Time Trends in Comorbidity and Management of Hypertension and Diabetes: A 15-year Nationwide Longitudinal Study of 18,380 Adults in China

Background: To examine time trends in comorbidity of hypertension and type 2 diabetes (T2DM) and their diagnosis, treatment, and management in China during 2000-2015 and study factors associated with these outcomes. Methods: Longitudinal data collected from the China Health and Nutrition Survey (CHNS) during 2000-2015 were analyzed. Of the 28,204 adults, 832 had both hypertension and T2DM were selected. Average systolic blood pressure (SBP) and diastolic blood pressure (DBP) and hypertension prevalence among T2DM patients, and treatment and control of hypertension and T2DM among patients with both conditions were examined for all and by sex and weight status. Mixed effects models assessed the associations. Results: From 2000 to 2015, among patients with T2DM, hypertension prevalence dropped from 88.4% to 83.0% and BPs decreased (P < 0.05). Men and overweight/obese patients had greater decreases in hypertension prevalence and DBP, while women had a larger decrease in SBP than men. Over time, among patients with both hypertension and T2DM, rates of hypertension treatment (45.3% to 57.7%), hypertension control (3.0% to 10.9%) and T2DM treatment (90.0% to 95.6%) increased, but were still very low except for T2DM treatment (all P < 0.001). Age, gender, smoking, drinking, household income, education, residence, and weight status were signicantly associated with prevalence, treatment, and control of hypertension, and T2DM treatment among patients with both hypertension and T2DM. Conclusion: Rates of hypertension treatment and control among patients with both hypertension and T2DM have improved in recent years, but were still low. overweight/obese individuals were more likely to be treated and have theirhypertension controlled.Third, higher social economic status,ever-smoking, andmore drinkingwere positively associated with hypertension prevalence and its treatmentor control rate among subjects with the comorbidity of hypertension and T2DM. control among overweight/obese patients.More vigorous and effective intervention efforts are needed for the management of the comorbidity hypertension and T2DM. This include programs such as health education, health insurance, regular blood pressure monitoring, strict adherence to prescribed medication, and lifestyle modication strategies. Multiple related stakeholders including patients, their families, and medical and public health agencies need work together well to achieve these goals.


Background
Hypertension and type 2 diabetes mellitus (T2DM) are the most common non-communicable diseases (NCDs) and are important global public health problems [1].Although they are two distinct medical conditions, they frequently coexist, leading to additive increases in the risk of cardiovascular diseases (CVDs). Research reported that among patients with T2DM, hypertension prevalence was 70.9 % in American adults [2], 54.6% in Korean adults [3], and49.9% to 60.6% in Chinese outpatients [4].Epidemiological studies and clinical trialshave demonstrated that lowering blood pressures (BPs) could effectively reduce CVDs mortality and morbidity in patients with T2DM [5,6].
Cross-sectional studies have indicated that compared with higher hypertension treatment rates, the control rate was relatively loweramong patients with both hypertension and T2DM in the US (87.8% vs. 29.6%, respectively), the UK (54.0% vs. 28.0%, respectively), Korea (86.7% vs. 14.9% respectively) and Canada (87.7% vs. 55.5%, respectively) [2,3,7,8]. Similar patternswere observed in hypertensivepatients in China [9,10].Results from the China Kadoorie Biobank Consortium showed that among adults with a diagnosis of hypertension, only 46.4% were treated; of those treated, only 29.6% had their hypertension controlled [10]. However, most previous studies were cross-sectional studies, focusedon a single disease, and were not based on long-term follow-up data.
With rapid social and economic developments during the past three decades, the prevalence of obesity and overweight in China has increased substantially [11].Accumulating evidence has indicated that having overweight and obesity are strongly associated with hypertension, diabetes,and CVDs in many populations [12].For example, one study reported that the hypertension rateincreased with body mass(normal-weight, 15%; overweight, 25%; obese, 40%) [13]. However, few studies have examined whether time trends in hypertension prevalence, treatment, and control rates varied depending on weight status.
To ll these knowledge gaps, we analyzed the longitudinal survey datacollected in the China Health and Nutrition Survey (CHNS)during 2000-2015, and aimed to: 1)describe the prevalence of hypertension and its time trend among patients with T2DM;2) examinethe rates ofhypertensiontreatment, T2DM treatment,and hypertension control and their time trendsamong patients with T2DM and comorbid hypertension; and 3) prospectively identify the factors associated withhypertension prevalence,control, and treatmentas well as T2DM treatmentamong patients with the comorbidity of hypertension and T2DM.
Methods And Materials

