Original Article
Prevalence and clinical characteristics of patients with
true resistant hypertension in central and Eastern
Europe: data from the BP-CARE study
Gianmaria Brambilla a, Michele Bombelli a, Gino Seravalle b, Renata Cifkova c, Stephane Laurent d,
Krzysztof Narkiewicz e, Rita Facchetti a, Josep Redon f, Giuseppe Mancia b, and Guido Grassi a,g
Objective: Scanty information is available on the clinical
characteristics of resistant hypertension in Central and East
European countries. The Blood Pressure (BP) control rate
and CArdiovascular Risk profilE (BP-CARE) study allowed us
to assess the prevalence and the main clinical features of
resistant hypertension in this population.
Design and method: The study was carried out in 1312
treated hypertensive patients living in nine Central and
East European countries.
Results: Four hundred and twenty-three patients had
apparent resistant hypertension, of whom 168 had
pseudo-resistant hypertension (noncompliant/white-coat)
and 255 were true treatment-resistant hypertension
patients (TRH). Clinical BP values in TRH amounted to
157.4
16.9/91.8
10.0 mmHg despite the daily use of
3.6
0.7 drugs. Their 24-h BP values were 149.5
16.5/
97.5
9.8 mmHg. Compared to controlled hypertensive
patients (n ¼ 368) and uncontrolled nonresistant
hypertensive patients (n ¼ 521), TRH were older with a
greater prevalence of women. They showed a higher rate
of previous cardiovascular events and a very high
cardiovascular risk profile. Estimated glomerular filtration
rate was significantly lower in TRH as compared to
controlled hypertensive patients and uncontrolled
nonresistant hypertensive patients. Overall, target organ
damage was more frequently detected in TRH than in
controlled hypertensive patients and uncontrolled
nonresistant hypertensive patients. The factor most
frequently associated with TRH was severity of
hypertension followed by age, total cholesterol, BMI and
history of heart failure.
Conclusions: The present study provides evidence that the
prevalence of TRH in Central and East European countries
is similar to that found in Western Europe and USA. It also
shows the very high cardiovascular risk of TRH and the
elevated association of this condition with obesity, renal
failure, organ damage and history of cardiovascular events.
Keywords: ambulatory blood pressure, antihypertensive
treatment, cardiovascular risk, resistant hypertension,
target organ damage
Abbreviations: BP, blood pressure; BP-CARE, Blood
Pressure rate control and CArdiovascular Risk profilE;
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MDRD, Modification of Diet in Renal Disease formula; TRH,
true treatment-resistant hypertension patients
INTRODUCTION
T
he condition of resistant hypertension is receiving
growing attention because of the worse prognosis
that characterizes these patients as compared with
other hypertensive patients, and the possible indication for
new therapeutic strategies – either pharmacological or
nonpharmacological [1–6]. In recent years, a number of
studies have been performed to determine the prevalence
of resistant hypertension [5,7–13], with marked discrepan-
cies in the results (5–30%), mainly because of the differ-
ences in the definition of this condition employed in the
various studies and frequently dependent on the
inadequate diagnostic approach used. In fact, the diagnos-
tic algorithm recommended by the American Heart Associ-
ation statement [14], and recently incorporated in other
documents on this issue [15], indicates the exclusion of
pseudo-resistant hypertensive patients such as those not
compliant to treatment, those with white-coat [5,10,14] or
secondary hypertension [5,14,16] and those with sleep
apnea syndrome [5,14,17]. In addition, data available in
the literature have been mainly collected in populations of
North America and Western Europe [7–13], whereas scanty
data are present on the prevalence of resistant hypertension
Journal of Hypertension 2013, 31:2018–2024
a
Clinica Medica, Università Milano-Bicocca, Ospedale San Gerardo dei Tintori, Monza,
b
Istituto Auxologico Italiano, Ospedale San Luca, Milan, Italy, cCenter for Cardiovas-
cular Prevention, Thomayer Hospital and Department of Preventive Cardiology,
Institute of Clinical and Experimental Medicine, Prague, Czech Republic,
d
Pharmacology Department and INSERM U970 Hopital Europeen Georges Pompidou,
Assistance-Publique Hopitaux de Paris, Paris-Derscartes University, France,
e
Department of Hypertension and Diabetology, Medical University of Gdansk,
Gdansk, Poland, fInternal Medicine, Hospital Clinico, University of Valencia, Valencia,
Spain and gIRCCS MultiMedica, Sesto San Giovanni, Milan, Italy
Correspondence to Professor Guido Grassi, Clinica Medica, Università Milano-Bicocca,
Ospedale San Gerardo, Via Pergolesi 33, 20900 Monza (MB), Italy Tel: +39 039 233
3357; fax: +39 039 322 274; e-mail: guido.grassi@unimib.it
Received 21 February 2013 Revised 8 May 2013 Accepted 22 May 2013
J Hypertens 31:2018–2024 ß 2013 Wolters Kluwer Health | Lippincott Williams &
Wilkins.
DOI:10.1097/HJH.0b013e328363823f
Volume 31  Number 10  October 2013

