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Journal of the American Society of Hypertension 12(12) (2018) 867–879

Research Article
A dose-response association of night sleep duration
with hypertension in a Chinese rural population: the
Henan Rural Cohort Study
Haiqing Zhang, MSa,1, Yuqian Li, PhDb,1, Zhenxing Mao, PhDa, Min Liu, PhDc,
Wenqian Huo, PhDd, Ruihua Liu, MSa, Xiaotian Liu, PhDa, Runqi Tu, PhDa,
Kaili Yang, MSa, Xinling Qian, MSa, Jingjing Jiang, MSa, Xia Zhang, MSa,
Zhongyan Tian, MSa, Ronghai Bie, PhDa,*, and Chongjian Wang, PhDa,*
a
Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, PR China;
b
Department of Clinical Pharmacology, School of Pharmaceutical Science, Zhengzhou University, Zhengzhou, Henan, PR China;
c
Department of Hypertension, Henan Provincial People’s Hospital, Zhengzhou, Henan, PR China; and
d
Department of Occupational and Environmental Health, College of Public Health, Zhengzhou University, Zhengzhou, Henan, PR China
Manuscript received April 27, 2018 and accepted October 13, 2018

Abstract

The purpose of the study was to determine if there was a relationship between night sleep duration and hypertension, and to
evaluate as to whether blood lipid levels played a role in this relationship. A total of 37,317 participants aged 18–79 years
were included in this study. Night sleep duration was classified as <5, 5-, 6-, 7-, 8-, 9-, and 10 hours. Logistic regression
and restricted cubic spline analysis was carried out to evaluate the association of sleep duration with hypertension. Compared
with reference sleep duration (7 hours), in males, the multivariate odds ratios (ORs) (95% confidence interval [95% CI]) of
the groups with longest sleep duration (10 hours) and shortest sleep duration (<5 hours) for hypertension was 1.52 (1.25–
1.84) and 1.07 (0.80–1.44), respectively. Similarly, the longest sleep duration was associated with diagnosed hypertension
(1.21, 1.00–1.45) in females. The OR for an indirect effect of sleep duration through low-density lipoprotein cholesterol

Grant Support: This research was supported by the National number: ChiCTR-OOC-15006699). http://www.chictr.org.cn/
Natural Science Foundation of China (Grant NO: 81573243, showproj.aspx?proj¼11375
81602925), Henan Natural Science Foundation of China (Grant What is already known on this topic?
NO: 182300410293), National Key Research and Development Previous studies have explored the effect between night sleep
Program Precision Medicine Initiative of China (Grant NO: duration and hypertension, but the studies covered populations and re-
2016YFC0900803), Science and Technology Foundation for Inno- gions are limited, especially in limited resource settings. The results
vation Talent of Henan Province (Grant NO: 164100510021), Sci- from these studies are inconsistent, as some studies did not find a rela-
ence and Technology Innovation Talents Support Plan of Henan tionship between sleep duration and hypertension.
Province Colleges and Universities (Grant NO: 14HASTIT035), What does this study add?
High-level Personnel Special Support Project of Zhengzhou Uni- The present study shows that longer night sleep duration correlates
versity (Grant NO: ZDGD13001). The funders had no role in the with a higher likelihood of undiagnosed and diagnosed hypertension
study design, data collection and analysis, decision to publish, or in the rural population. In addition, low-density lipoprotein cholesterol
preparation of the article. appeared to mediate the effect of sleep duration on hypertension in
Conflict of interest: None. males.
Supplemental Material can be found at www.ashjournal. *Corresponding authors: Dr Chongjian Wang, PhD and Dr
com. Ronghai Bie, PhD, Department of Epidemiology and Biostatistics,
Ethics approval: Ethical approval for this study was obtained College of Public Health, Zhengzhou University, 100 Kexue
from the ‘‘Zhengzhou University Life Science Ethics Commit- Avenue, Zhengzhou, 450001 Henan, PR China. Tel: (86) 371-
tee’’, and written informed consent was obtained from all partic- 67781452; Fax: (86) 371-67781919.
ipants. Ethic approval code: [2015] MEC (S128) E-mails: bierh2012@126.com, tjwcj2005@126.com
1
Clinical Trial Registration: The Henan Rural Cohort Study has Haiqing Zhang and Yuqian Li contributed equally to this work.
been registered at Chinese Clinical Trial Registry (Registration

1933-1711/$ - see front matter Ó 2018 American Heart Association. All rights reserved.
https://doi.org/10.1016/j.jash.2018.10.005

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868 H. Zhang et al. / Journal of the American Society of Hypertension 12(12) (2018) 867–879

(LDL-C) on hypertension was 1.085 (95% CI 1.038–1.137). Overall, a 3.5% possibility of hypertension being associated with
sleep duration was attributable to LDL-C. In summary, a relationship between sleep duration and hypertension was observed
in this rural population. LDL-C appeared to partially mediate the effect of sleep duration on hypertension in males. J Am Soc
Hypertens 2018;12(12):867–879. Ó 2018 American Heart Association. All rights reserved.
Keywords: Dose-response association; hypertension; mediation effect; night sleep duration.

