The prevalence, awareness, treatment and control of dyslipidemia among adults in China

Accepted Manuscript The prevalence, awareness, treatment and control of dyslipidemia among adults in China Ling Pan, Zhenhua Yang, Yue Wu, Rui-Xing Yin, Yunhua Liao, Jinwei Wang, Bixia Gao, Luxia Zhang PII:

S0021-9150(16)30046-6

DOI:

10.1016/j.atherosclerosis.2016.02.006

Reference:

ATH 14484

To appear in:

Atherosclerosis

Received Date: 6 October 2015 Revised Date:

17 January 2016

Accepted Date: 2 February 2016

Please cite this article as: Pan L, Yang Z, Wu Y, Yin R-X, Liao Y, Wang J, Gao B, Zhang L, on behalf of the China National Survey of Chronic Kidney Disease Working Group, The prevalence, awareness, treatment and control of dyslipidemia among adults in China, Atherosclerosis (2016), doi: 10.1016/ j.atherosclerosis.2016.02.006. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT 1

The prevalence, awareness, treatment and control of dyslipidemia among adults

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in China

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Ling Pan12※, Zhenhua Yang12※, Yue Wu12※, Rui-Xing Yin5,Yunhua Liao12, Jinwei

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Wang34, Bixia Gao34, Luxia Zhang34 on behalf of the China National Survey of

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Chronic Kidney Disease Working Group

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(※These authors contributed equally to this work)

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Institution

1. Renal Division, Department of Medicine, First Affiliated Hospital of Guangxi

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Medical University;

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2. Guangxi Medical University Institute of Urinology; Nanning 530021, Guangxi

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Zhuang Autonomous Region, China;

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3. Renal Division, Department of Medicine, Peking University First Hospital, Beijing,

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China;

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4. Peking University Institute of Nephrology, Peking University Health Science

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Center, Beijing, China.

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5. Cardiology Division, Department of Medicine, First Affiliated Hospital of Guangxi

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Medical University;

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ACCEPTED MANUSCRIPT Corresponding author

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Yun-hua Liao, MD

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Renal Division, Department of Medicine, First Affiliated Hospital of Guangxi

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Medical University, Guangxi Medical University Institute of Urology, Nanning

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530021, Guangxi Zhuang Autonomous Region, China.

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Tel: +86-771-5356707

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Fax: +86-771-5356707

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E-mail: [email protected]

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ACCEPTED MANUSCRIPT Abstract

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Objectives: To analyze the prevalence, awareness, treatment, control and

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epidemiological characteristics of dyslipidemia in Chinese adults.

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Methods: In this cross-sectional study, we adopted a multi-stage, stratified sampling

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method to obtain representative samples of the general population aged > 18 years

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from different urban and rural regions in China. All subjects completed a lifestyle and

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medical history questionnaire and were examined for risk factors. Dyslipidemia was

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defined according to criteria of the 2007 Chinese Guidelines on Prevention and

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Treatment of Dyslipidemia in Adults. Continuous variables were compared using

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variance analysis. Multivariate logistic regression analysis was performed to explore

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the risk factors of dyslipidemia.

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Results: The prevalence of dyslipidemia was 34.0% overall, and 35.1%, and 26.3% in

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urban and rural areas, respectively. The prevalence of dyslipidemia was significantly

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higher in men than women (41.9% vs 32.5%; P < 0.001). Rates of awareness,

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treatment, and control were 31.0%, 19.5%, and 8.9%, respectively. Increasing age

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(OR=1.012; 95% CI:1.010, 1.014), male sex (OR=1.411; 95% CI:1.318, 1.510),

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obesity (OR=1.424; 95% CI:1.345, 1.507), cardiovascular disease (OR=1.343; 95%

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CI:1.125, 1.603), diabetes (OR=1.955; 95% CI:1.751, 2.182), hypertension

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(OR=1.481; 95% CI:1.391, 1.577) and hyperuricemia (OR=2.223; 95% CI:2.060,

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2.399) were independent risk factors of dyslipidemia.

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Conclusion: The prevalence of dyslipidemia among Chinese adults was high but

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awareness, treatment, and control of dyslipidemia were low. Urban high income

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earners and rural medium income earners shows higher prevalence. Low income

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ACCEPTED MANUSCRIPT earners in urban and rural population have the worst awareness treatment, and control

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rate. There is an increased need for closely monitoring and controlling high risk

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factors in the populations including postmenopausal women, unhealthy lifestyle

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peoples and patients with chronic non-communicable diseases.

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Keywords: dyslipidemia ; epidemiology; China; prevalence

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Background Cardiovascular diseases (CVD) rank highest among the leading cause of death in

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developed countries1 and most of developing countries as well as in China. A 2010

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report on Great Britain suggested that 1.8 million people died of cardiovascular

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diseases, 800000 of which was attributed to coronary heart disease and 490000 to

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stroke2. According to data released by the National Center for Cardiovascular Disease

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in China in 2010, the number of deaths caused by cardiovascular disease in

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China has accounted for 40.4%, becoming the first cause of death3.

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CVD mortality rates are still rising in china4. Dyslipidemia is the leading cause

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of atherosclerosis, which is inextricably linked with the development of CVD5. It is

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also an independent risk factor for the development of coronary heart diseases6 and

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cerebral ischemic stroke7. Although the prevalence of dyslipidemia and lipid level in

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Chinese adults is by far lower than that of many adults in western countries8, but with

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changes that comes along with rapid socioeconomic growth, improved standard of

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living and change of lifestyle, the prevalence of dyslipidemia has been gradually

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increasing6. Dyslipidemia poses a serious threat to people’s health in the general

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population. Tightly control of dyslipidemia promotes decrease in mortality and

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morbidity of CVD and therefore should be given attention. Epidemiology surveys of

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our country showed，successfully controlling lipid level can decrease the risks of

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ischemic CVD6. Early screening and preventive measures are equally significant in

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achieving these goals. Analysis of dyslipidemia in Chinese adults was made based on

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prevalence, awareness, treatment, control and epidemiological characteristics. Below

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is the current report of the results which provides direct guidelines to prevent and treat

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hyperlipidemia and cardiovascular diseases.