in populations with high cardiovascular risk [18], such as the
ones living in Central and East European countries.
The aim of the present survey was to evaluate the preva-
lence of resistant hypertension, its clinical characteristics and
relationships with the metabolic profile, cardiovascular risk
and end-organ damage in hypertensive patients of Central
and Eastern Europe who participated in the Blood Pressure
rate control and CArdiovascular Risk profilE (BP-CARE)
study [18]. This was a large cross-sectional study carried
out between February 2008 and April 2008, to assess blood
pressure (BP) control and quantify cardiovascular risk in
patients living in nine countries of Central and Eastern
Europe (Albania, Belarus, Bosnia, Czech Republic, Lithuania,
Romania, Serbia, Slovakia and Ukraine).
METHODS
Study population
The BP-CARE study is a large cross-sectional survey whose
design has been described previously [18]. Briefly, the study
was conducted in approximately 8000 treated essential
hypertensive patients undergoing a complete clinical and
laboratory evaluation. No exclusion criteria were applied,
except for the need of patients’ written consent to collect
data, under an obligation to keep them confidentially, as
required by European law. The following information was
obtained from each patient: demographic and anthropo-
metric data (body weight, height and waist circumference,
which were measured in the standing position at the mid-
point between the lower ribs and the iliac crest, BMI being
calculated as the weight in kilograms divided by the square
of the height in meters); personal medical history, with
particular emphasis on previous cardiovascular events (cor-
onary artery disease, heart failure, cerebrovascular event),
presence/absence of diabetes and degree of hypertension
(grade I, II or III) before treatment initiation according to
the 2007 European Society of Hypertension/European
Society of Cardiology (ESH/ESC) guidelines [19], along with
a careful and complete recording of antihypertensive drugs
used (type and dose); recording of lifestyle habits (exercise
habit, cigarette smoking and alcohol consumption); labora-
tory examinations [glycemia, total cholesterol, high-density
lipoprtein (HDL)-cholesterol, triglycerides and plasma cre-
atinine) and data from instrumental examinations if per-
formed within a 12-month period prior to the present
survey. Clinic BP and heart rate values were the average
of three measurements taken after the patient had been
quietly sitting for 15 min. Ambulatory BP monitoring was
performed using validated equipment, set to obtain at least
four readings per hour during day and three readings per
hour during night. At least 70% of the BP measurements had
to be valid.
The diagnosis of resistant hypertension was established
according to the 2007 guidelines of the ESH/ESC [18].
Resistant hypertensive patients were defined as patients
with uncontrolled clinic BP (140/90 mmHg) despite the
implementation of nonpharmacological measures and
the use of the maximum tolerated dose of at least three
classes of antihypertensive drugs including a diuretic, or
patients taking four classes of antihypertensive drugs inde-
pendently of the values of their clinic BP [19]. Patients with
Journal of Hypertension
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Resistant hypertension BP-CARE study
uncontrolled clinic but controlled ambulatory BP (24-h
mean ambulatory BP 130/80 mmHg) were defined as
white-coat hypertensive patients [19]. For each patient,
the definition of the maximum tolerated daily dose of
antihypertensive drugs and the assessment of therapeutic
compliance were left to the physician’s judgment. Presence
of obesity was defined by a value of BMI above 30 kg/m2,
whereas central obesity was defined by a value of waist
circumference at least 102 cm in men and at least 88 cm in
women. Presence of renal failure was defined by personal
medical history and/or by an estimated glomerular filtration
rate below 60 ml/min per 1.73 m2 [Modification of Diet in
Renal Disease formula (MDRD)] [20,21]. Cardiovascular risk
and presence/severity of target organ damage were eval-
uated according to the 2007 ESH/ESC guidelines criteria
[18], whereas detection of the metabolic syndrome was
done according to the Adult Treatment Panel III criteria [22].
Data analysis
From the original study population sample [18], we
excluded patients without a reliable ambulatory BP
monitoring or without a complete and clearly legible case
report form. For the first step of the analysis aimed at
determining the prevalence of resistant hypertension, we
selected true treatment-resistant hypertension patients
(TRH), thereby excluding the pseudo-resistant patients
(white-coat hypertension or noncompliant to treatment;
Fig. 1). Compliance to treatment was assessed by the
general practitioner involved in the BP-CARE project and
in charge of the patient. This was done by checking the
regularity of prescription and/or asking the patients about
the modality of the prescribed drug intake. The second step
of the analysis was to define the clinical features of TRH and
its correlates [14].
The statistical evaluation was performed by analysis of
variance (ANOVA) (for mean values) and by the chi-square
test (for prevalence) with Bonferroni correction. Data were
analyzed before and after adjustment for age and sex
(Cochran–Mentel–Haenszel method for prevalence). To
identify factors independently predicting TRH in the whole
population sample, logistic regression models were used
