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Goal blood pressure in adults with hypertension

Goal blood pressure in adults with hypertension
Authors:
Johannes FE Mann, MD
Karl F Hilgers, MD
Section Editors:
George L Bakris, MD
William B White, MD
Scott E Kasner, MD
David M Nathan, MD
Deputy Editors:
John P Forman, MD, MSc
Jane Givens, MD, MSCE
Literature review current through: Nov 2022. | This topic last updated: Jun 15, 2022.

INTRODUCTION — The prevalence of hypertension is high worldwide, and treatment of hypertension is one of the most common reasons for office visits of nonpregnant adults and for use of prescription drugs [1-3].

An overview of initial management (ie, when to initiate antihypertensive drug therapy and with how many agents) and goal blood pressure in adults with hypertension is discussed in this topic.

Other issues in hypertensive adults are presented elsewhere:

Risk factors for and prevalence of hypertension in adults:

(See "Overview of hypertension in adults".)

(See "The prevalence and control of hypertension in adults".)

Screening for and diagnosis of hypertension in adults – (See "Overview of hypertension in adults".)

Measurement of blood pressure in the diagnosis and management of hypertension in adults:

(See "Blood pressure measurement in the diagnosis and management of hypertension in adults".)

(See "Out-of-office blood pressure measurement: Ambulatory and self-measured blood pressure monitoring".)

Initial evaluation of the hypertensive adult – (See "Initial evaluation of adults with hypertension".)

Lifestyle modifications to lower blood pressure in hypertensive adults:

(See "Overview of hypertension in adults".)

(See "Diet in the treatment and prevention of hypertension".)

(See "Salt intake, salt restriction, and primary (essential) hypertension".)

(See "Overweight, obesity, and weight reduction in hypertension".)

(See "Exercise in the treatment and prevention of hypertension".)

Choice of antihypertensive drug therapy in hypertensive adults:

(See "Choice of drug therapy in primary (essential) hypertension".)

(See "Antihypertensive therapy and progression of nondiabetic chronic kidney disease in adults".)

(See "Treatment of hypertension in patients with diabetes mellitus".)

(See "Antihypertensive therapy for secondary stroke prevention".)

Definition, evaluation, and management of adults with resistant hypertension:

(See "Definition, risk factors, and evaluation of resistant hypertension".)

(See "Treatment of resistant hypertension".)

OUR APPROACH TO GOAL BLOOD PRESSURE

Overview of our approach — A variety of randomized trials have addressed the issue of goal blood pressure in patients with hypertension. These trials, discussed in detail below, form the rationale for our approach to initial management of hypertension and goal blood pressure.

In general:

Our proposed blood pressure targets depend in part upon the method by which the blood pressure is measured (see 'Importance of how blood pressure is measured' below):

In particular, blood pressure that is measured in the office (ie, medical care setting) should be obtained in a standardized manner. There are two ways to performed high-quality office blood pressure measurement: automated oscillometric blood pressure monitoring (AOBPM), which requires specialized equipment, and standardized office-based measurement using proper preparation and technique (table 1), which requires only ordinary equipment. These two methods of measuring blood pressure in the office were used in nearly all outcome trials in hypertension and provide readings that approximate daytime ambulatory blood pressure (using ambulatory blood pressure monitoring [ABPM]) and self-measured (home) blood pressure monitoring. These techniques are described in detail elsewhere. (See "Blood pressure measurement in the diagnosis and management of hypertension in adults".)

Together, these four methods of blood pressure measurement are preferable to the manner by which blood pressure is typically measured in the medical care setting, in which blood pressure is measured (usually once) in the office with a stethoscope or oscillometric device and without proper patient preparation or technique. Due to the lack of standardization, this typical method of measurement can vary from office to office and from one medical provider to the next. Although it is an inferior method of measurement, it is faster and less cumbersome and therefore is the one primarily used worldwide. Henceforth in this topic, the four preferred options for blood pressure measurement will be referred to as "non-routine" since they are less commonly implemented. The non-preferred method will be referred to as "routine" since it is the method typically used in clinical practice. As noted above, one of the non-routine methods should ideally be used to make decisions about blood pressure management.

Blood pressure targets differ depending upon the technique of measurement because "routine" methods typically provide higher blood pressure readings compared with the preferred, "non-routine" methods. On a population level, routine measurements are generally 5 to 15 mmHg higher than non-routine measurements (although there will be uncertainty about the difference in any given individual). (See "Blood pressure measurement in the diagnosis and management of hypertension in adults".)

In addition, blood pressure targets are based upon the patient's risk for having a future cardiovascular event [4].

Specifically, we recommend or suggest, depending upon the strength of the evidence, a more intensive goal for most patients with one or more of the following higher-risk characteristics (table 2) (see 'Goal blood pressure in higher-risk patients' below):

Patients with established atherosclerotic cardiovascular disease (prior history of coronary disease, prior stroke or transient ischemic attack (TIA), or documented peripheral arterial disease) (see 'Patients with established atherosclerotic cardiovascular disease' below)

Patients with heart failure (see 'Patients with heart failure' below)

Patents with diabetes mellitus (see 'Patients with diabetes mellitus' below)

Patients with chronic kidney disease (CKD) (see 'Patients with chronic kidney disease' below)

Older adults (>65 years of age) (see 'Older adults' below)

Patients with multiple cardiovascular risk factors (and an estimated 10-year risk of future cardiovascular events of 10 percent or greater) (calculator 1) (see 'Patients with multiple cardiovascular risk factors' below)

Patients without any of these characteristics are considered lower risk; we recommend a less intensive goal in such patients.

There are strong data supporting treatment decisions in some patient populations, such as in those with severely elevated blood pressure (eg, diastolic pressure ≥110 mmHg), in those at high cardiovascular risk, and in older adults. However, data are weak and largely indirect for many other patient populations. As such, good clinical judgment and shared decision-making between patient and provider are paramount.

The lower blood pressure targets in higher-risk groups are relevant to a large segment of the population [5]. Pursuing more intensive blood pressure lowering in such patients is likely to be cost effective, despite the need for more medication and additional monitoring [6-9].

Importance of how blood pressure is measured — Blood pressure targets depend in part upon the method by which the blood pressure is measured (table 2). Blood pressure monitoring to determine whether the patient is at goal should ideally employ one of the following four methods: standardized office-based measurement, AOBPM, home blood pressure monitoring, or ABPM. The four methods, described briefly below, are referred to as "non-routine" in this topic because they are uncommonly implemented. The "routine" method that is typically used worldwide to measure blood pressure should ideally not be used for clinical decision-making.

A variety of methods and equipment are used to measure blood pressure in clinical practice; all methods of measurement, in particular office measurements, should follow specific standards (see "Blood pressure measurement in the diagnosis and management of hypertension in adults"):

"Routine" (typical/casual) office blood pressure (non-preferred method) – Routine office blood pressure is typically measured once at the beginning of the office visit, with a care provider in the room and without proper patient preparation (ie, without having the patient first empty their bladder, without having the patient appropriately seated and rested for three to five minutes with both feet on the ground, without refraining from conversation during measurement, without using the correct cuff size, etc). It is likely that such routine measurements are highly variable from office to office and from one care provider to the next.

"Non-routine" standardized methods (preferred method):

Standardized office-based measurement – Standardized office measurement does not require specialized equipment (blood pressure can be taken manually or with an oscillometric device) but does require proper patient preparation and proper technique (table 1).

AOBPM – AOBPM uses an oscillometric device that is programed to average multiple consecutive readings after the patient has rested in a seated position for approximately five minutes. The device is activated by a care provider, who then can leave the room. AOBPM requires specialized equipment.

Home blood pressure – Home blood pressure, typically using an automated oscillometric device (which has been checked for accuracy in the clinician's office), is self-measured by the patient while out of the office. Typically, multiple readings are obtained daily over several consecutive days and then these readings are averaged to guide clinical decision-making. A common scenario is to instruct patients to take two to four daily readings for five to seven days before attending the clinic. Proper technique should be followed (table 1).