Introduction duration and hypertension, and how much of the direct ef-
fect they might explain.
Hypertension has become a primary public health Change in sleep duration may contribute to adverse
concern globally, with growing prevalence in adults and physiological changes and increase morbidity.20 Studies
in children. Patients with hypertension are at greater risk on relationship of night sleep duration and hypertension
for myocardial infarction, coronary heart failure, and are scarce,15,21,22 especially among undeveloped rural pop-
stroke,1 and this may primarily be caused by the altered ulations in China. Thus, this study was conducted to
function of the vascular endothelium.2 High salt intake, examine whether night sleep duration was associated with
obesity, and cigarette smoking have been proven to be the undiagnosed and diagnosed hypertension in a Chinese rural
main risk factors for hypertension, but there still remain un- population aged 18–79 years. In addition, we hypothesized
identified factors.3 One third of our life is spent sleeping, that this relationship might be mediated by serum lipids,
which plays a vital role in our health. Increasingly, studies which are known risk factors for hypertension.
are evaluating the association between sleep quality and
adverse health outcomes, including type II diabetes melli- Materials and Methods
tus,4–6 coronary heart disease,7 and overall mortality.8
There are several studies that have examined the associ- Participants
ation of hypertension and sleep duration. One study showed The participants are from the Henan Rural Cohort Study
that sleep duration of 8 hour or longer per night was asso- which was conducted in Suiping, Yuzhou, Yima, Tongxu,
ciated with hypertension in a Saudi Arabian population.9 and Xinxiang counties of Henan province and registered
Other studies have found no relationship between the dura- in the Chinese Clinical Trial Registry (registration number:
tion of sleep and high blood pressure (BP) in the ChiCTR-OOC-15006699).23,24 A total of 39,259 people
elderly.10,11 A cross-sectional study involving a Korean were recruited. Exclusion criteria for this study were
population reported the association of short sleep duration missing data on hypertension or night sleep duration
and hypertension in nonobese premenopausal women.12 A (n ¼ 71), being a night shift worker (n ¼ 1,544), and pa-
prospective study conducted in an affluent area of China tients with tumors (n ¼ 327). We obtained a final sample
showed that shorter sleep duration was significantly associ- of 37,317 participants aged 18–79 years.
ated with hypertension among younger participants, but the The protocol of this study was approved by the Ethics Com-
sample size of the study was relatively small.13 A Chinese mittee of the Zhengzhou University Life Science Ethics Com-
study found that extreme sleep duration (>7 hours/night or mittee. Informed consent was obtained from all participants.
8–9 hours/night) increased the prevalence of hypertension
in middle-aged subjects.14 A study conducted on an elderly
Covariate Variables
rural population in China did not find significant associa-
tion of sleep duration and hypertension.15 Data were collected by trained investigators in face-to-face
In addition, it is reported that statin therapy can signifi- interviews. A structured questionnaire on demographic char-
cantly benefit secondary prevention of patients with hyper- acteristics (age, gender, and educational levels), lifestyle be-
tension,16,17 suggesting that factors of serum lipids might haviors (physical activities, intake of high fat diet,
be potential risk factors for prevalent hypertension. Gang- vegetables and fruit intake, high salt diet, smoking status,
wisch et al.18 have showed that short sleep duration is asso- and alcohol consumption), personal history of hypertension,
ciated with a greater risk of hypercholesterolemia in and family history of hypertension. Eating more than 500 g
adolescents. Another study reported that sleep duration is of vegetables and fruits each day were defined as high vegeta-
associated with serum lipid and lipoprotein levels among bles and fruit intake, eating 75 g or more of meat from live
Japanese adults.19 Thus, serum lipid profiles might be po- stock and poultry on average every day was defined as a
tential moderators in the relationship between sleep dura- high fat diet, and a high salt diet was defined by self-
tion and hypertension. As no prior study has reported on reported taste preferences. Marital status was classified as
whether serum lipid profiles mediate the association be- married/cohabitation and single/divorced/separated/wid-
tween sleep duration and hypertension, we asked what owed. Those who had smoked for at least half of one year
mediator variables might exist in the association of sleep and no less than 1 cigarette per day were defined as smokers

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and all other participants were classified as nonsmokers. Par- during the past 2 weeks.3 Participants with hypertension
ticipants consuming alcohol 12 or more times every year were who did not report having hypertension were defined as un-
considered as drinkers and respondents were grouped as non- diagnosed hypertension, whereas those with reported hy-
drinkers (including abstinence) and current drinker. Physical pertension including those on antihypertensive were
activity levels were divided into three categories: light, mod- defined as diagnosed hypertension.
erate, and vigorous according to the criteria derived from the
International Physical Activity Questionnaire.25
Anthropometric variables were measured in light clothing
and without shoes. Weight and height were measured twice Statistical Analysis
for each person to the nearest 0.5 kg and 0.1 cm, according
to a standard protocol. Weight (kg) was divided by the Data on baseline of the respondents are presented as
square of height (m2) to calculate body mass index (BMI). means (SD) for continuous variables and percentages for cat-
Venous blood samples were drawn from participants who egorical variables. The t-test and chi-square test were used to
had fasted overnight. Serum was separated through centri- compare continuous and categorical variables, respectively,
fugation with 2000 g rcf at room temperature for 10 minute among different categories of sleep duration. Analysis of
and stored at 20 C. Serum lipids included total choles- variance with covariates was performed to show age-
terol, triglyceride, low-density lipoprotein cholesterol adjusted means of BP values. Age-adjusted prevalence of
(LDL-C) and high-density lipoprotein cholesterol were hypertension was also presented. Multiple linear regression
measured by direct or enzymatic methods. models with SBP and DBP as continuous outcome variables
were created after adjusting for age, marital status, educa-
Assessment of Sleep Duration tional levels, average monthly income, smoking status,
drinking status, physical activity, intake of high fat diet,
Information about night sleep duration was collected using high vegetables and fruit intake, high salt diet, family history
the Pittsburgh Sleep Quality Index.26 Night sleep duration was of hypertension, BMI, napping duration, and LDL-C. To
taken from the following question of the Pittsburgh Sleep identify the relationship between night sleep duration and
Quality Index: ‘‘How many hours of actual sleep duration the prevalence of hypertension, logistic regression models
did you get at night during the past month?’’ People sleeping were generated after adjusting for the same factors as in
for 7–8 hours were viewed as enjoying optimal sleep duration the linear regression model. We examined potential gender
according to a prospective study that showed duration of 7–8 interactions by adding a multiplicative interaction term
hours was relatively normal.27 In addition, according to into the models between sleep duration (hour) and gender.
another two previous studies,6,28 sleep duration was grouped A nonlinear trend was also tested by including a quadratic
as <5 hour (shortest), 5–6, 6–7, 7–8 hours (reference), 8–9, term of sleep duration in the present study. A dose-
9–10, and 10 hours (longest). Furthermore, respondents response association of sleep duration and hypertension
were asked the question: ‘‘Did you have the habit of taking was analyzed by fitting restricted cubic spline logistic regres-
a nap after lunch over the past year?’’ Those who answered sion29 setting 3 knots placed at the 25th, 50th, and 75th per-
yes were further asked how long they sleep every day. centiles of sleep duration, with 7 hour as the reference group.
Finally, the proportion of the association between night sleep
Measurement of Blood Pressure duration and hypertension was calculated by mediation anal-
ysis based on factors of blood lipids (including total choles-
Participants were asked to avoid caffeine, exercise, and terol, triglyceride, LDL-C, and high-density lipoprotein
smoking for at least 30 minute before measurement of BP. cholesterol). Mediation analysis previously introduced else-
Respondents were to rest quietly in a chair for at least 5 mi- where30,31 was performed running the PROCESS for SPSS
nutes before measuring BP and remained in rested state for that the single independent variable must be either contin-
at least 30 seconds intervals between measurements. Three uous or dichotomous. Only continuous mediator was al-
BP recordings were obtained using an electronic sphygmo- lowed in this program. In short, a significant total effect
manometer (HEM-770AFuzzy, Omron, Japan) from the guarantees the further evaluation of mediation. A statistical
bare right arm supported at the level of heart. The mean of difference found in indirect effect but not in direct effect
the three measurements was used for the analyses. was called complete mediation. Partial mediation exists
when indirect and direct effects are significant. The propor-
Definition of Hypertension tion explained by the mediator was computed with the for-
mula (indirect effect/total effect).32 All statistical analyses
Hypertension was defined as systolic blood pressure were performed using SAS V.9.1 (SAS Institute) and SPSS
(SBP)  140 mm Hg and/or diastolic blood pressure software, version 21.0 (SPSS Inc., Chicago). Two-tailed P
(DBP) 90 mm Hg, or self-reported hypertension diag- values < .05 were considered statistically significant in
nosed by physician and use of antihypertensive medicines this study.

