Sex-specific Dose-response Associations between Night Sleep Duration and Hypertension in Iran: A Population-based Cross-sectional Study

doi:10.21203/rs.3.rs-2006158/v1

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Sex-specific Dose-response Associations between Night Sleep Duration and Hypertension in Iran: A Population-based Cross-sectional Study

https://doi.org/10.21203/rs.3.rs-2006158/v1

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High blood pressure is a serious public health concern that significantly increases the risks of cardiovascular and cerebrovascular events. Several studies suggested that sleep disorders have adverse effects on health. The current study aimed to evaluate the dose-response relationship between sleep duration and blood pressure in the Iranian large general population. A total of 9865 participants aged 35-65 were included. Night sleep duration was classified as ≤5 hours, 6-, 7-, 8-, 9- and ≥10-hour sleep duration. The relation between self-reported sleep duration and prevalent hypertension was examined using Logistic regression. Moreover, restricted cubic spline analysis showed the dose-response association between sleep duration and hypertension.

The age-adjusted prevalence of hypertension was 16.5%, 24.2%, and 20.5% in men, women, and the total population, respectively. Compared with reference sleep duration (7 hours) in the total population, the multivariate odds ratio (OR) for hypertension was 0.7 (95% CI: 0.55-0.88) for the group with 9-hour sleep duration and 0.9 (95% CI: 0.74-1.09) for the group with ≤5-hour sleep duration. However, there was no significant association between sleep duration and the prevalence of hypertension in the multivariable model. The age-adjusted cubic spline suggested a linear inverse association between sleep duration and prevalence of hypertension among men and the total population and a non-linear association among women. In conclusion, a 9-hour sleep duration has a negative association with prevalent hypertension. Moreover, an inverse linear association was found between night sleep duration and prevalent hypertension in the total population.

public health

risk

sleep disorders

high blood pressure

Hypertension is a serious public health concern that significantly increases the risks of cardiovascular and cerebrovascular events, including heart failure, stroke, and chronic kidney disease (CKD) (1). Analysis from the national data of an Iranian survey showed that among adults aged 25–70 years, the prevalence of pre-hypertension and hypertension were 25.6% and 39.8%, respectively (2). Moreover, the prevalence of hypertension among Iranian participants without taking any antihypertensive medication was 12.6% (3).

Behavioral risk factors, including low physical activity (PA), unhealthy diet, and smoking (4, 5), in addition to metabolic risk factors such as general and central obesity, type 2 diabetes mellitus (T2DM), and hypertriglyceridemia have been proven to be the main risk factors for incident hypertension (6). Recent studies suggested that sleep disorders have negative effects on health (7–9). A meta-analysis of 9 studies reported the dose-response association between sleep duration and hypertension; it demonstrated that sleeping less than 6 hours a day increases the risk of hypertension by 10% compared with sleeping 7 hours a day; this risk increased by 20–30% when the sleep duration was less than 5 hours a day (10). The Rotterdam Study found no association between hypertension and sleep duration among the elderly (11). However, the Whitehall II study indicated an association between hypertension and short sleep duration only among women(12). A cross-sectional study involving a Chinese population reported that longer (≥ 10 hours) or shorter (< 5 hours) sleep duration compared to average sleep duration (7 hours) was associated with the prevalence of hypertension(13). In another study, using the data from the 2007–2009 National Health Interview Surveys (NHISs), a “U”-shaped association was observed between sleep length and hypertension prevalence among all age and sex subgroups (14).

Although several studies have been conducted in Iran assessing the association between different sleep disorders and blood pressure (15, 16), there is still controversy about this association among the Iranian population. Moreover, only a few studies (12, 17, 18) have investigated the association between sleep duration and hypertension regarding sex. Therefore, in this study, we examined the sex-specific dose-response relationship between sleep duration and blood pressure using the Ravansar Non-Communicable Disease Cohort Study (RaNCD), a large general population.

2.1. Study Population and Design

The data for this cross-sectional study were obtained from the Ravansar Non-Communicable Disease (RaNCD) cohort study, which is part of the national cohort study of the Prospective Epidemiologic Research Studies of Iranian Adult (PERSIAN) to determine trends in the prevalence and incidence of non-communicable diseases (NCDs), its significant outcomes and the associations between its risk factors. We included 10065 rural and urban individuals aged 35–65 from November 2014 to February 2017. The design and methodology of the Ravansar study have been published in a previous study (19). This study is planned to continue for at least 15 years on a triennial basis.

