Guidelines for the

Management of
Hypertension
Aram V. Chobanian, MD

KEYWORDS
 Hypertension  Antihypertensive therapy  SPRINT study  Blood pressure goals
 Management of hypertension

KEY POINTS
 This article summarizes pertinent data from clinical trials on the effects of antihypertensive
therapy on cardiovascular complications.
 Prior definitions of hypertension and blood pressure goals of therapy are discussed, and
differences between national and international guidelines on such goals are summarized.
 The results of the SPRINT study are summarized, and the impact of this study on future
goals of treatment is discussed.
 New recommendations are provided on blood pressure goals, and the effects such goals
might have on clinical practice are discussed.

INTRODUCTION

Actuarial data indicated almost a century ago that elevated blood pressure (BP) short-
ened life expectancy,1 but it was not until many years later that much attention was
given to lowering BP because of fear of compromising perfusion to vital organs.2 How-
ever, a few pioneers, such as Walter Kempner, who used extreme dietary measures;
Reginald Smithwick, who used surgical lumbodorsal sympathectomy; and my mentor,
Robert Wilkins, using drug therapy, began to study the effects of BP lowering in persons
with marked elevations and demonstrated that reducing BP was in fact well-tolerated
by most.35 Such observations led to a rapid expansion of efforts by the pharmaceutical
industry to develop new therapies for hypertension. The advances made since then
have been truly remarkable. Several effective and well-tolerated antihypertensive drugs
were introduced (Box 1), and clinical trials were performed to study their effects in hy-
pertensive persons. Initially, proof of principle studies were carried out in persons with
malignant hypertension (whose life expectancy if untreated averages 612 months) and
showed major benefits in preventing congestive heart failure, renal failure, and hemor-
rhagic strokes, and in prolonging life.6 The landmark Veterans Administration

Department of Medicine, Boston University School of Medicine, Boston University, 72 East

Concord Street, E-7, Boston, MA 02118, USA
E-mail address: achob@bu.edu

Med Clin N Am 101 (2017) 219227

http://dx.doi.org/10.1016/j.mcna.2016.08.016 medical.theclinics.com
0025-7125/17/ 2016 Elsevier Inc. All rights reserved.
220 Chobanian

Box 1
Advances in the treatment of hypertension

Decade and Therapy

1940s
Potassium thiocyanate
Kempner diet
Surgical sympathectomy
1950s
Rauwolfia serpentina
Ganglionic blockers
Veratrum alkaloids
Hydralazine
Guanethidine
Thiazide diuretics
1960s
Alpha-2 adrenergic receptor agonists
Spironolactone
Beta adrenergic receptor antagonists
1970s
Alpha-1 receptor antagonists
Angiotensin-converting enzyme inhibitors
1980s
Calcium channel blocking drugs
1990s
Angiotensin receptor antagonists
2000s
Renin inhibitors
Renal sympathetic denervation (experimental)

Adapted from Chobanian AV. The Shattuck Lecture. The hypertension paradoxmore uncon-
trolled disease despite improved therapy. N Engl J Med 2009;361:87887; with permission.

Cooperative Trials then demonstrated benefits of treatment in those with diastolic BP

(DBP) in the 115 to 129 mm Hg range and subsequently in the 90 to 114 range.7,8
After epidemiologic data demonstrated that systolic BP (SBP) was a more important
cardiovascular disease (CVD) risk factor than DBP after age 50, placebo-controlled tri-
als were performed to investigate the benefits of decreasing SBP in older persons with
isolated systolic hypertension. Notable in this regard were the Systolic Hypertension in
the Elderly Program (SHEP) in which reducing SBP to lower than 160 mm Hg with
chlorthalidone-based therapy was associated with reductions in incidences of stroke
and cardiac diseases,9 and also the Systolic Hypertension in Europe Trial (Syst-Eur),
which showed broadly similar benefits but with nitrendipine-based treatment.10 These
and various other studies demonstrated that BP reduction in persons with hyperten-
sion can reduce the incidence of stroke, coronary heart disease (CHD), congestive
heart failure (CHF), and chronic renal disease, and that such benefits can be obtained
independent of age, gender, race, ethnicity, socioeconomic status, severity of hyper-
tension, or the presence or absence of target organ damage.11

