2025 WSO及WHL立场声明：高血压控制策略在卒中预防和管理中的应用

Abstract

Background and purpose: The goal of this consensus is to provide a comprehensive set of recommendations in regard to hypertension control strategies for the prevention and management of stroke. This document is intended for prehospital care providers, physicians, allied health professionals, and hospital administrators and healthcare policymakers.

Methods: Members of the writing group were representatives of the World Stroke Organization and World Hypertension League. The writing group reviewed articles searched from PubMed and Google Scholar using selected search strings. The document was sent to 12 peer reviewers. The writing group considered the feedback from peer reviewers and made revisions accordingly. Every member of the writing group gave their approval of the final document.

Results: This article details the various techniques for blood pressure (BP) measurement, BP classification, BP and stroke risk, antihypertensive drug therapy for the primary and secondary prevention of stroke, choice of antihypertensive drug therapy, optimal BP targets, non-drug approaches to the prevention of stroke through BP lowering, BP management separately for acute ischemic stroke and spontaneous intracerebral hemorrhage, and the implementation of BP prevention, treatment, and control in the community.

Conclusion: This article provides general recommendations based on currently available evidence to guide healthcare practitioners caring for adults with hypertension for the prevention and management of stroke. Future studies are needed to better define approaches to hypertension control in the community and high-risk groups.

Keywords

Stroke, hypertension, ischemic stroke, hemorrhagic stroke, prevention

Received: 7 October 2024; accepted: 12 November 2024

Introduction

The global prevalence of hypertension (average systolic blood pressure $(\mathrm{SBP})\,{\geqslant}\,140\,\mathrm{mm\,Hg},$ , or diastolic blood pressure $(\mathrm{DBP})\,{\geqslant}\,90\,\mathrm{mmHg},$ , or self-report of taking antihypertensive medication) among adults aged 20years or more was $31.1\%$ ( $95\%$ confidence interval $[\mathrm{CI}]=30–32.2\%)$ in 2010, which equates to 694 million (660–727 million) women and 694 million (659–730 million) men with hypertension. 1 However, a huge disparity exists in the absolute numbers between high-income countries (HICs, 349 million) and low- and middle-income countries (LMIC, 1.039 billion). During the period from 2000 to 2010, the agestandardized prevalence of hypertension decreased by $2.6\%$ in HICs but increased by $7.7\%$ in LMICs. In surveys conducted in 44 LMICs between 2005 and 2014, $32.3\%$ $95\%\,\mathrm{CI}=29.4–35.3)$ of all adults $(\geqslant\!15$ years) had hypertension (1.4 billion adults). 2 The highest prevalence estimates are reported in the Latin American and Caribbean regions $(39.1\%$ , $95\%$ CI = 33.1–45.2). 2 High blood pressure (BP) is one of the most important risk factors of cardiovascular disease (CVD) and approximately $54\%$ of stroke and $47\%$ of coronary heart disease events are attributable to high BP. 3

In 2019, there were 12.2 million incident cases of stroke, 101 million prevalent cases of stroke, 143 million disability adjusted life years (DALYs) due to stroke, and 6.55 million (6.00–7.02) deaths from stroke, worldwide. 4 Stroke was the second leading cause of death and the third leading cause of disability. Between 1990 and 2021, the absolute numbers of incident and prevalent cases, and deaths increased by $70\%$ , $85\%$ , and $43\%$ , respectively. 4 Stroke remains a major burden in LMIC despite the declining trend in HIC. Globally, hypertension is the leading risk factor for both ischemic and hemorrhagic strokes.

In 2010, $46.5\%$ of all adults were aware that they had hypertension, which means the other $53.5\%$ were unaware of the presence of this condition. 2 Overall, only $36.9\%$ reported that they were being treated with antihypertensive medication, and only $13.8\%$ were adequately controlled to an $\mathrm{SBP/DBP}\!<\!140/90\,\mathrm{mm\,Hg}$ , that is, approximately one in seven treated adults. 1

The voluntary global target on BP, endorsed by the 66th World Health Assembly in 2013, envisages a $25\%$ reduction in uncontrolled hypertension (including undiagnosed, diagnosed but untreated, and treated but uncontrolled) by 2025, as compared with 2010. The prevalence of uncontrolled hypertension declined slightly from $29\%$ in 2010 to $26\%$ in 2019, but remains insufficient to achieve the 2025 global target. 5

The World Stroke Organization (WSO) and World Hypertension League (WHL) are leading global organizations with complementary missions to reduce the burden of stroke and hypertension, respectively. The purpose of this joint WSO and WHL position statement is to (1)

review the association between BP and stroke; (2) provide pragmatic recommendations for the measurement of BP and detection of high BP for the diagnosis of hypertension in the community and clinical settings, where treatment should be initiated for the prevention of stroke (primordial, primary, and secondary); (3) identify hypertension control strategies at all levels of healthcare delivery; (4) recommend optimal BP treatment targets for stroke prevention (primary and secondary) and (5) in the acute phase of stroke; (6) define desirable collaboration between healthcare providers who focus on the prevention and management of stroke and hypertension; and (7) specify a joint plan of action to reduce the burden of illness due to BP-related stroke.