After excluding those with missing baseline data for body mass index (BMI), waist circumference (WC), creatinine (Cr), fasting plasma glucose (FPG), education, marital status, alcohol use, systolic blood pressure (SBP), diastolic blood pressure (DBP), smoking status, physical activity, total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and night sleep duration (n = 200, considering overlap features between missing values), 9865 individuals were eligible for the current study. The study protocol was approved by the Ethics Committee of the Kermanshah University of Medical Sciences. We used the STROBE checklist as a reporting guideline for this study.

2.2 Clinical and Laboratory Measurements

Information on demographic data, night sleep duration, smoking status, educational level, medications, and alcohol consumption during the past 12 months were obtained by a trained interviewer using a standard questionnaire. Anthropometric measurements, including height and weight, were recorded with shoes removed and wearing light clothing. Weight was measured to the nearest 100 grams. Height was measured in a standing position using a tape measure, while shoulders were in normal alignment. WC was measured with light clothing at the level of the umbilicus. Questions on physical activity had three components of physical activity during work time, leisure time, and doing sports. The time spent on physical activity during the week was asked, and metabolic equivalents (METs) were measured according to that.

Based on the Ravansar study design (19), two measures of SBP and DBP were performed on the right arm after a 10-min rest in a sitting position. The mean of two measurements was considered the subject’s blood pressure (BP). A blood sample was taken from all study participants between 7:00 and 9:00 AM after 8 to 12 hours of overnight fasting, using standard blood drawing vacationer techniques. FPG was measured by the enzymatic colorimetric method, using glucose oxidase, and their inter-and intra-assay coefficients of variation at baseline and follow‐up phases were < 2.3% and 2.3%, respectively. Total cholesterol was assayed using the enzymatic colorimetric method with cholesterol esterase and cholesterol oxidase, and both inter‐and intra‐assay coefficients of variation at baseline and follow‐up phases were 1.9%. Analyses were conducted using related kits and a Selectra 2 autoanalyzer (Vital Scientific). Additional details for laboratory measurements, including FPG, TC, TG, HDL-C, and Cr, were addressed previously (19).

2.3 Definition of Variables

BMI was calculated as weight (kg) divided by height (m²). Education was sorted into 3 groups: education lasting less than 6 years, 6–12 years, and greater than 12 years. Marital status was defined as single, married, and widowed/divorced. Smoking status was categorized into three groups; current smokers (who smoke daily or occasionally), former smokers (who used to smoke), and never smokers. Estimated Glomerular Filtration Rate (eGFR; mL/min per 1.73 m²) was estimated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) abbreviated prediction Eq. (20). CKD was defined as an eGFR of less than 60 mL/min per 1.73 m² for longer than 3 months. Diabetes was defined as having FPG ≥ 7 mmol/L or using anti-diabetic medications. Hypertension was defined as SBP ≥ 140 mm Hg or DBP ≥ 90 mm Hg or using anti-hypertensive medications or had been previously diagnosed by a doctor; pre-hypertension is defined as 130 ≤ SBP < 140 mm Hg or 80 ≤ DBP < 90 mm Hg without using anti-hypertensive medications (21). Dyslipidemia is defined as LDL cholesterol (mg/dL) ≥ 160 and/or total cholesterol (mg/dl) ≥ 240 and/or HDL cholesterol (mg/dL) < 40 and/or triglycerides (mg/dL) ≥ 200 and/or having a history of medication for Dyslipidemia.

2.4 Assessment of Sleep Duration

Data on night sleep duration were collected by interview. The total sleep time duration was measured by asking the participant when they usually go to bed and wake up.

As literature suggested (10, 12), we categorized sleep duration as ≤ 5 hours, 6 hours (> 5 and ≤ 6 hours), 7 hours (reference, > 6 and ≤ 7 hours), 8 hours (> 7 and ≤ 8 hours), 9 hours (> 8 and ≤ 9 hours), and ≥ 10 hours. Sleep duration of less than 1 hour is considered zero.

