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The influence of age and the beginning of menopause on the lipid status, LDL oxidation, and CRP in healthy women

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BIBLID: 0370-8179, 135(2007) 5-6, p. 280-285 UDC: 618.173-072.5:612.123.06

ISPITIVAWE UTICAJA STAROSTI I NASTANKA MENOPAUZE

NA LIPIDNI STATUS, OKSIDACIJU

LDL

ČESTICA I

C

-REAKTIVNI PROTEIN KOD ZDRAVIH ŽENA

Zorica­ČAPAREVIĆ,­Nada­KOSTIĆ

Endokrinološko odeqewe, Klinika za internu medicinu, Kliničko­bolnički centar „Dr­Dragiša­Mišović”­–­Dediwe,­Beograd

KRATAK SADRŽAJ

Uvod Ate­ro­ge­ni­pro­fil­li­pi­da­je­zna­ča­jan­fak­tor­ri­zi­ka­za­raz­voj­ate­ro­skle­ro­ze­kod­že­na­u­me­no­pa­u­zi.­Po­vi­še­ni­ni­voi­ ma­lih,­gu­stih­LDL­če­sti­ca­ko­je­su­pod­lo­žne­ok­si­da­ci­ji,­kao­i­po­vi­še­ni­ni­voi­po­ka­za­te­qa­za­pa­qe­wa­ta­ko­đe­su­udru­že­ni­s­ po­ve­ća­nim­ri­zi­kom­za­raz­voj­ate­ro­skle­ro­ze.

Ciq ra da Ciq­ra­da­je­bio­da­se­is­pi­ta­uti­caj­sta­ro­sti­i­na­stan­ka­me­no­pa­u­ze­na­li­pid­ni­sta­tus,­ok­si­da­ci­ju­LDL­če­sti­ca­ i C­re­ak­tiv­ni­pro­tein­(CRP)­kod­zdra­vih­že­na.

Me tod ra da Is­pi­ta­no­je­97­zdra­vih­že­na,­svr­sta­nih­u­tri­gru­pe­pre­ma­sta­ro­sti­(gru­pa­1:­15­že­na­mla­đih­od­45­go­di­na;­gru­ pa­2:­62­že­ne­sta­re­46­55­go­di­na;­gru­pa­3:­20­že­na­sta­rih­56­65­go­di­na)­i­pre­ma­pe­ri­o­du­me­no­pa­u­ze­(73­že­ne­u­me­no­pa­u­zi­i­ 24­že­ne­u­pre­me­no­pa­u­zi).­Kri­te­ri­ju­mi­za­is­kqu­če­we­iz­stu­di­je­bi­li­su:­di­ja­be­tes,­go­ja­znost,­ar­te­rij­ska­hi­per­ten­zi­ja,­is­he­ mij­ska­bo­lest­sr­ca,­ce­re­bro­va­sku­lar­na­obo­qe­wa.­Ni­jed­na­is­pi­ta­ni­ca­ni­je­ni­ka­da­uzi­ma­la­estro­pro­ge­sta­ge­ne.­Od­re­đi­va­ ne­su­vred­no­sti­kon­ven­ci­o­nal­nih­li­pi­da,­ok­si­di­sa­nog­LDL (Ox-LDL)­ho­le­ste­ro­la­i­CRP.

Re zul ta ti Kod­is­pi­ta­ni­ca­gru­pe­3­za­be­le­že­ne­su­sta­ti­stič­ki­zna­čaj­no­ve­će­vred­no­sti­ukup­nog­i­LDL­ho­le­ste­ro­la­(p<0,01)­ ne­go­kod­is­pi­ta­ni­ca­gru­pe­1.­Sta­ti­stič­ki­zna­čaj­no­po­ve­ća­we­ni­voa­Ox-LDL­ho­le­ste­ro­la­(p<0,05)­i­CRP (p<0,01)­uoče­no­je­kod­ is­pi­ta­ni­ca­gru­pe­3.­Vred­no­sti­tri­gli­ce­ri­da­i­HDL­ho­le­ste­ro­la­bi­le­su­pri­bli­žno­iste­u­sve­tri­gru­pe,­ali­je­kod­51%­že­ na­vred­nost­HDL­ho­le­ste­ro­la­bila­ma­wa­od­1,3­mmol/l.­Kod­že­na­u­me­no­pa­u­zi­sta­ti­stič­ki­zna­čaj­no­ve­će­vred­no­sti­(p<0,05)­ do­bi­je­ne­su­za­ukup­ni­i­LDL­ho­le­ste­rol­i­za­CRP,­dok­se­vred­no­sti­Ox-LDL­ho­le­ste­ro­la­ni­su­zna­čaj­no­raz­li­ko­va­le.­Stu­di­ja­ je­po­ka­za­la­po­zi­tiv­nu­ko­re­la­ci­ju­iz­me­đu­sta­ro­sti­i­po­vi­še­nih­vred­no­sti­Ox-LDL­ho­le­ste­ro­la­(p<0,01)­i­CRP (p<0,01).­Utvr­ đe­na­je­sta­ti­stič­ki­zna­čaj­na­po­zi­tiv­na­ko­re­la­ci­ja­Ox-LDL­ho­le­ste­ro­la­sa­CRP (p<0,01).­Kod­že­na­u­me­no­pa­u­zi­ta­ko­đe­je­za­be­ le­že­na­po­zi­tiv­na­ko­re­la­ci­ja­Ox-LDL­ho­le­ste­ro­la­sa­CRP (r=0,6296;­p<0,01),­dok­kod­že­na­u­pre­me­no­pa­u­zi­ni­je­bi­lo­zna­čaj­ ne­ko­re­la­ci­je.

