I HC HU

TRNG I HC Y DC

CHU M CHI

NGHIN CU S LIN QUAN GIA NNG ENZYME MYELOPEROXIDASE HUYT TNG VI B DAY

LP NI TRUNG MAC NG MACH CANH VA MT S YU T NGUY C TIM MACH BNH NHN AI THAO NG TYP 2

LUN N TIN S Y HC

HU - 2016

CH

U

M

CH

I L

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IN

S Y

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C

HU

- 2

01

6

176TR, 15BIA

I HC HU

TRNG I HC Y DC

CHU M CHI

NGHIN CU S LIN QUAN GIA NNG ENZYME MYELOPEROXIDASE HUYT TNG VI B DAY

LP NI TRUNG MAC NG MACH CANH VA MT S YU T NGUY C TIM MACH BNH NHN AI THAO NG TYP 2

Chuyn ngnh : NI TIT

M s : 62 72 01 45

LUN N TIN S Y HC

Ngi hng dn khoa hc:

1. GS.TS. NGUYN HI THY

2. PGS.TS. O TH DA

HU - 2016

c c thnh qu ngy hm nay, ti nhn c nhiu s

quan tm gip ca c quan, qu Thy C, gia nh v bn b.

Li u tin, ti xin trn trng gi li cm n chn thnh n

Ban gim c i hc Hu, Ban gim hiu Trng i hc Y

Dc Hu, Ban gim c Bnh vin Trung ng Hu, Ban

gim c Bnh vin a khoa Trung tm Tin Giang, Ban Ch

nhim cng cc Thy, C, Anh, Ch ng nghip trong B mn

Ni- Trng i hc Y Dc Hu to mi iu kin thun

li v h tr ti trong qu trnh hc tp v nghin cu.

c bit ti xin by t lng knh trng v bit n su sc n

GS.TS Nguyn Hi Thy, PGS.TS o Th Da l

nhng ngi Thy tn tnh ging dy, du dt, gip , khch l

ti trong qu trnh hc tp, lm vic v nghin cu. Cc Thy

dnh nhiu thi gian, tr tu trc tip hng dn ti thc hin v

hon thnh lun n ny.

Ti cng xin chn thnh cm n ThS L Th Phng

Anh, ThS L Th Diu Phng v nhn vin khoa Ha Sinh

tn tnh gip v thc hin xt nghim nghin cu.

Ti cm n chn thnh n nhng bnh nhn, nhng ngi

ng tham gia cng trnh nghin cu ny.

Cui cng, bng nhng tnh cm thn thng nht xin dnh

cho Ba, M, Chng, cc Con v nhng ngi thn trong gia nh

cho ti im ta v ngun ng vin tinh thn qu gi nht.

Mt ln na xin trn trng v tri n n tt c mi ngi.

Hu, 2015

Chu M Chi

LI CAM OAN

Ti xin cam oan rng: y l cng trnh nghin

cu ca ring ti. Cc s liu, kt qu trong lun n ny

l trung thc v cha tng c ai cng b trong bt k

mt cng trnh nghin cu no khc trc y.

K tn

Chu M Chi

MC LC

Trang

Trang ph ba

Li cam oan

Mc lc

Ch vit tt

Danh mc cc bng

Danh mc cc biu , s , th

Danh mc cc hnh

T VN .................................................................................................. 1

Chng 1. TNG QUAN TI LIU ............................................................ 4

1.1. Bnh mch mu ln i tho ng tp 2 .......................................... 4

1.2. Yu t nguy c tim mch bnh nhn i tho ng tp 2 ................ 9

1.3. Enzyme myeloperoxidase .................................................................... 19

1.4. Cc phng tin thm d tn thng x va ng mch cnh ........... 32

1.5. Cc nghin cu v myeloperoxidase lin quan n ti ................... 38

Chng 2. I TNG V PHNG PHP NGHIN CU ............. 42

2.1. i tng nghin cu .......................................................................... 42

2.2. Phng php nghin cu ...................................................................... 43

Chng 3. KT QU NGHIN CU ........................................................ 59

3.1. Mt s yu t nguy c truyn thng ca i tng nghin cu .......... 59

3.2. Mt s yu t nguy c khng truyn thng ca i tng nghin cu ..... 63

3.3. in tim v siu m tim ....................................................................... 68

3.4. Nng myeloperoxidase (MPO) huyt tng ca i tng nghin cu .. 70

3.5. S lin quan gia mpo vi cc yu t nguy c tim mch bnh nhn

i tho ng ...................................................................................... 73

3.6. Mi tng quan gia mpo vi mt s yu t nguy c bnh nhn i

tho ng ............................................................................................ 78

Chng 4. BN LUN ................................................................................. 89

4.1. Cc yu t nguy c tim mch truyn thng ca i tng nghin cu ..... 89

4.2. Cc yu t nguy c tim mch khng truyn thng ca i tng

nghin cu ............................................................................................ 98

4.3. in tim v siu m tim ..................................................................... 105

4.4. Nng enzyme mpo i tng nghin cu .................................. 108

4.5. S lin quan gia nng mpo huyt tng vi cc yu t nguy c

tim mch ............................................................................................ 112

4.6. S tng quan gia MPO v cc yu t nguy c .............................. 121

KT LUN .................................................................................................. 126

KIN NGH ................................................................................................. 128

DANH MC CC CNG TRNH KHOA HC LIN QUAN CNG B

TI LIU THAM KHO

PH LC

CH VIT TT

- AGEs : Advanced glycation end products

(Cc sn phm cui ca ng ha bc cao)

- BMI : Body Mass Index

(Ch s khi c th).

- CTA : Computed Tomographic Angiography

(Chp mch ct lp vi tnh)

- DSA : Digital subtraction angiography

(Chp mch mu s ha xa nn)

- MV : ng mch vnh

- TB : i thc bo

- T : i tho ng.

- EF : Ejection fraction

(Phn sut tng mu)

- eNOS : Endothelial nitric oxide synthase

(Enzyme tng hp nitric oxide ni mc)

- HDL-C : High density lipoprotein cholesterol

(Cholesterol lipoprotein t trng cao)

- hs-CRP : High-sensitivity C-reactive protein

(Protein phn ng C nhy cao)

- LDL-C : Low density lipoprotein cholesterol

(Cholesterol lipoprotein t trng thp)

- LDLoxh : LDL oxy ha

- IMT : Intima-media thickness

(B dy lp ni trung mc).

-LVMI : Left Ventricular Mass Index

(Ch s khi c tht tri)

- MACE : Major adverse cardiovascular event

(Bin c tim mch bt li chnh)

- MPO : Myeloperoxidase

- MRA : Magnetic Resonance Angiography

(Chp mch cng hng t)

- NMCT : Nhi mu c tim

- NO : Nitric oxide

- NOS : Nitric oxide synthase

(Enzyme tng hp nitric oxide)

- PAI-1 : Plasminogen activitor inhitor-1

(Cht c ch hot ha plasminogen 1)

- RLCNNM : Ri lon chc nng ni mc

- RLDN : Ri lon dung np

- RLLP : Ri lon lipid

- ROS : Reactive oxygen species

(Cc mu oxy phn ng)

- TC : Total cholesterol

(Cholesterol ton phn)

- TG : Triglycerid

- THA : Tng huyt p

- TMCT : Thiu mu c tim

- VB : Vng bng

- WHO : World Health Organization

(T chc Y t Th gii)

- XVM : X va ng mch.

- YTNC : Yu t nguy c

DANH MC CC BNG

Trang

Bng 2.1. Phn bo ph p dng cho ngi Chu - Thi Bnh Dng .... 48

Bng 3.1. Phn b t l tui v gii ca i tng nghin cu .................... 59

Bng 3.2. Phn b tnh trng THA nhm bnh ......................................... 60

Bng 3.3. c im chung v lipid mu nhm bnh ................................. 61

Bng 3.4. T l ri lon lipid mu nhm bnh ........................................... 61

Bng 3.5. T l kim sot lipid mu theo mc tiu nhm bnh ................. 62

Bng 3.6. Cc ch s sinh x va nhm bnh............................................ 62

Bng 3.7. Cc ch s sinh x va nguy c nhm bnh .............................. 63

Bng 3.8. c im BMI nhm bnh ........................................................... 63

Bng 3.9. T l bo ph dng nam nhm bnh ........................................... 64

Bng 3.10. c im glucose i v HbA1C nhm bnh ........................... 64

Bng 3.11. c im v CRP nhm bnh ................................................... 65

Bng 3.12. c im v Fibrinogen huyt tng nhm bnh ..................... 65

Bng 3.13. c im v bch cu nhm bnh ................................................ 66