Study design and study population
This study used data from the CHNS, an ongoing large-scale longitudinal and household-based survey, which was initiated in 1989 and has been followed up every 2-4 years since then [14]. A multistage, random cluster process was used to draw samples from nine provinces in the 2000 survey(Liaoning, Shandong, Henan, Jiangsu, Hubei, Hunan, Guizhou, Guangxi and Heilongjiang) [15]. Three megacities (Beijing, Chongqing, and Shanghai) were added in 2011, and three more provinces(Shaanxi, Yunnan, and Zhejiang) were added in 2015. Extra details regarding the study design and methods have been described elsewhere [15,16] and at the website https://www.cpc.unc.edu/projects/china. The study data collection was approved by theCarolina Population Center at the University of North Carolina at Chapel Hill, the National Institute for Nutrition and Health (NINH), and the Chinese Center for Disease Control and Prevention (China CDC). Written informed consents were obtained from all participants before any data were collected.
Between 2000 and 2015, there were 38,752 adults who participated in the interview and medical examination. After excluding subjectsyounger than 18 years (n = 6,022), pregnant women (n = 178) and those who had missing data on age, sex, SBP, orDBP(n = 4,528), 28,024 subjects were eligible for the study. Of them, 995 subjects with T2DM and 832 subjects with both T2DM and hypertension records were retained.
For cross-sectional data analysis, we used the rst available observation from the pooled data of the survey round during 2000-2015 to describe hypertension/T2DM status and demographic characteristics (n = 18,380), and compared them with those in 2015 (n = 3,478).For longitudinal data analysis, subjects were included if they had data both at baseline and in at least one follow-up during 2000-2015.

Data collection and measurement
All measurements were performed by trained examiners. Mercury sphygmomanometers were used to measure SBP and DBP on the right arm with appropriate cuff sizes in triplicate after a 10 minute seated rest, and the mean of the three measurements at each wave was used in analyses [15]. Height and weight weremeasured without shoes and in light clothing to the nearest 0.1 cm and 0.1 kg using a portable SECA stadiometer and a calibrated beam balance, respectively [15]. BMI was calculated as weight (kg) divided by height square (m 2 ). According to Guidelines for the Prevention and Control of Overweight and Obesity in Chinese Adults [17], normal weight, overweight, and obesity were de ned as 18.5 ≤BMI<24.0, 24.0 ≤BMI< 28.0, and BMI ≥28.0 kg/m 2 , respectively.
Data were collected using face-to-face interviews with questionnaires. Subjects were categorized into three age groups: 18-39, 40-59 and > 60 years.
Income level was divided into low, medium, and high levels according to tertiles of annual gross household income. Smoking status was de ned as non-smokers, current smokers, and ever-smokers. Drinking frequencies were classi ed into four groups as follows: never, 3 drinks/month or less, 1-2 drinks/week, and at least 3 drinks/week. Residence(rural, suburban/town, and urban areas), marital status (unmarried, currently married, and ever-married),educational level (illiteracy, primary/junior school, senior/secondary vocational school, college, and higher),gender (male/female), medical insurance (yes/no), nationality (Han/non-Han), and disease history(yes/no) were also considered.
3. De nitions of key outcome variables 1) T2DM was identi ed based on the questionnaire if an individual answered "yes" to the question "Have you ever been told by a doctor that you have diabetes?" or if an individual reported ever using insulin and/or an oral antidiabetic medication.
2)Hypertension was determined according to the Guidelines for the Prevention and Treatment of Hypertension (2018 revision) and T2DM (2017 edition) in China, issued by the Chinese Society of Cardiology (CSC) and the Chinese Diabetes Society (CDS), respectively [18,19].Hypertension was de ned as SBP ≥ 130 mmHg or DBP ≥ 80 mmHgfor individuals with T2DM [19],or the threshold of 140/90 mm Hg for individuals without T2DM [18],or if an individual answered "yes" to the question, "Have you ever been told by a doctor that you have hypertension?" or if an individual was currently receiving antihypertensive medications.
3) Hypertension treatment was de ned as taking any antihypertensive medications at present [18]. 4) Controlled hypertension was de ned as an average SBP below 130 mmHg and DBP below 80 mmHg among patients with T2DM [19]. For nondiabetic patients, control BP was de ned using the target of 140/90 mmHg [18]. 5)T2DM treatment was de ned as taking any control and treatment measures at present (including lifestyle interventions or/and medications) [19].