Za kqu čak Kod­zdra­vih­že­na­sta­rih­56­65­go­di­na­zna­čaj­no­su­po­vi­še­ne­vred­no­sti­ukup­nog,­LDL i Ox-LDL­ho­le­ste­ro­la­i­CRP.­ Kod­že­na­u­me­no­pa­u­zi­vred­no­sti­ukup­nog­i­LDL­ho­le­ste­ro­la,­kao­i­CRP­zna­čaj­no­su­po­vi­še­ne­u­od­no­su­na­že­ne­u­pre­me­no­ pa­u­zi.­Na­ve­de­ni­re­zul­ta­ti­su­ge­ri­šu­neo­p­hod­nost­pri­mar­ne­pre­ven­ci­je­že­na­ra­di­sma­we­wa­ri­zi­ka­od­kar­di­o­va­sku­lar­ nih­obo­qe­wa.

Kquč ne re či: li pi di; ok si di sa ni LDL (Ox-LDL)­ho­le­ste­rol;­CRP;­sta­rost;­me­no­pa­u­za;­zdra­ve­že­ne

UVOD

Ate ro skle ro za i bo le sti ko je su we na po sle di ca su vo de ći uzrok smrt no sti od ra slih qu di u sko ro svim ze mqa ma sve ta, a na ro či to u ze mqa ma u raz vo ju i tran­ zi­ci­ji­[1].­Ka­da­se­raz­ma­tra­ju­fak­to­ri­ri­zi­ka­za­raz­ voj ate ro skle ro ze, ne iz o stav no se raz ma tra ulo ga sta­ ro­sti­i­po­la.­Mno­ge­epi­de­mi­o­lo­ške­stu­di­je­su­po­ka­ za le da kod mla dih i „zdra vih” qu di uve li ko po sto­ je ate ro skle ro zni pla ko vi u ko ro nar nim ar te ri ja­ ma.­Po­re­me­ćaj­u­me­ta­bo­li­zmu­li­pi­da­i­ate­ro­skle­ro­ zu sva ka ko po ve zu je i po ve ća we pre va len ci je sa sta­ ro­šću­[2].­To­kom­re­pro­duk­tiv­nog­pe­ri­o­da­kar­di­o­va­ sku­lar­ni­si­stem­že­ne­je­pod­za­šti­tom­pol­nih­ste­ro­ i­da­–­estro­pro­ge­sta­ge­na­[3,­4].­Još­je­stu­di­ja­PRO CAM [5],­ko­ja­je­ob­u­hva­ti­la­oko­6.000­že­na­pro­seč­ne­sta­ ro­sti­od­30­do­48­go­di­na,­po­ka­za­la­da­je­in­ci­den­ci­ ja­kar­di­o­va­sku­lar­nih­bo­le­sti­ma­wa­kod­že­na­u­pre­ me­no­pa­u­zi­ne­go­kod­mu­ška­ra­ca.­Iz­u­ze­tak­su­že­ne­ko­ je­su­bi­le­na­kon­tra­cep­tiv­noj­te­ra­pi­ji­i­mla­de­že­ne­ pu­ša­či.­Sa­me­no­pa­u­zom­se­po­ve­ća­va­ri­zik­za­raz­voj­ kar­di­o­va­sku­lar­nih­bo­le­sti,­i­to­pri­lič­no­na­glo­[6,­ 7].­U­tom­ži­vot­nom­pe­ri­o­du­kod­že­na­se­če­šće­ja­vqa­ ju ne ki „kla sič ni” fak to ri ri zi ka, kao što su go ja­ znost i hi per ten zi ja, ali se me wa i me ta bo li zam li­

pi­da­[8].­U­me­no­pa­u­zi­do­la­zi­do­sni­že­wa­ni­voa­pol­ nih­hor­mo­na,­što­uz­dru­ge­či­ni­o­ce­kod­že­na­sta­ri­ jih­od­50­go­di­na­po­ve­ća­va­mo­guć­nost­na­stan­ka­kar­ di­o­va­sku­lar­nih­bo­le­sti­za­50%,­a­do­smrt­nog­is­ho­da­ do­vo­di­kod­30%­wih­[9].

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nost LPL, pa do la zi do ma weg pre la ska VLDL pre ko IDL u LDL.­Re­zul­tat­je­sma­we­we­ni­voa­LDL u cir ku­ la­ci­ji­pod­dej­stvom­estro­ge­na.­Ovi­ste­ro­i­di­sma­wu­ju­ ok si da ci ju LDL če sti ca naj ve ro vat ni je ta ko što de­ lu­ju­na­će­li­je­en­do­te­la­i­po­ve­ća­va­ju­oslo­ba­đa­we­an­ ti­ok­si­dant­nih­sup­stan­ci­[12,­13].

Sma we we ni voa estro ge na u me no pa u zi do vo di do ra znih po re me ća ja u me ta bo li zmu li pi da ko ji se na ro­ či­to­ogle­da­ju­u­sni­že­wu­ni­voa­HDL-2 če sti ca, po ve ća­ wu ni voa tri gli ce ri da i LDL­ho­le­ste­ro­la­[14].­Ura­ đe­na­su­i­is­tra­ži­va­wa­ko­ja­po­ka­zu­ju­da­je­u­me­no­pa­u­zi­ pro fil li pi da ate ro gen pre vas hod no zbog hi po e stro­ ge ne mi je, ne za vi sno od sta ro sti i in dek sa te le sne ma­ se (BMI)­[7].­Ta­ko­se­de­li­mič­no­mo­že­ob­ja­sni­ti­i­ma­ wi ri zik za na sta nak kar di o va sku lar nih bo le sti u re­ pro­duk­tiv­nom­pe­ri­o­du­u­od­no­su­na­me­no­pa­u­zu.