Bng 3.14. c im v b dy ng mch cnh (IMT) nhm bnh ............. 66

Bng 3.15. T l x va ng mch cnh nhm bnh ................................. 67

Bng 3.16. c im v QTc in tim nhm bnh .................................. 68

Bng 3.17. c im v ch s Sokolow-Lyon in tim nhm bnh .......... 68

Bng 3.18. c im v thiu mu c tim trn in tim nhm bnh .......... 69

Bng 3.19. c im v ch s khi c tht tri (LVMI) nhm bnh ......... 69

Bng 3.20. c im v EF nhm bnh ...................................................... 70

Bng 3.21. Nng MPO ca nhm chng ................................................... 70

Bng 3.22. Nng MPO ca nhm bnh ..................................................... 71

Bng 3.23. T l tng MPO X 2SD ca nhm bnh v nhm chng ........ 72

Bng 3.24. Lin quan gia MPO vi tui, thi gian pht hin bnh v

THA nhm bnh ........................................................................ 73

Bng 3.25. Lin quan MPO vi lipid mu v cc ch s lipid nhm bnh .. 74

Bng 3.26. Lin quan gia MPO vi vng bng v ch s khi c th .......... 75

Bng 3.27. Lin quan MPO vi ng huyt ................................................. 75

Bng 3.28. Lin quan MPO vi cc yu t vim ............................................ 76

Bng 3.29. Lin quan gia MPO vi IMT < 0,9 v IMT 0,9mm ................ 76

Bng 3.30. Lin quan gia MPO vi mng x va ........................................ 77

Bng 3.31. Lin quan MPO vi bt thng trn in tim .............................. 77

Bng 3.32. Lin quan gia MPO vi EF v LVMI trn siu m tim ............. 78

Bng 3.33. Tng quan gia MPO vi mt s yu t nguy c truyn thng .... 78

Bng 3.34. Tng quan gia MPO vi mt s yu t nguy c khng

truyn thng .................................................................................. 79

Bng 3.35. Tng quan gia MPO vi bin chng tim ................................. 81

Bng 3.36. Tng quan hi quy tuyn tnh a bin gia MPO vi cc YTNC .. 82

Bng 3.37. Din tch di ng cong ROC gia MPO vi vng bng

tng ng vi MPO330pmol/l ................................................... 83

Bng 3.38. Din tch di ng cong ROC gia MPO vi BMI tng

ng vi MPO330pmol/l ............................................................. 84

Bng 3.39. Din tch di ng cong ROC gia MPO vi IMT tng

ng vi MPO330pmol/l ............................................................. 85

Bng 3.40. Din tch di ng cong ROC gia MPO vi QTc tng

ng vi MPO330pmol/l ............................................................. 86

Bng 3.41. Ch s nguy c gia MPO vi IMT ............................................. 87

Bng 3.42. Ch s nguy c gia MPO vi mt s yu t ............................... 88

DANH MC CC BIU , S

Trang

Biu

Biu 3.1. Thi gian pht hin bnh i tho ng theo cc nhm. ....... 60

Biu 3.2. T l dy lp ni trung mc ng mch cnh nhm bnh ..... 67

Biu 3.3. So snh nng MPO ca nhm bnh v nhm chng .......... 71

Biu 3.4. Tng quan gia MPO v vng bng ...................................... 79

Biu 3.5. Tng quan gia MPO v BMI ................................................ 80

Biu 3.6. Tng quan gia MPO v IMT ................................................ 80

Biu 3.7. Tng quan gia MPO v mng x va .................................. 81

Biu 3.8. Tng quan gia MPO v QTc ................................................ 82

Biu 3.9. ng cong ROC gia MPO vi vng bng ........................... 83

Biu 3.10. ng cong ROC gia MPO vi BMI .................................... 84

Biu 3.11. ng cong ROC gia MPO vi IMT .................................... 85

Biu 3.12. ng cong ROC gia MPO vi QTc ..................................... 86

Biu 3.13. ng cong ROC gia MPO vi IMT, VB, BMI v QTc ...... 87

S

S 1.1. C ch gy x va ng mch ca LDL nh, m c ................ 11

S 1.2. Tc ng ca tng ng huyt v khng insulin ln to NO ...... 14

S 1.3. Tc ng gia vim, khng insulin v x va ng mch ............ 16

S 2.1. Cc bc tin hnh nghin cu ..................................................... 57

DANH MC CC HNH

Trang

Hnh 1.1. Cu trc enzyme myeloperoxidase ............................................... 20

Hnh 1.2. Phn ng to ra hypochlorite ........................................................ 20

Hnh 1.3. Tin trnh x va ng mch lin quan MPO .............................. 23

Hnh 1.4. Tc ng ca HOCl ln tho cp NOS to gc t do superoxide .... 27

Hnh 1.5. Tc dng bt li ca myeloperoxidase ......................................... 28

Hnh 1.6. C ch ca MPO trong x va ng mch ................................... 29

Hnh 1.7. C ch MPO tng tc vi gc t do chn lc nh hng bt li

trong lp ni mc .......................................................................... 31

Hnh 1.8. B dy lp ni trung mc ng mch cnh chung bn tri

dy 2,8mm .................................................................................... 32

Hnh 1.9. Hnh nh mng x va ng nht ................................................. 33

Hnh 1.10. Cc lp ca thnh ng mch trong qua IVUS ............................ 34

Hnh 1.11. Chp MRA ca ng mch cnh trong ........................................ 35

Hnh 1.12. Hnh chp CTA ng mch cnh ................................................. 36

Hnh 1.13. Chp DSA ng mch cnh trong ................................................ 37

Hnh 2.1. V tr t u d o IMT ng mch cnh.................................... 49

Hnh 2.2. Cch o b dy lp ni trung mc (IMT) ..................................... 51

1

T VN

1. TNH CP THIT CA TI NGHIN CU

i tho ng l mt bnh l ni tit chuyn ha ph bin, ngy cng

c khuynh hng gia tng trn khp th gii cng nh nc ta v ang tr

thnh mt thch thc chnh trong Th k XXI [4], [42], [171]. y l mt

nhm bnh chuyn ha vi c trng l tng glucose mu do thiu ht tng

i hay tuyt i v tit v hay l tc dng ca insulin trn t bo ch.

Khi ni n bnh i tho ng nht l i tho ng tp 2 ngi ta

thng lin tng n bin chng tim mch trong l tn thng mch mu

ln thng gp nh bnh l mch mu no, ng mch vnh v ng mch

hai chi di. Bin chng mch mu ln trong i tho ng thc cht l mt

th x va ng mch v i tho ng lin quan ti ri lon chuyn ha bao

gm tng glucose mu, tng huyt p, ri lon lipid v khng insulin [86].

X va ng mch bnh nhn i tho ng tp 2 xy ra sm hn, nng

hn, lan rng hn so vi ngi khng b bnh i tho ng v nh hng

khng nhng n cc ng mch gn m cn v tr xa gc. Cc bin chng

mch mu ln lm tng nguy c tai bin mch mu no cao gp 2 4 ln

ngi i tho ng so vi ngi khng b i tho ng [45]. Bin c

mch vnh l nguyn nhn hng u gy t vong trn bnh nhn i tho

ng (hn 65%) v tn thng ng mch hai chi di v ang tr thnh

nguyn nhn chnh gy ct ct chi bnh nhn i tho ng [36].

Bn cnh cc yu t nguy c truyn thng gy x va ng mch nh

bo ph, tng huyt p, tng glucose mu mn tnh, ri lon lipid mu

gy nhng bt thng thnh mch, ri lon chc nng ni mc mch mu,

tng ngng tp tiu cu v tng ng mu dn n nguy c tn thng mch

mu ln. Gn y vai tr ca cc yu t nguy c khng truyn thng c

2

cp nh cht c ch hot ha plasminogen-1, protein phn ng C,

microalbumin niu...[86] v nht l myeloperoxidase c nghin cu ghi

nhn c lin quan n x va ng mch nhng i tng c nguy c cao

trong c bnh i tho ng [106].

Vim v stress oxy ha ng vai tr quan trng trong tin trnh x va

ng mch [88]. Myeloperoxidase l enzyme c tit ra t bch cu, hot

ng nh yu t vim v stress oxy ha. Myeloperoxidase c vai tr quan

trng trong tin trin x va ng mch. C ch gy x va ng mch ca

myeloperoxidase th hin bng nhiu con ng bao gm myeloperoxidase

hot ng nh cht xc tc lm tng LDL oxy ha, kt qu lm tng thu nhn

LDL vo lp ni mc, gp phn hnh thnh v pht trin t bo bt, hnh

thnh mng bm; lm ri lon chc nng bo v ni mc ca HDL a n

ri lon chc nng ni mc; Myeloperoxidase trc tip qut dn nitric oxide,

hn ch sinh kh dng ca NO dn n co mch v thc y tn thng ni

mc mch. Ri lon chc nng ni mc pht trin sm trong giai on sm

ca i tho ng trc khi biu hin lm sng bng x va ng mch.