with stepwise selection (with alpha ¼ 0.05) of the possible
factors involved among those displaying a relationship with
TRH after correction for confounders (age, sex, BMI, waist
circumference, degree of hypertension before treatment
initiation, previous cardiovascular event, heart failure,
metabolic syndrome, cardiovascular risk, target organ dam-
age, total cholesterol, HDL-cholesterol and estimated glo-
merular filtration rate). Data are expressed as mean
SD or
as percentage values. A P value less than 0.05 was taken as
the level of statistical significance. All analyses were per-
formed with SAS software version 9.3 (SAS Institute Inc.,
Cary, North Carolina, USA).
RESULTS
Prevalence of resistant hypertension, controlled
and uncontrolled treated hypertension
Of the 7983 patients enrolled in the main study, 1312 were
eligible for the present analysis. Their mean age was
58.5
11.4 years with 52.6% of men. Mean clinic BP
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Brambilla et al.
Clinic BP ≥ 140/90
and
3 or more drugs including a diuretic
or
4 or more drugs including a diuretic
independently of clinic BP values
Yes
Resistant HT
Ambulatory BP ≥ 130/80
Yes
Compliance to treatment
Yes
Treatment resistant HT
FIGURE 1 Algorithm used for define treatment resistant hypertension. BP, blood pressure; HT, hypertension.
amounted to 146.4
17.8/87.8
9.6 mmHg and mean
24-h ambulatory BP to 137.4
18.0/81.9
10.6 mmHg.
The mean BMI was 29.0
4.5 kg/m2 with a mean waist
circumference value corresponding to 98.5
13.1 cm.
Prevalence of previous cardiovascular events, diabetes,
renal failure and metabolic syndrome was 58.7, 30.1,
21.2 and 69.6%, respectively.
Among the above-mentioned 1312 patients, 423 were
defined at the first analysis as apparent resistant hyper-
tensive patients. One hundred and sixty-eight of them
(12.8% of the total sample), however, were pseudo-
resistant hypertensive patients (70 noncompliant to the
antihypertensive treatment and 98 white-coat hypertensive
patients), whereas 255 (19.4% of the total sample) were
TRH. There were 368 (28.0%) patients with BP values well
controlled by the antihypertensive treatment (controlled
hypertensive patients), with 521 (39.7%) classified as
those with uncontrolled blood pressure values without
characteristics of resistant hypertension (uncontrolled non-
resistant hypertensive patients).
Clinical features of TRH
As expected, the TRH showed clinic and ambulatory BP
values that were higher not only when compared to
controlled hypertensive patients (P < 0.01) but also to
uncontrolled nonresistant hypertensive patients (P < 0.01;
Table 1). Heart rate was slightly higher in TRH as compared
to controlled hypertensive patients, but lower than uncon-
trolled nonresistant hypertensive patients (Table 1). TRH
showed a significantly higher proportion of women, values
of BMI, waist circumference and age, as compared to
controlled hypertensive patients and uncontrolled non-
resistant hypertensive patients (Table 1). Smoking habits
and alcohol consumption were comparable in all the three
groups. Compared to the two other groups, TRH showed a
higher prevalence of grade III hypertension (TRH: 36.5% vs.
2020 www.jhypertension.com
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No Clinic BP ≥ 140/90
Yes No
Uncontrolled HT Controlled HT
No White-coat HT
Pseudoresistant HT
No Noncompliant patient
controlled hypertensive patients: 10.6% and uncontrolled
nonresistant hypertensive patients: 16.8%; P < 0.01), and a
lower prevalence of grade I hypertension before treatment
(TRH: 12.5% vs. controlled hypertensive patients: 36.8%
and uncontrolled nonresistant hypertensive patients:
31.0%; P < 0.01). TRH represented about one-third of those
with grade III hypertension and showed a higher preva-
lence of obesity, central obesity, renal failure, heart failure,
previous cerebrovascular events and diabetes mellitus,
although this latter association did not achieve statistical
significance (Table 1). The prevalence of metabolic syn-
drome in TRH appeared to be the same as in uncontrolled
nonresistant hypertensive patients and slightly higher
(although not significant) than in the controlled hyper-
tensive patient group (Table 1).
Analysis of metabolic parameters showed that, com-
pared to controlled hypertensive patients, TRH were
characterized by significantly higher values of total serum
plasma cholesterol, low-density lipoprotein (LDL)-choles-
terol and HDL-cholesterol (Table 2). Fasting serum glucose
and triglycerides tender to be higher in TRH than in con-
trolled hypertensive patients (Table 2). No significant differ-
ence was observed in the metabolic parameters when TRH
were compared to uncontrolled nonresistant hypertensive
patients. The proportion of treated diabetic patients was
almost identical in the two groups (controlled hypertensive
patients: 83.9 vs. TRH: 82.4%). This was the case also for the
proportion of the population under lipid-lowering drug
treatment (controlled hypertensive patients: 63.1 vs. TRH:
65.1%). Although no difference was observed in plasma
creatinine value, glomerular filtration rate, estimated using
the MDRD formula, showed a tendency to be lower in TRH
as compared to the other two study groups (Table 2).
The evaluation of cardiovascular risk according to the
2007 ESH/ESC guidelines showed that in the TRH group,
the prevalence of the high cardiovascular risk category was
significantly higher as compared to controlled hypertensive
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 Resistant hypertension BP-CARE study