Method

A writing group was created from members of the WSO and WHL. A literature search was conducted using PubMed and Google Scholar. The following search strings were employed: “((hypertension) AND (primary prevention)) AND (stroke),” ”((hypertension) AND (primary prevention)) AND (guidelines),” “((hypertension) AND (primary prevention)) AND (guidelines) CVD,” “(hypertension) AND (prevention)) AND (CVD),” “(BP) AND (MEASUREMENT METHODS) AND (CVD),” “(blood pressure) OR (primary prevention)) OR (CVD)),” “(blood pressure) AND (primary prevention) AND (CVD),” “(blood pressure) AND (devices),” “(guideline) AND (BP) AND (physical activity),” “(physical activity) AND (hypertension) AND (CVD).”

For searching articles on acute stroke, the following search criteria were used: “(ischemic stroke) AND (BP) AND (GUIDELINES),” “(ischemic stroke) AND (BP) AND (GUIDELINES) AND (low and middle income countries),” “(ischemic stroke) AND (practice guidelines),” “((cerebral hemorrhage) AND (BP)) AND (GUIDELINES),” “(cerebral hemorrhage) AND (BP)) AND (GUIDELINES)) AND (low and middle income countries),” “(cerebral hemorrhage) AND (practice guidelines),” “(“intracerebral hemorrhage”) AND “blood pressure”).”

For searching articles on secondary prevention, the following search strings were used: “(hypertension) OR (blood pressure) AND (secondary prevention)) AND (acute stroke) AND (guidelines),” “(hypertension) OR (blood pressure)) AND (secondary prevention) AND (intracerebral hemorrhage),” “(hypertension)) OR (blood pressure)) AND (secondary prevention)) AND (acute ischemic stroke),” “(hypertension) OR (blood pressure)) AND (secondary prevention)) AND (cerebrovascular disease),” (hypertension) OR (blood pressure) AND (secondary prevention) AND (guidelines),” “(hypertension) OR (blood pressure) AND (secondary prevention) AND (stroke).”

![·Quietroomwithacomfortabletemperature. ·ClinicallyvalidatedBPmeasurementdevice;anautomateddevicemeasuringBPat thebrachial artery Step1 isrecommended. Facilityand ·Arange of cuff sizes to fitarange of upper-arm circumferences. equipment Step2 ·Trainedhealthcareprofessionalshouldperform theBPmeasurement.Annualre-trainingisrecommended. Personnel performing BPmeasurement ·Thepatientshouldbeprovidedwithinstructionstoabstainfromcaffeine,alcohol,nicotine,andexercise foratleast30minutespriortotheBPmeasurement. ·Eliminate discomfort such asa fullbladder. Step3 ·Priorto theBPmeasurement,thereshouldbeashortrestperiod(3-5minutes)withoutprovocation Preparethepatient （including talking,orbeing talked toin-personoronthephone). ·The healthcareprofessional should explain theprocedure,including thenumberof BPmeasurements tobe obtained. Step4 ·Use thearmwith thehigherSBPreadingsduring an initial visit,unlessa newmedical condition The measurement (e.g.,armischemia)hasdevelopedin theinterim in thatarm. procedure ·≥2measurementsshouldbeobtainedatleast30secondsapart;thevaluesshouldbeaveragedand [see figure below] recorded. No talkingduringrestperiod andbetweenmeasurements Applythecuff tobareupperarm, approximately2-3cmabovetheelbowcrease Arm bare andresting. Mid-armatheartlevel Back supported Feetflatonfloor ](https://venus-llm-1258344701.cos-internal.ap-guangzhou.tencentcos.cn/userUpload/is-62e36cd9/2025-03-15/0d29057f-a233-4f2d-b29f-dddfeee04a9a/0d29057f-a233-4f2d-b29f-dddfeee04a9a.jpg?q-sign-algorithm=sha1&q-ak=AKID61g5D5fy1TjiRv84nEOHtFJ8gyzjCPL0&q-sign-time=1741997187%3B1742000787&q-key-time=1741997187%3B1742000787&q-header-list=host&q-url-param-list=&q-signature=6f06515415ab0fe959f1f844103f2884b0bac9e6) Figure 1. Steps for the estimation of an individual’s usual level of BP using office or clinic measurements. BP: blood pressure; SBP: systolic BP.

Source: Published with permission from Cheung etal. 8

BP measurement

Although it is a relatively simple procedure, BP is frequently measured incorrectly in routine practice. Commonly, BP is overestimated which leads to an inappropriate diagnosis of hypertension in $10{-}15\%$ of adults, but it can be underestimated as well. 6,7 Unfortunately, the agreement intervals vary by level of BP, practice settings, and time, so there is a simple straightforward method to correct for errors in BP measurement. The only solution is to avoid systematic (predictable) errors by measuring BP accurately and to avoid random errors by estimating an individual’s usual level of BP by taking the average of ${\geqslant}2$ readings taken on ${\geqslant}2$

occasions. 8,9 The steps for accurate estimation of office BP are displayed in Figure 1 and are provided in greater detail as follows:

1. Preparation prior to the measurements that includes avoiding caffeine, exercise, and smoking for 30min prior to BP readings, emptying a full bladder, removing clothing from the upper arm, allowing for a period (3–5min) of quiet relaxation prior to the observations while sitting in a chair, back supported, and having the patient’s feet flat on the ground, and by ensuring there is no talking or any distractions during the rest period and BP readings.

2. Use of a BP measurement device that has been clinically validated. Listings of clinically validated devices can be found in a number of websites, including a US-validated BP device listing site (https://www.validatebp.org/) and a corresponding European site (https://stridebp.org/). Most BP guidelines recommend the use of an automated osilometric device, but auscultatory devices are still acceptable provided all the requirements for an accurate estimation of BP are otherwise met.

