2024 Thai guidelines on the treatment of hypertension

Level I means “Should be practiced” because the recommendation is highly reliable, beneficial, and worthwhile.

Level IIa means “Could be practiced” because the recommendation is moderately reliable, likely beneficial, and probably worthwhile.

Level IIb means “May be practiced” because the recommendation is not reliable enough, not sufficiently proven to be beneficial, and probably not worthwhile, but will not be harmful.

Level III means “Should not be practiced” or “Must not be practiced” because the recommendation is not beneficial and will probably be harmful.

A means the evidence from various high-quality randomized controlled trials (RCTs) or meta-analyses.

B means the evidence from at least 1 high-quality RCT or a large-scale non-RCT with definitive outcome on advantages or disadvantages.

C means the evidence from other types of high-quality studies, a retrospective descriptive study, a registry, or experts’ opinions.

Accurate BP measurement is the fundamental process both in the diagnosis and management of hypertension. However, this important process is usually overlooked [3]. Standard BP measurement techniques are usually not followed by healthcare providers [4–6]. Three methods of BP measurement performed in clinical practice are office BP measurement, home or self-BP measurement, and ambulatory BP measurement. BP information from all methods of BP measurements is complementary. It will help clinicians to make the correct hypertension diagnosis and deliver suitable treatment for their patients, so all types of BP measurement should be used for the diagnosis and treatment of hypertension (Strength of Recommendation I, Quality of Evidence A).

Preparation for BP measurements

Before BP measurements, the subject should be advised to avoid smoking, caffeine, and exercise for at least 30 min and should empty their bladder. The examination room should be quiet with a comfortable temperature and surroundings. The subject should sit on a chair with back support, upper arm bare, and rest on a table at heart level, legs uncrossed and feet flat on the floor (Figure 1). Subject should remain seated and relaxed for at least 3–5 min before measurements. Neither tightening nor gripping hands, and no talking, both before and between measurements.

Figure 1.

Subject preparation and standard position for BP measurement. BP, blood pressure.

The guidelines in hypertension diagnosis and treatment are mainly derived from research using office BP measurements. There are 2 methods to obtain a subject’s BP in the office: the auscultatory method and the oscillometric method. The auscultatory method is traditional and serves as a reference standard for other methods. However, it requires well-trained personnel and consumes more time than the oscillometric method. These limitations have placed the oscillometric method into today’s clinical practice. The THS encourages healthcare personnel to be aware of the key steps in the auscultatory BP measurement technique, which is still the fundamental standard for all types of BP measurement.

Key steps in proper office BP measurement:

• Wrap the proper size arm cuff over the subject’s upper arm 2–3 cm above the antecubital fossa to have the space for placing the stethoscope.

• The marker on the arm cuff, which indicates the center of the bladder, should be on the brachial artery.

• Estimate systolic blood pressure (SBP) by inflating the cuff while palpating the brachial pulse until brachial pulsation disappears. Then, release the cuff pressure slowly at around 2–3 mmHg/s until brachial pulsation resumes. SBP should be close to the pressure level, at which the arterial pulsation disappears and reappears.

• Wait at least 1 min to have normal blood recirculation of that arm before the next measurement. Pulse rate and pulse rhythm can be determined while waiting.

• Place the stethoscope over the brachial artery and raise the pressure to 20–30 mmHg over the estimated level of SBP from the palpation technique. Then, release the pressure slowly and listen to the Korotkoff sound, which will appear at intervals according to the heartbeat. The first sound heard is the Korotkoff sound phase 1; the pressure read at that time is the SBP. The BP at which the sound disappears, the Korotkoff sound phase 5, is the diastolic blood pressure (DBP).

• Orthostatic hypotension can be screened in subjects with diabetes mellitus (DM), the elderly, or those with orthostatic symptoms (Strength of Recommendation Ila, Quality of Evidence C). Measure BP when the subject is in the lying position first, followed by measurement after standing up for 1 min and 3 min consecutively. Orthostatic hypotension is defined as a BP lowering ≥20/10 mmHg within 3 min after standing up from the supine position [7].

• In subjects with arrhythmia, BP measurement with the auscultatory technique is preferred (Strength of Recommendation IIa, Quality of Evidence C). Using the average BP from multiple records is advised.

The oscillometric method has almost replaced this conventional method in clinical practice. After placing the arm cuff on the patient’s upper arm, press the start button. The device will inflate and deflate the cuff automatically. Arterial pulse waves will be detected and used for BP determination. SBP and DBP, together with pulse rate, will appear on the screen, usually within 1 min. In some models, multiple measurements can be taken to achieve average results. The oscillometric method can eliminate the terminal digit preference of healthcare providers, which is common in Thailand [4].

In the first office visit, BP should be measured simultaneously in both arms with an electronic device (Strength of Recommendation I, Quality of Evidence A). If an interarm SBP difference is >10 mmHg and confirmed with repeated measurements, the arm with the higher BP should be used for subsequent evaluation. If an interarm SBP difference is persistently between 15 mmHg and 20 mmHg, further investigations to confirm atherosclerosis or arterial diseases of the upper extremities are recommended. To avoid the white-coat effect, automated office blood pressure (AOBP) measurements can be done automatically in a quiet room without medical staff. This method is called unattended AOBP measurement. However, it is not possible in most hospitals in Thailand, and its BP threshold and target require more clinical outcome studies. THS strongly recommends standardized steps in office BP measurement for diagnosis and treatment of hypertension (Strength of Recommendation I, Quality of Evidence A).

Home BP measurement (HBPM) can confirm or exclude white-coat effect (higher office than out-of-office BP) and detect masked hypertension (masked hypertension is defined as normal office BP and high out-of-office BP), leading to a more precise diagnosis of BP phenotypes in hypertension. In pharmacologically treated cases, HBPM will enhance medication adherence of the patients, leading to better BP control. We, therefore, recommend using HBPM in all treated hypertensive cases (Strength of Recommendation I, Quality of Evidence A) unless the patient is incapable of performing it. Only validated oscillometric upper arm devices are recommended for home use (Strength of Recommendation I, Quality of Evidence A). Wrist or finger devices are not generally endorsed, but they may be required in markedly obese patients in whom BP measurement in the upper arm is too difficult to achieve or may be unreliable. Cuffless devices are still not standardized and cannot be advised for clinical use at this time (Strength of Recommendation III, Quality of Evidence C). Patients and/or their caregivers should learn about specific advice for the appropriate technique in using HBPM and how to record their BP properly (Table 2).