TABLE 1. Anthropometric, demographic, clinical and hemodynamic characteristics of the study population
Controlled Uncontrolled Treatment-resistant
hypertensive hypertensive hypertensive
Variable patients (n ¼ 368) patients (n ¼ 521) patients (n ¼ 255)
Male/female (%) 60.0/40.0 52.4/47.6 48.6/51.4
Age (years) 58.3
10.3 56.3
12.3 61.2
10.6,##
BMI (kg/m2) 27.9
4.3 28.9
4.3 29.9
4.7,##
Waist circumference (cm) 97.4
11.9 97.6
13.3 99.9
13.7,##
Obesity (%) 26.7 38.1 44.0
Central obesity (%) 52.4 55.5 61.6
History of CAD (%) 54.3 43.1 53.9##
History of CHF (%) 4.9 5.7 10.7,#
History of stroke (%) 4.2 3.7 10.3,##
History of TIA (%) 6.1 7.1 16.0,##
History of diabetes mellitus (%) 28.8 29.2 33.3
History of renal failure (%) 13.3 20.0 28.0,#
Metabolic syndrome (%) 64.1 71.6 70.5
Clinic SBP (mmHg) 127.9
3.4 153.2
12.0 157.4
16.9,##
Clinic DBP (mmHg) 79.6
5.8 91.5
7.9 91.8
10.0,
Heart rate (b.p.m.) 70.9
10.4 77.0
10.4 74.3
10.2,##
24-h SBP (mmHg) 124.1
13.2 142.8
14.5 149.5
16.5,##
24-h DBP (mmHg) 76.2
9 85.1
9.6 97.5
9.8,##
24-h heart rate (b.p.m.) 70.3
9.2 75.2
9.7 73.9
10.0,##