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870 H. Zhang et al. / Journal of the American Society of Hypertension 12(12) (2018) 867–879

Table 1
Demographic characteristics of participants in varied blood pressure situation status by gender
Variable Male
Normotensive All Hypertension P Undiagnosed Hypertension P Diagnosed Hypertension
N 9652 4822 2000 2822
Age (y), mean  SD 55.71  12.42 60.13  10.86 <.001 58.46  11.91 <.001 61.31  9.88
Married/cohabitation, n (%) 8691 (90.04) 4290 (88.97) .045 1788 (89.40) .384 2502 (88.66)
Educational levels, n (%) <.001 .020
Primary school or below 3256 (33.75) 1781 (36.93) 734 (36.70) 1047 (37.10)
Junior high school 4537 (47.03) 2137 (44.32) 877 (43.85) 1260 (44.65)
Senior high school or above 1855 (19.23) 904 (18.75) 389 (19.45) 515 (18.25)
Average income per month, n <.001 .016
(%)
<500 RMB 3496 (36.22) 1900 (39.40) 741 (37.05) 1159 (41.07)
500- RMB 3062 (31.72) 1544 (32.02) 681 (34.05) 863 (30.58)
1000 RMB 3094 (32.06) 1378 (28.58) 578 (28.90) 800 (28.35)
Smoker, n (%) 6869 (71.17) 3253 (67.46) <.001 1344 (67.20) <.001 1909 (67.65)
Drinker, n (%) 4961 (51.40) 2664 (55.25) <.001 1146 (57.30) <.001 1518 (53.79)
High vegetables and fruits 4459 (46.20) 1783 (36.98) <.001 700 (35.02) <.001 1083 (38.38)
intake, n (%)
High salt diet, n (%) 1831 (18.99) 1006 (20.89) .007 448 (22.47) <.001 558 (19.78)
High fat diet, n (%) 2541 (26.33) 1061 (22.00) <.001 506 (25.30) .342 555 (19.67)
Physical activity, n (%) <.001 <.001
Light 3110 (32.22) 2045 (42.41) 780 (39.00) 1265 (44.83)
Moderate 2770 (28.70) 1207 (25.03) 487 (24.35) 720 (25.51)
Vigorous 3772 (39.08) 1570 (32.56) 733 (36.65) 837 (29.66)
Family history of hypertension, n 1238 (12.83) 1270 (26.34) <.001 276 (13.80) .239 994 (35.22)
(%)
BMI(kg/m2), mean  SD 23.89  3.27 25.73  3.53 <.001 25.44  3.57 <.001 25.93  3.49
Night sleep duration(h), 7.70  1.25 7.85  1.32 <.001 7.89  1.32 <.001 7.82  1.32
mean  SD
Napping duration (min), 63.10  50.10 63.00  49.30 .910 59.15  48.73 .001 65.74  49.53
mean  SD
LDL-C (mmol/L), mean  SD 2.77  0.77 2.91  0.85 <.001 2.96  0.86 <.001 2.87  0.85
LDL-C, low-density lipoprotein cholesterol; BMI, body mass index; SD, standard deviation.

Results level, were unmarried, had a higher BMI, less physical ac-
tivity, and higher serum LDL-C.
Demographic Characteristics
Although we found no significant interactions (P > .05) Prevalence of Hypertension
for the effect of night sleep duration on hypertension by
gender, we show the analyses stratified by gender because Age-adjusted SBP, DBP, and prevalence of hypertension
previous studies reported a gender-specific association of by gender within each category of sleep duration (Table S1)
night sleep duration and hypertension.14,33 Table 1 presents is presented in Figure 1. The mean and 95% CI of age-
the demographic characteristics of the respondents. Among adjusted SBP and DBP values of the study subjects were
the 37,317 participants (14,474 males and 22,843 females), 130.27 (128.78–131.75) and 80.86 (79.89–81.83) mm Hg
the mean age was 56.00  12.06 and 12,333 demonstrated in males who had 10 hour night sleep duration, respec-
hypertension. The age-standardized prevalence of hyperten- tively. Compared with those who had 7 hour sleep duration,
sion was 21.24% for males and 15.95% for females. The the subjects who had 10 hour sleep duration had signifi-
age-standardized prevalence of undiagnosed and diagnosed cantly higher SBP (127.40, 126.19–128.60) and DBP
hypertension was 11.22% and 10.03% in males and 6.71% (77.45, 76.72–78.17). The age-adjusted prevalence of hy-
and 9.25% in females, respectively. Compared with those pertension were 33.77% in group of <5 hour and 40.27%
without hypertension, participants with hypertension had in category of 10 hour in males, respectively. Similar re-
longer night sleep duration, older age, lower education sults for females can be also observed (Table S2).