3. Support the individual’s arm (e.g. resting on a desk), select the proper cuff size, and position the mid-cuff at heart level.

4. At the first visit, record BP in both arms and use the arm with the higher readings for subsequent BP measurements. Record SBP and DBP, with repeated measurements separated by 1–2min. For auscultatory measurements, inflate the cuff to $10{-}20\ \mathrm{mm\,Hg}$ above the disappearance of the radial pulse, deflate the cuff slowly $(2\,\mathrm{mm\,Hg/s})$ ), use either the stethoscope bell or diaphragm to hear the Korotkoff (K) sounds, and use the nearest even number to record SBP at which K sounds are first heard (K1) and DBP as the BP below which K sounds disappear (K5). Except for a hypertensive emergency (detailed later), an average of ${\geqslant}2$ readings obtained at ${\geqslant}2$ visits should be used to estimate an individual’s usual level of BP.

A variety of BP measurement and certification programs are available online, including virtual courses for both office and home BP measurements that are jointly sponsored by the Pan American Health Organization, World Hypertension League, Lancet Commission on Hypertension, Hypertension Canada, and Resolve to Save Lives (https:// campus.paho.org/en/node/29166). Instructions for ambulatory BP monitoring (ABPM) measurements are available in most BP clinical practice guidelines but ABPM is generally best performed and interpreted by health professionals with specialist knowledge in this area. Both home BP monitoring (HBPM) and ABPM provide an opportunity to recognize masked hypertension (non-hypertensive BP level in the office but hypertensive levels outside the office) and white coat hypertension (hypertensive BP levels in the office but non-hypertensive levels outside the office). Adults with masked hypertension have a risk of stroke and other CVD events compared with those with sustained hypertension (hypertensive BP levels in and outside the office). As such, they should be treated with antihypertensive medication in addition to lifestyle counseling. In contrast, most adults with white coat hypertension can be managed with lifestyle counseling, but monitored annually for evidence of progression to sustained hypertension. ABPM allows for measurement of nighttime BP, which may provide the best BP-related estimation of stroke and

CVD risk. However, many patients find ABPM to be intrusive and are reluctant to agree to such measurements, especially repeated ABPM. HBPM is a much more acceptable and practical method of estimating BP outside the office in most countries. In addition, it is often useful to engage and empower patients in their own care. Use of a clinically validated BP measurement device and patient instruction in the correct methods for measurement of their BP are essential requirements for HBPM. Many HBPM devices allow programming for averaging of multiple readings, storage of the measurements on a memory chip, and automatic transmission of the information to a clinician’s office or monitoring facility.

BP classification

1. Schemas for the classification of BP categories are commonly used in clinical and public healthcare practice, but continue to evolve. In addition, these vary by country, depending upon the extent to which high BP is already being controlled and on prevailing clinical practice guidelines (CPG). Figure 2 provides categorization schemes that are currently recommended in the two most commonly cited CPG. 9,10 CPGs have traditionally defined hypertension as the SBP and/or DBP at which antihypertensive drug therapy is recommended in addition to lifestyle change. 11 In the United States, the American College of Cardiology (ACC)/American Heart Association (AHA) CPG recommends the diagnosis of hypertension in adults with an average, accurately measured, and confirmed office for $\mathrm{SBP}\!\geqslant\!130\,\mathrm{mm}\,\mathrm{Hg}$ and/or $\mathrm{DBP}\,{\geqslant}\,80\,\mathrm{mm\,Hg}$ , or a self-report of taking antihypertensive medication. 9 In other countries, higher SBP and DBP cut-points (usually $\geqslant140\,\mathrm{mm\,Hg}$ $\mathrm{{and/or}\!\geqslant\!90\,\mathrm{{mm}\,H\!g}}$ , respectively) are recommended for the diagnosis of hypertension. 12,13 Whichever cut-points are chosen for the diagnosis, the frequency of hypertension is very common: a global prevalence for $\mathrm{SBP}\,{\geqslant}\,140\,\mathrm{mm\,Hg}$ , $\mathrm{DBP}\!\geqslant\!90\,\mathrm{mm\,Hg},$ , or use of antihypertensive medication, of $31.1\%$ in 2010. 1 The prevalence of hypertension increases progressively with age, being $71\%$ and $79\%$ for US men ⩾ 75years using the 140/90 and 130/80 SBP/DBP cut-points, respectively. The corresponding estimates for women are $78\%$ and $85\%$ . 9 In the rare instance when the average BP at a single office visit is ${\geqslant}180/110\,\mathrm{mm\,Hg}$ and accompanied by evidence of active BP-related end-organ damage, a hypertensive emergency should be diagnosed, and the patient is admitted for carefully supervised immediate BP lowering. When a similar level of BP is measured in adults without evidence of active end-organ damage, outpatient management is appropriate. This often entails reinstitution of

Figure 2. Cut-points for classification of different blood pressure categories proposed by the American College of Cardiology/ American Heart Association and European Society of Hypertension. 9,14

|2017ACC/AHA|SBP||DBP|DBP|2023ESH| |---|---|---|---|---|---| |Normal||||||

antihypertensive medications in individuals who have previously been advised to lower their BP.

The corresponding 24-h ABPM cut-points for an office average of 130 and 140mmHg are 130/80 and 135/85mmHg, respectively, with 130/80 and $135/85\,\mathrm{mm\,Hg}$ also being used as daytime ABPM averages and 110/65 and $120/70\,\mathrm{mm\,Hg}$ for night time ABPM averages 9 The corresponding average home BP measurements are 130/80 and $135/85\,\mathrm{mm\,Hg}$ .