Data are expressed as mean
SDs or as percentage values. CAD, coronary arterial disease; CHF, congestive heart failure; TIA, transitory ischemic attack.

P < 0.05 vs. controlled.

P < 0.01 vs. controlled.
#
P < 0.05 vs. uncontrolled.
##
P < 0.01 vs. uncontrolled.

patients and uncontrolled nonresistant hypertensive
patients (Fig. 2). No difference in statistical significance
was observed after data adjustments for age and sex with
the exception of previous stroke or transitory cerebral
ischemia, waist circumference and LDL-cholesterol values.
Estimated glomerular filtration rate remained significantly
lower in TRH as compared to controlled hypertensive
patients (P < 0.05).
True treatment-resistant hypertension patients used a
greater average number of antihypertensive drugs
(3.6
0.7 pills) than the other two groups. Compared to
controlled hypertensive patients and uncontrolled nonre-
sistant hypertensive patients, in the TRH group, there was a
significant increase in the use of all classes of compounds
(Table 3), with the exception of angiotensin-converting
enzyme (ACE)-inhibitors and centrally acting agents. As
far as the use of diuretics in the TRH group is concerned,
two-thirds of the patients used thiazide diuretics followed
by loop diuretics (about one-third of the patients), whereas
antialdosterone drugs were employed only in a small
percentage of patients (about 10%). In more than half of
the cases, thiazide diuretics were given in fixed combi-
nations with other drugs in all the three groups.
In the TRH and uncontrolled nonresistant hypertensive
patient groups, Doppler ultrasound of the carotid arteries
and search for microalbuminuria were less frequently per-
formed than in controlled hypertensive patients (controlled
hypertensive patients: 42.6 vs. TRH: 27.7, and uncontrolled
nonresistant hypertensive patients: 31.4%, P < 0.01; con-
trolled hypertensive patients: 37.5 vs. TRH: 24.7 and uncon-
trolled nonresistant hypertensive patients 22.1%, P < 0.01,
respectively), whereas no differences in performing ECG
and fundoscopy were detected in the last year. Presence of
target organ damage at the level of the heart, vessels or
kidneys was more frequent in TRH than in uncontrolled
nonresistant hypertensive patients and controlled

TABLE 2. Biochemical data of the study population

Controlled Uncontrolled Treatment-resistant
hypertensive hypertensive hypertensive
Variable patients (n ¼ 368) patients (n ¼ 521) patients (n ¼ 255)
Total cholesterol (mg/dl) 202.2
44.2 219.6
49.3 222.7
50.2
LDL-cholesterol (mg/dl) 122.0
39.9 131.6
47.4 132.3
48.5
HDL-cholesterol (mg/dl) 44.4
13.9 50.5
26.5 53.8
30.0
Triglycerides (mg/dl) 176.0
107.5 185.7
117.3 188.7
94.0
Serum glucose (mg/dl) 111.7
41.0 110.2
33.4 114.7
37.1
Plasma creatinine (mg/dl) 1.0
0.5 1.0
0.3 1.1
0.3
eGFR (ml/min per 1.73 m2) 79.9
20.8 76.8
23.1 70.7
19.6,##

Data are expressed as mean
SDs or as percentage values. eGFR, estimated glomerular filtration rate; HDL, high-density lipoprotein; LDL, low-density lipoprotein.

P < 0.05 vs. controlled.

P < 0.01 vs. controlled.
#
P < 0.05 vs. uncontrolled.
##
P < 0.01 vs. uncontrolled.

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Brambilla et al.

Controlled Uncontrolled Treatment-resistant

hypertensives hypertensives hypertensives
1.4% 1.8% 0.8%
5.2%

8.9% 9.9%

20.3%

27.0% 27.4%

62.7% 60.9% 73.7%

FIGURE 2 Cardiovascular risk stratification in patients with controlled, uncontrolled and treatment-resistant hypertension according to the 2007 ESH/ESC guidelines. P value
less than 0.01 for distribution among groups was present before and after adjustments for age and sex. White: low added risk; light gray: moderate added risk; dark gray:
high added risk; black: very high added risk. Percentage of patients belonging to each group is expressed by number. ESH/ESC, European Society of Hypertension/European
Society of Cardiology.