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Methods

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Research object

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The China National Survey of Chronic Kidney Disease, conducted from January

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2007, to October 2010, was a cross-sectional study designed to provide reliable data

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for the prevalence of chronic kidney disease and associated factors in adults in China.

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The details of the study population and methods have been published elsewhere9. This

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research adopts the multi-stage stratified sampling method to obtain representative

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samples of the general population over the age of 18. The study was approved by the

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Ethics Committee of Peking University First Hospital. A written informed consent

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was given by all participants before the collection of data and conduction of the

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research. 50550 people were invited, and a total of 47204 people agreed to participate

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in the research. The response rate was 93.0%. Finally, 43368 cases with complete

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blood lipid data were included and analyzed.

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Screening protocol and assessment criteria

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All on-site screenings were conducted and completed from September 2009 to

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September 2010. Data were collected in examination centers at local health stations or

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community clinics in the participant’s residential area. All participants completed a

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questionnaire including socio-demographic status (e.g., age, gender, income, level of

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education, etc.), past medical history (e.g., hypertension, diabetes mellitus, hepatitis,

ACCEPTED MANUSCRIPT CVD, stroke, hyperlipidemia, chronic kidney disease, etc.), lifestyle (e.g., smoking,

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physical activity, and alcohol consumption) and family health history (hypertension,

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hyperlipidemia, diabetes mellitus, kidney diseases, etc.) under the supervision of

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doctors, medical students, trained general practitioners and nurses. Participants’ blood

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and urine samples are taken. All blood and urine samples were analysed at the central

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laboratory in each province. All the laboratories involved successfully completed a

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standardization and competency programe. Fasting venous blood was drawn from

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subjects for the measurements of levels of total serum cholesterol (TC), triglyceride

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(TG),

low

density

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lipoprotein

(LDL)

and

high

density

lipoprotein

(HDL) by automatic biochemistry analyzer. TC and TG were estimated using

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enzymatic method with commercially available reagents while HDL and LDL using a

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timed-endpoint colorimetric method. Anthropometric measurements were obtained

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(e.g., blood pressure，weight，BMI, waist circumference and body height). The

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severity of hypertension was classified according to modified JNC-6 criteria. An

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average blood pressure was recorded for each participant after three conservative

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measurements with a minute interval between measurements using mercury

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sphygmomanometer. An average of two closely conservative blood pressure readings

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was recorded as the final blood pressure if the difference between measurements was

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greater than 10mmHg. Glucose oxidase measurements was used to ascertain fasting

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blood glucose level.

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Diagnostic criteria

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Dyslipidemia is defined according to current lipids levels or use of

ACCEPTED MANUSCRIPT anti-dyslipidemia medications in the past two weeks. The cut-off values for higher

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cholesterol, higher low density lipoprotein, lower high density lipoprotein and higher

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triglyceride were 6.22 mmol/L, 4.14 mmol/L, 1.04 mmol/L and 2.26 mmol/L,

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respectively6.

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Dyslipidemia awareness is the percentage of dyslipidemic people self-reported as

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diagnosed with dyslipidemia. Treatment ratio is defined as percentage of those who

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adopted interventions (drugs and lifestyle intervention). Control ratio refers to the

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proportion between dyslipidemic people with those treated and reached the lipid

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standard.

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Lipid control standard is defined as cholesterol < 6.22 mmol/l(240 mg/dL)

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and/or low density lipoprotein < 4.14 mmol/l(160 mg/dL) and/or high density

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lipoprotein > 1.04 mmol/l(40 mg/dL) and/or triglyceride < 2.26 mmol/l(200mg/dl).

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Statistical analyses

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Statistical analyses were made based on different age, gender, geographical

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locality (urban or rural residency; North and South), and economic development as

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well as the influence of socioeconomic growth on Chinese adults with dyslipidemia.

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Continuous variables between groups were compared using variance analysis while

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categorical variables between groups were compared using Chi-square test. Relevant

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variables of descriptive statistics in accordance with the presence of stratified analysis

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was conducted for dyslipidemia. Prevalence rate was adjusted by age and gender

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using the Population of China in 2009 as a standard population. Multivariate logistic

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regression analysis was performed to explore associated risk factors of

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ACCEPTED MANUSCRIPT dyslipidemia. Covariates included in the multivariable logistic regression models were

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age (year), sex, smoking, drinking, obesity, CKD, hypertension, diabetes,

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hyperuricaemia, CVD, region (north vs south), family history of diabetes, family

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history of hypertension, family history of CVD and family history of CKD, etc.

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Epidata software (version 3.1) was used for data entry and management. All p values

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are bilateral, and a p value of less than 0.05 was considered significant. Analyses were

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done with SAS software, (version 9.1 SAS Institute Inc, Cary, NC, United States).

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Results

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43368 subjects included 18199 (41.96%) male and 25169 (58.04%) female. The

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mean age was 50.24±14.80 years (male mean age was 50.08 ±15.40 years and female

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mean age was 50.36 ±14.34 years). The number of cases represented by urban

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participants was 24191 (55.78%) and that of rural participants was 19177 (44.22%).