BP and stroke risk

BP is associated with elevated CVD risk, including stroke, in a direct log-linear fashion throughout the distribution of BP from an average SBP of $90{-}180\,\mathrm{mm\,Hg}$ . 15–17 Average DBP is similarly related to stroke and CVD risks. These risk associations are equally true for women and men. The BP-related relative risk of stroke is greater at younger ages when elevations of BP often present as relatively “isolated” indicators of CVD risk, but the absolute risk of stroke is far greater in older adults, in whom elevated BP is usually only one of several CVD risk factors. 15 At ages 40–69years, each difference of $20\,\mathrm{mm\,Hg}$ in usual SBP (or, approximately $10\,\mathrm{mm\,Hg}$ for usual DBP) and it is associated with more than a twofold difference in the stroke and ischemic heart disease death rates. 15 The burden of stroke deaths and DALY associated with high BP are enormous, being estimated as 30,810 deaths and 67,610 DALY, respectively, for an $\mathrm{SBP\!\geqslant\!110\!-\!115\,mm\,Hg}$ and 25,570 deaths and 47,361 DALY, respectively, for an $\mathrm{SBP}\,{\geqslant}\,140\,\mathrm{mm\,Hg}$ . 18

However, at any given level of BP, CVD risk can vary by as much as 30-fold, depending on the presence or absence of other CVD risk factors, which underscores the importance of estimating CVD when considering treatment options, especially in those with an SBP of 130– $139\,\mathrm{mm\,Hg}$ . 19 Many cohort studies have identified visit-tovisit variability in BP as a risk predictor for CVD events, including stroke, independent of average level of BP. However, the additional contribution of BP variability to traditional CVD risk factors in prediction of CVD events is modest and not yet relevant in the management of adults with stable elevations of BP. 20

Non-drug approaches to the prevention of stroke by lowering BP

Thus far, genetic abnormalities have only been shown to play an important role in hypertension risks. General environmental factors, especially air pollution, have been associated with clinically important higher levels of BP, an increase in emergency room visits, and CVD events in areas with high levels of ambient particulate matter. 21 Personal environmental exposures represent the most important and reversible risk predictors for higher levels of BP and hypertension. The six best proven nonpharmacological interventions for prevention and treatment of hypertension are displayed in Table 1.

Weight is directly associated with BP, such as being overweight or obese are not only important risk factors for hypertension but are increasingly prevalent in many countries. Helping patients to achieve their ideal body weight is an optimal goal, but any reduction in weight is beneficial

Table 1. Best proven nonpharmacological interventions for prevention and treatment of hypertension.

| Recommendation| Intervention|Dose|| Approximate impact on SBP (behavior change intervention) || |---|---|---|---|---|---| ||||||| ||||| Hypertension (mm Hg) | Non-HTN (mm Hg) | |Weight loss| Calorie reduction and physical activity || Best goal is ideal body weight. Expect about I mm Hg for every I-kg reduction in weight |-5|13| |Healthy Diet|DASH Diet|| Diet rich in fruits, vegetables, whole grains, low-fat dairy products, reduced saturated/total fat |-5|13| | Dietary sodium|Reduced intake|Optimal goal ||||

Source: Adapted, with permission, from Whelton etal. 9

because SBP is reduced by about $1\,\mathrm{mm}\,\mathrm{Hg}$ for every kg of weight loss. 22 Consumption of any heart healthy diet, including the Mediterranean Diet, will lower BP compared with consumption of the usual diets in almost all countries. The diet is a low-fat diet rich in fruits and vegetables that has been specifically formulated to prevent and treat hypertension. It is often combined with other non-drug approaches to lowering BP, such as sodium reduction and/ or physical activity. Natural foods tend to be very low in sodium and high in potassium, but most diets consumed in the community are high in sodium and low in potassium due to food processing and/or addition of sodium during food preparation. This combination is an important contributor to age-related increases in BP and hypertension. Reducing sodium intake results in a linear dose-dependent reduction in BP. 23 A high intake of potassium or of foods that are rich in potassium content is strongly associated with a lower risk of stroke as well as high BP. 23,24 In a large cluster-designed randomized controlled trial, use of a salt substitute with $25\%$ of the sodium chloride replaced by potassium chloride resulted in a significant reduction in stroke (rate ratio 0.86, 95 $\%\,\mathrm{CI}=0.77–0.96$ ) and all-cause mortality. 25

Physical activity is inversely associated with BP and CVD events, including stroke. All forms of physical activity lower BP, but the most robust clinical trial evidence comes from aerobic exercise interventions, including walking, swimming, and dancing. Common recommendations are for 150min of moderate aerobic activity or 75min of vigorous aerobic activity per week, but even more modest physical activity is helpful. Although regular exercise is desirable, “weekend warriors” also derive BP lowering and CVD prevention benefits. 26 Alcohol consumption has long been known to increase BP and clinical trials have convincingly demonstrated that a reduction or cessation in alcoholic consumption lowers BP. Even a low intake of alcohol (one drink per day) has been associated with a higher level of BP. 27 Usually, the best approach to nonpharmacological therapy is to intervene on the risk factors for high BP that are most prominent, and the ones for which the patient is most likely to implement the corresponding nonpharmacological interventions. Likewise, the best results are often obtained in patients who are the most committed to adhering to the intervention, including adults who are older, sicker, have more time, and are better educated and have a higher income.

