Hypertension and depression

Clinics vol.60 no.3 So Paulo June 2005

By Andria Zavaloni Scalco
I
; Mnica Zavaloni Scalco
II
; Joo Batista Serro Azul
III
;
Francisco Lotuo !eto
I
I
Psychiatry Institute, Hospital das Clnicas, Faculty of Medicine, University of So Paulo
So Paulo/SP, ra!il
II
"epart#ent of Psychiatry, University of $oronto $oronto/%ntario, Canada
III
Heart Institute, Hospital das Clnicas, Faculty of Medicine, University of So Paulo So
Paulo/SP, ra!il& '(#ail) ascalco*usp&+r
Ini lin, -e+site nya)
http://www.scielo.br/scielo.php?pid=S1807-
59322005000300010&script=sci_arttet
!"#$% '( )*"+", -
ABS"#A$"
"espite the hi.h prevalence of depression and hypertension, the relationship +et-een the
t-o diseases has received little attention& $his paper revie-s the epide#iolo.ical,
pathophysiolo.ical, and pro.nostic aspects of this association, as -ell as its i#plications
for treat#ent& / Medline search -as conducted usin. the follo-in. ,ey -ords) depression,
+lood pressure, +lood pressure varia+ility, physical #or+idity, hypertension, #ood, stress,
hypertension, antidepressive a.ents, and .enetics, fro# 0123 to 4335& 6e found
descriptions of increased prevalence of hypertension in depressed patients, increased
prevalence of depression in hypertensive patients, association +et-een depressive
sy#pto#atolo.y and hypotension, and alteration of the circadian variation of +lood
pressure in depressed patients& $here is considera+le evidence su..estin. that
hyperreactivity of the sy#pathetic nervous syste# and .enetic influences are the
underlyin. #echanis#s in the relationship +et-een depression and hypertension&
"epression can ne.atively affect the course of hypertensive illness& /dditionally, the use of
antidepressive a.ents can interfere -ith +lood pressure control of patients -ith
hypertension +y inducin. chan.es in +lood pressure and orthostatic hypotension&
%ey&ords' "epression& Cardiolo.y& Hypertension& lood pressure& /ntidepressive a.ents&
#(S)M*
/pesar das altas preval7ncias de hipertenso arterial sist7#ica e de depresso, o estudo
da rela8o entre depresso e presso arterial te# rece+ido pouca aten8o da literatura&
9esse arti.o so revisados os aspectos epide#iol:.icos, patofisiol:.icos, pro.n:sticos e
i#plica8;es no trata#ento, relacionados < associa8o entre depresso e hipertenso
arterial sist7#ica& % #=todo utili!ado foi consulta ao +anco de dados +i+lio.r>ficos
Medline, utili!ando(se as palavras chave depression, blood pressure, blood pressure
variability, physical morbidity, hypertension, mood, stress, hypertension, antidepressive
agents e genetics, no perodo de 0123 a 4335& 'ncontra#os descri8;es de preval7ncia
au#entada de hipertenso e# pacientes depri#idos, preval7ncia au#entada de
depresso e# pacientes hipertensos, associa8o entre sinto#atolo.ia depressiva e
hipotenso e altera8o da varia8o circadiana da presso arterial de pacientes depri#idos&
/credita(se ?ue #ecanis#os envolvendo hiperatividade de siste#a nervoso si#p>tico e
influ7ncias .en=ticas possa# ser a +ase fisiopatol:.ica da rela8o entre depresso e
hipertenso arterial sist7#ica& /l=# disso, a presen8a de depresso pode piorar o curso
da doen8a hipertensiva, e o uso #edica8;es antidepressivas pode indu!ir au#ento de
presso arterial, di#inui8o de presso arterial e hipotenso ortost>tica, dificultando o
#ane@o de pacientes co# hipertenso arterial sist7#ica&
)niter+os' "epresso& Cardiolo.ia& Hipertenso& Presso arterial& /ntidepressivos&


Several studies have focused on the association +et-een depression and cardiovascular
diseasesA ho-ever, the relationship +et-een depression and hypertension has received
less attention& 9evertheless, interactions +et-een +lood pressure BPC and psychic factors
have +een o+served& %DHare o+served that +y as,in. hypertensive patients to tal, a+out
health pro+le#s or other life stresses, he could induce su+stantial increases in their P,
and -hile after restin. ?uietly for 43 to 53 #inutes, they had lar.e drops in P&
0
%ver the
neEt several decades, these o+servations -ere replicated #any ti#es +y other
investi.ators -ho also found that P #easure#ents +y a doctor are fre?uently
acco#panied +y #ar,ed increased P and heart rate BHFC& $his increase Bna#ed the
G-hite(coatG effectC is ?uite co##on and is +elieved to +e a conse?uence of an anEiety
response to the doctorDs visit&
4
Since +oth hypertension and depression are hi.hly prevalent, it is eEtre#ely i#portant to
+etter understand the relationship +et-een the#&

M("H*,
$his paper revie-s the epide#iolo.ical, pathophysiolo.ical, and pro.nostic aspects of the
association +et-een hypertension and depression, as -ell as its i#plications for
treat#ent& $he #ethod -as a Medline search, -hich -as conducted usin. the follo-in.
