Mawardi Sahir C111 08 116 Hipertensi Sistolik Terisolasi Pada hipertensi sistolik terisolasi, tekanan sistolik mencapai 140

mmHg atau le ih, tetapitekanan diastolik kurang dari !0 mmHg dan tekanan diastolik masih dalam kisaran normal"Hipertensi ini sering ditemukan pada usia lan#ut" Se#alan dengan ertam ahn$a usia, hampirsetiap orang mengalami kenaikan tekanan darah% tekanan sistolik terus meningkat sampaiusia 80 tahun dan tekanan diastolik terus meningkat sampai usia &&'60 tahun, kemudian erkurang secara perlahan atau ahkan menurun drastis" (enis hipertensi ini dise a kan olehumur, mengkonsumsi tem akau,dia etes, dan diet $ang salah" Pada hipertensi ini, arterimen#adi kaku sehingga men$e a kan sistolik )tekanan darah saat #antung erkontraksi*sangat tinggi sedangkan diastolik )tekanan darah saat #antung istirahat* normal" +iasan$atekanan darah pada #enis ini erkisar antara 160,80 mm,Hg" Menurut -ra$ dkk ).00&*, aik pria maupun wanita hidup le ih lama dan &0/ dari mereka $ang erusia diatas 60 tahun kanmenderita hipertensi sistolik terisolasi )T0 sistolik 160 mmHg dan diastolik !0 mmHg*"Hipertensi sistolik terisolasi )1solated s$stolic h$pertension* ter#adi ila terdapat kenaikantekanan darah sistolik disertai penurunan tekanan darah diastolik" Selisih dari tekanan darahsistolik dan tekanan darah diastolik $ang dise ut se agai tekanan nadi )pulse pressure*,ter ukti se agai prediktor mor iditas dan mortalitas $ang uruk" Peningkatan tekanan darahsistolik dise a kan terutama oleh kekakuan arteri atau erkurangn$a elastisitas aorta"Pene alan dinding aorta dan pem uluh darah esar meningkat salah satun$a dise a kanpenumpukan lemak dalam pem uluh darah $ang iasa ter#adi pada orang o esitas" Peru ahanini men$e a kan penurunan compliance aorta dan pem uluh darah esar dan mengaki atkanpeningkatan tekanan darah sistolik" 2ekakuan arteri #uga isa dise a kan karena stres, $angmana stres dapat mempengaruhi s$ara3 simpatis sehingga otot'otot pem uluh darah men#adile ih tegang" Penatalaksanaan CC+ dihidropiridin sangate3ekti3 pada lansia denganhipertensi sistolik terisolasi) isolated s$stolic h$pertension *"(4C 5 tidak mencantumkanhipertensi sistolik terisolasi er eda dengan tipe hipertensilainn$a, dan diuretik tetap terapilini pertama" +agaimanapun,CC+ dihidropiridin long'actingdapat digunakan se agai terapitam ahan ila diuretik tia6idtidak dapat mengontrol tekanandarah, terutama pada pasienlansia dengan tekanan darahsistolik meningkat"

Which is more important, the bottom or the top number?

7e ha8e disco8ered that s$stolic lood pressure )the top num er or highest lood pressure when the heart is s9uee6ing and pushing the lood round the od$* is more important than diastolic lood pressure )the ottom num er or lowest lood pressure etween heart eats* ecause it gi8es the est idea o3 $our risk o3 ha8ing a stroke or heart attack" 7e know, 3or e:ample, that ha8ing a lood pressure o3 160,80mmHg is more ;risk$< than ha8ing a lood pressure o3 1&0,!0mmHg" Ha8ing a raised s$stolic lood pressure ut normal or low diastolic lood pressure is called 1solated S$stolic H$pertension )1SH* and carries an increased risk o3 de8eloping heart attacks or strokes and should e treated" Howe8er, there are some circumstances where diastolic lood pressure ma$ e more important than s$stolic" =or e:ample, some studies suggest that, in people aged $ounger than 40 $ears, diastolic lood pressure is a etter wa$ o3 assessing risk" Howe8er, $ounger people are less likel$ to ha8e a stroke or heart attack, so in3ormation on their risk o3 3uture pro lems is limited" 1t could e that diastolic lood pressure ecomes more important when it is 8er$ high" There is some e8idence to suggest that, 3or e:ample, a lood pressure o3 180,1.0mmHg gi8es a greater risk o3 stroke or heart attack than 180,100mmHg" The onl$ wa$ to resol8e this issue is to o tain data 3rom thousands o3 patients collected on a s$stematic asis" The statistical tests to in8estigate the relati8e importance o3 s$stolic and diastolic lood pressure are immensel$ complicated" Howe8er, current e8idence strongl$ suggests that, o8er the age o3 40, it is s$stolic pressure that is most important" For a blood pressure chart of readings, click here"

+ack to top

Only my top number is high - what does this mean?

