Abstract
Background
Sleep is an important determinant of cardiovascular health. We sought to investigate the longitudinal association between sleep duration and incident carotid plaque in a rural Chinese population.
Methods
This population‐based prospective cohort study included 1004 rural residents (age ≥40 years) who were free of carotid plaque and had no history of clinical stroke and transient ischemic attack at baseline (2017). Incident carotid plaques were detected by carotid ultrasound images at follow‐up (2021). Multivariable Cox regression was used to associate sleep duration with the presence and severity of incident carotid plaques. Restricted cubic splines analyses were conducted to assess dose–response association between sleep duration and incident carotid plaques.
Results
During the mean follow‐up of 3.95 (SD=0.14) years, 214 (21.3%) of the 1004 participants were found to have incident carotid plaques. A short sleep duration (<7 versus 7–9 hours) was associated with multivariable‐adjusted hazard ratio (95% CI) of 1.58 (1.10–2.28) for carotid plaques, 2.96 (1.38–6.36) for greater carotid plaque thickness, and 2.57 (1.33–4.97) for multiple carotid plaques; those associations remained significant in participants with low‐to‐intermediate traditional cardiovascular disease risk. Long sleep duration (>9 versus 7–9 hours) was not significantly associated with carotid plaques. Restricted cubic splines supported the association of short, but not long, sleep duration with increased risk of incident carotid plaques.
Conclusions
A short sleep duration is a risk factor for carotid plaques, even among individuals with low‐to‐intermediate cardiovascular disease risk. This suggests that short sleep duration may be a potential target for early interventions to delay carotid atherosclerosis.
Registration
URL: https://www.chictr.org.cn; Unique Identifier: ChiCTR1800017197.
Keywords: carotid arteries, carotid plaque, cohort study, incident atherosclerotic plaque, sleep duration
Subject Categories: Risk Factors, Cardiovascular Disease
Clinical Perspective.
What Is New?
A short sleep duration is a risk factor for incident carotid plaques in a rural Chinese population.
A short sleep duration is associated with greater carotid plaque thickness, multiple carotid plaques, and a more severe carotid plaque burden.
What Are the Clinical Implications?
Insufficient sleep might be a potential target for interventions to promote cardiovascular health.
Carotid atherosclerosis, a leading cause of ischemic stroke, is highly prevalent in the general adult population, affecting about one‐fifth of adults worldwide. 1 Individuals with cardiovascular risk factors have a higher risk and burden of carotid atherosclerosis. The pathological process of carotid atherosclerosis can begin early in life and gradually progress into subclinical and clinical stages (eg, stroke). Despite great efforts to actively control and manage traditional risk factors, such as hypertension, hyperlipidemia, diabetes, and smoking, people remain at a substantial risk of atherosclerotic cardiovascular disease (ASCVD), 2 indicating a role of unrecognized risk factors. Therefore, it is important to identify novel modifiable risk factors that can be targeted for early preventive interventions.
Sleep is an important physiological process that significantly impacts cardiovascular health. Previous studies have found that sleep disturbances are associated with increased risks of clinical stroke and cardiovascular disease. 3 However, subclinical atherosclerosis preceding clinical stroke in the general population has been rarely investigated. The cross‐sectional data from the Northern Manhattan Study of an ethnically diverse population suggested that long sleep duration (≥9 versus 7 to 9 hours) was associated with an increased likelihood of carotid plaques. 4 The association of sleep duration with carotid atherosclerosis has not yet been investigated in prospective cohort studies. Because sleep duration in the whole lifetime is a potentially modifiable factor, exploring the potential causal relationship between abnormal sleep duration and carotid atherosclerosis may help identify a target for early preventive interventions to delay occurrence and progression of carotid atherosclerosis.
Therefore, in this community‐based prospective cohort study, we aimed to investigate the longitudinal association of sleep duration with the risk and severity of incident carotid plaques in a rural Chinese population.
METHODS
Study Design and Participants
This population‐based cohort study used data from the Rose asymptomatic Intra‐Cranial Artery Stenosis (RICAS) study, as previously described. 5 , 6 The baseline examination of the RICAS study was carried out in October–November 2017 and the follow‐up assessment was performed in September–November 2021. In brief, a total of 2474 participants (age ≥40 years) who were free of clinical stroke and transient ischemic attack and living in Kongcun Town (hometown of Rose), Pingyin County, Shandong Province, undertook the baseline examination. Of those, 292 were excluded due to incomplete or missing data on baseline interview (n=163), carotid ultrasonography examination (n=112), and sleep duration (n=17), and an additional 865 participants were excluded due to having carotid plaques at baseline. We further excluded 289 participants who were lost to follow‐up (of those, 13 individuals died), 19 participants who took sleeping pills, and 5 participants who had extreme sleep duration (sleep duration <3 hours or >14 hours). Thus, the final analytical sample included 1004 participants who were free of carotid plaques, clinical stroke, and transient ischemic attack at baseline in 2017 and who completed the follow‐up assessment in 2021. Compared with persons who were excluded (n=313), individuals who were included in the analytical sample (n=1004) were less educated (illiteracy or primary school, 39.7% versus 32.9%, P=0.01), but the 2 groups did not significantly differ in mean age (54.31 versus 54.39 years, P=0.69) and distribution of sex (56.1% female versus 50.2% male, P=0.07) and marital status (married, 93.8% versus 93.9%, P=1.00). The Figure shows the flowchart of the study participants.