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Table 1 (continued)
Male Female
P Normotensive All Hypertension P Undiagnosed Hypertension P Diagnosed Hypertension P
15,332 7511 2722 4789
<.001 52.41  12.12 61.04  9.29 <.001 59.54  10.14 <.001 61.89  8.67 <.001
.033 14,005 (91.34) 6421 (85.49) <.001 2385 (87.62) <.001 4036 (84.28) <.001
.004 <.001 <.001 <.001
7216 (47.07) 4901 (65.26) 1659 (60.97) 3242 (67.70)
5955 (38.84) 2053 (27.34) 837 (30.76) 1216 (25.39)
2160 (14.09) 556 (7.40) 225 (8.27) 331 (6.91)
<.001 <.001 <.001 <.001

5128 (33.45) 3054 (40.66) 1032 (37.91) 2022 (42.22)


5185 (33.82) 2514 (33.47) 967 (35.53) 1547 (32.30)
5019 (32.74) 1943 (25.87) 723 (26.56) 1220 (25.48)
<.001 4343 (28.33) 1880 (25.03) <.001 644 (23.66) <.001 1236 (25.81) <.001
.025 508 (3.31) 145 (1.93) <.001 49 (1.80) <.001 96 (2.00) <.001
<.001 6748 (44.01) 2659 (35.40) <.001 953 (35.01) <.001 1706 (35.62) <.001
.351 2537 (16.56) 1222 (16.29) .603 450 (16.56) .993 772 (16.14) .491

<.001 2610 (17.02) 846 (11.26) <.001 346 (12.71) <.001 500 (10.44) <.001
<.001 <.001 <.001 <.001
4226 (27.56) 2598 (34.59) 847 (31.12) 1751 (36.56)
7126 (46.48) 2994 (39.86) 1093 (40.15) 1901 (39.70)
3980 (25.96) 1919 (25.55) 782 (28.73) 1137 (23.74)
<.001 2595 (16.93) 2095 (27.89) <.001 425 (15.61) .091 1670 (34.87) <.001

<.001 24.45  3.40 26.19  3.73 <.001 25.73  3.74 <.001 26.45  3.70 <.001
<.001 7.74  1.25 7.84  1.33 <.001 7.87  1.26 <.001 7.82  1.37 <.001

.014 53.46  50.60 54.67  50.03 .087 51.54  49.07 .061 56.45  50.49 <.001

<.001 2.82  0.80 3.07  0.87 <.001 3.13  0.87 <.001 3.03  0.87 <.001

Association Between Night Sleep Duration and (0.99, 0.79–1.24), and diagnosed hypertension (1.21,
Hypertension 1.00–1.45) were observed in those with a 10 hour sleep
duration among females. A U-shaped dose-response asso-
To further examine the association between sleep dura- ciation between sleep duration and hypertension was
tion and hypertension, analyses were performed using found in males (P for quadratic term <.001). The dose-
continuous SBP and DBP as outcomes by fitting multilin- response relationships of sleep duration with hypertension
ear regression models. Positive relationships between long were further demonstrated through the restricted cubic
sleep duration and either SBP or DBP were found in males spline curves in Figure 2, which suggests that the preva-
(Table 2). ORs and 95% CIs for hypertension associated lence of diagnosed hypertension may be higher with
with varied sleep duration are presented in Table 3, which longer sleep duration in males (P for non-linear
suggests that longest sleep duration (10 hours) is related trend ¼ .040), but not in females (P for non-linear
to higher odds of hypertension than in the reference group trend ¼ .307).
(7-hours) in the fully adjusted model in males (OR ¼ 1.52,
95% CI: 1.25–1.84). In the case of longer sleep duration, Mediation Effects
there was a 68% (95% CI: 32%–114%) and 32% (95% CI:
3%–69%) elevated prevalence for undiagnosed and diag- According to the theory of mediation analysis, mediation
nosed hypertension, respectively, in males. Compared effects were measured in males using as factors serum lipid
with reference (7-), ORs and 95% CIs of all hypertension values. The result is presented in Figure 3. The estimated
(OR 1.11, 95% CI: 0.95–1.30), undiagnosed hypertension OR for hypertension with longer sleep duration (total

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872 H. Zhang et al. / Journal of the American Society of Hypertension 12(12) (2018) 867–879

Figure 1. Age-adjusted SBP (A, B), DBP (C, D) and prevalence of hypertension (E, F) according to varied night sleep duration by
gender. SBP, systolic blood pressure; DBP, diastolic blood pressure.

effect, 1.089; 95% CI, 1.040, 1.139) was comprised of the adults was 20.94% for males and 18.85% for females.34
direct effect of sleep duration (OR, 1.085; 95% CI, 1.038, We observed an association of sleep duration with age-
1.137) and the indirect effect mediated by serum LDL-C adjusted BP values using analysis of variance, a method
(OR, 1.003; 95% CI, 1.001, 1.005) in males subjects. of controlling for confounders, which was used in previous
Approximately 3.5% (95% CI, 2.6%–3.8%) of the studies.35,36 The results of this study demonstrated that
increased odds of hypertension related to sleep duration longer habitual night sleep duration is strongly associated
was attributable to higher LDL-C (Table S3). We found with elevated BP in a Chinese rural population, which is
that no other factors of blood lipids mediated significantly consistent with a previous report.37 This effect was not sig-
the association between sleep duration and hypertension nificant in the group with short sleep duration.
(data not show). A U-shaped trend showing a correlation between sleep
duration and hypertension is not statistically significant
Discussion in the present study, in contrast to what was found in other
studies37,38; this might be because of the relatively fewer
This study demonstrated that there is a dose-response asso- participants in our study who had less than 5 hour of sleep
ciation between night sleep duration and hypertension in adult duration. The finding of an elevated prevalence of hyper-
males and that serum LDL-C is a mediating effect in the rela- tension with longer sleep duration is similar to that of
tionship between sleep duration and hypertension in these sub- earlier studies,39 which reported that longer sleep duration
jects. The present study is the first to focus on the sleep- (at least 9 hour) was associated with an increased preva-
hypertension association as well as mediation effects on sleep lence of hypertension. Furthermore, our findings revealed
duration and hypertension in a Chinese rural population. the importance of a comprehensive examination of poten-
Located in the central area of China, Henan province tial confounding mediators and factors when examining
with a population of 94 million in 2015 is an important the association between sleep duration and hypertension.
agricultural province and its rural population accounts for The effect sizes were attenuated after adjustment for a se-
53% of the total population. One previous study showed ries of factors including general characteristics and behav-
that the age-standardized prevalence of hypertension in ioral lifestyles. Several studies33,40–43 noted that short

