Version August 2024
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 (BP) in adults with hypertension is discussed in this topic.
Other issues in hypertensive adults are presented separately:
●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 BP 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 BP in hypertensive adults:
•(See "Overview of hypertension in adults".)
•(See "Diet in the treatment and prevention of hypertension".)
•(See "Salt intake and 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".)
BLOOD PRESSURE MEASUREMENT STRATEGY
Preferred BP measurement strategies — Goal BP targets depend in part upon the method by which the BP is measured [4]. BP should be measured using one of the following three preferred strategies listed below and in the table (table 1). These strategies are considered "preferred" for BP measurement and decision making because they most closely approximate daytime ambulatory BP, with less variability between offices and medical providers [5-7]. These are also the BP measurement methods used in contemporary trials of antihypertensive therapy.
●Ambulatory BP monitoring (ABPM).
●Self-measured BP (SMBP).
●Standardized (high-quality), office-based BP measurements, including manual and automated BP measurement. There are two ways to perform high-quality office BP measurement:
•Standardized office-based measurement using proper preparation and technique (table 2).
•Automated office BP monitoring (AOBPM), which requires specialized equipment.
These two methods of measuring BP in the office provide readings that most closely approximate daytime ambulatory BP (ie ABPM or SMBP) [5-7]. If possible, AOBPM should be performed without a medical professional in the clinic room (ie, "unattended"), since this avoids the "white coat" effect. (See "White coat and masked hypertension".)
Additional details on BP measurement, including practical aspects of ABPM, SMBP, and standardized office-based BP measurement (including AOBPM), are presented separately. (See "Blood pressure measurement in the diagnosis and management of hypertension in adults".)
Inferior (casual) BP measurement strategies — Many if not most medical offices measure BP without proper preparation and technique (table 2), regardless of whether the measurement is manual (using the auscultatory method) or oscillometric. Foregoing proper preparation and technique is common because it is faster and less cumbersome than the preferred methods. Although these inferior methods of measurement are widely employed, we recommend against using them to determine if a patient is at goal.
We classify these non-standardized methods as "casual" since they are the methods typically used in clinical practice. Due to the lack of standardization, casual methods of measurement can vary between offices and medical providers and provide BP readings that differ considerably from readings obtained by preferred methods; on average, casual systolic BP readings are 5 to 15 mmHg higher than those obtained by preferred methods, although there is substantial person-to-person variation. (See "Blood pressure measurement in the diagnosis and management of hypertension in adults", section on 'Routine office-based blood pressure' and 'Adjustment of BP target based on BP measurement strategy' below.)
OUR APPROACH TO GOAL BLOOD PRESSURE
Assessment of baseline cardiovascular risk — BP targets are based upon the patient's risk for having a future cardiovascular event [8]. 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 1) (see 'Intensive goal blood pressure targets for higher-risk patients' below):
•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)
•Heart failure (see 'Patients with heart failure' below)
•Diabetes mellitus (see 'Patients with diabetes mellitus' below)
•Chronic kidney disease (CKD) (see 'Patients with chronic kidney disease' below)
•Age >65 years (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. (See 'Less intensive goal blood pressure in lower-risk patients' below.)
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 'Intensive goal blood pressure targets for higher-risk patients' below and 'Less intensive 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 BP 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 [9]. Thus, for both patients presented above, antihypertensive therapy lowering systolic pressure by 10 mmHg 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 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 [10,11].
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 BP, which included their age, sex, body mass index, and prior history of cardiovascular disease, smoking, and diabetes [11]. 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).
Adjustment of BP target based on BP measurement strategy — BP targets may be modified, depending on the method by which the BP is measured [4]. As noted above, we only use preferred methods of measurement to determine if a patient is at goal, and we recommend against casual measurements to determine if a patient is at goal. Nevertheless, casual methods are frequently used in clinical practice to monitor patients with hypertension, and because they generally provide readings higher than those obtained from preferred methods, BP targets should differ.
