CME Author: Zeena Nackerdien
Study Authors: Fernando Domínguez, Valentin Fuster, et al.
Target Audience and Goal Statement:
Sleep specialists, pulmonologists, and cardiologists
The goal is to evaluate the association of actigraphy-measured sleep parameters with subclinical atherosclerosis in an asymptomatic middle-age population.
- Is there a link between actigraphy-measured sleep parameters and subclinical atherosclerosis?
- What are the interactions among sleep parameters, traditional cardiovascular risk factors, and lifestyle features?
Synopsis and Perspective:
How the body heals during sufficient sleep is a matter of record. About 50 to 70 million U.S. adults suffer from a sleep disorder or report insufficient sleep habitually, according to the American Heart Association (AHA). Based on a multinational study, oversleeping may elevate heart disease and death risks. In addition, U.S. adults who were short sleepers (<7 hours per 24-hour period) were more likely to report 10 chronic health conditions versus those who got enough sleep (≥7 hours per 24-hour period). Heart attack, coronary heart disease, stroke, and diabetes were among the adverse cardiometabolic risks of a short sleep duration.
Self-reported sleep questionnaires formed the basis of most studies reporting links between sleep quality/duration and the risk of coronary heart disease, stroke, and subclinical atherosclerosis. Many studies using actigraphy-based monitoring were small in size and included patients with sleep disorders, such as obstructive sleep apnea (OSA). Vascular imaging technologies have also advanced since poor sleep was first linked to greater carotid-intima thickness in men, and lower coronary calcification incidence in separate studies.
Taken together, evidence from the literature highlighted a gap in terms of the need to assess the link between actigraphy-measured sleep parameters and subclinical atherosclerosis using improved technologies.
State-of-the-art imaging methods were used to quantify noncoronary atherosclerosis and coronary calcification in participants in the Progression of Early Subclinical Atherosclerosis (PESA) study participants. They were employees of the Bank Santander headquarters in Madrid. Well over half (62.6% were men with a mean age 45.8 [n=3,974]) had a low prevalence of diabetes mellitus, high blood pressure, and no apparent heart disease.
Assessments of cardiovascular risk factors, metabolic syndrome, diet, psychosocial symptoms, inflammatory biomarkers, and self-reported sleeping patterns were also made during the study. Moreover, each person wore a sensor (Actigraph) to continuously assess sleep/wake activity for a period of 7 days, according to José Ordovás, PhD, of Tufts University in Boston, and colleagues.
They defined sleep fragmentation as the sum of the movement index and fragmentation index. Adjustments for the possible confounding effect of underdiagnosed OSA were also made in this analysis.
Participants were divided into four groups:
- Very short sleep duration (VSSD): <6 hours
- Short sleep duration (SSD): 6-7 hours
- Reference sleep duration: (RSD) 7-8 hours
- Long sleep duration (LSD): >8 hours
LSD was uncommon (4%) and 30.7% fell into the RSD group. Most participants had SSD or VSSD (combined, 65.3%). Notably, caffeine and alcohol intake were greater in participants with disrupted and short sleep.
The authors reported that while sensor measurements showed that 27.1% of participants were in the VSSD group, only 10.7% reported <6 hours sleep/day in the Sleep Habits Questionnaire.
Following adjustments for conventional risk factors, VSSD was independently associated with an increased atherosclerotic burden versus the reference group (odds ratio 1.27, 95% CI 1.06-1.52, P=0.008).
Participants within the highest quintile of sleep fragmentation presented a higher prevalence of multiple affected noncoronary territories (OR 1.34, 95% CI, 1.09-1.64, P=0.006).
The authors reported that coronary artery calcification (CAC) scores did not differ among the four groups and that inflammatory biomarkers were also not affected by sleep quality.
Ordovás and co-authors added caveats to their interpretations of the results. For instance, middle-age PESA participants with a generally low cardiovascular risk and a characteristic occupation and lifestyle might not be representative of the general population. Results from the LSD group (>8 h), which represented only 4% of the total cohort, may also not be as generalizable as in other groups.
Source Reference: Journal of the American College of Cardiology, 2019; 73:134-147; DOI: 10.1016/j.jacc.2018.10.060
Study Highlights: Explanation of Findings
Study strengths included a higher proportion of female participants than in other studies, and the well-characterized sleep and clinical data in this cohort. Objectively assessed sleep duration (SSD) and fragmented sleep patterns were independently associated with subclinical atherosclerosis in middle-age individuals after adjusting for other cardiovascular risk factors and OSA.
The VSSD group had a 27% greater likelihood of having atherosclerosis throughout the body compared with individuals who slept 7 to 8 hours. Likewise, poor sleep quality was associated with a 34% greater likelihood of having noncoronary atherosclerosis compared to good sleep quality.
Individuals with more fragmented sleep also had a higher burden of affected territories, as measured by 3D vascular ultrasound (VUS). Only a subgroup of men who slept 6 to 7 hours demonstrated a trend toward a higher risk for noncoronary atherosclerosis, possibly due to the fact that these participants presented with VSSD rather than SSD.
Consistent with prior studies, participants with SSD or VSSD had higher prevalence of classical cardiovascular risk factors. Participants with VSSD, SSD, and who exhibited more fragmented sleep (fourth and fifth quintiles) were also more overweight ( BMI >26); those with LSD and non-fragmented sleep presented with lower BMI values.
Ordovás and co-authors concluded that the findings support the potential role of healthy sleeping in protecting against subclinical atherosclerosis. The findings also suggested that a healthy sleep duration should be restricted to 7 to 8 hours. The authors also discussed their results within the context of other evidence from the literature.
The largest study to date analyzing the impact of sleep on subclinical atherosclerosis with objectively measured sleep parameters (n=1,844) used a different clinical endpoint — peripheral artery disease measured with ankle-brachial index. The 2016 study also included people with OSA. A 2015 study showed that greater CAC was associated with poorer sleep in 1,465 participants.
In an accompanying editorial, Daniel Gottlieb, MD, MPH, of VA Boston Healthcare System, and Deepak Bhatt, MD, MPH, of Harvard Medical School in Boston, stated that the study “extends the published reports on sleep duration and vascular disease to an early middle-aged cohort by using an objective measure of sleep duration and sensitive measures of atherosclerosis in multiple vascular territories.”
Commenting on whether the stronger association of actigraphy-derived sleep duration with plaque burden in women versus men seen by Ordovás and colleagues was meaningful, the editorialists said “This finding contrasts with the Coronary Artery Risk Development in Young Adults (CARDIA) study, in which actigraphy-derived sleep duration was inversely associated with carotid intima-media thickness in men, but not in women.”
“The most likely explanation is chance variation in the data,” they added. Past studies that included patients with established cardiovascular disease, hypertension, or diabetes, were limited, the editorialists pointed out. “Because these conditions and the medications used to treat them may affect sleep duration, causal interpretation of the data is often problematic,” they wrote.
Ordovás stated that many questions remain on this topic, such as a need to understand the mechanisms by which sleep contributes to the risk for subclinical atherosclerosis, independently of other risk factors. Confirmation of trial findings may also come from future intervention studies “to demonstrate that increasing the number of hours of sleep in poor sleepers bring down the risk of plaque development.”