,ey -ords) depression, +lood pressure BPC, +lood pressure varia+ility BPHC, physical
#or+idity, hypertension, #ood, stress, hypertension, antidepressive a.ents, and .enetics,
fro# 0123 to 4335&

#(S)L"S
(pide+iolo-ics aspects
oth hypertension and hypotension have +een o+served in association -ith depression or
depressive sy#pto#s&
Hypertension in depressive patients
/n increased prevalence of hypertension in depressed patients has +een descri+ed +y
/da#is and all&
I
$hey studied the co#or+idity +et-een psychiatric and physical diseases
in JK elderly psychiatric inpatients, and found that depressed patients had #ore
cardiovascular diseases and hypertension than other psychiatric patients&
I
9a,a.a-ara et
al&
5
also found an increased fre?uency of hypertension in depressed patients, +ut only in
those -ith #elancholic features&
/ depressive #ood has also +een associated -ith hi.her P levels,
K,L
+ein. positively
associated -ith hi.her levels of systolic P BSPC and diastolic P B"PC in 45(hour P
#onitorin. of K5 su+@ects over J days&
K
/dditionally, si.nificantly hi.her P -as found in
0K su+@ects -ith a clinical dia.nosis of depression&
K
Prospective studies have also su..ested that depression #ay +e a ris, factor for the
develop#ent of hypertension& In a study of 4114 nor#otensive su+@ects B4K to L5 yearsC
-ho -ere follo-ed for L to J years, to evaluate the prospective association +et-een
depressive sy#pto#s and develop#ent of hypertension, hi.h scores of depressive
sy#pto#s dou+led the ris, for hypertension, defined as a P of 0L3/1K ## H. or over, or
a prescription of antihypertensive #edications&
J
Sy#pto#s of depression and anEiety, #easured +y the Meneral 6ell(ein. Schedule -ere
also associated -ith elevated ris, of incident hypertension Bn N II03C, and this effect -as
#ore pronounced in +lac, -o#en BFF N I&04A 1KO CI N 0&45(J&22C co#pared to -hite
-o#en BFF N 0&JIA 1KO CI N 0&I3(4&I3C or #en BFF N 0&KLA 1KO CI N 0&32(4&4KC&
2
Depression in hypertensive patients
Increased prevalence of depression has +een descri+ed in hypertensive patients as -ell&
Fa+,in et al& found a I(fold hi.her fre?uency of #a@or depression in patients treated for
hypertension&
1
Hopelessness -as associated -ith increased incidence of hypertension in L0L initially
nor#otensive #en, in a 5(year follo-(up prospective study in Finland& Men reportin. hi.h
levels of hopelessness at +aseline -ere I ti#es #ore li,ely to +eco#e hypertensive than
#en -ho -ere not hopeless, after ad@ust#ents for a.e, +ody #ass indeE, +aseline restin.