DEFINITION OF HYPERTENSION

The definition of hypertension has changed over the past several years. BP on a
population-wide basis is a continuous variable with a Gaussian distribution and
 Guidelines for the Management of Hypertension 221

without any clear point that would denote abnormality. The relationship between both
SBP and DBP and CVD risk also appears continuous. In a large observational study
involving approximately 1 million individuals, mortality from heart disease and stroke
increased almost linearly from BP levels as low as 115/75 mm Hg with an approximate
doubling of risk for every 20/10 mm Hg increase above that level.12 The definition of
hypertension has reflected in part the level above which the benefits of treatment
outweigh the risks, so it is not surprising that as more effective and safer drugs
became available, the definition changed. In the late 1950s, when thiazide diuretics
first were introduced, hypertension was not well defined but generally was considered
to be associated with BP levels greater than 180/100 mm Hg. Succeeding decades
brought lower values (Table 1).11,13 Most current definitions denote hypertension as
SBP 140 mm Hg and/or DBP 90 mm Hg.
In prior classifications of BP, other categories were included, such as mild, moder-
ate, and severe hypertension; isolated systolic hypertension; and high normal BP. The
current classification, which was introduced in the Seventh Joint National Committee
(JNC-7) Report in 2003, simplifies previous versions (Table 2).11 Only 2 levels of
severity of hypertension are designated to reflect the view that any BP level 160/
100 mm Hg deserves aggressive therapy. A new category of prehypertension, as
defined by BP levels between 120 and 139/80 to 89 mm Hg was introduced to identify
individuals who could benefit most from lifestyle changes that would reduce BP or
delay its age-associated transition to hypertension.

TREATMENT APPROACHES
Lifestyle Modifications
The adoption of certain healthy lifestyles is recommended for all persons with hyper-
tension, whether or not they are receiving drug therapy. The most important of these
nondrug approaches are weight control, exercise, dietary sodium restriction, moder-
ation of alcohol intake, and use of the Dietary Approaches to Stop Hypertension
(DASH) eating plan, which emphasizes intake of fruits, vegetables, complex carbohy-
drates, legumes, and low-fat dairy products.14 Most persons with stage 1 hyperten-
sion can be treated initially with lifestyle modifications, and drug therapy can be
delayed for 4 to 6 months until the effects become apparent.
Drug Treatment
Thiazide-type diuretics, beta blockers (BB), angiotensin-converting enzyme inhibitors
(ACEI), angiotensin receptor blockers (ARB), and calcium channel blockers (CCB) are
the most useful classes of antihypertensive drugs, having been shown in clinical trials
to reduce CVD complications.11 The average BP reduction with each of these classes
is comparable at recommended dosages, although differences in response can exist
in individual patients. More than one-half of hypertensive persons will require 2 or
more antihypertensive medications to achieve goal BP, so fixed-drug combinations
are also useful.

Table 1
Definitions of hypertension 1950 to the present

Period Hypertension BP Level

1950s and 1960s >180/100 mm Hg
1970s1984 160/95 mm Hg
1985present 140/90 mm Hg
222 Chobanian

Table 2
Current classification of blood pressure in adults

Classification SBP, mm Hg DBP, mm Hg

Normal <120 and <80
Prehypertension 129139 and/or 8089
Stage 1 hypertension 140159 and/or 9099
Stage 2 hypertension 160 and/or 100

From Chobanian AV, Bakris GL, Black HR, et al. Seventh report of the Joint National Committee on
prevention, detection, evaluation, and treatment of high blood pressure. Hypertension
2003;42(6):120652; with permission.

