Prevalence and associated factors of uncontrolled hypertension among hypertensive patients: a nation-wide survey in Thailand

Objectives The objectives of the research were to determine the prevalence and factors associated of uncontrolled blood pressure among Thai hypertensive patients in a nationwide survey. Results A total of 65,667 patients with hypertension were included in this study. The greater proportion of participants, 40,834 (62.2%), were females. The average age of participants was 63.9 ± 11.1 years. Uncontrolled hypertension was detected among 16,122 patients (24.6%; 95% CI 24.2–24.9). Among males and females, uncontrolled hypertension was 25.6% (95% CI 25.1–26.2) and 23.9% (95% CI 23.5–24.3) respectively. Multivariate analysis showed that the uncontrolled hypertension was significantly associated with being male, age, regions, hospital levels, diabetes comorbidity, higher body mass index, low density lipoprotein cholesterol level and the number of antihypertensive medications.


Introduction
Hypertension is one of the most common cardiovascular disorders worldwide. Globally, 30.8% of adults have hypertension, and the estimated prevalence of hypertension among males and females is 32.1% and 29.5%, respectively [1]. Hypertension is a major modifiable risk factor for heart diseases, stroke, end stage renal failure and peripheral vascular disease. The Thai National Health Examination Survey (NHES) 2004 and the NHES 2009 data indicated that it affects nearly one in every five Thai adults [2]. Information on controlling blood pressure (BP) is available worldwide, and the prevalence of controlled BP reported in the US, UK, China and Japan were 68.9%, 60.8%, 37.5% and 37.1%, respectively [1,3]. However, limited information is available regarding the prevalence of uncontrolled hypertension in Thailand especially in nationwide studies. We aimed to use the information from the Thailand Diabetes Mellitus/Hypertension (DM/ HT) of the Medical Research Network of the Consortium of Thai Medical Schools (MedResNet) to determine BP control and risk factors associated with uncontrolled BP among Thai hypertensive patients from 2014 to 2015.

Main text
Methods A nationwide, cross-sectional survey was conducted from 2014 to 2015. The survey aimed to determine outcomes among patients with hypertension visiting clinics in Bangkok supported by the Thailand National Health Security Office's (NHSO) program, private hospitals and public hospitals of the Ministry of Public Health (MoPH) in Thailand.
This study was reviewed and approved by the Royal Thai Army Medical Department and local institutional review boards of the participating hospitals. For selecting national representative samples of patients with hypertension in Thailand, a stratified two-stage cluster sampling method proportional to the size was conducted. For Bangkok, the targeted hospitals included all hospitals and clinics under the NHSO. However, all university hospitals were excluded.
Hypertensive patients aged ≥ 18 years receiving medical treatment in a hospital, drawn from those sampling methods, during the previous 1 year were included. Any patient who had participated in a clinical trial was excluded. The number of participants totaled 65,667. The number of hospitals under the MoPH totaled 833 hospitals, including 717 community hospitals, 83 general hospitals and 33 regional hospitals. Hypertensive patients were selected by sampling and registered at each hospital. A standardized case report form was used to collect data from medical records of hypertensive treatment and was sent to the central data management unit. The data, including status of hypertensive complications and results of laboratory tests, were retrieved from patient's medical records.
Hypertension was defined by JNC's eight hypertension guidelines as high BP (SBP ≥ 140 mmHg or DBP ≥ 90 mmHg) and/or use of antihypertensive medicine [4]. Uncontrolled hypertension was defined by JNC's eight hypertension guidelines. The BP target is SBP < 140 mmHg or DBP < 90 mmHg among adults younger than 60 years and a BP goal of SBP < 150 mmHg and DBP < 90 mmHg in the general population aged ≥ 60 years [4]. BMI was calculated as body weight in kilograms (kg) divided by height in meters squared [weight (kg)/height (m) 2 ]. Waist circumferences were measure at the level of the umbilicus [5].
Data were coded, entered and analyzed using IBM SPSS Statistics for Windows, Version 23.0. Categorical data were presented as number and percentage, while continuous data were presented as mean and standard deviation (SD). Prevalence was analyzed using descriptive statistics and reported as percentage and 95% confidence interval. The Chi-square test was used to compare categorical data, while continuous data were compared using the t-test. The magnitude of association was presented as crude odds ratios (ORs) with 95% confidence interval. The final model with multivariate logistic regression analysis was created. A p-value < 0.05 was considered statistically significant.

Results
A total of 65,667 Thai patients with hypertension were enrolled in this study. The greater proportion of participants, 40,834 (62.2%), were females ( Table 1). The average age of participants was 63.9 ± 11.7 years, while the average duration of hypertension was 6.5 ± 4.1 years. The average SBP was 133.6 ± 15.2 mmHg while the average DBP was 75.9 ± 10.6 mmHg. Overall prevalence of  (Tables 2 and  3). The final model was adjusted for sex, age, regions, hospital levels, smoking, diabetes mellitus (DM) comorbidity, duration of hypertension, BMI, LDL level and the number of antihypertensive medications used. After adjusting, the factors associated with uncontrolled hypertension comprised being male, regions, hospital levels, DM comorbidity, higher BMI, higher LDL level and higher number of antihypertensive medications used; however, higher age was a protective factor for uncontrolled hypertension.