CIQ RADA

Ciq stu di je je bio da se is pi taju li pid ni sta tus, ok si da ci ja LDL če sti ca i C­re ak tiv nog pro te i na (CRP)­kod­zdra­vih­že­na­u­raz­li­či­tom­ži­vot­nom­do­ bu,­s­ak­cen­tom­na­pe­riod­me­no­pa­u­ze.

METOD RADA

Stu­di­jom­je­ob­u­hva­će­no­97­zdra­vih­že­na­is­pi­ta­ nih u en do kri no lo škoj am bu lant ni Kli ni ke za in­ ter nu me di ci nu Kli nič ko­bol nič kog cen tra „Dr Dra­gi­ša­Mi­šo­vić”­u­Be­o­gra­du.­Sve­is­pi­ta­ni­ce­su­ svr­sta­ne­u­tri­gru­pe­pre­ma­sta­ro­sti­(gru­pa­1:­15­že­na­ mla­đih­od­45­go­di­na;­gru­pa­2:­62­že­ne­sta­re­46­55­go­ di­na;­gru­pa­3:­20­že­na­sta­rih­56­65­go­di­na)­i­dve­gru­ pe pre ma po sto ja wu ili iz o stan ku me no pa u ze (pre me­ no­pa­u­zna­gru­pa:­24­že­ne­sta­re­37­51­go­di­nu;­me­no­pa­u­ zna­gru­pa:­73­že­ne­sta­re­47­64­go­di­ne).­Kri­te­ri­ju­mi­ za is kqu če we iz is pi ti va wa bi li su: di ja be tes, go­ ja znost (BMI­ve­ći­od­30­kg/m2), ar te rij ska hi per ten­ zi ja, is he mij ska bo lest sr ca, po re me ća ji rit ma ra da sr ca, ce re bro va sku lar na obo qe wa, hi po ti re o za, hi­ per­ti­re­o­za,­te­ška­in­su­fi­ci­jen­ci­ja­je­tre­i­bu­bre­ga.­ Ni jed na is pi ta ni ca ni ka da ni je uzi ma la estro pro­ ge­sta­ge­ne.­Pro­to­kol­is­pi­ti­va­wa­je­odo­brio­Etič­ki­ ko­mi­tet­KBC­„Dr­Dra­gi­ša­Mi­šo­vić”.

Krv­za­od­re­đi­va­we­gli­ke­mi­je,­ukup­nog,­HDL, LDL i ok si di sa nog LDL (Ox-LDL) ho le ste ro la, tri gli ce­ ri da i CRPuzi­ma­na­je­u­osam­ča­so­va­uju­tro.­Ove­ana­ li ze su oba vqe ne u Bi o he mij skoj la bo ra to ri ji KBC „Dr­Dra­gi­ša­Mi­šo­vić”.­Ukup­ni­ho­le­ste­rol­i­tri­ gli ce ri di su me re ni en zim skim me to dom na apa ra­ tu Ab bott spec trum.­Za­rad­je­ko­ri­šćen­ko­mer­ci­jal­ ni re a gens Ser bo lab.­Ni­vo­LDL ho le ste ro la je od re­ đen­pre­ma­Fri­dval­do­voj­(Fri ed wald) for mu li, a ni vo HDL ho le ste ro la po sle pre ci pi ta ci je hi lo mi kro­ na, LDL i VLDL sa do dat kom fos fo vol fram ske ki­ se­li­ne­i­jo­na­mag­ne­zi­ju­ma.­Ni­vo­Ox-LDL ho le ste ro­ la je me ren te stom ELI SA (di rekt na sen dvič­teh ni ka sa dva mo no klon ska an ti te la pro tiv odvo je nih an ti­ gen skih de ter mi nan ti na mo le ku lu ok si di sa nog mo­ le­ku­la­apo­li­po­pro­te­i­na).­Za­rad­je­ko­ri­šćen­ko­mer­ ci jal ni test ELI SA (Mer co dia AB, Up psa la, Swe den).­Re­ fe rent ne vred no sti za Ox-LDL­ho­le­ste­rol­su­26­117­ IU/l.­Gli­ke­mi­ja­je­od­re­đi­va­na­glu­ko­zo­ok­si­da­znim­me­ to dom, ki ne tič kim en zim skim me to dom, na apa ra tu Ab bott spec trum.­Za­rad­je­ko­ri­šćen­ko­mer­ci­jal­ni­re­ a gens Ser bo lab.­Vred­no­sti­CRP­su­od­re­đi­va­ne­he­mi­lu­ mi ni scent nim me to dom na apa ra tu Im mu li te-DPC.

Sta ti stič ka ob ra da po da ta ka vr še na je po mo ću pro gram skog pa ke ta SPSS 10.0.­Ko­ri­šće­ni­su­Stu­den­ tov t­test i Man­Vit ni jev (Mann-Whit ney) U­test.­Ko­ re­la­ci­je­su­od­re­đi­va­ne­mul­ti­plom­re­gre­siv­nom­ana­ li­zom.