If casual methods are used, a higher (by 5 mmHg) systolic BP target may be appropriate. On average, systolic pressure readings are typically 5 to 15 mmHg higher with casual measurement as compared with preferred measurement because of a "white coat" effect and because casual measurements are performed without proper patient preparation and technique [5,12-16].
Some studies have reported even more dramatic differences between preferred and casual measurement [14]. However, this average difference in BP between 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 a goal for patients who are managed using casual measurements. (See 'Preferred BP measurement strategies' above and "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".)
There are strong data supporting treatment decisions in some patient populations, such as in those with severely elevated BP (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 BP targets in higher-risk groups are relevant to a large segment of the population [17]. Pursuing more intensive BP lowering in such patients is likely to be cost effective, despite the need for more medication and additional monitoring [18-21].
Intensive goal blood pressure targets for higher-risk patients — An intensive BP goal of 120 to 125/80 mmHg is appropriate for higher-risk patients when preferred BP measurement strategies are used.
When treating to this goal, a patient may attain a BP below the target. Provided the patient does not develop symptoms, side effects, or adverse events as a result of the treatment regimen, then reducing or withdrawing antihypertensive medications is unnecessary [22,23].
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 BP of 120 to 125/<80 mmHg (using a preferred measurement method, including standardized office-based measurement, automated office BP monitoring [AOBPM], self-measured BP [SMBP], and ambulatory BP monitoring [ABPM]) or 125 to 130/<80 mmHg (using casual office measurements). These types of BP measurements are defined and discussed above. (See 'Preferred BP measurement strategies' above.)
The best data come from the Systolic Blood Pressure Intervention Trial (SPRINT), a multicenter, randomized, open-label trial performed in the United States [22,23]. SPRINT enrolled 9361 patients aged 50 years or older, more than 90 percent of whom were on antihypertensive therapy, who had a systolic BP 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 BP 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. BP during the trial was measured using attended or unattended AOBPM. AOBPM is discussed in detail elsewhere. (See 'Preferred BP measurement strategies' 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 BP target; other antihypertensive medications were added if needed. Medications were actively withdrawn in the standard treatment group if systolic BP 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) [24]. 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 [25].
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) [26]. However, this excess of new-onset CKD in the intensive group was accompanied by decreased, rather than increased, levels of kidney injury biomarkers [27]. This suggests that an increase in creatinine during intensive BP lowering may reflect a benign functional (and reversible) change in GFR due to reduced blood flow rather than parenchymal kidney damage [27-29].
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 [22,23].
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 [30]. There was also no increase in the development of dementia; conversely, intensive BP lowering reduced the rate of mild cognitive impairment (6.1 versus 7.5 percent over a median follow-up of 5.1 years) [31] and reduced the accumulation of cerebral white matter lesions (assessed by magnetic resonance imaging [MRI]) [32].
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.
●BP in SPRINT was measured using attended and unattended AOBPM, which corresponds more closely with mean daytime BP (using 24-hour ABPM) than with the casual BP measurements that are typically performed (see "Blood pressure measurement in the diagnosis and management of hypertension in adults", section on 'Technique of measurement'). Casual systolic pressure measurements are usually higher than AOBPM measurements (by 5 to 15 mmHg). Thus, if clinicians use casual BP 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 BP lowering produced cardiovascular benefits [33-36]. As an example, a meta-analysis of 19 goal BP trials (excluding SPRINT) combining 44,989 patients found a significant reduction in major cardiovascular events with more intensive as compared with less intensive BP lowering (RR 0.86, 95% CI 0.78-0.96) [33].
Evidence supporting lower BP 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 BP that was already below 140 mmHg (using standardized 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 versus 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 [37-49].
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 [50]. 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 BP 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 [51]. 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 BP 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 BP was <140/<90 mmHg did not benefit from antihypertensive therapy, while those with BP >143 mmHg did benefit [52]. (See 'Less intensive goal blood pressure in lower-risk patients' below.)
