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Official reprint from UpToDate www.uptodate.com ©2015 UpToDate

AuthorsJohannes FE Mann, MDKarl F Hilgers, MD

Section EditorsGeorge L Bakris, MDNorman M Kaplan, MD

Deputy EditorJohn P Forman, MD, MSc

Hypertension: Who should be treated?

All topics are updated as new evidence becomes available and our peer review process is complete.Literature review current through: Dec 2014. | This topic last updated: Sep 24, 2014.

INTRODUCTION — Treatment of hypertension generally begins with nonpharmacologic therapy, including moderate dietary sodium restriction, weight

reduction in the obese, avoidance of excess alcohol intake, and regular aerobic exercise (table 1) [1,2]. Institution of these modalities involves little or no

risk and they all may be beneficial from a general health viewpoint even in normotensive subjects. (See "Diet in the treatment and prevention of

hypertension".)

Drug therapy, in comparison, may be expensive and is often associated with side effects, some of which (hypokalemia and hyperlipidemia) may actually

increase coronary risk. (See "Causes of hypokalemia in adults", section on 'Diuretics' and "Antihypertensive drugs and lipids".)

Thus, there should be clear evidence of likely benefit before antihypertensive drugs are begun. Such evidence is available for most degrees of hypertension

(systolic pressure ≥140 mmHg in patients younger than 60 years, systolic pressure ≥150 mmHg in patients 80 years and older, and especially for diastolic

pressure persistently ≥90 mmHg regardless of age) [1,3,4].

The evidence that treating different degrees of hypertension is beneficial will be reviewed here, with recommendations for who should be treated. An

overview of the treatment of hypertension, the choice of antihypertensive drug as initial therapy, and goal blood pressure are discussed separately. (See

"Overview of hypertension in adults", section on 'Treatment' and "Choice of drug therapy in primary (essential) hypertension: Recommendations" and

"What is goal blood pressure in the treatment of hypertension?".)

DEFINITIONS — Major societies have published definitions of hypertension [5-7]. In general, hypertension was defined as a blood pressure ≥140/≥90

mmHg. However, subsequent trials have identified groups of patients at higher risk in whom goal blood pressures below this value may be associated with

improved outcomes. (See 'Goal blood pressure' below.)

The following definitions were suggested in 2003 by the seventh Joint National Committee (JNC 7) and reaffirmed by the American and International

Societies of Hypertension (ASH/ISH) in 2014, based upon the average of two or more properly measured readings at each of two or more visits after an

initial screen [2,5]:

®

®

Normal blood pressure: systolic <120 mmHg and diastolic <80 mmHg●

Prehypertension: systolic 120 to 139 mmHg or diastolic 80 to 89 mmHg●

Hypertension:●

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Isolated systolic hypertension is considered to be present when the blood pressure is ≥140/<90 mmHg and isolated diastolic hypertension is considered

to be present when the blood pressure is <140/≥90 mmHg.

These definitions apply to adults on no antihypertensive medications and who are not acutely ill. If there is a disparity in category between the systolic and

diastolic pressures, the higher value determines the severity of the hypertension. The systolic pressure is the greater predictor of risk in patients over the

age of 60 years [8].

Similar but not identical definitions were suggested in the European Societies of Hypertension and Cardiology (ESH/ESC) guidelines for the management

of arterial hypertension that were published in 2013 [1]:

Both JNC 7 [5] and ESH/ESC [1] guidelines provided different threshold levels to define hypertension when blood pressure was measured by 24-hour

ambulatory monitoring or by home blood pressure monitoring:

These definitions of hypertension using alternate measurement techniques are discussed elsewhere. (See "Ambulatory blood pressure monitoring and

white coat hypertension in adults", section on 'Interpretation of ABPM' and "Ambulatory blood pressure monitoring and white coat hypertension in adults",

section on 'Home BP measurements'.)

WHAT LEVEL OF BP INCREASES RISK? — The above definitions of hypertension were based upon studies demonstrating an increase in cardiovascular

risk that could be reduced by antihypertensive therapy.

Epidemiologic studies — In general, epidemiologic studies of treated and untreated patients reveal that there is a gradually increasing incidence of

Stage 1: systolic 140 to 159 mmHg or diastolic 90 to 99 mmHg

Stage 2: systolic ≥160 mmHg or diastolic ≥100 mmHg

Optimal blood pressure: systolic <120 mmHg and diastolic <80 mmHg●

Normal: systolic 120 to 129 mmHg and/or diastolic 80 to 84 mmHg●

High-normal: systolic 130 to 139 mmHg and/or diastolic 85 to 89 mmHg●

Hypertension:●

Grade 1: systolic 140 to 159 mmHg and/or diastolic 90 to 99 mmHg

Grade 2: systolic 160 to 179 mmHg and/or diastolic 100 to 109 mmHg

Grade 3: systolic ≥180 mmHg and/or diastolic ≥110 mmHg

Isolated systolic hypertension: systolic ≥140 mmHg and diastolic <90 mmHg

24-hour average blood pressure or the average of reading from home blood pressure monitoring − Normotension is defined as a blood pressure less

than 130/80 mmHg, and hypertension is defined as a blood pressure greater than or equal to 135/85 mmHg.

●

Daytime (awake) blood pressure by 24-hour ambulatory monitoring − Normotension is defined as a blood pressure less than 135/85 mmHg, and

hypertension is defined as a blood pressure greater than or equal to 140/90 mmHg.

●

Nighttime (asleep) blood pressure by 24-hour ambulatory monitoring − Normotension is defined as a blood pressure less than 120/70 mmHg, and

hypertension is defined as a blood pressure greater than or equal to 125/75 mmHg.

●

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coronary disease and stroke and cardiovascular mortality as the blood pressure rises above 110/75 mmHg, with some notable differences in risk based

upon age and underlying comorbid conditions (figure 1A-B) [5,9,10]. A similar relationship has been described in patients with known coronary disease

[11]. In addition, at any blood pressure, the cardiovascular risk is importantly affected by the presence or absence of other risk factors (figure 2) [12,13].