BP and stroke risk

1. Every unit increase in BP is associated with a higher risk of stroke death. 2. High BP and hypertension are associated with an enormous burden of illness due to stroke mortality and DALY. 3. Reducing SBP by $2\,\mathrm{mm}\,\mathrm{Hg}$ decreases the risk of stroke by $10\%$ .

Initiation of pharmacologic treatment

Most BP CPGs recommend nonpharmacological management, usually behavioral counseling, aimed at lifestyle improvement for adults with non-hypertensive BPs to prevent hypertension and reverse intermediate BP-related indicators of organ damage such as left ventricular hypertrophy 28 and to treat hypertension. There is general agreement that most adults with an average $\mathrm{SBP}\!\geqslant\!140\,\mathrm{mm}\,\mathrm{Hg}$ or $\mathrm{DBP}\!\geqslant\!90\,\mathrm{mm\,Hg}$ should also be treated with antihypertensive medication. Both the ACC/AHA BP CPG and World Health Organization (WHO) pharmacotherapy in adults with hypertension guidelines 13 identify a high risk of CVD as a history of CVD; meeting the criterion for high CVD risk based on use of a CVD risk calculator; or the presence of phenotypic indicators such as older age, diabetes mellitus, and/or chronic kidney disease. 9,13,29 In contrast, the European Society of Hypertension (ESH) guideline only recommends antihypertensive medication for those with an average SBP $130{-}139\;\mathrm{mm}\,\mathrm{Hg}$ or DBP $80{-}89\,\mathrm{mm\,Hg}$ in the presence of established CVD, especially coronary heart disease. Although there is general agreement for those with an average SBP between 130 and $139\,\mathrm{mm\,Hg}$ , the addition of antihypertensive medication is recommended when the underlying risk of CVD is high. Figure 3 displays the ACC/ AHA recommendations for addition of antihypertensive medication, which is also consistent with the WHO guideline.

Antihypertensive drug therapy for primary and secondary prevention of stroke

There is abundant evidence that antihypertensive drug therapy reduces the risk of stroke and other CVD events such as ischemic coronary heart disease, heart failure, and all-cause mortality. In a meta-analysis of 54 randomized controlled trials, antihypertensive drug treatment reduced the risk of stroke events by $27\%$ (relative risk (RR) 0.73, $95\%$ CI = 0.68–0.77). 30 The relative reduction in stroke risk was almost identical in those with and without a history of prior CVD. Likewise, a statistically significant stroke benefit was noted following introduction of antihypertensive medication in those with an SBP of $130{-}139\,\mathrm{mm\,Hg}$ (RR 0.73,

$95\%\mathrm{~CI}\,=\,0.62–0.85)$ and every higher category of SBP. Several studies have demonstrated that introduction of antihypertensive drug therapy results in almost all the stroke reduction benefit that is predicted from BP as a stroke risk predictor in observational studies. 31

Choice of antihypertensive drug therapy for prevention of stroke

A variety of drug classes are effective for BP lowering. In a meta-analysis of 68 randomized controlled trials, diuretics, $\upbeta$ -blockers, calcium channel blockers (CCB), angiotensinconverting enzyme inhibitors (ACEI), and angiotensin receptor blockers (ARB) were more effective than placebo for prevention of stroke and other CVD events. 32 In the largest and most carefully designed trial to compare the head-to-head efficacy of first-step therapy for prevention of stroke and other CVD events, the CCB amlodipine was no better than the long-acting thiazide-like diuretic chlorthalidone (RR 0.93, $95\%\,\mathrm{CI}=0.82\mathrm{-}1.06$ ) and the ACEI lisinopril was less efficacious compared with chlorthalidone (RR1.15, $95\%$ CI = 1.02–1.30) for stroke prevention. 33 Several meta-analyses of randomized controlled trials have demonstrated that first-step therapy with $\upbeta$ -blockers is inferior to treatment with a diuretic, CCB, ACEI, or ARB for prevention of stroke. 30,32 Although first-step treatment with an ACEI was better than a $\upbeta$ -blocker for stroke prevention, there was some evidence that ACEI treatment was slightly but significantly inferior to use of a diuretic, CCB, or ARB. Several meta-analyses suggest that first-step therapy with a CCB may be optimal for stroke prevention, but diuretics seem to provide the best overall CVD protection. Most adults with hypertension require more than one antihypertensive medication to control their BP. Trials with an SBP/ DBP target of ${<}140/90\,\mathrm{mm\,Hg}$ have generally required an average of two antihypertensive medications, while trials with an SBP target of ${<}120\,\mathrm{mm\,Hg}$ have required an average of three drugs. Recommended two-drug antihypertensive combinations include a diuretic or CCB with an ACEI or ARB, and the commonly recommended three-drug combination is a diuretic, CCB, and ACEI or ARB. Antihypertensive drug combinations are best given as a single pill combination (SPC) medication, when this is feasible, because SPC therapy is more effective than stepped-care therapy for control of hypertension, reduces the time necessary to achieve BP control, and improves medication adherence. However, lowering BP is more important than the choice of antihypertensive medication. A recent well-executed randomized controlled trial in which the treatment was led by community healthcare workers resulted in a net SBP reduction of ${>}21\,\mathrm{mm}\,\mathrm{Hg}$ , a $23\%$ reduction in stroke, and a $15\%$ reduction in all-cause mortality using a simple stepped-care approach compared with usual care. 34 Renal denervation (RDN) is a recently developing strategy for stroke patients for lowering of BP. However the recent

Figure 3. Blood pressure and cardiovascular disease risk thresholds for nonpharmacological and antihypertensive drug treatment in the American College of Cardiology/American Heart Association blood pressure clinical practice guideline. The recommendations for initiation of antihypertensive medication are identical in the World Health Organization pharmacotherapy in adults with hypertension guideline are identical.