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characteristics

of

participants

according

to

dyslipidemic

and

non-dyslipidemic status were shown in Table 1. Factors such as old age, male, urban

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participants, northern, higher income, high education, smoking, drinking, amount of

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physical activity, diabetes, hypertension, CKD, CVD, hyperglycemia, family history

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of high blood pressure, family history of CVD, family history of strokes, family

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history of diabetes, family history of CKD, long-term use antipyretic analgesics,

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central obesity, chronic kidney disease, high waist circumference, higher BMI, high

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uric acid, high blood pressure and low-eGFR had higher prevalence of dyslipidemia

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than normal population(P < 0.05, respectively), shown as Table 1.

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Table 2 presents prevalence of dyslipidemia among different age groups, gender,

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region (Northern and southern；urban and rural), income (urban GDP and rural GDP).

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After the adjustment, prevalence of dyslipidemia was 33.97%, the prevalence of

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hypercholesterolemia was 7.50%, decrease high density lipoprotein prevalence was

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15.31%,

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hypertriglyceridemia prevalence was 12.17%. The prevalence of dyslipidemia was

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significant higher in males than females (41.92% vs 32.47%, P < 0.001). There is an

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increase prevalence of dyslipidemia with increasing age in men and women (P <

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0.001, for both). Figure 1 presents women over the age of 50 have significant increase

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in the overall prevalence of dyslipidemia, with peak range ≥ 60 years; Figure 2

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presents men generally have increased prevalence with increasing age with peak

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range between 50-69 years. The prevalence of dyslipidemia is slightly higher in male

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than female before the age of 50. However, over the age of 50, female has a higher

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prevalence than male. A difference in prevalence between urban and rural areas was

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noted with urban being higher than rural areas (35.08% vs 26.33%, P < 0.001). High

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income earners in urban cities had a higher prevalence (P < 0.001) than middle/low

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income earners. Middle income earners in rural cities had a higher prevalence (P <

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0.001) than high/low income earners (shown in Figure 3 and 4) .

density

lipoprotein

prevalence

rate

was

7.96%,

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low

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elevated

The proportion of awareness was 31.01%, treatment proportion was 19.47%,

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and control proportion was 8.9% as shown in Table 3. Awareness, treatment and

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control proportion generally increases more obviously with increasing age among

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female, urban and northern residents of the country (P<0.001) when compared with

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their counterparts. Besides, those highly educated, with enough physical exercise,

ACCEPTED MANUSCRIPT relatively small workload and higher income earners, had a higher rate of awareness,

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treatment and successful control than those who are lowly educated, with less exercise,

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intensive workload and lower income earners (P<0.001). Higher income earners in

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rural population have the best awareness, treatment, control rate than their

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counterparts – middle/low income earners (P<0.001). Middle income earners in urban

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population have the best awareness, treatment, and control than their counterparts –

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high/low income earners (P<0.001). Both low income earners in urban and rural

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population have the worst awareness treatment, and control than other counterparts

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(P<0.001). In the dyslipidemia population, the proportion of the drug treatment,

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control diet, exercise and non conventional treatment is 7.72%, 14.28%, 12.20% and

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1.04%, respectively.

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Table 4 Multiple Logistic regression analysis also suggests age (increasing),

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gender (male), obesity, CVD, diabetes, hepertension, hyperuricaemia, family history

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of chronic kidney disease (CKD), family history of CVD, family history of diabetes,

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and non-minority are independent risk factors of dyslipidemia (P<0.001).

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Discussion

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Great progress has been made in the epidemiological studies of dyslipidemia in

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the past 20 years. Statistics from The National Health and Nutrition Examination

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Survey 2003-200610 showed that an estimated 53% of U.S. adults have lipid

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abnormalities, among which 27% have high LDL-C, 23% have low HDL-C, and 30%

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have high TG, 21% have mixed dyslipidemia (high LDL-C with either low HDL-C

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and/or high TG), with nearly 6% having all three lipid abnormalities. The Chinese

ACCEPTED MANUSCRIPT national nutrition and health survey in 2002 reported that the prevalence of

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dyslipidemia in Chinese adults was 18.6% and 22.2% in males and 15.9% in females,

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and the prevalence of hypercholesterolemia, hypertriglyceridemia, and low HDL

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cholesterol was 2.9%, 11.9%, and 7.4% respectively11. In 2008, a completed survey of

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adults in china over the age of 20 showed that the prevalence of hypercholesterolemia,

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low HDL cholesterol and high LDL cholesterol was 9.0%, 22.3% and 6.5%,

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respectively12. In this representative sample of Chinese adults of our study, the overall

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prevalence of dyslipidemia was 33.97% (Hypercholesterol proportion was 7.5 %,

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decrease high density lipoprotein proportion of 15.31 %, elevated low density

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lipoprotein proportion was 7.96%, and hypertriglycerides proportion was 12.17 %).

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Evidences showed that the prevalence of dyslipidemia in China has been increasing

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during

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hypertriglyceridemia are two major types of dyslipidemia in Chinese adults. The

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results are consistent with the large survey of domestic in 2002 to 201011-13. Robust

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evidence from several large epidemiological investigations in China had suggested

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that low HDL-cholesterol is most common part of dyslipidemia in China. Previous

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studies have shown a reverse relationship between high-density lipoprotein

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cholesterol (HDL-C) level and cardiovascular disease (CVD) risk14. HDL-cholesterol

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is believed to be protective because it increases the cholesterol efflux15. Recent studies

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also found that the ratio of TG/HDL-C is an independent risk factor for cardiovascular

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disease and an indirect assessment for insulin resistance16, which needs further

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confirmation.

past

decade.