HBPM should be done twice a day, in the morning and the evening. Morning measurement should be performed within 1 h after waking up, after urination, before taking the morning dose of antihypertensive drugs, and before breakfast. Evening measurements should be made before retiring to sleep. A physician may adjust the frequency and time for BP measurement as needed in specific circumstances. At least 2 measurements should be made on each occasion, 1 min apart between readings. All readings should be recorded without selection bias. Subjects should always show their BP records to their healthcare provider at the clinic visit. Home BP is evaluated by using the mean values of all measurements, both in the morning and evening. When HBPM activates anxiety or causes stress to the subjects, it should be stopped. More details on HBPM can be found in the 2022 Thai Hypertension Society guidelines on HBPM [8].

Ambulatory blood pressure measurement or monitoring (ABPM) is another type of out-of-office BP measurement, which provides intermittent BP records throughout the day when the subjects stay in their usual environment. The ambulatory BP device is fitted on an individual’s non-dominant arm and then programmed to work spontaneously at 20–30 min intervals (Figure 2). Like HBPM, this technique can avoid white-coat effects from office BP measurements and can detect masked hypertension. The advantage of ABPM over HBPM is the obtaining of nighttime BP and the rising patterns of BP around the awakening period, the so-called morning BP surge, and provides BP records throughout the whole day, so BP variability can be detected and clarified.

Figure 2.

The fitting of ABPM device on patient’s upper arm. ABPM, ambulatory blood pressure measurement.

The difference between daytime and nighttime BP can be categorized as shown in Table 3. Individuals with reduced-dippers and sometimes risers have higher cardiovascular (CV) risk as compared with those who are dippers [9, 10]. The absolute value of nighttime BP is also an important consideration. Nocturnal hypertension, as defined by average nighttime BP at least 120/70 mmHg, is associated with increased CV risk. Nighttime BP has better correlation with CV events than daytime or office BP [10]. It has been demonstrated that 74.0% of Thai hypertensive subjects treated at a university hospital have reduced dipping or rising BP patterns [11]. ABPM also helps to confirm hypotension due to excessive BP lowering and to assess extreme BP changes in patients with autonomic failure. When there is discordance between office and home BP, ABPM should be performed to make a precise diagnosis and assist in delivering the proper treatment. We recommend ABPM to determine specific diurnal BP patterns, nocturnal hypertension, morning BP surge, and BP variability (Strength of Recommendation I, Quality of Evidence A).

THS’ recommendations for BP measurement are summarized in Table 4.

According to the previous 2019 THS guidelines [12] and current international guidelines [13–16], hypertension is defined based on repeated office SBP values of at least 140 mmHg and/or DBP of at least 90 mmHg. However, there is a continuous relationship between BP and CV, renal adverse events, and mortality starting from an office SBP >115 mmHg and DBP >75 mmHg [17]. In the Asian population, the CV risks were shown to increase even with BP <140/90 mmHg [18–23]. Furthermore, RCTs have shown that lowering BP to <130/80 mmHg can reduce cardiovascular diseases (CVD) [24, 25]. These THS guidelines change the category of BP between 130–139 mmHg and/or 80–89 mmHg from the term high-normal BP to BP at risk to emphasize the importance of the increasing CV risk in this BP range (Strength of Recommendation I, Quality of Evidence A).

The definition and classification of the severity of hypertension, which is determined from the BP measured in clinics, hospitals, or public health centres, is shown in Table 5. The thresholds for diagnosis of hypertension using different methods of BP measurements are summarized in Table 6.

• White-coat hypertension (isolated office hypertension) is defined as high office BP (SBP ≥140 mmHg and/or DBP ≥90 mmHg) and normal out-of-office BP.

• Masked hypertension is defined as normal office BP (SBP <140 mmHg and DBP <90 mmHg) and high out-of-office BP.

Diagnosis of hypertension can be made if high BP, according to the criteria in Table 6, were detected repeatedly, usually by office BP measurement (Strength of Recommendation I, Quality of Evidence A). THS recommends the use of standard office BP measurement for better assessment of BP values, as mentioned above (Strength of Recommendation I, Quality of Evidence A). The Thai HBPM study showed a significant prevalence of white-coat hypertension and masked hypertension. Therefore, THS encourages the use of out-of-office BP monitoring to achieve a more accurate diagnosis (Strength of Recommendation I, Quality of Evidence A). Since high BP detected by out-of-office BP monitoring has better prognostic values than high office BP, if there is a discrepancy between these 2 measurement methods, the diagnosis should be considered based on out-of-office BP (Strength of Recommendation I, Quality of Evidence A). If out-of-office BP is not available and the previous BP reading was high, the diagnosis of hypertension should be made if repeated standardized office BP or AOBP in that visit is high (Strength of Recommendation I, Quality of Evidence A). Subject with office BP of 130–139/80–89 mmHg and normal out-of-office BP, hypertension should be diagnosed if the subject has hypertension-mediated organ damage (HMOD) (see Section “Evaluation of a patient with hypertension”) or CVD or DM or high CV risk (Strength of Recommendation I, Quality of Evidence A).

White-coat hypertension is diagnosed if normal out-of-office BP is detected in subjects with high office BP. In subjects with office BP between 130–139/80–89 mmHg, out-of-office BP monitoring should also be performed. If the out-of-office BP is high, masked hypertension is diagnosed.

If any person has severely elevated BP (grade 3 hypertension) while staying in the hospital, the clinical diagnosis of hypertension should be made even in the inpatient department setting (Strength of Recommendation I, Quality of Evidence A). In subjects with non-severely elevated BP during hospital admission, the follow-up schedule should be made after discharge, to properly screen for possible hypertension (Strength of Recommendation I, Quality of Evidence A). The diagnostic algorithm for hypertension is summarized in Figure 3.

