overall cardiovascular health and longevity.”

That said, questions remain regarding the mechanism at play, Ai said. While most studies to date have “focused on the memory function of delta wave activity during sleep, some evidence suggested that delta wave activity during sleep may be involved in metabolic regulation and autonomic nervous function in humans,” he explained.

It's about getting enough sleep of good quality, that's at the right time, that is relatively stable, and regular. Michael A. Grandner

Grandner pointed out that the study populations were limited to older adults, who inherently have less-robust delta wave activity than younger people. He also said a remaining unanswered question relates to whether the activity itself is the issue or “just a marker of something that's happening under the hood and if you change the superficial wave forms does that matter if you're not changing what's happening under the hood?”

This is the first study to link lower delta entropy with worse CVD and mortality outcomes, Tianyi Huang, ScD (Brigham and Women’s Hospital, Boston, MA), writes in an accompanying editorial. As such, it supports the notion that predicting CVD outcomes with delta entropy “is superior to other PSG-based sleep variables.”

But, like Grandner, Huang stresses the importance of understanding whether delta entropy is playing an active role or serving as a marker, especially given changes to sleep patterns with age. The changes researchers saw in this study could simply “be an indicator of accelerated aging that represents an overall deteriorated health profile, leading to higher CVD risk and mortality,” he notes.

He agrees, however, that further work needs to be done to explore mechanisms of action as well as to clarify the level of delta wave entropy below which problems arise, noting that these thresholds might vary by demographic factors. Huang also says he would like to see similar studies with measurements taken for more than a single night.

As a “modifiable risk factor,” sleep is a vital component to improving cardiovascular outcomes, Ai concluded. He urged patients to prioritize healthy sleep habits and address sleep disturbances to “reduce their risk of developing CVD and improve overall health outcomes. Moreover, raising awareness among both healthcare professionals and the general public about the importance of deep sleep for cardiovascular health is crucial for promoting preventive measures and optimizing patient care.”

Grandner agreed. “Sleep health is multidimensional,” he said. “This really highlights the point that healthy sleep isn't just about getting enough sleep. It's about getting enough sleep of good quality, that's at the right time, that is relatively stable, and regular. So it's: duration, quality, timing, regularity, and continuity. All of these are different dimensions in sleep health and they're all important.”