REZULTATI

U­ta­be­li­1­su­pri­ka­za­ni­re­zul­ta­ti­is­pi­ti­va­nih­ pa­ra­me­ta­ra­kod­že­na­svr­sta­nih­u­tri­gru­pe­pre­ma­ sta­ro­sti.­Vred­no­sti­BMI i gli ke mi je ni su se zna čaj­ no­raz­li­ko­va­le­u­is­pi­ti­va­nim­gru­pa­ma.­Vred­no­sti­ ukup nog i LDL ho le ste ro la bi le su sta ti stič ki zna­ čaj­no­ve­će­u­gru­pi­3­ne­go­u­gru­pi­1­(p<0,01).­Ta­ko­đe­je­ za­be­le­že­na­sta­ti­stič­ki­zna­čaj­na­raz­li­ka­u­vred­no­ sti ma ukup nog i LDL­ho­le­ste­ro­la­iz­me­đu­gru­pa­1­i­ 2 (p<0,05),­dok­se­u­gru­pa­ma­2­i­3­vred­no­sti­ukup­nog­ i LDL­ho­le­ste­ro­la­ni­su­zna­čaj­no­raz­li­ko­va­le.­Ni­je­ utvr­đe­na­sta­ti­stič­ki­zna­čaj­na­raz­li­ka­za­HDL ho­ le ste rol i tri gli ce ri de ni ti u jed noj is pi ti va noj gru­pi.­Vred­no­sti­Ox-LDL ho le ste ro la bi le su naj ve­ će­kod­is­pi­ta­ni­ca­gru­pe­3­sa­sta­ti­stič­ki­zna­čaj­nom­

TABELA 1.­Klinički­i­biohemijski­parametri­ispitanica­prema­starosti.

TABLE 1. Clinical and biochemical parameters in women dependent on age.

Parametar Parameter

Grupa 1 Group 1 (n=15)

Grupa 2 Group 2 (n=62)

Grupa 3 Group 3 (n=20)

Starost­(godine)­/­Age (years) 40.46±3.92 50.98±2.26 59.20±2.76

BMI 24.81±1.49­kg/m2 25.46±1.86­kg/m2 25.18±1.79­kg/m2

Glikemija­/­Blood glucose 4.84±0.45­mmol/l 5.04±0.36­mmol/l 5.10±0.38­mmol/l

Ukupni­holesterol­/­Total cholesterol 5.38±1.34­mmol/l 6.03±1.09­mmol/l* 6.09±0.96­mmol/l##

HDL­holesterol­/­HDL cholesterol 1.19±0.14­mmol/l 1.28±0.35­mmol/l 1.26±0.19­mmol/l LDL­holesterol­/­LDL cholesterol 3.34±1.20­mmol/l 4.13±0.97­mmol/l** 4.08±0.81mmol/l## Trigliceridi­/­Triglycerides 1.62±0.94­mmol/l 1.63±1.03­mmol/l 1.68±0.84­mmol/l Ox-LDL­holesterol­/­Ox-LDL cholesterol 77.66±21.21­IU/l 95.64±44.64­IU/l 107.85±49.43­IU/l#

CRP 0.51±0.33­mg/ml 1.41±1.28­mg/ml 2.02±1.82­mg/ml##

Sve­vrednosti­su­statistički­značajno­različite­u­odnosu­na­grupu­1:­*p<0,05;­**p<0,01;­#p<0,05;­##p<0,01

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raz­li­kom­u­od­no­su­na­gru­pu­1­(p<0,5).­Vred­no­sti­CRP bi­le­su­naj­ve­će­u­gru­pi­3­sa­sta­ti­stič­ki­zna­čaj­nom­ raz­li­kom­u­od­no­su­na­gru­pu­1­(p<0,01).

U­ta­be­li­2­su­pri­ka­za­ni­re­zul­ta­ti­is­pi­ti­va­nih­ pa­ra­me­ta­ra­kod­že­na­svr­sta­nih­u­dve­gru­pe­pre­ma­po­ sto­ja­wu­me­no­pa­u­ze.­Vred­no­sti­ukup­nog­i­LDL ho le ste­ ro la, kao i CRP su bi le sta ti stič ki zna čaj no ve će kod že­na­u­me­no­pa­u­zi­(p<0,05),­dok­su­vred­no­sti­Ox-LDL ho­le­ste­ro­la­ta­ko­đe­bi­le­ve­će­kod­ovih­is­pi­ta­ni­ca,­ ali­bez­sta­ti­stič­ki­zna­čaj­ne­raz­li­ke.

Ana­li­zi­ra­na­je­ko­re­la­ci­ja­iz­me­đu­svih­is­pi­ti­ va­nih­pa­ra­me­ta­ra­i­utvr­đe­no­je­da­je­po­sto­ja­la­po­ zi tiv na ko re la ci ja sta ro sti sa Ox-LDL ho le ste ro­ lom (r=0,3135;­p<0,01)­i­CRP (r=0,3817;­p<0,01).­Ta­ko­ đe­je­za­be­le­že­na­sta­ti­stič­ki­zna­čaj­na­po­zi­tiv­na­ko­ re la ci ja Ox-LDL ho le ste ro la sa CRP (r=0,680;­p<0,01).­ Vred no sti Ox-LDL ho le ste ro la su bi le u po zi tiv noj ko re la ci ji sa CRP u gru pi 2 (r=0,380;­p<0,01),­kao­i­ u­gru­pi­3­(r=0,002;­p<0,01).­Kod­že­na­u­me­no­pa­u­zi­ta­ ko­đe­je­za­be­le­že­na­po­zi­tiv­na­ko­re­la­ci­ja­ova­dva­pa­ ra me tra (r=0,296;­p<0,01),­dok­kod­že­na­u­pre­me­no­pa­ u­zi­zna­čaj­ne­ko­re­la­ci­je­ni­je­bi­lo.