A caveat to the following discussion is that epidemiologic observations of increased risk at blood pressures above 110/75 mmHg but below the

hypertensive range do not prove causality. As an example, increasing blood pressures below the hypertensive range could be associated with other risk

factors that could explain worse outcomes, such as increasing body weight and diabetes mellitus. Proof of causality can only be provided by randomized

trials that show that cardiovascular outcomes are improved by lowering the blood pressure. (See 'Decreased cardiovascular risk with therapy' below.)

The relative prognostic importance of different levels of blood pressure components in individuals of different ages was studied among participants in the

Second National Health and Nutrition Examination Survey (NHANES II) [10]. In this cohort study of 7830 participants between the ages of 30 to 74 years

who were initially free of cardiovascular disease, the baseline blood pressure was correlated with all-cause and cardiovascular mortality over a 15-year

follow-up; the analysis did not take into account whether the patients were or were not treated for hypertension. Over this period, 1588 patients died, with

cardiovascular disease being responsible for 582. Unlike other studies, the analysis was based upon a risk model that utilized the clear correlation

between systolic and diastolic blood pressures to estimate the risk for different baseline blood pressure combinations.

The following mortality results were obtained beyond the first two years of follow-up:

The Framingham Heart Study also reported an increased incidence of poor outcomes as the blood pressure rises, even with values within the "normal"

range. This study examined the risk of cardiovascular disease at 10-year follow-up among subjects with "high-normal" blood pressure at baseline

examination, which was defined as a systolic blood pressure of 130 to 139 mmHg, a diastolic pressure of 85 to 89 mmHg, or both, and with "normal" blood

pressure, which was defined as a systolic blood pressure of 120 to 129 mmHg, a diastolic pressure of 80 to 84 mmHg, or both [14].

After adjustment for cardiovascular risk factors and when compared with optimal blood pressure (defined as systolic and diastolic blood pressures of less

than 120 and 80 mmHg, respectively), the hazard ratios for a cardiovascular event at 10 years for those with high-normal values were 2.5 and 1.6 for

women and men, respectively. Patients with "normal" blood pressure values also had an increased hazard ratio for a cardiovascular event compared with

optimal blood pressure. Based in part upon this study, the seventh report of the Joint National Committee (JNC 7) added a new blood pressure category

Among participants less than 65 years of age, increases in the systolic blood pressure were linearly related to increases in cardiovascular and all-

cause mortality at all diastolic blood pressures (figure 3A-B). By comparison, the correlation between diastolic blood pressure and mortality was

"hockey stick-shaped." This shape corresponds to a flat region of risk with diastolic values below 80 mmHg, with a marked increase in risk occurring

with values above this level.

●

Among those greater than 65 years of age, increases in the systolic blood pressure were also linearly related to increased mortality at all diastolic

pressures. However, the risk with the diastolic blood pressure was J-shaped; thus, for a fixed systolic pressure, decreased blood pressures below

approximately 80 to 90 mmHg were associated with increasing mortality, while levels above approximately 80 to 90 mmHg were associated with an

enhanced risk. Why lower diastolic pressures were associated with increased risk is not known. It is generally thought that lower pressures identify

patients with more comorbid disease since treated isolated systolic hypertension improves outcomes even though diastolic pressures are in the

"enhanced risk" range. (See 'Isolated systolic hypertension' below.)

●

Increased pulse pressure was associated with marked variations in risk of mortality, depending upon age, and the exact systolic and diastolic

pressure.

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called prehypertension, which is defined as blood pressure of 120 to 139/80 to 89 mmHg [5]. (See 'Definitions' above.)

In a subsequent analysis of data from the Framingham Heart Study to determine the impact of prehypertension on specific cardiovascular events, it was

demonstrated that prehypertension was associated with an increased risk of myocardial infarction (relative risk 3.5) and coronary artery disease (relative

risk 1.7), but not stroke [15].

In addition to gender, other patient characteristics can influence the relationship between blood pressure and cardiovascular outcomes. In an analysis of

data on 8960 participants aged 55 to 64 years in the Atherosclerosis Risk in Communities (ARIC) study, individuals with high-normal (130 to 139/85 to 89

mmHg) and normal (120 to 129/80 to 85 mmHg) blood pressure had an increased risk of incident cardiovascular disease (RR 2.3 and 1.8, respectively)

compared to optimal blood pressure (<120/80 mmHg) [16]. The risk was substantially more pronounced among black, obese and diabetic individuals.

Relative to optimal blood pressure:

The risk with increased blood pressure also appears to vary markedly from population to population. As an example, the relationship between blood

pressure and mortality from coronary heart disease was evaluated in a 25-year follow-up study of over 12,000 men aged 40 to 59 years without heart

disease who resided in seven different countries [17]. Over this period, nearly 1300 died from coronary heart disease. The following results were noted:

In general, the observation that there is a gradually increasing incidence of coronary disease and stroke and cardiovascular mortality with a rising the blood

pressure does not prove a causal relationship. Rather, increasing blood pressure could be a marker for other risk factors such as increasing body weight,

which is associated with dyslipidemia, glucose intolerance, and the metabolic syndrome. (See "The metabolic syndrome (insulin resistance syndrome or

syndrome X)".)

Decreased cardiovascular risk with therapy — The best evidence for a causal role of increasing blood pressure in cardiovascular complications is an

improvement in outcome with antihypertensive therapy. Treatment studies have demonstrated the efficacy of lowering both diastolic and systolic pressures

in patients with hypertension [3,8,18-20].

Blood pressure control to achieve optimal cardiovascular outcomes includes achievement of goal blood pressure at the time of all or most measurements.

This was best studied in a post hoc analysis from the INVEST trial which compared the effectiveness of verapamil and atenolol in over 20,000 hypertensive

patients with known coronary artery disease [21]. All patients, regardless of initial randomization, were divided into four groups according to the proportion

of visits in which blood pressure was in control: <25, 25 to <50, 50 to <75, and ≥75 percent. The risk of the primary outcome (death, nonfatal MI, and

nonfatal stroke) decreased progressively and significantly from the group with the poorest control to the group with the best control during an average

follow-up of 2.7 years. (See "Choice of therapy in primary (essential) hypertension: Clinical trials", section on 'INVEST trial'.)

