Short sleep’s association with cardiovascular risk may be mediated in part by elevated homocysteine levels, suggests a new analysis of data from the 2005-2006 National Health and Nutrition Examination Survey (NHANES).
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The study, published in the Journal of Clinical Sleep Medicine, found that elevated homocysteine levels were only associated with short sleep duration for some populations, including women, non-Hispanic white individuals, and participants with obesity.
A total of 4,480 NHANES participants had serum homocysteine levels on record and were included in the study; of these, those with self-reported sleep duration of 7 hours had the lowest serum homocysteine levels. Those with the shortest sleep duration – 5 hours or less per night – had the highest homocysteine levels.
When participants were broken into subgroups by such factors as sex, ethnicity/race, and body mass index, the association between extremely short sleep and elevated homocysteine levels was retained for three groups: women, non-Hispanic white participants, and those with BMIs of 30 kg/m2 and higher.
“[T]his finding might suggest increased vulnerability to cardiovascular risk or other atherothrombotic events in these groups in the context of short sleep,” wrote Tien-Yu Chen, MD, of Tri-Service General Hospital, Taipei, Taiwan, and coauthors in the abstract accompanying the study.
In the NHANES questionnaire, participants were asked how much sleep they usually got, in whole hours. Answers were grouped into 5 hours or less, 6 hours, 7 hours, or 8 hours, and 9 hours or more. Serum homocysteine was measured once for each study participant.
Using multivariate linear regression, homocysteine was considered the dependent, continuous variable, and the association between sleep duration and homocysteine was assessed using three models that accounted for confounders. The first and simplest model accounted for age, sex, and race/ethnicity. The second model added BMI, several cardiometabolic laboratory values, and vitamin B6, vitamin B12, and folate levels. The third model included all previous factors and added patient characteristics and comorbidities, such as sleep disorders, mental health service use, cardiovascular disease and cancer diagnoses, and alcohol and tobacco use.
In their analysis, Dr. Chen and colleagues dichotomized homocysteine levels to above or below the 75th percentile of the log homocysteine level, which fell at 9.74 nmol/L.
After adjustment, women, but not men, had an association between short sleep and increased odds of elevated homocysteine (odds ratio, 2.691; P = .010). This association “persisted in fully adjusted models,” wrote Dr. Chen and coauthors.
For individuals with obesity (BMI of 30 or greater), the association between elevated homocysteine and extremely short sleep (5 hours or less) persisted in fully adjusted models (beta = .062; P = .039 for model 3).
When looking at ethnicity, the association between extremely short sleep and elevated homocysteine was only seen among non-Hispanic white participants; again, this association was seen after full adjustment for confounders (beta = .068; P = .032). Small sample sizes limited some of the racial/ethnic analyses, noted the investigators.
Homocysteine, explained Dr. Chen and coauthors, is associated with a variety atherogenic changes, and elevated levels are associated with increased risk for cardiovascular disease and mortality. Short sleep is also associated with increased cardiovascular risk, as is long sleep in some studies.
However, though preliminary work had shown that short sleep had an association with homocysteine levels, the relationship is unclear since that study had many potential cardiovascular confounders, said Dr. Chen and coauthors.
The association between extremely short sleep duration and cardiovascular events has been well established, with increased inflammation playing a potential role, although the reasons for the association are still being elucidated. “Because increased homocysteine levels are considered an independent risk factor for cardiovascular diseases, further studies are needed to better understand the relationships among short sleep duration, homocysteine levels, and cardiovascular events,” the investigators wrote.
Whether menstrual variations in serum homocysteine and sleep may have played a part in the significant association seen in women, but not men, was not ascertainable from the NHANES data, which introduces possible confounding, the authors noted.
Similarly, there may be ethnic differences in baseline serum homocysteine levels, said Dr. Chen and his colleagues.
The study’s strengths include the large sample size and ability to control for many demographic and individual characteristics, including comorbidities. However, sleep duration was based on self-report and did not include information about napping or sleep-wake times. Also, sleep quality was not assessed beyond a question about snoring or snorting and a question about a prior diagnosis of a sleep disorder.
“Further longitudinal investigations concerning the effect of sleep deprivation on homocysteine alteration might help provide a better understanding of the pathogenesis of cardiometabolic risk,” concluded Dr. Chen and colleagues.
One of the coauthors reported financial relationships with multiple pharmaceutical companies and UpToDate. The authors reported no external sources of funding.
SOURCE: Chen T-Y et al. J Clin Sleep Med. 2019;15(1):139-48.