Association between sleep duration on workdays and blood pressure in non-overweight/obese population in NHANES: a public database research

This study aimed to explore the association between sleep duration on workdays and blood pressure (BP) including systolic blood pressure (SBP) and diastolic blood pressure (DBP) in non-overweight/obese population. A cross-sectional study composed of 2887 individuals from NHANES was conducted. Subjective sleep duration on workdays were evaluated by the questionnaire. Multiple linear regression analyses were done to explore the relationship between sleep duration and BP. Compared with sleep duration of 6–8 h, both sleep duration < 6 h and ≥ 8 h on workdays were significantly associated with increased SBP (β, 3.58 [95% CI 1.60, 5.56] and 1.70 [95% CI 0.76, 2.64], respectively). However, the significant association was not founded in DBP. The stratified analyses showed that in females, sleep duration (< 6 h or ≥ 8 h) on workdays were associated with SBP (β = 5.99 and 2.41, respectively, both P < 0.0005). In addition, the SBP levels were much higher among participants aged (≥ 60) with sleep duration < 6 h. The effect size was 7.23 (P = 0.0217). In the subgroup classified by race, a significantly positive association between sleep duration (< 6 h, ≥ 8 h) and SBP can be seen in the White population (β = 6.64 (P = 0.0007) and 1.91 (P = 0.0215), respectively). In non-overweight/obese population, both short sleep duration (< 6 h) and long sleep duration (≥ 8 h) on workdays were correlated with higher level of SBP.

disturbances in autonomic and hormone balances, and also lead to increased obesity and metabolic disorders, and circadian rhythm disorders 8 . Meta-analysis showed that short sleep time was associated with an increased risk of hypertension 9 . Growing evidence has showed that BP is influenced by sleep duration [10][11][12][13][14][15][16] , which is based on different age, genders, and races to explore the association.
However, few studies have been performed to investigate the relationship between sleep duration and BP in people with different body mass indexes (BMI). Previous research has identified that people who are overweight and obesity were both strong influence factors on BP 17,18 . So far, few studies have been done to explore the possible relationship between sleep duration and elements of BP in people who are not overweight or obese. Hence, this study aimed to determine the association between sleep duration on workdays and BP in non-overweight/ obese population.

Study population. The National Health and Nutrition Examination Survey (NHANES) is the only national
survey that offers a cross-sectional view of nutrition and health in the United States population. It collects information about demographics, health and health behaviors. Data researchers and users can use the survey data of the NHANES on the Internet. Details statistics of NHANES can be found on www. cdc. gov/ nchs/ nhanes/. All methods in our research were performed in accordance with the Declaration of Helsinki.
Definition. Sleep duration on workdays was evaluated by the questionnaire with the following questions: "Number of hours usually sleep on weekdays or workdays". Sleep duration was divided into three groups, which were < 6 h, 6-8 h, ≥ 8 h respectively, of which 6-8 h was used as the reference group.
The trained and certified examiners used the standardized protocols and calibrated equipment to get the blood pressure readings. Three consecutive BP readings were acquired via ausculatory means. If a BP measurement was not successfully completed, a fourth measurement was implemented. The average of all available measures was used.  consumption was defined as the response to the question:"In the past 12 months, how often did you drink any type of alcoholic beverage?", the responses was classified into three groups: drinking, no drinking, not recorded.
Smoking was defined as the response to the question:"Do you now smoke cigarettes?", the responses was classified into three groups: smoking, not smoking, not recorded. Diabetes was defined as the responses to the question:"Have you ever been told by a doctor or health professional that you have diabetes or sugar diabetes?", the responses was classified into four group: yes, no, borderline, not recorded. Hypertension was defined as the response to the question: "Have you ever been told by a doctor or other health professional that you had hypertension, also called high blood pressure?". The response was classified into three group: yes, no, and not recorded. The snort or stop breathing was defined as the response to the question: "In the past 12 months, how often did you snort, gasp, or stop breathing while you were asleep?". The answers were classified into three group: yes, no, and not recorded. The method of obtaining other covariates, include gender, age, albumin, creatinine, hemoglobin, total cholesterol (TC), aspertate aminotransferase (AST), high-density lipoprotein (HDL), body mass index (BMI), can be found at www. cdc. gov/ nchs/ nhanes/. Among this covariates, age, albumin, creatinine, hemoglobin, TC, AST, HDL, BMI as continuous variables. Gender, alcohol consumption, diabetes, smoking, race, hypertension, snort or stop breathing as categorical variables.
Statistical analysis. All estimates were calculated accounting for NHANES sample weights. A weighted multiple linear regression model was used to assess the correlation between sleep duration on workdays and BP including systolic blood pressure(SBP) and diastolic blood pressure(DBP). The covariates mentioned above were adjusted as potential effect modifiers. The mean ± S.D and percentage were used to represent continuous variables and categorical variables, respectively. To calculate the differences between males and females, weighted linear regression models were used for continuous variables or weighted chi-square tests for categorical variables. The values of missing continuous covariates were indicated by dummy variables, including albumin, hemoglobin, creatinine and TC, AST, HDL and the missing ratios were 7.8%, 6.3%, 7.8%, 7.7%, 8.0%, 7.7% respectively. The missing categorical variables were included in the analysis as a single group. The statistical software packages R (http:// www.R-proje ct. org) and EmpowerStats (http:// www. empow ersta ts. com) were used for the data analyses. When the P value was < 0.05, it was considered statistically significant.

