8. KRVNI TLAK Draženka Pongrac Barlovič, Jelka Zaletel Vrtovec, Rok Accetto, Jana Brguljan-Hitij, Primož Dolenc, Barbara Salobir

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1 8. KRVNI TLAK Draženka Pongrac Barlovič, Jelka Zaletel Vrtovec, Rok Accetto, Jana Brguljan-Hitij, Primož Dolenc, Barbara Salobir Zvišan krvni tlak je pomemben in pogost dejavnik tveganja za žilne zaplete pri bolnikih s sladkorno boleznijo tipa 2. PRIPOROČILA 1. Krvni tlak izmerimo praviloma ob vsakem obisku, vendar najmanj enkrat na leto. Uporabljamo priporočeno metodo (Pojasnilo 1a). Ob ugotovljenem zvišanem krvnem tlaku ocenjujemo klinično okvaro organov oziroma aktivno iščemo morebitno prisotnost subklinične okvare organov (Pojasnilo 1b). Strategijo obravnave zvišanega krvnega tlaka določimo glede na krvni tlak in oceno okvare organov (Pojasnilo 1c). (E*) 2. Ciljni krvni tlak je pod 130 mmhg sistoličnega in pod 80 mmhg diastoličnega krvnega tlaka. (E) 3. Zdravljenje Vsem bolnikom z zvišanim krvnim tlakom priporočimo izboljšanje življenjskih navad (glej Nefarmakološko zdravljenje) (E*). Zdravljenje z zdravili uvedemo glede na srčno-žilno ogroženost pri vseh bolnikih s sladkorno boleznijo s krvnim tlakom 140 mmhg sistoličnega, oziroma 90 mmhg diastoličnega ali več. Pri bolnikih s sladkorno boleznijo in prizadetostjo organov (glej Pojasnila točka 1b) uvedemo zdravila, če je sistolični krvni tlak med 130 in 139 mmhg ali diastolični krvni tlak med 80 in 89 mmhg. (E*) Kadar je zdravljenje z zdravili že uvedeno, terapijo titriramo do ciljnega krvnega tlaka 130 mmhg sistoličnega in 80 mmhg diastoličnega. (E*) 4. Zdravljenje z zdravili začnemo s kombinacijo dveh zdravil, sploh če gre za bolj ogrožene bolnike ob prisotni klinični ali subklinični okvari organov. (E*) Zaželeno je, da je eno od zdravil zaviralec angiotenzinske konvertaze ali antagonist angiotenzinskih receptorjev* (E*). Priporočene začetne kombinacije antihipertenzivov z dokazanim učinkom na zmanjšanje srčno-žilnih zapletov so (E*): zaviralec angiotenzinske konvertaze in diuretik antagonist angiotenzinskih receptorjev in diuretik zaviralec angiotenzinske konvertaze in kalcijev antagonist 5. Priporočamo merjenje krvnega tlaka doma. Pomembno je, da bolnik uporablja ustrezno validiran merilnik za merjenje in da je poučen o njegovi pravilni rabi. Bolniku natančno pojasnimo ciljne vrednosti, pravilno beleženje meritev in ga opozorimo, naj brez dogovora z zdravnikom ne spreminja antihipertenzivnega zdravljenja. Normalna vrednost ob meritvah doma je nižja kot ob meritvah v zdravstveni ustanovi (glej dodatek 1) ( 1, 2, 3, 7). (E*) POJASNILA

2 Ad 1. Razvrstitev krvnega tlaka in diagnostični postopki so enaki kot pri bolnikih brez sladkorne bolezni (določitev krvnega tlaka z večkratnimi meritvami, izključitev sekundarnih vzrokov hipertenzije, ocena okvare organov). a) Metode merjenja krvnega tlaka in merila za normalne vrednosti. Meritev krvnega tlaka v zdravstveni ustanovi Razvrstitev krvnega tlaka: Sistolični krvni tlak Diastolični krvni tlak Optimalni krvni tlak pod 120 mmhg in pod 80 mmhg Normalni krvni tlak 120 do 129 mmhg in 80 do 84 mmhg Visoko normalni krvni tlak 130 do 139 mmhg oziroma 85 do 89 mmhg Hipertenzija 1. stopnje 140 do 159 mmhg oziroma 90 do 99 mmhg Hipertenzija 2. stopnje 160 do 179 mmhg oziroma 100 do 