News | Cardiovascular Clinical Studies | March 29, 2023

Multi-Ethnic Study of Atherosclerosis Sheds Light on Sleep Irregularity and Cardiovascular Disease

Irregular sleep patterns may play a role in the pathophysiologic development of cardiovascular disease, according to a research article published in the Journal of the American Heart Association, JAHA.

Irregular sleep patterns may play a role in the development of cardiovascular disease, according to a research article published in the Journal of the American Heart Association, JAHA. Photo credit: Getty Images

March 29, 2023 — Irregular sleep patterns may play a role in the pathophysiologic development of cardiovascular disease, according to a research article published in the Journal of the American Heart Association, JAHA.

In “Sleep Irregularity and Subclinical Markers of Cardiovascular Disease: The MultiEthnic Study of Atherosclerosis,” lead author Kelsie M. Full, PhD, MPH, Department of Medicine, Vanderbilt University Medical Center, and co-authors, wrote: Poor sleep, including poor quality, abnormal quantity, and fragmented sleep, is associated with cardiovascular risk factors, incident cardiovascular disease (CVD), and CVDrelated mortality.123456 Questions remain about which dimensions of sleep may drive the pathophysiologic development of CVD7 and be promising intervention targets for improving cardiovascular health."1 

The researchers examined crosssectional associations of actigraphyassessed sleep duration and sleep timing regularity with subclinical atherosclerosis in the communitybased MESA (MultiEthnic Study of Atherosclerosis). In this large, racially and ethnically diverse, communitybased cohort, researchers noted sleep duration irregularity (variation in sleep duration >120 minutes in a week) was associated with measures of subclinical atherosclerosis.

Sleep irregularity, particularly sleep duration irregularity, was associated with several measures of subclinical atherosclerosis, according to the researchers in sharing the findings. The authors assessed that sleep regularity may be a modifiable target for reducing atherosclerosis risk, and that future investigation into cardiovascular risk reduction interventions targeting sleep irregularity may be warranted. Encouraging regular sleep schedules may be an important part of clinical lifestyle recommendations for the prevention of cardiovascular disease.

The study is one of the first studies to provide evidence that irregular sleep duration and timing are associated with measures of subclinical atherosclerosis, according to the authors. The development of atherosclerosis is a long process, allowing time for intervention before plaques have formed and hardened and can cause severe stenosis or rupture. Encouraging maintenance of regular sleep schedules with consistent sleep durations may be an important part of lifestyle recommendations provided in clinical practice for the prevention of CVD.

In addition to Full, other researchers of the MESA Sleep Ancillary Study included Tianyi Huang, Neomi A. Shah, Matthew A. Allison, Erin D. Michos, Daniel A. Duprez, Susan Redline and Pamela L. Lutsey. The MESA Sleep Study was supported by National Institutes of Health grant HL56984, and Full was partially supported by National Institute of Health grant HL007779.

Methods and Results

Full et all detailed the methodology, writing: MESA Sleep Ancillary Study participants (N=2032; mean age, 68.6±9.2 years; 37.9% White) completed 7day wrist actigraphy. Participants underwent assessments of coronary artery calcium, carotid plaque presence, carotid intimamedia thickness, and the anklebrachial index. Sleep regularity was quantified by the 7day within person SD of sleep duration and sleep onset timing. Models were adjusted for demographics, cardiovascular disease risk factors, and other objectively assessed sleep characteristics including obstructive sleep apnea, sleep duration, and sleep fragmentation.

Summarizing the results, the authors found that after adjustment, compared with participants with more regular sleep durations (SD ≤60 minutes), participants with greater sleep duration irregularity (SD >120 minutes) were more likely to have high coronary artery calcium burden (>300; prevalence ratio, 1.33 [95% CI, 1.03–1.71]) and abnormal anklebrachial index (<0.9; prevalence ratio, 1.75 [95% CI, 1.03–2.95]). Compared with participants with more regular sleep timing (SD ≤30 minutes), participants with irregular sleep timing (SD >90 minutes) were more likely to have high coronary artery calcium burden (prevalence ratio, 1.39 [95% CI, 1.07–1.82]). Associations persisted after adjustment for cardiovascular disease risk factors and average sleep duration, obstructive sleep apnea, and sleep fragmentation.