This is called isolated s$stolic h$pertension and is more common as people get older" 1t is important that it is treated e8en though it is onl$ the s$stolic num er that is raised"

Pathophysiology of Systolic Hypertension in the lderly

Se8eral 3unctional and structural a normalities are in8ol8ed in the rise o3 s$stolic +P with aging and conse9uentl$ the de8elopment o3 isolated s$stolic h$pertension in the elderl$" >ndothelial d$s3unction together with 8ascular remodeling and 3i rosis will decrease arterial elasticit$ or increase arterial sti33ness" Conse9uentl$ there will e an increase o3 the arterial wa8e re3lections leading to an increased second s$stolic peak and enhanced de8elopment o3 s$stolic h$pertension" ?@A The reninB angiotensinBaldosterone s$stem pla$s a ke$ role in sodium handling, 8ascular remodeling and in3lammation"?4A =igure 1 illustrates the pathogenesis o3 s$stolic h$pertension in the elderl$ and the clinical conse9uences" Cging is associated with increased arterial sti33ness due to endothelial d$s3unction, 8ascular remodeling and a change in the e:tracellular matri:" There is a decrease in elastin 3i ers and an increase in collagen 3i ers in the arterial wall" 1ncreased arterial sti33ness and arterial wa8e re3lections will lead to a rise in s$stolic +P and, conse9uentl$, to the de8elopment o3 isolated s$stolic h$pertension" The increased arterial load due to increased s$stolic +P and arterial wa8e re3lections will promote le3t 8entricular h$pertroph$ and conse9uentl$ heart 3ailure, atherosclerotic disease resulting in coronar$ heart disease, cere ro8ascular disease and aortic aneur$sms"

)>nlarge 1mage* Figure !" Pathogenesis o3 s$stolic h$pertension in the elderl$ and clinical conse9uences" C20D Chronic kidne$ disease% EFD Ee3t 8entricular% EFHD Ee3t 8entricular h$pertroph$" The elderl$ merit special consideration 3or +P measurement" These h$pertensi8e patients are prone to ha8e autonomic 3ailure with postural h$potension and, there3ore, +P should e measured in supine, sitting and standing positions e3ore starting antih$pertensi8e therap$"

>lderl$ h$pertensi8e patients are at higher risk 3or arrh$thmias )e"g", atrial 3i rillation*" 1n such patients +P measurement ma$ e di33icult and the mean o3 a num er o3 measurements ma$ ha8e to e estimated" +ilateral measurements should e made on 3irst consultation and, i3 persistent di33erences greater than .0 mmHg 3or s$stolic or 10 mmHg 3or diastolic +P are present on consecuti8e readings, arterial disease o3 the upper e:tremities should e ruled out" Measurement o3 +P at home can e use3ul" This can e done either $ the patient or with the help o3 a home'health nurse" 1n case o3 a di33icult'to'treat arterial h$pertension, a .4'h am ulator$ +P monitoring can help us to estimate the +P 8aria ilit$ )more pronounced in the elderl$* and also o tain the nocturnal pattern o3 the +P )dipping 8s nondipping*" Se8eral studies ha8e demonstrated that am ulator$ +P is a etter predictor o3 cardio8ascular, cere ral and renal disease in older h$pertensi8e patients, 3or e:ample, 7hite et al. showed that .4'h s$stolic +P is associated with progression o3 micro8ascular disease o3 the rain and with a 3unctional decline in mo ilit$ and cognition in older people"?&A

#reatment $oals

The primar$ goal o3 antih$pertensi8e treatment in the elderl$ with s$stolic h$pertension is to reduce cardio8ascular mor idit$ and mortalit$" The goal is to lower s$stolic +P elow 140 mmHg and diastolic +P elow !0 mmHg" 1n case o3 h$pertension in presence o3 dia etes or kidne$ disease, the +P target is 1@0,80mmHg" 1n .011 the Cmerican Heart Cssociation and Cmerican College o3 cardiolog$ pu lished speci3ic therapeutic considerations 3or the treatment o3 h$pertension in the elderl$"?6A (4C 8 guidelines are e:pected to replace the (4C 5,?5A which were written nearl$ a decade ago, and the most recent >SH,1SH guidelines, which were pu lished in .005"?8A The cornerstone o3 all these recommendations is to start with li3est$le changes"