P, physical activity, s#o,in., alcohol consu#ption, education, and parental history of
hypertension&
03
Hypotension and Depression
Conversely, the concept of a Ghypotensive syndro#eG e#er.ed in the 0123s& It consisted
of so#atic sy#pto#s such as tiredness, di!!iness, headaches, -ith occasional #inor
psychiatric sy#pto#s such as anEiety and depression&
00
9u#erous treat#ents -ere tried,
ran.in. fro# har#less tonics to di.oEin, a#pheta#ine, and er.ota#ine& %ther associated
sy#pto#s included .eneral fati.ue, overeEertion, psychoso#atic sy#pto#s, readiness to
cry, feelin. scared and panic,y, feelin. under strain, una+le to en@oy nor#al activities, and
una+le to concentrate&
00(05
Several authors su..ested that a pri#ary psychiatric disorder
such as depression could account for the sy#pto#s of the syndro#e and could +e related
to lo- P as -ell&
$here are also recent descriptions of lo- P associated -ith depressive sy#pto#s& In a
study of 4J4I elderly persons livin. in the co##unity, hypotension -as associated -ith
increased depressive sy#pto#atolo.y, after ad@ust#ents for a.e, .ender, and
prescriptions for antihypertensives& Hypotensive su+@ects also had lo-er self(estee#&
0K
/n inverse relationship +et-een lo- diastolic P B"PC and depressive sy#pto#s -as
de#onstrated in a populational study -ith 25L elderly #en -ithout a psychiatric
dia.nosis& Hi.her levels of depressive sy#pto#s and #ore dia.nosis of depression -ere
found in those su+@ects -ith "P PJK ## H.& Men -ith diastolic hypertension had #ore
affective and so#atic sy#pto#s, such as fati.ue, pessi#is#, sadness, and loss of
appetite, -ei.ht loss, and preoccupation -ith health&
0L
Abnormal Circadian Blood Pressure Regulation
/+nor#al circadian P re.ulation has +een associated -ith depression&
0J
"epressive
sy#pto#s -ere associated -ith a hi.her ni.ht/day systolic P BSPC ratio in 04L #en -ho
-ere -ithout psychiatric diseases and #edication(free&
0J
/utono#ic nervous syste#
dysfunction and a+nor#al hor#onal re.ulation have +een hypothesi!ed to eEplain the
results&
0J
In another study, self(reported depression -as associated -ith hi.her SP and "P
#easure#ents and lo-er day/ni.ht P ratios&
02
9evertheless, 45 h +lood pressure #onitorin. revealed an increased #ean 45 h SP +ut
nor#al ni.htti#e P level in a su+stantial su+.roup of depressed inpatients, resultin. in a
hi.h day/ni.ht P ratio& $he su+@ects had no hypertension +ut presented #ore
cardiovascular reactivity durin. the day and difficulty in fallin. asleep in the evenin.&
01

/dditionally, less effective P re.ulation in response to an orthostatic challen.e has +een
associated -ith depression in II su+@ects&
43
/nother indicator of poor P re.ulation in depressive patients -as the lar.er postprandial
drop in systolic P detected +y Sch-art! et al&
40
$here are also studies that failed to find an association +et-een depression and P& 9o
si.nificant differences in P -ere found +et-een depressed and nondepressed psychiatric
inpatients Bn N 035LC&
44
$he C/F"I/ Study B011LC eEa#ined cross(sectional relationships
a#on. depressive sy#pto#s, anEiety, alcohol inta,e, and +lood pressure in a sa#ple of
5IK4 adults and found that depressive sy#pto#s and anEiety -ere unrelated to P&
4I
.at/op/ysiolo-y
Depression and Autonomic Nervous System (ANS
$he physiolo.ical #echanis#s underlyin. the relationship +et-een depression or anEiety
and P pro+a+ly involve the effect of the sy#pathetic nervous syste#&
4I,45
"ata availa+le at present sho- that sy#pathetic activation is a specific feature of essential
hypertension, and it #ay play a patho.enic role in this disease& / #etanalysis sho-ed
that plas#a noradrenaline, as an indirect #ar,er of sy#pathetic tone, -as elevated in
patients -ith essential hypertension&
4K
In addition, it -as sho-n that the rate of
noradrenaline spillover fro# sy#pathetic nerve ter#inals -as so#eti#es increased in
essential hypertension&
4L
/dditional data have e#er.ed fro# direct #easure#ents of
sy#pathetic nerve traffic to s,eletal #uscle circulation usin. a #icroelectrode techni?ue
B#icroneuro.raphyC& Most studies usin. this #ethod have de#onstrated increased
sy#pathetic nerve activity in patients -ith essential hypertension& In contrast, patients