2.5 Statistical Analysis

Baseline characteristics of the study population were described as mean (standard deviation: SD) values for continuous variables and as frequencies (%) for categorical variables. For covariates with a skewed distribution (e.g., TG), the median (interquartile range: IQR) was reported. We compared the baseline characteristics of men and women among those with and without prevalent hypertension using the Student’s t-test for normally distributed continuous variables, the Chi-squared test for categorical variables, and the Mann-Whitney U statistic for skewed and ordered variables.

Age-adjusted prevalence of hypertension was also presented for different night sleep duration groups. To be able to capture a potential dose-response association between the night sleep duration and prevalent hypertension, age-adjusted restricted cubic splines with 4 knots defined at the 5th, 25th, 75th, and 95th percentile were used, a method that enabled us to flexibly model across the groups of night sleep duration with considering dose-response relationship (22).

Potential risk factors suggested by the previous studies were included in the Logistic regression model to evaluate associations between prevalent hypertension and night sleep duration. Confounding variables were adjusted in five models: Model 1 was a univariate model that included only the night sleep duration variable. Model 2 was a multivariate model adjusted for age and sex (only for the total population). Model 3 was adjusted for other confounding covariates such as education, marital status, physical activity, current smoking, alcohol use, and menopause status for women. In model 4, we further adjusted with anthropometric covariates, including BMI and WC. Model 5 was a full model adjusted for the previously mentioned availability of diabetes, dyslipidemia, and CKD. Moreover, the dose-response association per hour (as a continuous covariate) between sleep duration and hypertension was also assessed.

The multicollinearity of the variables included in the model was examined by the variance inflation factor (VIF) (23). We did not find evidence of collinearity in the model (mean VIF of = 1.44).

The Odds ratios (OR) and 95% confidence intervals (95% CI) were reported. However, there was no sex interaction with night sleep duration (P-value = 0.9), but all analyses were done separately in men and women. Additionally, the sex interaction with alcohol intake and BMI was also checked, and since no interaction was observed (p-value = 0.9 and p-value = 0.15, respectively), the adjusted model was reported. As a sensitivity analysis, we examined the association between night sleep duration and prevalence of hypertension according to the menopausal status. All analyses were conducted using STATA version 14 SE (StataCorp, TX, USA), and a two-tailed p-value < 0.05 was considered significant.

The study population consisted of 4668 men and 5197 women at baseline with a mean (SD) age of 47.8 (8.0) and 48.3 (8.4) years, respectively. The baseline characteristics of those with and without hypertension among men and women are shown in Table 1. In both men and women, those with hypertension had higher BMI, WC, TC, HDL-c, and eGFR and lower levels of TG, education, physical activity, and smoking rates.