Relative risk was 3.3 for high-normal blood pressure among blacks●

Relative risk was 4.1 for high-normal blood pressure among diabetics●

Relative risk was 3.6 for high-normal blood pressure among individuals with a BMI >30 kg/m● 2

Among all populations, the relative increase in mortality from heart disease for a given increase in blood pressure was similar. When adjusted for

individual variability, the relative risk of death was 1.28 for a 10 mmHg increase in systolic blood pressure.

●

The risk of death in those with a blood pressure of 140/85 mmHg was over three times higher among subjects from the United States and northern

Europe compared to those from Japan and southern Europe (70 versus 20 deaths per 10,000 person-years).

●

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Lowering the blood pressure is also beneficial in some patients who have blood pressures near but not in the hypertensive range, primarily with

concomitant conditions such as diabetes and chronic kidney disease [5]. (See "What is goal blood pressure in the treatment of hypertension?".)

Systolic and diastolic hypertension — Randomized controlled trials of antihypertensive therapy demonstrated significant cardiovascular benefit in

patients with systolic and diastolic hypertension that was most pronounced in severe and moderate disease. Although the number of patients was small in

the severe and moderate hypertension trials, the magnitude of benefit was extremely high.

The best data on the treatment of severe diastolic hypertension come from a trial in the 1960s of 143 men with diastolic pressures of 115 to 129 mmHg

(average clinic blood pressure 186/121 mmHg) who were randomly assigned to antihypertensive therapy or placebo, the incidence of cardiovascular events

was 3 percent at 21 months in the treated group versus 39 percent at 16 months in the placebo group (p<0.001) [22]. The shorter follow-up in the placebo

group was due to the high number of terminating events. The average blood pressure during the trial was significantly lower in the treated group (143/91

mmHg versus no significant change in the placebo).

The efficacy of treating moderate diastolic hypertension was demonstrated in a trial of 210 men with diastolic pressures of 105 to 114 mmHg who were

randomly assigned to antihypertensive drugs or placebo. The incidence of cardiovascular events at three and a half years was significantly lower in the

treated group (8 versus 32 percent; the difference in blood pressure between the groups was -31/-19 mmHg) [23].

The absolute benefit of blood pressure lowering is much lower in patients with mild hypertension (diastolic pressure of 90 to 104 mmHg). A summary of the

results from 17 controlled trials of mild to moderate diastolic hypertension (almost all also had systolic hypertension) in adults under age 65 years found

that active treatment with antihypertensive medications led to a statistically significant 16 percent reduction in the number of coronary events and a 40

percent reduction in stroke [24].

In the aggregate, antihypertensive therapy of mild hypertension for four to five years prevented a coronary event in 0.7 percent of patients and a

cerebrovascular event in 1.3 percent for a total benefit of approximately 2 percent; this included a reduction in cardiovascular mortality of 0.8 percent

(figure 4). Thus, 100 patients must be treated for four to five years to prevent a complication in two.

Two potential pitfalls must also be considered in evaluating these findings:

A report from the Framingham Heart Study confirmed the benefit of long-term antihypertensive therapy on cardiovascular disease incidence and mortality

[26]. All-cause mortality and cardiovascular mortality over 10 years were significantly lower with antihypertensive therapy:

Even greater benefits have been shown with the treatment of elderly hypertensives (over age 65 years), most of whom have isolated systolic hypertension

They may overestimate the benefit in mild hypertension since patients with moderate hypertension (diastolic pressure as high as 115 mmHg in some

studies) were also included.

●

They may underestimate the total long-term benefit since the studies were of relatively short duration and mild hypertension is a minor short-term

risk. Thus, some have proposed an actuarial approach in which the benefits expected from the treatment of mild hypertension are estimated by

comparison with insurance company actuarial data prior to the availability of antihypertensive therapy [25].

●

In men, all-cause mortality was reduced from 43 to 31 percent and cardiovascular mortality was reduced from 28 to 13 percent●

In women, all-cause mortality was reduced from 34 to 21 percent and cardiovascular mortality was reduced from 19 to 9 percent●

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[27]. Because the elderly start at such higher overall cardiovascular risk, short-term reductions in their hypertension provide apparently greater benefits

than that observed in younger patients. However, among treated elderly patients with isolated systolic hypertension, there is a concern that the low

diastolic pressure after therapy may interfere with tissue, particularly coronary, perfusion and possibly increase cardiovascular risk. (See "Treatment of

hypertension in the elderly patient, particularly isolated systolic hypertension".)

The related issue of goal blood pressure in hypertensive patients who are treated is discussed separately. (See "What is goal blood pressure in the

treatment of hypertension?", section on 'Systolic and diastolic hypertension'.)

Low-risk patients — The benefit from antihypertensive therapy is unproven in patients with mild hypertension who also have no preexisting

cardiovascular disease. The meta-analysis described above suggested that, in patients with mild hypertension, antihypertensive therapy significantly

reduced cardiovascular events by 2 percent [24]. However, some of the patients included in this meta-analysis had moderate rather than mild

hypertension, and some had preexisting cardiovascular disease.

A subsequent meta-analysis combined four placebo-controlled trials totalling 8912 patients with mild hypertension and no preexisting cardiovascular

disease [28]. During four to five years of follow-up, antihypertensive therapy produced lower rates of mortality (1.7 versus 2 percent) and stroke (0.3 versus

0.6 percent) but higher rates of myocardial infarction (2 versus 1.8 percent); none of these findings were statistically significant. The total number of events

was small in this study, as would be expected among patients with mild hypertension and no cardiovascular disease. In addition, the four- to five-year

follow-up was relatively short; a benefit from antihypertensive therapy among low-risk patients might require a substantially longer period of time to

manifest. Finally, the Felodipine Event Reduction trial (FEVER) was not included in this meta-analysis, even though patients in the FEVER trial were

similar to those enrolled in the trials that were included. As discussed elsewhere, the antihypertensive therapy in the FEVER trial significantly reduced

mortality and cardiovascular events. (See "What is goal blood pressure in the treatment of hypertension?", section on 'Benefit in those with mild

hypertension'.)