Gim nitric oxide v tng stress oxy ha l nhng yu t quan trng trong

sinh bnh hc ca bin chng i tho ng. Cc mu oxy ha phn ng

ng vai tr quan trng trong ri lon chc nng ni mc qua trung gian tng

ng huyt v bin chng mch mu. Myeloproxidase l du ch im cho

ri lon chc nng ni mc v l cht to ra cc mu oxy ha phn ng tng

trong i tho ng. Nng myeloperoxidase tng bnh nhn i tho

ng tp 2 c ghi nhn.

Bin chng tim mch l nguyn nhn gy t vong hng u ngi b

i tho ng. V vy vic nghin cu cc yu t nguy c tim mch bnh

nhn i tho ng lun thu ht c s quan tm ca cc nh chuyn mn.

Do lm th no pht hin sm v iu chnh kp thi cc yu t nguy c

3

tim mch l iu rt quan trng v n gip ngi bnh nng cao cht lng

cuc sng v ko di tui th.

Song song vi vic pht hin yu t nguy c, nhiu phng php

nh gi x va ng mch giai on sm nh o dy lp trung ni mc

ng mch cnh qua siu m l phng php khng xm nhp, c nhy

cao cng c ng dng trn lm sng. Chng trnh gio dc cholesterol

quc gia v Hip hi Tim mch Hoa K chp thun o b dy lp ni

trung mc ng mch cnh nh gi nguy c tim mch [45].

Lin quan gia nng myeloperoxidase huyt tng v bt thng

cu trc ni mc mch mu ngoi bin bnh nhn i tho ng tp 2

ti Vit Nam cha thy cp. Xut pht l do trn chng ti tin hnh

nghin cu ti ny.

2. MC TIU NGHIN CU

2.1. Xc nh mt s yu t nguy c tim mch, b dy lp ni trung mc ng

mch cnh v nng myeloperoxidase huyt tng trn bnh nhn i tho

ng tp 2.

2.2. nh gi mi lin quan v tng quan gia nng myeloperoxidase

huyt tng vi b dy lp ni trung mc ng mch cnh v mt s yu t

nguy c tim mch truyn thng (tui, tng huyt p, ri lon lipid mu) v

khng truyn thng (HbA1C, CRP, fibrinogen huyt tng, bch cu..) trn

nhng bnh nhn i tho ng tp 2 ny.

4

Chng 1

TNG QUAN TI LIU

1.1. BNH MCH MU LN I THO NG TP 2

1.1.1. Dch t hc i tho ng tp 2 v bin chng tim mch

i tho ng (T) tp 2 l mt bnh ri lon chuyn ha vi c

trng bi tng glucose mu mn tnh, khng insulin v thiu insulin

nhiu mc khc nhau. T tp 2 thng khng c chn on nhiu

nm trc do biu hin lm sng kn o. Tuy nhin ngay trong giai on

thm lng ny bnh c nguy c bin chng mch mu.

T tp 2 chim trn 90% cc trng hp T [42], ang ngy cng

gia tng trn ton th gii trong c Vit Nam v ang tr thnh mt thch

thc ca y hc. Theo T chc Y t Th gii nm 2000 c khong 157,3 triu

ngi mc bnh T v d bo n nm 2025 con s ny s l 300 triu

ngi [4]. Theo Lin on T Quc t nm 2011 c khong 366 triu ngi

mc bnh T v c on n nm 2030 s ngi mc bnh T l 552

triu, ring Vit Nam nm 2011 c 1,7 triu ngi mc bnh T th n

nm 2030 s ln n 3,1 triu ngi ln tui t 20-79 mc bnh T [171].

T chu chim hn 60% v Vit Nam l mt trong 10 quc gia c s

ngi mc bnh T cao nht Chu [65].

Khi ni n T tp 2 ngi ta thng lin tng n bin chng tim

mch [49]. Bin chng tim mch l nguyn nhn chnh gy t vong, tn

ph v tn km nht trong chi ph trc tip v gin tip bnh nhn T.

Nguyn nhn t vong bnh nhn T tp 2 do chng mch mu ln

chim 75% [138]. Theo Hip hi Tim mch Hoa K T c xem

tng ng nh mt bnh mch vnh [104]. Trong nghin cu East-West

Study Phn Lan ko di 7 nm cho thy t l nhi mu c tim gp 6 ln

5

bnh nhn T so vi khng T. Mt nghin cu on h theo di 18

nm ghi nhn bnh nhn T khng c thiu mu c tim trc c nguy

c t vong do bnh l tim mch cao hoc nguy c cao hn bnh nhn

khng c T m c nguy c thiu mu c tim trc [42].

1.1.2. C ch bnh mch mu ln bnh nhn i tho ng

Bin chng mch mu ln trong T thc cht l mt th x va ng

mch (XVM) v T c lin quan ti ri lon chuyn ha bao gm tng

glucose mu, tng huyt p, ri lon lipid v khng insulin. Bin chng

mch mu ln nh nhi mu c tim, t qu thng xy ra t ngt nhng

XVM hin din trong thi gian di v khng c triu chng.

S tin trin ca XVM bnh nhn T tp 2 c mt s c im

nh bt thng v chc nng ni mc mch mu xut hin sm, tng hot

ng ca tiu cu, thc y tng sinh t bo c trn v c cht sau khi ng

mch b tn thng, khuynh hng ti to mch mu bt li, tn thng s

thoi bin fibrin vi khuynh hng to huyt khi v phn ng vim.

1.1.2.1. Ri lon chc nng ni mc mch mu

Ri lon chc nng ni mc (RLCNNM) l du hiu sm ca tn thng

XVM v xy ra rt sm ngay t giai on tin T bnh nhn T tp 2

c l lin quan n tng glucose mu, tng huyt p, ri lon lipid mu v

khng insulin. V th RLCNNM l du ch im sm ca bin chng vi mch

v mch mu ln ca T tp 2 [36].

T bo ni mc sn xut nhiu cht trung gian ha hc trong c nitric

oxide (NO) l cht gin mch ph thuc ni mc c vai tr iu ha trng

lc mch mu. V phng din sinh hc, RLCNNM bnh nhn T tp 2

rt a dng lin quan n NO nh gim sn xut NO, NO b bt hot bi cc

mu oxy phn ng (reactive oxygen species- ROS), ri lon s sao chp NO.

Tng glucose mu lm hot ha protein kinase C thng qua tng stress oxy

6

ha, sn xut cht diacylglycerol hoc cc sn phm cui ca s ng ha

bc cao (AGEs- advanced glycation end products) [66], [163]. Con ng

chuyn ha protein kinase C c c trng v lin quan vi mt vi bt

thng chc nng t bo, bao gm gia tng co mch v RLCNNM qua trung

gian endothelin 1, angiotensin II, enzyme NO synthase ni mc (endothelial

nitric oxide synthase-eNOS) [36].

RLCNNM cn lin quan n cc cytokin vim. Mt s nghin cu cho

thy c mi lin quan gia nng cc cytokin nh cht interleukine-6 (IL-6) v

CRP vi s pht trin T tp 2 v bo ph dng nam [36], [88].

1.1.2.2. Tng hot tnh tiu cu

Chc nng tiu cu bnh nhn T bt thng nh tng dnh, qu

nhy cm vi cc cht tin kt dnh, tng prostaglandin v thromboxan A2,

i sng tiu cu gim [11]. Tiu cu thng c kch thc ln hn, c s

lng th th glycoprotein (GP)IIb/IIIa nhiu hn v trn thc nghim ghi

nhn s ngng tp sn sng hn so vi ngi khng T [36]. Cc yu t

ny gp phn lm tng hot tnh tiu cu bnh nhn T tp 2 [86].

Knobler v cng s ghi nhn kt dnh v ngng tp tiu cu tng bnh

nhn T hn khng T. Sheachter v cng s chng minh mc glucose

huyt tng l yu t ch yu tin on huyt khi ph thuc tiu cu. Nng

glucose, apolipoprotein B v magnesium ni bo tng quan vi huyt

khi ph thuc tiu cu bnh nhn c bnh l mch vnh n nh [21].

Prostacyclin (PGI2) v NO l 2 phn t c trng vi thuc tnh chng

ngng tp tiu cu, c phng thch t ni mc mch mu v c ch cc

tc dng ca mt s tc nhn tin ngng tp. S suy gim hot ng chng

ngng tp ca PGI2 v NO ng vai tr then cht trong bnh sinh ca chc

nng tiu cu T tp 2. Hn na cc cht tin ngng tp c dn cht t

tiu cu b iu ha ngc bnh nhn T tp 2 v khng insulin lm

7

bnh nhn T tp 2 c khuynh hng c huyt khi qua trung gian tiu

cu [36]. Gorudko v cng s cho thy MPO tc ng gin tip lm tng

hot ng ca tiu cu [91].