Several studies have been performed to determine whether any particular antihy-
pertensive drug class or combination of drugs is superior to any other, but in general,
only slight differences in clinical outcomes between the drug classes has been shown
as long as equivalent reductions in BP are achieved.15 However, in the Losartan Inter-
vention for Endpoint Reduction in Hypertension (LIFE) study, losartan-based therapy
was found to be superior to atenolol-based treatment.16 Additional studies also sug-
gested that BBs were not as effective in reducing stroke as other antihypertensive
medications, so BBs are not recommended for initial treatment unless a compelling
indication exists for their use.15
Compelling indications for selection of specific drug classes include use of ACEIs
and ARBs in patients with chronic renal disease, diabetes, heart failure, and post
myocardial infarction; and BBs in those with angina pectoris, arrhythmias, post
myocardial infarction, and heart failure.11
A treatment algorithm for hypertension is shown in Fig. 1. As noted, in stage 1 hy-
pertension (SBP 140159 mm Hg and/or DBP 9099 mm Hg), treatment can be initi-
ated with lifestyle modifications and drugs added if goal BP is not reached. As already
indicated, the initial selection of either a diuretic, ACEI, CCB, or ARB is appropriate
depending on physician experience and patient acceptance or the presence of a
compelling indication. A second, and if needed, a third drug from a different class
can be added, although a combination of an ACEI and ARB is not indicated. Doses
should be optimized and adherence to therapy assessed if the response is still
insufficient.
With stage 2 hypertension (BP 160/100 mm Hg), the initial approach, although
broadly similar to that indicated for stage 1 hypertension, should be more aggressive.
Drug treatment should not be delayed and can be started with 2 drugs or a combina-
tion preparation. Should goal BP not be attained after concurrent use of 3 antihyper-
tensive medications, then the addition of an aldosterone antagonist to the regimen is
particularly useful to control the refractory hypertension. Poor adherence to therapy,
insufficient dosages of medications, and possible salt retention should be ruled out.
Such refractory patients also should be evaluated for secondary causes of hyperten-
sion, including use of recreational drugs and excessive intake of alcohol.

BLOOD PRESSURE GOALS OF ANTIHYPERTENSIVE THERAPY

A DBP goal of lower than 90 mm Hg has been considered appropriate for most adults,
but the target for SBP has been more controversial. In the SHEP trial, the reduction of
SBP from pretreatment levels of 160 mm Hg to 143 mm Hg with active treatment and
to 155 mm Hg with placebo was associated with a 36% reduction in stroke incidence
 Guidelines for the Management of Hypertension 223

Stage 1 Hypertension Stage 2 Hypertension

(blood pressure 140159/9099 mm Hg (blood pressure 160/100 mm Hg

Lifestyle modicaon Two-drug regimen for most

Step 1 paents plus lifestyle
Alcohol restricon
DASH diet modicaon
Exercise ACE inhibitor
Salt reducon ARB
Weight control Beta-blocker
Calcium-channel blocker
Diurec

Drug treatment Add third drug of dierent class

Step 2
ACE inhibitor Assess adherence
ARB Opmize doses
Calcium-channel blocker
Diurec
Control other
cardiovascular disease
risk factors

Add second drug of dierent Add spironolactone or drug of

Step 3 class dierent class
ACE inhibitor Assess salt retenon
ARB
Beta-blocker
Calcium-channel blocker
Diurec

Step 4 Add third drug of dierent class Evaluate for secondary

Assess adherence hypertension including
Opmize doses alcohol excess and
recreaonal drugs

Fig. 1. Algorithm for management of hypertension. (Adapted from Chobanian AV. The
Shattuck Lecture. The hypertension paradox more uncontrolled disease despite improved
therapy. N Engl J Med 2009;361:87887; with permission.)

and 54% in heart failure with drug treatment.9 The Hypertension in the Very Elderly
Trial focused on those older than 80 with systolic hypertension who were treated
with either a placebo or a combination of an ACEI and a thiazide-type diuretic.17
Reduction of SBP to an average of 143 mm Hg with medications was associated
with a significant reduction in CVD events.
Many hypertension treatment guidelines have been published in the past few years.
How these have addressed the treatment goals is worth reviewing because of the lack
of agreement existing between them. As examples, the National Institute for Clinical
Excellence (NICE) has recommended drug therapy for those with SBP 140 mm Hg
who are diabetic or who have a history of chronic renal disease or CVD. However, in
those at low risk for CVD, only lifestyle changes are advocated by NICE unless SBP
is 160 mm Hg.18 The joint European Society of Hypertension/European Society of
224 Chobanian

