Control of cardiovascular disease risk factors among patients with type II diabetes in a primary-care setting in Beijing

Accepted Manuscript Control of cardiovascular disease risk factors among patients with type 2 diabetes in a primary care setting in Beijing Hui-Juan Zuo, Wen-Hua Wang, Li-Qun Deng, Jiang-Lian Su PII:

S1933-1711(17)30419-9

DOI:

10.1016/j.jash.2017.12.006

Reference:

JASH 1109

To appear in:

Journal of the American Society of Hypertension

Received Date: 28 October 2017 Accepted Date: 10 December 2017

Please cite this article as: Zuo H-J, Wang W-H, Deng L-Q, Su J-L, Control of cardiovascular disease risk factors among patients with type 2 diabetes in a primary care setting in Beijing, Journal of the American Society of Hypertension (2018), doi: 10.1016/j.jash.2017.12.006. 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 Control of cardiovascular disease risk factors among patients with type 2 diabetes in a primary care setting in Beijing Hui-Juan Zuo1, Wen-Hua Wang2, Li-Qun Deng3, Jiang-Lian Su1

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1 Department of Community Health Research, Beijing Anzhen Hospital affiliated to the Capital University of Medical Sciences, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, China

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University of Medical Sciences, Beijing 100029, China

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2 Department of CVD prevention and control, Beijing Anzhen Hospital affiliated to the Capital

3 Department of General Practice, Beijing Anzhen Hospital affiliated to the Capital University of Medical Sciences, Beijing 100029, China

Corresponding author: Hui-Juan ZUO, Department of Community Health Research, Beijing Anzhen

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Hospital affiliated to the Capital University of Medical Sciences, Beijing Institute of Heart, Lung and Blood Vessel Diseases, No.2 Road Anzhenli, Chaoyang District, 100029 Beijing, China. Tel: 86-10-6445-6357

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E-mail: [email protected]

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Competing interests

The authors declare that they have no competing interests. Funding

Research progress and transformation of scientific and technological achievements in heart lung and blood vessel diseases, funded by the Beijing Municipal Health Bureau (TG-2015-33)

ACCEPTED MANUSCRIPT Abstract The aim of this study was to assess the control of blood glucose, blood pressure, serum low density lipoprotein cholesterol (LDL-c), and other cardiovascular disease (CVD) risk factors among patients

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with type 2 diabetes in a primary care setting in Beijing. We performed a cross-sectional, multi-center survey of 4056 patients with type 2 diabetes ≥40 years old. In total, 22.6% were current smokers,

10.8% often drank alcohol, 29.0 were obesity, and 67.4% participated in adequate levels

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of physical activity. About 70% of patients reported comorbid hypertension or dyslipidemia. Of

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these, 70.8% were being treated for diabetes and 79.3% for hypertension; 20.5% were receiving statins and 28.5% aspirin. The proportions of patients achieving their therapeutic target were 52.6% for fasting plasma glucose (FPG), 58.2% for blood pressure, and 33.0% for LDL-c. Only 11.1% achieved all three goals. Among 1960 (48.3%) patients with a record of hemoglobin A1C (HbA1c), 27.8% achieved the

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HbA1c target (<6.5 mmol/L). These data suggest that blood glucose and blood pressure were more likely to be well-controlled than LDL-c, that the likelihood of control of multiple risk factors is low, and that statin and aspirin use should be intensified in patients with a substantial risk of CVD.

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Key words: Diabetes; Cardiovascular Disease; Risk factor; Control Rate

ACCEPTED MANUSCRIPT Introduction Diabetes is a major risk factor for ischemic heart disease and stroke. It has been estimated that 12.9 million people died globally because of diabetes in 2010 1, 2, and that it accounted for 21% of all deaths

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from ischemic heart disease and 13% of all deaths from stroke worldwide. Eighty-four percent of these deaths with cardiovascular disease (CVD) were in low and middle-income countries

3, 4

. A survey

conducted by the Chinese Diabetes Society of the Chinese Medical Association (24,496 in-patients

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from 30 provinces) showed the prevalence rates of chronic diabetic complications were 31.9% for