Do bt thng chc nng tiu cu ni trn, c nhiu nghin cu cho

thy vic s dng thuc chng ngng tp, cc dn cht thienopyridin v c

ch th th GPIIb/IIIa c li l ci thin bin c tim mch. iu chnh trc

GPIIb/IIIa bnh nhn T tp 2 c hi chng mch vnh cp v/ hoc l

can thip mch vnh qua da lm ci thin d hu cho bnh nhn T [36].

1.1.2.3. Tng sinh t bo v lng ng c cht ni mc mch mu

Bnh nhn T tp 2 c t l ti hp cao hn bnh nhn khng T sau

khi can thip ng mch vnh qua da c ghi nhn qua cc nghin cu.

S ti hp mch mu sau khi nong bng bng l do s tc nghn mch mu

t ngt, ti to ng mch bt li v tng sinh tn to ni mc ng mch.

S ra i ca gi (stent) ci thin t l thng mch mu do lm

gim tn sut ti hp bnh nhn T hoc khng T bng cch loi tr

s tc nghn mch mu t ngt, ti to ng mch bt li sau khi can thip

ng mch vnh qua da [36]. Trong th nghim Stent-PAMI, bnh nhn T

b nhi mu c tim cp c t stent gim ng k t l phi ti to mch mu

v t l cc bin chng tim mch chnh. Tuy nhin, t l ti hp nhm T

cao hn nhm khng b T [39].

Ti hp sau t stent cn lin quan tng sinh tn to ni mc mch. C

insulin ln glucose u lin quan n tng sinh tn to ni mc mch T

tp 2. Tng glucose mu tc ng n cc yu t tng trng nh yu t tng

trng nguyn bo si v yu t tng trng chuyn dng alpha. Tng

glucose mu lm tng s tng hp cc thnh phn cht nn, gim sn xut

cht heparin sulfate dn n gim c ch tng sinh t bo. Tng glucose to

nhiu cht AGEs, cht gy tng sinh t bo v tuyn m t bo vim. Bin i

8

cht AGEs v th th ca chng lm gim ng k tng sinh tn to ni mc

mch trong nghin cu ti hp mch chut Zucker khng insulin.

Mc d vai tr sinh hc ca insulin cha r, khng insulin thng phi

hp vi ti hp mch mu. Mt nghin cu gn y ghi nhn khng insulin

gia tng nguy c ti hp sau nong mch vnh qua da [36].

1.1.2.4. Ti to ng mch bt li

Bnh nhn T thng biu hin s tin trin XVM bao gm khuynh

hng ti to mch bt li trong nhng giai on u ca XVM, thiu s

hnh thnh tun hon ph v tng nguy c tc nghn mch mun sau khi nong

vnh bng bng.

Glagov v cng s ghi nhn hin tng gin ng mch cn b sm hin

din lp ni mc ca giai on u XVM ng mch vnh thn chnh

tri (left main trunk) ca xc cht. S gin mch cn b ny ln n 40%.

Nhng bnh nhn T thay v c s p ng gin ng mch thch nghi th

li c biu hin co tht mch lm cho lng mch c mng va hp ng k. V

vy, ng mch vnh ca bnh nhn T thng nh hn, chiu di tn

thng di hn v bnh l c tnh cht lan ta. y l nt c trng v hnh

thi lm tng t l bin chng sau can thip ng mch vnh qua da [36].

Bnh nhn T vi bnh l ng mch in hnh ny lm t l tc

nghn ng mch mun cn cao d c nong vnh bng bng. Van

Belle ghi nhn nghn mch mu mun chim t l 15% sau nong vnh bng

bng. Ti hp tc nghn c nguy c t vong tim mch trong vng 10 nm

cao. Marso v cng s nghin cu 673 bnh nhn c hi chng mch vnh

cp c can thip ti thng ng mch vnh qua da, trong c 119 bnh

nhn T, theo di trung bnh l 3,4 nm th bnh nhn T c ti nhp

vin, ti thng mch mu nhiu hn, tn thng mng x va ln hn, di

hn v lng mch cng hp hn so vi khng c T [122].

9

1.2. YU T NGUY C TIM MCH BNH NHN I THO

NG TP 2

Bnh l tim mch l nguyn nhn chnh gy t vong bnh nhn

T tp 2. Ngoi cc yu t nguy c (YTNC) truyn thng th bnh nhn

T tp 2 cn c cc YTNC khng truyn thng [131].

1.2.1. Cc yu t nguy c truyn thng

1.2.1.1. Tng huyt p

T v tng huyt p (THA) l 2 bnh l bn ngoi c v khc bit

nhng thc t thng xy ra trn cng bnh nhn T, c bit bnh nhn

T tp 2. THA trong T tp 2 thng l mt trong nhng biu hin

ca hi chng chuyn ha, khng insulin. Phi hp THA v T lm gia

tng nguy c bin chng v t vong tim mch bnh nhn T [48]. C t

nht 88% bnh nhn T c THA c iu tr hoc khng kim sot. THA

khng nhng c tn sut cao ngi T m cn tin on tin trin ca

T. Mt khi THA c chn on, nguy c T trong 5 nm tip theo

gp 2,5 ln [42].

Nghin cu Whitehall Anh theo di trong 10 nm, nguy c t vong do

bnh tim mch bnh nhn T c THA nhiu hn, tn sut THA T

tp 2 tng 2,5 ln so vi ngi khng T. THA nguyn pht pht trin

thnh T l do ri lon thnh phn t chc c vn (nhiu m v gim cc

si co c nhy cm chm vi insulin), gim lu lng mu n t chc c

lm mch mu ph i, tha tht, co mch v ri lon p ng iu ha hu

th th i vi insulin [36].

1.2.1.2. Ri lon lipid mu

Ri lon lipid (RLLP) mu l yu t quan trng gy XVM bnh nhn

T nht l T tp 2, lin quan n thiu insulin v hay l khng

insulin [35]. T l RLLP bnh nhn T tp 2 cao gp 2-3 ln so vi ngi

10

khng bnh T [5],[140]. RLLP hin din ngay c khi c bt thng dung

np glucose. iu ny nguy him cho nhng i tng ny l ch h khng

bit mnh b mc bnh phng v mc nguy c vi tai bin tim mch

ca h khng khc g so vi ngi mc bnh T tp 2 [5].

Nhiu nghin cu chng minh t l nhi mu c tim, cn au tht ngc

bnh nhn T cao hn bnh nhn khng T. T l ny tng song hnh vi

tng nng lipid mu. Nghin cu UKDPS cho thy T c tng cholesterol

lipoprotein t trng thp (low density lipoprotein cholesterol ; LDL-C), tng

triglycerid, gim cholesterol lipoprotein t trng cao (high density lipoprotein

cholesterol ; HDL-C) trong mu. Nhng ri lon ny lun kt hp vi tng nguy

c mc bnh mch vnh. Tin lng bnh l mch vnh c ci thin ng k,

thm ch gim c t vong do mch vnh nh iu chnh c cc RLLP [5].

RLLP mu l YTNC bnh nhn T thng c bt thng v cht lng

lipoprotein lin quan ti khng insulin. RLLP bnh nhn T c c trng

l tng triglycerid v nng HDL-C huyt tng thp. Nng LDL-C ngi

khng insulin khng khc bit vi ngi cn nhy insulin. Tuy nhin c s thay

i cht lng trong ht LDL l ht LDL nh hn d b oxy ha lm cho qu trnh

XVM s mnh hn. LDL kch thc nh, m c ngm vo thnh ng mch

nhanh hn v kt li ti protein glycat ha hn so vi cc ht LDL ln hn [96].

khng m m do tng hot ng hormon nhy lipase v lm tng

tan v triglycerid d tr. Cc acid bo t do gii phng t t bo m c vn

chuyn ti gan tng hp triglycerid v cholesterol lipoprotein t trng rt

thp (very low density lipoprotein cholesterol VLDL). S gia tng VLDL

thay i t HDL-C lm HDL-C trong huyt tng thp. Ni cch khc acid

bo t do tng c vai tr trong khng insulin [57].

Hin nay triglycerid bnh nhn T tp 2 c quan tm, bnh tim

thiu mu lin quan triglycerid. Tng triglycerid lc i lin quan n tai bin

mch vnh T tp 2 v nhm c ri lon dung np glucose [36].

11

S 1.1. C ch gy x va ng mch ca LDL nh, m c [36]

1.2.1.3. Ht thuc l

Ht thuc l l yu t nguy c gy XVM c th thay i c. Ht

thuc l lin quan cc yu t vim, cc du ch im lm gim chc nng

ni mc, tng stress oxy ha. Ht thuc l cn lm tng kt dnh tiu cu,

tng nht v lm tng ng. Ngi ht thuc l c khng insulin cao

hn ngi khng ht thuc l, nng HbA1C cao v cung cp oxy cho

cc m thp [165]. Bnh nhn T c ht thuc l lm nguy c bnh tim

mch, t vong sm tng v tng t l bin chng vi mch trn T. Cc phn

tch gp cho thy ht thuc l lm tng pht trin T tp 2, nguy c b T

ln n 44%. Ht thuc l lm khng insulin v p ng tit insulin khng

y . Mt nghin cu bnh nhn T tp 2 mi chn on c ht thuc

l khi ngng ht thuc l trong 1 nm s ci thin cc thng s chuyn ha,

gim huyt p v gim albumin niu [65].

