Prevalence of Resistant Hypertension in the United
Stephen D. Persell
See Editorial Commentary, pp 1045–1046
Abstract—The prevalence of resistant hypertension is unknown. Much previous knowledge comes from referral
populations or clinical trial participants. Using data from the National Health and Nutrition Examination Survey from
2003 through 2008, nonpregnant adults with hypertension were classified as resistant if their blood pressure was
?140/90 mm Hg and they reported using antihypertensive medications from 3 different drug classes or drugs from ?4
antihypertensive drug classes regardless of blood pressure. Among US adults with hypertension, 8.9% (SE: 0.6%) met
criteria for resistant hypertension. This represented 12.8% (SE: 0.9%) of the antihypertensive drug–treated population.
Of all drug-treated adults whose hypertension was uncontrolled, 72.4% (SE: 1.6%) were taking drugs from ?3 classes.
Compared with those with controlled hypertension using 1 to 3 medication classes, adults with resistant hypertension
were more likely to be older, to be non-Hispanic black, and to have higher body mass index (all P?0.001). They were more
likely to have albuminuria, reduced renal function, and self-reported medical histories of coronary heart disease, heart failure,
stroke, and diabetes mellitus (P?0.001). Most (85.6% [SE: 2.4%]) individuals with resistant hypertension used a diuretic. Of
this group, 64.4% (SE: 3.2%) used the relatively weak thiazide diuretic hydrochlorothiazide. Although not rare, resistant
hypertension is currently found in only a modest proportion of the hypertensive population. Among those classified here as
resistant, inadequate diuretic therapy may be a modifiable therapeutic target. Cardiovascular diseases, diabetes mellitus,
obesity, and renal dysfunction were all common in this population. (Hypertension. 2011;57:1076-1080.)
Key Words: hypertension/epidemiology ? hypertension/drug treatment ? drug resistance
? antihypertensive agents/classification/therapeutic use ? diuretics ? United States/epidemiology
of antihypertensive medications from ?3 drug classes. Indi-
viduals with controlled blood pressure using ?4 drug classes
are also considered to have resistant hypertension. Preferably,
the regimen would include a diuretic, and all doses would be
optimal.1–3Although it is somewhat arbitrary and imprecise,
this designation has been suggested to identify patients for
whom special diagnostic investigations into reversible causes
of hypertension may be warranted or those who may benefit
from specific therapeutic considerations. The prevalence of
resistant hypertension is unknown, but it is thought to be a
common problem.1Much of the evidence about the charac-
teristics of individuals with resistant hypertension comes
from studies conducted in referral populations that might not
be generalizable to the overall population.
The National Health and Nutrition Examination Survey
(NHANES) uses standardized assessments of blood pressure
esistant hypertension has been defined as blood pressure
that remains above goal in spite of the concomitant use
and prescription medications among a representative sample
of the US population. It provides an opportunity to assess the
prevalence of drug-resistant hypertension among US adults
and to examine the characteristics of these individuals.
Data from the NHANES from 2003 through 2008 were used in these
analyses. NHANES uses a multistage sampling design and appro-
priate weighting to provide a nationally representative sample of the
noninstitutionalized US population. NHANES participants provided
written informed consent, and the study was approved by the
National Center for Health Statistics Research Ethics Review Board.
NHANES data sets, study procedures, and questionnaires are publi-
cally available from the National Center for Health Statistics.4This
study was limited to participants selected for the mobile examination
sample of the NHANES who were nonpregnant and were ?18 years
Blood pressures were measured by physicians using a standard-
ized protocol. Participants were instructed to sit quietly for 5 minutes
before the readings were taken. Three measurements were attempted.
Received January 17, 2011; first decision February 6, 2011; revision accepted March 21, 2011.
From the Division of General Internal Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL.
The sponsor had no role in the design and conduct of the study; in the data collection, analysis, and interpretation of data; or in the presentation, review,
or approval of the article.
S.D.P. had full access to the study data and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Correspondence to Stephen D. Persell, Division of General Internal Medicine, Northwestern University, 750 N Lake Shore Dr, 10th Floor, Chicago,
IL 60611. E-mail email@example.com
© 2011 American Heart Association, Inc.
Hypertension is available at http://hyper.ahajournals.org DOI: 10.1161/HYPERTENSIONAHA.111.170308
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If 3 readings were obtained, the first value was not used, and the
mean of the subsequent systolic and diastolic readings was consid-
ered to be the average blood pressure, or if only 2 readings were
obtained, the second reading alone was used. If only 1 reading was
obtained, it was considered to be the average blood pressure.5
Among the 15 968 nonpregnant adult participants, 13 154 had 3
blood pressure readings, 1916 had 1 or 2 readings, and 898 had none.