Figure 3.

Diagnostic algorithm for hypertension. ABPM, ambulatory blood pressure measurement; AOBP, automated office blood pressure; BP, blood pressure; CV, cardiovascular; CVD, cardiovascular disease; DM, diabetes mellitus; HBPM, home blood pressure measurement; OPD, outpatient department.

The purpose of the patient evaluation in hypertension is to identify factors contributing to the development of hypertension (such as diet, physical inactivity, concomitant medications, or family history), to screen for secondary causes of hypertension, to identify concomitant CV risk factors (e.g., DM, dyslipidemia, obesity), to establish whether there are evidences of HMOD or existing CV, or renal disease and, to estimate the patient’s total CV risk to guide threshold for treatment initiation, to guide BP target and the use of statins. Patient evaluation should be initiated starting from individuals with BP at risk and every patient with hypertension [12–16].

A detailed medical history should include duration of hypertension, record of current and past BP values, antihypertensive medications, including their effectiveness and intolerance, family history of hypertension, history of CVD, kidney disease, and history of erectile dysfunction. History of possible secondary hypertension, concomitant CV risk factors, history, and symptoms of HMOD are also required. Lifestyle evaluation, including exercise levels, body weight changes, diet, smoking status, alcohol consumption, use of licorice, recreational drug use, the individual’s stress level, and sleep history are needed. Thorough physical examination gives important indications of potential causes of secondary hypertension, signs of comorbidities, and HMOD. Physical examination should include body habitus, including waist circumference, fundoscopic examination for hypertensive retinopathy, heart and carotid artery auscultation, palpation of peripheral pulses, neurological examination, and look for signs of secondary hypertension, co-existing diseases, and HMOD. Ankle-brachial index (ABI) and pulse wave velocity (PWV) may be considered if possible (Strength of Recommendation Ilb, Quality of Evidence B).

HMOD refers to structural or functional changes in target end organs (heart, blood vessels, brain, eyes, and kidneys) caused by high BP. The recommended laboratory tests are hemoglobin and/or hematocrit, fasting plasma glucose and glycated hemoglobin, blood lipid profiles, serum creatinine for glomerular filtration rate estimation (eGFR), potassium, sodium, uric acid, and urine analysis. Additional investigations of screening for HMOD are recommended in Table 7.

For Thai individuals, a normal body mass index (BMI) ranges from 18.5 kg/m² to 22.9 kg/m² and a waist circumference <90 cm (36 inches) for men and <80 cm (32 inches) for women or not exceeding half of their height (a waist-to- height ratio <0.5) for both sexes. To achieve long-term weight reduction and control, it is recommended to focus on cognitive-behavioral therapy processes [26]. In cases where weight loss cannot be achieved through lifestyle modifications alone, consideration may be given to weight loss medications and/or bariatric surgery as indicated.

The prototype dietary pattern for reducing BP is the Dietary Approaches to Stop Hypertension (DASH) diet [27, 28]. Moreover, other healthy dietary patterns also have evidence that they can contribute to reducing BP levels, such as a lactoovo vegetarian diet (which incorporates eggs and dairy products as protein sources), the Mediterranean diet [29]. These diets emphasize the consumption of unprocessed foods, whole grains, unrefined carbohydrates, legumes, vegetables, and fruits. They also focus on low-fat protein sources such as lean meats, plant-based proteins, low-fat dairy, and dairy products. However, it is not recommended to rely on potassium and/or magnesium supplements in the form of dietary supplements to reduce BP. For chronic kidney disease (CKD) patients, it is advisable to seek guidance on appropriate dietary recommendations from a physician or dietitian. It is also advisable to avoid dietary supplements or herbal extracts that may potentially increase BP, such as Ma Huang (Ephedra), licorice, bitter orange, and Yohimbe.

Following the recommendations of the World Health Organization (WHO), it is advised to consume no >2 g of sodium per day to prevent non-communicable diseases (NCDs) and help lower BP in individuals with hypertension. Increasingly strict sodium limitations to no >1.5 g/d may further aid in reducing BP. A sodium intake of 2 g is equivalent to approximately 1 teaspoon of salt (5 g of sodium chloride) or 3 teaspoons of fish sauce or soy sauce. Using salt substitutes can be an alternative option for reducing sodium intake. These products often partially replace sodium salts with potassium salts; therefore, patients with CKD should receive appropriate advice from a physician or dietitian. It is also recommended to consume fresh, minimally processed foods and avoid highly processed foods and excessive seasoning to reduce or prevent excessive sodium intake.

Regular aerobic exercise with appropriate intensity and duration is recommended, with no >2 consecutive days of rest. Individuals can choose from various intensity levels of exercise, including:

• Moderate intensity: Exercise that elevates heart rate to 50.0%–70.0% of maximum heart rate (calculated as 220 minus age). This level of exercise should be maintained for an average of 150 min/week.

• Vigorous intensity: Exercise that elevates heart rate beyond 70.0% of maximum heart rate. This level of exercise should also be maintained for an average of 75 min/week.

Isometric exercises, such as weightlifting, which involve muscle contraction against resistance, may increase BP levels. Therefore, if BP is not well controlled, it is advisable to consult a physician before starting such exercises. Additionally, it is recommended to reduce daily sedentary time and increase movement whenever possible [26, 30].

For overall health, individuals who do not consume alcohol should not be encouraged to start, and those who do consume alcohol should limit their intake. Specifically, women should not exceed 1 standard drink per day, and men should not exceed 2 standard drinks per day (1 standard drink is equivalent to a beverage containing approximately 10 g of alcohol). Additionally, it is recommended to have alcohol-free days each week [31].

For individuals who smoke, it is recommended to quit smoking, including both traditional cigarettes, e-cigarettes (vaping), and waterpipe smoking [32, 33]. Physicians or healthcare professionals should advise patients to quit smoking or encourage them to feel motivated to quit smoking (Strength of Recommendation I, Quality of Evidence A). For individuals who do not smoke, it is advisable to avoid second-hand smoke exposure.

Emotional stress increases the risk of hypertension and CVD [34, 35]. It is recommended to manage stress appropriately, along with using complementary techniques such as meditation, breathing exercises, music, and yoga [36–39].