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hypertension, 12.2% for cerebrovascular diseases, and 15.9% for cardiovascular diseases5. The prevalence of diabetes has increased significantly in China in recent years. In national surveys conducted in 2000 and 2007 the prevalence rates of diabetes were 5.5% and 9.7%, respectively 6, 7. The latest national survey in 2010 reported the estimated prevalence of diabetes among Chinese adults aged

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≥18 years to be 11.6%, and the prevalence of pre-diabetes to be 50.1%, implying that ~113.9 million adults had diabetes and a further ~493.4 million could develop it in the future 8. According to the latest guidelines on cardiovascular disease prevention, health professionals are

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encouraged to take account of the overall risk assessment and risk stratification of a patient. They

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emphasize the control of hypertension, diabetes, and dyslipidemia, smoking cessation, and aspirin use, as the primary preventive measures 9. Community-based strategies have been shown to improve healthcare and have an impact on the total burden of disease if they manage to reduce risk even to a small degree in a large proportion of the population, especially in low income communities

9,10

. The latest guidelines in China recommend that

the management of type 2 diab etes includes control of blood glucose, high blood pressure (BP), and high low density lipoprotein cholesterol (LDL-c), the use of aspirin and angiotensin-converting enzyme

ACCEPTED MANUSCRIPT inhibitors (ACEIs), and the cessation of smoking and alcohol consumption

11

. Despite these

recommendations, control of the multiple risk factors associated with diabetes is still insufficient. Optimal control of all risk factors was present in only 2.6%–7% of patients according to studies by

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Mostaza-Prieto et al. 12-13, and was also low in Chinese patients (5.6%) 14. Because of the scale of the diabetes pandemic, The Chinese government decided in 2009 that diabetes and hypertension were contained in primary healthcare. Accordingly, policy strategies have

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been implemented to make community healthcare accessible and affordable. However, few studies

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have been conducted to evaluate the outcomes of primary healthcare management of diabetes in China. Therefore, our study aimed to identify the efficacy of control of multiple risk factors in type 2 diabetic patients in a primary care setting. Materials and Methods

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Participants

We assessed blood glucose and other risk factors for CVD, including BP and LDL-c, and aspirin use, in patients with type 2 diabetes between October and December 2015. The study used a representative

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cross-sectional design, with participants randomly sampled from 40 primary care clinics in Beijing.

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The target sample size was 4000 patients aged ≥40 years. Inclusion criteria were age ≥40 years, a diagnosis of type 2 diabetes ≥6 months beforehand, and the provision of informed consent. Exclusion criteria were the presence of type 1 diabetes, a diagnosis of type 2 diabetes <6 months beforehand, or the presence of type 2 diabetes in a terminal phase, or a very poor quality of life. Data collection Demographic information, medical history, details of lifestyle, treatment for hyperglycemia or hypertension, and the use of statins or aspirin, were collected by trained research staff using a standard

ACCEPTED MANUSCRIPT questionnaire. Height, weight and BP were measured. Systolic BP (SBP) and diastolic BP (DBP) were measured using a standard mercury sphygmomanometer cuff placed on the right arm, supported at the level of the heart. Participants rested for at least 5 min in a seated position, then BP was measured

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twice, with a 30 s interval, and the mean of these two measurements was recorded. FPG during the last month and LDL-c during the last year were recorded in the questionnaire, or these were measured if records could not be provided.

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Measurement and diagnostic criteria

being current smokers

15

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Current smoking was defined as the patient having smoked at least 100 cigarettes in their lifetime and . Current drinking was defined as alcohol intake more than once per week

during the previous 12 months of >50 ml liquor, >300 ml beer, or >100 ml wine. Adequate physical activity was defined as exercise being taken on at least 5 days a week lasting over 30 min (total time

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≥150 min/week). Body mass index (BMI) was calculated as body mass in kilograms divided by height in meters squared. Overweight was defined as a BMI of 24.0–27.9 and obesity as a BMI of ≥28.0 16. A family history of diabetes was defined by a diagnosis of diabetes in a first-degree relative of a

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participant (sibling or parent). A history of ischemic stroke was defined by a history of two of:

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symptoms/signs such as numbness, abnormal speech, transient blindness, vertigo, nausea, deviated eyes and mouth, hemiplegia, or dribbling; consistent signs on a brain CT or MR; and the diagnosis of ischemic stroke by a neurologist (including diagnoses of cerebral thrombosis or lacunar infarction). The presence of coronary heart disease (CHD) was defined by a history of coronary artery bypass grafting or coronary stent implantation, or hospitalization for myocardial infarction. The presence of dyslipidemia was defined by a previous diagnosis of dyslipidemia by a doctor. Cardiovascular risk was calculated using Chinese Risk Tables, which estimate the 10-year risk of suffering a coronary event,

ACCEPTED MANUSCRIPT angina, or fatal or non-fatal myocardial infarction (ISCVD) 17. Low cardiovascular risk was considered to be represented by a 10-year risk of ISCVD <10%. Good control of hypertension was defined as a mean SBP <140 mmHg and a mean DBP <85 mmHg.

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Good control of hypercholesterolemia was defined as an LDL-c <2.6 mmol/L (100 mg/dl) for patients without CVD, and <1.8 mmol/L (70 mg/dl) for patients with CVD. Good control of blood glucose was defined as an FPG <7 mmol/L (126 mg/dl), or an HbA1c <6.5 mmol/L 9, 17.

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Statistical analysis

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Statistical analysis was performed using SPSS software for Windows (version 18.0; SPSS, Inc., Chicago, IL, USA). The chi-square test was used to compare differences in proportions between groups. All reported P-values are two-tailed and P < 0.05 was considered to be statistically significant. Results

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General information and cardiovascular risk factors

A total of 4056 patients with type 2 diabetes were recruited, whose mean age was 60.3 years (range 40–81, SD 9.2; 65.3% were women). The mean duration of diabetes was 6.9 years (SD 6.0). A total of

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22.6% of the patients were current smokers, 10.8% often drank alcohol, 29.0 were obesity, and 67.4%

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of the patients participated in adequate levels of physical activity. Approximately 17% of patients reported a history of CVD. The prevalence rates of hypertension, dyslipidemia and obesity were 70.4%, 66.5%, and 29.0%, respectively. The percentage of patients with three or more cardiovascular risk factors was 75.5%. Using Chinese Risk Tables, 73.4% of patients had a high risk of CVD (10-year risk of ISCVD risk factors are listed in Table 1. Blood glucose control

10%). The general characteristics and presence of CVD

ACCEPTED MANUSCRIPT Of the participants, 70.8% were taking antidiabetic therapy, 60.2% of them were taking oral antidiabetic drugs, and 10.7% were administering insulin, either alone or in combination with oral drugs. Blood glucose was controlled in 52.6% (2132/4056) of the patients, and in 64.9% of patients

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who were under treatment. No significant differences in antidiabetic therapy were identified among patients with different sex, age, duration of diabetes, BMI, or CVD status. The use of the various diabetes therapies is shown in Table 2.

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Only 1960 (48.3%) patients had a record of their HbA1c within the preceding 3 months. Of these,

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the proportion achieving control of HbA1c was 27.8% (<6.5 mmol/L), and 51.8% for FPG (<7.0 mmol/L), while 24.7% (484/1960) showed optimal control of both FPG and HbA1c. Among the patients with HbA1c >7.0 mmol/l, 24.5% demonstrated optimal control of FPG. These data are shown in full in Table 3.

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Blood pressure control

2856 patients had been diagnosed with hypertension, blood pressure controlled in 45.4% (1296/2856) of those patients. 2264 of them (79.3%) were taking antihypertensive medication, and the

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prevalence of hypertension control was 48.3% (1105/2264). In total, 58.2% (2360/4056) of participants

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had an ideal BP. In patients who did not diagnosed with hypertension, 11.3% (136 /1200) had abnormal BP.

Control of LDL-c

20.5% (832/4056) of patients were being treated with statins, and patients with dyslipidemia or CHD were significantly more likely to be on this type of medication. 33.0% of patients had a normal LDL-c (1340/4056), and this figure was 44.2% (368/832) in treated patients (Table 4). Prevalence of control of the three CVD risk factors

ACCEPTED MANUSCRIPT The three risk factors were well controlled in just 11.1% of the participants (452/4056), none of the three factors were well controlled in 15.7% (636/4056), and one or two risk factors were well controlled in 36.0% and 37.2%, respectively.