-ith secondary hypertension did not differ fro# nor#otensive patients&
4L
$here is also reported evidence sho-in. a+nor#al autono#ic nervous syste# function in
depression, specifically re.ardin. increased sy#pathetic activity and poor va.al control&
Several studies have eEa#ined cere+rospinal fluid BCSFC, plas#a or urinary levels of
norepinephrine B9'C and its #a@or central nervous syste# #eta+olite, I(#ethoEy(5(
hydroEyphenyl.lycol BMHPMC& Plas#a 9' and/or MHPM levels have +een reported to +e
elevated in depressive patients&
4J(I3
9orepinephrine -as si.nificantly elevated in
depressive patients co#pared -ith controls, althou.h the rate of 9' clearance fro#
plas#a -as si#ilar in +oth .roups&
I0
Maes et al& #easured the 45 h urinary eEcretion of
noradrenaline B9/C, adrenaline B/C, dopa#ine B"/C, and MHPM in depressed su+@ects&
$here -ere si.nificant positive correlations +et-een sleep disorders and 9/, /, and "/
eEcretion& $he eEcretion of MHPM -as ne.atively related to anEiety and hypochondriasis&
It -as su..ested that these relationships +et-een these sy#pto#s and the dysfunction in
the turnover of catechola#ines could reflect the occurrence of a hyperarousal state in
so#e #a@or depressive disorders&
I4
%ther indicators of sy#pathetic nervous activity have also +een studied in depressive
patients& Qechin et al& found hi.her heart rate increases durin. orthostasis and eEercise
periods and .reater 9/ values in depressed patients, su..estin. #aEi#al neural
sy#pathetic activity in the#&
II
runo et al& assessed cardiovascular autono#ic functionin.
in 44 unipolar depressive inpatients& Sy#pathetic choliner.ic, alpha( and +eta(adrener.ic
activity -as assessed via the #easure#ent of forear# +lood flo- BFFC and the cardiac
pre(e@ection period BP'PC& Si.nificant ne.ative correlations -ere found +et-een depressive
sy#pto#s and FF and si.nificant positive correlations -ere found +et-een depressive
sy#pto#s and P'P& It -as concluded that the autono#ic profile of depression is
characteri!ed +y a decrease in central sy#pathetic choliner.ic outflo-, coupled -ith
increases in alpha(adrener.ic and in +eta(adrener.ic activity&
I5
"i#inished heart rate
varia+ility BHFHC also reflects increased sy#pathetic activity and decreased
parasy#pathetic activity in depressive patients&
IK(53
$-enty(four hour 'CM recordin.s -ere
o+tained fro# #a@or depressive patients, nor#al controls, and #edically healthy volunteer
participants& Hi.h(fre?uency varia+ility -as #ar,edly di#inished in depressed patients,
indicatin. that they #ay have an a+nor#ality in parasy#pathetic nervous syste#
activity&
50
In another study, I23 acute #yocardial infarction BMIC patients -ith depression
and 545 acute MI patients -ithout depression -ere co#pared& /ll +ut one HFH indeE
re#ained si.nificantly lo-er in patients -ith depression than in patients -ithout
depression, su..estin. increased sy#pathetic activity and/or decreased parasy#pathetic
#odulation&
IJ
Increases in HFH -ere positively correlated -ith post(treat#ent Ha#ilton
Fatin. Scale for "epression BH/M("C scores after a therapeutic trial of various
antidepressant #edications&
54,5I
%n the other hand, patients treated -ith #irta!apine or
a#ytriptiline sho-ed si.nificant decreases in HFH after the treat#ent&
55
$he hypothesis of hyperactivity of the sy#pathetic nervous syste# is not the only possi+le
eEplanation for the relationship +et-een depression and P& Siever and "avis
5K
proposed
that the activity of neurotrans#itter syste#s in affective disorders #ay +e +etter
understood as a reflection of a relative failure in their re.ulation, rather than si#ple
increases or decreases in their activity& $hus, the i#pair#ent in the re.ulation of the
noradrener.ic syste# -ould +e eEpected to distur+ the individual affective responsiveness
to eEternal or internal sti#uli& Stressful sti#uli that episodically increase noradrener.ic
activity -ould +e associated -ith dysphoric hyperarousal +ecause this arousal -ould not
+e easily da#pened +y feed+ac, #echanis#s& "ecreases in noradrener.ic availa+ility
secondary to depletion +y periodic eEcessive release could easily +e seen as #ediatin.