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Table 2
Association of night sleep duration with systolic and diastolic blood pressures
BP Night Sleep Duration, (h)
<5 10
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5- 6- 7- 8- 9-
SBP
Male
All hypertension

H. Zhang et al. / Journal of the American Society of Hypertension 12(12) (2018) 867–879
Model 1 0.29 (2.67, 2.09) 0.77 (2.26, 0.71) 0.74 (1.64, 0.15) 0 2.07 (1.28, 2.85) 2.81 (1.77, 3.85) 5.92 (4.32, 7.52)
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Model 2 1.29 (3.62, 1.05) 0.72 (2.13, 0.69) 0.66 (1.51, 0.19) 0 1.66 (0.91, 2.41) 1.89 (0.89, 2.90) 4.77 (3.20, 6.34)
Undiagnosed hypertension
Model 1 0.22 (2.14, 2.58) 0.36 (1.83, 1.12) 0.54 (1.43, 0.36) 0 1.82 (1.04, 2.61) 2.54 (1.49, 3.59) 4.48 (2.82, 6.15)
Model 2 1.18 (3.36, 1.01) 0.78 (2.14, 0.57) 0.44 (1.26, 0.38) 0 1.49 (0.77, 2.21) 1.75 (0.79, 2.71) 4.34 (2.85, 5.82)
Diagnosed hypertension
Model 1 1.81 (4.00, 0.38) 0.65 (1.97, 0.67) 0.37 (1.16, 0.43) 0 1.33 (0.62, 2.04) 1.42 (0.47, 2.37) 3.75 (2.26, 5.24)
Model 2 0.38 (2.53, 1.76) 0.62 (1.96, 0.72) 0.31 (1.12, 0.50) 0 1.36 (0.64, 2.07) 1.74 (0.78, 2.70) 3.28 (1.75, 4.81)
Female
All hypertension
Model 1 0.92 (1.26, 3.09) 0.79 (2.18, 0.60) 0.03 (0.87, 0.80) 0 0.41 (0.27, 1.10) 3.10 (2.19, 4.01) 6.02 (4.59, 7.44)
Model 2 0.12 (1.96, 2.20) 0.69 (1.98, 0.60) 0.48 (1.26, 0.30) 0 0.00 (0.64, 0.64) 2.05 (1.19, 2.91) 2.64 (1.24, 4.04)
Undiagnosed hypertension
Model 1 1.81 (0.35, 3.97) 0.56 (1.95, 0.83) 0.21 (0.63, 1.05) 0 0.36 (0.33, 1.05) 2.63 (1.70, 3.55) 6.29 (4.85, 7.73)
Model 2 2.36 (4.22, 0.50) 2.23 (3.42, 1.04) 0.86 (1.57, 0.14) 0 0.34 (0.24, 0.93) 1.29 (0.50, 2.07) 1.91 (0.67, 3.14)
Diagnosed hypertension
Model 1 2.35 (4.17, 0.52) 1.78 (2.92, 0.65) 0.93 (1.61, 0.25) 0 0.23 (0.33, 0.79) 1.03 (0.27, 1.78) 0.52 (0.72, 1.77)
Model 2 1.44 (3.28, 0.40) 2.00 (3.18, 0.81) 0.65 (1.37, 0.06) 0 0.33 (0.26, 0.92) 1.01 (0.22, 1.80) 2.41 (1.17, 3.66)
DBP
Male
All hypertension
Model 1 0.11 (1.64, 1.41) 0.69 (1.64, 0.26) 0.56 (1.13, 0.02) 0 0.46 (0.04, 0.96) 0.20 (0.47, 0.87) 1.86 (0.83, 2.88)
Model 2 0.95 (2.52, 0.61) 0.87 (1.82, 0.08) 0.70 (1.27, 0.13) 0 0.34 (0.16, 0.84) 0.01 (0.67, 0.68) 1.79 (0.74, 2.85)
Undiagnosed hypertension
Model 1 0.11 (1.62, 1.40) 0.53 (1.48, 0.41) 0.40 (0.98, 0.17) 0 0.31 (0.19, 0.81) 0.32 (0.36, 0.99) 1.23 (0.16, 2.30)
Model 2 0.22 (1.61, 1.17) 0.87 (1.73, 0.01) 0.49 (1.01, 0.03) 0 0.57 (0.11, 1.03) 0.77 (0.15, 1.38) 2.60 (1.66, 3.55)
Diagnosed hypertension
Model 1 0.84 (2.28, 0.60) 0.86 (1.73, 0.01) 0.55 (1.07, 0.03) 0 0.52 (0.06, 0.99) 0.69 (0.06, 1.31) 2.60 (1.62, 3.58)
Model 2 0.07 (1.43, 1.30) 0.78 (1.64, 0.07) 0.40 (0.91, 0.12) 0 0.45 (0.00, 0.91) 0.82 (0.21, 1.44) 1.85 (0.87, 2.82)
Female
All hypertension
Model 1 0.26 (1.45, 0.93) 1.01 (1.77, 0.24) 0.19 (0.65, 0.27) 0 0.04 (0.34, 0.41) 0.73 (0.23, 1.23) 1.18 (0.40, 1.96)
Model 2 1.04 (2.24, 0.15) 0.89 (1.63, 0.15) 0.47 (0.92, 0.02) 0 0.09 (0.45, 0.28) 0.31 (0.19, 0.80) 0.22 (0.59, 1.02)
Undiagnosed hypertension
Model 1 0.23 (0.96, 1.42) 0.87 (1.64, 0.10) 0.05 (0.51, 0.41) 0 0.06 (0.32, 0.44) 0.66 (0.15, 1.17) 1.36 (0.57, 2.16)
Model 2 0.78 (1.87, 0.30) 1.20 (1.90, 0.50) 0.48 (0.90, 0.06) 0 0.14 (0.20, 0.48) 0.54 (0.08, 1.00) 0.58 (0.14, 1.30)

873
(continued)
874 H. Zhang et al. / Journal of the American Society of Hypertension 12(12) (2018) 867–879

sleep duration could enhance the incidence of hyperten-

0.16 (0.60, 0.92)

Model 2: adjusted for age, high salt diet, high vegetables and fruits intake, high fatty diet, physical activity, marital status, smoking status, drinking status, educational levels,
0.84 (0.11, 1.57)
sion, in contrast to our findings. Possible reasons are dif-
ferences in the study populations including living region,
belonging to a different race, having different cultural
backgrounds and lifestyles,44 age differences13 and even
10

gender differences (eg, some included only women).