Examples include avoiding places with noise pollution and air pollution [40, 41] (Strength of Recommendation IIa, Quality of evidence C).

Recommendations for lifestyle modifications to control and prevent hypertension are summarized in Table 8.

The decision to start antihypertensive medication(s) in patients with hypertension is based on 4 key consideration factors: the average standardized office BP measurement together with out-of-office BP measurement if available, the individual’s CV risk level, co-existing disease(s) in that individual, especially CVD and DM, and lastly the status of HMOD. BP threshold and use of risk estimation to guide pharmacological treatment of hypertension are summarized in Table 9.

Suggested target BP levels for drug treatment are summarized in Tables 10 and 11. Nevertheless, there are 2 points of caution. First, the patients’ BP should initially be lowered to under 140/90 mmHg, and if they show good tolerance, then BP should be further reduced to 130/80 mmHg or less. Second, data show some detrimental effects of BP that is too low, especially for elderly, frail patients, patients with pre-existing CVD or comorbidity. For some of these patients, the treatment target should be individualized.

Five major drug classes are recommended as first-line agents for the treatment of hypertension. These 5 major drug classes are angiotensin converting enzyme inhibitors (ACEis), angiotensin receptor blockers (ARBs), beta-blockers, calcium-channel blockers (CCBs), and thiazide/thiazide-like diuretics. The selection of 5 major drug classes as first-line agents was based on the following criteria: 1. a proven ability to reduce BP as monotherapy, 2. evidence from RCTs that they can reduce morbidity and mortality from high BP, and 3. a favorable safety and tolerability profile. To select the appropriate BP medication, physicians have to consider the pre-existing comorbidities other than high BP, as well as the contraindications of each class of drugs.

In the year 2021, angiotensin receptor-neprilysin inhibitor (ARNI) was approved for the treatment of hypertension in Thailand. ARNI is a combination of an ARB (valsartan) and a neprilysin inhibitor (sacubitril), which simultaneously blocks the effects of angiotensin II at the AT-1 receptor and inhibits the degradation of natriuretic peptides, thus promoting peripheral vasodilatation and reducing BP [42]. In a recent meta-analysis of 10 studies including 5,931 hypertensive patients, ARNI reduced office SBP by 6.5 mmHg and DBP by 3.3 mmHg compared with placebo [43]. 24-h SBP and DBP were also reduced by 7.0 and 3.2 mmHg, respectively. Because of a lack of evidence to demonstrate its efficacy to reduce overall CV events in patients with hypertension, it cannot be recommended as 1 of the first-line agents for hypertension therapy. Nevertheless, ARNI may be an appropriate choice, however, in patients with true resistant hypertension (Strength of Recommendations Ilb, Quality of Evidence B) and should be used in patients with heart failure with reduced ejection fraction (HFrEF) instead of a renin angiotensin system (RAS) blocker. (Strength of Recommendations I, Quality of Evidence A).

Selective sodium-glucose cotransporter-2 inhibitors (SGLT2i) have demonstrated significant BP-lowering effects through various mechanisms such as natriuresis and reduction of sympathetic tone [44]. A meta-analysis of 43 RCTs with 22,528 diabetic patients confirmed the efficacy of SGLT2i in BP lowering [45]. Glucagon-like peptide 1 receptor agonists (GLP1-RA) also have potential for BP reduction. The reduction in BP, shown in randomized clinical trials, was observed early in the treatment, before any significant weight loss occurred, suggesting independent action of GLP1-RA on BP [46]. The proposed mechanisms for its effects might include natriuresis, direct vasodilatation, decreased sympathetic activity, or improved endothelial function [47]. However, there are no RCTs of these medications dedicated to general hypertensive patients, and they have not been approved for BP reduction indication in Thailand. However, they can be used as an ancillary treatment in hypertensive patients with comorbidities that indicate the use of SGLT2i or GLP1-RA. (Strength of Recommendation IIa, Quality of Evidence A).

We recommend the use of 2 antihypertension drugs as a single-pill combination (SPC) in hypertensive patients wherever and whenever available (Strength of Recommendation I, Quality of Evidence A), because reducing the number of pills to be taken daily can improve adherence to treatment and increase the rate of BP control. Recently, the START-Study has shown that antihypertensive combination therapy using SPC could reduce all-cause mortality and CV events when compared to identical drugs prescribed as multi-pill [48]. The THS recommendations for antihypertensive drug treatment are summarized in Table 12.

The primary goal of antihypertensive treatment is to provide BP control over 24 h. Antihypertensive drugs that have a long duration of action that can cover the 24 h with a single daily administration should be preferred. Most of the evidence on the benefit of BP-lowering treatment has come from clinical trials using morning dosing of antihypertensive agents. The Treatment in Morning versus Evening (TIME) study, published in 2022, showed no significant difference in the primary outcome (hospitalization for major CV events and vascular death) between groups of patients randomized to the evening-dosing and the morning-dosing [49]. The reported non-adherence to therapy was significantly higher with evening versus morning dosing (39.0 versus 22.5%, P < 0.0001), with no reported safety concerns. THS suggests the appropriate timing of prescribed antihypertensive drugs in Table 13.

Individuals with white-coat hypertension have less prevalence of HMOD than those with sustained hypertension and have a lower risk of CV events. However, compared with true normotensive individuals, persons with white-coat hypertension have increased adrenergic activity [50], a greater prevalence of metabolic risk factors, a more frequent asymptomatic HMOD [51], a higher risk of new-onset DM, and are more likely to progress to sustained hypertension and have a higher risk of CV mortality [52–54]. Ideally, out-of-office BP measurements should include both ABPM and HBPM because the 2 measurement values can give discrepant results. Although the CV risk of people with white-coat hypertension, in whom both ABPM and HBPM are normal, appears to be low and close to that of normotensive individuals [55], they need to regularly follow up. Usually, antihypertensive drug treatment effectively lowers office BP in white-coat hypertensive patients, but the effect on out-of-office BP is small and variable [56]. Whether patients with white-coat hypertension should receive antihypertensive drugs is still unresolved; however, drug treatment can be given in such patients with HMOD and/or high CV risk (Strength of recommendation IIa, Quality of Evidence C) as in Table 14.