109 mmhg Hipertenzija 3. stopnje 180 mmhg ali več oziroma 110 mmhg ali več Izolirana sistolična hipertenzija 140 mmhg ali več in pod 90 mmhg Priporočamo uporabo živosrebrnega sfigmomanometra ali drugega merilnika, ki je preverjen s standardiziranimi protokoli. Uporabljamo primerno široko manšeto glede na obseg nadlakti. Krvni tlak v ordinaciji izmerimo po nekajminutnem počitku, sede, z manšeto v višini srca, upoštevajoč prvo in peto fazo Korotkovovih tonov. Napravimo vsaj dve meritvi s presledkom ene ali dveh minut; če je razlika velika, so potrebne še dodatne meritve. Ob prvem pregledu izmerimo tlak na obeh nadlakteh in upoštevamo meritev na nadlakti z višjo vrednostjo. Ob sumu na ortostatsko hipotenzijo izmerimo krvni tlak po eni in po petih minutah stoječega položaja. 24-urno merjenje krvnega tlaka Uporabljamo lahko tudi 24-urno merjenje krvnega tlaka, pri čemer je normalna vrednost krvnega tlaka nižja. Metoda je še posebej primerna, kadar je ob meritvah v zdravstveni ustanovi krvni tlak zelo variabilen, kadar izmerimo visok krvni tlak pri bolniku z nizkim srčno-žilnim tveganjem, ob pomembnih odstopanjih med meritvami v zdravstveni ustanovi in doma, kadar je hipertenzija odporna na zdravila, kadar sumimo na hipotenzijo ter ob sumu na preeklampsijo, če je krvni tlak v zdravstveni ustanovi visok. Merjenje krvnega tlaka doma Priporočamo uporabo preverjenih merilnikov z nadlahtno manšeto. Seznam neodvisno ocenjenih zanesljivih in natančnih merilnikov lahko najdemo na internetnih straneh Ko merimo krvni tlak doma, ne uživamo cigaret ali kave 30 min pred merjenjem, krvni tlak merimo sede, s stopali položenimi na tla, po vsaj 5 minutnem počitku. Manšeto namestimo v sredino nadlahti v višini srca na tisti roki, kjer smo izmerili višji tlak. Med merjenjem ne govorimo in ne križamo nog. Krvni tlak merimo zjutraj in zvečer, vsakič dvakrat, po 1 minutnem presledku, neprekinjeno teden dni. Meritve zapisujemo v dnevnik

3 meritev. Z merjenjem doma preverjamo učinkovitost zdravljenja v obdobju med odmerki zdravil in vzpodbujamo redno in pravilno jemanje zdravil. Merjenje doma odsvetujemo, kadar bolniku povzroča nelagodje ali vzpodbudi bolnika, da sam spreminja shemo zdravljenja. Normalen krvni tlak glede na metodo meritve: Sistolični krvni tlak(mmhg) Diastolični krvni tlak(mmhg) Krvni tlak v zdravstveni ustanovi Povprečje 24-urnih meritev Povprečje dnevnih meritev Povprečje nočnih meritev Samomeritve krvnega tlaka doma b) Ocena okvare organov Subklinična okvara organov: Glede na enostavnost, široko dostopnost in ceno v rutinski uporabi iščemo: mikroalbuminurijo proteinurijo ocenjeno glomerulno filtracijo (z MDRD enačbo) pod 60 ml/min/1.73m2 hipertrofijo levega prekata (ocenjeno z EKG). Če imamo možnost, lahko pri oceni subklinične okvare upoštevamo tudi ultrazvočno (ali kako drugače, npr. z MRI) ocenjeno hipertrofijo levega prekata, prisotnost sprememb na vratnih arterijah, zvečano togost aorte. Klinična okvara organov: možgansko-žilna bolezen: ishemična možganska kap, možganska krvavitev, tranzitorna ishemična ataka srčna bolezen: miokardni infarkt, angina pektoris, koronarna revaskularizacija, srčno popuščanje ledvična bolezen: diabetična ledvična bolezen, serumski kreatinin nad 133 µmol/l pri moških, nad 124 µmol/l pri ženskah, proteinurija več kot 30 g/mol kreatinina