Several studies explored the association between sleep
0.41 (0.05, 0.87)
0.46 (0.01, 0.92)

duration and hypertension stratified by gender, but statis-


tical differences were not found in males with longer sleep
SBP, systolic blood pressure; DBP, diastolic blood pressure, LDL-C, low-density lipoprotein cholesterol; BMI, body mass index; BP, blood pressure.

durations, again inconsistent with our results.13,14 For the


gender-specific relationship the underlying mechanisms
are not clear, and there are several possible explanations.
9-

One potential reason is that gender discrepancies in health


may be explained by the differences in educational
0.10 (0.24, 0.44)
0.14 (0.21, 0.48)

level.45 In addition, it is possible that the psychosocial


factors and stress differ in males and females. Finally,
males may suffer greater fatigue because work conditions
often differ between genders. Accordingly, males may
have greater susceptibility to hypertension.
8-

Mediation effects were analyzed in relation to sleep


duration and hypertension using as factors serum lipid
7-

0
0

levels. We found that serum LDL-C acted as a mediator


0.57 (0.99, 0.15)

in the effect of sleep duration and hypertension. LDL-C


0.36 (0.78, 0.06)

mediates a part of the association of sleep duration and hy-


pertension, which indicates that this association may be ex-
plained by mechanism of sleep.
average monthly income, family history of hypertension, napping duration, BMI and LDL-C.

Possible mechanisms that might account for the relation-


ship between sleep duration and hypertension have been re-
ported in a variety of previous studies, although they are
6-

controversial.42 Several hypotheses have been put forward.


0.88 (1.57, 0.19)
1.06 (1.76, 0.36)

Primarily, it might be because of changes in normal BP


change as determined by circadian rhythms. The fall in
BP during sleep might be weakened because of insufficient
sleep.46 Moreover, short sleep duration might reduce the
secretion of melatonin leading to an elevated BP.47 There
has been little literature discussing the potential mecha-
5-

nisms behind the association of long sleep duration with


Night Sleep Duration, (h)

hypertension. Long-term long sleep duration might be


1.20 (2.31, 0.08)

linked to poor sleep quality,48 which might be associated


0.33 (1.41, 0.75)

with gender differences. Thus, future research is needed


to elicit the mechanism by which long sleep duration pro-
motes hypertension.
The strengths of this study include elaborate epidemio-
logic profiles, thorough analysis of the association between
<5

sleep duration and undiagnosed and diagnosed hyperten-


sion. The assessment of the mediating effect of serum lipids
Diagnosed hypertension

on the relationship between sleep duration and hyperten-


sion is particularly novel. In addition, few studies have
Model 1: unadjusted.

studied rural populations, who form a large proportion of


Table 2 (continued )

Chinese population and have peculiar lifestyle including


Model 1
Model 2

sleep habits.
Several limitations should not be overlooked in this
study. First, this was a cross-sectional study, and there is
the possibility of reversed causality. Second, some nonhy-
BP

pertensive subjects may inevitably be misclassified as

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Table 3
The relationship between night sleep duration and prevalent hypertension
Hypertension Night Sleep Duration, (h) Py for Trend

H. Zhang et al. / Journal of the American Society of Hypertension 12(12) (2018) 867–879
<5 5- 6- 7- 8- 9- 10
For personal use only. No other uses without permission. Copyright ©2019. Elsevier Inc. All rights reserved.

Male
All hypertension
Patients*/n 85/246 215/691 716/2489 1585/4980 1377/3865 588/1624 256/579
Model 1 1.13 (0.86–1.48) 0.97 (0.81–1.15) 0.86 (0.78–0.96) 1.00 1.19 (1.08–1.30) 1.21 (1.08–1.37) 1.70 (1.43–2.02) <.001
Model 2 1.07 (0.80–1.44) 0.94 (0.78–1.13) 0.87 (0.78–0.98) 1.00 1.13 (1.03–1.25) 1.11 (0.97–1.26) 1.52 (1.25–1.84) <.001
Undiagnosed hypertension
Patients*/n 28/189 87/563 294/2067 660/4055 573/3061 239/1275 119/442
Model 1 0.89 (0.59–1.35) 0.94 (0.74–1.20) 0.85 (0.73–0.99) 1.00 1.18 (1.05–1.34) 1.19 (1.01–1.40) 1.89 (1.51–2.37) <.001
Model 2 0.84 (0.55–1.27) 0.94 (0.73–1.20) 0.87 (0.75–1.02) 1.00 1.15 (1.01–1.30) 1.13 (0.96–1.34) 1.68 (1.32–2.14) <.001
Diagnosed hypertension
Patients*/n 57/218 128/604 422/2195 925/4320 804/3292 349/1385 137/460
Model 1 1.30 (0.95–1.77) 0.99 (0.80–1.21) 0.87 (0.77–0.99) 1.00 1.19 (1.06–1.32) 1.24 (1.07–1.42) 1.56 (1.26–1.92) <.001
Model 2 1.34 (0.94–1.90) 0.92 (0.72–1.16) 0.88 (0.76–1.02) 1.00 1.12 (0.99–1.27) 1.10 (0.94–1.30) 1.32 (1.03–1.69) .010
Female
All hypertension
Patients*/n 128/373 290/975 1140/3518 2353/7532 2186/6765 1020/2753 394/927
Model 1 1.15 (0.92–1.43) 0.93 (0.81–1.08) 1.06 (0.97–1.15) 1.00 1.05 (0.98–1.13) 1.29 (1.18–1.42) 1.63 (1.42–1.87) <.001
Model 2 0.87 (0.68–1.12) 0.82 (0.69–0.96) 0.97 (0.88–1.07) 1.00 1.02 (0.94–1.10) 1.11 (1.00–1.24) 1.11 (0.95–1.30) <.001
Undiagnosed hypertension
Patients*/n 34/279 100/785 392/2770 886/6065 811/5390 383/2116 116/649
Model 1 0.81 (0.56–1.17) 0.85 (0.68–1.07) 0.96 (0.85–1.10) 1.00 1.04 (0.93–1.15) 1.29 (1.13–1.47) 1.27 (1.03–1.57) <.001
Model 2 0.67 (0.46–0.98) 0.79 (0.63–1.00) 0.94 (0.82–1.07) 1.00 1.03 (0.93–1.15) 1.15 (1.00–1.32) 0.99 (0.79–1.24) <.001
Diagnosed hypertension
Patients*/n 94/339 190/875 748/3126 1467/6646 1375/5954 637/2370 278/811
Model 1 1.35 (1.06–1.73) 0.98 (0.83–1.16) 1.11 (1.00–1.23) 1.00 1.06 (0.98–1.15) 1.30 (1.17–1.45) 1.84 (1.58–2.15) <.001
Model 2 0.99 (0.75–1.31) 0.84 (0.69–1.02) 1.00 (0.89–1.13) 1.00 1.00 (0.91–1.10) 1.07 (0.94–1.21) 1.21 (1.00–1.45) .034
LDL-C, low-density lipoprotein cholesterol; BMI, body mass index.
Model 1: unadjusted.
Model 2: adjusted for age, high salt diet, high vegetables and fruits intake, high fatty diet, physical activity, marital status, smoking status, drinking status, educational levels,
average monthly income, family history of hypertension, napping duration, BMI, and LDL-C.
* The number of people with hypertension.
y
Quadratic trend test.