 Source: Figure reproduced from Whelton etal. 9 with permission.

study by Mahfoud etal. 35 showed that after renal denervation, a $10\%$ increase in time in therapeutic range (TTR) after RDN through 6months was associated with a significant reduction in office and ambulatory systolic blood pressure (OSBP and ASBP) from 6 to 36months of $23\%$ for stroke.

Optimal BP targets during antihypertensive drug therapy: how low to go?

A variety of design assessments have been employed to compare the efficacy of achieved BP in meta-analyses of clinical trials, including the comparison of trials that randomized participants to different BP targets, active antihypertensive medication or placebo, and different intensities of antihypertensive drug therapy. Meta-analyses based on inclusion of all three of these types of trials have repeatedly demonstrated greater stroke and CVD event prevention for lower versus higher achieved BPs. Figure 4 provides an example of this type of comparison from a network

meta-analysis of 42 randomized controlled trials. 36 The greatest reduction in stroke risk was seen for comparisons in those with the biggest difference in achieved SBP, but a statistically significant benefit was still noted for the comparison of an achieved SPB of 120–124 versus 135– $139\,\mathrm{mm\,Hg}$ (relative risk 0.57, $95\%$ CI = 0.30–1.00). A consistent finding in these types of meta-analyses is the demonstration of stroke prevention for an achieved $\mathrm{SBP}\!<\!130\,\mathrm{mm\,Hg}$ compared with higher achieved pressures. A systematic review and meta-analysis restricted to randomized trials to randomized participants in the more intensively treated arm to an $\mathrm{SBP}\!<\!130\,\mathrm{mm\,Hg} $ or $<\!120\,\mathrm{mm\,Hg}$ provided strong evidence for cardiovascular and all-cause mortality benefit in adults randomized to an $\mathrm{SBP}\!<\!130$ versus $\geqslant\!130\,\mathrm{mm\,Hg}$ , including a significant $26\%$ reduction in stroke. Those randomized to more intensive treatment to ${<}120\,\mathrm{mm\,Hg}$ also benefited, including a significant $19\%$ reduction in stroke, but this was based on only four trials. 37

The ACC/AHA BP CPG recommendation is for an SBP/DBP target of $<\!130/80\,\mathrm{mm\,Hg}$ $(\mathrm{SBP}\,{<}\,130\,\mathrm{mm\,Hg}$

 Figure 4. Network meta-analysis of 42 randomized controlled trials that compared the efficacy of different levels of achieved systolic blood pressure for the prevention of stroke.

Source: Reproduced, with permission, Mahfoud etal. 35

in adults 65years). Most of the major BP guidelines also recommend an SBP target ${<}130\,\mathrm{mm\,Hg}$ in adults with a history of CVD, or a high risk of CVD, including those with comorbidities such as diabetes mellitus and chronic kidney disease. Surveys have demonstrated that many adults over the age of 40years seen in clinical settings are at high risk for CVD. 38,39 For adults with hypertension who are not at high risk for CVD, some guidelines recommend a higher SBP/DBP target of $140/90\,\mathrm{mm\,Hg}$ . All four pivotal trials (ACCORD BP, SPRINT, RESPECT, and ESPRIT) undertaken in adults with hypertension with a high risk for CVD reported greater CVD prevention in those randomized to an SBP target of ${<}120$ versus ${<}140\,\mathrm{mm\,Hg}$ , with the differences between the two treatment groups being significant in two of the trials and representing a nonsignificant trend for less CVD events in the other two trials. 40–43 Three large ongoing event-based trials, which target SBP of 120 versus $140\,\mathrm{mm\,Hg}$ (OPTIMAL-Diabetes and OPTIMAL Stroke are being conducted in Brazil; and BPROAD being conducted in China) will help clarify the situation.

BP management in acute ischemic stroke

There have been many countries and societies with their own guidelines, but most of them are in line with that proposed by the American Heart Association. 44–56 In patients with acute ischemic stroke, hypovolemia and hypotension should be corrected to maintain systemic perfusion and support organ function. The management of BP in the acute phase depends on the decision to administer intravenous thrombolysis and the status of recanalization after endovascular therapy. The current consensus is that in patients with acute ischemic stroke who are eligible for intravenous thrombolysis, the BP should be reduced to ${<}185/110\,\mathrm{mm\,Hg}$ prior to thrombolysis and to maintain it ${<}180/105\,\mathrm{mm\,Hg}$ post thrombolysis for a period of up to $24\,\mathrm{h}$ .