Statistical analysis
First, demographic status, health-related outcomes, and lifestyle characteristics were described based on cross-sectional data analysis of the pooled data and the 2015 data according to T2DM status. The chi-square test and t-test were used to compare differences between groups with and without T2DM for categorical and continuous variables, respectively. A linear regression model was conducted to test time trends of comorbidity of T2DM and hypertension.
In longitudinal data analysis, we estimated the mean SBP and DBP and the hypertension prevalence among patients with T2DM, as well as hypertension treatment and control and T2DM treatment among patients with both T2DM and hypertension, which was standardized to the age distribution of CHNS data in 2015 by the direct method.
A mixed effects model was conducted to test time trends using estimated mean values, prevalence, treatment, or control rates as dependent variables and survey years as independent variables,and to assess theassociations between risk factors and hypertension prevalence among patients with T2DM, and hypertension treatment/control and T2DM treatment among patients with both hypertension and T2DM.All models adjusted for age, gender, smoking status, drinking status, household income, weight status, region, education level, medical insurance and disease history. The effect size was presented as an odds ratio (OR) and a 95% con dence interval (95% CI).
All analyses were conducted using Stata software version 14 (StataCorp, College Station, Texas, USA). All statistical signi cance was set at P < 0.05. Of the total subjects in the pooled data from 2000-2015, 3.6% and 28.4% participants were diagnosed with T2DM and hypertension, respectively.Hypertension prevalence was much higher among T2DM patients than those without T2DM (83.9% vs.26.3%, respectively).