ABPM – ABPM is determined using a device (worn by the patient) that takes blood pressure measurements over a 24-hour period, usually every 15 to 30 minutes during the daytime and every 30 to 60 minutes during sleep.

The auscultatory method of measurement using a manual cuff is the most common technique employed in clinical practice and, in addition, was the technique used in most early clinical trials of antihypertensive therapy. In newer trials, oscillometric devices have been used. In all trials, standardized preparation and technique were followed (table 1).

AOBPM (attended and unattended) is less frequently employed in clinical practice but was the technique that was used in the Systolic Blood Pressure Intervention Trial (SPRINT) and the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Goal blood pressure trials that used home blood pressure measurement or ABPM are lacking.

On average, systolic pressure readings are typically 5 to 15 mmHg lower with non-routine compared with routine measurement because the "white coat" effect may be absent and because routine measurements are performed without proper patient preparation and technique [10-15]. Some studies have reported even more dramatic differences between non-routine and routine measurement [13]. However, it is critical to realize that this average difference in blood pressure between measurement methodologies applies to the population and not the individual. Some patients do not experience a white coat effect, and there is therefore some uncertainty in setting goals according to the method of measurement. (See "Blood pressure measurement in the diagnosis and management of hypertension in adults" and "Out-of-office blood pressure measurement: Ambulatory and self-measured blood pressure monitoring".)

Why baseline risk matters: Absolute versus relative risk — The management of adults diagnosed with hypertension depends in part upon the patient's risk for future cardiovascular events. (See 'Goal blood pressure in higher-risk patients' below and 'Goal blood pressure in lower-risk patients' below.)

In general, therapeutic decisions should be made based upon the absolute benefits and harms of a particular treatment and not the relative benefits and harms. Suppose, for example, that a blood pressure reduction of 10/5 mmHg produces a 20 percent relative risk reduction (ie, a relative risk [RR] of 0.80) for major cardiovascular events. Now suppose there are two hypertensive patients:

The first patient is a 50-year-old, nonsmoking, nondiabetic, African-American woman with a total cholesterol of 190 mg/dL, a high-density lipoprotein (HDL) cholesterol of 45 mg/dL, and a systolic pressure of 135 mmHg. This patient has a predicted 10-year risk of having a major atherosclerotic cardiovascular event of 3 percent (calculator 1).

The second patient is a 50-year-old, diabetic, African-American woman who smokes cigarettes, has a total cholesterol of 200 mg/dL, an HDL cholesterol of 35 mg/dL, and a systolic pressure of 135 mmHg. This patient has a predicted 10-year risk of having a major atherosclerotic cardiovascular event of 20 percent (calculator 1).

Usually, the relative risk reduction of a treatment is similar across different patients and populations with different baseline risk [16]. Thus, for both patients presented above, antihypertensive therapy would reduce the relative risk of cardiovascular events by 20 percent. However, the first patient would have an absolute risk reduction of 0.6 percent (from 3 percent to 2.4 percent), and the second patient would have an absolute risk reduction of 4.0 percent (from 20 percent to 16 percent). In a population similar to the first patient, 167 patients would need antihypertensive therapy for 10 years to prevent one major cardiovascular event; in a population similar to the second patient, 25 patients would require therapy for 10 years to prevent one event.

The conclusion from this hypothetical example, that the absolute benefit from therapy is larger among higher-risk as compared with lower-risk patients despite similar reductions in relative risk, is supported by various studies [17,18].

As an example, in a 2014 meta-analysis of 11 randomized trials comparing antihypertensive therapy with placebo, patients were risk stratified according to their estimated five-year risk of having a major cardiovascular event (ie, myocardial infarction, stroke, heart failure) using information in addition to their blood pressure, which included their age, sex, body mass index, and prior history of cardiovascular disease, smoking, and diabetes [18]. The relative risk of major cardiovascular events was significantly reduced by antihypertensive therapy to a similar degree regardless of the overall five-year risk. However, the absolute benefit varied significantly, for example:

In patients with the highest overall cardiovascular risk (ie, those with a five-year risk of more than 21 percent), the absolute risk reduction was 3.8 percent (number needed to treat was 26 patients for five years).

In patients with the lowest overall cardiovascular risk (ie, those with a five-year risk of approximately 6 percent), the absolute risk reduction was 1.4 percent (number needed to treat was 71 patients for five years).

Goal blood pressure in higher-risk patients — In general, more aggressive blood pressure goals are appropriate for higher-risk patients.

Patients with established atherosclerotic cardiovascular disease — In patients with established atherosclerotic cardiovascular disease (prior history of coronary, cerebrovascular, or peripheral arterial disease), we recommend a goal blood pressure of 120 to 125/<80 mmHg (using the non-routine [preferred] measurement methods including standardized office-based measurement, AOBPM, home blood pressure, and ABPM) or 125 to 130/<80 mmHg (using routine office measurements). These types of blood pressure measurements are defined and discussed above. (See 'Importance of how blood pressure is measured' above.)

The best data come from SPRINT, a multicenter, randomized, open-label trial performed in the United States [19,20]. SPRINT enrolled 9361 patients aged 50 years or older, more than 90 percent of whom were on antihypertensive therapy, who had a systolic blood pressure of 130 to 180 mmHg. In addition, they had to have one or more of the following additional risk factors for cardiovascular disease: age greater than or equal to 75 years, clinically evident cardiovascular disease (ie, previously documented coronary, peripheral arterial, or cerebrovascular disease [except for stroke]), subclinical cardiovascular disease (ie, an elevated coronary artery calcification score by computed tomography (CT) scan, left ventricular hypertrophy, or an ankle-brachial index <0.9), an estimated glomerular filtration rate (eGFR) of 20 to 59 mL/min/1.73 m2, or a 10-year Framingham Risk Score greater than or equal to 15 percent. SPRINT excluded patients with diabetes, symptomatic heart failure, a history of stroke, proteinuria (≥1 g/day total protein or ≥600 mg/day albumin), and nursing home residents. The mean age at baseline was 68 years, the mean body mass index was 30 kg/m2, the mean Framingham 10-year Risk Score was 20 percent, and the mean blood pressure was 140/78 mmHg. Clinical or subclinical cardiovascular disease was present in 22 percent of patients.

Patients were randomly assigned to a standard treatment group (targeting the systolic pressure to <140 mmHg) or an intensive treatment group (targeting the systolic pressure to <120 mmHg); the diastolic pressure goal in both groups was <90 mmHg. Blood pressure during the trial was measured using attended or unattended AOBPM. AOBPM is discussed in detail elsewhere. (See 'Importance of how blood pressure is measured' above and "Blood pressure measurement in the diagnosis and management of hypertension in adults", section on 'Type of measurement devices'.)

Antihypertensive therapy consisted of an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB; but not both), a long-acting dihydropyridine calcium channel blocker (typically amlodipine), or a thiazide-like diuretic (ie, chlorthalidone rather than hydrochlorothiazide) or a combination of these drugs to achieve the blood pressure target; other antihypertensive medications were added if needed. Medications were actively withdrawn in the standard treatment group if systolic blood pressure was below 130 to 135 mmHg, even in asymptomatic patients. In both groups, medications were altered or discontinued if patients developed adverse effects, and, at one year, approximately one-half of the patients in the intensive-treatment arm attained a systolic pressure less than 120 mmHg; the mean systolic pressures in the two groups at one year were 121 and 136 mmHg, and the mean number of antihypertensive medications used were 2.8 and 1.8.

The trial was halted early for benefit after a median follow-up of 3.33 years; the key findings from SPRINT are as follows:

Intensive as compared with standard treatment significantly reduced the rate of the primary endpoint, a composite of myocardial infarction, acute coronary syndrome, stroke, heart failure, or cardiovascular death (5.6 versus 7.6 percent). This difference was due to differences in the rates of heart failure (1.4 versus 2.2 percent), myocardial infarction (2.2 versus 3.0 percent), and cardiovascular death (0.9 versus 1.5 percent). Among those with known cardiovascular disease at baseline, the risk of the primary endpoint was also lower (11.0 versus 13.3 percent), although this was not statistically significant.