Thus, low-risk patients with mild hypertension and no preexisting cardiovascular disease who fail to reduce their blood pressure with lifestyle modification

should receive antihypertensive therapy.

Isolated systolic hypertension — The systolic pressure is the most important determinant of risk in hypertensive patients, particularly in patients over

the age of 50 to 60 years [8]. The value of treating isolated systolic hypertension has been demonstrated in multiple clinical trials. In the Systolic

Hypertension in the Elderly Program (SHEP) trial, for example, it was estimated that approximately 18 patients had to be treated for five years to prevent a

major cerebrovascular or cardiac event in one [29]. However, these results underestimate the true benefit of effective therapy since about 30 percent of

treated patients did not reach goal blood pressure and 44 percent of patients in the placebo group ended up being treated at five years. These issues are

discussed in detail separately. (See "Treatment of hypertension in the elderly patient, particularly isolated systolic hypertension".)

Isolated diastolic hypertension — Isolated diastolic hypertension (IDH) is defined as a diastolic pressure ≥90 mmHg with a systolic pressure less

than 140 mmHg. IDH is more common in younger men [30,31] who are overweight or obese [32] and, in individuals under age 40 years, it is more common

than systolic and diastolic hypertension (SDH) or isolated systolic hypertension (ISH) [30]. The magnitude of this effect was illustrated in a 2001 report

from the National Health and Nutrition Examination Survey (NHANES) III in the United States of untreated patients with hypertension [30]. IDH accounted

for almost 60 percent of cases under age 40 years, approximately 35 percent between the ages of 40 and 49 years, and was rare in patients over age 60

years.

In contrast to the demonstrated efficacy in the preceding sections of treating SDH and ISH, there are no randomized trials evaluating the efficacy of

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therapy in patients with IDH. Thus, decisions about antihypertensive therapy are based upon the natural history of IDH and the risk of cardiovascular

complications.

The natural history of untreated IDH was evaluated in a report from the Framingham Heart Study [31]. Among 193 individuals with new onset IDH, 106

progressed to systolic and diastolic hypertension at a mean follow-up of 6.7 years (55 percent, adjusted hazard ratio 23 compared to optimal blood

pressure [<120/<80 mmHg]).

The risk of cardiovascular complications appears to be lower with IDH than with SDH and ISH [20,33-35]. This could reflect one or both of the following:

most patients are under age 40 years; and IDH may be associated with a lower cardiovascular risk. Furthermore, some [20,33,36] but not all studies [35]

have suggested that IDH is not associated with an increase in risk compared to normotensive individuals [20,33,36]. A limitation to all of these studies is

that it is not clear that the initial classification at baseline remained applicable during follow-up.

The conflicting findings on prognosis of IDH can be illustrated by the following observations:

There are no definitive data that address optimal therapy in patients with IDH. There is agreement among the authors and editors of this topic on the

following steps:

Treatment with antihypertensive drugs is warranted in all patients with IDH who have evidence of end-organ damage. Most experts also suggest the use of

antihypertensive drugs in patients without end-organ damage based upon the general recommendation in major society guidelines that the general goal

blood pressure is <140/<90 mmHg, with lower values suggested in selected patients at increased risk [1,2,38,39]. (See "What is goal blood pressure in

the treatment of hypertension?".)

Most patients with IDH should be able to attain goal blood pressure with a single drug. The choice of drug is discussed in detail elsewhere and depends in

part upon whether there are specific indications for a particular class of drug (eg, beta blockers or nondihydropyridine calcium channel blockers for rate

control in atrial fibrillation). Among patients without an indication for a particular class of drugs, younger patients such as those with IDH generally respond

No increase in all-cause mortality with IDH as defined above was noted at up to 32 years of follow-up in a prospective cohort study from Finland of

3267 initially healthy men 32 to 45 years of age who were not receiving antihypertensive drugs [20]. The patients with IDH also had a low rate of using

antihypertensive drugs during follow-up.

●

In contrast, a high rate of progression of IDH to systolic and diastolic hypertension (55 percent in 6.7 years) was noted in the Framingham Heart

Study [31]. In addition, a 10-year follow-up Chinese study of over 26,500 subjects who were 35 years of age or older at baseline found that patients

with IDH had, compared to normotensive patients, a significantly increased risk of stroke (relative risk 2.16 compared to 2.96 and 2.35 in patients

with SDH and ISH, respectively).

●

The blood pressure as in all patients should be measured on at least three separate occasions to confirm the diagnosis. (See "Blood pressure

measurement in the diagnosis and management of hypertension in adults".)

●

Nonpharmacologic therapy is warranted, particularly salt restriction and weight loss in patients who are overweight which, as noted above, is

common in IDH [32].

●

The patient should be tested for evidence of end-organ damage, such as proteinuria and left ventricular hypertrophy on ECG, and for hypothyroidism,

which has been associated with a rise in blood pressure more pronounced with diastolic compared to systolic pressure [37].

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better to monotherapy with an ACE inhibitor or angiotensin II receptor blocker than a dihydropyridine calcium channel blocker. (See "Choice of drug

therapy in primary (essential) hypertension: Recommendations", section on 'Monotherapy based upon age and race'.)

Increased pulse pressure — It has been suggested that there is an enhanced risk for cardiovascular events associated with increases in the pulse

pressure (defined as the systolic minus diastolic pressure). This issue is discussed in detail separately. (See "Increased pulse pressure".)

Goal blood pressure — Goal blood pressure depends upon age and the presence of comorbid conditions (see "What is goal blood pressure in the

treatment of hypertension?" and "Treatment of hypertension in the elderly patient, particularly isolated systolic hypertension" and "Antihypertensive

therapy and progression of nondiabetic chronic kidney disease in adults" and "Treatment of hypertension in patients with diabetes mellitus"):

The above recommendations are consistent with most major societies and organizations [1,2,38-40], although members of the eighth Joint National

Committee (JNC 8) did not suggest pharmacotherapy to lower the systolic pressure below 140 mmHg in older adults [4]. In addition, the 2013 ESH/ESC

guidelines recommended a goal blood pressure of <150/<90 mmHg, rather than <140/90 mmHg, in those 80 years of age or older.