periferna arterijska žilna bolezen napredovala retinopatija: krvavitve ali eksudati, edem papile (E*). c) Pogostost meritev krvnega tlaka in hitrost titracije zdravil do ciljnih vrednosti krvnega tlaka je odvisna od višine krvnega tlaka in okvare organov. V fazi titracije zdravil bolnike naročamo na kontrolo na 2-4 tedne z namenom prilagajanja odmerkov, dodajanja zdravil, preverjanja morebitnih stranskih učinkov. Ob dosegu ciljnega krvnega tlaka in ureditvi tudi drugih reverzibilnih dejavnikov srčno-žilnega tveganja so kontrole lahko redkejše. Pri bolnikih brez okvare organov in z blago zvišanim začetnim krvnim tlakom so lahko kontrole vsakih 6 mesecev. Pri bolnikih z visokim začetnim krvnim tlakom ali okvaro organov pa naj bodo kontole pogostejše. Enako velja za bolnike, ki se zdravijo le z izboljšanjem življenjskih navad. (E*) Ad 3. Bolnika seznanimo s tveganjem zaradi visokega krvnega tlaka, pojasnimo mu pomen doseganja ciljnih vrednosti krvnega tlaka in ga spodbujamo za dolgoročno sodelovanje v zdravljenju (2, 3). (E*)

4 Ad 4. Kombinacija blokatorjev receptorjev beta in tiazidnih diuretikov lahko privede do poslabšanja presnovne urejenosti. Ciljni krvni tlak lahko pogosto dosežemo šele z več kot dvema ali tremi zdravili! UTEMELJITEV Pričujoče priporočilo je pripravljeno na podlagi tujih 1,2,3 in slovenskih priporočil 4,5 s področja sladkorne bolezni in arterijske hipertenzije, pri čemer se večinoma nanaša na zadnje evropske smernice 2 in ponovno oceno evropskih smernic za zdravljenje hipertenzije 3. V utemeljitvi podajamo predvsem razlago novosti. V zadnjem evropskem dokumentu priporočil za zdravljenje arterijske hipertenzije je posebna pozornost pri obravnavi bolnikov z zvišanim krvnim tlakom namenjena subklinični okvari tarčnih organov. V času od zadnjih smernic iz leta 2007 je namreč bilo objavljenih nekaj dodatnih raziskav 6,7,8 ki so še podkrepile pomembnost povezave med prisotnostjo subklinične okvare organov in srčno-žilnimi dogodki. V pričujočih smernicah smo kot pomoč pri oceni bolj ogroženih bolnikov z arterijsko hipertenzijo na podlagi evropskih smernic iz leta 2007 in nove ocene evropskih smernic iz leta 2009 zbrali kriterije, ki nam pomagajo pri oceni subklinične in klinične okvare organov in jih oblikovali v Pojasnilu 1b. Ciljni krvni tlak v pričujočih smernicah je opredeljen kot sistolični krvni tlak 130 mmhg in diastolični krvni tlak 80 mmhg. V ponovni oceni evropskih smernic za arterijsko hipertenzijo iz leta je poudarjeno dejstvo, da nam primanjkuje dokazov iz randomiziranih kliničnih raziskav, ki bi potrdile, da je ciljni krvni tlak pri bolnikih s sladkorno boleznijo dosledno pod 130/80 mmhg, predvsem iz razloga, da nimamo kliničnih raziskav, v katerih bi bolniki s sladkorno boleznijo tipa 2 dosegali krvni tlak nižji od 130/80 mmhg. Več randomiziranih raziskav je sicer pokazalo ugodni učinek znižanja diastoličnega krvnega tlaka na vrednost 80 mmhg ali pod to vrednost pri bolnikih s sladkorno boleznijo, 9,10,11 mejna vrednost sistoličnega krvnega tlaka pod 130 mmhg pa ni tako nedvoumno podprta z dokazi. Imamo pa trdne dokaze iz UKPDS 11 in HOT 9 raziskave, da je večje znižanje krvnega tlaka boljše od manjšega znižanja. Poleg tega so imeli bolniki s sladkorno boleznijo in sistoličnim krvnim tlakom 132 in 128 mmhg v ABCD raziskavi boljši izid s strani srčno-žilnih dogodkov v primerjavi s skupino, ki je imela sistolični krvni tlak 138 in 137 mmhg. 12 Prav tako so bili vidni ugodni učinki na makrovaskularne in mikrovaskularne zaplete sladkorne bolezni ob krvnem tlaku pod 135 mmhg v primerjavi s krvnim tlakom 140 mmhg v raziskavi ADVANCE. 