Prior history of ischemic stroke or transient ischemic attack — With some exceptions, our suggestions for target BP 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, patients with uncorrected hemodynamically significant large artery disease (ie, of the internal carotid, middle cerebral, vertebral, or basilar artery) may develop ischemic symptoms with intensive BP lowering and are at higher risk for recurrent stroke [53,54]. 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 BP 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 BP target of either 130 to 149 mmHg or less than 130 mmHg (using standardized measurements) [55]. 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 BPs 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 BP 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 [55]:
●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 BP 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 BP group.
●The rate of intracerebral hemorrhage was significantly reduced in the lower-target BP 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 BP target of less than 130 mmHg (using standardized BP 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 BPs 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 BP lowering (targeting a systolic pressure of <130 mmHg) or standard BP lowering (targeting a systolic pressure of <140 mmHg) [56]. 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 BP, a post hoc analysis of the Perindopril Protection Against Recurrent Stroke Study (PROGRESS) trial addressed the issue of whether the baseline BP affected the benefit from antihypertensive therapy, including the possibility that patients with normal BP (<120 mmHg systolic) at baseline might be harmed from such therapy [57]. 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) BP; most, but not all, found that lower achieved BP was associated with fewer recurrent strokes [57-60].
Patients with heart failure — In patients with heart failure and reduced ejection fraction (HFrEF), we suggest a goal BP of 120 to 125/<80 mmHg (using preferred measurement methods, including standardized office-based measurement, AOBPM, SMBP, and ABPM) or 125 to 130/<80 mmHg (using casual office measurements). However, such patients are often prescribed multiple specific drugs to improve survival and reduce morbidity, independent of the BP, 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 BP in these patients is frequently much lower than these thresholds. Many experts consider the goal of therapy to be the lowest BP 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 BP of <120 to 125/<80 mmHg (preferred measurement methods) or 125 to 130/<80 mmHg (casual 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 BP lowering can reduce incident heart failure and heart failure-associated morbidity, there are no specific trials of goal BP in patients with HFrEF or HFpEF. Thus, our suggested targets in patients with heart failure are based upon low-quality data.
Casual and preferred BP measurements are defined and discussed above. (See 'Blood pressure measurement strategy' above.)
Patients with diabetes mellitus — In patients with diabetes, we suggest a goal BP of 120 to 125/<80 mmHg (using preferred measurement methods, including standardized office-based measurement, AOBPM, SMBP, and ABPM) or 125 to 130/<80 mmHg (using casual office measurements). These types of BP measurements are defined and discussed above. (See 'Blood pressure measurement strategy' above.)
Support for our recommendations comes from randomized trials, meta-analyses, and large observational studies [33-35,61-66]. The largest trial (Action to Control Cardiovascular Risk in Diabetes [ACCORD]) was a goal BP trial that found no benefit from a more intensive goal (systolic BP less than 120 mmHg) as compared with a less intensive goal (systolic BP less than 140 mmHg), other than a 53 percent relative reduction in the risk of stroke [62]. 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 BP group had fewer major cardiovascular events [67]. In addition to ACCORD, meta-analyses of trials suggest that, in diabetic patients, more aggressive BP lowering generally reduces the risk of cardiovascular events and that, in patients whose baseline systolic pressure is <140 mmHg, further lowering of the BP can prevent stroke and retinopathy [33,34].
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 BP goal less than 120 mmHg or a systolic BP goal less than 140 mmHg. BP was measured with AOBPM. The goals were achieved; the mean attained systolic BPs 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 [62,67]:
●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 BP 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, HR 1.07, 95% CI, 0.85 to 1.35) or in the rate of death from cardiovascular causes between groups (0.52 versus 0.49 percent, HR 1.06, 95% CI, 0.74-1.52).
●Intensive BP 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 [67]. 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 BP lowering produced cardiovascular benefits in diabetic patients [33-35]. As an example, a meta-analysis of 19 goal BP 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 BP lowering (RR 0.86, 95% CI 0.78-0.96) [33]. The effect of intensive BP 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).