Pharmacological #reatment

Medical treatment 3or elderl$ h$pertensi8e patients has een generall$ recommended" Gne needs to e cautious in the elderl$ ecause the ma#orit$ o3 older h$pertensi8e patients ha8e other medical conditions, which need to e treated medicall$% are at higher risk 3or orthostatic h$potension% and are at risk 3or drug interaction and decreased drug meta olism" The target 3or h$pertensi8e elderl$ patients is ased on e:pert opinion rather than on data 3rom randomi6ed controlled trials" 1t is unclear whether target S+P should e the same in elderl$ patients o8er a wide age range starting at 6& $ears" Multiple drug classes, with di33erent mechanisms o3 action and di33erent side e33ects, are a8aila le 3or the treatment o3 h$pertension"?5,8A Se8eral classes o3 antih$pertensi8e drugs, including diuretics, calcium channel lockers, angiotensin'con8erting en6$me inhi itors )CC>1s*, and angiotensin 11'receptor lockers )CH+s*, are suita le 3or the initiation and maintenance o3 antih$pertensi8e therap$" a' and I' lockers are less 3a8ored $ man$ clinicians and guidelines as 3irst'line therap$"

%rug treatment of isolated systolic hypertension

1 Peter C" 8an Jwieten K Cuthor C33iliations Departments of Pharmacotherapy, Cardiology and Cardiothoracic Surgery, Academic Medical Centre, University of Amsterdam, Meibergdreef, Amsterdam, The etherlands

4e:t Section

&ntroduction

Lntil the 1!80s diastolic lood pressure )0+P* was assumed to e the most rele8ant haemod$namic parameter as a predictor o3 prognosis in h$pertensi8e patients" Cccordingl$, most clinical studies particularl$ addressed 0+P, and 0+P8alues were put 3orward as goals 3or treatment ? 1A" Since then a radical change in thinking, ased upon epidemiological studies has led to the recognition o3 ele8ated s$stolic lood pressure )S+P* as a risk 3actor at least as important as high 0+P ?1B&A" Certain studies would e8en indicate that S+P is a more rele8ant predictor o3 prognosis than 0+P, in particular with respect to the risk o3 stroke ?1A" =or this and other reasons, the term Misolated systolic hypertensionN )1SH* has een introduced 3or those su #ects with ele8ated S+P and normal )or e8en lower* 0+P" This condition is 3ound particularl$ in elderl$ h$pertensi8es, since S+P is known to rise with ad8ancing age, whereas 0+P usuall$ le8els o33 and then tends to decrease in the elderl$" Conse9uentl$, pulse pressure )S+P minus 0+P* will increase in such patients" 1t appears that ele8ated pulse pressure is an e8en etter predictor o3 cere ro and cardio8ascular e8ents in elderl$ h$pertensi8es than a high S+P as such ?1,.A" 1ndeed, 1SH is the most common t$pe o3 h$pertension in the elderl$, and it is the most pre8alent t$pe o3 untreated h$pertension among persons o8er 60 $ears o3 age" Cccording to modern de3initions, e:pressed in the (4CF1 ?16A and 1!!! 7HG,1SH-uidelines ?5A 1SH is now de3ined as +P O140,P!0mmHg" These criteria are more MstringentN than the older de3inition o3 1SH at O160,P!0mmHg" The de8elopment o3 1SH with increasing age is e:plained $ a deterioration o3 arterial compliance, in particular that o3 the large conduit arteries" Such increasing arterial sti33ness is caused $ structural and 3unctional changes in the 8ascular wall, a33ecting collagen, e:tracellular protein matri:, and elastin" The proli3eration o3 connecti8e tissue results in intimal thickening and 3i rosis" The increasing 8ascular sti33ness causes a reduction in arterial compliance and the decrease o3 the M7indkessel 3unctionN o3 the large arteries" Cccordingl$, pulse pressure and pulse wa8e 8elocit$ increase, associated with an earlier and enhanced re3lection o3 pressure wa8es 3rom the peripher$ ?1,.A, thus causing a disproportionate increase in S+P" 0+P, howe8er, does not increase and ma$ e8en e lowered as a result o3 increased arterial sti33ness" Pre8ious Section4e:t Section