Table 1

Demographic characteristics of study participants in men and women by different blood pressure categories: The RaNCD cohort study
		Men (N = 4,668)			Women (N = 5,197)
	Total (N = 9865)	Without hypertension (N = 3898)	With hypertension (N = 770)	p-value	Without hypertension (N = 3940)	With hypertension (N = 1257)	p-value
Age, years	48.1(8.2)	46.6(7.6)	53.5(7.6)	< 0.0001	46.5(7.8)	54.1(7.5)	< 0.0001
Body mass index, kg/m²	27.5(4.6)	26.08(4.0)	27.7(4.14)	< 0.0001	28.2(4.8)	29.8(4.9)	< 0.0001
Waist circumference, cm	97.3(10.6)	95.5(9.3)	99.8(10.5)	< 0.0001	97.3(11.2)	101.5(10.8)	< 0.0001
Systolic blood pressure, mm Hg	109.9(17.5)	103.2(12.6)	133.9(20.6)	< 0.0001	106.8(12.1)	125.6(20.2)	< 0.0001
Diastolic blood pressure, mm Hg	70.7(10.2)	69.3(8.2)	82.8(11.1)	< 0.0001	67.3(8.0)	78.6(11.8)	< 0.0001
Marital status, n (%)				0.06			< 0.0001
₋ Single	413(4.19)	87(2.23)	7(0.91)		304(7.72)	15(1.19)
₋ Married	8904(90.26)	3779(96.95)	757(98.31)		3298(83.71)	1070(85.12)
₋ Divorced /widow	548(5.55)	32(0.82)	6(0.78)		338(8.58)	172(13.68)
Education, years				< 0.0001			< 0.0001
- < 6	6209(62.94)	1528(39.20)	417(54.16)		3100(78.68)	1164(92.6)
- 6–12	2885(29.24)	1831(46.97)	265(34.42)		706(17.92)	83(6.60)
- ≥ 12	771(7.82)	539(13.83)	88(11.43)		134(3.40)	10(0.80)
Smoking status, n (%)				< 0.0001			< 0.0001
- Never	7904(80.12)	2498(64.08)	479(62.21)		3790(96.19)	1137(90.45)
- Current	1149(11.65)	918(23.55)	129(16.75)		63(1.60)	39(3.10)
- Former	812(8.23)	482(12.37)	162(21.04)		87(2.21)	81(6.44)
Alcohol use, yes	622(6.31)	536(13.75)	82(10.65)	0.02	4(0.1)	-	0.26
Physical activity, n (%)				< 0.0001			< 0.0001
- Light	2696(27.33)	1234(31.66)	307(39.87)		817(20.74)	338(26.89)
- moderate	5084(51.54)	1323(33.94)	240(31.17)		2702(68.58)	819(65.16)
- vigorous	2085(21.14)	1341(34.4)	223(28.96)		421(10.69)	100(7.96)
Post-menopause women, yes	1370(26.36)	-	-		771(19.57)	599(47.65)
Fasting blood sugar, mmol/L	5.4(1.7)	5.3(1.6)	5.8(2.1)	< 0.0001	5.2(1.4)	5.9(2.2)	< 0.0001
Total cholesterol, mmol/L	4.8(1.0)	4.7(0.93)	4.8(1.0)	0.02	4.8(1.0)	5.1(1.03)	< 0.0001
Triglycerides, mmol/L	1.3(0.95–1.3)	1.37(0.97–1.98)	1.5(1.10–2.10)	< 0.0001	1.21(0.88–1.68)	1.46(1.06–2.01)	< 0.0001
High-density lipoprotein cholesterol, mmol/L	1.2(0.3)	1.11(0.26)	1.08(0.25)	0.003	1.29(0.29)	1.26(0.30)	0.001
eGFR, ml/min/1.73 m²	70.0(15.2)	63.3(11.1)	58.4(12.0)	< 0.0001	78.4(14.7)	71.7(15.1)	< 0.0001
Low-density lipoprotein cholesterol, mmol/L	2.6(0.66)	2.61(0.63)	2.7(0.68)	0.08	2.63(0.67)	2.8(0.69)	< 0.0001
Hypertension drug, yes	1136(11.52)	-	364(47.27)	-	-	772(61.42)
Diabetes drug, yes	451(4.57)	129(3.31)	61(7.92)	< 0.0001	118(3.0)	143(11.38)	< 0.0001
Lipid-lowering drug, yes	398(4.03)	82(2.10)	67(8.7)	< 0.0001	98(2.50)	151(12.01)	< 0.0001
Diabetes, yes	801(8.12)	249(6.39)	116(15.06)	< 0.0001	217(5.51)	219(17.42)	< 0.0001
Dyslipidemia, yes	4375(44.35)	2005(51.44)	473(61.43)	< 0.0001	1296(32.89)	601(47.81)	< 0.0001
Chronic kidney disease, yes	2594(26.29)	1570(40.28)	425(55.19)	< 0.0001	333(8.45)	266(21.16)	< 0.0001
Night sleep duration, hour	7.05(1.2)	7.0(1.2)	6.9(1.2)	0.28	7.2(1.2)	7.0(1.3)	< 0.0001
eGFR: estimated glomerular filtration rate disease. Values are shown as Mean (SD) and number (%), for continuous and categorical variables, respectively; TG values are shown as Median (Interquartile range).