Participants with no recorded blood pressures were excluded. Par-
ticipants were considered to have hypertension if the average systolic
blood pressure was ?140 mm Hg, the average diastolic blood
pressure was ?90 mm Hg, or they reported that they were currently
taking a prescribed medication for hypertension or high blood
pressure. Blood pressure was considered uncontrolled if the average
systolic blood pressure was ?140 mm Hg or the average diastolic
blood pressure was ?90 mm Hg.
In this study, participants were classified as having resistant
hypertension if their blood pressure was ?140/90 mm Hg (either
systolic or diastolic) and they reported using antihypertensive med-
ications from 3 different drug classes in the past 1 month or they
reported using drugs from ?4 antihypertensive drug classes in the
past month regardless of blood pressure. Medication usage was
assessed during home interviews, and interviewers reviewed pre-
scription containers whenever available. Drug classes included
angiotensin-converting enzyme inhibitors, angiotensin receptor
blockers, ?-blockers, dihydropyridine calcium channel blockers,
nondihydropyridine calcium channel blockers, thiazide-like diuret-
ics, loop diuretics, potassium-sparing diuretics, peripheral
?-adrenergic receptor antagonists, central-acting and other antiad-
renergic drugs, direct vasodilators, and direct renin inhibitors.
Prescription containers were directly observed for 89.8% of antihy-
pertension medications. Participants reported that they had been
taking the medication for ?30 days for 2.0% of antihypertensive
Participants with hypertension receiving drug treatment who were
not classified as resistant were classified in 2 other groups, uncon-
trolled (?140/90 mm Hg) using ?2 drug classes or controlled
(?140/90 mm Hg) receiving ?3 drug classes. Glomerular filtration
rate was estimated from the serum creatinine using the Modification
of Diet in Renal Disease equations.6Participants self-reported
comorbidities. Characteristics of participants with resistant hyper-
tension were compared with participants in these other 2 groups with
All of the analyses used SAS 9.2 (SAS Institute, Inc, Cary, NC).
Analyses were performed using appropriate NHANES sample
weights that account for the probability of selection and nonre-
sponse. Descriptive statistics and comparisons between groups used
SAS survey procedures (SURVEYFREQ, SURVEYMEANS, and
SURVEYREG) to account for the complex multistage sampling
design. Comparisons between groups used the ?2test for categorical
variables and linear regression for continuous variables.
In 2003–2008, among noninstitutionalized nonpregnant US
adults with hypertension, 8.9% (SE: 0.6%) met the criteria for
resistant hypertension used here. This represented 12.8% (SE
0.9) of all drug-treated hypertensive adults (Table 1). Among
all of the drug-treated hypertensive adults whose blood
pressure was uncontrolled, 72.4% (SE: 1.6%) were taking
antihypertensive drugs from ?3 drug classes.
Table 2 provides the characteristics of individuals with
resistant hypertension, uncontrolled drug-treated hyperten-
sion using ?2 medications, and drug-treated hypertension
controlled using ?3 medications. Adults with resistant hy-
pertension differed in many ways from drug-treated hyper-
tensive adults with blood pressure ?140/90 mm Hg using 1
or 2 medications. Those with resistant hypertension were
more likely to be non-Hispanic black and have higher mean
body mass index, microalbuminuria and macroalbuminuria,
an estimated glomerular filtration rate of ?60 mL/min, and
self-reported medical history of coronary heart disease, heart
failure, stroke, and diabetes mellitus. Differences between
those with resistant hypertension compared with drug-treated
hypertensive individuals whose blood pressure was ?140/
90 mm Hg using 1 to 3 antihypertensive medication classes
were similar. Those with resistant hypertension were also
significantly older (Table 2).
The number and type of antihypertensive medications used
by adults with resistant hypertension within the past month
are provided in Tables 3 and 4, respectively. Use of diuretics,
?-blockers, calcium channel blockers, angiotensin-converting
enzyme inhibitors, and angiotensin receptor blockers were all
common, and 9.1% (SE: 1.3%) used both an angiotensin-
converting enzyme inhibitor and an angiotensin receptor
blocker. Most (85.6%) individuals with resistant hypertension
used a diuretic. Of the diuretic users, 64.4% (SE: 3.2%) used
hydrochlorothiazide (55.1% of the total resistant hypertension
population). Hydrochlorothiazide accounted for nearly all of
the thiazide-like diuretic use (94.3% [SE: 1.4%]). Thiazide-
like and loop diuretic use differed for resistant hypertensive
participants with an estimated glomerular filtration rate ?30
mL/min compared with others (Table 5). Although loop
diuretic use and combination diuretic use were more common
among persons with glomerular filtration rate ?30 mL/min,
33.4% (SE: 11.2%) of this group did not use a loop diuretic.