13 Tudi nedavno objavljeni rezultati raziskave ACCORD 14 potrjujejo to razmišljanje, saj so bolniki v intenzivni skupini, kjer so dosegli sistolični krvni tlak celo pod 120 mmhg imeli primerljivo pojavnost srčnožilnih dogodkov, manj pa možganskih kapi v primerjavi z manj intenzivno skupino, ki je dosegla krvni tlak 132 mmhg. Na podlagi omenjenih raziskav in zaradi izsledkov raziskav HOT 9 in Syst-Eur, 15 ki kažejo, da že majhne razlike v krvnem tlaku pri bolnikih s sladkorno boleznijo povzročijo absolutno večje znižanje srčno-žilnih dogodkov, se kljub pomanjkanju absolutnih dokazov zdi smiselno ciljni krvni tlak pri bolnikih s sladkorno boleznijo vzdrževati okoli 130/80 mmhg. Glede pričetka medikamentoznega zdravljenja zvišanega krvnega tlaka se pa pričujoče smernice razlikujejo od smernic iz leta Pri bolnikih brez okvare organov je čas pričetka

5 medikamentoznega zdravljenja ob sistoličnem krvnem tlaku nad 140 mmhg oziroma diastoličnem krvnem tlaku nad 90 mmhg, v čemer so pričujoče smernice v skladu z najnovejšimi evropskimi priporočili. Le-ta priporočajo začetek zdravljenja ob krvnem tlaku med in /ali mmhg v primeru prisotnosti subklinične ali klinične okvare organov (točka 3). Meja, do katere je koristno zniževati krvni tlak pri bolnikih z arterijsko hipertenzijo, ni znana. Nedvomno obstaja vrednost krvnega tlaka, pod katero se poveča srčno-žilno tveganje. Drži pa, da se pri znižanju krvnega tlaka v območje /70-80 mmhg razlike v krvnem tlaku v tem intervalu ne prenesejo več v občutno znižanje srčno-žilne ogroženosti. 16 Možno je tudi, da imajo bolniki z večjo srčno-žilno ogroženostjo tudi višji prag, pod katerim se zmanjša prekrvavitev organov. 17 Vendar pa tega praga z dosedanjimi raziskavami ni bilo možno potrditi ali natančneje opredeliti, niti pri bolnikih z arterijsko hipertenzijo, kaj šele pri bolnikih s pridruženo sladkorno boleznijo. Priporočena izbira antihipertenzivnega zdravljenja se v novih smernicah ne razlikuje bistveno od prejšnjih. Med antihipertenzivi pri sladkornem bolniku svetujemo vedno zaviralec ACE ali antagonist angiotenzinskih receptorjev. Še vedno priporočamo uvedbo kombinacijskega zdravljenja kot prvi korak pri bolnikih z visokim tveganjem za srčno-žilnimi boleznimi ali pri tistih z visokim začetnim krvnim tlakom. Čeprav nimamo prospektivnih raziskav, ki bi dokazale, da je začetno kombinacijsko zdravljenje ugodnejše od postopnega večanja odmerka enega zdravila, so razlogi za pričetek s kombinacijskim zdravljenjem večje znižanje krvnega tlaka, hitrejše doseganje ciljnega tlaka in boljše sodelovanje bolnikov. Priporočene začetne kombinacije so navedene v priporočilih pod točko 4. Za vse navedene kombinacije obstajajo klinične raziskave, ki so dokazale njihovo učinkovitost in varnost pri bolnikih s sladkorno boleznijo. Med kombinacijami ni navedenega zaviralca angiotenzinskih receptorjev z blokatorjem kalcijev kanalčkov, ker nimamo objavljene klinične raziskave, ki bi neposredno potrdila uspešnost te kombinacije. Sicer pa ni razloga, ki bi nakazoval, da ta kombinacija ni primerna kot začetno zdravljenje pri hipertenzivnih bolnikih s sladkorno boleznijo. *pri predpisovanju zdravil upoštevamo veljavna pravila ZZZS. Literatura 1. American Diabetes Association. Standards of Medical Care in Diabetes Diabetes Care 2010; 30 (Suppl. 