In those patients with acute ischemic stroke who are ineligible for intravenous thrombolysis, BP needs to be lowered only if it is ${\geqslant}220/120\,\mathrm{mm\,Hg}$ or in those in whom there is a hypertensive emergency with coexistent serious medical conditions such as hypertensive encephalopathy,

Table 2. Table showing BP targets in different clinical settings.

| Clinical setting BP targets| |---| |Acute ischemic stroke eligible for IV thrombolysis BP|

nephropathy, cardiac failure, myocardial infarction, aortic dissection, or pre-eclampsia/eclampsia. In patients with B $_\mathrm{P}{>}220/120\,\mathrm{mm\,Hg}$ and who are not candidates for IV thrombolysis or mechanical thrombectomy, the benefit of BP reduction in the first $48–72\,\mathrm{h}$ is uncertain. It may be useful to reduce the BP by $15\%$ in the first $24\,\mathrm{h}$ and subsequently gradually to achieve BP targets for secondary prevention. 44

Rapid BP reduction should be avoided in acute ischemic stroke to prevent induction or precipitation of ischemia in patients with intra- or extra-cranial vessel occlusion. 44 Patients who undergo mechanical thrombectomy should have their BP maintained to less than $180/105\,\mathrm{mm\,Hg}$ without reducing systolic BP to ${<}130\,\mathrm{mm\,Hg}$ during and after the procedure for a duration of 24h. 45 It is prudent to avoid large SBP drops in those who undergo mechanical thrombectomy for large vessel occlusion. The recent Society of Vascular and Interventional Neurology (SVIN) and Taiwan guidelines state that in patients with successful reperfusion (mTICI 2b-3) following mechanical thrombectomy, maintaining SBP at lower value with ${<}140/90\,\mathrm{mm\,Hg}$ can be considered. 45,49,57 In patients who are not candidates for any reperfusion therapy, routine usage of vasopressors to augment BP is not recommended. 46

Labetalol, nicardipine, hydralazine, and enalaprilat have been recommended for usage in acute BP reduction. 47 Although the etiological subtype of the ischemic stroke may have a bearing on the rate of BP decline after the acute stage, 54 no specific recommendations have been made with regard to the control of BP in the acute setting based on the etiological subtypes.

Recommendations for acute ischemic stroke (Table 2):

1. In patients with acute ischemic stroke who are eligible for thrombolysis, BP should be reduced to ${<}185/110\,\mathrm{mm\,Hg}$ prior to thrombolysis and maintained at less than 180/105 up to 24h later. 2. BP lowering is recommended in those with $\mathrm{BP}\!\geqslant\!220/120\,\mathrm{mm\,Hg}$ in acute ischemic stroke in non-thrombolyzed patients and in those with hypertensive emergency. 3. It is prudent to avoid large fluctuations in SBP.

4. In patients with successful reperfusion following mechanical thrombectomy (mTICI 2b-3), maintaining $\mathrm{BP}\!<\!140/90\,\mathrm{mm\,Hg}$ should be considered.

Spontaneous intracerebral hemorrhage

Many guidelines exist regarding the BP management following an intracerebral hemorrhage (ICH), 44,52,56,58 with the most recent recommendations coming from the AHA. 57 The Canadian guidelines recommend assessing BP at arrival and then every 15min thereafter until the desired target BP is achieved and maintained for the first 24h. 58 For patients with ICH who require acute BP lowering, starting treatment as early as possible to reach a target $\mathrm{SBP}\!<\!140\,\mathrm{mm\,Hg}$ within 30min to 1h can be beneficial by reducing hematoma expansion and improve functional outcome. As it is recommended to avoid BP peaks and large SBP variability, it is important to ensure a smooth control of BP to optimize patient outcomes. 59

For ICH with mild to moderate severity, who have SBP between 150 and $220\,\mathrm{mm\,Hg},$ , it is safe to reduce SBP to $140\,\mathrm{mm\,Hg}$ and maintaining between 130 and $150\,\mathrm{mm\,Hg}$ is reasonable for improving functional outcomes, while ensuring that the magnitude of SBP drop does not exceed $60\,\mathrm{mm\,Hg}$ within 1 h of starting treatment. 56 Acutely reducing BP to less than $130\,\mathrm{mm\,Hg}$ may be harmful in such instances and is not recommended. The implementation of an intensive care bundle to reach target BP has been shown to be safe and results in improved outcomes at 6 months. 60 It is recommended to reduce SBP to ${<}140\,\mathrm{mm\,Hg}$ in patients with onset ${<\!6\,\mathrm{h}}$ , those with presenting $\mathrm{SBP}\!<\!220$ $\mathrm{mm\,Hg}$ , those on anticoagulation therapy, imaging markers of hematoma expansion, and normal renal function. 61 The decision to reduce BP in those with $\mathrm{SBP}\!>\!220\,\mathrm{mm\,Hg}$ or presentation after 6h onset is to be made on a case-by-case basis weighing the risks versus benefits. 62

In patients with large or severe ICH and those requiring surgical decompression, neither the safety nor the benefit of intensive BP lowering is well established. The National: National Institute for Health and Clinical Excellence (NICE) guidelines advise against rapid BP reduction in the

following subgroups: patients with underlying structural cause for ICH (arteriovenous malformations, aneurysms, tumors, etc.), coma, massive hematoma with an expected poor prognosis, and those requiring early neurosurgical hematoma evacuation. 58

Drugs such as labetalol, nicardipine, hydralazine, and/or enalapril may be considered for use in the acute phase without any strong guidance over the choice of drug. 57,60

Recommendations for acute ICH:

1. BP reduction starting within 2h of onset and achieving treatment targets within 1h can be beneficial in reducing hematoma expansion and improving functional outcomes. 2. In patients with ICH of moderate severity, who have SBP between 150 and $220\,\mathrm{mm\,Hg}$ , it is safe to reduce SBP to ${<}140\,\mathrm{mm\,Hg}$ , maintaining between 130 and $150\,\mathrm{mm\,Hg}$ . 3. It is important to avoid large fluctuations in SBP and to avoid rapidly reducing SBP to ${<}130\,\mathrm{mm\,Hg}$ in acute ICH. 4. In patients with large or severe ICH and those requiring surgical intervention, the safety or benefit of intensive BP lowering is not well established.