The mean age-adjusted SBP among men and women on hypertension medication was 130 (95% CI:128.3-132.8) and 124.2 (95% CI:122.8-125.6) mmHg, respectively; among those not on hypertensive medications, the mean SBP was 109.6 (95% CI:109.2-110.1) in men and 105.9 (95% CI:105.5-106.4) in women. The mean age-adjusted DBP among men and women on hypertension medication was 79.8 (95% CI:78.6–80.9) and 77.6 (95% CI:76.8–78.5) mmHg, respectively; among those not on hypertensive medications, the mean DBP was 70.8 (95% CI:70.6–71.1) in men and 68.7 (95% CI:68.4–68.9) in women. Age-adjusted SBP and DBP regarding sex and hypertension medications within each group of sleep duration are shown in Fig. 1. The age-adjusted prevalent hypertension was 16.5% in men, 24.2% in women (17% in pre-menopause and 44.3% in post-menopause), and 20.5% in total population. The age-adjusted prevalence of hypertension was 17.3% in men with ≤ 5-hour sleeping duration and 15.3% in the group with ≥ 10-hour sleeping duration; the p-for trend was not significant (p for trend-value = 0.39). However, among women, the age-adjusted prevalence of hypertension shows a significant decrease by increasing sleeping hours; 26.6% in the group with ≤ 5-hour sleep duration and 21.0% in the group with ≥ 10-hour sleeping duration (p for trend-value = 0.017) (Table 2).

Table 2

Age-adjusted prevalence of hypertension by gender: The RaNCD cohort study
	Male, %	Women, %	Total population*, %
Night sleep duration (hour)
≤ 5	17.3(15.2–19.3)	26.6(24.2–28.9)	20.5(18.3–22.8)
6-	16.9(15.5–18.2)	24.4(23.9–26.9)	21.4(19.8–23.0)
7-	16.5(15.5–17.5)	24.3(23.2–25.3)	21.5(20.2–22.8)
8-	16.1(14.7–17.4)	23.2(21.8–24.5)	20.0(18.6–21.4)
9-	15.7(13.7–17.7)	22.1(20.1–24.1)	16.2(13.7–18.6)
≥ 10	15.3(12.6–18.1)	21.0(18.4–23.7)	19.5(13.4–25.6)
p-for trend	0.39	0.017	0.016
* Age and gender adjusted prevalence

The dose-response relationships of sleep duration with prevalent hypertension are represented using the age-adjusted restricted cubic spline curves in Fig. 2, which suggests a linear inverse association between sleep duration and prevalence of hypertension among men and the total population; however, a non-linear association was observed among women.

ORs and 95% CIs for hypertension associated with different sleep durations are presented in Table 3. In comparison with women with 7-hour sleeping duration in model 2, only women with 9-hour sleeping duration had the age-adjusted OR [95% CI] of 0.62 [0.47–0.862]; after further adjustment in model 5, the corresponding OR [95% CI] reached 0.65 [0.48–0.86], while no association was detected among men.

Table 3

Odds Ratios (OR) and 95% Confidence Intervals (CI) night sleep duration with prevalent hypertension by Gender: The RaNCD cohort study
	Night sleep duration (hour)
	≤ 5	6-	7-	8	9	≥ 10	p-for trend
Male
n /N^†	89/471	172/1051	259/1572	202/1241	40/288	8/45
Model 1	1.18(0.9–1.54)	1.0(0.8–1.22)	Reference	0.98(0.80–1.20)	0.82(0.57–1.17)	1.10(0.50–2.38)	0.45
Model 2	0.97(0.73–1.29)	0.94(0.75–1.18)	Reference	0.91(0.74–1.13)	0.78(0.53–1.14)	0.83(0.36–1.91)	0.19
Model 3	0.96(0.73–1.28)	0.93(0.75–1.17)	Reference	0.93(0.75–1.15)	0.80(0.55–1.18)	0.84(0.36–1.96)	0.26
Model 4	0.93(0.70–1.25)	0.90(0.72–1.13)	Reference	0.93(0.75–1.16)	0.85(0.57–1.26)	0.97(0.40–2.32)	0.38
Model 5	0.94(0.70–1.26)	0.89(0.71–1.12)	Reference	0.93(0.75–1.16)	0.83(0.56–1.23)	0.89(0.36–2.16)	0.31
Women
n /N^†	134/459	277/1012	417/1646	322/1452	86/534	21/94
Model 1	1.21(0.96–1.53)	1.11(0.93–1.33)	Reference	0.84(0.71–0.99)	0.56(0.44–0.73)	0.85(0.51–1.39)	< 0.0001
Model 2	0.91(0.71–1.16)	1.03(0.85–1.25)	Reference	0.89(0.74–1.07)	0.62(0.47–0.82)	0.88(0.51–1.53)	0.013
Model 3	0.91(0.71–1.17)	1.04(0.86–1.26)	Reference	0.91(0.76–1.08)	0.63(0.48–0.84)	0.91(0.52–1.58)	0.025
Model 4	0.86(0.67–1.12)	1.03(0.85–1.26)	Reference	0.93(0.77–1.11)	0.65(0.49–0.87)	1.11(0.63–1.95)	0.1
Model 5	0.89(0.68–1.15)	1.03(0.84–1.25)	Reference	0.94(0.78–1.13)	0.65(0.48–0.86)	1.05(0.59–1.86)	0.09
Total population
n /N^†	223/930	449/2063	676/3218	524/2693	126/822	29/139
Model 1	1.19(1.0-1.41)	1.05(0.91–1.20)	Reference	0.91(0.80–1.03)	0.68(0.55–0.84)	0.99(0.65–1.50)	0.002
Model 2	0.93(0.77–1.15)	0.99(0.86–1.15)	Reference	0.90(0.78–1.03)	0.66(0.53–0.83)	0.86(0.55–1.36)	0.005
Model 3	0.93(0.77–1.12)	0.99(0.86–1.15)	Reference	0.91(0.79–1.04)	0.68(0.54–0.85)	0.88(0.56–1.40)	0.01
Model 4	0.89(0.73–1.07)	0.98(0.84–1.13)	Reference	0.92(0.80–1.06)	0.71(0.56–0.89)	1.07(0.67–1.08)	0.06
Model 5	0.90(0.74–1.09)	0.97(0.83–1.12)	Reference	0.92(0.80–1.07)	0.70(0.55–0.88)	0.99(0.61–1.60)	0.04
† n: number of hypertension patients; N: Number of populations Model 1: unadjusted Model 2: adjusted for age and sex (for total population) Model 3: model 2 + education, marital status, physical activity, current smoking, alcohol use, and menopause status for women Model 4: model 3 + BMI, WC Model 5: model 4 + diabetes, dyslipidemia, CKD p-value for gender interaction with night sleep duration is 0.9 BMI: Body mass index; WC: waist circumference; CKD; chronic kidney disease

