Download Orthostatic Hypotension in Treated Hypertensive Patients

Orthostatic Hypotension in Treated Hypertensive Patients
JESSICA BAROCHINER, J. ALFIE, L. APARICIO, M. RADA, MARGARITA MORALES,
PAULA CUFFARO, C. GALARZA, G. WAISMAN
Hypertension Section, Internal Medicine Department, Hospital Italiano de Buenos Aires
Introduction. Orthostatic hypotension (OH) is a risk factor for morbidity and mortality and
one of the causes of non compliance to treatment among medicated hypertensive subjects. Our
objective was to assess the prevalence of OH among treated hypertensive patients and its association
with clinical characteristics and antihypertensive drug class.
Methods. This was a cross-sectional study in which we assessed the prevalence of OH, defined
according to the American Autonomic Society and American Academy of Neurology guidelines,
among adult treated hypertensive patients who performed a home blood pressure monitoring at our
institution. We also determined the prevalence of OH according to age group (< 65, 65-79 and > 80),
antihypertensive drug class, office and home hypertension control status.
Results. We included 302 medicated patients in the study. Mean age was 66.6(+13.8), 67%
were women. We found a 9.7% global prevalence of OH, which was significantly higher among older
individuals (3.6% among patients < 65 years-old, 12.2% in the 65-79 year-old group and 16.7%
among octogenarians, p = 0.02) and those who consumed alpha-blockers (75 vs. 8.5%, p < 0.01).
Uncontrolled hypertensive patients at office and/or at home had also a significantly higher prevalence
of OH: uncontrolled vs. controlled office blood pressure (BP), 14.3 vs. 6.5%, p = 0.03 and
uncontrolled vs. controlled home BP, 15.1 vs. 6.6%, p = 0.02. Remarkably, 64% of patients with OH
had their BP under control when considering office-standing BP.
Conclusion. OH is a prevalent entity among treated hypertensive patients and systematic
measurement of standing BP should be mandatory in the evaluation of these patients.
Key words: Orthostatic hypotension, prevalence, hypertension, medication, home blood
pressure monitoring.
Orthostatic hypotension (OH) is a phenomenon
in which postural hemodynamic homeostasis is not
preserved, leading to a significant blood pressure
drop [1], which in turn may cause falls, syncope
and functional impairment [2][3]. Moreover, in the
last years OH has been identified as an independent
risk factor for cardiovascular morbidity, including
stroke and coronary heart disease, and all-cause
mortality [4-9].
On the other hand, hypertension is an agerelated disease [10], expected to increase as worldwide population ages, and previous studies have
shown that OH is also related to age [11][12],
rendering hypertension management in this expanding
group of already fragile elderly individuals more
complex.
International hypertension guidelines state
that hypertension is scantly controlled all over the
world and lack of compliance with treatment is a
major factor accounting for this phenomenon [1315]. This could be due in part to adverse effects
related to antihypertensive drugs, orthostatic hypotension being one of them [16]. Thus, ascertaining
ROM. J. INTERN. MED., 2012, 50, 3, 203–209
the prevalence of OH among medicated hypertensive patients and establishing associated factors
is of capital importance to improve hypertension
management.
The purpose of this study was to assess the
prevalence of orthostatic hypotension among patients
under antihypertensive treatment and its association
with clinical characteristics and antihypertensive
drug classes.
MATERIALS AND METHODS
Selection of patients
This was a cross-sectional study that included
hypertensive patients 18 years or older receiving
antihypertensive treatment, who came to our institution to perform a Home Blood Pressure Monitoring
(HBPM) indicated by their treating physician. All
patients that accepted to participate in the study
gave written informed consent and completed a
questionnaire regarding risk factors (diabetes,
smoking status, sedentary lifestyle, family history
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of cardiovascular disease), history of cardiovascular
disease (coronary heart disease, cerebrovascular
disease, peripheral artery disease) and antihypertensive –drug consumption (class and number).
Sedentary lifestyle was defined as physical
activity with a frequency <1 times per week;
coronary heart disease was defined as a history of
myocardial infarction, unstable angina, chronic
stable angina or coronary by-pass surgery; cerebrovascular disease was defined as a history of stroke
or transient ischemic attack; and peripheral artery
disease, as intermittent claudication, abnormal arterial
doppler or peripheral revascularization in the lower
limbs.