Insights into Sleep Quality Implications

To explore mechanisms through which poor sleep may lead to CVD development, researchers reported they examined associations of various dimensions of sleep with noninvasive measures of atherosclerosis, which showed to be strongly associated with incident CVD.89101112 They added that there is a consistent line of crosssectional131415 and prospective1416 evidence to suggest adults with abnormal sleep characteristics are more likely to have significant subclinical atherosclerosis.

An emerging area of interest is whether sleep irregularity, estimated by variation in sleep durations and sleep timing across nights,117 is associated with CVD risk. Irregular sleep patterns and nighttonight variations in sleep timing may be indicators of circadian misalignment, or desynchronization of sleep–wake timing, which has been linked to cardiometabolic risk factors.181920 Initial studies on regularity of sleep patterns and CVD risk were focused on nurses and shift workers with pronounced variations in sleep schedules.212223 However, recent evidence has connected irregular sleep patterns to cardiovascular health in the general population. 2024252627

It remains unknown whether irregularity in sleep durations and timing plays a role in the development of atherosclerosis.27 The MESA (MultiEthnic Study of Atherosclerosis) includes objectively measured sleep data and numerous noninvasive measures of subclinical atherosclerosis, assessed in a diverse sample of older adults. In this study, the researchers specified that they tested the hypotheses that more irregular sleep durations and sleep timing were associated with subclinical atherosclerosis (including prevalent coronary artery calcium [CAC], prevalent carotid plaque, abnormal carotid intimamedia thickness [cIMT], and abnormal anklebrachial index [ABI]), after adjustment for cardiovascular risk factors and objectively measured obstructive sleep apnea (OSA), sleep duration, and sleep fragmentation. We were also interested in understanding whether associations were consistent across several subclinical markers.

Sleep Irregularity and CVD Risk Factors

In further analysis of findings, the authors wrote that the in this racially and ethnically diverse sample of older adults, participants with greater sleep duration irregularity were more likely to have a high burden of atherosclerosis as measured across several subclinical markers, specifically higher CAC and an abnormally low ABI. These associations persisted after adjusting for BMI and prevalent CVD risk factors. When the researchers examined sleep timing regularity, they observed an association between greater sleep timing irregularity and high CAC burden, but not with other measures of subclinical CVD. Importantly, the associations observed also persisted after adjustment for severe OSA, average sleep duration, and sleep fragmentation. These results suggest that sleep regularity may have a unique etiologic link to subclinical CVD. Additional insights from the research paper follow.

Sleep regularity may be a modifiable dimension of sleep that can be targeted to reduce CVD risk in aging adults.20 In fact, notes the report, maintaining a regular sleep schedule and decreasing variability in sleep is a key component of clinical sleep hygiene recommendations.46 The authors’ findings suggest that these recommendations — developed to improve sleep — also may be useful as a cardiovascular health promotion strategy. Clinical trials, testing the role of interventions aimed at improving sleep duration regularity as a lifestyle component for CVD risk reduction intervention are warranted.

Almost all major cardiovascular functions, including heart rate, blood pressure, vascular tone, and endothelial functions, are regulated by circadian clock genes.4748 

Disruption or misalignment of circadian rhythms can interrupt these important cardiovascular functions, resulting in the promotion of chronic inflammation, alterations in glucose metabolism, heightened sympathetic nervous system activation, and increases in arterial pressures, all predisposing to the risk of atherosclerosis progression.22 

These hypotheses are further supported by previous studies that have reported increased inflammatory markers, including interleukin6 and highsensitivity Creactive protein, in individuals with irregular sleep patterns4950 and increased white blood cell count in individuals with excessive sleep disruption.51 It is also plausible, offered the authors, that irregular sleep patterns may be a marker of irregular health behaviors in general, including irregular timing of meals or exercise, which may contribute to circadian disruption.2052

For more information: www.ahajournals/org


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