Multivariate OR [95% CI] of prevalent hypertension per additional night sleep hour among both men and women are shown in Fig. 3. When night sleep duration was adjusted with age in model 2, each additional night sleep hour was associated with the OR [95% CI] of 0.93 [0.87–0.99] for women and 0.98 [0.972–1.05] for men, which were to be significant among women. However, after further adjustment in multivariate model 5, the OR [95% CI] for each additional sleep hour reach 0.96[0.90–1.01] among women and 1.0 [0.94–1.07] among men.

As a sensitivity analysis, we examined the association between night sleep duration and prevalence of hypertension according to the menopausal status. Among premenopausal women, in comparison with 7-hour night sleep duration in model 5, women with 9-hour night sleep duration had the age-adjusted OR [95% CI] of 0.62 [0.42–0.90]. Among post-menopausal women, no significant association was observed between night sleep duration and prevalence of hypertension (Table 4).

Table 4

Odds Ratios (OR) and 95% Confidence Intervals (CI) night sleep duration in relation to prevalent hypertension by menopausal status: The RaNCD cohort study
Menopause status	Night sleep duration (hour)
	≤ 5	6-	7-	8	9	≥ 10	p-for trend
Post-menopause
n /N^†	71/167	127/293	201/443	144/328	43/115	13/24
Model 1	0.89(0.62–1.27)	0.92(0.68–1.24)	Reference	0.94(0.71–1.26)	0.72(0.47–1.10)	1.42(0.62–3.24)	0.47
Model 2	0.85(0.59–1.23)	0.91(0.67–1.24)	Reference	0.93(0.69–1.25)	0.65(0.42-1.00)	1.20(0.52–2.78)	0.28
Model 3	0.83(0.57–1.20)	0.90(0.66–1.22)	Reference	0.93(0.69–1.26)	0.66(0.43–1.01)	1.17(0.50–2.71)	0.3
Model 4	0.78(0.54–1.15)	0.92(0.67–1.25)	Reference	0.97(0.72–1.32)	0.66(0.73–1.03)	1.42(0.60–3.37)	0.52
Model 5	0.82(0.54–1.17)	0.92(0.67–1.26)	Reference	0.98(0.72–1.33)	0.68(0.43–1.06)	1.30(0.54–3.16)	0.54
Pre-menopause
n /N^†
Model 1	1.26(0.92–1.72)	1.20(0.95–1.52)	Reference	0.86(0.69–1.07)	0.52(0.37–0.74)	0.59(0.28–1.25)	0.001
Model 2	0.95(0.68–1.32)	1.12(0.87–1.43)	Reference	0.87(0.69–1.09)	0.61(0.42–0.88)	0.71(0.33–1.56)	0.025
Model 3	0.96(0.68–1.34)	1.13(0.88–1.45)	Reference	0.88(0.70–1.11)	0.63(0.43–0.90)	0.74(0.34–1.63)	0.04
Model 4	0.91(0.64–1.28)	1.10(0.86–1.42)	Reference	0.89(0.71–1.13)	0.65(0.45–0.95)	0.89(0.40–1.97)	0.1
Model 5	0.93(0.66–1.31)	1.08(0.83–1.39)	Reference	0.90(0.71–1.14)	0.62(0.42–0.90)	0.86(0.39–1.90)	0.08
† n: number of hypertension patients; N: Number of populations Model 1: unadjusted Model 2: adjusted for age and sex (for total population) Model 3: model 2 + education, marital status, physical activity, current smoking, and alcohol use Model 4: model 3 + BMI, WC Model 5: model 4 + diabetes, dyslipidemia, CKD BMI: Body mass index; WC: waist circumference; CKD; chronic kidney disease