Anthropometric and blood pressure
measurement
We assessed weight, height and waist circumference for all patients and subsequently measured
blood pressure (BP) twice in the non-dominant
arm, two minutes apart, with a validated automated
oscillometric device Omron 705 CP (Omron Corp.,
Tokyo, Japan), after a five minute rest with the
patient in a sitting position, and using an appropriate
cuff size according to the arm circumference. We
then measured BP with the same device after the
patient was standing for two minutes and repeated
the reading after two more minutes, always with
the arm supported at heart level.
Home Blood Pressure Monitoring (HBPM)
Patients returned home with the oscillometric
device after appropriate training in its use and
registered duplicate blood pressure readings (two
minutes apart) in the non-dominant arm for four
days, in the morning (before breakfast and medication), afternoon and evening. First day-measurements were discarded from analysis. Patients with
less than 16 home blood pressure readings were
excluded from analysis.
Definition of orthostatic hypotension (OH),
office and home hypertension control status
Orthostatic hypotension was defined as a BP
fall from sitting to standing position of >20 mmHg
for systolic BP or >10 mmHg for diastolic BP,
considering the average of the two readings (at
minute 2 and 4).
We considered hypertension was under
control at office when the average of the two sitting
measurements was < 140/90 mmHg; and at home
2
when the average of all measurements (discarding
first day) was < 135/85 mmHg.
Statistical analysis
We determined the prevalence (%) of OH in
the study population and compared clinical
characteristics of patients with and without OH,
using chi-square test for categorical and Student T
test for continuous variables. A p-value <0.05 was
considered as statistically significant.
We also assessed the prevalence of OH by
age-group: 65 years-old, 65-79 years-old and >80
years-old, by antihypertensive drug class, and by
hypertension control status at office and at home.
RESULTS
Among 302 medicated patients included in
the study, 13 had insufficient home blood pressure
readings, so 289 patients were included in the
analysis, 67% women, with an average age of 66.6
(+13.8) years-old. Global prevalence of OH was
9.7%. Patients with OH were significantly older,
consumed more antihypertensive drugs and had a
higher systolic BP at office and home compared to
those without OH (Table I).
According to age-group, prevalence of OH
was 3.6% among patients younger than 65 yearsold, 12.2% in the 65-79 year-old group and 16.7%
among octogenarians, p = 0.02.
Regarding antihypertensive drug class,
prevalence of OH was significantly higher among
those treated with alpha-blockers: 75 vs. 8.5%, p <
0.01. Prevalence of OH was not significantly higher
for other antihypertensive drug classes (Fig. 1).
Finally, orthostatic systolic BP variation
(sitting BP – standing BP) showed a significant
correlation with office sitting-systolic BP (Fig. 2).
Moreover, prevalence of OH was significantly
higher in patients with uncontrolled hypertension at
office (14.3 vs. 6.5%, p = 0.03) and at home (15.1
vs. 6.6%, p = 0.02) (Fig. 3). Remarkably, although
a minority of patients (28.6%) with OH had their
hypertension under control considering sitting BP,
the proportion of patients with OH that had their
hypertension controlled (< 140/90 mmHg at office)
increased to 64.3% taking into account standing
BP. Interestingly, when we analyzed quintiles of
standing systolic blood pressure, 39.3% of patients
with OH belonged to the lowest quintile, i.e.
standing systolic blood pressure < 117.5 mmHg
(Fig. 4).