RECOMMENDATIONS — Using the above definitions from the Joint National Committee (JNC), European Societies of Hypertension and Cardiology

(ESH/ESC), and American and International Societies of Hypertension (ASH/ISH), the following general approach can be used to determine which patients

with hypertension require antihypertensive therapy [1,2,4,5,7,41,42]. This approach assumes accurate measurement of the blood pressure [5]. The

potential errors involved with this procedure are discussed elsewhere. (See "Blood pressure measurement in the diagnosis and management of

hypertension in adults".)

All patients should undergo appropriate lifestyle (nonpharmacologic) modification (table 1). In the absence of evidence for hypertensive target-organ

damage, the following decisions about antihypertensive medications are generally not made until there has been an adequate trial of nonpharmacologic

therapy. However, if there is evidence for target-organ damage, decisions on antihypertensive medications may be warranted earlier.

Goal blood pressure is less than 140/90 mmHg in patients younger than 60 years.●

In the general hypertensive population of older adults (ie, 60 years and older, nondiabetic, no chronic kidney disease), goal blood pressure is

<150/<90 mmHg and, in patients aged 60 to 79 years, the systolic pressure should be further reduced to <140 mmHg if it can be achieved without

producing significant side effects. In older patients with diabetes or chronic kidney disease, the blood pressure goal is <140/<90 mmHg.

●

These systolic blood pressure targets also apply to older adults with isolated systolic hypertension. However, as described elsewhere, the diastolic

blood pressure should be reduced to a minimum posttreatment diastolic pressure of >60 mmHg overall or perhaps >65 mmHg in patients with known

coronary artery disease unless symptoms that could be attributable to hypoperfusion occur at higher pressures.

Lower goals are suggested for patients with certain comorbid conditions, such as those with atherosclerotic cardiovascular disease or in patients

with proteinuric chronic kidney disease. In addition, antihypertensive drugs are given to improve survival in a number of conditions (eg, heart failure,

post-myocardial infarction), independent of the blood pressure. In these cases, lower blood pressure levels may be accepted to permit sufficient drug

doses. (See "What is goal blood pressure in the treatment of hypertension?", section on 'Lower goal in patients at increased risk' and "Blood

pressure management in patients with atherosclerotic cardiovascular disease", section on 'Goal blood pressure' and "Antihypertensive therapy and

progression of nondiabetic chronic kidney disease in adults", section on 'Blood pressure goal'.)

●

In the absence of end-organ damage, a patient should not be labeled as having hypertension unless the blood pressure is persistently elevated after●

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In a number of conditions (eg, heart failure, post-myocardial infarction), antihypertensive drugs are given to improve survival, independent of the blood

pressure. These uses are discussed separately in the appropriate topic reviews.

The importance of other risk factors on both cardiovascular risk (figure 2) [13,48] and the likelihood of a beneficial response to antihypertensive therapy

should not be underestimated [12]. In the MRC trial, for example, the number of patients with mild hypertension who had to be treated for five years to

prevent one cardiovascular complication was 262 in the absence of any risk factors but only four in high-risk patients who smoked, were older than 55

years, and had a systolic pressure above 160 mmHg [48]. (See "Estimation of cardiovascular risk in an individual patient without known cardiovascular

three to six visits over a several-month period. In one study, for example, there was a mean 15/7 reduction in blood pressure in untreated patients

between the first and third visits to a new clinician [43]. This difference has prognostic importance. The Medical Research Council Mild Hypertension

Trial found a close correlation between cardiovascular risk and the systolic pressure measured three months after entry into the trial [44]. In contrast,

a transient increase in systolic pressure at entry due to a white coat response was not associated with increased risk. During the initial evaluation

period before a therapeutic decision is made, patients should also be encouraged to measure their blood pressure at home or work. (See 'Definitions'

above.)

Antihypertensive medications should generally be begun if the systolic pressure is persistently ≥140 mmHg (in patients younger than 60 years)

and/or the diastolic pressure is persistently ≥90 mmHg in the office and at home, despite attempted nonpharmacologic therapy. The same applies to

patients 60 to 79 years, although such patients are somewhat more likely to develop side effects from therapy. In patients 80 years and older,

antihypertensive medications should generally be started if the systolic pressure is persistently ≥150 mmHg and/or the diastolic pressure is

persistently ≥90 mmHg. (See 'Goal blood pressure' above.)

Thus, systolic and diastolic hypertension, isolated systolic hypertension, and isolated diastolic hypertension all should be treated. Isolated diastolic

hypertension is associated with increased cardiovascular risk, but there are no treatment trials to prove benefit from antihypertensive therapy.

●

Starting with two drugs may be considered in patients with a baseline blood pressure more than 20/10 mmHg above goal. This strategy may increase

the likelihood that target blood pressures are achieved in a reasonable time period, but should be used cautiously in patients at increased risk for

orthostatic hypotension (such as diabetics and the elderly). (See "Choice of drug therapy in primary (essential) hypertension: Recommendations".)

●

In some patients with proteinuric chronic kidney disease or known cardiovascular disease, antihypertensive therapy may be indicated when the

systolic pressure is persistently above 130 mmHg and/or the diastolic pressure is above 80 mmHg. The benefit of such blood pressure lowering in

patients with chronic kidney disease is probably limited to patients excreting more than 0.5 to 1 g of protein per day. (See "What is goal blood

pressure in the treatment of hypertension?" and "Antihypertensive therapy and progression of nondiabetic chronic kidney disease in adults" and

"Blood pressure management in patients with atherosclerotic cardiovascular disease".)

●

Patients with office hypertension, normal values at home, and no evidence of end-organ damage should undergo ambulatory blood pressure

monitoring to see whether they are truly hypertensive. (See "Ambulatory blood pressure monitoring and white coat hypertension in adults".)

On the other hand, 5 to 20 percent of patients with normal office readings have been found to have elevated out-of-the office readings by 24-hour

automatic ambulatory blood pressure monitoring [45,46]. These patients with "masked" hypertension appear to have an increased cardiovascular risk

similar to those with elevated office and ambulatory readings [47]. Trials in patients with masked hypertension are lacking, as are recommendations

for which patients with normal office readings should be evaluated for masked hypertension.