1.2.2. Cc yu t nguy c khng truyn thng

1.2.2.1. khng insulin

Cc nghin cu tin cu cho thy tng insulin mu l YTNC quan trng

trong bnh thiu mu c tim. Nghin cu Quebec Heart 1898 nam t 45-

76 tui, khng c thiu mu c tim, trong 5 nm theo di c 114 nam b

12

thiu mu c tim, nng insulin tng 18% so vi chng. Nghin cu

Helsinki Policemen Study trn 970 cnh st nam theo di t vong trong 22

nm cng ghi nhn tng insulin mu lin quan vi tt c nguyn nhn tng

t vong tim mch c lp vi cc YTNC khc. Mt phn tch gp ca Marja

Pyorala v cng s cc YTNC c trong thnh phn trng tm ca hi chng

khng insulin 164 bnh nhn nam c bin c tim mch v 70 nam b t

qu. Kt qu cho thy ch c yu t khng insulin d on nguy c t

qu v bnh tim mch c lp vi cc YTNC khc. Nhn chung, cc nghin

cu cho rng thnh phn ca hi chng c mt trong nhiu nm trc khi

khi pht bnh T tp 2 v "ng h cho bnh tim mch bt u hn gi

trc khi khi pht T lm sng".

C ch khng insulin lin quan vi cc YTNC tim mch khc biu

hin trong hi chng chuyn ha nh bo ph, THA, RLLP mu, bt thng

tn hiu insulin v tng insulin mu. khng insulin l bt thng ch yu

ni kt T tp 2 v bnh tim mch, n lin kt gn vi YTNC tim mch

truyn thng v cng lin quan ng k vi cc YTNC khng truyn thng.

Bo ph

Theo WHO (1998): Bo ph hin ang l mt i dch ti cc quc gia

pht trin v ang gia tng nhanh chng nhiu nc ang pht trin, c

bit l vng Chu - Thi Bnh Dng [29]. Trong s nhng ngi tr T

c khong 10,4% tha cn v 79,4% bo ph [48].

Bo ph lin quan ti mt lot cc YTNC ca XVM v bnh tim

mch gm THA, khng insulin, ri lon dung np ng, cholesterol

cao, tng triglycerid, gim HDL-C, tng fibrinogen huyt tng, RLCNNM

v vim. Kt qu t nhng nghin cu Framingham, Nurses Health Study

v mt s nghin cu khc cho thy tng quan thun gia bo ph v bnh

mch vnh.

13

T bo m c kh nng tng hp v tit ra cc cht nh adiponectin,

resistin, leptin, PAI-1, yu t hoi t u alpha (Tumor necrosis factor-, TNF-

) v interleukin-6 (IL-6) [32].

Adiponectin tham gia vo iu ha tnh nhy cm ca insulin v qu

trnh oxy ha lipid. Adiponectin lin c tc dng chng XVM, chng vim.

Ngi bo ph th adiponectin gim, ngc li khi gim cn th nng

adiponectin tng [32]. Resistin l mt protein c lin quan n khng insulin.

Resistin tng gy khng insulin v ngc li. Bo ph ni tng lin quan vi

tng PAI-1. Cht hot ha plasminogen thp so vi PAI-1 l mt yu t tin on

cho bnh tim mch. Tng insulin s kch thch sn xut PAI-1 v mc yu t x va

ny cao trong T tp 2 khng insulin.

M m c xem l c quan ni tit tit nhiu loi hormone v cytokin.

Nhiu nghin cu cho thy c mi lin quan gia bo ph v CRP, TNF v

IL6 v cc cytokine ny tin on cho bnh tim mch. CRP huyt tng tng

ngi bo ph c c trng khc ca hi chng chuyn ha. ngi bo

ph tng TNF trong m m. TNF thc y bch cu n nhn tng kt dnh

vo ni mc v c ch enzyme tng hp NO (NOS). IL-6 c l cng thc y

cc cytokin ni mc lm RLCNNM [86].

1.2.2.2. Ri lon chc nng ni mc mch mu

RLCNNM l bt thng sm trong din tin t nhin ca bnh tim mch

v c th l yu t tin on sm bin c tim mch [150]. Tm quan trng ca

n trong T c cng nhn.

Caballero v cng s nghin cu phn ng mch mu cng nh cc du

hiu sinh ha ca chc nng ni mc 143 ngi, tui t 25-70, chia thnh 4

nhm. Nhm 1 gm 30 ngi khe mnh c glucose bnh thng, tin s gia

nh khng bnh T; nhm 2 gm 39 ngi khe mnh c glucose bnh

thng, tin s cha hoc m b T; nhm 3 gm 32 ngi ri lon dung np

(RLDN) glucose v nhm 4 gm 42 bnh nhn T tp 2 khng bin chng

14

mch mu. Gin mch p ng vi acetylcholine chloride gim nhm

RLDN glucose v T so snh vi nhm chng; endothelin-1 nhm chng

cao hn cc nhm; vWF ch cao nhm T; phn t bm dnh ni bo

(intracellular adhesion molecule-ICAM) cao trong nhm RLDN glucose v

T; ngc li phn t kt dnh t bo mch mu (vascular cell adhesion

molecule-VCAM) cao trong nhm tin s gia nh c T v nhm c T.

iu ny phn nh bt thng phn ng mch mu v du hiu sinh ha ca

hot ha t bo ni mc hin din sm ngi nguy c pht trin T tp 2,

ngay c giai on dung np glucose bnh thng [63].

Khng insulin bnh nhn T tp 2 gy tnh trng RLCNNM c

chng minh. Insulin tc ng qua 2 c ch: trc tip v insulin l cht truyn

tin th 2 trong qu trnh tng hp NO c s v gin tip qua hot ho tng

hp NO theo con ng t L- arginin. Trong tnh trng khng insulin, s sn

xut NO b gim xung ng thi c s tng sn xut cc acid bo t do nn

cng lm suy gim chc nng t bo ni mc [105].

i tho ng tp 2

Tng ng huyt khng insulin

Hot ng arginase Hot ng NOS

Ornithine + Urea Arginase L-Ariginin --- NOS- NO + L-Citrulline

NO v ROS

khng insulin

Vim

Ri lon chc nng ni mc

X va ng mch

S 1.2. Tc ng ca tng ng huyt v khng insulin ln to NO [105]

15

1.2.2.3. Ri lon tiu si huyt

H thng tiu si huyt ni sinh c s cn bng gia hot ha plasminogen

m (tPA) v PAI-1. c ch qu mc tiu si huyt s lm ng mu v huyt

khi gy bin c tim mch. Hot ng v nng PAI-1 huyt tng tng

ngi c khng insulin. Tng insulin mu lin quan vi gim tiu si huyt

ngi dung np glucose bt thng. Ngi bo ph, m vng bng tng sn xut

PAI-1 kt hp vi khng insulin. bnh nhn T tp 2 vim mn lm tng

fibrinogenPhn tch ha m min dch nhng tn thng t bnh nhn ng

mch vnh cho thy c s mt cn bng h thng tiu si huyt ti ch vi tng

PAI-1 trong m bnh nhn T [86].

C ch l do mt cn bng chc nng gia tPA v PAI-1. Insulin,

proinsulin, VLDL, cc cytokine khc iu ha tng hp v phng thch PAI-

1. PAI-1 tng ng k khi kt hp vi tng insulin, glucose mu v tng acid

bo t do ngi bo ph khng insulin v tiu si huyt gim lin quan

gn vi hi chng chuyn ha [86].

1.2.2.4. Vim

Khi vim, gan sn xut CRP trong p ng sn xut cytokin (IL-6, IL-1,

TNF). Vim lin quan vi bin c tim mch c nghin cu [69]. CRP

c nhy cao (hs-CRP) c s dng nh gi vim trn lm sng [138].

Cc d liu gn y cho thy hs-CRP cao c nguy c T trong tng lai

nh nghin cu CHS (the Cardiovascular Health Study) v IRAS (the Insulin

Resistance Atherosclerosis Study). Trong nghin cu WSCPS (the West of

Scotland Coronary Prevention Study), mu CRP huyt tng 5.245 nam,

trong 127 chuyn t kim sot ng huyt bnh thng sang T trong

sut nghin cu. CRP l tin on quan trng ca s pht trin T trong

phn tch n bin. Trong phn tch a bin, CRP l yu t d bo pht trin

T c lp vi d bo lm sng khc [77].