Our

research

showed

that

low

HDL-C

and

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ACCEPTED MANUSCRIPT However, the main types of dyslipidemia in western countries were high

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cholesterol and high LDL-C. The difference may be related to low dietary fat

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and cholesterol intake in Chinese residents. The 2010 overall rate of prevalence of

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CVD in American was 35.5%17, while the 2010 overall rate of prevalence of CVD in

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China was 16.8%18. As is known to all, dyslipidemia was one of the major risk factors

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of CVD, and cohort study showed that the serum cholesterol or LDL are major risk

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factors for coronary heart disease and ischemic stroke5, 19. Varieties of guidelines

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calling for strict LDL control goal are effective in reducing the morbidity and

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mortality of CVD and thus improve clinical outcomes20. Therefore, the difference in

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types of dyslipidemia may be the cause of lower prevalence of heart disease in China

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than in America21, 22.

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Dyslipidemia is a major pathogenic factor of atherosclerosis, and one of the

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independent risk factors for cardiovascular disease such as coronary heart disease and

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stroke. Increasing the awareness and management of patients with dyslipidemia has a

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positive impact on cardiovascular disease prevention. Despite the rising prevalence in

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china, the proportion of awareness, treatment, and control is low. A China survey in

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2008 showed that among all participants who had borderline high total cholesterol ( ≥

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5.18 mmol/l) or who reported using cholesterol-lowering medications, the proportions

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of those who were aware of their condition were 12.8% in men and 9.3% in women,

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the proportions of those who were treated were 6.1% in men and 4.1% in women, and

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the proportions of those who had a total cholesterol concentration < 5.18 mmol/l were

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3.3% in men and 2.2% in women12. In 2010, Li et al. reported that the awareness,

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ACCEPTED MANUSCRIPT treatment and control of dyslipidemia in Chinese adults were 10.93%, 6.84%, 3.53%,

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respectively23. Among the population who were young, or who were from rural area

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or western China, the rates were even lower23. Our study showed that the awareness,

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treatment and control of dyslipidemia in Chinese adults were 31.01%, 19.47% and

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8.9%, respectively. Over the past decade, the great improvements in LDL-C goal

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attainment have been made in China. Results of the DYSlipidemia International

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Study-China (DYSIS-China) in 2012, a cross-sectional trial included 25,697 patients

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treated with lipid-lowering drugs, showed that the rate of statins treatment in

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hospitalized patients was 88.9%. 38.5% of patients did not achieve the therapeutic

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goal for low-density lipoprotein cholesterol (LDL-C), either as a single lipid anomaly

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or associated with low high-density lipoprotein cholesterol (HDL-C), elevated

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triglycerides, or both24. The awareness, treatment and control of dyslipidemia in our

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research compared with survey on nationwide by 2002 to 2008 were increased. This

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showed that in recent years, with the attention increasingly given to screening, health

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education and intervene therapy, China's adult disease prevention and awareness is

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being improved.

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In 2002, the prevalence of dyslipidemia in urban and rural areas was 21.0% and

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17.7%, respectively. In our study, the prevalence of dyslipidemia in urban and rural

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areas was 35.08% and 26.33%, respectively. Unlike developed countries, there have

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been tremendous changes in China's urban and rural areas, socioeconomic status and

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lifestyle within the past 10 years. Our study suggests high-income people in cities and

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middle-income people in the countryside are higher risk groups and should be the

ACCEPTED MANUSCRIPT focus for monitoring and controlling blood lipid. The treatment, control and

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successful control rates in both the rural and urban low-income earners are low and

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there is need for increase health care work, publicity, and education for low-income

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groups.

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Our study showed the incidence of dyslipidemia is still higher in males than in females（41.92% vs 32.47%）, similar with

the study results of 2002（22.2% vs

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15.9%）. In the past ten years, this difference is growing, which may be associated

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with poor diet habits and lifestyle of males. Although the increase of the prevalence of

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dyslipidemia in male was higher than in females，the rate of awareness, treatment and

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control in male was significantly lower than in females. Our study shows that, the rate

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of awareness, treatment and control in male was 30.12%, 18.90% and 7.27%, while in

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female was 31.84%, 20.01% and 9.62%, respectively. Males had worse attentions

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than females, so males should be the key objects of prevention and treatment. But

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postmenopausal women show high prevalence in relation to high-density lipoprotein

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levels. The Chinese national nutrition and health survey in 2002 and the China

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chronic disease surveillance survey in 2010 reported that the levels of total

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cholesterol and low density lipoprotein cholesterol in women aged 50 years and above

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were significantly higher than that of males of the same age8, 13, which consistent with

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the findings of our survey. Europe and America dyslipidemia management guidelines

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considered postmenopausal women as special populations3,

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dyslipidemia management

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priority management group. The hormonal changes of menopause are associated with

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guidelines

also post

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; our country's

postmenopausal

women as

a

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atherogenic

lipid

profile.

Many

researches

showed

that

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the estrogen replacement therapy in postmenopausal women can effectively prevent

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the occurrence of coronary heart disease, and other researches showed that therapy

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with estrogen plus progestin has beneficial effects on lipoprotein levels26. On the

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other hand, estrogen replacement therapy also increased triglycerides and very

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low-density lipoprotein cholesterol27. This provides both an opportunity and a

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challenge for the aggressive management of dyslipidemia.

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In addition, chronic non-communicable diseases such as obesity, hypertension,

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hyperglycemia, uremia, CKD and cardio-cerebrovascular disease are risk factors of

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hyperlipidemia. Patients with underlying chronic disease are at higher prevalence for

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hyperlipidemia and should be carefully monitored. There are similar founds in other

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foreign and domestic researches. Our study also suggests that obesity, smoking,

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drinking, inadequate exercise, increased work intensity, northerner，increased BMI,

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and increased waist circumference are associated risk factors for dyslipidemia.