The optimal approach for detecting masked hypertension is challenging. An office BP in the BP at risk range is associated with a higher likelihood of masked hypertension. Masked hypertension has been reported to be associated with HMOD and has an increased risk of developing DM and sustained hypertension [53, 57]. Meta-analysis has shown that the CV risk in patients with masked hypertension is substantially greater than that of individuals with true normotension and even close to the risk of patients with sustained hypertension [58, 59]. No therapeutic RCT has ever been done on masked hypertension. However, given the adverse prognostic nature of masked hypertension, we recommend the management of masked hypertension as in Table 15.

Increased BP, starting from 115/75 mmHg, is associated with coronary artery disease (CAD)-related mortality [17]. BP reduction can decrease the incidence of CAD in hypertensive individuals regardless of the type of antihypertensive medication used [60]. Many randomized placebo-controlled trials involving patients with CAD showed that strict SBP lowering prevented complications of CAD. There were concerns about the possibility that an excessive lowering of DBP may increase the incidence of CV events in patients with CAD, the so-called J-curve phenomenon. However, from a systematic review and meta-analysis of 7 randomized placebo-controlled trials enrolling 34,814 CAD patients who achieved DBP <80 mmHg included in the drug-intervention group, the intervention was associated with an 11% reduction in coronary revascularization and a 31.0% reduction in heart failure (HF) [61]. Also, a meta-analysis of 4 RCTs, in which the achieved DBP was <75 mmHg, showed that the drug intervention was associated with a 22.0% reduction in HF [61] (Table 16).

HF is a significant health problem in Thailand. Between 2008 and 2013, the HF hospitalization rate in Thailand gradually increased from 61,594/year to 80,246/year [62]. Data from an HF registry and a real-world hospital database in Thailand consistently show that hypertension is a significant comorbidity in HF patients. According to the Thai Acute Decompensated Heart Failure Registry (ADHERE), which collected data from 1,612 patients with acute decompensated heart failure (ADHF) admitted during 2006–2007, the prevalence of hypertension in Thai HF patients was around 65.0% [63]. Ten-year follow-up data from the ADHERE registry shows that the mortality rate was above 70%; having hypertension at baseline was more common in those who died compared to those who survived [64].

According to contemporary randomized control trials in HF, 4 drug classes are recommended for treatment of HFrEF: ACEi or ARB or ARNI, beta-blocker, spironolactone, and SGLT2i [69]. ACEi, ARB, or ARNI and beta-blockers are part of the basic antihypertensive treatment strategy in Thailand. Spironolactone is recommended in patients with resistant hypertension. Curiously, SGLT2i has shown an important additional aspect that they can reduce office BP and average BP from ABPM significantly in randomized controlled CV outcome trials in patients with type 2 DM [70]. Apart from these 4 major drug classes, diuretics are recommended to manage fluid balance and reduce congestion in HF patients. Thiazide or thiazide-like diuretics are preferable if fluid retention is not a significant problem. Loop diuretic, on the other hand, is given to patients who suffer from fluid retention, especially if they have pulmonary edema or advanced CKD (eGFR <30 mL/min/1.73 m²) (Table 18).

The significance of hypertension as a risk factor for both ischemic and hemorrhagic stroke is well established. Importantly, by effectively reducing BP, the risk of stroke can be reduced. Aggressive BP control through lifestyle modifications and pharmacological interventions can significantly decrease the risk of stroke occurrence and recurrence in hypertensive individuals. Another challenge lies in the management of BP during the acute phase of stroke. In patients with ischemic stroke, remarkably high BP has been linked to hemorrhagic transformation and brain edema, while in patients with intracerebral hemorrhage, high BP may experience hematoma expansion. Conversely, excessively low BP in patients with acute ischemic stroke may be associated with cerebral hypoperfusion and clinical deterioration. Acknowledging this phenomenon emphasizes the need for careful monitoring during the acute phases of stroke. Timely intervention is crucial to reduce complications associated with stroke [95–109] (Table 22).

The high BP associated with atherosclerosis is a key pathology for the development of peripheral artery disease (PAD). Regular BP monitoring and control of BP can help prevent the development and progression of PAD and reduce the risk of complications associated with this condition [110]. No RCT has been conducted specifically to explore the optimal BP target for preventing PAD. Nonetheless, evidence suggests that SBP below 120 mmHg or above 160 mmHg is associated with a higher risk of PAD-related adverse outcomes, compared to maintaining an SBP within the 120–129 mmHg range [111]. All major BP-lowering medications are equally recommended [111, 112] (Table 23).

Hypertension is common in both type 1 and type 2 diabetes. In type 1 diabetes, hypertension usually develops at least 5–10 years after the diagnosis of diabetes and parallels the development of diabetic kidney disease [113–116]. In type 2 diabetes, hypertension is usually associated with metabolic syndrome and may already be present at the time of diagnosis of diabetes [115]. Overall, the prevalence of hypertension in people with diabetes is 60.0%–70.0% [117, 118]. Coexistence of diabetes and hypertension markedly increases the risk of both micro- and macrovascular complications [116]. Hypertension is therefore considered one of the major treatment goals in people with diabetes, in addition to glucose, lipid, and body weight control [116, 119].