Table 5

Summary table
What is known about topic
• Sleep disorders have adverse effects on health • There is an association between sleep duration and hypertension • There is controversy about this association among the Iranian population
What this study adds
• This is the first large-scale study in Iran to examine this association regarding gender and dose-response. • The age-adjusted prevalence of hypertension was 16.5% and 24.2% in men and women, respectively. • 9-hour sleep duration has a negative association with prevalent hypertension. • There is a dose-response association between sleep duration and hypertension.

The present study indicated that a long sleep duration of 9 hours is associated with lower prevalent hypertension in the Iranian community-based population. The association of sleep duration with hypertension persisted after adjustment for potential confounders, including age, education, marital status, physical activity, alcohol use, current smoking, BMI, and waist circumference. The same results were observed only among women.

Moreover, analyses also showed that the association of sleep duration with hypertension was not confounded by diabetes, dyslipidemia, and CKD. This study also demonstrated a dose-response association between sleep duration and prevalent hypertension; however, this association was not linear among women.

The current study indicated a sex-related difference in the relationship of sleep duration with hypertension (a U-shaped pattern for women vs. a linear pattern for men). Obstructive sleep apnea is more prevalent among men (24) while women experience more insomnia (25); both are independent risk factors for hypertension (26, 27). Accordingly, they can influence the association between sleep duration and hypertension and must be considered in adjusted models. In a review, Burgard et al. explained that women sleep more than men; we also indicated this in our study (Table 2) (28), so this can influence the association between hypertension and sleep duration in terms of gender (a U-shaped pattern in women vs. a linear decreasing pattern of hypertension odds with sleep duration among men) (Fig. 2). Furthermore, sleep loss and excessive sleep may produce more cardiovascular consequences among women. It has been shown that the association of sleep problems with high blood pressure is more prevalent among women (12, 29). It is hypothesized that shorter sleep makes women more vulnerable to poor cardiovascular outcomes. Gender influence on the association of sleep duration needs more clarification of underlying mechanisms and further population-based studies based on more objective measures of sleep duration (30).

According to the National Sleep Foundation report, the optimal sleep duration for being healthy is 7–9 hours a day among adults aged 18–64 years (31). The principal findings of the current study showed that sleep duration ≤ 5 hours a day was associated with grated prevalent hypertension, the negative association was observed with 9-hour sleep duration. A study using data from National Health Interview Survey (NHIS) showed that among adults aged over 18 years, short (< 6 h for men and < 8 h for women) and long (≥ 10 h for men) sleep durations were associated with a higher likelihood of hypertension(14).

Najafian et al. evaluated the association between hypertension and self-reported sleep duration among the Iranian population living in central Iran. They reported a positive association between sleeping for less than 5 hours a day and prevalent hypertension even after adjustment with age, sex, BMI, and abdominal obesity, among individuals over 19 years. However, sleep duration over 9 hours was negatively associated with prevalent hypertension, but this association was not significant (32). These findings agree with ours; however, after further adjustment with potential confounders among those with a sleeping duration of ≤ 5 hours, we did not observe a positive association with hypertension.