Cardiology committee has recommended an SBP goal of lower than 140 mm Hg, except
in those older than 80, in whom the recommended goal is 140 to 150 mm Hg.19 In the
American Society of Hypertension and International Society of Hypertension joint report,
a goal of 150/90 mm Hg is advocated for those 80 years of age.20 The report by mem-
bers of the JNC-8 Committee originally appointed by the National Heart, Lung, and
Blood Institute (NHLBI) but later disenfranchised by it added to the confusion. Unlike
prior JNC groups, JNC-8 focused primarily on data obtained from randomized
controlled clinical trials rather than considering the totality of clinical evidence as had
been done by prior JNC groups. The JNC-8 Report advocated a target BP of lower
than 140/90 mm Hg in those younger than 60 and lower than 150/90 mm Hg in persons
60 years or older.21 However, the Committee was divided on increasing the goal for the
older age group, so much so that a minority report was also published by a subgroup of
the Committee advocating a target of lower than 140/90 mm Hg in those older than 60.22

SYSTOLIC BLOOD PRESSURE INTERVENTION TRIAL

All of the treatment goals noted previously probably need to be reconsidered now
because of the recently published findings from the Systolic Blood Pressure Interven-
tion Trial (SPRINT).23,24 SPRINT was a randomized, controlled, open-labeled study
funded by the NHLBI that involved more than 9300 individuals 50 years of age and
older who had SBP in the 130 to 180 mm Hg range. They either had evidence of prior
CVD events or were at high risk for CVD. Persons with diabetes were excluded
because another NHLBI-funded study with a similar protocol, the ACCORD trial, dealt
exclusively with diabetic persons.25 Other exclusions in SPRINT included individuals
with a history of stroke or those who were not ambulatory or who were confined to in-
stitutions. Office BP measurements were made after a period of rest with an auto-
mated device. The main objective of SPRINT was to determine whether lowering
SBP to lower than 120 mm Hg (intensive therapy) caused a lower incidence of CVD
events than when SBP was lowered to lower than 140 mm Hg (standard therapy).
The selection of antihypertensive medications was left to the discretion of the clinician,
although chlorthalidone was preferred as the thiazide-type diuretic and amlodipine
as the preferred CCB, consistent with the use of these 2 drugs in other recent
NHLBI-sponsored trials. As shown in Table 3, impressive benefits were observed in
the intensive group, which had a 25% lower incidence of composite primary events
(myocardial infarction, other coronary syndromes, CHF, stroke, or death from CVD).
In addition, total mortality was 27% lower with intensive as compared with standard
therapy. Because of these remarkable findings, the study was terminated prematurely
after an average follow-up of 3.3 years. In a subgroup analysis of individuals 75 years
or older included in the trial, the results were comparable to those observed in the total
SPRINT cohort with a 34% lower incidence of the primary outcome and a 33% lower
total mortality with intensive therapy.24 Of interest with respect to prior concerns about
the risk of lowering DBP excessively in the elderly was the finding that CHD incidence
in the SPRINT elderly group was significantly lower with intensive therapy, even
though DBP was reduced to an average level of 62 mm Hg or 5 mm Hg lower than
that achieved with standard therapy.
The safety data available currently for SPRINT have been somewhat reassuring in
that no major problems have been reported as yet with intensive treatment except
for slight increases in incidence of hypotension, syncope, electrolyte abnormalities,
and acute changes in renal function. Additional information about these and other po-
tential problems including the effects of treatment on cognitive function will be impor-
tant to examine before the full significance of the study can be determined.
 Guidelines for the Management of Hypertension 225

Table 3
Benefits of intensive versus standard therapy in SPRINT

Outcome Relative Risk Reduction

Composite primary endpoint 25%
Secondary endpoints
Myocardial infarction 17%
Heart failure 38%
Death from cardiovascular causes 43%
Death from all causes 27%

Adapted from SPRINT Research Group, Wright JT Jr, Williamson JD, Whelton PK, et al. A random-
ized trial of intensive versus standard blood-pressure control. N Engl J Med 2015;373:210316.

