Increased risk of subclinical multi-territory non-coronary atherosclerosis with short and fragmented sleep in middle-aged subjects
Association of Sleep Duration and Quality With Subclinical Atherosclerosis
Introduction and methods
Although sleep quality and duration have been associated with the risk of CAD, stroke , and subclinical atherosclerosis , most studies rely on self-reported questionnaires of sleep assessment [2-3]. Previous studies that objectively investigated sleep have shown an association between shorter sleep duration and greater carotid intima-media thickness in men , and between longer sleep and lower coronary calcification incidence . However, studies using newer and more reliable imaging techniques for measuring atherosclerosis are missing. Moreover, the association between multi-territory atherosclerosis and sleep has not been assessed yet. This study therefore evaluated the association between actigraphy-measured sleep parameters and subclinical atherosclerosis in an middle-aged population.
The observational prospective Progression of Early Subclinical Atherosclerosis–Centro Nacional de Investigaciones Cardiovasculares (PESA-CNIC)-Santander cohort study recruited male and female employees of Santander Bank in Madrid aged 40-54 years without known CVD or obstructive sleep apnea resulting in 3974 eligible participants. Quantity of sleep was assessed by triaxial accelerometry using Act Trainers accelerometers for seven days. Sleep quality was assessed by the total sleep fragmentation index defined as the sum of the movement index and fragmentation index. Participants also completed the Sleep Habits Questionnaire from the Sleep Heart Health Study . Non-coronary atherosclerosis and coronary calcification were quantified using 3-dimensional vascular ultrasound and cardiac computer tomography (CT).
Sleep duration was defined as: very short (VSSD [<6 h]), short (SSD [6-7 h]), normal/reference (RSD [7-8 h]), and long (LSD [>8 h]). Participants were divided into quintiles according to sleep fragmentation and those with less fragmented sleep (first quintile) were considered as reference. Non-coronary atherosclerosis was defined as plaque presence in the carotid and femoral arteries using the Manheim criteria for 2-dimensional VUS , and the number of affected territories (1 to 4) was also recorded. Atherosclerosis was classified as mild, moderate, or severe based on tertiles of cumulative plaque volume. The Agatston coronary calcium score was measured by CT scan, and data was categorized by 0, <1, 1-100, 101-400 and >400.
- After multivariable adjustments, VSSD was independently associated with a higher non-coronary atherosclerotic plaque burden, compared with RSD (OR: 1.27, 95%CI: 1.06-1.52, P=0.008).
- Participants with VSSD showed a trend towards more extensive atherosclerosis with more affected vascular territories (OR: 1.21, 95%CI: 1.02-1.45, P=0.03), but the differences between sleep duration groups were not significant (P-overall=0.18).
- Using the Sleep Habits Questionnaire, plaque burden and the number of affected vascular territories were not significantly different between the different sleep groups in the overall association tests (P=0.33 and P=0.20, respectively), highlighting the importance of objective sleep data.
- Participants in the fifth quintile of sleep fragmentation showed significantly more affected non-coronary territories (OR for the 5th quintile of sleep fragmentation group: 1.34, 95%CI: 1.09-1.64, P=0.006), compared to the reference group.
- In the different sleep groups, no differences regarding coronary artery calcification score were observed.
In this observational study, objectively measured short sleeping times and fragmented sleep were associated with an increased risk of subclinical atherosclerosis in middle-aged subjects. These data highlight the importance of healthy sleep habits for the prevention of CVD.
In their editorial comment , Gottlieb and Bhatt discuss several limitations of the study conducted by Dominguez et al., including the limited power with only 18% of participants with a coronary artery calcium score >0, the lack of a test for significance of reported sex differences and the bias in comparison of subjective questionnaire-derived sleep duration with actigraphy-derived sleep duration. The authors also emphasize the lack of sufficient measures of blood pressure and glucose metabolism, which are associated with sleep deprivation and sleep fragmentation, and unknown causes of short sleep duration and sleep fragmentation since insomnia and apnea are associated with increased risk of vascular disease and sleep fragmentation, respectively. Finally, given the cross-sectional study design, it remains unknown whether the association between sleep duration and quality, and atherosclerosis is affected by confounders, such as smoking, sedentary lifestyle and poor diet, indicating the need of more research. The authors conclude: ‘Modifying sleep behaviors will be challenging even for short-term studies of intermediate outcomes such as blood pressure and glucose metabolism. The potentially enormous impact of sleep deprivation and disruption on population health, reinforced by the present study, is ample justification for such trials, which are needed to place sleep with confidence alongside diet and exercise as a key pillar of a healthy lifestyle.’