Figure 1. Flowchart of the study participants.
RICAS indicates Rose asymptomatic IntraCranial Artery Stenosis.
All parts of the RICAS study were approved by the Ethics Committee of Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China. Written informed consent was obtained from all participants. This study was conducted in accordance with the principles expressed in the Declaration of Helsinki. The RICAS study was registered in the Chinese Clinical Trial Registry (registration number: ChiCTR1800017197).
Assessment of Carotid Plaque
The operational procedure for detecting carotid plaques has been described in detail in our previous study. 6 In brief, B‐mode ultrasound examination with a 7‐MHz linear transducer (ACUSONP 500, Siemens) was performed by the same 2 experienced physicians both at baseline (2017) and subsequent follow‐up visits (2021). The presence of carotid plaque is defined as a carotid intima‐media thickness value ≥1.5 mm in any segment of carotid arteries. Severity of carotid plaque was categorized according to the maximum carotid plaque thickness and number of carotid arteries affected, which were found to be associated with cardiovascular events. 7 , 8 , 9 Maximum carotid plaque thickness was evaluated at the cutoff level of 75th percentile of the plaque thickness distribution, as previously suggested. 7 The number of carotid arteries affected was categorized into single and multiple (≥2) carotid plaques.
Assessment of Sleep Duration
Participants were asked about their sleep habits during the baseline survey in 2017 and 2021. Sleep duration was ascertained according to the participant's answer to the question: “On average, how many hours do you usually sleep in a 24‐hour period?” The answer was given in detailed hours and minutes. We divided sleep duration into 3 categories: short sleep duration (<7 hours), normal sleep duration (7–9 hours), and long sleep duration (>9 hours). A sleep duration of 7 to 9 hours was considered as reference because previous studies suggested that a sleep duration of 7 to 9 hours was optimal for adults. 10 Additionally, changes in sleep duration from baseline to follow‐up were classified into persistent short, persistent normal, persistent long, and increase and decrease in sleep duration. Daytime napping was determined via interview according to answer to the question: “Do you habitually take a nap?” Respondents were divided into 3 categories: almost always, only in summer, and no. Habitual snoring was queried through the question: “Do you snore during the night?” We categorized all respondents into almost always, sometimes, and no or unknown.
Definitions and Assessment of Covariates
Data on sociodemographics (eg, age, sex, educational attainment, and marital status) and behavioral factors (eg, alcohol drinking and smoking) were collected by trained medical staff through face‐to‐face interviews, as previously reported. 11 Body mass index was calculated as measured body weight (kilograms) divided by the square of height (meters). Hypertension was defined as blood pressure ≥140/90 mm Hg, use of antihypertensive medication, or self‐reported physician diagnosis of hypertension. Diabetes was defined as fasting plasma glucose ≥7.0 mmol/L, use of blood glucose–lowering drugs, insulin injection, or self‐reported history of diabetes. Dyslipidemia was defined as total cholesterol ≥6.2 mmol/L, low‐density lipoprotein cholesterol ≥4.1 mmoL/L, high‐density lipoprotein cholesterol <1.0 mmol/L, triglycerides ≥2.3 mmol/L, or self‐reported use of lipid‐lowering medications, in accordance with the 2016 Chinese Adult Dyslipidemia Prevention Guideline. 12 Participants were considered to have a history of coronary heart disease if they had been diagnosed with myocardial infarction, angina, or coronary heart disease. Physical activity was assessed by the International Physical Activity Questionnaire Short Form (IPAQ‐SF)‐Chinese version and classified into 3 groups (high, moderate, and low) according to IPAQ‐SF scoring protocol. 13 Fasting peripheral blood samples were taken and serum high‐sensitivity C‐reactive protein was measured in the laboratory of Shandong Provincial Hospital affiliated with Shandong First Medical University in Jinan. The prediction for ASCVD risk in China (China‐PAR project) model was used to assess the 10‐year ASCVD risk, which included age, sex, waist circumference, systolic blood pressure (treated or untreated), total cholesterol, high‐density lipoprotein cholesterol, current smoking, diabetes, geographic region (Northern China/Southern China), urbanization (urban/rural), and family history of ASCVD. 14 Study participants were then divided into a low‐to‐intermediate risk group (<10%) and a high‐risk group (≥10%) according to the 10‐year risk of cardiovascular disease. 15