DISKUSIJA

U­no­men­kla­tu­ri­li­pi­da­ho­le­ste­rol­je­pri­vu­kao­ naj­ve­ću­pa­žwu­zbog­ja­sne­ve­ze­s­na­pred­nom­ate­ro­skle­ ro­zom­i­kar­di­o­va­sku­lar­nim­bo­le­sti­ma.­Po­stig­nut­ je kon sen zus oko to ga da se ho le ste rol ozna či vo de­ ćim či ni o cem ri zi ka za na sta nak bo le sti ko ro nar­ nih­ar­te­ri­ja­[15­17].­Pi­o­nir­ska­is­tra­ži­va­wa­Bra­u­na­ (Brown) i Gold staj na (Gold stein)­[18],­do­bit­ni­ka­No­ be­lo­ve­na­gra­de­za­fi­zi­o­lo­gi­ju­i­me­di­ci­nu­1985.­go­ di ne, do ve la su do ot kri ća LDL re cep to ra i pre po­ zna va wa li po pro te i na ma le gu sti ne (low den sity li po-pro ten – LDL) kao li pid ne če sti ce ko ja u naj ve ćoj me­ ri­do­pri­no­si­raz­vo­ju­ate­ro­skle­ro­ze.

Ciq na še stu di je je bio da ot kri je mo da li po sto je po re me ća ji li pid nog sta tu sa i u ko jem sta ro snom do­ bu­že­ne­su­naj­i­zra­že­ni­ji,­s­ak­cen­tom­na­pe­riod­me­no­ pa u ze, kao i da li po sto ji ko re la ci ja sa pa ra me tri ma ok si dant nog stre sa (Ox-LDL) i za pa qe wa (CRP).­Po­ sma­tra­wem­li­pid­nog­sta­tu­sa­kod­že­na,­re­zul­ta­ti­is­ pi­ti­va­wa­su­po­ka­za­li­da­po­sle­45.­go­di­ne­vred­no­sti­ ukup nog i LDL ho le ste ro la po či wu da se po ve ća va ju, ali­da­je­to­po­ve­ća­we­zna­čaj­no­na­ro­či­to­po­sle­56.­go­ di­ne.­Ana­li­zom­li­pid­nog­sta­tu­sa­že­na­u­me­no­pa­u­zi­ po ka za no je da su vred no sti ukup nog i LDL ho le ste­ ro la bi le zna čaj no ve će u tom pe ri o du, što je u sa gla­ sno­sti­i­sa­po­da­ci­ma­iz­li­te­ra­tu­re­[19­22].

Stu­di­ja­zdra­vih­že­na­(The He althy Wo men Study) [23]­je­po­ka­za­la­po­zi­tiv­nu­ko­re­la­ci­ju­iz­me­đu­ate­ro­ skle ro znih pla ko va i po ve ća nih vred no sti LDL ho­ le ste ro la, tri gli ce ri da, in su li na, BMI i vi si ne si­ stol­nog­pri­ti­ska,­dok­je­za­be­le­že­na­obr­nu­ta­ko­re­la­ ci­ja­iz­me­đu­HDL ho le ste ro la i kar di o va sku lar nih bo­le­sti.­Re­zul­ta­ti­na­še­stu­di­je­ni­su­po­ka­za­li­zna­ čaj nost raz li ka u vred no sti ma tri gli ce ri da i HDL ho­le­ste­ro­la­kod­svih­is­pi­ta­ni­ca.­Tri­gli­ce­ri­di­su­ ina­če­kod­že­na­ose­tqi­vi­ji­pre­dik­tor­bu­du­ćeg­raz­vo­ ja­ko­ro­nar­ne­bo­le­sti­[24]­ne­go­kod­mu­ška­ra­ca.­Na­i­ me,­hi­per­tri­gli­ce­ri­de­mi­ja­je­udru­že­na­sa­sni­že­nim­ ni vo om HDL ho le ste ro la i po vi še nim ni vo om ma­ lih gu stih i vr lo ate ro ge nih LDL­če­sti­ca­[25].­Hel­ sin ška stu di ja (Hel sin ki He art Study)­[26]­i­stu­di­ja­ PRO CAM­[5,­27]­su­po­ka­za­le­da­je­hi­per­tri­gli­ce­ri­ de mi ja ne sa mo u uzroč noj ve zi s is he mij skom bo le­ sti sr ca, već i ne za vi san či ni lac ri zi ka ovog obo­ qe­wa.­Stu­di­ja­PRO CAM je po ka za la da, osim ukup nog i LDL ho le ste ro la, po vi šen ni vo tri gli ce ri da po­ ve ća va in ci den ci ju in fark ta mi o kar da čak i ka da je ni vo LDL­ho­le­ste­ro­la­nor­ma­lan.­Pre­ma­po­da­ci­ma­ Fra­min­gam­ske­stu­di­je­[28],­kod­že­na­sa­sni­že­nim­ni­ vo om HDL­ho­le­ste­ro­la­(<1,30­mmol/l) zna čaj no i vi­ še stru ko po ve ća we in ci den ci je ko ro nar ne bo le sti je ve će ka da je ni vo tri gli ce ri da nor ma lan, a na ro­ či­to­ako­je­po­vi­šen.­Lon­gi­tu­di­nal­na­ana­li­za­stu­di­ je PRO CAM­[5]­uka­zu­je­na­to­da­HDL ho le ste rol ima naj­ve­ću­pre­dik­tiv­nu­vred­nost.­Obr­nu­ta­ko­re­la­ci­ja­ iz­me­đu­HDL ho le ste ro la i kar di o va sku lar nih bo le­ sti­za­be­le­že­na­je­ne­sa­mo­kod­mu­ška­ra­ca,­već­i­kod­ že­na.­Pre­ma­re­zul­ta­ti­ma­ove­stu­di­je,­kod­19,8%­že­na­ je­utvr­đen­ni­vo­HDL­ho­le­ste­ro­la­ni­ži­od­1,3­mmol/l, dok­je­hi­per­tri­gli­ce­ri­de­mi­ja­za­be­le­že­na­kod­4,2%­ že­na.­Na­še­is­pi­ti­va­we­je­po­ka­za­lo­da,­i­po­red­to­ga­ što se is pi ta ni ce ni su raz li ko va le pre ma vred no­ sti ma HDL­ho­le­ste­ro­la,­vred­no­sti­ni­že­od­1,3­mmol/l utvr­đe­ne­su­kod­51%­wih,­što­ja­sno­uka­zu­je­na­to­da­ je­kod­po­lo­vi­ne­is­pi­ta­nih­že­na­bio­po­ve­ćan­ri­zik­ za­na­sta­nak­kar­di­o­va­sku­lar­nih­obo­qe­wa.­Kam­pa­wo­ li (Cam pag no li)­i­sa­rad­ni­ci­[29]­sma­tra­ju­da­je­sma­ we na vred nost HDL ho le ste ro la naj bo qi pre dik tor ri­zi­ka­za­kar­di­o­va­sku­lar­na­obo­qe­wa­kod­že­na­ko­je­ ne­pri­ma­ju­estro­pro­ge­sta­ge­ne.