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Antithrombotic therapy 28.5% of patients were taking antiplatelet drugs. There was no significant difference in aspirin use between the sexes, but it appeared to be higher in older patients, patients with three risk factors,

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patients with CVD, or those with 10-year risk of ISCVD ≥15%. The use of aspirin is described in Table

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5. Conclusions

The latest guidelines on cardiovascular disease prevention emphasize the control of hypertension, diabetes, and dyslipidemia, the cessation of smoking, and aspirin use as primary preventive measures 9

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In this study ~70% of patients reported comorbid hypertension or dyslipidemia. High proportions were taking hypoglycemic agents and/or antihypertensive agents, but a lower prevalence of statin use was recorded. The proportions of patients achieving their control targets were 52.6% for FPG, 58.2% for

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BP, and 33.0% for blood lipids, but only 11.1% achieved all three goals.

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In this study, the most prevalent cardiovascular risk factors were hypertension (70.4%), dyslipidemia (66.5%), and obesity (29.0%), while 22.6% of the patients were current smokers and 10.8% often drank alcohol. Another study conducted in China reported that 72% had comorbid hypertension, dyslipidemia, or both 8. A similar result was reported in the study by Lucas Mengual et al.: the most prevalent cardiovascular risk factors were again hypertension (73.0%), dyslipidemia (58.2%), and obesity (44.8%), while 11.1% of the participants were current smokers

14

. In this study, we calculated the

10-year risk of ISCVD for each participant, and found that 63.3% of patients had a high risk according

ACCEPTED MANUSCRIPT to the Chinese Risk table. In the Mengual study, 39% of participants were defined as very high-risk patients according to different criteria 14. The control of the multiple risk factors associated with diabetes in the patients was insufficient. In

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this study the percentages of patients achieving the targets were relatively low: they were 52.6% for FPG, 58.2% for BP, and 33.0% for LDL-c, and indeed they were lower than those reported in national population-based surveys conducted in China. In the International Collaborative Study of

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Cardiovascular Disease in ASIA (InterASIA), among patients who reported a prior diagnosis of

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diabetes, 85.2% were taking prescription medication and 35% had FPG <126 mg/dl 6, and in another survey only 25.8% were receiving treatment and 39.7% of those being treated showed adequate blood glucose control 8.

Studies of outpatients have also been conducted. In the 3B study, 25,817 adults with type 2 diabetes

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were enrolled at 104 hospitals, of which 47.7%, 28.4%, and 36.1% of patients achieved their targets for HbA1c, BP, and TC (total cholesterol <4.5 mmol/L) 15. In a second study of 1151 patients conducted in six tertiary hospitals in Beijing the percentage of patients achieving their targets for HbA1c was 37.8%;

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for BP was 65.6%, and for LDL-c was 34.0% 19. A study conducted in a primary care setting in other

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countries reported that the percentages of diabetic patients with stable coronary disease that had achieved their targets for HbA1c, BP, and LDL-c were 49.7%, 38.2% and 29.0%, respectively 13, while in another two studies, the percentages were 50.6%–54.8% for HbA1c, 7.8%–24.7% for BP, and 5.9–40.6% for LDL-c

15, 20

. In our study, 11.1% of participants had optimal control of all three of the

risk factors, which was notably higher than in other studies (2.6–7%)

13–15

. In this study, risk factors

were more likely to be treated than in other studies, but there was limited use (10.7%) of insulin and statins (20.5%). In contrast, 15.6% of participants with diabetes in another primary care study were

ACCEPTED MANUSCRIPT using insulin and 47.2% were using statins 14. However, not just patients with diabetes, but also patients with CHD or dyslipidemia are less likely to be prescribed statins in China 21, 22. A meta-analysis of 16 studies showed that administration of aspirin as the primary preventive 23

and a second showed that

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measure could significantly reduce the risk of CVD in high risk patients

low dose aspirin (75–150 mg daily) was an effective antiplatelet regimen for long term use

24

. The

latest guidelines recommend that diabetes patients with high cardiovascular risk should take 75–150

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and by 40.2% of patients with 10-year risk of ISCVD ≥15%.