Intensive treatment also significantly reduced mortality (3.5 versus 4.6 percent).

Acute kidney injury (AKI) occurred more frequently among patients assigned to intensive therapy (3.8 versus 2.3 percent) [21]. However, in the majority of patients, AKI was either mild (61 percent overall had stage 1 AKI) or moderate (17 percent had stage 2), and AKI completely or partly resolved in approximately 95 percent of patients. Mild to moderate AKI does not typically warrant reduction of antihypertensive therapy unless hyperkalemia is also present [22].

In addition, the incidence of CKD (defined as a substantive decline in eGFR from ≥60 to <60 mL/min/1.73 m2) was higher in patients assigned intensive therapy (3.7 versus 1.0 percent) [23]. However, this excess of new-onset CKD in the intensive group was accompanied by decreased, rather than increased, levels of kidney injury biomarkers [24]. This suggests that an increase in creatinine during intensive blood pressure lowering may reflect a benign functional (and reversible) change in GFR due to reduced blood flow rather than parenchymal kidney damage [24-26].

Syncope (3.2 versus 2.1 percent) and hyponatremia (4.0 versus 2.2 percent) were also more common with intensive therapy, but the rates of injurious falls (falls leading to evaluation in the emergency department or hospitalization) were similar between the groups [19,20].

In addition, there were no differences between treatment groups with respect to physical and mental health-related quality of life, symptoms of depression, or satisfaction with care [27]. There was also no increase in the development of dementia; conversely, intensive blood pressure lowering reduced the rate of mild cognitive impairment (6.1 versus 7.5 percent over a median follow-up of 5.1 years) [28] and reduced the accumulation of cerebral white matter lesions (assessed by magnetic resonance imaging [MRI]) [29].

The findings from SPRINT suggest that, among older, hypertensive, nondiabetic adults at high risk for cardiovascular disease, targeting AOBPM to <120 mmHg can reduce mortality and prevent cardiovascular events. However, a variety of factors are likely to affect the applicability of the findings:

Many patients enrolled in SPRINT had controlled hypertension at baseline; also, patients enrolled in clinical trials, in general, are usually healthier than other patients with the same disorder. Thus, the rate of adverse events reported in SPRINT may be an underestimate of the adverse event rate that would be seen with intensive treatment in routine practice. In addition, patients in routine practice may require more antihypertensive medications than participants in SPRINT (the average was three in the intensive treatment group, and approximately one-fourth required four or more medications), and this could increase risk of adverse events.

Blood pressure in SPRINT was measured using attended and unattended AOBPM, which corresponds more closely with mean daytime blood pressure (using 24-hour ambulatory monitoring) than with the routine (casual) blood pressure measurements that are typically performed (see "Blood pressure measurement in the diagnosis and management of hypertension in adults", section on 'Technique of measurement'). Routine systolic pressure measurements are usually higher than AOBPM measurements (by 5 to 15 mmHg). Thus, if clinicians use routine blood pressure measurement (the most common method in clinical practice) rather than AOBPM, then targeting a systolic pressure of <120 mmHg is likely to increase the risk of hypotensive adverse events.

Most patients enrolled in SPRINT had diastolic pressures greater than 70 mmHg at baseline, and these pressures remained above 65 mmHg during the course of the trial in the majority, even in the intensive treatment group. By contrast, many older adults with isolated systolic hypertension have low diastolic pressure (ie, less than 60 to 65 mmHg) at baseline; such patients may not tolerate aggressive lowering of the systolic pressure, particularly those who have existing coronary artery disease. (See 'Older adults with isolated systolic hypertension' below.)

In addition, high-quality meta-analyses found that more versus less intensive blood pressure lowering produced cardiovascular benefits [30-33]. As an example, a meta-analysis of 19 goal blood pressure trials (excluding SPRINT) combining 44,989 patients found a significant reduction in major cardiovascular events with more intensive as compared with less intensive blood pressure lowering (RR 0.86, 95% CI 0.78-0.96) [30].

Evidence supporting lower blood pressure targets also comes from trials that examined the effects of adding an antihypertensive medication, as compared with placebo, to the existing regimen among patients with known cardiovascular disease and a baseline blood pressure that was already below 140 mmHg (using routine measurements). Most, but not all, of these placebo-controlled trials, including Heart Outcomes Prevention Evaluation (HOPE), European Trial on Reduction of Cardiac Events with Perindopril in Stable Coronary Artery Disease (EUROPA), Prevention of Events with Angiotensin-Converting Enzyme Inhibition (PEACE), Comparison of Amlodipine vs Enalapril to Limit Occurrences of Thrombosis (CAMELOT), Telmisartan Randomised Assessment Study in ACE-Intolerant Subjects with Cardiovascular Disease (TRANSCEND), and Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR), evaluated the hypothesis that ACE inhibitors or ARBs might have a direct and clinically significant cardiovascular benefit [34-46].

A 2009 meta-analysis focused on seven trials that limited therapy to either an ACE inhibitor or an ARB versus placebo in patients with ischemic heart disease and preserved left ventricular systolic function [47]. In six trials, ACE inhibitor therapy (including HOPE, EUROPA, CAMELOT, and PEACE) significantly reduced both total mortality (RR 0.87, 95% CI 0.81-0.94) and nonfatal myocardial infarction (RR 0.83, 95% CI 0.73-0.94). A limitation to this meta-analysis is that it did not distinguish between angiotensin inhibition and lower attained blood pressure as the mechanism of benefit. This limitation was overcome in a 2011 meta-analysis that included 25 placebo-controlled trials with more than 63,000 patients in which active treatment consisted of all major classes of antihypertensive drugs, including ACE inhibitors, ARBs, beta blockers, calcium channel blockers, diuretics, or combination therapy [48]. Drug therapy significantly lowered the risks of all-cause mortality and myocardial infarction to the same degree as in the earlier meta-analysis (pooled RR 0.87, 95% CI 0.80-0.95 and 0.80, 95% CI 0.69-0.93, respectively), suggesting that there was no specific benefit from therapy with angiotensin inhibitors compared with other antihypertensive drugs. Rather, the benefit seen likely resulted from blood pressure lowering. The absolute risk reductions in all-cause mortality and myocardial infarction were 14 and 13 per 1000 persons treated.

However, recommendations based upon SPRINT and these meta-analyses should not necessarily be applied to patients who are at low risk of having a cardiovascular event. In the Third HOPE trial (HOPE-3; discussed below), for example, patients at low or moderate risk for cardiovascular events whose blood pressure was <140/<90 mmHg did not benefit from antihypertensive therapy [49]. (See 'Goal blood pressure in lower-risk patients' below.)

Prior history of ischemic stroke or transient ischemic attack — Our suggestions for target blood pressure in patients with a prior ischemic stroke or TIA are, for the most part, the same as in other patients with established cardiovascular disease. (See 'Patients with established atherosclerotic cardiovascular disease' above.)

However, some patients, such as those with uncorrected hemodynamically significant large artery disease (ie, of the internal carotid, middle cerebral, vertebral, or basilar artery), may develop ischemic symptoms with intensive blood pressure lowering and are at higher risk for recurrent stroke [50,51]. Such patients require a less intensive goal. (See "Antihypertensive therapy for secondary stroke prevention" and "Evaluation of carotid artery stenosis".)