Strategies for implementation of BP treatment and control in the community: hypertension control strategies

Opportunistic screening for hypertension in a healthcare setup can be conducted in clinics, hospitals, and primary healthcare facilities (Figure 5). In addition, screening and public awareness can be implemented by training lay people like barbers, religious leaders, and so on. 62,63 Task sharing or task shifting has been effectively used to screen and manage patients with hypertension in the population. Community health workers, nonprofessional health workers, and pharmacists have been used to successfully in different communities. 64,65

Integrating hypertension control with an existing national control program for infectious diseases such as HIV/AIDS in South Africa has helped in effectively tackling both the diseases when there are limited resources. 66 HBPM and telemonitoring are being used widely to monitor and treat hypertension and their use has expanded substantially following the COVID pandemic. 67 In the India Hypertension control initiative (IHCI), 68 five core strategies were followed: standard treatment protocol, reliable supply of free antihypertensive drugs, team-based care, patient-centered care, and an information system to track individual patient treatment and BP control. The program was rolled out in primary care facilities in 5 States and 26 districts. All states implemented simple treatment protocols

with three drugs: a long-acting dihydropyridine CCB (amlodipine), ACEI (telmisartan), and thiazide or a thiazide-like diuretic (hydrochlorothiazide or chlorthalidone). Medication supplies were adequate to support at least 1month of treatment. Overall, 570,365 hypertensives were enrolled in the program for 1year. The clinic level BP control ranged from $22\%$ to $79\%$ . 69

Use of a polypill strategy has been studied in large clinical trials to control BP and lipids and to prevent and reduce stroke. These studies have demonstrated the benefit of a fixed-dose combination treatment strategy for primary prevention and risk reduction in stroke with estimates of a $50\%$ reduction in the 5-year stroke incidence. 70 Such a polypill implementation is well suited for L/MICs that tend to have a high average risk of CVD and younger populations than HICs.

Mobile (smartphone), computer, and web-based technologies, as well as tools ranging from applications (apps) and text messaging to mobile Health (mHealth) telemedicine, and artificial intelligence are being used successfully for control of risk factors, including hypertension for CVD and stroke prevention. 68 Digital technologies can be used for individual and population-wide control of risk factors. This is a low-cost intervention which can be easily adapted. 68

The WHO HEARTS Package provides a strategic approach to improving CVD health globally. It comprises six modules and an implementation guide. 71 This package provides ministries of health and the wherewithal to strengthen CVD management in primary healthcare settings. The program focuses on healthy-lifestyle counseling, adapting evidence-based treatment protocols, continuous access to medicines and technology, riskbased CVD management, team-based care, systems monitoring, and tool for developing protocol for treatment of hypertension and diabetes. 71 This program is being implemented in many countries that are members of the WHO and are being supported by the WHL, WSO, Resolve to Save Lives (https://resolvetosavelives.org/), and many other partner organizations. Early results are promising and it is hoped that implementation of the HEARTS initiative will have a major positive long-term impact in managing hypertension and in the prevention of stroke and heart attack.

Limitations

Our recommendations may not necessarily be generalizable to all settings. This position statement was prepared based on systematic review and various strategies approved and promoted by both WSO and WHL. It also focuses on the screening and control of hypertension in resource limited settings, hence countries need to identify the best strategy which would be applicable to their region.

 Figure 5. Implementation of blood pressure treatment and control in the community: hypertension control strategies.

Summary

This collaboration of WSO and WHL is timely and important given the strong causal relationship between BP and stroke, and because there have been several recent diagnostic and therapeutic advances in prevention and management of both hypertension and stroke. Nonetheless, there are prevailing gaps in evidence that are ideally addressed by a multidisciplinary team approach. Issues such as the timing of BP treatment after a stroke remains a critical consideration and are best addressed with the input of stroke and hypertension investigators and thought leaders. Elevated BP in acute stroke after several hours beyond onset is related to a larger stroke deficit with associated brain swelling. While there is evidence that good BP control improves outcomes for acute ICH, uncertainty persists over the timing, speed, and choice of antihypertensive agents. There is evidence that intensive BP reduction is associated with a lower risk of ICH. For management of acute ischemic stroke, the effects of antihypertensive treatment vary according to the timing of the intervention and patient characteristics. Globally, there is a huge burden of hypertension and stroke. Although there are several risk factors for

stroke, hypertension is the leading cause of ischemic and hemorrhagic strokes. Primordial, primary, and secondary prevention of stroke are the mainstay in reducing the burden of stroke. Opportunistic screening, raising public awareness, self-management of BP, out-of-clinic BP measurement, polypill, digital technology with task sharing to community health workers, HEARTS program, and national hypertension control initiatives will go a long way in the control of hypertension and reduction of stroke burden. However, effective implementation is dependent on the commitment and collaboration of hypertension and stroke professionals.

Declaration of conflicting interest

The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: S.O.M. declares receiving research funding from the Ministry of Health of Brazil/Hospital Moinhos de Vento through the PROADI-SUS Program to PROMOTE Trial, RESILIENT Direct TNK, RESILIENT Extend IV, and TRIDENT and declares receiving honoraria as a speaker from Boehringer Ingelheim, Medtronic, Penumbra, Novartis, Novo Nordisk, and Servier.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

ORCID iDs


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