Because of the exclusion criteria used, the SPRINT findings are not applicable to
persons with diabetes or prior stroke. The ACCORD study of individuals with type 2
diabetes failed to show a reduction in the composite primary endpoint with intensive
BP lowering.25 However, there was a significant decrease in stroke incidence in this
group and a nonsignificant reduction in primary events. It has been speculated that
because ACCORD involved a much smaller group than SPRINT, it was not powered
sufficiently to detect a significant effect on primary outcomes.23

NEW RECOMMENDATIONS ON BLOOD PRESSURE GOALS

The SPRINT findings require a reassessment of the goals, notwithstanding the fact that
subjects recruited into SPRINT were probably not representative of those seen in clinical
practice who typically have more concurrent illnesses and are on more other medications.
In addition, the office BP measurements in SPRINT were made under relatively basal con-
ditions, and the values recorded and used for treatment decisions were probably less than
if obtained in busy office settings in which a white coat effect would be more likely.
Nevertheless, the SPRINT findings are so impressive that they cannot be disregarded.
What should we now conclude regarding BP goals? For most hypertensive adults
younger than age 50, I think that a BP goal of 120 to 125/80 to 85 mm Hg is reasonable
based on the available data from both clinical trials and epidemiologic and observa-
tional studies. For most nondiabetic persons 50 to 74 years of age, including those
with CVD or chronic renal disease, an SBP goal of lower than 130 mm Hg seems
appropriate (although a somewhat lower goal may be indicated in those with CHF).
A goal of lower than 120 mm Hg in the 50-year to 74-year age group would not be
appropriate despite the SPRINT data because the SBP actually achieved with inten-
sive therapy in SPRINT averaged 123 and not lower than 120 mm Hg and because
of the possible measurement issues noted previously.
In the 75 years of age or older group, although a goal of lower than 130 mm Hg might be
reasonable for many, I would advocate a stepwise approach to achieving such a target to
minimize adverse events. An initial SBP goal of lower than 140 mm Hg is appropriate and
perhaps adequate in some, but if well-tolerated, a further titration to lower than 130 mm
Hg could be considered. However, there should not be any urgency in pursuing this goal.
Such patients should be monitored closely for adverse effects, such as orthostatic hypo-
tension, syncope, and changes in cognition and renal function. Treatment of nonambu-
latory, institutionalized, or frail persons should be managed on an individual basis.
Currently, using the lower than 140/90 mm Hg goal level, slightly more than 50% of
hypertensive persons in the United States would be considered as controlled.26
226 Chobanian

Lowering the SBP goal to lower than 130 mm Hg would mean that between one-half to
two-thirds of hypertensive persons are inadequately treated. The impact on clinical
practice could be considerable. Additional antihypertensive medications would
need to be used in some, and closer monitoring of patients and more frequent clinic
visits might be required. It therefore becomes even more important to use nurse prac-
titioners, physician assistants, and other nonphysician personnel, as well as treatment
algorithms, and other approaches to optimize follow-up care.

PUBLIC HEALTH CONSIDERATIONS

The prevention and management of hypertension remains a major public health prob-
lem in the United States and the rest of the world. Although the major focus of this
article has been on drug treatment and treatment goals, measures to prevent or
slow the onset of hypertension should not be disregarded, as the prevalence of hyper-
tension continues to increase steadily worldwide. In 1988, its prevalence in the United
States was estimated at 57 million,11 and currently the estimates are between 75 and
78 million. Changes in lifestyles, although difficult to achieve, could not only slow the
rate of development of hypertension but have the additional benefit of reducing other
cardiovascular risk factors as well. Unfortunately, such preventive measures continue
to receive relatively low priority in this country, where the major emphasis is still being
placed on drug treatment of established disease.
Despite many remaining uncertainties regarding the management of hypertension,
the progress made to date in achieving its control and reducing its complications has
been one of the major success stories in medicine in the past half century. Hopefully, a
similar degree of progress can be made in the future to prevent hypertension.

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