aner.ic and ve.etative sy#pto#s& $he eEact confi.uration of these a+nor#alities #i.ht
vary dependin. on the individual and/or phase of the illness, so that appetite, sleep, and
#otor activity #ay +e decreased or increased in depression&
5K
Siever and "avisD theory
see#s very interestin. and could eEplain the increased vulnera+ility for hypertension in
depression& In addition, this theory is in accordance -ith the #iEed P findin.s in
depressive patients&
Sloan et al& also associated autono#ic control and P to depression& 'sta+lished
psycholo.ical/+ehavioral ris, factors for coronary artery disease BC/"C, such as
depression, hostility, and anEiety, are associated -ith di#inished control of the heart,
-hich #ay disinhi+it patho.enic P varia+ility BPHC&
5L
lood pressure oscillates at hi.h
B3&0K(3&K H!C and lo-er fre?uencies B3&34(3&0K H!C& /n intact autono#ically #ediated
cardiac control syste#, includin. +arorefleEes, acts to +uffer fluctuations in P, especially
in response to challen.e& $his increased PH is har#ful to the coronary arteries,
contri+utin. to pla?ue for#ation, pla?ue rupture, and acute coronary events& It is also
related to .reater left ventricular #ass, hi.her urinary al+u#in eEcretion, carotid
atherosclerosis, and cardiovascular #or+idity in hypertensive su+@ects&
5L
In C/" patients,
depression -as associated -ith lo- +arorefleE sensitivity&
5J
Stress and ANS
$here is a considera+le a#ount of data lin,in. sy#pathetic nervous syste#
hyperresponsivity to the develop#ent of hypertension& Hyperresponsivity is #anifested +y
eEa..erated HF and P responses to psycholo.ical sti#uli, eEperienced as en.a.in.,
challen.in., or aversive&
52
%ne line of evidence su..estin. a lin, +et-een hyperreactivity
and hypertension is the si#ilarity +et-een autono#ically(#ediated cardiovascular chan.es
in the presence of +orderline hypertension and those evo,ed in #ore reactive
nor#otensive persons durin. certain types of +ehavioral events& Studies of he#odyna#ics
in +orderline hypertensive patients have sho-n an increased cardiac output, #ediated +y
enhanced +eta(adrener.ic activity and decreased parasy#pathetic sti#ulation of the
heart&
0
Patients -ith esta+lished hypertension have +een o+served to sho- .reater HF and P
increases than nor#otensive su+@ects in response to +ehavioral events such as difficult
#ental arith#etical operations, or interpersonal interactions desi.ned to arouse fear or
an.er or to eEpose personal conflicts&
0
Hyperreactivity see#s to +e related to psychosocial aspects& 'levation of P -as
associated -ith certain personality traits, such as an.er and its suppression, and also to
uneEpected unfortunate life events&
51,K3
'vidence a+out the relationship +et-een these
factors and hypertension also points to an autono#ic nervous dysfunction&
0,51
Co#pared -ith nonhostile individuals, hostile su+@ects #anifest hi.her HF and P
responses to physiolo.ical sti#uli, such as #ental tas,s, as -ell as hi.her a#+ulatory P
levels durin. daily(life activity&, 'vidence also su..ests that hostile individuals are #ore
li,ely to eEhi+it hypercortisole#ia and hi.h levels of circulatin. catechola#ines, as -ell as
di#inished +eta(adrener.ic receptor function of #ononuclear leu,ocytes, di#inished va.al
#odulation of heart function, and increased platelet reactivity&
52
$he G-hite(coat effectG -as addressed +y Mrassi et al& +y ?uantifyin. the sy#pathetic
outflo- to #uscle and s,in +y #icroneuro.raphy& Measure#ents -ere perfor#ed in
hypertensive su+@ects durin. a control period, durin. a visit +y a doctor unfa#iliar to the
patient, and durin. a recovery period& $he doctorDs visit induced a sudden, #ar,ed, and
prolon.ed P and HF response, acco#panied +y a si.nificant increase in s,in and
sy#pathetic nerve traffic, characteri!ed +y activation of the adrener.ic nervous syste#&
K0
Interestin.ly, +orderline hypertensive su+@ects -ith P hyperreactivity also had hi.her
ne.ative affect scores after tas,s, su..estin. an association +et-een depressive
sy#pto#s and hyperreactivity&