Od­in­te­re­sa­je­bi­lo­be­le­že­we­vred­no­sti­Ox-LDL ho le ste ro la i CRP­kod­že­na,­jer­glav­no­me­sto­u­ini­ ci ja ci ji dis funk ci je en do te la pred sta vqa mo di fi­ ka ci ja LDL če sti ce u ob li ku ok si dant no mo di fi ko­ va ne LDL če sti ce (Ox-LDL)­[30].­Ok­si­dant­na­mo­di­ fi ka ci ja LDL če sti ce uglav nom se od vi ja u zi du krv­

TABELA 2.­Klinički­i­biohemijski­parametri­ispitanica­prema­ postojawu­menopauze.

TABLE 2. Clinical and biochemical parameters in women dependent

on menopause.

Parametar Parameter

Premenopauzna grupa Premenopausal

group (n=24)

Menopauzna grupa Menopausal

group (n=73)

Starost (godine)

Age (years) 43.83±4.45 53.54±4.17

BMI 24.86±1.37­kg/m2 25.48±1.90­kg/m2

Glikemija

Blood glucose 4.55±0.35­mmol/l 5.20±0.25­mmol/l

Ukupni­holesterol

Total cholesterol 5.62±1.39­mmol/l 6.05±1.00­mmol/l* HDL­holesterol

HDL cholesterol 1.23±0.22­mmol/l 1.27±0.32­mmol/l LDL­holesterol

LDL cholesterol 3.66±1.20­mmol/l 4.11±0.91­mmol/l*

Trigliceridi

Triglycerides 1.52±0.82­mmol/l 1.68±1.02­mmol/l Ox-LDL­holesterol

Ox-LDL cholesterol 76.54±23.90­IU/l 101.36±46.64­IU/l

CRP 0.71±0.73­mg/ml 1.72±1.51­mg/ml*

(4)

nog su da, gde se na la zi ve ća ko li či na re doks­ak tiv­ nih­me­ta­la­oslo­bo­đe­nih­iz­cir­ku­li­šu­ćih­an­ti­ok­si­ dan­sa­u­uslo­vi­ma­ok­si­dant­nog­stre­sa­[31].­Ox-LDL ho­ le­ste­rol­mo­že­bi­ti­kquč­ni­an­ti­gen­ko­ji­do­vo­di­do­ za pa qe wa ar te rij ske in ti me, što je jed na je od glav­ nih­od­li­ka­ate­ro­skle­ro­ze.­Sma­tra­se­da­aku­mu­la­ci­ja,­ agre ga ci ja i ok si dant na mo di fi ka ci ja LDL če sti ce igra­ju­va­žnu­ulo­gu­u­ak­ti­vi­ra­wu­za­pa­qew­skih­pro­ ce­sa­ko­ji­pod­sti­ču­stva­ra­we­ate­ro­skle­ro­znih­le­zi­ja.­ Po ve ća ni ni voi Ox-LDL ho le ste ro la uka zu ju na to da je­pro­ces­raz­vo­ja­ate­ro­skle­ro­ze­ubr­zan­i­da­od­re­đi­va­ we­vred­no­sti­ovog­ho­le­ste­ro­la­mo­že­bi­ti­od­ve­li­kog­ zna­ča­ja­za­ra­no­ot­kri­va­we­ovog­oboqewa­[32­35].­U­na­ šoj stu di ji naj vi še vred no sti Ox-LDL ho le ste ro la za­be­le­že­ne­su­kod­že­na­sta­ri­jih­od­56­go­di­na­(gru­pa­ 3).­Ka­da­je­reč­o­vred­no­sti­Ox-LDL­ho­le­ste­ro­la­že­na­ u pe ri o du me no pa u ze, iako je ni vo Ox-LDL ho le ste­ rol bio vi ši u tom pe ri o du, ni je bi lo zna čaj ne raz­ li­ke­u­od­no­su­na­že­ne­u­pre­me­no­pa­u­zi.