Statistical Analysis
SPSS 22.0 for Windows (IBM Corporation, released 2013, Armonk, NY) and R studio, v4.3.1 (RStudio, Inc., Boston, MA) were used for all statistical analyses. The characteristics of the study participants were presented as means±SD for continuous variables and as frequencies (percentage) for categorical variables. Analysis of variance or Mann–Whitney rank test was used for comparison of continuous variables, and χ2 test was used for comparison of categorical variables. Cox proportional hazard models were used to examine the association of carotid plaques with sleep duration, and the assumption of proportional hazards was confirmed using the Schoenfeld residual test. We reported the main results from 3 models: Model 1 was unadjusted (crude or univariable model). Model 2 was adjusted for age, sex, marital status, education, current smoking, current alcohol drinking, hypertension, diabetes, dyslipidemia, body mass index, coronary heart disease, physical activity, and serum high‐sensitivity C‐reactive protein. In Model 3, we further adjusted for daytime napping and habitual snoring to examine whether the association between sleep duration and carotid plaques was present independent of other sleep‐related parameters. Finally, the restricted cubic splines analyses with 3 knots at 10th, 50th, and 90th percentiles were conducted to model and visualize the nonlinear patterns of association between sleep duration and risk of incident carotid plaques, maximum carotid plaque thickness, and multiple carotid plaques. Multivariable logistic regression models were used to analyze the cross‐sectional association between longitudinal changes in sleep duration changes from baseline to follow‐up examination and carotid plaques detected at follow‐up. Two‐tailed P<0.05 was considered statistically significant for all statistical tests.
RESULTS
Baseline Characteristics of Participants
The mean age of the 1004 participants was 54.31 years (SD=8.83), and 56.1% were women. Participants with short sleep duration were less educated and less likely to report daytime napping. The prevalence of current smoking, current alcohol drinking, hypertension, diabetes, dyslipidemia, coronary heart disease, physical activity, and serum high‐sensitivity C‐reactive protein did not differ significantly across the 3 sleep duration groups (Table 1).
Table 1.
Baseline Characteristics of Study Participants in the Total Sample and by Sleep Duration (n=1004)
| Characteristics* | Total | Sleep duration (h) | P value | ||
|---|---|---|---|---|---|
| sample | <7 | 7–9 | >9 | ||
| No. of participants | 1004 | 146 | 669 | 189 | |
| Age (y), mean ±SD | 54.31±8.83 | 56.29±8.84 | 53.11±8.29 | 57.00±9.78 | <0.001 |
| Men, n (%) | 441 (43.9) | 60 (41.1) | 296 (44.2) | 85 (45.0) | 0.75 |
| Married, n (%) | 942 (93.8) | 135 (92.5) | 633 (94.6) | 174 (92.1) | 0.33 |
| Education, n (%) | 0.003 | ||||
| Illiteracy or primary school | 399 (39.7) | 66 (45.2) | 238 (35.6) | 95 (50.3) | |
| Middle school | 483 (48.1) | 62 (42.5) | 345 (51.6) | 76 (40.2) | |
| High school or college | 122 (12.2) | 18 (12.3) | 86 (12.9) | 18 (9.5) | |
| Current smoking, n (%) | 192 (19.1) | 25 (17.1) | 124 (18.5) | 43 (22.8) | 0.34 |
| Current alcohol drinking, n (%) | 315 (31.4) | 43 (29.5) | 206 (30.8) | 66 (34.9) | 0.48 |
| BMI, kg/m2, mean ±SD | 25.29±3.40 | 24.99±3.61 | 25.45±3.40 | 24.93±3.18 | 0.08 |
| Hypertension, n (%) | 577 (57.8) | 76 (52.1) | 389 (58.6) | 112 (59.6) | 0.30 |
| Diabetes, n (%) | 112 (11.6) | 17 (12.1) | 73 (11.3) | 22 (12.0) | 0.95 |
| Dyslipidemia, n (%) | 235 (24.2) | 35 (24.8) | 156 (24.1) | 44 (23.9) | 0.98 |
| Coronary heart disease, n (%) | 29 (2.9) | 5 (3.4) | 20 (3.0) | 4 (2.1) | 0.75 |
| Daytime napping, n (%) | <0.001 | ||||
| Always | 302 (30.1) | 27 (18.5) | 187 (28.0) | 88 (46.6) | |
| Only in summer | 316 (31.5) | 40 (27.4) | 218 (32.6) | 58 (30.7) | |