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Therefore a good lifestyle, healthy diet, as well as exercise are also crucial in

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controlling dyslipidemia. Presence of dyslipidemia was significantly associated with

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increasing age, male, urban region, higher body mass index, lower income, higher

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blood glucose concentration, higher diastolic blood pressure, smoking, high

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cholesterol diet and sedentary lifestyle10, 28. Lifestyle modifications can have similar

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therapeutic effects as statins that are widely used in lowering blood lipid levels and

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can effectively control blood lipid levels, thereby reduce the prevalence of CVD.

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Our research adopted the group investigation standard design and was conducted

ACCEPTED MANUSCRIPT based on the strict quality control to ensure a good representation of the study

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population as well as reasonable research methods and quality control to ensure the

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reliability of data obtained. But our research also had some limitations. To begin with,

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our judgment in this study was based on fasting blood glucose and diabetic history;

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postprandial blood glucose and oral glucose tolerance test were not measured.

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Secondly, this study is a cross-sectional study without strict follow-up desigh,, which

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is prone to be affected by bias and unmeasured confounding, especially the causal

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relationship of chronic noncommunicable diseases.

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In conclusion, there is a high prevalence of dyslipidemia among adults in China,

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and the prevalence of dyslipidemia in China has been increasing. Awareness,

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treatment and control rate are not optimistic; there is an increased need for closely

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monitoring and controlling high risk factors including postmenopausal women,

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unhealthy lifestyle populations and patients with chronic non-communicable diseases.

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Free screening protocols, increased publicity and lifestyle modifications should be

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equally emphasized. Moreover, urban high income earners and rural medium income

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earners show higher prevalence and need further prevention and control. Awareness,

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control and compliance rate in low income earners are still low, and there is need for

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increase health care work, publicity, and education.

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Financial disclosure

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The research support for this work was provided by the National Key

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Technology R&D Program during the 11th Five-Year Period from the Ministry of

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Science and Technology of the People’s Republic of China (2007BAI04B10); the

ACCEPTED MANUSCRIPT Research Special Fund for Public Welfare Industry of Health from National Health

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and Family Planning Commission of the People’s Republic of China (201002010);

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National Key Technology R&D Program of the Ministry of Science and Technology

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(2011BAI10B01); Establishment of Early Diagnosis Pathway and Model for

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Evaluating Progression of Chronic Kidney Disease (D131100004713007) from the

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Beijing Science and Technology Committee; the Program for New Century Excellent

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Talents in University (BMU2009131) from the Ministry of Education of the People’s

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Republic of China; the grants for the Capital Development Funding (2009-Z-SQ01)

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from the Beijing Municipal Health Bureau; the grants for the Early Detection and

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Prevention of noncommunicable Chronic Diseases from the International Society of

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Nephrology Research Committee; and the grants from the China Health and Medical

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Development Foundation.

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References

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[1] Roger, VL, Go, AS, Lloyd-Jones, DM, et al., Heart disease and stroke statistics--2011 update: a

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report from the American Heart Association, Circulation, 2011;123:e18-e209. [2] Rabar, S, Harker, M, O'Flynn, N, et al., Lipid modification and cardiovascular risk assessment for

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the primary and secondary prevention of cardiovascular disease: summary of updated NICE guidance, BMJ, 2014;349:g4356.

[3] Reiner, Z, Catapano, AL, De Backer, G, et al., [ESC/EAS Guidelines for the management of dyslipidaemias], Revista espanola de cardiologia, 2011;64:1168 e1161-1168 e1160. [4] Beaglehole, R, Global cardiovascular disease prevention: time to get serious, Lancet, 2001;358:661-663.

[5] Expert Panel on Detection, E and Treatment of High Blood Cholesterol in, A, Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III), Jama, 2001;285:2486-2497. [6] Joint Committee for Developing Chinese guidelines on, P and Treatment of Dyslipidemia in, A, [Chinese guidelines on prevention and treatment of dyslipidemia in adults], Zhonghua xin xue guan bing za zhi, 2007;35:390-419.

ACCEPTED MANUSCRIPT [7] Pisciotta, L, Bertolini, S and Pende, A, Lipoproteins, Stroke And Statins, Current vascular pharmacology, 2013. [8] Zhao, WH, Zhang, J, You, Y, et al., [Epidemiologic characteristics of dyslipidemia in people aged 18 years and over in China], Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine], 2005;39:306-310. [9] Zhang, L, Wang, F, Wang, L, et al., Prevalence of chronic kidney disease in China: a cross-sectional survey, Lancet, 2012;379:815-822.

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[10] Toth, PP, Potter, D and Ming, EE, Prevalence of lipid abnormalities in the United States: the National Health and Nutrition Examination Survey 2003-2006, Journal of clinical lipidology, 2012;6:325-330.

[11] Wu, Y, Huxley, R, Li, L, et al., Prevalence, awareness, treatment, and control of hypertension in China: data from the China National Nutrition and Health Survey 2002, Circulation,

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2008;118:2679-2686.

[12] Yang, W, Xiao, J, Yang, Z, et al., Serum lipids and lipoproteins in Chinese men and women, Circulation, 2012;125:2212-2221.

[13] Li, JH, Wang, LM, Li, YC, et al., [Epidemiologic characteristics of dyslipidemia in Chinese adults

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2010], Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine], 2012;46:414-418. [14] Feig, JE, Hewing, B, Smith, JD, et al., High-density lipoprotein and atherosclerosis regression: evidence from preclinical and clinical studies, Circulation research, 2014;114:205-213. [15] van de Woestijne, AP, van der Graaf, Y, Liem, AH, et al., Low high-density lipoprotein cholesterol is not a risk factor for recurrent vascular events in patients with vascular disease on intensive lipid-lowering medication, Journal of the American College of Cardiology, 2013;62:1834-1841. [16] Sonmez, A, Yilmaz, MI, Saglam, M, et al., The role of plasma triglyceride/high-density

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lipoprotein cholesterol ratio to predict cardiovascular outcomes in chronic kidney disease, Lipids in health and disease, 2015;14:29.