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mg aspirin per day 25. In our study, antiplatelet treatment was being used by 28.5% of all the patients

Healthcare priorities continue to shift towards population health management, and diabetes outcomes can be dramatically improved by the use of community resources. In China, a series of documents has been issued by the government to promote the development of community health services 26, 27. Besides

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for the control of blood glucose, blood pressure, serum low density lipoprotein cholesterol (LDL-c), and use of aspirin as primary and secondary prevention strategy for cardiovascular disease, policy and healthcare professionals focus on fighting smoking, obesity, alcohol consumption and physical

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inactivity to decrease the risk of CVD among patients with type 2 diabetes. The Chinese guidelines for

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the management of diabetes focus on the following management measures: health education sessions at least once a month, face-to-face follow-up at least four times per year, blood glucose monitoring, adherence to the therapeutic regimens, and free medical examination for patients over 65 27. To attain optimal type 2 diabetes health outcomes, self-care programs have been implemented in most community health settings, including the provision of dietary recommendations, regular exercise, and the monitoring of blood glucose and compliance with medication 28.

ACCEPTED MANUSCRIPT There were some limitations to this study. First, the subjects were only selected from a primary care setting; therefore, the study does not reflect the level of treatment and control status across the whole community. Second, HbA1c level was considered to be an important index of blood glucose control,

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but only 48.3% of participants had a record of their HbA1c values for the preceding three

months. Thus, we had to assess their glycemic control using blood glucose values instead of HbA1c.

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Acknowledgements

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The program was conducted in 40 community health service centers in Beijing. All the general practitioners took an active part in the program, and we thank them for their important roles in obtaining high quality data. We also thank Liwen Bianji, Edanz Group China (www.liwenbianji.cn/ac),

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for editing the English text of a draft of this manuscript.

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ACCEPTED MANUSCRIPT Table 1 General characteristics of and cardiovascular risk factors present in patients with diabetes Number

Percentage (%)

Female

2648

65.3

＜45

112

2.8

45-64

2616

64.5

≥65

1328

32.7

primary school

916

22.6

Middle school

1556

38.4

High school

1020

25.1

College and over

564

13.9

＜5

2180

53.7

6-10

1116

27.5

≥11

760

Education degree

Duration of diabetes (years)

916

Current drinking

440

Adequate physical activity

2732

BMI

<24 24-27.9 ≥28

Family history of diabetes Hypertension Dyslipidaemia

Coronary Heart Disease Number of CVD risk factors

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67.4

27.0

1784

44.0

1176

29.0

1920

47.3

2856

70.4

2696

66.5

428

10.6

9.5

<3

300

7.4

≥3

3064

75.5

With ISCVD

692

17.1

<10%

1488

36.7

10-14.9%

1560

38.5

≥15%

1008

24.9

ISCVD: ischemic cardiovascular disease BMI: body mass index

10.8

384

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10-year risk of ISCVD

22.6

1096

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Ischemic stroke

18.7

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Current smoking

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Age group (years)

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Characteristics

ACCEPTED MANUSCRIPT Table 2 Prevalence rates of treatment and control among patients with diabetes [n (%)] Characteristics

Hypoglycemic therapy

Blood glucose control

Not treatment

Oral drug only

Insulin

Treated patients

All patients

Male

352 (25.0)

920 (65.3)

136 (9.7)

620 (62.2)

704 (50.0)

Female

832 (31.4)

1520 (57.4)

296 (11.2)

1244 (66.3)

1428 (53.9)

<45

36 (32.1)

60 (53.6)

16 (14.3)

56 (66.7)

64 (57.1)

45-64

840 (32.1)

1476 (56.4)

300 (11.5)

1168 (66.1)

1364 (52.1)

≥65

308 (23.2)

904 (68.1)

116 (8.7)

640 (62.7)

704 (53.0)

<5

876 (40.2)

1080 (49.5)

224 (10.3)

1164 (75.4) 1#

1328 (60.9) 1*

6-10

196 (17.6)

816 (73.1)

104 (9.3)

472 (58.1)

524 (47.0)

≥11

112 (14.7)

544 (71.6)

104 (13.7)

228 (44.2)

280 (36.9)