A similar conclusion was reached in a network meta-analysis that compared outcomes among 59,934 patients with diabetes who were enrolled in 30 goal BP trials (including 12 trials of diabetic patients and 18 trials with a diabetes subgroup) [68]. Compared with higher BP categories, patients who achieved a systolic BP of 120 to 124 mmHg had the lowest rates of major cardiovascular disease (HR 0.73, 95% CI 0.52-1.02) and stroke (HR 0.19, 95% CI 0.07-0.57).
Based upon data from goal BP trials in diabetic patients, plus indirect data from SPRINT (which included patients who, like those with diabetes, have a high cardiovascular risk) [22,23,69], we suggest a goal systolic pressure of 120 to 125 mmHg if preferred readings are used or 125 to 130 mmHg if casual measurements are used to measure BP, 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 BP (to a systolic of 125 to 130 mmHg) among those who can tolerate such therapy [70,71].
We recognize that, even with the large number of trials and total patients studied, the BP 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 BP control, despite the risk of modest adverse events.
Patients with chronic kidney disease — In patients with CKD, we recommend a goal BP of 120 to 125/<80 mmHg (using preferred measurement methods, including standardized office-based measurement, AOBPM, SMBP, and ABPM) or 125 to 130/<80 mmHg (using casual office measurements). The different types of BP measurement are defined and discussed above. (See 'Blood pressure measurement strategy' above.)
Our advice is broadly consistent with guidelines from the Kidney Disease: Improving Global Outcomes clinical practice statement [72] and is mainly justified by a reduction in cardiovascular disease and mortality and not by a reduction in CKD progression [73].
Overall, the best evidence supports the following points:
●More intensive versus less intensive BP 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 BP 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 BP 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 BP lowering on the progression of CKD, as well as the risk of death, in patients with and without proteinuria [74-78]. 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) [76]. More intensive BP 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 BP 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 BP trials and 8127 patients (not including the SPRINT-CKD cohort) reported no effect of intensive BP lowering on CKD progression, cardiovascular events, or mortality at 3.3 years of follow-up [77]. 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 BP trials of patients with CKD (AASK, MDRD, and SPRINT) included different patient populations, examined different BP targets, and used different methodology to measure BP. Yet, as noted above, all three reached similar conclusions about the benefit of more intensive BP 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 BP goals (using standardized office BP): less than or equal to 92 mmHg or 102 to 107 mmHg [79]. The attained BPs 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 BP target for everyone was <130/80 mmHg [80]. During the cohort phase, which lasted approximately five years, the mean BP 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 BP 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 kidney 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 [76]. The effect of more intensive BP 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/day and HR 1.05, 95% CI 0.83-1.32 in patients with lower amounts of proteinuria). By contrast, the benefit of aggressive BP lowering on mortality did not vary according to proteinuria (HR 0.81, 95% CI 0.68-0.98).
●MDRD – The MDRD trial compared usual BP control (target mean arterial pressure less than 107 mmHg) with more aggressive control (target mean arterial pressure less than 92 mmHg), using standardized office BP measurements, over a three-year period [81]. 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 BP control.
•Patients excreting between 1 and 3 g/day had more rapid progression and a modest benefit for GFR loss from aggressive BP 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 BP control (rate of GFR decline of 10.2 with conventional versus 6.7 mL/min per year with aggressive BP control).
A subsequent study reported the long-term outcomes of patients enrolled in the initial MDRD study [82]. 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 BP between the two groups during the trial phase was 7.6/3.8 mmHg; BP 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 an HR was not provided for mortality alone.
However, a subgroup analysis of this extended follow-up revealed that the benefit from aggressive BP control was only significant in patients with protein excretion exceeding 1 g/day (HR approximately 0.6 to 0.7). The HR 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 HR 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 <1 g/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 [73]. Achieved BP, 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 BP 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 BP 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 BP; 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 BP of 120 to 125/<80 mmHg (using preferred measurement methods, including standardized office-based measurement, AOBPM, SMBP, and ABPM) or 125 to 130/<80 mmHg (using casual office measurements). These types of BP measurements are defined and discussed above. (See 'Blood pressure measurement strategy' above.)