The main trial evaluating specific blood pressure targets in patients with ischemic stroke was the Secondary Prevention of Small Subcortical Strokes (SPS3) study, which randomly assigned 3020 patients (mean age of 63 years) with recent (two weeks to six months) lacunar (ie, small vessel) infarction to a systolic blood pressure target of either 130 to 149 mmHg or less than 130 mmHg (using routine measurements) [52]. Treatment was open label, using drugs from each of the major classes of antihypertensive medications prescribed by the local clinician. At one year, the achieved average systolic blood pressures for the higher- and lower-target groups were 138 and 127 mmHg, respectively, and the mean 11 mmHg difference between the groups was sustained for the duration of the study. Patients assigned to the lower blood pressure target group were treated with a greater number of antihypertensive medications compared with the higher-target group (mean of 2.4 versus 1.8). The following outcomes were reported [52]:

At study end, with a mean follow-up of 3.7 years, there were 277 first recurrent strokes; the annualized rate of all recurrent stroke was nonsignificantly reduced in the lower-target compared with the higher-target blood pressure group (2.25 versus 2.77 percent, hazard ratio [HR] 0.81, 95% CI 0.64-1.03). Similarly, the rate of a composite outcome of myocardial infarction or vascular death was nonsignificantly reduced in the lower blood pressure group.

The rate of intracerebral hemorrhage was significantly reduced in the lower-target blood pressure group (HR 0.37, 95% CI 0.15-0.95), but the small number of events (n = 22) limits the strength of this finding.

There were few serious adverse events in the higher- and lower-target groups (annualized rate of 0.4 versus 0.3 percent), and the difference was not significant.

Thus, the SPS3 results suggest, but do not establish, that a systolic blood pressure target of less than 130 mmHg (using routine blood pressure measurement) is beneficial and safe for preventing recurrent stroke in patients with small vessel ischemic stroke.

In addition to SPS3, findings from other trials also suggest that lower blood pressures are associated with better outcomes. As an example, the Prevention After Stroke-Blood Pressure (PAST-BP) trial assigned 529 patients with a history of stroke or TIA and a systolic pressure of at least 125 mmHg to intensive blood pressure lowering (targeting a systolic pressure of <130 mmHg) or standard blood pressure lowering (targeting a systolic pressure of <140 mmHg) [53]. This trial had many limitations, including a nearly 30 percent drop-out rate, a low number of events, and a minimal systolic pressure separation between the intensive and standard groups (127 versus 129 mmHg, respectively). However, the rate of major cardiovascular events was nonsignificantly lower in the intensive treatment group (1 versus 5 events).

Although not a trial of goal blood pressure, a post hoc analysis of the Perindopril Protection Against Recurrent Stroke Study (PROGRESS) trial addressed the issue of whether the baseline blood pressure affected the benefit from antihypertensive therapy, including the possibility that patients with normal blood pressure (<120 mmHg systolic) at baseline might be harmed from such therapy [54]. Among patients in the combination antihypertensive therapy arm, the relative risk reduction in stroke was similar at all levels of baseline systolic pressure (ranging from <120 to ≥160 mmHg). This suggests no harm from therapy in patients with low baseline pressures; however, there were so few events (six) in the subgroup of 146 patients with a systolic pressure of <120 mmHg at baseline that one cannot have confidence in these results.

A variety of other trials in patients with prior stroke examined attained (rather than target) blood pressure; most, but not all, found that lower achieved blood pressure was associated with fewer recurrent strokes [54-57].

Patients with heart failure — In patients with heart failure and reduced ejection fraction (HFrEF), we suggest a goal blood pressure of 120 to 125/<80 mmHg (using the non-routine [preferred] measurement methods including standardized office-based measurement, AOBPM, home blood pressure, and ABPM) or 125 to 130/<80 mmHg (using routine office measurements). However, such patients are often prescribed multiple specific drugs to improve survival and reduce morbidity, independent of the blood pressure, including inhibitors of the renin-angiotensin system (eg, ACE inhibitors, ARBs, or ARB-neprilysin inhibitors), beta blockers, diuretics, and, in selected patients, mineralocorticoid receptor antagonists and sodium-glucose co-transporter 2 (SGLT2) inhibitors. Thus, achieved blood pressure in these patients is frequently much lower than these thresholds. Many experts consider the goal of therapy to be the lowest blood pressure that is not associated with symptoms of hypotension or evidence of hypoperfusion (eg, worsening azotemia). In some patients with severe HFrEF, this may be a systolic pressure as low as 90 mmHg. (See "Overview of the management of heart failure with reduced ejection fraction in adults".)

For patients who have heart failure with preserved ejection fraction (HFpEF), we suggest a goal blood pressure of <120 to 125/<80 mmHg (non-routine measurement) or 125 to 130/<80 mmHg (routine measurement). These goals are consistent with those for other patients at high cardiovascular risk. (See "Treatment of hypertension in patients with heart failure".)

Although various trials and meta-analyses have found that more intensive blood pressure lowering can reduce incident heart failure and heart failure-associated morbidity, there are no specific trials of goal blood pressure in patients with HFrEF or HFpEF. Thus, our suggested targets in patients with heart failure are based upon low-quality data.

Routine and non-routine blood pressure measurements are defined and discussed above. (See 'Importance of how blood pressure is measured' above.)

Patients with diabetes mellitus — In patients with diabetes, we suggest a goal blood pressure of 120 to 125/<80 mmHg (using the non-routine [preferred] measurement methods including standardized office-based measurement, AOBPM, home blood pressure, and ABPM) or 125 to 130/<80 mmHg (using routine office measurements). These types of blood pressure measurements are defined and discussed above. (See 'Importance of how blood pressure is measured' above.)

Support for our recommendations comes from randomized trials, meta-analyses, and large observational studies [30-32,58-63]. The largest trial (ACCORD) was a goal blood pressure trial that found no benefit from a more intensive goal (systolic blood pressure less than 120 mmHg) as compared with a less intensive goal (systolic blood pressure less than 140 mmHg), other than a 53 percent relative reduction in the risk of stroke [59]. However, patients in ACCORD were also randomized to intensive or standard glycemic control (ie, it was a two-by-two factorial trial), and, in the standard glycemic control arm, the more intensive blood pressure group had fewer major cardiovascular events [64]. In addition to ACCORD, meta-analyses of trials suggest that, in diabetic patients, more aggressive blood pressure lowering generally reduces the risk of cardiovascular events and that, in patients whose baseline systolic pressure is <140 mmHg, further lowering of the blood pressure can prevent stroke and retinopathy [30,31].

The ACCORD trial enrolled 4733 patients with type 2 diabetes and either known cardiovascular disease or at least two additional cardiovascular risk factors; patients were randomly assigned to either systolic blood pressure goal less than 120 mmHg or a systolic blood pressure goal less than 140 mmHg. Blood pressure was measured with AOBPM. The goals were achieved; the mean attained systolic blood pressures in the two groups were 119 and 134 mmHg, respectively, compared with 139/76 mmHg at baseline.

At a mean follow-up of 4.7 years, the following findings were noted:

There was no significant difference in the annual rate of the primary composite outcome of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes between the intensive versus standard therapy groups (1.87 versus 2.09 percent, HR 0.88, 95% CI 0.73-1.06).

There was no difference in the annual all-cause mortality rate between intensive and standard therapy groups (1.28 versus 1.19 percent) or in the rate of death from cardiovascular causes between groups (0.52 versus 0.49 percent).

Intensive therapy was associated with significant reductions in the annual rates of total stroke and nonfatal stroke (0.32 versus 0.53 percent, HR 0.59, 95% CI 0.39-0.89, for total stroke, and 0.3 versus 0.47 percent, HR 0.63, 95% CI 0.41-0.96, for nonfatal stroke).

Serious adverse events attributable to antihypertensive drugs (eg, hypotension, syncope, bradycardia or arrhythmia, hyperkalemia, angioedema, and kidney failure) occurred significantly more frequently in the intensive versus standard therapy group (3.3 versus 1.3 percent). Intensive therapy was also associated with a significantly higher rate of an increase in serum creatinine of more than 1.5 mg/dL (133 micromol/L) in men or more than 1.3 mg/dL (115 micromol/L) in women.