[17] Go, AS, Mozaffarian, D, Roger, VL, et al., Executive summary: heart disease and stroke statistics--2014 update: a report from the American Heart Association, Circulation, 2014;129:399-410. [18] Hu, SS, Kong, LZ, Gao, RL, et al., Outline of the report on cardiovascular disease in China, 2010,

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Biomedical and environmental sciences : BES, 2012;25:251-256. [19] Zhang, X, Patel, A, Horibe, H, et al., Cholesterol, coronary heart disease, and stroke in the Asia Pacific region, International journal of epidemiology, 2003;32:563-572. [20] Grundy, SM, Cleeman, JI, Merz, CN, et al., Implications of recent clinical trials for the National

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Cholesterol Education Program Adult Treatment Panel III Guidelines, Journal of the American College of Cardiology, 2004;44:720-732. [21] Rosamond, W, Flegal, K, Furie, K, et al., Heart disease and stroke statistics--2008 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee, Circulation, 2008;117:e25-146. [22] Ford, ES and Capewell, S, Coronary heart disease mortality among young adults in the U.S. from 1980 through 2002: concealed leveling of mortality rates, Journal of the American College of Cardiology, 2007;50:2128-2132. [23] Li, JH, Wang, LM, Mi, SQ, et al., [Awareness rate, treatment rate and control rate of dyslipidemia in Chinese adults, 2010], Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine], 2012;46:687-691. [24] Wang, F, Ye, P, Hu, D, et al., Lipid-lowering therapy and lipid goal attainment in patients with

ACCEPTED MANUSCRIPT metabolic syndrome in China: subgroup analysis of the Dyslipidemia International Study-China (DYSIS-China), Atherosclerosis, 2014;237:99-105. [25] Jellinger, PS, Smith, DA, Mehta, AE, et al., American Association of Clinical Endocrinologists' Guidelines for Management of Dyslipidemia and Prevention of Atherosclerosis, Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists, 2012;18 Suppl 1:1-78. lipid metabolism], Clinical calcium, 2007;17:1366-1371.

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[26] Wakatsuki, A, [Hormone replacement Up-to-date. Effects of estrogen replacement therapy on [27] Utian, WH, Archer, DF, Bachmann, GA, et al., Estrogen and progestogen use in postmenopausal women: July 2008 position statement of The North American Menopause Society, Menopause (New York, N.Y.), 2008;15:584-602.

[28] Wang, S, Xu, L, Jonas, JB, et al., Prevalence and associated factors of dyslipidemia in the adult Chinese population, PloS one, 2011;6:e17326.

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ACCEPTED MANUSCRIPT Characteristics of participants according to dyslipidemia status

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Table 1

ACCEPTED MANUSCRIPT Dyslipidemia Number

Normal

P

15801

27567

Age (years)

53.79±13.88

48.22±14.92

<0.001

Gender (male)

7629(48.28)

10570(38.34)

<0.001

Rural residents (%)

5551(35.13)

13626(49.43)

<0.001

Family Income ( per month)

<0.001 1034(8.14)

2908(11.90)

501-1000

1983(15.62)

4489(19.02)

1001-3000

5189(40.86)

9380(39.75)

3001-5000

2827(22.26)

4409(18.69)

5001-10000

1367(10.76)

2028(8.59)

≥10000

298(2.35)

481(2.04)

Have health insurance (%)

13476(87.91)

Currently smoke (%)

4260(26.96)

Currently drink (%) Exercise ≥3.5 hr/week History of kidney disease

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7182(45.62)

11539(41.96)

<0.001

23043(86.83)

0.0014

6033(21.88)

<0.001

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≥ High school education (%)

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≤500

4279(27.08)

7446(23.38)

<0.001

4848(39.92)

6364(28.40)

<0.001

971(6.15)

1239(4.49)

<0.001

607(3.84)

783(2.84)

<0.001

623(4.31)

437(1.74)

<0.001

1937(12.27)

1183(4.29)

<0.001

4068(25.75)

5905(21.42)

<0.001

Systolic blood pressure (mmHg)

132.00±21.05

124.63±20.37

<0.001

Diastolic blood pressure (mmHg)

82.60±11.61

78.73±11.50

<0.001

25.19±3.60

23.21±3.49

<0.001

Chronic use of NSAIDS (%) History of cardiovascular disease (%) a

Diabetes (%)

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Family history of hypertension (%)

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BMI (kg/m ) BMI categories

<0.001

325(2.07)

1747(6.38)

18.5≤ BMI<24.0 (%)

5569(35.55)

15490(56.59)

24.0≤ BMI<28.0 (%)

6635(42.36)

7703(28.14)

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BMI<18.5 (%)

BMI≥28.0 (%)

3138(20.03)

2430(8.88)

84.84±10.18

78.50±11.20

<0.001

7538(47.71)

8648(31.37)

<0.001

326.19±98.99

283.92±84.16

<0.001

Cholesterol (mmol/L)

5.28±1.21

4.57±0.74

<0.001

Triglyceride (mmol/L)

1.99±1.09

1.00±0.44

<0.001

LDL cholesterol (mmol/L)

3.37±1.02

2.68±0.68

<0.001

HDL cholesterol (mmol/L)

1.23±0.36

1.48±0.30

<0.001

Serum Creatinine (µmol/L)

76.17±21.60

72.60±20.64

<0.001

eGFR (mL/min per 1·73m²)

98.90±26.90

104.50±28.84

<0.001

7.41(3.72,15.55)

6.56(3.28,13.11)

<0.001

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Waist circumference (cm) b

Central obesity (%)

Uric acid (µmol/L)

c

ACR (mg/g) Region

0.0008 North

8149(51.58)