Mno ge stu di je su po ka za le da su i po vi še ni ni­ voi CRP­u­se­ru­mu­udru­že­ni­s­po­ve­ća­nim­ri­zi­kom­za­ na pre do va we ate ro skle ro znog pro ce sa i za is he mij­ sku­bo­lest­sr­ca­[36­39].­Rid­ker­(Rid ker) i sa rad ni ci [40]­su­uoči­li­da­se­kod­zdra­vih­že­na­s­po­vi­še­nim­ vred no sti ma CRP is he mij ska bo lest sr ca ja vqa dva­ tri pu ta če šće, čak i on da ka da su im vred no sti ho­ le­ste­ro­la­nor­mal­ne.­Ra­ni­je­po­me­nu­ta­Stu­di­ja­zdra­ vih­že­na­(The He althy Wo men Study)­[23]­po­ka­za­la­je­ da je po vi šen ni vo CRP u ve zi sa dru gim fak to ri ma ko ji po ve ća va ju ri zik za na sta nak is he mij ske bo le­ sti­sr­ca­kod­že­na,­kao­što­su­sta­rost,­pu­še­we­ci­ga­ re ta, ni zak ni vo HDL ho le ste ro la, vred no sti BMI i po­vi­šen­krv­ni­pri­ti­sak.­Po­ve­ća­we­vred­no­sti­CRP kod­is­pi­ta­ni­ca­u­na­šem­is­tra­ži­va­wu­be­le­ži­se­po­ sle­45.­go­di­ne,­da­bi­naj­ve­će­vred­no­sti­do­sti­gle­po­ sle­56.­go­di­ne.­S­ob­zi­rom­na­to­da­si­stem­ski­od­go­ vor na za pa qe we do vo di do po ve ća ne ok si dant ne mo­ di fi ka ci je LDL­ho­le­ste­ro­la­[41,­42],­to­i­ob­ja­šwa­ va­da­je­u­gru­pa­ma­že­na­kod­ko­jih­je­ni­vo­CRP bio po­ vi šen i vred nost Ox-LDL­ho­le­ste­ro­la­naj­ve­ća.­Na­ ša­stu­di­ja­je­po­ka­za­la­po­zi­tiv­nu­ko­re­la­ci­ju­iz­me­đu­ sta ro sti i po vi še nih vred no sti Ox-LDL ho le ste ro­ la i CRP.­Ta­ko­đe­je­utvr­đe­na­po­zi­tiv­na­ko­re­la­ci­ja­ Ox-LDL ho le ste ro la sa CRP,­na­ro­či­to­kod­že­na­sta­ ri­jih­od­56­go­di­na.

Re zul ta ti na šeg is pi ti va wa su ja sno po ka za li da se sa sta ro šću, a na ro či to u pe ri o du me no pa u ze, me wa li pid ni sta tus u prav cu ate ro ge nog li pid nog pro fi­ la, što po ve ća va ri zik za raz voj kar di o va sku lar nih bo­le­sti.­Ta­ko­đe,­vred­no­sti­po­ka­za­te­qa­ok­si­dant­nog­ stre sa (Ox-LDL ho le ste rol) i za pa qe wa (CRP) se po­ ve ća va ju sa sta ro šću i na ro či to sa na stan kom me no­ pa­u­ze.­Zbog­to­ga­je­neo­p­hod­no­pra­vo­vre­me­no­ot­kri­ va we po re me ća ja li pid nog sta tu sa, po ka za te qa ok si­ dant nog stre sa i za pa qe wa, kao naj e fi ka sni ja i naj­ jef ti ni ja me ra pre ven ci je is he mij ske bo le sti sr ca, či­je­je­le­če­we­ve­o­ma­sku­po­a­is­hod­ne­iz­ve­stan­[43].

Pri me na hor mon ske sup sti tu ci o ne te ra pi je (HST), tj.­pri­me­na­estro­ge­na­ili­kom­bi­na­ci­je­estro­ge­na­i­ pro ge sta ge na, mo gla bi ima ti pro tek tiv ni efe kat za kar­di­o­va­sku­lar­ne­bo­le­sti­kod­že­na­[44].­Estro­gen­ska­ sup­sti­tu­ci­ja­mo­že­da­sma­wi­raz­voj­kar­di­o­va­sku­lar­ nih­obo­qe­wa­i­za­50%,­ali­je­po­treb­no­da­se­sma­wi­ni­

vo LDL­ho­le­ste­ro­la­za­35%­ili­vi­še.­Estro­ge­ni­ipak­ ne sma wu ju ta ko in te ziv no ni vo LDL ho le ste ro la, pa je wi hov za štit ni efe kat ve ro vat no po sle di ca i ne­ kih­dru­gih­de­lo­va­wa,­mo­žda­di­rekt­no­na­ko­ro­nar­ne­ krv­ne­su­do­ve,­mi­o­kard­ili­aor­tu.­Du­go­roč­na­pla­ce­bo­ kon tro li sa na stu di ja HERS­[45]­ni­je­do­ka­za­la­sma­we­ we­kar­di­o­va­sku­lar­nog­mor­ta­li­te­ta­kod­že­na­na­HST,­ čak­je­i­trom­bo­em­bo­lij­skih­kom­pli­ka­ci­ja­bi­lo­vi­še.­ U­stu­di­ji­WHI (Wo men’s He alth Ini ti a ti ve)­[46]­se­is­po­ qio ne po vo qan efe kat HST na is he mij sku bo lest sr­ ca.­Da­nas­se­HST,­i­po­red­po­zi­tiv­nog­efek­ta­na­li­ pid ni sta tus, ne pre po ru ču je u pre ven ci ji is he mij­ ske­bo­le­sti­sr­ca­že­na­u­me­no­pa­u­zi­[47].­Ipak,­de­fi­ ni tiv ni sta vo vi se tek oče ku ju za ne ko li ko go di na, dok­se­ne­za­vr­ši­ne­ko­li­ko­ve­li­kih­stu­di­ja.