875
876 H. Zhang et al. / Journal of the American Society of Hypertension 12(12) (2018) 867–879

Figure 2. Odds ratios (ORs; solid lines) and 95% confidence intervals (CIs, dashed lines) of night sleep duration for hypertension (A, B),
undiagnosed (C, D) and diagnosed hypertension (E, F) from restricted cubic splines. Adjusted for age, physical activity, high salt diet,
high vegetables and fruit intake, high fat diet, marital status, smoking status, alcohol consumption status, educational level, average
monthly income, family history of hypertension, napping duration, BMI, and LDL-C. LDL-C, low-density lipoprotein cholesterol;
BMI, body mass index.

hypertensive patients, which would lead to information In conclusion, this study found that longer sleep duration
bias. Third, the data of sleep duration were self-reported, might contribute to the increased prevalence of hyperten-
which might introduce recall bias. However, previous sion and higher BP in a Chinese rural population. A
research has found good correlation between self-reported dose-response association between night sleep duration
sleep duration and sleep duration measured by polysom- and hypertension was found in this population. Moreover,
nography or actigraphy.49 Therefore, future prospective LDL-C slightly mediates the association of sleep duration
and polycentric studies are needed to identify this and hypertension among males, and further studies are
association. necessary to clarify this mechanism. Longer sleep duration

Figure 3. Mediation analysis to examine


the association between night sleep dura-
tion and hypertension through LDL-C in
males. Adjusted for age, high salt diet,
high vegetables and fruit intake, high fat
diet, marital status, physical activity,
smoking status, alcohol consumption sta-
tus, educational level, average monthly
income, family history of hypertension,
napping duration, and BMI. LDL-C,
low-density lipoprotein cholesterol;
BMI, body mass index.

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may not be beneficial for health. It is suggested that people CKB study in Zhejiang rural area, China. Acta Diabetol
should develop a good sleeping habits to prevent longer or 2017;54:81–90.
shorter night sleep duration. 7. Yang LL, Yang HD, He MA, Pan A, Li XL, Min XW,
et al. Longer sleep duration and midday napping are
associated with a higher risk of CHD incidence in
Acknowledgments middle-aged and older Chinese: the dongfeng-tongji
cohort study. Sleep 2016;39:645–52.
The authors especially are grateful to the participants, all 8. Xiao Q, Keadle SK, Hollenbeck AR, Matthews CE.
research staff of the present study and administrators for Sleep duration and total and cause-specific mortality
their support during the study. The authors would like to in a large US cohort: interrelationships with physical
acknowledge Tanko Abdulai and Prof. Ling Wang for activity, sedentary behavior, and body mass index.
English-language editing. Am J Epidemiol 2014;180:997–1006.
Authors’ contributions: During the research, C.W. and 9. Brocato J, Wu F, Chen Y, Shamy M, Alghamdi MA,
R.B. designed the study. H.Z., Y.L., Z.M., M.L.,W.H., Khoder MI, et al. Association between sleeping hours
R.L., X.L., R.T., K.Y., X.Q., J.J., X.Z. and Z.T. directed and cardiometabolic risk factors for metabolic syn-
the collection of the data. R.L. and Y.L. analyzed the drome in a Saudi Arabian population. BMJ Open
data. H.Z. and Y.L. wrote the article. R.L., X.L. and X.Q. 2015;5:e008590.
provided writing assistance. All authors read and approve 10. Robillard R, Lanfranchi PA, Prince F, Filipini D,
this version of the article. Carrier J. Sleep deprivation increases blood pressure
in healthy normotensive elderly and attenuates the
blood pressure response to orthostatic challenge. Sleep
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46. Kario K, Schwartz JE, Pickering TG. Changes of tion how similar are they? Epidemiology 2008;19:
nocturnal blood pressure dipping status in 838–45.

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879.e1
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Table S1
Age-adjusted BP values of all, undiagnosed, and diagnosed hypertension by gender
BP Night Sleep Duration, (h) P for Trend

H. Zhang et al. / Journal of the American Society of Hypertension 12(12) (2018) 867–879
<5 5- 6- 7- 8- 9- 10
For personal use only. No other uses without permission. Copyright ©2019. Elsevier Inc. All rights reserved.