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Orthostatic hypotension in treated hypertensive patients
205
Table I
Participant characteristics
Total
With OH
Without OH
289 (100%)
28 (9.7%)
261 (90.3%)
Women (%)
67.5
82.1
65.9
NS
Age (+SD)
66.6 (+13.8)
73.8 (+13.4)
65.8 (+13.6)
0.003
BMI (+SD)
28.4 (4.6)
26.9 (3.9)
28.6 (4.7)
NS
Waist circumference (+SD)
96.3 (12.4)
93 (9.6)
96.7 (12.7)
NS
2.1 (0.9)
2.4 (0.9)
2.1 (0.9)
0.049
Current smokers (%)
4.8
7.1
4.6
NS
Diabetes (%)
8.3
14.3
7.7
NS
Sedentary lifestyle (%)
49.8
39.3
51
NS
History of ischemic Heart disease (%)
4.8
10.7
4.2
NS
History of cerebrovascular disease (%)
5.5
3.6
5.7
NS
History of peripheral artery disease (%)
4.2
3.6
4.2
NS
Family history of cardiovascular disease (%)
55.7
57.1
55.6
NS
Office sitting-systolic BP (mmHg) (+SD)
137.2 (18.35)
146.79 (20.63)
136.17 (17.83)
0.003
Office sitting-diastolic BP (mmHg) (+SD)
77.39 (10.39)
78.25 (11.84)
77.29 (10.25)
NS
Office standing systolic BP (mmHg) (+SD)
133.79 (17.57)
129.18 (20.27)
134. 29 (17.23)
NS
Office standing diastolic BP (mmHg) (+SD)
78.59 (10.28)
71.12 (10.55)
79.39 (9.94)
<0.001
3.41 (9.84)
17.61 (12.13)
1.89 (8.24)
<0.001
-1.21 (6.49)
7.14 (7.39)
-2.1 (5.72)
<0.001
130.74 (14.21)
137.36 (15.75)
130.03 (13.88)
0.01
72.89 (8.68)
69.79 (11.21)
73.23 (8.32)
NS
n (%)
p-value
Demographic characteristics
Number of antihypertensive drugs (+SD)
Risk factors or history of cardiovascular disease
Blood pressure profile
Orthostatic systolic BP variation (sitting systolic BPstanding systolic BP) (mmHg; +SD)
Orthostatic diastolic BP variation (sitting diastolic
BP-standing diastolic BP) (mmHg; +SD)
Home systolic BP (mmHg; +SD)
Home diastolic BP (mmHg; +SD)
BMI: body mass index; BP: blood pressure; NS: non-significant; OH: orthostatic hypotension.
Fig. 1. Prevalence of orthostatic hypotension (OH) according to antihypertensive drug class.
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Fig. 2. Correlation between orthostatic systolic blood pressure (BP) variation and office sitting systolic BP.
Fig. 3. Prevalence of orthostatic hypotension (OH) according to hypertension control status.
Fig. 4. Distribution of patients with orthostatic hypotension (OH) according to standing systolic blood pressure (BP) quintile.
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Orthostatic hypotension in treated hypertensive patients
DISCUSSION
We found in our study a global 9.7% prevalence of orthostatic hypotension (OH). Patients
with OH were significantly older and their hypertension was significantly uncontrolled compared to
patients without OH. Regarding antihypertensive
drug classes, patients with OH were more
frequently receiving alpha-blockers. Several studies
have assessed the association between anti-hypertensive drugs and OH, with contrasting results [1719]. One limitation of our study is that we did not
consider subtypes of drugs among classes, for
example, second versus first-generation betablockers or different types of diuretics. Although
from a pathophysiological point of view it is
reasonable to consider all-class diuretics as a
common cause of OH, some studies, including this
one, have failed to demonstrate this association
[17][20]. In our case there was a tendency towards
such an association, without reaching statistical
significance. This could be due to a low statistical
power. OH is a well-known side-effect related to
alpha-blockers, especially in older patients, and this
was consistent with our findings and with other
studies assessing this subject [21][22]. Even though
alpha-blockers are not first-line drugs for hypertension treatment, they are usually used in prostatic
hyperplasia, a prevalent condition among elder
men [23][25].
We failed to find, consistently with other
studies [11][18], an association between OH and
diabetes, an entity in which autonomic dysfunction
has been well documented. One possible explanation
is that diabetes was recently diagnosed or was wellcontrolled among our patients. We do not have
information on the possible presence of diabetic
neuropathy in our population.
Another finding of our study was an association
between age and OH, which has been previously
described, with a significant higher prevalence of
OH in elderly and very elderly individuals
compared to younger ones [26]. We also found, in
accordance with previous studies [12][27], that OH
was more often present among patients with
uncontrolled hypertension. These two findings
underlie the existence of a group of patients who
207
are extremely fragile: on the one hand, they are
older and more exposed to medication related sideeffects; on the other hand, they would probably
receive more drugs on the basis of office or home
sitting-high blood pressure. In has been suggested
that physicians need not to be afraid of intensively
treating such patients, as a better BP control would
reduce the likelihood of developing OH [28]. In
our opinion, the finding that OH is more prevalent
in sitting uncontrolled hypertensive patients is a
strong argument to systematically measure standing
BP in all uncontrolled hypertensives, especially
older patients. Such a simplistic approach will
probably prevent over-medication in vulnerable
patients. In support to this opinion, we found in our
population that more than 60% of patients with OH
had their hypertension under control when
considering standing BP. Moreover, more than one
third of these patients belonged to the lowest
quintile of systolic BP, i.e. standing systolic BP
<117.5 mmHg. If only sitting BP is taken into
account, a more aggressive treatment would probably
worsen OH and its clinical consequences, such as
falls, syncope, functional impairment, hospitalizations and cardiovascular morbidity and mortality.