16

IL-6 TNF-

GAN

LYMPHO T/MONOCYTE/MACROPHAGE

CRP

KHNG INSULIN CHEMOKINES X VA NG MCH

S 1.3. Tc ng gia vim, khng insulin v x va ng mch [86]

1.2.2.5. Microalbumin niu

Microalbumin niu c xem nh l bin chng ca T do tng

ng huyt lm bin i th pht thn. Microalbumin niu d bo tin

trin bnh thn T. Mt s nghin cu cho thy microalbumin niu xut

hin trc v d bo pht trin T tp 2 v microalbumin niu lin quan

vi d on xu cho nguy c tim mch.

Microalbumin niu l mt trong nhng YTNC tim mch v l mt trong

nhng thnh t c dng xc nh hi chng chuyn ha v microalbumin

niu lin quan vi mc insulin, nhy ca mui, bo ph trung tm, ri lon

lipid mu, ph i tm tht tri v mt khong trng huyt p v m. THA tm

thu l du hiu ca microalbumin niu v tin trin m niu bnh nhn T

tp 2. bnh nhn khng insulin, microalbumin niu c th l du hiu ca

RLCNNM cho thy tng tnh thm ni m v lin quan ti b dy lp ni trung

mc ng mch cnh. Microalbumin niu phn nh albumin qua hng ro ni

mc tng v o lng d dng trn lm sng [86].

M M

VIM

17

1.2.2.6. Tng homocystein mu (tHcy)

Nhiu nghin cu dch t cho thy tng tHcy lin quan vi bnh XVM,

l YTNC tim mch c lp c bnh nhn T v khng T.

Trong mt nghin cu trn 300 bnh nhn T tp 2, ghi nhn nng

tHcy lin quan mnh m v c lp vi hin din bnh tim mch. Mi mol/l

tng ln ca nng tHcy lin quan bnh tim mch vi t l chnh l 1,45.

Trong nghin cu khc t l chnh mi 5 mol/l tng tHcy trong huyt tng

cho bt k bnh tim mch l 1,38 ngi c dung np glucose bnh thng;

1,55 ngi c RLDN glucose v 2,33 bnh nhn T tp 2 [86]. Nghin

cu ca tc gi Munshi v cng s cng cho thy tHcy tng bnh nhn T

hn so vi nhm chng v hay gp bnh nhn c bnh mch mu ln.

Bng chng tng tHcy mu lin quan ti RLCNNM l phn ng mch

mu, gin mch c lp v l thuc ni mc gim c ngha bnh nhn

T tp 2 ln tui c tng tHcy. Tng tHcy mu lin quan vi albumin niu

v suy thn. Bnh nhn T c microalbumin niu th c tHcy cao hn

bnh nhn c bi tit albumin niu bnh thng. Insulin iu ha chuyn ha

tHcy bng chng c ch lin kt gia tHcy v T [86].

1.2.2.7. Bt thng thnh mch - Dy lp ni trung mc mch mu v

cng thnh mch

Ch s huyt p c chn / cnh tay l phng php thm d khng xm

nhp, hu ch pht hin bnh ng mch ngoi bin di lm sng v c

th cung cp thm thng tin ngoi o lng cc YTNC tim mch.

o b dy lp ni trung mc (IMT) ng mch cnh pht hin s thay

i v cu trc v chc nng xy ra trong thnh mch. IMT tng trong T

tp 2. Mt nghin cu gp IMT ng mch cnh bnh nhn T tp 2 v

ri lon dung np glucose ca G. Brohall v cng s t 23 nghin cu

18

24.111 i tng; 4.019 T v 1.110 ri lon dung np glucose. Trong 20

ca 21 nghin cu, bnh nhn T c IMT ln hn nhm chng. S khc

nhau trung bnh c tnh trong IMT l 0,13 mm (95% tin cy:0,12-0,14).

Trong 3 ca 9 nghin cu, bnh nhn ri lon dung np glucose c IMT ng

mch cnh cao hn nhm chng l 0,04mm [60].

Cng thnh mch l du hiu khc ca XVM T tp 2. Cng thnh

mch c nh gi bng o p lc mch hoc o vn tc sng mch ng

mch ch. o cng ng mch trong mt s nghin cu v d bo bin c

tim mch trong T tp 2 cho thy cng thnh ng mch lin quan vi

khng insulin, tng quan vi IMT ng mch cnh v RLCNNM [86].

C ch l c s lin kt gia tng IMT ng mch cnh, khng insulin v

tng ng huyt (Nghin cu IRAS -The Insulin Resistance Atherosclerosis

Study). Tng cng thnh mch ngi T c l lin quan glycat ha

collagen ng mch v elastin v tch ly AGEs [86].

1.2.2.8. Tng ng huyt sau n

Tng ng huyt sau n l YTNC tim mch. bnh nhn T, tng

ng huyt sau n lin quan bin chng T giai on mun.

Cc nghin cu dch t cho thy nng glucose 2 gi sau np

glucose l YTNC tim mch c lp v trc tip. Tng ng sau dung np

glucose ng ung s tng nguy c tim mch. Hn na, nng glucose

bnh nhn T sau dung np cng nh sau n lin quan trc tip vi

bnh tim mch, c lp vi ng huyt i v cc YTNC khc.

Nghin cu DECODE nh gi nguy c t vong kt hp tiu ch

glucose lc i ca Hip hi T Hoa K vi tiu ch glucose 2 gi sau

np ca WHO. C s d liu c phn tch t 13 nghin cu on h ca

Chu u, gm 18.048 nam v 7.316 n t 30 tui tr ln. Thi gian theo

19

di trung bnh 7,3 nm. Bnh nhn T mi chn on bi tiu ch lc i

ca ADA c t l ri ro cht cao hn c ngha so vi ngi c ng

huyt i bnh thng. i vi ngi c glucose i ri lon, t s ri ro

tng nam nhng khng tng n. i vi tiu ch WHO t l gia tng

ng k c nam v n bnh nhn T mi chn on cng nh

ngi RLDN glucose. T vong tng bnh nhn c ng huyt 2 gi sau

n tng. Nng ng huyt i mt mnh khng xc nh tng nguy c

t vong lin quan tng ng huyt. Test dung np glucose bng ng

ung cung cp thm thng tin tin on v cho php pht hin cc i

tng bt thng dung np glucose c nguy c cao nht cho t vong. D

liu ny ng h mnh m quan im tng ng huyt sau n l mt YTNC

ca bnh tim mch [86].

1.3. ENZYME MYELOPEROXIDASE

1.3.1. Ngun gc, cu to v hot ng sinh l ca myeloperoxidase

1.3.1.1. Ngun gc ca myeloperoxidase

Myeloperoxidase (MPO) c tng hp ngay t ty xng, enzyme ny

c cha trong cc ht ban u ca bch cu n nhn v a nhn trung tnh.

MPO khng c phng thch ra ngoi ti khi hot ha bch cu v qu trnh

mt ht ca bch cu [177]. MPO c vai tr trong cc c ch phng th v

p ng min dch [88].

1.3.1.2. Cu to ca myeloperoxidase

MPO c trng lng phn t khong 150 kDa, gm mt cp chui

nng v mt cp chui nh. Tiu n v nng ca chng ni vi nhau bng

lin kt disulfur. Hot tnh peroxidase ca MPO ph thuc vo nhm hem

tng tc vi cu trc protein c 3 lin kt ng ha tr v 8 lin kt

hydrogen [110].

20

Hnh 1.1. Cu trc enzyme myeloperoxidase [73]

1.3.1.3. Hot ng sinh l ca myeloperoxidase

MPO to ra cht oxy ha c vai tr trong phn ng oxy ha thnh

mch [74]. MPO xc tc bin i gc tyrosyl, chlorination sinh ra tyrosine

peroxide v oxy ha lipoprotein huyt tng [75]. MPO to ra

hypochlorous acid (HOCl) t phn ng hydrogen peroxide (H2O2) v ion

clo (Cl-) [76]. HOCl l cht oxy ha mnh c tc dng chng khun. Tuy

nhin, vic sn xut HOCl ko di v thng xuyn gy tn thng m v

khi u v tin trin bnh mch mu [75], [134]. MPO l mt enzyme

mang in tch dng mnh nn d dng gn vo mng sinh hc mang in

tch m, c bit ch vim nh glycosaminoglycan ca cht nn ngoi

bo, lipoprotein LDL [176].

Hnh 1.2. Phn ng to ra hypochlorite

S clo ha bi HOCl: MPO l enzyme duy nht ngi sinh ra HOCl

[120]. HOCl l tc nhn oxy ha mnh c kh nng oxy ha phn t sinh hc

Dit khun

i thc bo

Tn thng

vt ch

../../TLTK%20%20T%20NCS.%20CHI/TLTK%20tu%2036-52/41.%20Zhang.Leukocyte.doc

21

nh carbohydrate, acid nucleic, lin kt peptide, amino acid. HOCl oxy ha

nhm sulfhydryl v thioether ca protein, clo ha nhm amino thnh

chloramine, chuyn L-tyrosine thnh 3- chlorotyrosine, chuyn cholesterol

thnh phc hp clo ha [120], [144].