Although the results from ACCORD found that intensive blood pressure lowering did not reduce cardiovascular events apart from stroke, patients were also randomized to intensive or standard glycemic control (ie, it was a two-by-two factorial trial), and the effect of intensive blood pressure lowering can also be analyzed according to glycemic control assignment [64]. Compared with patients assigned to standard blood pressure/standard glycemic control, the hazard ratios for major cardiovascular events among those assigned intensive blood pressure/standard glycemic control and intensive blood pressure/intensive glycemic control were 0.74 (95% CI 0.55-1.00) and 0.71 (95% CI 0.52-0.96), respectively. This result is important because the intensive glycemic goal implemented in the ACCORD trial is not recommended (owing to a higher rate of cardiovascular disease and mortality). Nevertheless, the benefits of a lower goal blood pressure may not extend to patients with relatively strict glycemic control.

In addition, three high-quality meta-analyses found that more intensive blood pressure lowering produced cardiovascular benefits in diabetic patients [30-32]. As an example, a meta-analysis of 19 goal blood pressure trials (including 5 trials of diabetic patients) combining 44,989 patients found a significant reduction in major cardiovascular events with more intensive as compared with less intensive blood pressure lowering (RR 0.86, 95% CI 0.78-0.96) [30]. The effect of intensive blood pressure lowering in the 5 trials of diabetic patients was similar (RR 0.83, 95% CI 0.71-0.96) to the effect in the other trials. All-cause mortality was also lower with intensive treatment, but this was not statistically significant (RR 0.91, 95% CI 0.81-1.03).

Based upon data from goal blood pressure trials in diabetic patients, plus indirect data from SPRINT (which included patients who, like those with diabetes, have a high cardiovascular risk) [19,20,65], we suggest a goal systolic pressure of 120 to 125 mmHg if non-routine readings are used or 125 to 130 mmHg if routine measurements are used to measure blood pressure, rather than a goal systolic pressure of less than 140 mmHg. Goal diastolic pressure is <80 mmHg. These recommendations are broadly consistent with those made by the American Diabetes Association (ADA), which suggests attaining a lower blood pressure (to a systolic of 125 to 130 mmHg) among those who can tolerate such therapy [66].

We recognize that, even with the large number of trials and total patients studied, the blood pressure goals we propose are based upon studies with a variety of patient populations, treatment goals, treatment approaches, and primary endpoints. Overall, however, the available data suggest important benefits from intensive blood pressure control, despite the risk of modest adverse events.

Patients with chronic kidney disease — In patients with CKD, we recommend a goal blood pressure of 120 to 125/<80 mmHg (using the non-routine [preferred] measurement methods including standardized office-based measurement, AOBPM, home blood pressure, and ABPM) or 125 to 130/<80 mmHg (using routine office measurements). The different types of blood pressure measurement are defined and discussed above. (See 'Importance of how blood pressure is measured' above.)

Our advice is broadly consistent with guidelines from the Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice statement [67] and is mainly justified by a reduction in cardiovascular disease and mortality and not by a reduction in CKD progression [68].

Overall, the best evidence supports the following points:

More intensive versus less intensive blood pressure lowering reduces the risk of end-stage kidney disease (ESKD) in patients with proteinuric CKD but not in patients with nonproteinuric CKD.

However, more intensive blood pressure lowering may reduce mortality in patients with CKD (whether they have proteinuria or not), even though there is no benefit on kidney endpoints among patients without proteinuria. The mortality benefit from aggressive blood pressure lowering is most evident when patients are followed over the long term (ie, during post-trial follow-up), although an early reduction in mortality was noted in SPRINT.

Several meta-analyses have synthesized the effects of more intensive blood pressure lowering on the progression of CKD, as well as the risk of death, in patients with and without proteinuria [69-73]. Proteinuria was variably defined in these studies as a protein-to-creatinine ratio greater than 0.22 g/g or a 24-hour protein excretion greater than 300 mg. The following examples are illustrative:

The most informative study was a meta-analysis that combined patient-level data on long-term follow-up from the two largest trials (African American Study of Kidney Disease [AASK] and Modification of Diet in Renal Disease [MDRD], with 14 to 19 years of follow-up) [71]. More intensive blood pressure control was associated with reduced overall mortality (HR 0.87, 95% CI 0.76-0.90), and the reduction in death was similar in patients with and without proteinuria. Aggressive blood pressure lowering also reduced the progression to ESKD (HR 0.88, 95% CI 0.78-1.00), but the benefit was confined to those with proteinuric CKD.

A larger meta-analysis of nine goal blood pressure trials and 8127 patients (not including the SPRINT-CKD cohort) reported no effect of intensive blood pressure lowering on CKD progression, cardiovascular events, or mortality at 3.3 years of follow-up [72]. However, long-term (post-trial) follow-up of those patients with proteinuria revealed a benefit on the incidence of ESKD (RR 0.91, 95% CI 0.85-0.99). The investigators did not report the risk of death during long-term follow-up.

The three major goal blood pressure trials of patients with CKD (AASK, MDRD, and SPRINT) included different patient populations, examined different blood pressure targets, and used different methodology to measure blood pressure. Yet, as noted above, all three reached similar conclusions about the benefit of more intensive blood pressure lowering:

AASK trial – In the AASK trial, 1094 African Americans with long-standing hypertension, otherwise unexplained slowly progressive CKD, and usually mild proteinuria (median approximately 100 mg/day) were randomly assigned to one of two mean arterial blood pressure goals (using standardized office blood pressure): less than or equal to 92 mmHg or 102 to 107 mmHg [74]. The attained blood pressures were 128/78 and 141/85 mmHg. At a mean follow-up of approximately four years, the mean rate of change in GFR and other kidney parameters was not different between the two groups.

Following completion of the trial phase, participants were invited to continue in a cohort phase of the study, in which the blood pressure target for everyone was <130/80 mmHg [75]. During the cohort phase, which lasted approximately five years, the mean blood pressure was 131/78 and 134/78 mmHg in the intensive control and standard control groups, respectively. The use of ACE inhibitors and ARBs was similar in the two groups. As was observed during the trial phase, there was no difference between groups in the progression of kidney disease (defined as doubling of the serum creatinine, a diagnosis of ESKD, or death). However, among patients with a baseline urine protein-to-creatinine ratio of greater than 0.22 (corresponding to absolute protein excretion of 300 mg/day; the median 24-hour protein excretion in these patients was approximately 1000 mg/day), there was a significant reduction in risk of progression with intensive blood pressure control (HR 0.73, 95% CI 0.58 to 0.93). By contrast, patients with urine protein-to-creatinine ratios less than 0.22 (median 24-hour protein excretion was 60 mg [ie, nonproteinuric]) showed no benefit from intensive therapy.

After the cohort phase was complete, AASK participants were followed for a median of 14 years for the occurrence of ESKD and death using the United States Renal Data System (USRDS), the national ESKD registry, and the Social Security Death Index [71]. The effect of more intensive blood pressure control on the incidence of ESKD depended upon whether or not patients had proteinuria (HR 0.59, 95% CI 0.41-0.85 in patients with proteinuria >1 g/d and HR 1.05, 95% CI 0.83-1.32 in patients with lower amounts of proteinuria). By contrast, the benefit of aggressive blood pressure lowering on mortality did not vary according to proteinuria (HR 0.81, 95% CI 0.68-0.98).

MDRD – The MDRD trial compared usual blood pressure control (target mean arterial pressure less than 107 mmHg) with more aggressive control (target mean arterial pressure less than 92 mmHg), using standardized office blood pressure measurements, over a three-year period [76]. The achieved mean arterial pressures were 96 and 91 mmHg (equivalent to 130/80 and 125/75 mmHg, respectively).

The results in 585 patients with a mean baseline GFR of 39 mL/min and mean urinary protein excretion of 1.1 g/day can be summarized as follows (figure 1):

The loss of GFR was lowest in patients excreting less than 1 g/day (2.8 to 3.0 mL/min year), but no benefit for GFR loss was seen with aggressive blood pressure control.