&solated systolic hypertension as a risk factor

The widened pulse pressure 3ound so t$picall$ in the elderl$ re3lects oth an increase in s$stolic and a decrease in diastolic pressure" Se8eral studies, including the =ramingham stud$, documented the risk o3 high S+P in particular with respect to stroke and, less clearl$, ischaemic heart disease ?8A" Similarl$, in the MH=1T stud$ S+P was 3ound to e a stronger predictor o3 outcome than 0+P ?!A" Howe8er, it should e reali6ed that too low a 0+P is also dangerous ?10B1.A" These o ser8ations once more emphasi6e the important role o3 widened pulse pressure as a risk 3actor" Con8ersel$, se8eral inter8ention studies in patients with 1SH, to e discussed in a su se9uent paragraph, ha8e demonstrated the ene3icial e33ect o3 the treatment o3 1SH, and more generall$ o3 treatment o3 h$pertension in the elderl$" Ct least on theoretical grounds it seems desira le to lower S+P in such patients, without simultaneousl$ lowering 0+P, in order to a8oid a 3urther widening o3 pulse pressure" Pre8ious Section4e:t Section

'enefit of treatment of &SH

1n general terms, the ene3icial e33ect o3 treatment o3 1SH runs in parallel with that o3 the treatment o3 h$pertension in the elderl$" 1n general, this issue has een addressed since the 1!!0s $ means o3 inter8ention trials" Se8eral trials such as STGP1, STGP., and MHC >lderl$ ha8e clearl$ shown that treatment o3 h$pertension in the elderl$ protects against the complications o3 h$pertension, particularl$ stroke )3or re8iew see ?1@A*" 1n most o3 these trials no clear distinction was made etween

1SH and Mordinar$N h$pertension" There is no dou t, howe8er, that a ma#or percentage o3 the elderl$ h$pertensi8e patients enrolled in these studies displa$ed the haemod$namic characteristics o3 1SH" C 3ew clinical trials ha8e deli eratel$ addressed a population o3 patients with 1SH as such"

Systolic Hypertension in the lderly Program (SH P) *!+,

Patients with wellde3ined 1SH were treated with lowdose chlorthalidone )with the option to add atenolol or reserpine*, and this was compared with administration o3 place o" Chlorthalidone treatment caused the 3ollowing reductionsD non3atal strokeD Q@5/% non3atal M1D Q@@/% EF 3ailureD Q&4/" There were o 8ious trends 3or a decrease in T1Cs )Q.&/* as well as in total )Q1@/*, cardio8ascular )Q.0/*, cere ro8ascular )Q.!/*, and coronar$ )Q1&/* mortalit$"

Systolic Hypertension in urope (S-S# ./) ,!0*

1n a large num er o3 patients with 1SH, the calcium antagonist nitrendipine )with optional add on enalapril and,or h$drochlorothia6ide* was compared in a dou le lind randomi6ed design with place o" Ccti8e treatment with nitrendipine caused a signi3icant and striking reduction in the incidence o3 stroke $ 4./, and there was also a clear tendenc$ towards a reduction o3 m$ocardial in3arction" This reduction did not achie8e statistical signi3icance howe8er, pro a l$ ecause the trial had een stopped prematurel$ 3or ethical reasons" Total mortalit$ )all causes* was not in3luenced $ acti8e treatment" 1nterestingl$, the rate o3 8ascular dementia was reduced ) $ Q&0/* in the stud$ area with nitrendipine treatment ?16A"

S-S#1hina trial ,!2*

Chinese patients with 1SH were treated with nitrendipine or place o" The trial design was 8er$ similar to that o3 SRST>LH" Ccti8e treatment with nitrendipine signi3icantl$ reduced the 3ollowing endpointsD total strokeD Q@8/% stroke mortalit$D Q&8/% all cause mortalit$D Q@!/% cardio8ascular mortalit$D Q@!/% 3atal and non3atal c8 e8entsD Q@5/"