Of those classified as resistant, 71.2% (SE: 2.8%) had
blood pressure ?140/90 mm Hg taking antihypertensive
drugs from ?3 drug classes, and the remainder had blood
pressure ?140/90 mm Hg using ?4 drug classes. Approxi-
mately half, 49.5% (SE: 4.3%), of adults with resistant
hypertension who used ?4 antihypertensive medications had
a blood pressure that was uncontrolled.
This analysis indicates that 8.9% of all US adults with
hypertension and 12.8% of antihypertensive drug-treated
adults meet the operational definition of resistant hyperten-
sion used here. Most drug-treated adults with uncontrolled
hypertension are receiving medications from only 1 or 2
Classification of Adults With Hypertension in the
Adults, % (SE)
Adults, % (SE)
Uncontrolled, no drug
uncontrolled, ?3 drugs or
controlled ?4 drugs
203540.8 (1.1) 58.9 (1.2)
113619.6 (0.8) 28.3 (1.1)
5398.9 (0.6)12.8 (0.9)
Uncontrolled indicates a mean systolic pressure of ?140 or diastolic
?90 mm Hg.
PersellResistant Hypertension in the United States
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pharmaceutical classes. At the population level, the underuse
of adequate drug therapy for hypertension appears much
more widespread than the lack of drug effectiveness.
The multidrug treatment regimens frequently used in the
United States may often be less than optimal. Before consid-
ering someone to have resistant hypertension, treatment with
?3 antihypertensive medications from different classes
should be used together at sufficient doses. Preferably, a
diuretic should be included.1–3Expert opinion and some
empirical evidence support the use of diuretics of sufficient
potency to control the volume expansion that may contribute
to drug resistance.1–3,7–9Individuals with renal dysfunction,
glomerular filtration rates ?30 mL/min, may require loop
diuretics. Although 86% of NHANES participants with resis-
tant hypertension were using a diuretic, many may have
inadequate diuretic treatment. Hydrochlorothiazide use was
reported by 55% of adults classified as resistant, and it
accounted for nearly all of the thiazide-like diuretic use in the
resistant group. Although hydrochlorothiazide is part of most
combination antihypertensive pills which include a diuretic
marketed in the United States, there is evidence to suggest
that it is not as effective as the diuretic chlorthalidone.10
Among adults with resistant hypertension and reduced renal
function, many did not use a loop diuretic.
Several studies have shown that the use of aldosterone
antagonists (spironolactone or eplerenone) may be a valuable
strategy for individuals with difficult to control hyperten-
sion.1,11–13During the time period studied (2003–2008), use
of these agents among adults with resistant participants was
The characteristics of individuals with drug resistance
observed in this cross-sectional study are concordant with
previous observations, showing that increasing age, obesity,
black race, and renal dysfunction are associated with drug
resistance or lack of blood pressure control.14–18This study
also confirms a high prevalence of comorbid cardiovascular
Drug-Treated Hypertension Among Adults in the 2003–2008 National Health and Nutrition
Uncontrolled, ?3 Drugs
or Controlled ?4
Drugs (N? 539)
Age in y, mean
Body mass index in kg/m2, mean†
Estimated GFR in mL/min, mean‡
Estimated GFR ?60 mL/min, %‡
Serum potassium, mmol/L, %‡
Albumin:creatinine ratio, %§
30 to 300 mg/g
Coronary heart disease, %
Heart failure, %
Diabetes mellitus, %
Numbers in parentheses represent SEs. GFR indicates glomerular filtration rate.
*Data show the P value compared with the resistant hypertension group.
†Data are available for 97.9%.
‡Data are available for 94.2%.
§Data are available for 96.9%.