Gc tyrosine: MPO cng hot ng nh peroxidase kinh in v khong

5% ca hydrogen peroxide tiu th bi enzyme to ra gc tyrosyl. Chuyn l-

tyrosine thnh gc tyrosine c s tham gia ca cc cht oxy ha nh peroxide

ha lipid LDL. Gc tyrosine c th thc y oxy ha lipid v protein. C 3-

nitro v 3- chlorotyrosine tng trong mng XVM [103].

Mu phn ng nitrogen: MPO c xem nh mt oxy ha NO quan

trng trong mch mu, c th oxy ha nitrite (NO2) thnh dng phn ng.

MPO dng NO2- phn ly, thnh cht trung gian clo ha v nitrate ha [120].

1.3.1.4. Cc bnh l lm tng myeloperoxidase

Hot ng ca MPO lin quan n qu trnh vim. Mc MPO tng

bnh nhn bnh ng mch vnh. Qu trnh oxy ha gii phng MPO cn gp

bnh ri lon thoi ha thn kinh, ung th, bnh l ng h hp, vim

khp dng thp, tn thng thn v x va ng mch.

D liu gn y cho thy s lin kt gia tng nng MPO v pht

trin bnh i tho ng lin quan n enzyme vai tr l cht xc tc cho

phn ng oxy ha thnh mch mu. MPO tham gia iu chnh nitric oxide

l phn t c vai tr quan trng trong trong sinh l bnh [88].

1.3.2. Vai tr ca myeloperoxidase trong x va ng mch

Thut ng stress oxy ha c dng m t tnh trng tn thng oxy

ha t bo, t chc hoc c quan gy ra bi cc sn phm oxy ha phn ng

[95], [105], [120]. Nu stress oxy ha mc nh th cc phn t sinh hc

b tn thng c th sa cha hoc thay th bng cch gia tng kh nng

chng oxy ha nhng nu mc trm trng v ko di c th gy ra tn

22

thng hoc cht t bo, bao gm hoi t v cht theo chng trnh. Cc

cytokine gia tng sau tn thng ni mc, stress bin dng v ph v c hc

iu ha to ROS. Bnh hc ca XVM l tng ROS [120].

Superoxide (O2-), hydrogen peroxide (H2O2), hydroxyl (

.OH), oxidize

nitric (NO2-), peroxynitrite (OONO-), hypochlorous acid (HOCl) l nhng gc

t do tham gia qu trnh XVM [100].

MPO c kh nng to ROS nh HOCl, chloramin, gc v NO2. Cc cht

ny oxy ha protein, lipid v cc thnh phn chng oxy ha ca LDL [148].

HOCl bin i protein c tm thy trong tn thng x va v v th MPO

lin quan vi s oxy ha LDL qua trung gian i thc bo [133], [144].

1.3.2.1. Lin kt myeloperoxidase v bnh l tim mch

Ngy nay vim v stress oxy ha to cc gc t do gp phn vo pht

trin v tin trin ca qu trnh XVM. MPO l mt phn t tin vim c lin

quan trong vic thc y v lan rng ca XVM. MPO c tit ra t bch

cu ti cc v tr vim s chuyn LDL vo mu x va, to ra nhiu ROS v

lm gim NO sn c, qua gp phn lm RLCNNM. S tch ly MPO trong

cc mng x va gy nn s khng n nh ca cc mng x va ny dn n

bong mng x va v sau cng nh hnh thnh cc cc nghn mch [68].

Nhiu bng chng cho thy MPO ng mt vai tr trong XVM nh

nghin cu on h ca Clair L.Heslop v cng s trn 885 bnh nhn theo

di 13 nm t vong do mch vnh cho thy mc MPO cao th nguy c gp

i gy t vong tim mch. o lng c MPO v CRP cung cp thm li ch

cho d bo nguy c hn l ch CRP mt mnh [99]. Nhng ngi c MPO

tng c th c bnh mch vnh trong tng lai c chng minh. MPO

tch t trong thnh ng mch v tng v tr tn thng nhng bnh nhn

t t do tim. MPO cao d on sm nguy c tim mch tng lai v c

lp nhng bnh nhn hi chng mch vnh cp trc 24 thng. Tri li

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nhng ngi thiu MPO hon ton hoc gn hon ton do khim khuyt

bm sinh (tn xut khong 1/2000-1/5000 Hoa K v Chu u, 1/55000

Nht) th t c kh nng mc bnh mch vnh [133], [144].

Hnh 1.3. Tin trnh x va ng mch lin quan MPO [133]

Cc nghin cu lm sng cho thy o nng MPO c gi tr trong

nh gi tnh trng bnh l ca nhng bnh nhn au ngc, cc trng hp

nghi ng c hi chng mch vnh cp v suy tim. MPO l yu t c lp gip

nh gi nguy c khng ph thuc vo cht ch im sinh hc khc nh men

tim CK-MB (Creatine kinase-myocardial band) hay CRP. o nng MPO

kt hp vi peptid li niu loi B (BNP-B-type natriuretic peptide) c gi tr

tin lng trn nhng bnh nhn suy tim. Nghin cu cho thy nhng trng

hp c tng c MPO v BNP th t l sng cn thp nht. o MPO cung cp

thm thng tin tin lng trn nhng bnh nhn c hi chng mch vnh cp.

Brennan v cng s nghin cu cc bnh nhn t t v nguyn nhn

tim mch, nng MPO bch cu tng nhng mng x va l th phm

lm mng x va b v hoc nt. Nghin cu cho thy mi lin kt c ch

gia MPO vi c vim ln bnh tim mch. Cc tc gi nh gi vai tr

ca nng MPO huyt tng trong vic d on cc bin c tim mch v

Tn thng c tim Hot ha Protease Ti to tm tht bt li

Suy tim

Mng va ban u/tin trin Gim xc tc NO

To lipid hot ng sinh hc Ha hng ng bch cu

To LDL gy x va

To HLD ri lon chc nng

Mng va tn thng Hot ha yu t m

Hot ha Protease

T bo ni mc cht theo chng trnh

24

nh gi tng quan gia nng MPO v cc bin c tim mch chnh nh

nhi mu c tim (NMCT), nhu cu ti thng mch vnh hay t vong trc

mt (30 ngy) v lu di (6 thng) 604 bnh nhn n phng cp cu v

au ngc. Nghin cu cho thy nng MPO huyt tng d on NMCT

ngay c nhng ngi lc u c troponin T m tnh. Nng MPO cng

d on t l b cc bin c tim mch trc mt v lu di (p

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di lp ni mc to LDL l mc tiu chnh cho s oxy ha bi tin cht oxy

ha c sn xut bi t bo thnh ng mch. MPO l mt protein mang

in tch dng mnh v c th ni kt t bo ni mc, bch cu v LDL. S

kt hp MPO vi LDL lm tng oxy ha ca lipoprotein ny. MPO sinh ra

ROS, chng oxy ha protein, lipid v hp cht chng oxy ha ca LDL.

Nhiu sn phm oxy ha ban u khng n nh v hot ng nh l cht

trung gian thc y hn na to LDLoxh v c l dn n lin kt ngang v

khi kt tp. Tyrosine sau khi bin i cn li 3-nitrotyrosine v 3-

chlorotyrosine l nhng cht c trng nht ca cht oxy ha n nh ny.

MPO cng lin quan ti chuyn i tyrosin thnh 3-nitrotyrosin t cc dng

phn ng nitrogen bn cnh nhng c ch khc cng to 3-nitrotyrosin nh

peroxynitrite (sn phm phn ng ca nitric oxide v superoxide). Tri vi 3-

nitrotyrosine, 3-chlorotyrosine c to ra duy nht bi MPO v c l l cht

ch im phn t duy nht cho s oxy ha cht xc tc MPO [148].

Hazen, Heinecke v cc cng s bo co rng 3-chlorotyrosine cao

gp 6 ln bnh nhn c tn thng XVM so vi m ng mch ch bnh

thng. Hn na, nng 3-chlorotyrosine trong LDL lin quan t ni mc

x va cao gp 30 ln LDL trong huyt tng. Nhng d liu ny a ra gi

thuyt mnh m rng MPO lin quan trong vic bin i LDLoxh ni mc

mch mu, kt qu lm chuyn LDL vo lp x va [144], [148].

Myeloperoxidase lm suy gim chc nng ca HDL

Bn cnh vai tr chnh l a cholesterol v vn chuyn ngc cholesterol,

HDL cn c vai tr chng vim v chng oxy ha. Mc d c ch chnh xc

khng c hiu y , mt vi apolipoprotein v enzyme lin quan ti ht nh

HDL c kh nng cha ng cc cht chng oxy ha. Sau khi hp thu bi HDL,

cc sn phm oxy ha ny c cc enzyme lin quan HDL nh cht kt dnh

tiu cu acetylhydrolase v paraoxonase thy phn hoc vn cn lin kt vi

26

HDL v cui cng b loi ra khi tun hon sau khi gan hp thu HDL. Hot ng

khng vim ca HDL gn lin hot ng chng oxy ha ca n, bi v cc lipid

b oxy ha thnh cht tin vim mnh v gy vim ng mch. HDL lm gim

gn kt bch cu ln t bo ni mc v c ch bm dnh ca bch cu ti cc t

bo ny v a cc t bo vim vo trong ni mc.