Male
SBP (mm Hg), mean (95% CI)
All hypertension 125.39 125.51 125.58 126.19 127.75 127.70 130.27 <.001
(123.12–127.67) (124.15–126.87) (124.87–126.30) (125.68–126.69) (127.17–128.32) (126.81–128.59) (128.78–131.75)
Undiagnosed hypertension 120.32 121.22 121.38 121.98 123.35 123.14 125.63 <.001
(118.07–122.58) (119.92–122.53) (120.69–122.06) (121.50–122.47) (122.79–123.91) (122.27–124.01) (124.15–127.11)
Diagnosed hypertension 122.76 122.67 122.62 123.01 124.35 124.43 125.96 <.001
(120.50–125.02) (121.31–124.03) (121.91–123.34) (122.50–123.51) (123.77–124.93) (123.53–125.33) (124.40–127.51)
DBP (mm Hg), mean (95% CI)
All hypertension 78.55 77.83 77.95 78.54 79.13 79.07 80.86 <.001
(77.07–80.04) (76.94–78.71) (77.48–78.42) (78.21–78.87) (78.75–79.50) (78.49–79.65) (79.89–81.83)
Undiagnosed hypertension 75.53 75.44 75.56 76.29 76.78 76.69 78.68 <.001
(74.01–77.05) (74.56–76.32) (75.10–76.02) (75.96–76.62) (76.41–77.16) (76.10–77.27) (77.68–79.68)
Diagnosed hypertension 76.63 76.11 76.21 76.65 77.05 77.19 78.19 <.001
(75.16–78.10) (75.22–76.99) (75.75–76.68) (76.31–76.98) (76.67–77.43) (76.60–77.78) (77.17–79.20)
Female
SBP (mm Hg), mean (95% CI)
All hypertension 123.24 123.35 125.10 125.64 125.82 126.73 127.40 <.001
(121.35–125.14) (122.18–124.52) (124.49–125.72) (125.22–126.07) (125.38–126.27) (126.03–127.43) (126.19–128.60)
Undiagnosed hypertension 117.70 118.23 119.38 120.20 120.21 120.94 120.38 <.001
(115.86–119.55) (117.13–119.33) (118.79–119.96) (119.80–120.59) (119.79–120.63) (120.27–121.61) (119.17–121.59)
Diagnosed hypertension 120.95 120.32 122.11 122.44 122.66 123.28 124.68 <.001
(119.07–122.84) (119.16–121.49) (121.49–122.73) (122.01–122.86) (122.21–123.10) (122.57–123.99) (123.46–125.90)
DBP (mm Hg), mean (95% CI)
All hypertension 76.18 75.77 76.77 77.05 77.05 77.41 77.45 <.001
(75.03–77.32) (75.06–76.48) (76.40–77.14) (76.80–77.31) (76.78–77.32) (76.99–77.83) (76.72–78.17)
Undiagnosed hypertension 73.19 73.53 74.08 74.60 74.51 74.72 74.47 <.001
(72.02–74.36) (72.84–74.23) (73.71–74.45) (74.35–74.85) (74.25–74.78) (74.30–75.15) (73.71–75.24)
Diagnosed hypertension 75.07 74.31 75.33 75.49 75.52 75.80 76.05 <.001
(73.93–76.22) (73.60–75.03) (74.96–75.71) (75.23–75.75) (75.25–75.79) (75.37–76.23) (75.31–76.80)
SBP, systolic blood pressure; DBP, diastolic blood pressure; BP, blood pressure.
Table S2
Age-adjusted prevalence of hypertension by gender
Prevalence Night Sleep Duration, (h) P for Trend
<5 10
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5- 6- 7- 8- 9-
Male (%)
All hypertension 33.77 31.55 29.17 31.99 34.70 33.51 40.27 <.001
(28.10–39.95) (28.14–35.18) (27.39–31.02) (30.69–33.32) (33.19–36.24) (31.24–35.86) (36.31–44.35)

H. Zhang et al. / Journal of the American Society of Hypertension 12(12) (2018) 867–879
Undiagnosed hypertension 14.46 15.46 14.32 16.31 18.36 17.80 25.13 <.001
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(10.16–20.18) (12.70–18.70) (12.87–15.90) (15.20–17.49) (17.03–19.77) (15.82–19.98) (21.34–29.34)


Diagnosed hypertension 24.70 20.95 19.17 20.96 22.64 21.70 24.90 <.001
(19.43–30.86) (17.85–24.42) (17.55–20.90) (19.75–22.22) (21.22–24.12) (19.63–23.92) (21.24–28.95)
Female
(%)
All hypertension 27.39 26.08 30.50 29.97 30.16 31.58 32.48 <.001
(23.15–32.08) (23.39–28.96) (28.93–32.11) (28.89–31.08) (29.00–31.33) (29.78–33.43) (29.43–35.68)
Undiagnosed hypertension 9.20 10.70 12.79 13.40 13.53 14.75 13.13 <.001
(6.57–12.73) (8.82–12.93) (11.61–14.07) (12.56–14.29) (12.63–14.48) (13.34–16.29) (10.91–15.72)
Diagnosed hypertension 19.80 17.21 20.86 19.58 19.71 20.22 22.55 <.001
(16.10–24.11) (14.92–19.77) (19.44–22.35) (18.60–20.59) (18.67–20.79) (18.64–21.90) (19.86–25.49)

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Table S3
Mediation analysis of the relationship between night sleep duration and hypertension by LDL-C
Mediation Analysis Parameter Estimate OR (95% CI)
(95% CI)
All hypertension
Total effect 0.085 (0.039, 0.130) 1.089 (1.040, 1.139)
Direct effect—path 0.082 (0.037, 0.128) 1.085 (1.038, 1.137)
c
Path a 0.022 (0.006, 0.038) -
Path b 0.112 (0.058, 0.165) 1.119 (1.060, 1.179)
Indirect effect— 0.003 (0.001, 0.005) 1.003 (1.001, 1.005)
path ab
LDL-C, low-density lipoprotein cholesterol; BMI, body mass index.
Adjusted for age, high salt diet, high vegetables, and fruit intake, high fatty diet, physical activity, marital status, smoking status, drinking
status, educational level, average monthly income, family history of hypertension and napping duration, BMI.
Path ab coefficients represent 10,000 bootstrapped samples and bias-corrected 95% CIs.

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