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disease".)

Furthermore, cessation of smoking alone rapidly decreases coronary risk by approximately 35 to 40 percent, a benefit that is independent of the duration

of smoking [49]. (See "Patterns of tobacco use" and "Smoking and hypertension".)

Prehypertension — Patients with prehypertension (systolic 120 to 139 mmHg and/or diastolic 80 to 89 mmHg), but without diabetes, chronic kidney

disease, or cardiovascular disease are treated with nonpharmacologic therapies such as weight reduction, sodium restriction, and avoidance of excess

alcohol (table 1). They should also have their blood pressure measured at least annually, or more frequently if home monitoring is available, since they are

at significant risk of developing hypertension over time. (See "Prehypertension".)

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 5 to 6 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 10 to 12 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.)

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REFERENCES

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2. Weber MA, Schiffrin EL, White WB, et al. Clinical practice guidelines for the management of hypertension in the community a statement by theAmerican Society of Hypertension and the International Society of Hypertension. J Hypertens 2014; 32:3.

3. Blood Pressure Lowering Treatment Trialists' Collaboration, Turnbull F, Neal B, et al. Effects of different regimens to lower blood pressure on majorcardiovascular events in older and younger adults: meta-analysis of randomised trials. BMJ 2008; 336:1121.

4. James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panelmembers appointed to the Eighth Joint National Committee (JNC 8). JAMA 2014; 311:507.

5. Chobanian AV, Bakris GL, Black HR, et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatmentof High Blood Pressure: the JNC 7 report. JAMA 2003; 289:2560.

6. Krause T, Lovibond K, Caulfield M, et al. Management of hypertension: summary of NICE guidance. BMJ 2011; 343:d4891.

7. Mancia G, Fagard R, Narkiewicz K, et al. 2013 Practice guidelines for the management of arterial hypertension of the European Society of

th th

th th

Beyond the Basics topics (see "Patient information: High blood pressure in adults (Beyond the Basics)" and "Patient information: High blood

pressure treatment in adults (Beyond the Basics)" and "Patient information: High blood pressure, diet, and weight (Beyond the Basics)").

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Hypertension (ESH) and the European Society of Cardiology (ESC): ESH/ESC Task Force for the Management of Arterial Hypertension. JHypertens 2013; 31:1925.

8. Franklin SS, Larson MG, Khan SA, et al. Does the relation of blood pressure to coronary heart disease risk change with aging? The FraminghamHeart Study. Circulation 2001; 103:1245.

9. Lewington S, Clarke R, Qizilbash N, et al. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data forone million adults in 61 prospective studies. Lancet 2002; 360:1903.

10. Pastor-Barriuso R, Banegas JR, Damián J, et al. Systolic blood pressure, diastolic blood pressure, and pulse pressure: an evaluation of their jointeffect on mortality. Ann Intern Med 2003; 139:731.

11. Sipahi I, Tuzcu EM, Schoenhagen P, et al. Effects of normal, pre-hypertensive, and hypertensive blood pressure levels on progression of coronaryatherosclerosis. J Am Coll Cardiol 2006; 48:833.

12. Mancia G, De Backer G, Dominiczak A, et al. 2007 Guidelines for the Management of Arterial Hypertension: The Task Force for the Management ofArterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens 2007; 25:1105.

13. Jackson R, Lawes CM, Bennett DA, et al. Treatment with drugs to lower blood pressure and blood cholesterol based on an individual's absolutecardiovascular risk. Lancet 2005; 365:434.

14. Vasan RS, Larson MG, Leip EP, et al. Impact of high-normal blood pressure on the risk of cardiovascular disease. N Engl J Med 2001; 345:1291.

15. Qureshi AI, Suri MF, Kirmani JF, et al. Is prehypertension a risk factor for cardiovascular diseases? Stroke 2005; 36:1859.

16. Kshirsagar AV, Carpenter M, Bang H, et al. Blood pressure usually considered normal is associated with an elevated risk of cardiovascular disease.Am J Med 2006; 119:133.

17. van den Hoogen PC, Feskens EJ, Nagelkerke NJ, et al. The relation between blood pressure and mortality due to coronary heart disease amongmen in different parts of the world. Seven Countries Study Research Group. N Engl J Med 2000; 342:1.

18. Domanski M, Mitchell G, Pfeffer M, et al. Pulse pressure and cardiovascular disease-related mortality: follow-up study of the Multiple Risk FactorIntervention Trial (MRFIT). JAMA 2002; 287:2677.

19. Benetos A, Thomas F, Bean K, et al. Prognostic value of systolic and diastolic blood pressure in treated hypertensive men. Arch Intern Med 2002;162:577.

20. Strandberg TE, Salomaa VV, Vanhanen HT, et al. Isolated diastolic hypertension, pulse pressure, and mean arterial pressure as predictors ofmortality during a follow-up of up to 32 years. J Hypertens 2002; 20:399.

21. Mancia G, Messerli F, Bakris G, et al. Blood pressure control and improved cardiovascular outcomes in the International Verapamil SR-TrandolaprilStudy. Hypertension 2007; 50:299.

22. Effects of treatment on morbidity in hypertension. Results in patients with diastolic blood pressures averaging 115 through 129 mm Hg. JAMA 1967;202:1028.

23. Effects of treatment on morbidity in hypertension. II. Results in patients with diastolic blood pressure averaging 90 through 114 mm Hg. JAMA 1970;213:1143.

24. Hebert PR, Moser M, Mayer J, et al. Recent evidence on drug therapy of mild to moderate hypertension and decreased risk of coronary heartdisease. Arch Intern Med 1993; 153:578.

25. Zanchetti A, Mancia G. Benefits and cost-effectiveness of antihypertensive therapy. The actuarial versus the intervention trial approach. J Hypertens1996; 14:809.

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26. Sytkowski PA, D'Agostino RB, Belanger AJ, Kannel WB. Secular trends in long-term sustained hypertension, long-term treatment, andcardiovascular mortality. The Framingham Heart Study 1950 to 1990. Circulation 1996; 93:697.