Discussion
These results revealed important implications to the Thai public health system because hypertension is a major risk factor for cerebrovascular events and cardiovascular diseases. A secondary intervention is necessary to reduce any complications. This study comprised the largest research in Southeast Asia, focusing on uncontrolled hypertension. The present nationwide survey from 2014 to 2015 showing the prevalence of uncontrolled hypertension among Thai adults with hypertension was 24.6%.
The prevalence of uncontrolled hypertension in the current study was lower than that previously reported for US and China [6,7]. However, in Thailand one related study in 2009 reported the prevalence of uncontrolled hypertension was 75.6% [2]. Thus, in the present study, the prevalence of uncontrolled hypertension was lower than that in the 2009 survey. This situation could be explained by several points. Firstly, the related study [2] was conducted by a national health examination in a field survey while the present study was conducted among hypertensive patients receiving medical treatment in a hospital.
In 2012, Thai guidelines on treating hypertension were released to direct any physician including general practitioners and specialists. Therefore, Thai patients with hypertension have been receiving appropriate medical treatment. Consequently, patients with hypertension, who follow-up with their physicians, have obtained more proper medical care. In the present study, patients with hypertension obtaining medical treatment in hospitals under the MoPH all over Thailand were enrolled. However, those with high BP treated at primary care units or university hospitals were not included in the current study; thus, the prevalence of uncontrolled hypertension may be underestimated. The present study showed that patients with hypertension at higher ages tended to be at lower risk for uncontrolled hypertension, similar to other studies [7,8]. Hypertensive complications and end organ damage will not occur in the early period of hypertension. Thus, younger hypertensive patients lack awareness of complications; moreover, working age people may not follow up their appointment with medical doctors resulting from the available time mismatch between working age patients and healthcare services [9]. However, some studies have shown that the prevalence of uncontrolled hypertension among elderly hypertensive patients was more likely to be higher [10][11][12]. Similarly, some related studies conducted in the US and China revealed that males had a higher risk for uncontrolled hypertension than females [10,[13][14][15] due to biological factors [16] including hormonal effects on increased BP. These related studies have shown that females have lower prorenin and renin levels than males, causing BP among males to be higher than females [16,17]. Nevertheless, another study reported hypertension could be better controlled among males [18].
Our findings showed that the prevalence of uncontrolled hypertension differed by region. In the northeast area, the prevalence of uncontrolled hypertension was significantly lower than that in other regions. The finding could be explained by behavioral and local cultural factors. Patients in this area enjoyed consuming vegetable and fruits, which may have decreased body adiposity   [19][20][21]. Nevertheless, after adjusting, both residing in northeast Thailand and BMI were associated with controlled BP. Another explanation is that northeast Thailand is mainly an agricultural area. As a result, the patients with hypertension in this area are agriculturists; moreover, traditional dancing and playing of northeastern Thai games creates more physical activities. More physical activities can decrease both systolic and diastolic BP including decreased risks for high BP [22,23]. Our study has shown that hypertensive patients receiving medical treatment at middle level hospitals and standard/advanced level hospitals tended to indicate a higher prevalence of uncontrolled hypertension compared with those at first level hospitals. Similarly, one related study in Kenya illustrated that hypertensive patients in provincial hospitals could control their BP more effectively than those in national hospitals [24]. Patients with uncontrolled hypertension in first level hospitals may be referred to high potential hospitals for proper medical management. Consequently, high level hospitals are permeated with hypertensive patients with poorly controlled BP. The study reported hypertensive patients with diabetes comorbidity were associated with BP control. This result was similar to that of related studies in Europe [25,26], showing that diabetes was associated with a high risk of poor BP control. This effect may have resulted from insulin resistance and endothelial dysfunction; thus, increasing BP [27][28][29]. Several studies reported similar results with this study revealing a relationship between BMI and controlled BP [30][31][32][33]. The study found that patients with hypertension presenting BMI more than 25 kg/m 2 tended to be higher at risk of uncontrolled BP. Notably, patients with BMI > 35 kg/m 2 were 1.7 times at higher  [34,35]. The present study reported that increasing LDL level was associated with uncontrolled hypertension. Our findings agree with related studies [26,36,37] supporting the relationship between the cholesterol level and increased BP. Evidence supports the results that LDL cholesterol elevation leads to increased stability of mRNA for AT1 receptors regarding angiotensin II. Moreover, LDL density at vascular level is proportional to cholesterolemia, contributing to vasoconstriction and pressure in response to angiotensin II infusion [38]. Our data showed a relationship between increasing amounts of antihypertensive medications used and uncontrolled BP, firstly, illustrating that other studies reported similar results, followed by various factors [39,40]. Patients experiencing difficulty controlling BP are likely to be treated with multiple medications. Therefore, this result might be a consequence of uncontrolled hypertension. However, we found that some patients with hypertension without using antihypertensive medication could control their BP.
The strength of this study includes its nationwide scope for uncontrolled hypertension, the largest sample size in Southeast Asia. Thus, the findings of the study could be generalized and applied in similar hypertension populations. One implication of the study is to reduce the prevalence of uncontrolled hypertension, resulting from improving hypertension management. Moreover, hypertensive patients should control their modifiable risk factors. Healthcare services access of hypertensive patients especially at working age should be adjusted for appropriate situations. Above all, MoPH's managers and physicians should provide further preventative strategies to attenuate cardiovascular risk factors.

Limitations
The study employed a cross-sectional design, and as such, the results could show only factors associated with uncontrolled hypertension. The data presented in the present study were obtained in the 2014 to 2015 Thailand DM/HT of the NHSO from MedResNet central data management, so we were aware of missing data from this observational study. However, this represents a relatively large sample size and some data were missing as from the nationwide observational study, so associations between factors and outcomes could be presented.