| No | 386 (38.4) | 79 (54.1) | 264 (39.5) | 43 (22.8) | |
| Habitual snoring, n (%) | 0.41 | ||||
| Always | 263 (26.2) | 37 (25.3) | 185 (27.7) | 41 (21.7) | |
| Sometimes | 193 (19.2) | 32 (21.9) | 120 (17.9) | 41 (21.7) | |
| No or unknown | 548 (54.6) | 77 (52.7) | 364 (54.4) | 107 (56.6) | |
| Physical activity, n (%) | 0.37 | ||||
| Low | 72 (7.3) | 12 (8.3) | 45 (6.8) | 15 (8.1) | |
| Moderate | 174 (17.5) | 23 (23) | 110 (16.6) | 41 (22.2) | |
| High | 746 (75.2) | 110 (75.9) | 507 (76.7) | 129 (69.7) | |
| ASCVD risk, n (%) | 0.008 | ||||
| Low‐to‐intermediate risk | 658 (69.5) | 96 (69.1) | 453 (72.2) | 109 (60.2) | |
| High risk | 289 (30.5) | 43 (30.9) | 174 (27.8) | 72 (39.8) | |
| Serum hs‐CRP, mg/L | 1.38 (3.71) | 1.14 (1.55) | 1.51 (4.41) | 1.11 (1.56) | 0.36 |
| Follow‐up time, y | 3.95 (0.14) | 3.93 (0.11) | 3.95 (0.15) | 3.94 (0.14) | 0.35 |
ASCVD indicates atherosclerotic cardiovascular disease; BMI, body mass index; and hs‐CRP, high‐sensitivity C‐reactive protein.
Number of participants with missing data was 2 for BMI, 6 for hypertension, 35 for diabetes, 31 for dyslipidemia, 57 for ASCVD risk, 12 for physical activity, and 68 for serum hs‐CRP. In the subsequent analyses, categorical variables with missing data was replaced with a dummy variable and continuous variable with missing data was replaced with a mean value.
During the mean follow‐up of 3.95 (SD=0.14) years, 214 participants were detected with newly developed carotid plaques at the follow‐up examination. Short sleep duration (<7 versus 7–9 hours) was significantly associated with higher risk of carotid plaques after adjusting for multiple confounding variables (hazard ratio [HR]=1.58 [95% CI, 1.10–2.28]; P=0.01) (Table 2). When the sleep duration was analyzed as a continuous variable, per 1‐hour increase in sleep duration was associated with an ≈9% decreased risk of carotid plaques (HR=0.91 [95% CI, 0.84–0.99]; P=0.03). There was no significant statistical interaction of age groups (<55 versus ≥55 years) and sex with sleep duration on risk of incident carotid plaques (for the interaction, P=0.62 and P=0.93, respectively). The subgroup analyses stratified by age groups, sex, and various cardiovascular risk factors found no significant associations between sleep duration and carotid plaques in any stratum (Figure S1). We further evaluated the association between sleep duration and severity of carotid plaques. Short sleep duration was significantly associated with increased risks of maximum carotid plaque thickness (>2.34 mm (HR, 2.96 [95% CI, 1.38–6.36]; P=0.005), multiple carotid plaques (HR,2.57 [95% CI, 1.33–4.97]; P=0.005) after adjusting for multiple confounding variables (Table 3). When analyzing sleep duration as a continuous variable, an increased sleep duration was significantly associated with a reduced risk of multiple carotid plaques (P <0.05), but not with the risk of having greater maximum carotid plaque thickness (P >0.05) (Table 3).
Table 2.
Association of Sleep Duration With Incident Carotid Plaques From Cox Proportional Hazards Models (n=1004)
| Sleep duration | n/N | Hazard ratio (95% CI), incident carotid plaques | |||||
|---|---|---|---|---|---|---|---|
| Model 1 | P value | Model 2 | P value | Model 3 | P value | ||
| Sleep duration, categorical | |||||||
| 7 h | 43/146 | 1.77 (1.25–2.50) | 0.001 | 1.58 (1.10–2.26) | 0.01 | 1.58 (1.10–2.28) | 0.01 |
| 7–9 h | 125/669 | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | |||
| 9 h | 46/189 | 1.38 (0.98–1.93) | 0.07 | 1.06 (0.74–1.51) | 0.76 | 1.07 (0.74–1.53) | 0.73 |
| Sleep duration, continuous | |||||||
| Per 1‐h increase | 214/1004 | 0.94 (0.87–1.02) | 0.15 | 0.91 (0.84–0.99) | 0.02 | 0.91 (0.84–0.99) | 0.03 |
n/N indicates no. of cases with incident carotid plaques/no. of study participants. Model 1 was a crude model (unadjusted); Model 2 was adjusted for age, sex, marital status, education, current smoking, current alcohol drinking, hypertension, diabetes, dyslipidemia, body mass index, coronary heart disease, physical activity, and high‐sensitivity C‐reactive protein; Model 3 was adjusted for age, sex, marital status, education, current smoking, current alcohol drinking, hypertension, diabetes, dyslipidemia, body mass index, physical activity, high‐sensitivity C‐reactive protein, daytime napping, and habitual snoring.