Epidemiological studies demonstrated a positive correlation between BP levels and incident CVD in both individuals with and without diabetes [120–122]. Randomized control trials have shown significant benefits of BP-lowering treatment in individuals with SBP of 130 mmHg or higher and additional CV risk factors [123–125]. However, in individuals with diabetes, clinical trials that demonstrated the benefit of reducing BP to <140/90 mmHg were limited. The Action to Control Cardiovascular Risk in Diabetes, Blood Pressure (ACCORD BP) trial is the largest RCT aiming for different SBP targets in people with type 2 diabetes [126]. The primary composite outcome of the study, which included non-fatal MI, non-fatal stroke, or death from CV causes, was not significantly different between the intensive therapy (targeting SBP below 120 mmHg) and standard therapy (targeting SBP below 140 mmHg) groups. However, the prespecified secondary outcome of stroke was significantly reduced by 41.0% in the intensive treatment group. The SPRINT trial [24], which enrolled non-diabetic individuals with increased CV risk to intensive treatment (SBP target of <120 mmHg) versus standard treatment (SBP target of <140 mmHg) demonstrated that the primary composite outcome of MI, acute coronary syndromes, stroke, HF, or death from CV causes was significantly reduced by 25.0% in the intensive treatment group. Despite some apparent discrepant results between the 2 trials, most experts agree that both the ACCORD and SPRINT trials convey the same message of a greater CV benefit with more aggressive BP lowering [127]. Moreover, a recent network meta-analysis of BP control in type 2 diabetes found that the lowest risk of major CVD was found in patients with achieved SBP levels of 120–124 mmHg [128]. Diagnosis and treatment of hypertension in patients with diabetes [28, 119, 129–143] are summarized in Table 24.

The WHO reports that, in 2020, nearly 1 billion people, or 14.0% of the global population, had obesity (BMI ≥30 kg/m²), and Thailand is not immune to this challenge [144]. Similarly, a 2023 WHO global report on hypertension stated that over 1.3 billion adults, or one-third of the worldwide population, are affected by hypertension [145]. The American Heart Association raises concerns about obesity and hypertension as global public health crises [146, 147]. The association between obesity and hypertension is well documented [148–151]. Obesity is linked to hypertension through several mechanisms [152, 153]. These include hyperleptinemia, increased sympathetic activity, and activation of the renin-angiotensin-aldosterone system. These mechanisms lead to vasoconstriction and shift the pressure-natriuresis curve to the right, resulting in salt and water retention. Vascular and kidney dysfunction caused by low-grade inflammation and lipotoxicity also contribute to hypertension in obese individuals. Additionally, obstructive sleep apnea (OSA) is a significant risk factor for hypertension in obese individuals, as it disrupts sleep patterns and oxygen levels, contributing to increased inflammation and sympathetic activity [154–156]. Effective BP control is crucial for obese individuals with hypertension [157]. An important consideration in managing hypertension in obese individuals is the accurate measurement of BP. Appropriate cuff size is emphasized to ensure correct measurement of BP [158, 159].

While target BP goals are generally the same for individuals with and without obesity, achieving these goals can be more challenging in obese individuals. This often requires a more intensive approach of combining comprehensive lifestyle modifications, especially weight reduction, and titrated medication regimens [153, 160–172]. In individuals who, despite lifestyle modifications and obesity pharmacotherapy, cannot significantly reduce body weight, bariatric or metabolic surgery may be considered. Candidates for this procedure are those with a BMI ≥40 kg/m² or those with a BMI of 35-39.9 kg/m² and having comorbid conditions [173, 174]. Individuals with type 2 diabetes and BMI ≥30 kg/m² are also candidates for metabolic surgery if they are not in good glycemic control while on reasonable medical therapy [175]. Before implementing treatment with bariatric surgery, it is essential that individuals fully understand the potential risks and long-term commitments associated with bariatric surgery. Despite various strategies to reduce body weight, many obeseindividuals may still have high BP and thus require antihypertensive medications [176–181]. A summary of recommendations for the treatment of hypertension in patients with obesity is shown in Table 25.

The prevalence of OSA in the Thai population was 4.4%-11.4%, depending on the definition of OSA [182]. The prevalence of hypertension in OSA ranges from 35.0%-80.0% [183] and may be related to the severity of obstruction. The pathogenesis of OSA-associated hypertension may be caused by intermittent hypoxia that leads to systemic inflammation and increased oxidative stress [183]. The characteristics of hypertension in OSA are a non-dipping pattern and nocturnal hypertension, which lead to an increased risk of vascular complications [184]. In patients with OSA, the prevalence of masked hypertension and resistant hypertension is higher than in the general population [185]. THS recommendations for treatment of hypertension in patients with OSA are summarized in Table 26.

Normotensive atrial fibrillation (AF) patients have a 2-fold mortality rate, 5-fold stroke, and 3-fold risk of developing HF when compared to individuals with a normal sinus rhythm. Hypertension is an independent risk for stroke in AF by 1.8–2.0 fold when compared to normotensive AF [186], therefore, hypertension with AF is a high risk. The prevalence of hypertension in AF patients is 62.0% by the Joint National Committee 8 definition and 79.0% by the American College of Cardiology/American Heart Association 2017 definition [186]. The diagnosis of hypertension in AF patients is ≥130/80 mmHg and is the threshold for treatment to the target BP of 120–129/<80 mmHg. Because of beat-to-beat BP variability, the BP measurement in AF needs at least 3 readings of office BP by auscultatory sphygmomanometer (Strength of Recommendation IIa, Quality of Evidence B) or automated oscillatory BP device with satisfactory SBP, but DBP may be overestimated by 2.1 mmHg [187] (Strength of Recommendation IIa, Quality of Evidence B). Some automated BP devices have been validated to detect AF during BP measurement, which is helpful to detect asymptomatic AF with a sensitivity of 0.98 and a specificity of 0.92 [188]. Recommendations for prevention and treatment of AF in hypertensive patients [189–200] are summarized in Table 27.

The threshold office BP to consider treatment is the same as the younger age group (Strength of Recommendation I, Quality of Evidence A), and there are 2 target BP levels to reach sequentially.

No attempt should be made to reduce BP <120/70 mmHg (Strength of Recommendation III, Quality of Evidence C).

The physical activity recommendations are adjusted according to functional limitations for individual persons. The low salt diet or weight reduction may be applied cautiously, as it may cause loss of appetite or sarcopenia. There are more side effects of drug treatment in elderly persons, so “start low, go slowly” is a good strategy [213]. The choice of antihypertensive drugs can be any of the 5 major classes. However, beta-blockers can be used if there are compelling indications. The screening for orthostatic hypotension should be scheduled systematically (Strength of Recommendation I, Quality of Evidence C) as it is frequently found in elderly persons taking antihypertensive drugs. HBPM and ABPM are helpful to verify antihypertensive-related hypotension, postprandial hypotension, which can be aggravated by diuretics and vasodilators. ABPM can detect non-dipper, reverse dipper, and early morning surge phenotypes, and is useful for dose and timing adjustment of antihypertensive drugs in the elderly.