&3S&$H# study ,!4*

The 14S1-HT stud$ has dealt with a population o3 h$pertensi8e patients with an additional risk 3actor, such as dia etes mellitus, h$percholesteraemia, etc" Treatment consisted o3 ni3edipine )in the -1TS 3ormD CdalatGHGSS* vs h$drochlorothia6ide" 14S1-HT was not a selecti8e 1SHtrial, ut it contained a su group o3 patients with 1SH" This su group was anal$sed separatel$ ?1!A" These patients appeared to e more responsi8e to treatment with ni3edipine-1TS than those with Mordinar$N h$pertension" 1nterestingl$, in this stud$ patients with 1SH whose 0+P signi3icantl$ decreased under treatment were smokers with e8idence o3 atherosclerosis" C series o3 outcome trials in patients with 1SH was recentl$ su #ected to a meta anal$sis ? .0A" Ccti8e treatment reduced total mortalit$ $ 1@/, cardio8ascular mortalit$ $ 18/, all cardio8ascular complications $ .6/, stroke $ @0/ and coronar$ e8ents $ .@/" 0rug therap$ appeared to o33er etter protection against stroke than against acute coronar$ s$ndromes" The a solute ene3it was est in patients older than 50 $ears, and in those with a histor$ o3 cardio8ascular complications or a high pulse pressure )i"e" wide lood pressure amplitude*" 1n a series o3 smaller studies it has een shown that in 1SH patients thia6ide diuretics are more protecti8e than ! lockers ?.1B.@A" 4ewer drugs such as CC>inhi itors ?.4A and CT1 lockers ?.&A are also suita le 3or lood pressure control in 1SH, although data on an epidemiological scale are not $et a8aila le" Gmapatrilat, a com ined inhi itor o3 neutral endopeptidase and CC> showed a stronger

e33ect on S+P than on 0+P ?.6A" Pre8ious Section4e:t Section

3ew approaches in the treatment of &SH

Ct least on theoretical grounds it would seem desira le to 3ind antih$pertensi8e drugs which reduce S+P more markedl$ than 0+PD )i* Spironolactone, an aldosterone antagonist, is not onl$ a )rather weak* natriuretic agent" 1t also inhi its the s$nthesis o3 collagen and m$ocardial and 8ascular 3i rosis pro8oked $ aldosterone ?.5A" =or this reason spironolactone ma$ counteract the arterial sti33ness which underlies the pathogenesis o3 1SH" Studies ?.A ha8e indeed documented 3a8oura le e33ects o3 spironolactone in 1SH patients" More detailed and larger studies are there3ore clearl$ indicated to 3urther address this matter, )ii* >plerenone is a newer aldosterone antagonist with much weaker endocrine acti8ities than spironolactone, so that one would e:pect 3ewer endocrine sidee33ects such as g$naecomastia% )iii* 4itrates, as 4G generators, ma$ also e considered as a potential new approach in the treatment o3 1SH" 1sosor ide dinitrate has een shown to selecti8el$ lower s$stolic lood pressure without changing diastolic pressure in elderl$ patients with isolated s$stolic h$pertension ?.,.8A" 1t took 8 weeks o3 treatment e3ore the e33ect on s$stolic lood pressure ecame mani3est" The selecti8e e33ect on s$stolic lood pressure is assumed to e e:plained $ the drugTs in3luence on pressure wa8e re3lection in the large conduit arteries" Similar 3indings concerning s$stolic pressure ha8e een o tained with transdermal nitrogl$cerine and molsidomine ?.,.8A" 1t is there3ore elie8ed that these ene3icial e33ects are e:plained $ the increased release o3 4G as the underl$ing principle" So 3ar no data are a8aila le concerning the protecti8e e33ects o3 longterm nitrate treatment on the se9uelae o3 h$pertension" Pre8ious Section4e:t Section

1onclusions and recommendations

1solated s$stolic h$pertension is characteri6ed $ a widened pulse pressure" 1t has een recogni6ed as an important entit$, which re9uires consistent treatment" Cpart 3rom the wellknown ad8ices 3or li3e st$le modi3ication, drug treatment is re9uired in the ma#orit$ o3 patients with 1SH" The data so 3ar a8aila le indicate that lowdose thia6ide diuretics and slow,long acting calcium antagonists are the drugs o3 3irst choice" C slow reduction o3 s$stolic pressure in the mostl$ elderl$ patients is mandator$" C target le8el o3 S+P around 140mmHg seems desira le" 4ewer drugs such as CC>inhi itors, CT1 lockers and omapatrilat are e33ecti8e in lowering S+P in 1SH patients, ut large scale data concerning their protecti8e e33ects are not a8aila le" =inall$, aldosterone antagonists and nitrates )as 4G generators* deser8e 3urther in8estigation as drugs which ma$ reduce arterial sti33ness, the pathogenetic mechanism underl$ing 1SH" Pre8ious Section4e:t Section

Footnotes

Correspondence and offprint re"uests toD P" C" 8an Jwieten, 0epartments o3 Pharmacotherap$, Cardiolog$ and Cardiothoracic Surger$, Ccademic Medical Centre, Lni8ersit$ o3 Cmsterdam, Mei ergdree3 1&, 110& CJ Cmsterdam, The 4etherlands" >uropean Henal Cssociation'>uropean 0ial$sis and Transplant Cssociation

Pre8ious Section

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