K4
Studies have de#onstrated that relaEation trainin. and +iofeed+ac, can lead to si.nificant
in(clinic P reductions& It is su..ested that individuals reportin. hi.h levels of anEiety
should +e considered initially for relaEation trainin.&
KI
$he P lo-erin. effects attri+uta+le
to relaEation and +iofeed+ac, trainin. -ere carried over to the -or,in. day&
K5
Initial
evidence su..ests that the lon.(ter# effects of practice of these procedures are
consistent -ith the decreased responsitivity to plas#a norepinephrine&
KI
/ follo-(up study
de#onstrated that the advanta.e for relaEation trainin. -as #aintained 0K #onths after
treat#ent&
KI
9evertheless, the specific physiolo.ic and neurohor#onal #echanis#s +y
-hich these effects are o+tained are not ,no-n&
KI
!enetic "ulnerability
It is also -idely accepted that P and suscepti+ility to hypertension are influenced +y
.enetic factors&
KK
Fecently, t-in, adoption, and fa#ily studies have su..ested that .enetic
factors are i#portant in the etiolo.y of #ood disorders&
KL
So#e studies have su..ested
that a shared .enetic vulnera+ility could eEplain the relationship +et-een depression and
hypertension&
Mre-en et al&
KK
investi.ated -hether parental history of hypertension BFHRC enhances the
i#pact on a#+ulatory +lood pressure B/PC of depressed #ood as indeEed +y the ec,
"epression Inventory B"IC, Bn N I05C& Hi.her "I scores -ere si.nificantly associated
-ith hi.her 45(hour /P in FHR su+@ects, +ut not in participants -ithout parental history
of hypertension BFH(C& Felationships -ere si.nificantly stron.er in those -ith 4
hypertensive parents vs& those -ith 0 vs& those -ith no hypertensive parents& In contrast,
interaction -as least predictive of P levels durin. sleep, su..estin. that the influence of
depression on P in FH( su+@ects is #anifested durin. responses to everyday stresses and
strains&
KK
Su+@ects -ith a positive fa#ily history of hypertension eEhi+ited hi.her tonic levels of P
and HF at rest, durin. #ental stress tas,s, and durin. recovery&
KJ
Individuals -ith positive
fa#ily histories reported #ore depression durin. the tas,s, su..estin. that .enetic and
psycholo.ical factors are involved -ith cardiovascular hyperreactivity&
KJ
Fats that -ere .enetically prone to hypersensitivity had a very hi.h propensity for
developin. depression Blearned helpless +ehaviorC& Moreover, hyporesponsive functionin.
of the hypothala#uspituitaryadrenal BHP/C aEis correlates -ith a propensity for learned
helpless +ehavior&
K2
Interestin.ly, the +loc,ade of the reninan.iotensin syste# -ith the
an.iotensin convertin. en!y#e inhi+itor reversed the learned helplessness in rodents&
K1

/dditionally, several clinical investi.ations have su..ested that captopril, an an.iotensin(
convertin. en!y#e inhi+itor eEhi+its antidepressant properties in hu#ans, su..estin. that
the reninan.iotensin syste# #ay not only participate in the elevation of P +ut #ay also
contri+ute to depression, althou.h its #echanis# is un,no-n&
K2
Ho-ever, there are controversial findin.s& "epressive sy#pto#s #easured +y the C'S("
BCenters for 'pide#iolo.ical Studies("epression ScaleC -ere associated -ith #ean arterial
pressure BM/PC in 2J #ono!i.otic t-in pairs and 2L di!i.otic t-in pairs&
L3
9evertheless,
the association accounted for an environ#ental effect that -as independent of .enetic
effects&
L3
/nother study found no association +et-een depression and .enetic
poly#orphis#s related to vascular disease&
L0
$o+plications
/lthou.h there is no definitive evidence of an association +et-een depression and
develop#ent of hypertension, depression can i#pair the #ana.e#ent and pro.nosis of
hypertension&
L4,LI
/n epide#iolo.ical study analy!ed the lon.itudinal association +et-een depressive
sy#pto#atolo.y and P control, stro,e, and cardiovascular(related #ortality in the
elderly& $his study de#onstrated an increased ris, of stro,e a#on. older patients -ith
hypertension and hi.h levels of depressive sy#pto#s, and the association appeared to +e
a function of P control, particularly in -o#en&