Patients excreting between 1 and 3 g/day had more rapid progression and a modest benefit for GFR loss from aggressive blood pressure control.

Patients excreting 3 g/day or more had the fastest rate of progression but a clinically and statistically significant slowing of the rate of progression with aggressive blood pressure control (rate of GFR decline of 10.2 with conventional versus 6.7 mL/min per year with aggressive blood pressure control).

A subsequent study reported the long-term outcomes of patients enrolled in the initial MDRD study [77]. After the study was completed in 1993, all participants were passively followed until 2000 for the incidence of kidney failure (defined as dialysis or kidney transplantation) and all-cause mortality. The mean difference in blood pressure between the two groups during the trial phase was 7.6/3.8 mmHg; blood pressure was not recorded during passive follow-up. On intention-to-treat analysis, patients in the aggressive control group were significantly less likely to experience kidney failure (adjusted HR 0.68, 95% CI 0.57-0.82) or either kidney failure or death (0.77, 95% CI 0.65-91). Kidney failure accounted for approximately 90 percent of events, and a hazard ratio was not provided for mortality alone.

However, a subgroup analysis of this extended follow-up revealed that the benefit from aggressive blood pressure control was only significant in patients with protein excretion exceeding 1 g/day (HR approximately 0.6 to 0.7). The hazard ratio was higher and not significant in patients excreting 300 to 1000 mg/day or less than 300 mg/day (HR of 0.8 and >0.9, respectively). When all patients with protein excretion of 1000 mg/day or less were combined, there was a significant reduction in the hazard ratio for kidney failure (0.79, 95% CI 0.63-0.99) but not for the composite outcome of kidney failure and death.

SPRINT – The CKD subgroup in SPRINT included 2646 patients with an eGFR of 20 to 59 mL/min/1.73 m2 and proteinuria <1g/day; the mean age of this subgroup was 72 years, the mean eGFR was 48 mL/min/1.73 m2, and 78 percent had a 10-year Framingham Risk Score greater than or equal to 15 percent [68]. Achieved blood pressure, which was measured using attended and unattended AOBPM, was 123/67 mmHg in the intensive goal group and 137/74 mmHg in the standard goal group. The following findings were noted among SPRINT participants who had CKD at baseline:

Intensive blood pressure lowering significantly reduced all-cause mortality (annual mortality of 1.6 versus 2.2 percent).

The primary outcome, a composite of myocardial infarction, acute coronary syndrome, stroke, heart failure, or cardiovascular death, was also less frequent in the intensive goal group (2.7 versus 3.2), and this was consistent with data from the entire SPRINT population. However, the result in the CKD subgroup was nonsignificant, possibly because of reduced statistical power.

There was no difference in the incidence of ESKD or a 50 percent or greater decline in eGFR. By contrast, intensive blood pressure lowering increased the risk of a 30 percent or greater decline in eGFR. However, this decline principally occurred in the first six months of the trial, suggesting an acute hemodynamic effect of a lower blood pressure; after six months, the rate of change in eGFR differed only slightly (annual decline of 0.47 versus 0.32 mL/min/1.73 m2 in the intensive and standard groups, respectively) (figure 2).

Older adults — In most older adults (defined as age 65 years or older), we recommend a goal blood pressure of 120 to 125/<80 mmHg (using the non-routine [preferred] measurement methods including standardized office-based measurement, AOBPM, home blood pressure, and ABPM) or 125 to 130/<80 mmHg (using routine office measurements). These types of blood pressure measurements are defined and discussed above. (See 'Importance of how blood pressure is measured' above.)

However, we suggest a less aggressive systolic goal blood pressure of 135 to 140 mmHg (routine measurements) or 130 to 135 mmHg (nonroutine measurements) in patients with a reduced life expectancy, for example, because of a high burden of comorbidity. Individualization of blood pressure management is key in this population since the clinical benefit from intensive control is unlikely to be realized within one to two years [78]. We also individualize goals and share decision-making with patients and caretakers in those with postural hypotension, severe frailty, those with dementia, and/or in patients who are nonambulatory or institutionalized (eg, reside in a skilled nursing facility).

Goal blood pressure in older adults, measured using AOBPM, was examined in SPRINT [79]. SPRINT enrolled a subgroup of more than 2600 ambulatory adults aged 75 years or older with a baseline blood pressure of 142/71 mmHg (consistent with isolated systolic hypertension), including 349 categorized as being fit, 1456 as less fit, and 815 as frail according to a validated frailty index. At 3.1 years, rates of both the primary cardiovascular endpoint and all-cause mortality were significantly lower among those assigned more intensive (goal of <120 mmHg; mean achieved systolic blood pressure 123) versus less intensive (goal of <140 mmHg; mean achieved systolic blood pressure 135) systolic blood pressure lowering (2.6 versus 3.8 percent and 1.8 versus 2.6 percent, respectively). The benefit from more intensive blood pressure control was present in both fit and frail older adults. Serious adverse events were similar in the two treatment groups and did not depend upon frailty.

A meta-analysis of 10,857 hypertensive adults aged 65 years or older combined these results from SPRINT with three other large randomized goal blood pressure trials [80]. After a mean follow-up of 3.1 years, more intensive versus less intensive blood pressure lowering reduced the rates of major adverse cardiovascular events (3.7 versus 5.2 percent), cardiovascular mortality (1.1 versus 1.7 percent), and heart failure (1.3 versus 2.0 percent). Rates of stroke and myocardial infarction were also lower, but the results were not statistically significant. Similarly, a subsequent trial of 199 high-risk hypertensive patients aged ≥75 years found that intensive blood pressure lowering (24-hour systolic pressure goal ≤130 compared with ≤145 mmHg) resulted in a reduction in cardiovascular morbidity at three years (4 versus 17 percent); in addition, all patients had hyperintense white matter lesions in the brain at baseline, and intensive therapy slowed the accrual of such lesions [81].

A large trial published after this meta-analysis assigned 8511 Chinese adults aged 60 to 80 years to either a more intensive (goal systolic pressure <130 mmHg) or less intensive (systolic pressure <150 mmHg) goal blood pressure strategy [82]. At baseline, mean age was 66 years, mean blood pressure was 146/82 mmHg, and 65 percent had a calculated Framingham Risk Score greater than or equal to 15 percent. Achieved systolic blood pressure, assessed using standardized office-based blood pressures (table 1), was 127 mmHg in the more intensive group and 136 mmHg in the less intensive group. At 3.3 years, the rates of stroke (1.1 versus 1.7 percent), acute coronary syndrome (1.3 versus 1.9 percent), and heart failure (0.1 versus 0.3 percent) were modestly decreased with intensive blood pressure lowering. All-cause mortality was not significantly different (1.6 versus 1.5 percent). Hypotension was more common in the intensive group, but other major adverse events (eg, syncope, fracture, worsening kidney function) were similar between the groups. The findings from this trial are generally consistent with those from SPRINT, although the population studied was lower risk at baseline and the difference in attained systolic blood pressure was smaller than in SPRINT.

Blood pressure goals may not be easy to achieve in older adults, particularly in those with a baseline systolic pressure greater than 160 mmHg. If attaining goal blood pressure proves difficult or overly burdensome for such patients, the systolic pressure that is reached with two or three antihypertensive agents (even if above target) may be a reasonable interim goal. Once maximally tolerated therapy is reached and blood pressure control remains suboptimal, then additional efforts to engage older adults in healthful lifestyle change can facilitate better blood pressure control.

One potential limitation to achieving goal blood pressure is that lowering the blood pressure may impair mental function, leading to manifestations such as confusion or sleepiness. In such patients, antihypertensive therapy should be reduced, and the systolic pressure should be allowed to rise to a level at which these symptoms resolve. More gradual and much slower lowering of blood pressure may then be pursued in an attempt to attain goal blood pressure [28].