27. Wang JG, Staessen JA. Antihypertensive drug therapy in older patients. Curr Opin Nephrol Hypertens 2001; 10:263.

28. Diao D, Wright JM, Cundiff DK, Gueyffier F. Pharmacotherapy for mild hypertension. Cochrane Database Syst Rev 2012; 8:CD006742.

29. Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the SystolicHypertension in the Elderly Program (SHEP). SHEP Cooperative Research Group. JAMA 1991; 265:3255.

30. Franklin SS, Jacobs MJ, Wong ND, et al. Predominance of isolated systolic hypertension among middle-aged and elderly US hypertensives:analysis based on National Health and Nutrition Examination Survey (NHANES) III. Hypertension 2001; 37:869.

31. Franklin SS, Pio JR, Wong ND, et al. Predictors of new-onset diastolic and systolic hypertension: the Framingham Heart Study. Circulation 2005;111:1121.

32. Chirinos JA, Franklin SS, Townsend RR, Raij L. Body mass index and hypertension hemodynamic subtypes in the adult US population. Arch InternMed 2009; 169:580.

33. Pickering TG. Isolated diastolic hypertension. J Clin Hypertens (Greenwich) 2003; 5:411.

34. Strandberg TE, Pitkala K. What is the most important component of blood pressure: systolic, diastolic or pulse pressure? Curr Opin NephrolHypertens 2003; 12:293.

35. Fang XH, Zhang XH, Yang QD, et al. Subtype hypertension and risk of stroke in middle-aged and older Chinese: a 10-year follow-up study. Stroke2006; 37:38.

36. Hozawa A, Ohkubo T, Nagai K, et al. Prognosis of isolated systolic and isolated diastolic hypertension as assessed by self-measurement of bloodpressure at home: the Ohasama study. Arch Intern Med 2000; 160:3301.

37. Julius S, Nesbitt SD, Egan BM, et al. Feasibility of treating prehypertension with an angiotensin-receptor blocker. N Engl J Med 2006; 354:1685.

38. Rosendorff C, Black HR, Cannon CP, et al. Treatment of hypertension in the prevention and management of ischemic heart disease: a scientificstatement from the American Heart Association Council for High Blood Pressure Research and the Councils on Clinical Cardiology andEpidemiology and Prevention. Circulation 2007; 115:2761.

39. Hackam DG, Quinn RR, Ravani P, et al. The 2013 Canadian Hypertension Education Program recommendations for blood pressure measurement,diagnosis, assessment of risk, prevention, and treatment of hypertension. Can J Cardiol 2013; 29:528.

40. Wright JT Jr, Fine LJ, Lackland DT, et al. Evidence supporting a systolic blood pressure goal of less than 150 mm Hg in patients aged 60 years orolder: the minority view. Ann Intern Med 2014; 160:499.

41. Whitworth JA, World Health Organization, International Society of Hypertension Writing Group. 2003 World Health Organization (WHO)/InternationalSociety of Hypertension (ISH) statement on management of hypertension. J Hypertens 2003; 21:1983.

42. Williams B, Poulter NR, Brown MJ, et al. British Hypertension Society guidelines for hypertension management 2004 (BHS-IV): summary. BMJ2004; 328:634.

43. Hartley RM, Velez R, Morris RW, et al. Confirming the diagnosis of mild hypertension. Br Med J (Clin Res Ed) 1983; 286:287.

44. Millar JA, Isles CG, Lever AF. Blood pressure, 'white-coat' pressor responses and cardiovascular risk in placebo-group patients of the MRC MildHypertension trial. J Hypertens 1995; 13:175.

45. Pickering TG. Effects of stress and behavioral interventions in hypertension: what is masked hypertension? J Clin Hypertens (Greenwich) 2003;5:171.

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46. Lurbe E, Torro I, Alvarez V, et al. Prevalence, persistence, and clinical significance of masked hypertension in youth. Hypertension 2005; 45:493.

47. Bobrie G, Chatellier G, Genes N, et al. Cardiovascular prognosis of "masked hypertension" detected by blood pressure self-measurement in elderlytreated hypertensive patients. JAMA 2004; 291:1342.

48. Stroke and coronary heart disease in mild hypertension: risk factors and the value of treatment. Medical Research Council Working Party. Br Med J(Clin Res Ed) 1988; 296:1565.

49. Kannel WB, Higgins M. Smoking and hypertension as predictors of cardiovascular risk in population studies. J Hypertens Suppl 1990; 8:S3.

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GRAPHICS

Lifestyle modifications in the management of hypertension

Modification RecommendationApproximate systolic

BP reduction, range*

Weight reduction Maintain normal body weight (BMI, 18.5 to 24.9 kg/m ) 5 to 20 mmHg per 10 kg

weight loss

Adopt DASH

eating plan

Consume a diet rich in fruits, vegetables, and low-fat dairy products with a

reduced content of saturated and total fat

8 to 14 mmHg

Dietary sodium

reduction

Reduce dietary sodium intake to no more than 100 meq/day (2.4 g sodium

or 6 g sodium chloride)

2 to 8 mmHg

Physical activity Engage in regular aerobic physical activity such as brisk walking (at least 30

minutes per day, most days of the week)

4 to 9 mmHg

Moderation of

alcohol

consumption

Limit consumption to no more than 2 drinks per day in most men and no

more than 1 drink per day in women and lighter-weight persons

2 to 4 mmHg

For overall cardiovascular risk reduction, stop smoking. The effects of implementing these modifications are dose and time

dependent and could be higher for some individuals; they are not all additive.

BMI: body mass index; BP: blood pressure; DASH: Dietary Approaches to Stop Hypertension.

Reproduced from: The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood

Pressure. Available at http://www.nhlbi.nih.gov/guidelines/hypertension/jnc7full.pdf.

Graphic 62129 Version 3.0

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CHD mortality related to blood pressure and age

Coronary heart disease (CHD) mortality rate, pictured on a log scale with 95 percent

confidence intervals, in each decade of age in relation to the estimated usual systolic

and diastolic blood pressure at the start of that decade. CHD mortality increases with

both higher pressures and older ages. For diastolic pressure, each age-specific

regression line ignores the left-hand point (ie, at slightly less than 75 mmHg) for which

the risk lies significantly above the fitted regression line (as indicated by the broken line

below 75 mmHg).