The same strategies, “start low, go slowly,” should be applied (Strength of Recommendation I, Quality of Evidence C). The beneficial effects of BP-lowering intervention are evident in the very elderly persons who are of good functionality to moderately frail [214, 215] but not in very frail individuals. In this group, frailty and functionality should be assessed before initiation of treatment and repeated annually to monitor the evolution of individuals’ status (Strength of Recommendation I, Quality of Evidence C).

BP threshold for initiation of drug treatment is 160 mmHg SBP (Strength of Recommendation I, Quality of Evidence A). The threshold of 140–159 mmHg may be considered in selected cases (Strength of Recommendation IIb, Quality of Evidence C) with target SBP of 140–150 mmHg and DBP <80 mmHg (Strength of Recommendation I, Quality of Evidence A). An optional target SBP of 130–139 mmHg, if well tolerated to treatment, is advised, although cautiously in individuals with DBP <70 mmHg (Strength of Recommendation IIb, Quality of Evidence B).

The reduction of treatment can be considered in persons ≥80 years with SBP <120 mmHg or severe orthostatic hypotension, or high frailty level (Strength of Recommendation IIa, Quality of Evidence C).

The mental functionality can be assessed by using the minimental state examination (MMSE)-Thai 2002 from the Thai Ministry of Public Health. The physical limitation and dependency in daily life activities can be evaluated by Katz index from 0 (completely dependent) to 6 (completely autonomous) in bathing, dressing, toileting, transferring, feeding, and continence. For each daily activity, “0” means the person is unable to do it without assistance, 0.5 needs some assistance, and 1 means no need for any assistance. The MMSE score, Katz score, and other comorbidities are used to classify the level of frailty into 3 groups.

The treatment should be individualized in persons with moderate to severe levels of frailty/functionality and/or dementia (Strength of Recommendation I, Quality of Evidence C).

The definition of isolated systolic hypertension (ISH) is SBP ≥140 mmHg and DBP <90 mmHg. ISH is commonly found in persons >50 years of age, especially >70 years, women, and overweight individuals [216]. The meta-analysis suggested that treatment of ISH could reduce CVD outcomes by 26.0%, CV mortality by 18.0%, and all-cause mortality by 13.0% [217]. Because of BP variability in the elderly, HBPM and repeatedly averaged office BP may help in the diagnosis of ISH (Strength of Recommendation I, quality of evidence C).

The threshold BP to initiation of pharmacological treatment in ISH is ≥140 mmHg of SBP with consideration of functionality, frailty, and comorbidity. The primary target of SBP is 140–150 mmHg (Strength of Recommendation I, Quality of Evidence A), and the secondary SBP target is 130–139 mmHg, if well tolerated to treatment and DBP is not <70 mmHg (Strength of Recommendation IIb, Quality of Evidence B) [214].

ISH is difficult to treat, and a balance should be made between SBP reduction without too low DBP, causing organ hypoperfusion [218]. The drugs of choice are CCBs and thiazide/thiazide-like diuretics (Strength of Recommendation I, Quality of Evidence A), while ACEis and ARBs have lesser efficacy. Free or fixed combination therapy with ACEis or ARBs and CCBs or thiazide/thiazide-like diuretics should also be considered, particularly when compelling indications such as CAD, CKD, diabetes, and congestive HF coexist (Strength of Recommendation I, Quality of Evidence B). We recommend starting with dual combination therapy for older people with ISH who are not too frail (Strength of Recommendation I, Quality of Evidence C).

Effective treatment of resistant hypertension requires life-style modification, along with a stepwise approach using antihypertensive medications with different mechanisms of action and considering device-based treatment when necessary. A suggested algorithm for managing resistant hypertension is shown in Figure 6.

Figure 6.

Recommendations for the management of resistant hypertension. ACEI, angiotensin converting enzyme inhibitors; ARB, angiotensin receptor blockers; ARNI, angiotensin receptor-neprilysin inhibitor; ASCVD, atherosclerotic cardiovascular disease; BP, blood pressure; eGFR, glomerular filtration rate estimation; HMOD, hypertension-mediated organ damage; RAS, renin angiotensin system.

A few patients with resistant hypertension still have uncontrolled hypertension despite using full medication and having good adherence. Some of these patients may develop adverse reactions to various BP-lowering drugs, and the medications cannot be titrated to the required maximum doses. In these scenarios, consideration of device-based treatment is necessary. The device-based treatment that has been widely confirmed to be effective in resistant hypertension is catheter-based renal denervation therapy (RDN). To date, many clinical trials have proven that RDN can lower BP in patients with resistant and even refractory hypertension. However, the BP reduction after RDN can vary among patients. Since RDN is an invasive and costly treatment, we suggest using RDN only after careful and appropriate patient selection, such as refractory hypertension (Strength of Recommendation I, Quality of Evidence C) or resistant hypertension with established clinical ASCVD or progressive HMOD (Strength of Recommendation IIa, Quality of Evidence B) [222].

To guide management strategies, this guideline introduces the term “pre-critical symptomatic hypertension (PSH)” as a replacement for “hypertensive urgency.” The traditional terminology lacks specificity regarding symptoms or clinical severity, often leads to confusion, and may result in inappropriate practices, such as overly rapid BP reduction using intravenous antihypertensives.

Distinguishing between a hypertensive emergency and PSH is crucial. PSH, defined as a significant and acute elevation in BP (often exceeding grade 3 hypertension), may present with symptoms such as mild headaches, dizziness, lightheadedness, or nausea, without evidence of organ damage [224].

Management strategies should encompass comprehensive evaluation for the presence of organ damage [223] (Strength of Recommendation I, Quality of Evidence B), including (1) CV system: acute coronary syndromes, HF, and aortic dissection, (2) renal system, namely, AKI, (3) central nervous system: hypertensive encephalopathy, stroke (both ischemic and hemorrhagic), and TIA, or malignant hypertension, (4) ocular changes: retinopathy, including hemorrhages and papilledema, and (5) other clinical presentations such as hypertensive thrombotic microangiopathy, which causes severe BP elevation associated with hemolysis, and thrombocytopenia in the absence of other causes and improvement with lowering BP.