L4
"epression has also +een associated -ith hi.her ris, of stro,e in the elderly& In a
prospective study, depressive sy#pto#s -ere predictive of ische#ic stro,e in 130
su+@ects in a Sapanese rural area durin. a 03(year period&
L5
6assertheil(S#oller et al&
LI

detected that a si.nificant eEcess ris, of death and stro,e or #yocardial infarction -as
associated -ith an increase in depressive sy#pto#s in patients -ith L3 years of a.e or
#ore Bn N 5JILC and -ith systolic hypertension BSHC, defined as SP T0L3 ## H. and
"P P13 ## H.&
"epression -as independently associated -ith a su+stantial increase in the ris, of heart
failure a#on. 5KI2 persons a.ed L3 years and older -ith isolated systolic hypertension in
a study for -hich the avera.e follo-(up period -as 5&K years BFF N 4&K1A 1KO CI) 0&KJ(
5&4JC&
LK
"epressed persons also had hi.her SP levels&
LK
"epression independently increased the ris, of #ortality in the 5(year follo-(up period of
425J su+@ects -ith KK to 2K years old&
LL
$he relative ris, for #ortality -as 0&L B1KO CI)
0&3(4&JC in su+@ects -ith #inor depression and cardiac disease, 0&K B1KO CI) 3&1(4&LC in
su+@ects -ith #inor depression -ithout cardiac disease, I&3 B1KO CI) 0&0(J&2C in su+@ects
-ith #a@or depression and cardiac disease and I&1 B1KO CI) 0&5(03&1C in su+@ects -ith
#a@or depression -ithout cardiac disease& / dose(response effect -as de#onstrated in
that the #ore severe the depression, the hi.her the #ortality ris,&
LL
Hei.htened suscepti+ility to platelet activation #ay +e a #echanis# underlyin. the
increased ris, of ische#ic heart and cere+rovascular disease and/or #ortality after MI in
depression&
LJ
Hypertensive patients -ith hi.her scores on standardi!ed depression ratin.
scales sho-ed si.nificantly .reater platelet reactivity follo-in. serotonin sti#ulation
co#pared to patients -ith lo-er depression scores&
L2
%n the other hand, hypertension has +een proposed as a ris, factor for the develop#ent
of depression& 9euroi#a.in. studies reveal hi.her fre?uency of ische#ic a+nor#alities in
late(life depression&
L1
/ccordin. to the theory of vascular depression, these a+nor#alities
could represent a vulnera+ility to depression&
I
Antidepressive treat+ent
/nother i#plication of the presence of depression in hypertensive patients is represented
+y the side effects of antidepressive a.ents& $ryciclic antidepressants B$C/sC and
#onoa#ine oEidase inhi+itors BM/%IDsC have +een associated -ith +oth reduction and
elevation in systolic and diastolic P&
04
/lthou.h serotonin selective reupta,e inhi+itors
BSSFIsC produce fe-er he#odyna#ic effects, hypertension in patients ta,in. SSFIs has
also +een reported&
04
/ #etanalysis of P chan.es in patients treated -ith venlafaEine,
i#ipra#ine, or place+o de#onstrated a dose(dependent increase in P -ith venlafaEine
treat#ent&
J3
Sustained hypertension Bdefined as a restin. diastolic P value U13 ## H.
plus a U03 ## H. rise a+ove +aseline diastolic P for at least I consecutive clinical visitsC
-as o+served in 5&2O of patients treated -ith venlafaEine, 5&JO of those treated -ith
i#ipra#ine, and 4&0O of those receivin. the place+o& $he lar.est increases B0I&4OC
occurred at doses UI33 #. daily&
J3
Interestin.ly, #ore than one third of the hypertensive
patients also sho-ed a spontaneous reduction in P durin. continued venlafaEine
treat#ent& Patients -ith a history of preeEistin. hypertension or pretreat#ent diastolic P
U13 ## H. did not de#onstrate a .reater ris, for developin. dru.(induced
hypertension&
J3
/nother #etanalysis -as perfor#ed usin. ori.inal P data of IJ55
patients -ith #a@or depression studied in controlled clinical trials co#parin. venlafaEine,
i#ipra#ine, and place+o& HenlafaEine and i#ipra#ine -ere associated -ith s#all, +ut
statistically si.nificant increases in supine diastolic P& $he effect of venlafaEine -as dose(
dependent as -ell and did not adversely affect the control of P for patients -ith
preeEistin. hi.h P& Ho-ever, the P elevations -ere persistent durin. continuation of