Data from: Prospective Studies Collaboration, Lancet 2002; 360:1903.

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Stroke mortality related to blood pressure and age

Stroke mortality rate, pictured on a log scale with 95 percent confidence

intervals, in each decade of age in relation to the estimated usual systolic and

diastolic blood pressure at the start of that decade. Stroke mortality increases

with both higher pressures and older ages. For diastolic pressure, each age-

specific regression line ignores the left-hand point (ie, at slightly less than 75

mmHg), for which the risk lies significantly above the fitted regression line (as

indicated by the broken line below 75 mmHg).

Data from Prospective Studies Collaboration, Lancet 2002; 360:1903.

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Additive effects of risk factors on cardiovascular disease at five

years

Cumulative absolute risk of CVD at five years according to systolic blood pressure and

specified levels of other risk factors. The reference category is a nondiabetic,

nonsmoking 50-year-old woman with a serum TC of 154 mg/dL (4.0 mmol/L) and HDL-

cholesterol of 62 mg/dL (1.6 mmol/L). The CVD risks are given for systolic blood

pressure levels of 110, 130, 150, and 170 mmHg. In the other categories, the

additional risk factors are added consecutively. As an example, the diabetes category

is a 50-year-old diabetic man who is a smoker and has a TC of 270 mg/dL (7 mmol/L)

and HDL-cholesterol of 39 mg/dL (1 mmol/L).

CVD: cardiovascular disease; TC: total cholesterol.

Adapted from: Jackson R, Lawes CM, Bennett DA, et al. Lancet 2005; 365:434.

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Joint effect of systolic and diastolic blood pressure

on mortality

Among participants in the NHANES II who were <65 years of age, the

figure shows a three dimensional surface representing the relative risk

for all-cause mortality (vertical axis) with different combinations of

the diastolic blood pressure (right diagonal arrow axis) and the

systolic blood pressure (left diagonal arrow axis). For a fixed diastolic

blood pressure, for example, the effect of different systolic blood

pressures can be evaluated by following the risk surface along lines

parallel to the systolic blood pressure axis. This effect is known as the

conditional effect of systolic blood pressure. Similarly, for a fixed

systolic blood pressure, the conditional effect of diastolic blood

pressure can be evaluated by following the risk surface along lines

parallel to the diastolic blood pressure axis.

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Redrawn from: Pastor-Barriuso R, et al. Ann Intern Med 2003; 139:731.

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Joint effect of systolic and diastolic blood pressure on

mortality

Among participants in the NHANES II who were ≥65 years of age, the

figure shows a three dimensional surface representing the relative risk

for all-cause mortality (vertical axis) with different combinations of the

diastolic blood pressure (right diagonal arrow axis) and the systolic

blood pressure (left diagonal arrow axis). For a fixed diastolic blood

pressure, for example, the effect of different systolic blood pressures

can be evaluated by following the risk surface along lines parallel to the

systolic blood pressure axis. This effect is known as the conditional

effect of systolic blood pressure. Similarly, for a fixed systolic blood

pressure, the conditional effect of diastolic blood pressure can be

evaluated by following the risk surface along lines parallel to the

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diastolic blood pressure axis.

Redrawn from: Pastor-Barriuso R, et al. Ann Intern Med 2003; 139:731.

Graphic 57839 Version 3.0

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Cardiovascular benefit of treating mild hypertension

Reduced incidence of fatal and total coronary heart disease (CHD) events

and strokes following antihypertensive therapy in 17 controlled studies

involving almost 48,000 patients with mild to moderate hypertension. The

number of patients having each of these events is depicted, with active

treatment lowering the incidence of coronary events by 16 percent and

stroke by 40 percent. However, the absolute benefit—as shown, in

percent, by the numbers at the top of the graph—was much less.

Treatment for approximately 4 to 5 years prevented a coronary event or a

stroke in two percent of patients (0.7 + 1.3), including prevention of death

in 0.8 percent.

CVA: cerebrovascular accident (stroke).

Data from: Hebert PR, Moser M, Mayer J, et al. Recent evidence on drug therapy of

mild to moderate hypertension and decreased risk of coronary heart disease. Arch

Intern Med 1993; 153:578.

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Disclosures: Johannes FE Mann, MD Grant/Research/Clinical Trial Support: Novo Nordisk [Diabetes (Liraglutide)]; AbbVie [Diabetes (Linagliptine)]; Boehringer Ingelheim [Diabetes(Atrasentan)]. Speaker's Bureau: Hoffman-La Roche [Hypertension (Antihypertensive drugs)]; Amgen [Hypertension (Antihypertensive drugs)]; Novartis [Hypertension(Antihypertensive drugs)]; Fresenius SE [Hypertension (Antihypertensive drugs)]; Boehringer Ingelheim [Hypertension (Antihypertensive drugs)]. Consultant/Advisory Boards: NovoNordisk [Kidney disease (Liraglutide)]; AbbVie [Kidney disease (Endothelin antagonists)]; ZS Pharma [Kidney disease (Potassium binders)]; Takeda [Kidney disease (Iron)]. Karl FHilgers, MD Grant/Research/Clinical Trial Support: Astellas [kidney transplantation (tacrolimus)]; Novartis [kidney transplantation (ciclosporin, everolimus)]. George L Bakris, MDGrant/Research/Clinical Trial Support: Medtronic; Relypsa [Hypertension, hyperkalemia]. Consultant/Advisory Boards: Medtronic; Relypsa; Bayer; Novartis; DSI; Boehringer-Ingelheim;Lexicon; Janssen; Astra-Zeneca; Kona [Diabetes, hyperkalemia, resistant hypertension (Canaglif lozin, dapaglif lozin, empaglif lozin)]. Norman M Kaplan, MD Nothing to disclose. John PForman, MD, MSc Employee of UpToDate, Inc.

Contributor disclosures are review ed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and throughrequirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence.

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