hypertensive patients (74.1 vs. 63.1 and 67.0%). In the
stepwise regression analysis, the independent variable
most closely related to true treatment-resistant hyperten-
sion was found to be the presence of grade III hypertension
before treatment initiation (x2 score ¼ 46.32, P < 0.0001),
followed by age (x2 score ¼ 19.22, P < 0.0001), total cho-
lesterol (x2 score ¼ 9.42, P < 0.01), BMI (x2 score ¼ 8.31,
P < 0.01) and history of heart failure (x2 score ¼ 4.4,
P < 0.05) (Fig. 3). In contrast, detection of target organ
damage did not appear to be a variable significantly related
to true treatment-resistant hypertension.
DISCUSSION
The present study addresses the problem of determining
the prevalence of treatment-resistant hypertension in a
population known for its high cardiovascular risk, such
as the one living in Central and East European countries, by
making use of both clinic and ambulatory BP values [18]. It
also examines in a detailed fashion the main clinical fea-
tures of resistant hypertension, including the association
with cardiometabolic disease and target organ damage. As
far as the prevalence of this clinical condition is concerned,
it should be emphasized that, although at an initial assess-
ment the prevalence seemed greater than that reported in
other populations, the implementation of appropriate
screening and exclusion criteria [14] allowed us to more
precisely define the prevalence of resistant hypertension
with figures similar (or only slightly increased) with those
observed in other studies carried out in North America or
Western Europe [7–13]. This, in our opinion, underlines the
importance of using proper diagnostic approaches (includ-
ing 24-h ambulatory BP measurements) and a proper
algorithm for detecting TRH [14]. Furthermore, in our data-
base, the percentage of severe hypertension was greater in
TRH as compared with the two other groups, although TRH
represented only one-third of the patients with severe
hypertension at diagnosis. This suggests the need for a
greater attention to identify TRH among patients who dis-
play for the first time elevated BP values.
The data of our study confirm in East European popu-
lations the relationships, already seen in other studies
[7–13], between true treatment-resistant hypertension
and other conditions characterized by a high or very
high cardiovascular risk such as age, obesity and
history of previous cardiovascular events (heart failure,

TABLE 3. Antihypertensive treatment of the study population

Controlled Uncontrolled Treatment-resistant
hypertensive hypertensive hypertensive
Variable patients (n ¼ 368) patients (n ¼ 521) patients (n ¼ 255)
Mean number drugs (n) 2.2
0.8 2.0
0.8 3.6
0.7,##
Lifestyle modifications (%) 86.2 89.1 91.0
ACE-inhibitors (%) 64.9 66.4 73.3
Beta-blockers (%) 63.3 54.1 72.5,##
Angiotensin receptor antagonists (%) 13.9 11.9 28.2,##
Calcium antagonists (%) 42.7 43.4 67.1,##
Diuretics (%) 31.5 14.7 100.0,##
Alpha-blockers (%) 2.4 2.9 6.7,#
Centrally acting drugs (%) 1.9 3.6 5.5

Data are expressed as mean
SDs or as percentage values. ACE, angiotensin-converting enzyme.

P < 0.05 vs. controlled.

P < 0.01 vs. controlled.
#
P < 0.05 vs. uncontrolled.
##
P < 0.01 vs. uncontrolled.