Table 3.
Association of Sleep Duration With Characteristics of Carotid Plaques From Cox Proportional Hazards Models (n=1004)
| Sleep duration | n/N | HR (95% CI) | P value |
|---|---|---|---|
| Severe carotid plaques (maximum plaque thickness ≥2.34 mm vs no or maximum thickness ≤2.34 mm) | |||
| Categorical | |||
| 7 h | 13/146 | 2.96 (1.38–6.36) | 0.005 |
| 7–9 h | 20/669 | 1.00 (reference) | |
| 9 h | 17/189 | 2.38 (1.15–4.93) | 0.02 |
| Continuous | |||
| Per 1‐h increase | 50/1004 | 0.93 (0.78–1.10) | 0.39 |
| Multiple carotid plaques (≥2 plaques vs no or a single plaque) | |||
| Categorical | |||
| 7 h | 17/146 | 2.57 (1.33–4.97) | 0.005 |
| 7–9 h | 29/669 | 1.00 (reference) | |
| 9 h | 14/189 | 1.05 (0.52–2.12) | 0.88 |
| Continuous | |||
| Per 1‐h increase | 60/1004 | 0.84 (0.73–0.98) | 0.02 |
Hazard ratio and 95% CI were derived from the Cox regression models that were adjusted for age, sex, marital status, education, current smoking, current alcohol drinking, hypertension, diabetes, dyslipidemia, coronary heart disease, body mass index, physical activity, high‐sensitivity C‐reactive protein, daytime napping, and habitual snoring. N indicates no. of study participants and n indicates no. of cases with incident carotid plaques. and HR, hazard ratio.
We further conducted the analyses stratified by the 10‐year risk for ASCVD. Among participants with low‐to‐intermediate 10‐year risk for ASCVD (n=658, 99 with incident carotid plaques), a short sleep duration was still significantly associated with increased risks of incident carotid plaques (HR, 2.02 [95% CI, 1.20–3.37]; P=0.008), maximum carotid plaque thickness >2.34 mm (HR, 6.60 [95% CI, 2.17–20.10]; P=0.001), and multiple carotid plaques (HR, 5.49 [95% CI, 1.60–18.82]; P=0.007) (Table 4). Among participants with high 10‐year risk for ASCVD (n=289, 104 with incident carotid plaques), short sleep duration was not significantly associated with incident carotid plaques, maximum carotid plaque thickness, and multiple carotid plaques (Table 4).
Table 4.
Association of Sleep Duration With Incident Carotid Plaques by 10‐Year Atherosclerotic Cardiovascular Disease Risk From Cox Proportional Hazards Models (n=947)
| Sleep duration | Participants with low‐to‐intermediate 10‐y risk for ASCVD (n=658) | Participants with high 10‐y risk for ASCVD (n=289) | ||||
|---|---|---|---|---|---|---|
| n/N | HR (95% CI) | P value | n/N | HR (95% CI) | P value | |
| Presence of carotid plaques (yes vs no) | ||||||
| 7 h | 21/96 | 2.02 (1.20–3.37) | 0.008 | 20/43 | 1.46 (0.85–2.48) | 0.17 |
| 7–9 h | 62/453 | 1.00 (reference) | 57/174 | 1.00 (reference) | ||
| 9 h | 16/109 | 0.98 (0.54–1.76) | 0.94 | 27/72 | 1.13 (0.70–1.84) | 0.61 |
| Severe carotid plaques (maximum plaque thickness>2.34 mm vs no or maximum thickness ≤2.34 mm) | ||||||
| 7 h | 7/96 | 6.60 (2.17–20.10) | 0.001 | 5/43 | 2.19 (0.69–6.99) | 0.19 |
| 7–9 h | 8/453 | 1.00 (reference) | 10/174 | 1.00 (reference) | ||
| 9 h | 7/109 | 4.02 (1.26–12.83) | 0.02 | 9/72 | 1.99 (0.76–5.21) | 0.16 |
| Multiple carotid plaques (≥2 plaques vs no or a single plaque) | ||||||
| 7 h | 5/96 | 5.49 (1.60–18.82) | 0.007 | 10/43 | 2.16 (0.97–4.82) | 0.06 |
| 7–9 h | 7/453 | 1.00 (reference) | 20/174 | 1.00 (reference) | ||
| 9 h | 5/109 | 2.72 (0.76–9.75) | 0.12 | 9/72 | 1.11 (0.49–2.53) | 0.80 |
Of the 1004 participants, 57 were excluded from this analysis due to missing data on ASCVD risk. n/N indicates no. of cases with incident carotid plaques/no. of study participants. Hazard ratio and 95% CI of incident carotid plaques were derived from the models that were adjusted for sex, marital status, education, current alcohol drinking, body mass index, physical activity, high‐sensitivity C‐reactive protein, daytime napping, and habitual snoring. ASCVD indicates atherosclerotic cardiovascular disease; and HR, hazard ratio.