13756(49.90)

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7650(48.42)

13810(50.10)

Minority (%)

1136(7.19)

3258(11.82)

<0.001

1757(11.55)

2194(8.15)

<0.001

Hyperuricaemia （%）

2308(22.26)

1974(10.21)

＜0.001

Stroke（%）

444（2.94）

344（1.32）

＜0.001

d

CKD （%） e

f

Hypertension （%）

7336（46.72）

7726（28.19）

＜0.001

Family history of

CHD (%)

1313（8.31）

1733（6.29）

＜0.001

Family history of

Diabete (%)

1602（5.81）

＜0.001

608（3.83）

786（2.85）

＜0.001

Family history of

536（3.39）

798（2.89）

0.0039

CKD (%)

a

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1362（8.62）

Family history of Stroke (%)

Diabetes was defined by fasting blood glucose (FBG) ≥7 mmol/L and/or diagnosed of diabetes mellitus

and currently on anti-glycemic agents. b

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Central Obesity was defined by waist circumference >90cm for male and >80cm for female.

c

Urinary albumin to creatinine ratio (ACR) was calculated. Patients with ACR higher than 30mg/g

creatinine were defined as having albuminuria. ACR deviated from normal distribution, represented by

means of Wilcoxon rank sum test. d

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median represents 25% and 75% of quantile distribution obtained by comparing data between groups by

The diagnosis of CKD is made based on one of these criteria: albuminuria, decreased renal function.

Decreased renal function was defined as an eGFR less than 60 mL/min/1.73 m2, the eGFR was calculated using the CKD-EPI equation. e

Hyperuremia was defined by plasma uric acid concentration >422 umol/L for men and >363 umol/L for

women. f

Hypertension was defined by systolic blood pressure(SBP) ≥140 mm Hg and/or diastolic blood pressure

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(DBP) ≥90 mm Hg, and/or diagnosed of hypertension and is currently on hypertensive medications.

ACCEPTED MANUSCRIPT Prevalence of dyslipidemia in Chinese population

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Table 2

ACCEPTED MANUSCRIPT H-TC

H-LDL

L-HDL

H-TG

dyslipidemia

Total

4115(9.49%)

4378(10.10%)

6185(14.26%)

5520(12.73%)

15801(36.43%)

age/sex adjusted

4115(7.50%)

4378(7.96%)

6185(15.31%)

5520(12.17%)

13753(33.97%)

18-29

49(2.41%)

43(2.12%)

417(20.52%)

157(7.73%)

562(27.66%)

30-39

140(5.12%)

173(6.33%)

557(20.37%)

472(17.26%)

1042(38.11%)

40-49

340(8.22%)

355(8.58%)

810(19.58%)

860(20.79%)

1804(43.61%)

50-59

384(8.94%)

448(10.43%)

909(21.16%)

772(17.97%)

2011(46.81%)

60-69

318(11.40%)

370(13.27%)

551(19.76%)

400(14.34%)

1262(45.25%)

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Men

297(13.43%)

398(18.00%)

239(10.81%)

948(42.88%)

1686(9.26%)

3642(20.01%)

2900(15.93%)

7629(41.92%)

p<0.001

p<0.001

P=0.068

18-29

43(1.97%)

38(1.74%)

190(8.70%)

30-39

111(3.08%)

88(2.44%)

40-49

287(4.57%)

304(4.84%)

50-59

905(13.80%)

60-69 ≥70

Total

622(9.90%)

474(7.54%)

1474(23.46%)

915(13.95%)

696(10.61%)

858(13.08%)

2619(39.94%)

771(19.55%)

839(21.27%)

467(11.84%)

637(16.15%)

1672(50.00%)

515(19.85%)

508(19.58%)

273(10.52%)

395(15.23%)

1208(46.57%)

2632(10.46%)

2692(10.70%)

2543(10.10%)

2620(10.41%)

8172(32.47%)

p<0.001

p<0.001

p<0.001

p<0.001

p<0.001

P=0.515

P=0.183

P=0.0008

2483(11.57%)

3084(14.37%)

2685(12.51%)

7650(35.65%)

1895(8.65%)

3100(14.15%)

2834(12.94%)

8149(37.20%)

P<0.001

P<0.001

P<0.001

P<0.001

646(8.52%)

1893(24.96%)

879(11.59%)

3240(42.72%)

North

1534(7.00%) P<0.001

GDP per head, 525(6.92%)

969(10.14%)

967(10.12%)

1297(13.57%)

1505(15.74%)

3867(40.45%)

1253(17.78%)

1483(21.04%)

746(10.59%)

940(13.34%)

3143(44.60%)

2747(12.81%)

3096(12.80%)

3936(16.27%)

3324(13.74%)

8704(35.08%)

P<0.001

P<0.001

P<0.001

p<0.001

P<0.001

369(5.54%)

244(3.67%)

588(8.84%)

631(9.48%)

1385(20.81%)

608(9.67%)

642(10.21%)

865(13.75%)

650(10.33%)

2135(33.94%)

391(6.27%)

396(6.35%)

796(12.77%)

915(14.68%)

2031(32.59%)

1368(7.13%)

1282(6.69%)

2249(11.73%)

2196(11.45%)

5049(26.33%)

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GDP per head,

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p<0.001

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2581(12.03%)

tertile 2 (4.6-7.9)

301(13.70%) 598(16.58%)

South

GDP per head,

80(3.66%)

176(4.88%)

p<0.001

Urban

P=0.031

295(8.18%)

Total Region

p<0.001

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Women

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252(11.40%) 1483(8.15%)

≥70

tertile 3 (8.8-22.4) Total Rural

GDP per head,

tertile 1 (0.2-2.3) GDP per head, tertile 2 (2.4-3.6) GDP per head, tertile 3 (2.4-7.5) Total

GDP per head was based on data from the subdistrict, which is why the tertiles do not cover all values.GDP=gross domestic product (per CN\10 000).