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Variable Unit
Grade III vs. grade I hypertension
Age Year
Total cholestrol mg/dl
Body mass index kg/m2
History of heart failure No vs. Yes
0.5
FIGURE 3 Odds ratios (ORs) for the factors associated with treatment-resistant hypertension in the stepwise analysis. CI, confidence interval.
cerebrovascular events), although the relationships with
stroke and transient ischemic attack was no more detectable
following data adjustment for age and sex. We also
observed a relationship between renal failure and true
treatment-resistant hypertension, a finding that may reflect
the greater difficulty in the achievement of the therapeutic
BP goals in the presence of a reduction in the glomerular
filtration rate. The design of our study, however, did not
allow us to determine the possible cause–effect relation-
ships between true treatment-resistant hypertension and
several high-risk conditions mentioned above. It also pre-
vented us to determine the pathophysiological mechanisms
responsible for this relationship, although the hypothesis
can be advanced that the hyperadrenergic state character-
izing true treatment-resistant hypertension [23] may
represent the factor that, in association with other hemo-
dynamic or nonhemodynamic mechanisms, is involved in
the above-mentioned cardiovascular complications. The
presence of these concomitant conditions and the persist-
ent elevation of BP values potentiate the cardiovascular risk
of the TRH [24], making it much higher than the one
detectable in the other two groups and justifying the need
for paying particular attention to this condition [25].
Several other results of our study deserve to be briefly
discussed. First, the analysis of the use of specific drugs
shows that antialdosterone compounds are less frequently
prescribed in the setting of true treatment-resistant hyper-
tension as compared with what was observed in other
studies [7–9]. Another problem is the use of inadequate
doses of diuretics, especially when these drugs are part of
fixed combinations. A low dose of a diuretic could be
insufficient to counteract the sodium retention typical of
different conditions, such as obesity and chronic renal
failure, often associated with true treatment-resistant hy-
pertension [7–13]. Second, treated hypertensive patients
whose BP is not adequately controlled by antihypertensive
therapy (uncontrolled nonresistant hypertensive patients)
appear to be under a smaller number of antihypertensive
drugs as compared to what seen in treated patients with
well controlled BP values. This may suggest that one of the
reasons for the lack of achieving BP targets in treated
hypertensive patients is the therapeutic inertia [26]. Finally,
in the multivariate analysis, the factor most closely related to
true treatment-resistant hypertension is higher initial BP
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Resistant hypertension BP-CARE study
Or (95% Cl) Or 95% Cl P value
3.171 2.008–5.008 <0.0001
1.033 1.018–1.049 <0.0001
1.005 1.002–1.007 <0.01
1.048 1.016–1.082 <0.01
1.73 1.033–2.898 <0.05
1 2 5 10
values followed by advanced age, increase in total choles-
terol, elevated BMI and history of heart failure, but not
presence of target organ damage.
The present study has a number of limitations. First, the
prevalence of true treatment-resistant hypertension could
have been overestimated due to the lack of information
related to sleep apnea syndrome which is frequently detect-
able in resistant hypertension especially considering the
high prevalence of obesity [5,14,16]. Second, general prac-
titioners and specialists involved in this survey were highly
motivated, often working in university hospitals, and this
may have resulted in a higher chance to recruit TRH,
contributing with the above-mentioned factor to the over-
estimation of the prevalence of true treatment-resistant
hypertension. Third, the method we used in the present
study to assess compliance to drug treatment was by no
means optimal, as it was based on the physician’s judge-
ment of the patient’s adherence to treatment. This might
have led to an underestimation of the true prevalence of
pseudo-resistant hypertension in the BP-CARE population.
Finally, although almost all recruited patients had an ECG or
a fundoscopic examination, a substantial fraction of
patients (about two-thirds) did not have a carotid ultra-
sound or microalbuminuria estimation in the year before
the evaluation. The lack of information about vascular and
renal target organ damage might have led to an under-
estimation of the cardiovascular risk of these patients,
particularly in the TRH group.
ACKNOWLEDGEMENTS
Funding: The BP-CARE study was supported by an unre-
stricted grant by Menarini International.
Conflicts of interest
There are no conflicts of interest.
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Reviewers’ Summary Evaluations
Reviewer 1
Strengths: Survey in a population not previously subject to
scrutiny with regard to the characteristics and prevalence of
patients with true resistant hypertension (TRH). Also,
robust criteria for definition of TRH, including ABPM.
Weaknesses: Reliance on interview data for confirmation
of compliance with prescribed medication.
2024 www.jhypertension.com
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
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G, et al. Management of Arterial Hypertension of the European Society
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fication of Diet in Renal Disease formula for estimating GFR with
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2497.
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25. Gupta AK, Nasothimiou EG, Chang CL, Sever PS, Dahlöf B, Poulter NR,
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26. Glynn LG, Murphy AW, Smith SM, Schroeder K, Fahey T. Interventions
used to improve control of blood pressure in patients with hyperten-
sion. Cochrane Database Syst Rev 2010; 3:CD005182.
Reviewer 2
Strengths: The study reports the prevalence of true resistant
hypertension in Central and Eastern Europe; assesses its
main clinical features in association of cardiometabolic
disorders and a very high cardiovascular risk of resistant
hypertension.
Weaknesses: The compliance to drug treatment of
hypertensive patients was assessed by asking the patient
about drug assumption.
Volume 31  Number 10  October 2013