Data relating OH and home blood pressure
are limited and, in that sense, our study contributes
to establish that a similar phenomenon is seen at
office and at home: a higher prevalence of office
OH in uncontrolled hypertensive subjects. Lack of
measurement of standing BP at home constitutes a
limitation of our study.
Home blood pressure monitoring is becoming
a useful and expanding tool to assess hypertension
control and has shown to be a better predictor of
target organ damage and cardiovascular outcomes
than office BP [29][32]. Thus, we feel that
prospective studies designed to assess predictive
factors of uncontrolled hypertension at home
among individuals with OH should be performed in
order to assess this issue.
In conclusion, OH is a prevalent entity in
treated hypertensive patients, especially elderly and
very elderly who receive alpha-blockers and those
in which hypertension is uncontrolled. Systematic
measurement of standing BP should be an essential
part of the evaluation of medicated hypertensives.
Hipotensiunea arterială ortostatică (hTAO) este un factor de risc pentru
morbiditate şi mortalitate şi una dintre cauzele de neconformitate la tratament,
printre subiecţi trataţi cu medicamente hipertensive.
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Jessica Barochiner et al.
6
Obiectivul nostru a fost de a evalua prevalenţa în rândul pacienţilor trataţi
cu medicamente hipertensive şi asocierea lor cu caracteristicile clinice şi clasa de
medicament antihipertensiv.
Metode. Acesta a fost un studiu transversal în care am evaluat prevalenţa
hipotensiunii arteriale ortostatice, definite conform Societăţii Americane şi
Academiei Americane de Neurologie, liniile directoare, printre pacienţi adulţi
trataţi cu medicamente hipertensive în care presiunea arterială a fost monitorizată
acasă şi în instituţia noastră. Am stabilit, de asemenea, prevalenţa hipotensiunii
ortostatice în funcţie de grupa de vârstă ( <65, 65-79 şi >80), clasa de
medicamente antihipertensive; la birou şi acasă; hipertensiune statutul de
control.
Rezultate. Am inclus 302 de pacienţi, cu medicaţie în studiu. Vârsta medie a
fost de 66.6 (13.8), 67% dintre pacienţi au fost femei. Am găsit o prevalenţă de 9.7
la nivel mondial a hipotensiunii ortostatice, care a fost semnificativ mai mare în
rândul persoanelor mai în vârstă (3.6% în rândul pacienţilor cu vârsta de sub
65 de ani; 12.2% la pacienţii cu vârste cuprinse între 65-79 de ani, şi de 16.7% în
rândul pacienţilor cu vârsta peste 80 ani; p = 0.02 şi cei care au consumat alfablocante (75 faţă de 8.5%, p < 0.01). Pacienţii hipertensivi cu TA necontrolată, la
birou şi/sau la domiciliu au avut, de asemenea, o prevalenţă semnificativ mai mare
de hipotensiune ortostatică necontrolată faţă de tensiunea arterială controlată de
la birou, de 14.3 faţă de 6.5%, p = 0.03 şi acasă tensiunea arterială ortostatică
necontrolată faţă de tensiunea arterială controlată, de 15.1 faţă de 6.6%, p = 0.02.
De remarcat că 64% dintre pacienţii cu hipotensiune arterială ortostatică au avut
la birou – tensiune arterială sub control.
Concluzie. Hipotensiunea arterială ortostatică este o entitate răspândită
printre pacienţii hipertensivi trataţi şi măsurarea sistematică a tensiunii arteriale
ar trebui să fie obligatorie în evaluarea acestor pacienţi.
Corresponding author: Dr. Jessica Barochiner
Postal address: Juan D. Perón 4190 (C1181ACH) Buenos Aires, Argentina. Phone number: (5411)4959-0200
Fax number: (5411)4958-4454
E-mail address: [email protected]
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Received August 1st, 2012