Older adults with isolated systolic hypertension — When treating older patients with isolated systolic hypertension, we and others suggest a minimum on-treatment diastolic pressure of 55 to 60 mmHg (using office-based blood pressure) [83-85]. In such cases, the level of systolic blood pressure that is reached with two or three antihypertensive agents (even if greater than the goal presented above) may be a more reasonable goal [86]. (See "Treatment of hypertension in older adults, particularly isolated systolic hypertension".)

A concern when treating older adult patients with isolated systolic hypertension is that the low diastolic pressure after therapy may impair tissue perfusion (particularly coronary perfusion) and possibly increase cardiovascular risk (ie, the "J-curve") (figure 3 and figure 4) [87-92].

Various long-term observational studies in patients with hypertension have reported a nadir of cardiovascular complications at a diastolic pressure of approximately 80 mmHg. Thus, the incidence of cardiovascular complications is higher among those who achieve diastolic pressures greater than 80 to 85 mmHg, as well as among those who achieve diastolic pressures less than 75 to 80 mmHg (and particularly below 70 mmHg) [84,90,92-100].

Although lower attained diastolic pressures are associated with worse outcomes (both cardiovascular and noncardiovascular) in these studies, this finding is present in both treated and untreated (ie, placebo-treated) patients and also in trial patients assigned to less intensive blood pressure goals (figure 5) [101,102]. These findings suggest that the worse outcomes at lower diastolic pressures are probably explained by poor health in patients who have lower diastolic pressures and not necessarily an adverse effect of antihypertensive therapy. (See "Treatment of hypertension in older adults, particularly isolated systolic hypertension", section on 'Importance of diastolic pressure'.)

Nevertheless, there may be a threshold diastolic blood pressure below which adverse cardiovascular outcomes might increase in older adult patients, particularly in those with coronary heart disease because much of coronary filling occurs during diastole.

Patients with multiple cardiovascular risk factors — In patients with multiple cardiovascular risk factors (but without established cardiovascular disease), we recommend a goal blood pressure of 120 to 125/<80 mmHg (using the non-routine [preferred] measurement methods including standardized office-based measurement, AOBPM, home blood pressure, and ABPM) or 125 to 130/<80 mmHg (using routine office measurements) if the estimated 10-year risk of a future cardiovascular event is 15 percent or greater (calculator 1); we suggest (a weaker recommendation) these lower goals in patients whose estimated 10-year risk is 10 to 14 percent. Non-routine and routine blood pressure measurements are defined and discussed above. (See 'Importance of how blood pressure is measured' above.)

The best data come from SPRINT, which are presented above in detail. (See 'Patients with established atherosclerotic cardiovascular disease' above.)

One inclusion criteria in SPRINT was an estimated 10-year risk for a future cardiovascular event of 15 percent or greater; 7103 patients met this criteria (76 percent of those enrolled) [19,20]. In this subgroup, intensive blood pressure lowering significantly reduced the rate of myocardial infarction, acute coronary syndrome, stroke, heart failure, or cardiovascular death (4.0 versus 5.6 percent).

A subsequent meta-analysis of 16 goal blood pressure trials and 52,235 patients examined the relative and absolute effects of more versus less intensive blood pressure lowering [17]. A standardized 10/5 mmHg reduction in systolic/diastolic pressure resulted in the following [17]:

Significant reductions in the relative risks of stroke (0.71, 95% CI 0.60-0.84), coronary heart disease (0.80, 95% CI 0.68-0.95), and cardiovascular death (0.79, 95% CI 0.63-0.97). Nonsignificant relative risk reductions were found for heart failure (0.80, 95% CI 0.49-1.31) and all-cause mortality (0.83, 95% CI 0.69-1.03).

Relative risk reductions were similar regardless of the cardiovascular risk at baseline (ie, patients whose estimated 10-year risk of having an event was <5 percent had the same relative benefit from blood pressure lowering as those whose event risk was >10 percent). However, absolute benefits from blood pressure lowering were greater among patients who were higher risk at baseline. In patients whose baseline cardiovascular risk was estimated to be >10 percent, for example, a 10 mmHg reduction in systolic pressure in 1000 patients over five years prevented 66 strokes, 94 coronary heart disease events, 31 heart failure events, and 128 deaths (including 75 from cardiovascular disease). By contrast, in lower-risk patients (ie, those with an estimated risk of <5 percent), a similar blood pressure reduction in 1000 patients over five years prevented only 4 strokes, 4 coronary heart disease events, and 4 deaths; none of these absolute risk reductions in low-risk patients were statistically significant.

Thus, patients with an estimated 10-year cardiovascular disease event risk of 10 percent or greater appear to derive an important benefit from intensive blood pressure lowering, although it is likely that the benefit is greater among those whose risk is 15 percent or greater compared with those whose risk is 10 to 14 percent.

Goal blood pressure in lower-risk patients — In lower-risk patients (ie, those without any of the higher-risk characteristics mentioned above), we recommend a goal blood pressure of 125 to 135/<90 mmHg (using the non-routine [preferred] measurement methods including standardized office-based measurement, AOBPM, home blood pressure, and ABPM) or 130 to 139/<90 mmHg (using routine office measurements). (See 'Importance of how blood pressure is measured' above.)

However, there is some disagreement among UpToDate authors and editors. Some experts suggest that lower-risk patients with stage 2 hypertension (ie, patients with systolic pressure at least 140 mmHg or diastolic pressure at least 90 mmHg and who therefore qualify for antihypertensive therapy) should have the same goal blood pressure as patients who are higher risk.

The absolute benefit of blood pressure lowering is much lower in lower-risk as compared with higher-risk patients, although relative risk reductions are similar. (See 'Why baseline risk matters: Absolute versus relative risk' above.)

There are no goal blood pressure trials (ie, trials that compared different target blood pressures) in lower-risk patients. However, there are three large trials of lower-risk patients that compared antihypertensive therapy with placebo. Two of these (the Medical Research Council [MRC] trial and the Hypertension Detection and Follow-up Program [HDFP] trial) enrolled patients whose baseline blood pressure was ≥140/≥90 mmHg; in the other trial (HOPE-3), approximately two-thirds of the study population had a blood pressure at entry that was <140/<90 mmHg. All three trials performed standardized office blood pressure measurement. In general, these studies suggest benefit from blood pressure lowering to <140/<90 mmHg but not to <130/<80 mmHg:

HOPE-3 – The most informative data come from the HOPE-3 trial, in which 12,705 patients at moderate risk for cardiovascular disease (none had preexisting cardiovascular disease, and only 38 percent were hypertensive at baseline) were randomly assigned to receive a fixed-dose combination of candesartan plus hydrochlorothiazide or placebo [49]. Active treatment lowered blood pressure by 6/3 mmHg over the course of the trial. At 5.6 years, fewer cardiovascular events occurred among those treated with the fixed-dose combination, although this was not statistically significant. However, among the subgroup whose initial systolic pressure was in the highest tertile (ie, greater than 143 mmHg), antihypertensive therapy reduced the incidence of major cardiovascular events (5.7 versus 7.5 percent, absolute benefit of 1.8 percent). By contrast, those patients whose initial blood pressure was <140 mmHg derived no cardiovascular benefit. There was no effect on all-cause mortality.

MRC trial – In the MRC trial, 17,354 patients with a baseline diastolic pressure 90 to 109 mmHg were randomly assigned to bendrofluazide, propranolol, or placebo for up to five years [103]. The mean baseline blood pressure was approximately 161/98 mmHg; the mean attained blood pressure was approximately 137/86 mmHg in the two treated groups and 150/92 mmHg in the placebo group. The treated groups had significantly lower rates of all cardiovascular events (6.7 versus 8.2 per 1000 patient-years) and of stroke but not of coronary events or mortality.