However, we suggest a less aggressive systolic goal BP of 135 to 140 mmHg (casual measurements) or 130 to 135 mmHg (preferred measurements) in patients with a reduced life expectancy, for example, because of a high burden of comorbidity. Individualization of BP management is key in this population since the clinical benefit from intensive control is unlikely to be realized within one to two years [83]. 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 BP in older adults, measured using AOBPM, was examined in SPRINT [84]. SPRINT enrolled a subgroup of more than 2600 ambulatory adults aged 75 years or older with a baseline BP 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 BP 123) versus less intensive (goal of <140 mmHg; mean achieved systolic BP 135) systolic BP lowering (2.6 versus 3.8 percent and 1.8 versus 2.6 percent, respectively). The benefit from more intensive BP 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 BP trials [85]. After a mean follow-up of 3.1 years, more intensive versus less intensive BP 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 BP 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 [86].
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 BP strategy [87]. At baseline, mean age was 66 years, mean BP was 146/82 mmHg, and 65 percent had a calculated Framingham Risk Score greater than or equal to 15 percent. Achieved systolic BP, assessed using standardized office-based BPs (table 2), 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 BP 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 BP was smaller than in SPRINT.
BP 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 BP 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 BP control remains suboptimal, then additional efforts to engage older adults in healthful lifestyle change can facilitate better BP control.
One potential limitation to achieving goal BP is that lowering the BP 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 BP may then be pursued in an attempt to attain goal BP [31].
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 BP) [88-90]. In such cases, the level of systolic BP that is reached with two or three antihypertensive agents (even if greater than the goal presented above) may be a more reasonable goal [91]. (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) [92-97].
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) [89,95,97-105].
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 BP goals (figure 5) [106,107]. 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 BP 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. However, this hypothesis has yet to be examined in a randomized trial.
Patients with multiple cardiovascular risk factors — In patients with multiple cardiovascular risk factors (but without established cardiovascular disease), we recommend a goal BP of 120 to 125/<80 mmHg (using preferred measurement methods, including standardized office-based measurement, AOBPM, SMBP, and ABPM) or 125 to 130/<80 mmHg (using casual 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. Preferred and casual BP measurements are defined and discussed above. (See 'Blood pressure measurement strategy' 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) [22,23]. In this subgroup, intensive BP 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 BP trials and 52,235 patients examined the relative and absolute effects of more versus less intensive BP lowering [10]. A standardized 10/5 mmHg reduction in systolic/diastolic pressure resulted in the following [10]:
●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 BP lowering as those whose event risk was >10 percent). However, absolute benefits from BP 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 BP 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 BP 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.
Less intensive 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 BP of 125 to 135/<90 mmHg (using preferred measurement methods, including standardized office-based measurement, AOBPM, SMBP, and ABPM) or 130 to 139/<90 mmHg (using casual office measurements). (See 'Blood pressure measurement strategy' 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 BP as patients who are higher risk.