therapy&
J0
/nother study eEa#ined P in J1L depressed patients ta,in. fluoEetine 43 #. daily for up
to 04 -ee,s& / #odest reduction in SP and "P #easures -as o+served& Patients
pretreated -ith "P PL3 ## H. sho-ed a #odest increase in #ean "P& Patients -ith
preeEistin. cardiovascular disease, includin. hypertension, sho-ed no si.nificant P
chan.es&
04
Potentiation of noradrener.ic neurotrans#ission #ay +e a #echanis# +y -hich
antidepressants increase P& In hypertensive crises associated -ith M/%I therapy, hi.h
levels of un#eta+oli!ed tyra#ine or sy#patho#i#etics tri..er norepinephrine release
fro# peripheral sy#pathetic neurons&
J0
/ re.ional increase of cardiac noradrener.ic
activity #ay the #echanis# +y -hich desipra#ine Ba potent norepinephrine reupta,e
inhi+itorC increases P&
J4
/nother hypothesis is that central serotoniner.ic trans#ission #ay have an essential role
in P re.ulation& $he serotonin reupta,e +loc,ade could initiate a cascade of chan.es in
central serotonin neurotrans#ission that results in an enhance#ent of autono#ic tone&
04

Mru++ et al& have consistently de#onstrated that fluoEetine and sertraline can increase
and sta+ili!e lo- P in patients -ith neurocardio.enic hypotension and also provide
sustained prophylaEis a.ainst recurrent hypotension&
JIJL
In clinical ter#s, the ris, of orthostatic hypotension B%HC durin. the tricyclic
phar#acotherapy is far #ore i#portant than elevations of P& $he M/%Is also cause
relatively hi.h rates of %H&
J0
$he elderly are #ore vulnera+le to %H& %ccurence of %H and its association -ith the
co#plaint of di!!iness -as studied in depressive elderly -o#en receivin. nortriptyline IK
to 033 #. daily for 2 -ee,s&
JJ
9or#otensive and hypertensive su+@ects BP controlled
-ith thia!ide diureticsC -ere co#pared& P and HF -ere assessed at +aseline and at every
4 -ee,s, and a tilt(ta+le test -as perfor#ed +efore and after treat#ent& $here -as an
increase in the SP drop on orthostasis in +oth .roups Bthe #ean SP drop -as 03&K ##
H. for hypertensive and J&J ## H. for nor#otensive -o#enC and an increase in HF
B#ean increase of 05 +p#C BFi.& 0C& %rthostatic hypotension -as o+served in 40O of
patients at +aseline and in IIO after 2 -ee,s treat#ent& Fesults of tilt(ta+le tests
confir#ed this increase in the fre?uency of %H after treat#ent BFi.& 4C& $here -as no
correlation +et-een %H and su+@ective co#plaints of di!!iness +efore or after treat#ent&
"i!!iness -as reported +y KIO and I2O of patients +efore after treat#ent, respectively,
su..estin. that depression -as pro+a+ly involved -ith the fre?uency of co#plaints of
di!!iness&
JJ




"epressive patients have +een considered to have a hi.her ris, of %H -hile receivin.
tricyclic antidepressants co#pared to controls&
J2
/utono#ic dysfunction associated -ith
depression could contri+ute to the vulnera+ility& /dditionally, hi.her postprandial SP
drops have +een descri+ed in the su+syndro#al depressed elderly&
J1
/ reduction of the physiolo.ic nocturnal drop of P has also +een reported in depressed
elderly -o#en durin. 2 -ee,s of treat#ent -ith nortriptyline& $his could +e eEplained +y
sy#pathetic hyperactivity leadin. to peripheral vascular dilatation, su..estin. that
nortriptyline can affect P in depressed elderly individuals&
23

$*!$L)SI*!
$he relationship +et-een depression and P is a co#pleE issue& Pu+lished reports descri+e
hi.her P levels, hi.her incident hypertension, hypotension, and circadian variation
a+nor#alities in depressed patients& Several causative factors have +een proposed to
eEplain this association, such as autono#ic nervous syste# dysfunction, and #ore
recently, .enetic influences& $he clinical relevance of this the#e is clear, since depressive
sy#pto#atolo.y is associated -ith poor P control in hypertensive patients and -ith the
develop#ent of co#plications of hypertension& Finally, eEtra care #ust +e ta,en -ith
depressive hypertensive patients to #ini#i!e the side effects on P of antidepressants&

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