Discussion
Using longitudinal data collected from a nationwide study sample during 2000-2015, we examined time trends in hypertension prevalence among patients with T2DM, hypertensionand T2DM treatment, and hypertension control rates among patients with both hypertension and T2DM in Chinese adults, and identi ed the associated factors with these rates. To our knowledge, this is the rst study examining these rates in subjects with the comorbidity of hypertension and T2DM using longitudinal data from China. We found, rst, that hypertension prevalence and BPs levels decreased from 2000 to 2015, but were still higher among patients with T2DM.Ageand being overweight/obese were positively associated with hypertension.Second,hypertension treatment and control rates increased among patients with both hypertension and T2DM over 2000-2015, but the control rate was low at less than 30%. Older patients, women, and overweight/obese individuals were more likely to be treated and have theirhypertension controlled.Third, higher social economic status,ever-smoking, andmore drinkingwere positively associated with hypertension prevalence and its treatmentor control rate among subjects with the comorbidity of hypertension and T2DM.
Hypertension and T2DM frequently coexist, leading to additive increases of CVDs risk [20,21]. With the rapid social and economic developments during the past three decades, China is facing a growing threat from NCDs, and hypertension is one of the most common NCDs in China and many other countries [22].We found hypertension prevalence decreased from 88.4% to 83.0% during 2000-2015, but it was still at a higher level among patients with T2DM compared with that in Western societies [2,3,8,23].Thismay be the diagnosis of hypertension in patients with T2DM seems different in Guidelines from China compared to western countries, for example, the 2019 European Society of Cardiology (ESC)/ European Atherosclerosis Society (EAS)Diabetes guidelines, which is 130/80 mmHg compared to 140/90 mmHg in ESC/EAS. Hypertensiontreatment and controlamong patients with both hypertension and T2DM play an important role in preventing morbidity and mortality from CVDs [5,6,24].Cross-sectional studies conducted in some European countries and the U.S. had reported that the hypertension treatment rate was higher, while the control rate was lower among patients with both hypertension and T2DM than in others [2,3,7,8]. Surveys in China showed that about half of diagnosed hypertension was treated, while only less than 25% of them had their hypertension controlled [11,25]. However, those previous studies were cross-sectional studies and had focused on T2DM or hypertension.Our study using longitudinal data found that hypertension treatment and control rates among patients with both T2DM and hypertension increased from 2010 to 2015,but only 57.7% were treated and only 10.9% had their hypertension controlled.Those with better socio-economic status were more likely to receive treatment and gain control of their hypertension. This may be due to their better access to higher quality medical care services [26].
Among patients with both hypertension and T2DM, 90% of them reported having received T2DM treatment, which was much higher than two previous studies conducted in Portugal (79.7%) and China (51.3%) among T2DM patients [27,28]. The disparity may be mainly due to different subjects and de nitions of T2DM treatment. The de nition of T2DM treatment in those two previous studies was only persons who took hypoglycemic therapy, while in the present study"treated T2DM" was de ned as taking any control and treatment measures, including lifestyle interventions or/and medications [19].
In the present study,oldersubjects and womenwere more likely to have hypertension, receive hypertension and T2DM treatment, and havetheir hypertensioncontrolled, which was consistent with previous studies [11,29].Older subjectscared for theirhypertension and T2DM more and were more likely to be coveredby medical insurance and have access to basic medical and public health services than younger adults [30,31]. It is reported that compared with men, womenaremore likely to visit doctors and receive timely treatment [32,33].Women are also more sensitive to antihypertensive drugsthan men and might bene tfrom the protective effects of estrogen [34].These factors may help explain why Chinese women have higher hypertension treatment and control rates than men.
Smoking and drinking alcohol were highly associated with T2DM and hypertension risks [35,36]. It has since long been known that smokers have lower BP and higher in ever-smokers [37]. Consistently, we observed patients who had ever smoked or drank heavily had higher hypertension prevalence and treatment rates, but only ever-/current smokers were likely to have their hypertension controlled. Previous studies also reported that ever-smokers were more likely to have hypertension due to excessive weight gain after smoking cessation [38,39]. Guo and colleagues [11] suggested that patients who were ever-/current smokers or drank frequency may experience more complications of health problems and have a stronger desire to receive relevant treatment. During hypertension treatment, ever-/current smokers with hypertension were commonly asked to reduce their cigarette consumption [40].Comparedwith patients who continue to smoke, patients who quitsmoking may be more health conscious and visit the physicianmore often after a diagnosis of hypertension, resulting in better blood pressure control than current smokers [41], which has signi cantly contributed to decreased BPs as well as BP control in ever-and current smokers. In addition, subjects with a cancer history had worse control of hypertension, which might due to the severity and complexity of their medical condition and poor treatment compliance.
We foundoverweight and obese patients had higherhypertension prevalenceand hypertension and T2DM treatment, but a lowerhypertension control rate. This was in agreement with other studies [25,42].Overweight and obesity increase hypertension and T2DM risks. There is research reporting that obese patients have received medications to lower their lipid, BPs, and plasma glucose levels, but this was correlatedinversely to how well their BP was controlled [43,44].
China faces a severe threat from NCDs. Prevention of NCDs including hypertension and diabetes through promoting healthy lifestyles has become a national priority. That BP in diabetic patients is inadequately controlled may be due to many patient, clinician, and disease factors [45].The need for intensive BP control in patients with diabetes is recognized in clinical practice guidelines. The Chinese national standards emphasize the need for diabetic patients to control their BP to ≤ 130/80mmHg [18,19].
This study has several strengths. First, this is the rst study in China to evaluatethe trends in the prevalence, treatment, and control rates of hypertension among subjectswiththe comorbidity of T2DM and hypertension, and to determine factors associated with these outcomes using a large longitudinal data set. Second, the longitudinal data with large sample sizes enabled us to track the dynamics of BP levels, T2DM and hypertension management during 2000-2015.However, some limitations should be noted. First, the CHNS 2000-2015 data was collectedfrom 15 provinces across China, which amounts to less than half of all provinces. Second, T2DM status was based on self-reported questionnaires, and we cannot calculate the T2DM control rate due tolack of blood glucose data.

Conclusions
In conclusion, data collected during 2000-2015in a nationwide study showed thatalthough the prevalence of hypertension among patients with T2DMdecreased, it isstill high in China. The treatment of hypertension and T2DM among patients with both conditions has improved over time, but the hypertension control rate remains very low, especially among overweight/obese patients.More vigorous and effective intervention efforts are needed for the management of the comorbidity of hypertension and T2DM. This may include programs such as health education, health insurance, regular blood pressure monitoring, strict adherence to prescribed medication, and lifestyle modi cation strategies. Multiple related stakeholders including patients, their families, and medical and public health agencies need to work together well to achieve these goals.

Authors' contributions
Research conception and design was made by JW, YL, XJW and YW. Data analysis was conducted by YL, XS and YW. The manuscript was draft by YL, and was critically revised by all coauthors. YW secured administration and nancial support for the study. All authors have read and approved the nal manuscript. Ethics approval and consent to participate Not applicable.

Consent for publication
Not applicable.

Competing interests
The authors declare that they have no competing interests.