The restricted cubic spline analysis suggested a nonlinear trend in the association between sleep duration and the risk of incident carotid plaques (P for nonlinearity=0.07) (Figure S2). There was a nonlinear association of sleep duration with risk of having severe carotid plaque thickness (P for nonlinearity <0.001), with the inflection point being ≈8 hours, such that among participants with sleep duration ≤8 hours, a decreased sleep duration was significantly associated with an increased risk of severe carotid plaque thickness (per 1‐hour decrease in sleep duration, HR, 1.53 [95% CI, 1.14–2.04]; P=0.004), whereas among participants with sleep duration >8 hours, an increased sleep duration was associated with a nonsignificantly increased risk of severe carotid plaque thickness (per 1‐hour increase in sleep duration, HR, 1.63 [95% CI, 0.92–2.89]; P=0.09). Similarly, a nonlinear association was identified between sleep duration and multiple carotid plaques (P for nonlinearity=0.045), with the inflection point being ≈8.6 hours. Among participants with sleep duration ≤8.6 hours, a decreased sleep duration was significantly associated with an increased risk of multiple carotid plaques (per 1‐hour decrease in sleep duration, HR, 1.44 [95% CI, 1.12–1.85]; P=0.004), whereas among participants with sleep duration >8.6 hours, sleep duration was not significantly associated with the risk of multiple carotid plaques (per 1‐hour increase in sleep duration, HR, 1.25 [95% CI, 0.74–2.11]; P=0.40).
We examined the pattens of changes in sleep duration from baseline to follow‐up in association with carotid plaques detected at the follow‐up. Compared with persistent normal sleep duration, a persistent short sleep duration was significantly associated with increased risks of carotid plaques (in the fully adjusted model: OR, 2.08 [95% CI, 1.03–4.20]; P=0.04), whereas the significant associations of persistent long sleep duration and an increase in sleep duration with carotid plaques in the unadjusted models became statistically nonsignificant when controlling for multiple potential confounders (Table 5).
Table 5.
Association of Sleep Duration Changes From Baseline to Follow‐Up With Incident Carotid Plaques (n=916)
| Patterns of sleep duration changes | n/N | Odds ratio (95% CI), incident carotid plaques | |||||
|---|---|---|---|---|---|---|---|
| Model 1 | P value | Model 2 | P value | Model 3 | P value | ||
| Persistent normal (7–9 h) | 79/461 | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | |||
| Persistent short (<7 h) | 15/52 | 1.96 (1.03–3.74) | 0.04 | 1.98 (1.00–3.95) | 0.05 | 2.08 (1.03–4.20) | 0.04 |
| Persistent long (>9 h) | 14/40 | 2.60 (1.30–5.21) | 0.007 | 1.74 (0.80–3.76) | 0.16 | 1.80 (0.81–3.96) | 0.15 |
| Increase in sleep duration | 39/131 | 2.05 (1.31–3.20) | 0.002 | 1.60 (0.98–2.62) | 0.06 | 1.55 (0.94–2.56) | 0.08 |
| Decrease in sleep duration | 45/232 | 1.16 (0.78–1.75) | 0.46 | 0.94 (0.61–1.46) | 0.78 | 0.95 (0.61–1.49) | 0.84 |
Of the 1004 participants, 88 were excluded from this analysis due to missing data on sleep duration in the 2021 follow‐up examination. n/N indicates no. of cases with incident carotid plaques/no. of study participants. Model 1 was a crude model (unadjusted); Model 2 was adjusted for age, sex, marital status, education, current smoking, current alcohol drinking, hypertension, diabetes, dyslipidemia, body mass index, coronary heart disease, physical activity, high‐sensitivity C‐reactive protein, and time of follow‐up; Model 3 was adjusted for age, sex, marital status, education, current smoking, current alcohol drinking, hypertension, diabetes, dyslipidemia, coronary heart disease, body mass index, daytime napping, habitual snoring, physical activity, high‐sensitivity C‐reactive protein, and follow‐up time.