HDFP trial – In stratum I of the HDFP trial, 7825 patients with mild hypertension (diastolic pressure of 90 to 104 mmHg) were randomly assigned to intensive therapy in special clinics (stepped care) or to usual source-of-care therapy in the community [104]. The main endpoint was total mortality at five years, which was significantly lower with stepped care (5.9 versus 7.4 percent, absolute benefit 1.5 percent, 95% CI 0.4-2.6 percent). The magnitude of benefit was similar but not quite significant for the almost 3000 patients with an entry diastolic pressure of 90 to 94 mmHg (absolute benefit 1.6 percent, 95% CI -0.2 to +3.4 percent) [105]. The average attained diastolic pressure was 85 to 90 mmHg in the stepped care; systolic pressures were not given.

Although these data do not support a target blood pressure below 130/80 mmHg in lower-risk patients, HOPE-3 followed patients for only five to six years. Because blood pressure lowering in such patients is likely to reduce the relative risk, and because blood pressure is unlikely to spontaneously decrease, treatment to below this threshold may eventually produce an important absolute risk reduction over the long term. Thus, some expert contributors to UpToDate, as well as some guideline statements [1], suggest the more intensive blood pressure goal for lower-risk in addition to higher-risk patients.

RECOMMENDATIONS OF OTHERS — Many professional organizations have published guidelines for the management of hypertension; those that were released after the publication of the SPRINT trial, and which incorporated the results of this trial in their recommendations, include the 2017 American College of Cardiology/American Heart Association (ACC/AHA) guidelines [1], the 2018 European Society of Cardiology/European Society of Hypertension (ESC/ESH) guidelines [106], the 2019 Canadian Hypertension Education Program (CHEP) guidelines [107], the 2016 National Heart Foundation of Australia guidelines [108], the National Institute for Health and Care Excellence (NICE) guidelines, the American College of Physicians/American Academy of Family Physicians (ACP/AAFP) guidelines [109], and the 2021 Kidney Disease Improving Global Outcomes (KDIGO) guidelines (table 3) [67]. The ACC/AHA, ESC/ESH, CHEP, and the National Heart Foundation of Australia guidelines are broadly similar to recommendations made by UpToDate. However, the ACP/AAFP guidelines depart from our recommendations by suggesting a goal systolic pressure of <150 mmHg in adults 60 years of age and older plus consideration of a goal of <140 mmHg in patients at high cardiovascular risk. We disagree with the ACP/AAFP, as noted above. (See 'Overview of our approach' above.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Hypertension in adults".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Beyond the Basics topics (see "Patient education: High blood pressure in adults (Beyond the Basics)" and "Patient education: High blood pressure treatment in adults (Beyond the Basics)" and "Patient education: High blood pressure, diet, and weight (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

Our proposed blood pressure targets depend in part upon the method by which the blood pressure is measured (see 'Importance of how blood pressure is measured' above):

In particular, blood pressure that is measured in the office (ie, medical care setting) should be obtained in a standardized manner. There are two ways to performed high-quality, standardized office blood pressure measurement: automated oscillometric blood pressure monitoring (AOBPM), which requires specialized equipment, and standardized office-based measurement using proper technique (table 1), which requires only ordinary equipment. These two methods of measuring blood pressure in the office provide readings that approximate daytime ambulatory blood pressure (using ambulatory blood pressure monitoring [ABPM]) and self-measured (home) blood pressure monitoring. These four methods, while superior, are uncommonly performed and therefore are referred to as "non-routine."

Although not the preferred method, the way blood pressure is typically obtained in the medical care setting, in which blood pressure is measured (usually once) with a stethoscope or oscillometric device, lacks proper patient preparation and proper technique. Although it is an inferior method of measurement, it is faster and potentially less cumbersome and is the one primarily used in clinical practice (and therefore is referred to as "routine" measurement).

Blood pressure targets differ depending upon the technique of measurement because "routine" methods typically provide higher blood pressure readings compared with the preferred, "non-routine" methods. (See "Blood pressure measurement in the diagnosis and management of hypertension in adults".)

In addition, blood pressure targets are based upon the patient's risk for having a future cardiovascular event (table 2) (see 'Goal blood pressure in higher-risk patients' above):

In most patients with established atherosclerotic cardiovascular disease (prior history of coronary, cerebrovascular, or peripheral arterial disease), we recommend a goal blood pressure of 120 to 125/<80 mmHg (using the non-routine [preferred] measurement methods including standardized office-based measurement, AOBPM, home blood pressure, and ABPM) or 125 to 130/<80 mmHg (using routine [non-preferred] office measurements) (Grade 1B). (See 'Patients with established atherosclerotic cardiovascular disease' above.)

However, in hypertensive patients who have had a recent (two weeks to six months) stroke associated with uncorrected hemodynamically significant large artery disease (ie, of the internal carotid, middle cerebral, vertebral, or basilar artery), we suggest cautious blood pressure lowering as tolerated but without a specific blood pressure goal other than a minimum reduction of 10/5 mmHg (Grade 2C). (See 'Prior history of ischemic stroke or transient ischemic attack' above.)

In patients with heart failure, we suggest a goal blood pressure of 120 to 125/<80 mmHg (using the non-routine [preferred] measurement methods including standardized office-based measurement, AOBPM, home blood pressure, and ABPM) or 125 to 130/<80 mmHg (using routine [non-preferred] office measurements) (Grade 2C). (See 'Patients with heart failure' above.)

In most patients with diabetes, we suggest a goal blood pressure of 120 to 125/<80 mmHg (using the non-routine [preferred] measurement methods including standardized office-based measurement, AOBPM, home blood pressure, and ABPM) or 125 to 130/<80 mmHg (using routine [non-preferred] office measurements) (Grade 2B). (See 'Patients with diabetes mellitus' above.)

In patients with chronic kidney disease (CKD), we recommend a goal blood pressure of 120 to 125/<80 mmHg (using the non-routine [preferred] measurement methods including standardized office-based measurement, AOBPM, home blood pressure, and ABPM) or 125 to 130/<80 mmHg (using routine [non-preferred] office measurements) (Grade 1B). (See 'Patients with chronic kidney disease' above.)

In most older adults (defined as age 65 years or older), we recommend a goal blood pressure of 120 to 125/<80 mmHg (using the non-routine [preferred] measurement methods including standardized office-based measurement, AOBPM, home blood pressure, and ABPM) or 125 to 130/<80 mmHg (using routine [non-preferred] office measurements) (Grade 1B). (See 'Older adults' above.)

However, we suggest a less aggressive systolic goal blood pressure of 135 to 140 mmHg (routine measurements) or 130 to 135 mmHg (non-routine measurements) in patients with a high burden of comorbidity and also in older adults with postural hypotension.

In older adults with severe frailty, dementia, and/or a limited life expectancy or in patients who are nonambulatory or institutionalized (eg, reside in a skilled nursing facility), we individualize goals and share decision-making with the patient, relatives, and caretakers, rather than targeting one of the blood pressure goals mentioned above.

In patients with multiple cardiovascular risk factors (but without established cardiovascular disease), we recommend a goal blood pressure of 120 to 125/<80 mmHg (using the non-routine [preferred] measurement methods including standardized office-based measurement, AOBPM, home blood pressure, and ABPM) or 125 to 130/<80 mmHg (using routine [non-preferred] office measurements) if the estimated 10-year risk of a future cardiovascular event is 15 percent or greater (calculator 1) (Grade 1A); we suggest (a weaker recommendation) these lower goals in patients whose estimated 10-year risk is 10 to 14 percent (Grade 2B). (See 'Patients with multiple cardiovascular risk factors' above.)

In lower-risk patients (ie, those without any of the higher-risk characteristics mentioned above), we recommend a goal blood pressure of 125 to 135/<90 mmHg (using the non-routine [preferred] measurement methods including standardized office-based measurement, AOBPM, home blood pressure, and ABPM) or 130 to 139/<90 mmHg (using routine [non-preferred] office measurements) (Grade 1B). (See 'Goal blood pressure in lower-risk patients' above.)

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References