The evaluation of acute organ damage involves a thorough physical examination as well as a series of diagnostic tests, including but not limited to creatinine, sodium, potassium levels, complete blood count, urine analysis, point of care ultrasonography, electrocardiogram, chest X-ray, fundoscopy, cardiac troponin levels, transthoracic echocardiogram, computed tomography angiography of the thorax or abdomen, and computerized tomographic or magnetic resonance imaging of the brain, as needed [223].

It is crucial to initiate treatment without delay (Strength of Recommendation I, Quality of Evidence A) to reduce the risk of further organ damage, morbidity, and mortality. The acute phase treatment in patients with hypertensive emergencies based on organ damage is shown in Table 34 [223, 225–227]. Evaluation and treatment of PSH and hypertensive emergency are summarized in Table 35.

The major problems in hypertension control in Thailand are the increasing prevalence in the adult population and the inadequacy of awareness, treatment, and control, all of which have become worse in recent years [2].

The low level of awareness in Thailand can be explained not by the lack of systemic screening, but by the lack of confidence in the diagnosis of this mostly asymptomatic disease. The lack of confidence among patients results from the improper BP measurement technique used in the screening process, leading to unacceptable variations in BP. This discrepancy becomes apparent when patients discover that the screened BP significantly differs from previous or later measurements. Poor patients’ confidence is also a result of the inadequacy of time that healthcare personnel can spend explaining and answering many important questions that patients like to know. The inertia in diagnosis from healthcare personnel, especially the physician who should be the responsible person, is also very important. Unpublished data from many hospitals in Thailand showed that there was no proper diagnosis of hypertension, even when the in-hospital BP measurement was beyond grade 2. If there is still no general agreement in making a diagnosis, even among physicians, then there will be no trust among patients, who will be very confused about the diagnosis.

The lack of proper hypertension treatment in Thailand persists even years after the Thai government has provided full treatment coverage for almost the entire Thai population. The overpopulation of clinics can partly explain this in almost every government-supported health center. The long waiting time, the neglected feelings after very short attention by the physician, never having enough time to explain and ask about any possible adverse reaction from the treatment, and prescribing that remains the same almost every visit, whatever the BP is, are among the main factors that discouraged many patients from regular follow-up.

Despite numerous clinical studies suggesting benefits from starting treatment with antihypertensive medication in the form of a SPC [48], no antihypertensive medication in this form has been approved for use in the Thai National Essential Drug List.

The higher prevalence of hypertension in the Thai adult population is caused by high salt intake, an increase in overweight and obesity, and air pollution. Trying to control all these risk factors systematically is not easy and will not be addressed here (Table 37).

From many observational cohort studies among Asian populations, individuals with BP 130–139/80–89 mmHg have a higher CV risk than those with a BP <120/80 mmHg [239–241]. This office BP category was previously classified as “high-normal” in the 2012, 2015, and 2019 Thai Hypertension Guidelines. The term “high-normal” creates the perception that this BP category is benign and requires no special attention. In this new guideline, we reclassify this BP category as “BP at risk.” Hopefully, this new classification will increase awareness among both patients and healthcare workers in Thailand.

A low level of awareness is partly due to a lack of confidence in hypertension diagnosis. The suggested strategies that we recommend in this guideline are:

• Always use standardized BP measurement both in diagnosis and follow-up to guarantee the precision and quality of diagnosis (Strength of Recommendation I, Quality of Evidence A).

• Provide enough time for explaining and answering questions from the patients, especially when the first diagnosis is made (Strength of Recommendation I, Quality of Evidence C).

• Use HBPM (Strength of Recommendation I, Quality of Evidence B).

The most important steps to limit doctors’ inertia in making diagnoses and in starting and adjusting antihypertensive medications are to improve knowledge about the increased CV risk associated with hypertension and the protective effects of adequate BP control. This goal needs the wide dissemination of treatment guidelines. Patient knowledge and empowerment, as well as HBPM use, are also important for providing appropriate and timely feedback to the doctor. We recommend using HBPM to prevent inertia in starting and adjusting proper antihypertensive medication (Strength of Recommendation I, Quality of Evidence B) [242]. The possibility of a more widely used tele-transmission of home BP measurement can be helpful, but it is still not widely available in Thailand at this time. The advent of technology has now allowed the use of telehealth and health-related mobile applications that can be installed on smartphones. These interventions can improve patients’ education and lead to greater BP reduction; however, at present, it is premature to conclude on the benefits of these approaches in general. This new system can be useful but requires more responsible healthcare personnel to guarantee its effectiveness. Due to the limited manpower in most government-supported NCD clinics, the application of this system may be slow and will be available only in some clinics.

Other considerations include more frequent patient visits, a simple hospital treatment protocol, and the allowance of medication adjustments from nurse specialists or pharmacists under a doctor’s supervision. There was a proposal to give incentives to treatment units or doctors based on the number of patients achieving good BP control. The suggestion of combining 3 approaches, which are (a) measure BP accurately, (b) act rapidly, and (c) partner with the patients, has been shown to improve BP control and reduce therapeutic inertia in a large group of hypertensive patients [243].

Therapeutic inertia can also occur from patients’ reluctance and refusal to increase the number of doses of the medications. Changing the medication to an SPC with fewer pills per day, even with a larger dose, and allowing time for a good discussion with the patients can solve these problems in most cases.

A patient-centered approach is the foundation of the care plan for patients with hypertension. The patient empowerment process will enable patients to access the correct information and actively participate in their medical decisions. This process offers a better chance to improve adherence to medications and lifestyle modification [238, 244, 245]. Patient empowerment can be useful in sharing decisions in goal setting, provision of feedback channels, self-monitoring, education, and motivation, which the use of telemedicine and mobile health technologies can assist. Successful providerpatient interaction needs a team-based approach with professionals and a multidisciplinary team of health providers. All these approaches need to be personalized under careful consideration of the cultural, economic, and social variables of each patient.