Ethics approval and consent to participate. The ethics review board of the National Center for Health
Statistics approved all NHANES protocols. Informed consent was obtained from all subjects and/or their legal guardian(s). Association between sleep duration on workdays and blood pressure. The results of multiple linear regression analysis used to explore the relationship between sleep duration and SBP were shown in

Subgroup analyses of factors influencing the association between sleep duration and SBP.
In the subgroup analysis stratified by gender, age and race, the association between sleep duration and SBP was explored in Table 4. The positive effect was evident in most subgroups. All the potential confounding factors except the subgroup variable were adjusted. It showed that in females, sleep duration (< 6 h, ≥ 8 h) on workdays was associated with SBP (β = 5.99, 2.41, respectively, all P < 0.0005). Moreover, the association was much more obvious among participants aged (≥ 60) with sleep duration < 6 h. The effect size was 7.23 (P = 0.0217). In the subgroup classified by race, a significantly positive association was found in White whose sleep duration < 6 h or ≥ 8 h (β = 6.64 (P = 0.0007), and 1.91 (P = 0.0215), respectively). In others race, sleep duration (≥ 8 h) was associated with SBP (β = 2.06, P = 0.0097).

Discussion
The sleep duration of the general population has been affected by modern life, which also has been an important public health issue that has attracted the attention of researchers. Previous studies proved that sleep duration might also contribute to the increase in blood pressure [10][11][12]15 . We found sleep duration in non-overweight/obese people positively correlated with SBP. In females, sleep duration < 6 h or ≥ 8 h on workdays were associated with SBP. In middle and old age, insufficient sleep duration (< 6 h) can lead to higher levels of SBP. In comparison with other ethnic groups, sleep duration < 6 h or ≥ 8 h was also associated with higher SBP among the White population. A lot of cross-sectional and longitudinal epidemiological studies were used to explore the connection among sleep duration and hypertension. In the 2007-2009 National Healthy Interview Surveys (NHIS)(n = 71,455), compared with the 8-h group, adults who slept for less than 6 h or 6 h were more likely to develop hypertension (odds ratio (OR): 1.49 (1.34-1.64) and 1.15 (1.08-1.23), respectively) 11 . Several meta-analysis researches  19,20 . However, few studies supported that short sleep duration had no impact on hypertension 21 .
As to long sleep duration, the relationship was not very clear but increasingly of interest. One sleep heart health study with 5910 participants discovered that compared to the 7-8 h of sleep duration, the adjusted OR of 8-9 h and ≥ 9 h of sleep duration to hypertension were 1.19 (1.04-1.37) and 1.30 (1.04-1.62), respectively 22 . The data of 71,455 participants from 2007 to 2009 NHIS also demonstrated that sleep ≥ 10 h was associated with a 20% higher risk of hypertension than sleep of 8 hours 11 . But, two meta-analyses showed that no significant relationship was found between long sleep duration and the occurrence of hypertension 9,20 .
The biological mechanisms underlying the association of sleep duration with blood pressure isn't clear. Sleep duration, especially short sleep, may affect BP, by increasing sympathetic nerve excitement, reducing parasympathetic nerve activity 8 . These changes in autonomic nerve tension will lead to faster heart rate, increased heart rate orthostatic reactivity, and decreased high-frequency heart rate variability 23 . Short sleep duration means sleeping too late or getting up too early. It also means being exposed to light much longer. Light transmits non-image forming function light information to the brain through retinal ganglion cells, such as sleep-wake and circadian rhythm regulation 24 . So short sleep duration will disrupt 24 h sleep-wake cycle, which is an integrated process involving rhythmic changes in endocrine, autonomy, movement, sensation and brain activity. This change will inevitably have a certain impact on blood pressure 25 . Research have shown that when a person's sleep-wake cycle is inconsistent with the external environment, the average arterial pressure will increase by 3% 26 . The inflammatory process may also play a vital role in the pathogenesis and pathophysiology of the relationship between short or long sleep duration and BP 27 . Inflammatory factors such as c-reactive protein and interleukin-6 is increased with prolonged sleep duration, which can cause drowsiness and fatigue, and may also increase the risk of hypertension in people with long sleep duration 27 . Another study showed that short sleep duration was associated with elevated C-reactive protein level 28 . Long sleep duration was also associated with an increased risk of obesity, metabolic syndrome, and type 2 diabetes 7 .The underlying mechanisms were that long sleep duration could disrupt circadian clocks and decrease insulin sensitivity, leading to unhealthy eating habits, decreased calorie consumption, and elevated systemic inflammation 29 . Additionally, long sleep duration has been identified to be related to sleep fragments, which could activate sympathetic nervous system and lead to increased BP 30,31 .
Our research can bring some inspiration to clinical work. For example, for non-overweight/obese female patients with borderline hypertension or poor blood pressure control, we can improve SBP by adjusting sleep time. We need to pay more attention to the impact of sleep duration on SBP among non-overweight/obese people, especially in regards to females and the elderly.
Like most studies, our study also has some shortcomings. Firstly, sleep duration was only based on subjective evaluation. However, subjective sleep time and objective sleep time were only moderately correlated, and there might be a certain bias 32 . Secondly, another issue to consider was the lack of a consistent standard for long and short sleep duration. At last, we did not consider other potential confounding factors, such as sleep quality, the use of sleeping pills, socio-economic status and educational status. Further studies with more variables and larger populations should be done for validating our results.

Conclusions
In non-overweight/obese population, especially in females, both short sleep duration(< 6 h) and long sleep duration(≥ 8 h) on workdays were correlated with higher levels of SBP. In old age populations, insufficient sleep duration (< 6 h) was associated with higher levels of SBP. Compared with other ethnic groups, sleep duration (< 6 h or ≥ 8 h) was also associated with higher SBP in Whites.