ACCEPTED MANUSCRIPT Awareness, treatment and control of dyslipidemia Awareness (%)

Treatment (%)

Control (%)

4891(31.01%)

3077(19.47%)

1341(8.9%)

X2=547.977

X2=302.714

X2=111.495

P<0.001

P<0.001

P<0.001

18-29

40(4.64%)

30(3.48%)

15(1.74%)

30-39

292(17.84%)

166(10.12%)

75(4.57%)

40-49

946(28.89%)

623(19.01%)

50-59

1667(36.06%)

1103(23.82%)

60-69

1205(37.38%)

707(21.86%)

≥70

741(34.47%)

448(20.78%)

X2=5.453

X2=3.077

P=0.0195

P<0.001

male

2296(30.12%)

1442(18.90%)

555(7.27%)

female

2595(31.84%)

1635(20.01%)

786(9.62%)

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Table 3

X2=1500.312

X2=637.393

P<0.001

P<0.001

526(6.88%)

207(2.71%)

2550(31.29%)

1133(13.90%)

X2=74.630

X2=70.581

P<0.001

P<0.001

681(21.02%)

247(7.62%)

1615(41.80%)

1028(26.58%)

496(12.83%)

1218(39.01%)

572(18.20%)

249(7.92%)

X2=153.441

X2=111.853

X2=16.809

P<0.001

P<0.001

PP=0.0002

118(8.53%)

84(6.06%)

55(3.97%)

483(22.63%)

331(15.50%)

150(7.03%)

505(24.88%)

381(18.76%)

144(7.09%)

X2=460.966

X2=291.726

X2=83.333

P<0.001

P<0.001

P<0.001

< high school education

2030(23.76%)

1244(14.53%)

567(6.62%)

≥ high school education

2844(39.67%)

1821(25.36%)

768(10.69%)

X2=203.240

X2=112.981

X2=30.105

P<0.001

P<0.001

P<0.001

1727(30.34%)

880(15.42%)

378(6.62%)

Total

X2=907.957 Region P<0.001 South

1489(19.54%)

North

3401(41.75%) X2=123.745

Urban P<0.001 GDP per head, tertile 1 952(29.40%)

270(8.24%)

484(10.45%)

286(8.84%)

211(9.79%)

X2=27.897

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P<0.001

GDP per head, tertile 2 (4.6-7.9) GDP per head, tertile 3 (8.8-22.4)

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GDP per head, tertile 1

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(0.2-2.3)

GDP per head, tertile 2 (2.4-3.6)

GDP per head, tertile 3 (2.4-7.5)

Education

Occupation Mild

ACCEPTED MANUSCRIPT Morderate

471(20.49%)

211(9.15%)

100(4.34%)

Heavy

154(12.76%)

73(6.05%)

40(3.31%)

X2=395.673

X2=579.937

X2=190.112

P<0.001

P<0.001

P<0.001

<3.5 hr/week

1948(26.71%)

1265(17.34%)

563(7.72%)

≥3.5 hr/week

2138(44.13%)

1778(36.67%)

760(15.68%)

Exercise

values.GDP=gross domestic product (per CN\10 000).

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GDP per head was based on data from the subdistrict, which is why the tertiles do not cover all

Mild intensity physical activity is difined 75% of the time sitting or standing at work, 25% of the time standing activities; Morderate intensity physical activity is difined 25% of the time sitting or standing at work, 75% of the time at particular occupational activities, such as driving and lathe operation; Heavy intensity physical activity is

difined 40% of the time sitting or standing at work, 60% of the time at special professional activities, such as

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agricultural labor, sports activities.

Exercise including physical exercise or recreational exercise, such as walking, dancing, running and so on, but

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ACCEPTED MANUSCRIPT Table 4

Risk factors associated with dyslipidemia

Adjusted OR

Wald

Risk factors

OR 95%CI

2

evaluation

1.014 1.510 1.507 2.182 1.603 1.098 1.018 1.160 1.718 1.268 2.399 1.577 1.718 1.362 1.571

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OR: odds ratio, CI: confidence interval

1.010 1.318 1.345 1.751 1.125 0.922 0.874 1.017 1.300 0.942 2.060 1.391 1.300 0.935 1.062

125.5105 97.8315 148.3175 143.0643 10.6554 0.0203 2.2433 6.0204 146.3644 1.3722 422.2398 151.7255 31.7760 1.5938 6.5563

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vs female) Central Obesity (yes vs no) Diabete (yes vs no) CVD (yes vs no) CKD (yes vs no) Currentl Drink (yes vs no) Region (North vs South) Minority (yes vs no) Chronic use of NSAIDS (yes vs no) Hyperuricaemia (yes vs no) Hypertension (yes vs no) Family history of Diabete (yes vs no) Family history of Stroke (yes vs no) Family history of CKD (yes vs no)

Upper

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Lower

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1.012 1.411 1.424 1.955 1.343 1.006 0.944 1.086 1.494 1.093 2.223 1.481 1.494 1.129 1.292

Age (years)

χ Value

P Value

＜0.001 ＜0.001 ＜0.001 ＜0.001 0.0011 0.8868 0.1342 0.0141 ＜0.001 0.2414 ＜0.001 ＜0.001 ＜0.001 0.2068 0.0105

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ACCEPTED MANUSCRIPT


Update in epidemiology of dyslipidemia in Chinese adults.
The prevalence of dyslipidemia in China has been increasing during the past decade.

adults.

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Postmenopausal women show high prevalence.

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L-HDL and H-TG are major two types of dyslipidemia in Chinese