The absolute benefit of BP 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 BP trials (ie, trials that compared different target BPs) 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 BP was ≥140/≥90 mmHg; in the other trial (HOPE-3), approximately two-thirds of the study population had a BP at entry that was <140/<90 mmHg. All three trials performed standardized office BP measurement. In general, these studies suggest benefit from BP 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 pre-existing 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 [52]. Active treatment lowered BP 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 BP 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 [108]. The mean baseline BP was approximately 161/98 mmHg; the mean attained BP 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 [109]. 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) [110]. 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 BP below 130/80 mmHg in lower-risk patients, HOPE-3 followed patients for only five to six years. Because BP lowering in such patients is likely to reduce the relative risk, and because BP 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 BP goal for lower-risk patients with a longer life expectancy 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 2023 European Society of Hypertension (ESH) guidelines [111], the 2020 Canadian Hypertension Education Program (CHEP) guidelines [112], the 2016 National Heart Foundation of Australia guidelines [113], the National Institute for Health and Care Excellence guidelines, the American College of Physicians/American Academy of Family Physicians (ACP/AAFP) guidelines [114], and the 2021 Kidney Disease: Improving Global Outcomes guidelines (table 3) [72]. The current ACC/AHA, ESH, CHEP, and 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 'Assessment of baseline cardiovascular risk' 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
●Blood pressure measurement strategy – Our proposed blood pressure (BP) targets depend in part upon the method by which the BP is measured (see 'Blood pressure measurement strategy' above):
•In particular, BP that is measured in the office (ie, medical care setting) should be obtained in a standardized manner. There are two ways to perform high-quality, standardized office BP measurement: automated office BP monitoring (AOBPM), which requires specialized equipment, and standardized office-based measurement using proper technique (table 2). These two methods of measuring BP in the office provide readings that approximate daytime ambulatory BP (using ambulatory BP monitoring [ABPM] and self-measured BP [SMBP]). Collectively, these four methods are the preferred methods for determining if a patient is at goal.
•Although not the preferred method, the typical method of BP measurement in the medical care setting, in which BP is measured (usually once) with a stethoscope or oscillometric device, lacks proper patient preparation and proper technique. BP measurement using these inferior methods is referred to as "casual" BP measurement. Although it is an inferior method of measurement, it is faster and potentially less cumbersome and is the one primarily used in clinical practice. However, we recommend against casual BP measurement to determine if a patient is at goal.
•BP targets differ depending upon the technique of measurement because casual methods typically provide higher BP readings compared with the preferred methods. (See "Blood pressure measurement in the diagnosis and management of hypertension in adults".)
●Assessment of baseline risk in determining goal BP – BP targets are also based upon the patient's risk for having a future cardiovascular event (table 1) (see 'Intensive goal blood pressure targets for 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 BP of 120 to 125/<80 mmHg (using preferred measurement methods, including standardized office-based measurement, AOBPM, SMBP, and ABPM) or 125 to 130/<80 mmHg (using casual 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 BP lowering as tolerated but without a specific BP 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 BP of 120 to 125/<80 mmHg (using preferred measurement methods, including standardized office-based measurement, AOBPM, SMBP, and ABPM) or 125 to 130/<80 mmHg (using casual office measurements) (Grade 2C). (See 'Patients with heart failure' above.)
•In most patients with diabetes, we suggest a goal BP of 120 to 125/<80 mmHg (using preferred measurement methods, including standardized office-based measurement, AOBPM, SMBP, and ABPM) or 125 to 130/<80 mmHg (using casual office measurements) (Grade 2B). (See 'Patients with diabetes mellitus' above.)
•In patients with chronic kidney disease, we recommend a goal BP of 120 to 125/<80 mmHg (using preferred measurement methods, including standardized office-based measurement, AOBPM, SMBP, and ABPM) or 125 to 130/<80 mmHg (using casual 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 BP of 120 to 125/<80 mmHg (using preferred measurement methods, including standardized office-based measurement, AOBPM, SMBP and ABPM) or 125 to 130/<80 mmHg (using casual office measurements) (Grade 1B). (See 'Older adults' above.)
However, we suggest a less aggressive systolic goal BP of 135 to 140 mmHg (casual measurements) or 130 to 135 mmHg (preferred 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 BP goals mentioned above.
•In patients with multiple cardiovascular risk factors (but without established cardiovascular disease), we recommend a goal BP of 120 to 125/<80 mmHg (using preferred measurement methods, including standardized office-based measurement, AOBPM, SMBP, and ABPM) or 125 to 130/<80 mmHg (using casual 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 BP of 125 to 135/<90 mmHg (using preferred measurement methods, including standardized office-based measurement, AOBPM, SMBP, and ABPM) or 130 to 139/<90 mmHg (using casual office measurements) (Grade 1B). (See 'Less intensive goal blood pressure in lower-risk patients' above.)
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