DISCUSSION
In this population‐based prospective cohort study of the rural Chinese population, we found that short sleep duration (<7 versus 7–9 hours) was associated with an increased risk of incident carotid plaques. Furthermore, when the severity and extent of incident carotid plaque were analyzed, short sleep duration (<7 versus 7–9 hours) was associated with increased risks of greater carotid plaque thickness and multiple carotid plaques. Notably, the aforementioned associations remained even among participants with low‐to‐intermediate traditional 10‐year ASCVD risk. To the best of our knowledge, this is the first community‐based prospective cohort study to investigate the longitudinal association of sleep duration with incident carotid plaques and the plaque severity.
The findings from our prospective cohort study of middle‐aged and older people, which were overall consistent with those from a few previous cross‐sectional studies, provided further evidence for the view that short sleep duration may be a risk factor for carotid atherosclerosis. For example, a cross‐sectional study of community‐dwelling adults in the Study of Health in Pomerania (SHIP) found that a sleep duration of 5 hours (versus 8 hours) was associated with higher intima‐media thickness. 16 Similarly, a population‐based cross‐sectional study of Chinese adults suggested that sleep duration <5 hours (versus ≥5 hours) was associated with an increased likelihood of carotid plaques. 17 The US CARDIA study of young adults also found a linear association of objectively assessed short sleep duration with increased intima‐media thickness in men but not in women. 18 Additionally, a population‐based study of middle‐aged adults in Spain who were free of cardiovascular disease showed that an objectively assessed short sleep duration (<6 versus 7–8 hours) was independently associated with subclinical multiterritorial atherosclerosis. 19 Of note, different cutoffs for normal sleep duration were used in these previous studies, making the results across studies not directly comparable. We used 7 to 9 hours as normal sleep duration and <7 hours as short sleep duration, which is in accordance with the Life's Essential 8 for adults recommended by the American Heart Association. 10 In line with these reports, when analyzing the patterns of changes in sleep duration over time, we found that persistent short sleep duration was associated with an increased likelihood of carotid plaques.
A few cross‐sectional studies have also suggested the association of long sleep duration with carotid plaques. 4 , 20 The cross‐sectional study from the Northern Manhattan cohort found that long sleep duration (≥9 versus 7 to <9 hours) was associated with an increased odds ratio of carotid plaques. 4 Two other community‐based studies in Niigata (Japan) and Pomerania (Germany) showed that a long sleep duration was associated with increased intima‐media thickness. 17 , 20 Our prospective cohort study did not show convincing evidence for the association of long sleep duration with incident carotid plaques. This difference may be partly explained by differences in demographic characteristics of the study population (eg, age, sex, and education) and study design (eg, cross‐sectional versus longitudinal study). For instance, the mean age of the study populations in those previous studies was nearly 10 years older than our study population. This is important because long sleep duration is often linked to older age and more comorbidity, and thus, the association between long sleep duration and carotid plaques may be confounded by those factors. Notably, although we found no significant association of long sleep duration with incident carotid plaques, our data did show that a long sleep duration (>9 versus 7–9 hours) was associated with greater maximum carotid plaque thickness and that restricted cubic spline analysis suggested a marginal association between longer sleep duration (>8 hours) and greater carotid plaque thickness. Furthermore, our study also showed that a persistent long sleep duration and an increase in sleep duration over time were associated with increased likelihoods of carotid plaques, although the associations became statistically marginal when controlling for a range of potential confounders (Table 5). Thus, the longitudinal association between long sleep duration and carotid plaques deserves further investigation in large‐scale population‐based cohort studies in the future.
The plaque number and thickness both represent the severity of atherosclerosis. Previous studies suggested that the progression of atherosclerosis and risk of vascular events were increased with an increasing number and thickness of carotid plaques. 7 , 8 , 21 Our cohort study indeed found that a short sleep duration was also associated with increased risks of greater carotid plaque thickness and multiple carotid plaques, suggesting that short sleep duration may be involved in the progression and development of complications of atherosclerosis. Taken together, evidence from our study and the current literature supports the role of a short sleep duration in carotid atherosclerosis, which provides insights into the risk stratification for preventive interventions.
Short sleep duration is often correlated with other sleep dimensions such as obstructive sleep apnea and daytime napping. 22 Snoring, a major feature of obstructive sleep apnea, and daytime napping have been associated with atherosclerosis, which might potentially confound the observed association between sleep duration and carotid plaques, but this issue has not been considered in the analysis of previous studies. 23 , 24 Our study did not show associations of snoring and daytime napping with increased risks of carotid plaques (Table S1). Importantly, the association between short sleep duration and carotid plaque was present independent of habitual snoring and daytime napping in our cohort study, indicating that sleep duration is an important sleep component that may contribute to carotid atherosclerosis.