Pri me na sta ti na u le če wu po re me ća ja li pi da u me­ no­pa­u­zi­je­ta­ko­đe­zna­čaj­na,­na­ro­či­to­ako­su­po­ve­ća­ ne vred no sti LDL i Ox-LDL­ho­le­ste­ro­la­[48].­Raz­lo­ zi za pri mar nu pre ven ci ju za sni va ju se na mno gim po da ci ma o po ve za no sti po vi še nih vred no sti LDL ho le ste ro la i po ve ća nog ri zi ka za is he mij sku bo­ lest sr ca i im pre siv nom bro ju kli nič kih i eks pe­ ri men tal nih po da ta ka ko ji po ka zu ju da sma we we ni­ voa LDL ho le ste ro la uspo ra va na pre do va we ate ro­ skle­ro­ze­i­mo­že­da­do­vo­de­od­re­gre­si­je­ate­ro­skle­ro­ zne­le­zi­je.­Sta­ti­ni,­osim­to­ga­što­sma­wu­ju­ate­ro­ge­ ne li pid ne pot frak ci je, do vo de do po boq ša wa i re­ sta u ra ci je funk ci je en do te la, po ve ća va ju sta bil nost ate ro skle ro znog pla ka, po ka zu ju an ti ok si dant no dej­ stvo (sma we we ose tqi vo sti LDL če sti ca pre ma slo­ bod nim ra di ka li ma) i an ti in fla ma tor no de lo va we iz­ra­že­no­u­sma­we­wu­ni­voa­CRP.­Od­mno­gih­stu­di­ja­ ko je su ukqu či le ve li ki broj is pi ta ni ca na te ra pi ji sta ti ni ma naj zna čaj ni je su 4S (Scan di na vian Sim va sta-tin Sur vi val Study)­[49]­i­CA RE (Cho le ste rol and Re cur-rent Events)­[50],­ko­je­su­po­ka­za­le­sma­we­we­kar­di­o­va­ sku­lar­nog­mor­ta­li­te­ta­že­na.­Tre­nut­no­su­u­to­ku­još­ ne ke stu di je o pri me ni sta ti na ko je će da ti još bo qe od go vo re na pi ta we da li su sta ti ni lek iz bo ra ka ko u se kun dar noj, ta ko i u pri mar noj pre ven ci ji kar di­ o­va­sku­lar­nih­bo­le­sti­i­kod­že­na­u­me­no­pa­u­zi.

ZAKQUČAK

Kod­zdra­vih­že­na­sta­rih­56­65­go­di­na­zna­čaj­no­su­ po vi še ne vred no sti ukup nog, LDL i Ox-LDL ho le ste­ ro la i CRP.­Kod­že­na­u­me­no­pa­u­zi­vred­no­sti­ukup­ nog i LDL ho le ste ro la, kao i CRP zna čaj no su ve će ne­ go­kod­že­na­u­pre­me­no­pa­u­zi.­Na­ve­de­ni­re­zul­ta­ti­su­ ge­ri­šu­neo­p­hod­nost­pri­mar­ne­pre­ven­ci­je­že­na­ra­ di sma we wa ri zi ka za na sta nak kar di o va sku lar nih obo­qe­wa.

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Introduction Atherogenic lipid profile is an important risk fac-tor in development of atherosclerosis in menopausal women. High level of small dense LDL, that is more susceptible to oxida-tion, and high levels of inflammatory markers are also associated with an increased risk for development of atherosclerosis. Objective The aim of this study was to investigate the rela-tionship between lipid profile, oxidized LDL (Ox-LDL) and C-re-active protein (CRP) as inflammatory reaction in healthy wom-en depwom-endwom-ent on age and mwom-enopause.

Method The study included a group of clinically healthy wom-en (total of 97 womwom-en). Group 1: 15 womwom-en younger than 45 years; group 2: 62 women between 46 and 55 years, group 3: 20 women between 56 and 65 years, group of menopausal wom-en (73) and group of premwom-enopausal womwom-en (24). None of the women had history of obesity, diabetes mellitus, cerebrovas-cular, ischaemic heart disease, and hypertension. Lipid profiles were measured by enzymatic methods. Ox-LDL was measured by using a specific monoclonalantibody, mAb4E6. CRP was measured using hemiluminiscent methods (Immulite-DPC). Results Results showed significantly higher levels of total cho-lesterol (p<0.01) and LDL chocho-lesterol (p<0.01) in women over 56 years compared with women younger than 45 years. We also found similar results in menopausal women. Levels of Ox-LDL (p<0.05) and CRP (p<0.01) showed significantly higher levels in women over 56 years. In menopausal women, we found

signif-icantly higher levels of CRP (p<0.05). There was no significant difference in the levels of oxLDL between the menopausal and premenopausal women. Levels of triglycerides and HDL cho-lesterol were not different among groups. We found that 51% women had levels of HDL cholesterol lower than 1.3 mmol/L. In all groups of women, we found positive correlation among age, Ox-LDL (p<0.01) and CRP (p<0.01). Ox-LDL also positively corre-lated with CRP (p<0.01).

Conclusion In healthy women older than 56 as in menopausal women, we found significantly higher levels of LDL cholester-ol and inflammatory markers. These results suggest that strate-gies of primary prevention in women are needed to reduce the risk of developing cardiovascular disease.

Key words: lipids; oxidized LDL (Ox-LDL); C-reactive protein (CRP); age; menopause; healthy women.

Zorica ČAPAREVIĆ Endokrinološko odeljenje Klinika za internu medicinu

Kliničko-bolnički centar „Dr Dragiša Mišović” – Dedinje Heroja Milana Tepića, 11000 Beograd

Tel.: 011 2667 122 Faks: 011 367 2025 E-mail: capar@eunet.yu

THE INFLUENCE OF AGE AND THE BEGINNING OF MENOPAUSE ON

THE LIPID STATUS, LDL OXIDATION, AND CRP IN HEALTHY WOMEN

Zorica ČAPAREVIĆ, Nada KOSTIĆ

Department of Endocrinology, Clinical Centre “Dr Dragiša Mišović” – Dedinje, Belgrade

Imagem

TABELA 1.­Klinički­i­biohemijski­parametri­ispitanica­prema­starosti.
TABELA 2. ­Klinički­i­biohemijski­parametri­ispitanica­prema­

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