1): S Mancia G, de Backer G, Dominiscaz A, et.al 2007 Guidelines for the Management of Arterial Hypertension. Journal of Hypertension 2007; 25: Mancia, G, Laurent S, Agabiti-Rosei E, et al. Reappraisal of European guidelines on hypertension management: a European Society of Hypertension Task Force document. J of Hypertension 2009; 27: Accetto R, Dobovišek J, Dolenc P, Salobir B. Slovenske smrnice za obravnavo arterijske hipertenzije (2003). Zdravniški Vestnik 2004; 73: Združenje endokrinologov Slovenije, Diabetes forum in KO za endokrinologijo, diabetes in presnovne bolezni. Slovenske smernice za zdravstveno oskrbo bolnikov s sladkorno boleznijo tipa 2. ISIS, 2007, Suppl, Verdecchia P, Angeli F, Cavallini C et al. The voltage of R wave in lead avl improves risk stratification in hypertensive patients without ECG left ventricular hypertrophy. J Hypertens 2009; 27: Cirillo M, Lanti MP, Menotti A et al. Definition of kidney disfunction as a cardiovascular risk factor: use of urinary albumin excretion and estimated glomerular filtration rate. Arch Intern Med 2008; 168: Ninomiya T, Perkovic V, degalan BE et al. Albuminuria and kidney function independently predict cardiovascular and renal outcomes in diabetes. J Am Soc Nephrol 2009; 20:

6 9 Hansson L, Zanchetti A, Carruthers SG, Dahlof D, Julius S, Menard J, et al. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. Lancet 1998; 351: Schrier RW, Estacio RO; Esler A, Mehler P. Effects of aggressive blood pressure control in normotensive type 2 diabetic patients on albuminuria, retinopathy and stroke. Kidney Int 2002; 61: UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrocascular and microvascular complications in type 2 diabetes: UKPDS 38. British Medical Journal 1998; 317: Schrier RW, Estacio RO; Esler A, Mehler P. Effects of aggressive blood pressure control in normotensive type 2 diabetic patients on albuminuria, retinopathy and stroke. Kidney Int 2002; 61: ADVANCE Collaborative Group. Effects of a fixed combination of perindopril and indapamide on macrovascular and microvascular outcomes in patients with type 2 diabetes mellitus (the ADVANCE trial): a randomised controlled trial. Lancet 2007; 370: ACCORD Study Group, Cushman WC, Evans GW et al. Effects of intensive blood-pressure control in type 2 diabetes mellitus. New EnglJ Med 2010; 362: Tuomilehto J, Rastenyte D, Birkenhager WH et al. Effects of calcium channel blockade in older patients with diabetes and systolic hypertension. Systolic hypertension in Europe Trial Investigators. N Engl J Med 1999; 340: Zanchetti A, Grassi G, Mancia G. When should antihypertensive drug treatment be initiated and to what levels should systolic blood pressure be lowered? A critical appraisal. J Hypertens 2009; 27: Zanchetti A, Mancia G, Black HR et al. Facts and fallacies of blood pressure control in recent trials: implications in the management of patients with hypertension. J Hypertens 2009; 27:673-9.

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