Sleep Irregularity and Subclinical Markers of Cardiovascular Disease: The Multi-Ethnic Study of Atherosclerosis

Abstract

Background Sleep irregularity has been linked to incident cardiovascular disease. Less is known about associations of sleep regularity with atherosclerosis. We examined cross-sectional associations of actigraphy-assessed sleep duration and sleep timing regularity with subclinical atherosclerosis in the community-based MESA (Multi-Ethnic Study of Atherosclerosis). Methods and Results MESA Sleep Ancillary Study participants (N=2032; mean age, 68.6±9.2 years; 37.9% White) completed 7-day wrist actigraphy. Participants underwent assessments of coronary artery calcium, carotid plaque presence, carotid intima-media thickness, and the ankle-brachial index. Sleep regularity was quantified by the 7-day with-in person SD of sleep duration and sleep onset timing. Relative risk regression models were used to calculate prevalence ratios and 95% CIs. Models are adjusted for demographics, cardiovascular disease risk factors, and other objectively assessed sleep characteristics including obstructive sleep apnea, sleep duration, and sleep fragmentation. 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 ankle-brachial 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. Conclusions Sleep irregularity, particularly sleep duration irregularity, was associated with several measures of subclinical atherosclerosis. Sleep regularity may be a modifiable target for reducing atherosclerosis risk. Future investigation into cardiovascular risk reduction interventions targeting sleep irregularity may be warranted.

Keywords: cardiovascular disease; circadian rhythms; lifestyle; risk factors.

Figure 1. Flow chart of MESA Sleep participants in analytic sample.

Of 2261 eligible participants, 2147 had valid actigraphy and subclinical marker data. Participants were excluded who had <5 days of actigraphy wear (n=18) and extreme sleep duration regularity or sleep onset regularity (n=73). Final sample sizes varied by subclinical marker.

Figure 2. Sleep duration regularity and prevalent subclinical CVD in the MESA sleep study.

Adjusted for age, sex, race and ethnicity, site, education, yearly income, work schedule, smoking status, alcohol consumption, physical activity, body mass index, systolic blood pressure, diastolic blood pressure, antihypertensive medication use, statin medication use, low‐density lipoprotein cholesterol, high‐density lipoprotein cholesterol, and prevalent diabetes; regular sleep duration: ≤60 minutes; irregular sleep duration: >120 minutes. ABI indicates ankle‐brachial index; CAC, coronary artery calcium; cIMT, carotid intima‐media thickness; CVD, cardiovascular disease; and MESA, Multi‐Ethnic Study of Atherosclerosis.

Figure 3. Sleep timing regularity and prevalent subclinical CVD in the MESA Sleep Study.

Adjusted for age, sex, race and ethnicity, site, education, yearly income, work schedule, smoking status, alcohol consumption, physical activity, body mass index, systolic blood pressure, diastolic blood pressure, antihypertensive medication use, statin medication use, low‐density lipoprotein cholesterol, high‐density lipoprotein cholesterol, and prevalent diabetes; regular sleep timing: ≤30 minutes; irregular sleep timing: >90 minutes. ABI indicates ankle‐brachial index; CAC, coronary artery calcium; cIMT, carotid intima‐media thickness; CVD, cardiovascular disease; and MESA, Multi‐Ethnic Study of Atherosclerosis.