<24

332 (30.3)

660 (60.2)

104 (9.5)

628 (76.2 ) 2#

684 (62.4) 2*

24-27.9

548 (30.7)

1072 (60.1)

164 (9.2)

764 (63.2)

900 (50.4)

≥28

304 (25.9)

708 (60.2)

164 (13.9)

472 (56.5)

548 (46.6)

Yes

104 (24.3)

264 (61.7)

60 (14.0)

180 (56.3)

196 (45.8)

No

1080 (29.8)

2176 (60.0)

372 (10.3)

1684 (66.0)

1936 (53.4)

Yes

128 (33.3)

204 (53.1)

52 (13.5)

156 (60.0)

192 (50.0)

No

1056 (28.8)

2236 (61.0)

376 (10.3)

1708 (65.4)

1940 (52.8)

<10%

440 (29.6)

832 (55.9)

216 (14.5)

756 (72.1) 3#

840 (56.5) 3*

10-14.9%

496 (31.8)

912 (58.5)

152 (9.7)

700 (65.8)

844 (54.1)

≥15%

248 (24.6)

696(69.0)

64 (6.3)

408 (53.7)

448 (44.4)

Sex

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Age group

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BMI

Ischemic stroke

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Coronary heart disease

10-year risk of ISCVD

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Duration of diabetes

Note: ISCVD: ischemic cardiovascular disease BMI: body mass index

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1#: (χ2=47.027, P=0.000), 2#: (χ2=18.931, P=0.000), 3#: (χ2=16.609, P=0.000) 1*: (χ2=37.609, P=0.000), 2*: (χ2=15.647, P=0.000), 3*: (χ2=9.288, P=0.01)

ACCEPTED MANUSCRIPT Table 3 Fasting plasma glucose and hemoglobin A1c in 1960 patients HbA1c（mmol/l）

FPG（mmol/l） 6.1-7.0

≥7.0

208（38.2）

276（50.7）

60（11.0）

6.5-7.0

172（39.4）

120（27.5）

144（33.0）

≥7.0

112（11.4）

128（13.1）

740（75.5）

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EP

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M AN U

SC

RI PT

＜6.1 ＜6.5

ACCEPTED MANUSCRIPT Table 4 Statin use and control of LDL-c control in patients with diabetes [n (%)]

Characteristics

LDL-c control Treated patients

All patients

Male

264 (18.8)

136 (51.5)

556 (39.5)

Female

568 (21.5)

232 (41.1)

784 (29.7)

<65

540 (19.8)

228 (42.5)

900 (33.0)

≥65

292 (22.0)

140 (47.9)

440 (33.1)

Dyslipidlimae

788 (29.2)

356 (45.4)

Ischemic stroke

112 (26.2)

40 (35.7)

Coronary Heart Disease

144 (37.5)

80 (55.6)

880 (32.7)

136 (31.8)

156 (40.6)

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M AN U

SC

Age group

RI PT

Sex

Statin use

ACCEPTED MANUSCRIPT Table 5 Aspirin use in patients with diabetes χ2

P

Male

416 (29.5)

0.289

0.591

Female

740 (27.9)

Age group

<45

20 (17.9)

11.7

0.003

45-64

668 (25.5)

≥65

468 (35.2)

Number of risk factors

<3

52 (17.3) 808 (26.3)

≥3

296 (42.8)

<10%

267 (17.9)

10-14.9%

484 (31.0)

≥15%

405 (40.2)

153.721

AC C

EP

TE D

M AN U

CVD risk of 10 years

With ICVD

23.59

SC

Gender

RI PT

Aspirin use n (%)

Characteristics

＜0.001

＜0.001

ACCEPTED MANUSCRIPT Highlights




This study conducted to assess the status of cardiovascular disease (CVD) risk factors among patients with type 2 diabetes in a primary care setting in Beijing To evaluate the control of blood glucose, blood pressure, serum low density lipoprotein

RI PT




cholesterol (LDL-c), and use of aspirin as primary and secondary prevention strategy for cardiovascular disease among patients with type 2 diabetes in a primary care setting in Beijing

SC

The study used a representative sample with participants randomly sampled from 40 community

EP

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M AN U

clinics in Beijing

AC C