Another study in China showed a positive association among those with a sleep duration of over 10 hours a day and a negative association among those with a sleep duration of 6 hours a day(13). They also found a U-shaped (non-linear) trend between sleep duration and hypertension in both males and females; in the current study, only women showed a non-linear trend. A linear negative dose-response relation was detected among the total population. In addition, one systematic review of 36 studies (26 cross-sectional and 10 cohorts) reported that short sleep duration was related to higher blood pressure and hypertension (33).

Grandner et al., consistent with our findings, indicated higher odds for long sleepers ( > = 10 hours a day) in the non-adjusted model of their study covariates (18). However, in their study, both 9 and > = 10-hour groups were found to have higher odds for hypertension in the adjusted model. This difference in findings may be due to different measures of sleep duration between these two studies (sleep duration in a day vs. sleep duration at night in our study) and also different covariates in adjusted models.

Race and ethnicity can also affect the association between sleep duration and hypertension, as indicated by Gardner et al. study, among different ethnicities; in black ethnicity, the odds of hypertension were increased in the 10-hour sleep duration group compared to other ethnicities (18). So, the difference between Iranian ethnicity and other populations may explain higher odds of hypertension in the group with > = 10 hours of sleep. Covariates such as employment status (18), obstructive sleep apnea (27), and insomnia (26) may also be the other explanations that need further evaluation. Accordingly, the limitation of data on these covariates in our adjusted models may have led to the reverse association of sleep duration and hypertension. Furthermore, the measure of sleep duration differs among the studies; Different measures of sleep, such as sleep duration during 24 hours or during a specific period (one week, etc.), and self-reported or objective measurements of sleep duration could lead to a discrepancy in findings on the association of sleep duration and high blood pressure. Additionally, as described before, race and ethnicity may explain different findings of the current study.

In the current study, we evaluated the association among adults aged 35–65 years, while the mechanism of the sleep duration on hypertension might differ in children, adolescents, young adults, or the elderly (33, 34). This will be a serious concern if we know that each 10 mm Hg increase in adolescent SBP/DBP increases the risk of early adulthood hypertension by 4% during 10 years of follow-up(35).

The strength of this study includes an epidemiological profile through the assessment of the dose-response relationship in a large sample of men and women in the Middle East and North Africa region (MENA). However, several limitations need to be considered. Firstly, this study was a cross-sectional study, and we were not able to check the causality. Secondly, the current study used a self-reported measure of sleep duration. Objective data on sleep duration by instruments such as actigraphy and polysomnography could provide more detailed findings on people’s sleep characteristics. The quality of sleep, daytime dysfunction, reported difference between weekday and weekend sleep duration, and interference of sleep duration with daily activities also could influence the association of high blood pressure and sleep duration. Covariates like insomnia, obstructive sleep apnea, employment status, and shiftwork could affect both hypertension and sleep duration and require consideration in future studies.

4.1. Conclusion

This study found that longer sleep duration negatively correlates with prevalent hypertension. Moreover, an inverse linear association was found between night sleep duration and prevalent hypertension in the total population. Further studies suggested a causal relationship between hypertension and sleep duration to find the related risk factors.

Availability of data and materials: Datasets generated during the current study are not publicly available but are accessible upon reasonable request from the corresponding author.

Funding: None

Acknowledgments: We acknowledge the staff and participants in the RaNCD cohort study for their cooperation.

Declaration of interest: None

Authors' contributions:

Substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work: S.AS, S.AK, A.Na, F.N, and R.SF

Drafting the work or revising it critically for important intellectual content: S.AS, A.Na, S.AK, F.N, A.B, and R.SF. Final approval of the version to be published: All authors

Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved: all authors

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There is NO conflict of interest to disclose.

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Sex-specific Dose-response Associations between Night Sleep Duration and Hypertension in Iran: A Population-based Cross-sectional Study

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1. Introduction

2. Materials And Methods

2.1. Study Population and Design

2.2 Clinical and Laboratory Measurements

2.3 Definition of Variables

2.4 Assessment of Sleep Duration

2.5 Statistical Analysis

3. Results

4. Discussion

4.1. Conclusion

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Acknowledgments: We acknowledge the staff and participants in the RaNCD cohort study for their cooperation.

References

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