Month Among Adults With Resistant Hypertension
No. of Antihypertensive Medications Used in the Past
No. of Hypertensive Medication Drug Classes*N % (SE)
*Drug classes considered were angiotensin-converting enzyme inhibitors,
angiotensin receptor blockers, ?-blockers, dihydropyridine calcium channel
blockers, nondihydropyridine calcium channel blockers, thiazide-like diuretics,
loop diuretics, potassium-sparing diuretics, peripheral ?-adrenergic receptor
antagonists, central-acting and other anti-adrenergic drugs, direct vasodilators,
and direct renin inhibitors. No individuals surveyed with resistant hypertension
were taking a direct renin inhibitor.
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disease and diabetes mellitus among adults with resistant
hypertension.17Unlike a referral population in which lower
levels of serum potassium were found in resistant hyperten-
sion patients,19in this population-based cohort, potassium
levels were identical in the resistant and nonresistant drug-
It is important to be aware of the limitations of these data
when interpreting these results. The estimates provided here
may overestimate the true prevalence of resistant hyperten-
sion in the current US adult population for several reasons.
The medication use questionnaire used in NHANES does not
distinguish whether medications were used consistently, only
that they were used at all during the month before the
examination. Some participants who were not fully adherent
to their antihypertensive medication, discontinued a medica-
tion, or switched from one medication to another within the
past month could be falsely classified as resistant. The
NHANES did not record dose or frequency of medications;
therefore, some individuals receiving drugs at low doses or
with inadequate frequency (eg, once-daily short-acting loop
diuretics) could have been falsely classified as resistant.
Some individuals may have been falsely classified as resistant
because of the white coat phenomenon if their examination
blood pressure measurements were higher than what would
have been observed using ambulatory blood pressure moni-
toring.20However, the estimate of the cross-sectional preva-
lence of resistant hypertension provided here likely underes-
timates what the prevalence would be if all of the adults with
uncontrolled hypertension were treated with adequate 3-drug
regimens, because some individuals currently uncontrolled
with ?3 drugs would remain uncontrolled even if 3 drugs
were used. Lastly, the proportion with resistant hypertension
would have been greater had a lower cut point for control
been used for participants with diabetes mellitus or renal
disease. The blood pressure target of ?130/80 mm Hg is
recommended by the Seventh Report of the Joint National
Committee on Prevention, Detection, Evaluation, and Treat-
ment of High Blood Pressure for individuals with diabetes
mellitus and renal disease, and lower targets may also be
appropriate for individuals with ischemic vascular disease or
others at high cardiovascular risk.2,21Use of different target
blood pressures was not used here for several reasons. There
is no way to know the goal blood pressure selected by
participants’ treating clinicians; different cut points would
have greatly complicated the comparisons of characteristics
between groups, and in light of recent findings in the Action
to Control Cardiovascular Risk in Diabetes Study, the goal
blood pressure that will be selected in future guidelines for
individuals with diabetes mellitus is uncertain.22Lastly,
interpretation of diuretic use among individuals with resistant
hypertension and glomerular filtration rates ?30 mL/min
should be done cautiously, because few participants meeting
these criteria were surveyed.
Resistant hypertension is not a rare phenomenon, but use of
inadequate medical regimens for hypertension appears to be
observed far more often than true resistance to a regimen that
includes drugs from 3 different pharmaceutical classes. The
group identified as resistant has many high-risk features,
including a substantial burden of cardiovascular disease,
stroke, diabetes mellitus, and underlying renal dysfunction.
Special consideration may be needed to help mitigate these
risks. More clinical research is needed to determine optimal
therapeutic strategies for those with resistant hypertension.
I thank Heather L. Heiman for helpful editorial advice on a draft of
Sources of Funding
S.D.P. receives research grant support from the Agency for Health-
care Researchand Quality
Past Month Among Adults With Resistant Hypertension
Type of Antihypertensive Medications Used in the
Calcium channel blocker
Central-acting and other
108 17.7 (1.7)
58 10.0 (1.4)
ACE indicates angiotensin-converting enzyme; ARB, angiotensin receptor
blocker; HCTZ, hydrochlorothiazide.
Resistant Hypertension by Renal Function
Diuretic Use in the Past Month Among Adults With
Thiazide-like and loop diuretic use
Neither thiazide-like nor loop diuretic
Thiazide-like diuretic only
Loop diuretic only
Thiazide-like and loop diuretic
Potassium sparing diuretic use
Data are among the 503 of 539 resistant hypertension participants with
creatinine data available. GFR indicates glomerular filtration rate.
Persell Resistant Hypertension in the United States
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Stephen D. Persell
Prevalence of Resistant Hypertension in the United States, 2003
Print ISSN: 0194-911X. Online ISSN: 1524-4563
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2011;57:1076-1080; originally published online April 18, 2011;
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