We further analyzed the associations of sleep duration with incident carotid plaques stratified by the 10‐year ASCVD risk assessed with the approach from the prediction for ASCVD risk in China project. The prediction for ASCVD risk in China score is a reliable indicator for the 10‐year ASCVD risk among the Chinese adult population, and the score comprises traditional cardiovascular risk factors such as age, sex, blood pressure, diabetes, cholesterol, high‐density lipoprotein cholesterol, and smoking. Our study confirmed that the association between short sleep duration and an increased risk of incident carotid plaques remained even among individuals with low‐to‐intermediate 10‐year ASCVD risk. In the past few decades, along with optimal treatment and management of relevant traditional risk factors (eg, smoking, hypertension, diabetes, and high cholesterol), the incidence of cardiovascular events has steadily declined in many high‐income countries, but the residual risk remains a concern. 2 The strong association between short sleep duration and increased risk of incident carotid plaques among individuals with low‐to‐intermediate ASCVD risk revealed in our study suggests that short sleep duration may be a novel risk factor for atherosclerotic disorders beyond traditional risk factors, which supports the view that sleep is a crucial component of cardiovascular health. More importantly, short sleep duration is a modifiable dimension of sleep, which may be a potential target for interventions to reduce residual ASCVD risk.
Activated inflammation in response to sleep disturbances may play an important role in the association between short sleep duration and accelerated atherosclerosis. Inflammatory biomarkers, such as increased serum C‐reactive protein, interleukin‐6, and interferon‐γ, have been associated with short sleep duration or sleep deprivation. 25 , 26 , 27 Similarly, data from the US Multi‐Ethnic Study of Atherosclerosis showed that short sleep duration was associated with increased vascular inflammation assessed using hybrid positron emission tomography/magnetic resonance imaging. 28 Additionally, short sleep duration may also induce alterations in autonomic nervous system, endothelial dysfunction, oxidative stress, and metabolic dysregulation, thus promoting atherosclerosis. 25
This prospective cohort study engaged a middle‐aged and older rural population in China, a sociodemographic group that has been substantially underrepresented in the current literature of the research topic. Thus, findings from this study may help bridge the knowledge gaps. However, the results from our study should be interpreted in the context of the following limitations. Firstly, information on sleep duration, daytime napping, and habitual snoring was assessed via self‐report, which may be prone to recall bias and misclassification. Sleep health is a multidimensional construct, and objective and comprehensive assessment approaches are needed to better characterize sleep metrics. Secondly, although we accounted for a range of potential confounding factors in our analysis, the residual confounding cannot be completely ruled out due to the observational nature of the study. Thirdly, our cohort study had a relatively small sample and a short follow‐up period, which may have limited power to detect the weak‐to‐moderately‐strong associations between sleep duration and incident carotid plaques. Finally, the study participants were from 1 rural area of Chinese Han population, and approximately one‐fifth of participants who were free of carotid plaques at baseline were lost to follow‐up; thus, caution was required when generalizing our study results to other populations.
In conclusion, this population‐based prospective cohort study provides evidence that short sleep duration is a risk factor for incident carotid plaques in a rural Chinese population, even among individuals with low‐to‐intermediate 10‐year ASCVD risk. This underscores the importance of sufficient sleeping for cardiovascular health. Future large‐scale prospective cohort studies among ethnically, geographically, and socioculturally diverse populations are needed to increase the generalizability of these findings and to further explore the potential mechanisms linking short sleep duration with subclinical carotid atherosclerosis. This will pave the way for preventive interventions by targeting short sleep duration to reduce the occurrence and progression of carotid atherosclerosis, and thus, prevent ASCVD such as clinical stroke and coronary heart disease.
Sources of Funding
This study was supported in part by grants from the Department of Science and Technology of Shandong Province (ZR2017MH114, ZR2020QH109, and ZR2022LSW010), the National Natural Science Foundation of China (8171101298, 81971128, and 82201477), and the Ministry of Science and Technology of the People's Republic of China (2017YFC1310100). C. Qiu received grants from the Swedish Research Council (2017‐05819 and 2020‐01574) and the Swedish Foundation for International Cooperation in Research and Higher Education (CH2019‐8320), Stockholm, Sweden. This content is solely the responsibility of the authors and does not necessarily represent the official views of the funding sources.
Disclosures
None.
Supporting information
Table S1
Figures S1–S2
Acknowledgment
The authors would like to thank all the study participants, the staff of the participating hospitals, and the members of the RICAS Study (Rose Asymptomatic Intracranial Artery Stenosis) Steering Committee at Shandong Provincial Hospital, Jinan, China.
This manuscript was sent to Peng Li, PhD, Assistant Editor, for review by expert referees, editorial decision, and final disposition.
Supplemental Material is available at https://www.ahajournals.org/doi/suppl/10.1161/JAHA.124.039215
For Sources of Funding and Disclosures, see page 9.
Contributor Information
Chengxuan Qiu, Email: chengxuan.qiu@ki.se.
Qinjian Sun, Email: sqj1210@163.com.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Table S1
Figures S1–S2