Trong cc bnh chuyn ha lin quan tc XVM, cc ht HDL c th

tr nn khim khuyt chc nng. Cc ht HDL ri lon chc nng mt i c

tnh chng x va v thc y tc dng tin vim. MPO c lin quan ti ri

lon chc nng to hnh ca HDL. Apolipoprotein A-I (apoA-I) l mt mc

tiu u tin cho qu trnh oxy ha xc tc MPO, c chng minh bng cch

cho gp 100 c 3-nitrotyrosine v 3-chlorotyrosine vo apoA-I thu li t HDL

tun hon so snh protein khc trong tun hon. Hn na s thm vo ca cc

bin i oxy ha trong apoA-I lin quan t mng XVM ngi thm ch cn

cao hn. Hm lng 3-nitrotyrosine v 3-chlorotyrosine ca HDL cao lin

quan vn chuyn ngc cholesterol ca HDL b gim. S lin quan mnh m

gia s bin th apoA-I v t l ca bnh tim mch c quan st, hm

lng apoA-I 3-chlorotyrosine trong tam phn v cao nht nhiu kh nng b

bnh tim mch gp 16 ln khi so snh vi ngi c hm lng apoA-I 3-

chlorotyrosine trong tam phn v thp nht [134]. Mc tiu MPO la chn

apoA-I c gii thch l do apoA-I c v tr gn kt c hiu vi MPO [148].

HDL b bin i do MPO cng lm tng i lc lin kt HDL vi

MPO hn na, dn n vng ln qun ca s bin i HDL ph thuc

MPO ni vim mn. Nitrotyrosine v chlorotyrosine l du ch im

phn t ca MPO lin quan trong vic bin i oxy ha ca HDL lm

HDL ri lon chc nng [144], [148].

Myeloperoxidase lm gim kh nng sinh hc ca nitric oxide (NO)

NO c sn xut bi eNOS. NO l cht gin mch mnh v c vai

tr then cht trong iu ha mch mu. NO cn ngn chn s kt ni cc

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t bo trong h tun hon ti lp ni mc v c ch s pht trin ca cc

t bo c trn vo thnh mch mu. Do , s sn xut khng y v

hoc tng thu dn ca NO lm suy yu chc nng mch mu v thc y

XVM [167]. MPO c vai tr iu ha NO c cp nhiu

nghin cu [88].

Mt s c ch ca MPO lm gim tnh sinh kh dng ca NO [148]:

- NO ng vai tr l cht nn cho peroxidase v MPO xc tc.

- NO b tng thu dn t cc cht phn ng do MPO to ra dn n lm

gim kh nng sinh hc ca NO.

- HOCl c th phn ng vi nguyn t nitrogen ca NOS l cht nn

arginin sn xut cc dng chlorinat arginin chng c ch ng dng ca

NOS lm gin mch ph thuc ni mc ng mch suy gim.

- HOCl tc dng tho cp i eNOS mnh do vic to NO t eNOS

gim v NOS tr li to enzyme sn xut superoxide.

Hnh 1.4. Tc ng ca HOCl ln tho cp NOS to gc t do superoxide [88]

Tho cp eNOS xy ra khi tetrahydrobiopterin ca L-arginine gim

hoc b bin i. eNOS chuyn to gc superoxide lm sn xut NO gim.

S c ch

cht nn

Nitrat ha protein Oxy ha lipid Oxy ha protein

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Nh vy, MPO bng tin trnh xc tc cng nh khng xc tc lm

suy yu NO thnh mch. S ng thun ny c quan st trong

nghin cu mi lin quan mnh m gia nng MPO trong huyt tng

v gin mch ng mch cnh tay c ngha sau khi iu chnh cc YTNC

tim mch v CRP. Trong nghin cu ca Baldus v cng s, s phng

thch MPO t mch mu di ni mc khi truyn heparin lm tng gin

mch dng chy cnh tay v tng dng mu cnh tay do acetylcholine kt

qu lm ci thin chc nng mch mu ph thuc lp ni [148],[170].

Dng mu

Lp o trong

T bo c trn

Vn chuyn ngc

cholesterol

Nt mng bm

Vt m

TB bt

Hnh 1.5. Tc dng bt li ca myeloperoxidase [148]

LDL vo ni mc thnh LDLoxh. Bch cu vo ni mc thnh i thc

bo (TB). TB hp thu LDLoxh thnh t bo bt. MPO t TB phng thch

xc tc to ROS. ROS to t MPO (MDRS) s dng clorua, thiocyanate hoc

NO lm cht nn v H2O2 lm ng cht nn. Thu dn NO lm gin mch b

suy yu. MPO thc y XVM bng cch bin LDL thnh LDLoxh, thc y

to HDLoxh lm ri lon chc nng HDL, mt n nh cc mng x va.

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Myeloperoxidase lm tn thng mng x va ng mch

Cc mng x va ng mch vnh b vim d b tn thng b v v

xi mn c th gy ra cn au tht ngc khng n nh. Mng x va bt

n v v l tin trnh ch yu trong qu trnh bnh tim mch cp [62].

Rossi v cng s tm thy t l mng x va khng n nh cao bnh

nhn NMCT cp. MPO gp phn lm bt n mng x va bng cch hot

ha men tiu protein (metalloproteinase) t lm suy yu v bc mng

x va. iu ny c mt vi nghin cu cho thy mi lin quan

thun gia MPO v t vong do bnh tim mch bnh nhn bnh mch

vnh cp [93], [148].

Hnh 1.6. C ch ca MPO trong x va ng mch [144]

Cc bng chng v vai tr ca MPO trong mng x va khng n nh

c th hin t nhng nghin cu sinh bnh hc. Mng x va tn thng

hot ha bch cu dn n phng thch MPO. Malle v cng s quan st s

bin mu ca MPO v protein bin i hypochlororite trong tn thng

XVM [148]. Sugiyama v ng s cng chng minh trong mng x va

Gii phng cc mu oxy phn ng (ROS)

Bin i LDL hnh

thnh dng tin x va

i thc bo thu nhn

LDL-C trung gian

Gim chc nng vn

chuyn ngc ca HDL

Tiu th xc tc NO

Ri lon chc nng ni mc

T bo ni mc cht

theo chng trnh

Hot ha men tiu

protein

Kt dnh tiu cu

thun li

Tng phn ng mch mu

Mng bm khng n nh

30

ca bnh nhn t t cc ch v, xi mn v li lipid th giu MPO, trong khi

cc vt m cha ng t hoc khng c MPO [144]. Ph hp vi quan st ny

cc nh nghin cu tm thy nng tp trung ca protein bin i bi

HOCl cao trong mng x va b xi mn hoc b v mng khi so snh vi

mng n nh. Tm li, cc d liu cung cp bng chng mnh m rng MPO

tham gia vo chuyn XVM giai on cui vo bin c tim mch cp [148].

1.3.2.3. Vai tr ca myeloperoxidase trong i tho ng

Ri lon chc nng ni mc l yu t gp phn chnh ti bnh sinh ca

bin chng mch mu T. Nng glucose tng cao v ko di trong T

l yu t chnh dn n hng lot ri lon chuyn ha v c th gy stress oxy

ha to ra ROS [107]. ROS nh superoxide v hydrogen peroxide (H2O2) l

phn t quan trng trong sinh bnh hc ca bin chng mch mu T bao

gm RLCNNM. Cht oxy ho NAD(P)H, cht oxy ha khng t bch cu,

c chng minh l ngun gc chnh ca ROS trong mch mu T [176].

Bch cu ng vai tr quan trng trong sinh bnh hc ca bin chng

mch mu T. Ngoi ra, nhim trng ti din l mt trong nhng c im

lm sng chnh ca bnh nhn T v vim do nhim trng s lm nng

thm tn thng mch mu T.

MPO l mt hem protein phng thch t bch cu, ng vai tr quan trng

trong tn thng mch mu gin tip phn ng khi b kch thch trong bnh

mch mu vim nh XVM. MPO bin i LDL. Mc MPO cao, MPO phng

thch 3-chlorotyrosine v HOCl-bin i LDL c pht hin tn thng

XVM ngi. MPO c vai tr trong bnh ng mch vnh v hi chng

mch vnh cp c ghi nhn trong nghin cu lm sng.

Ngy nay, thy rng MPO gy RLCNNM ph thuc H2O2. Kh nng sinh

ha NO gim lm RLCNNM bin i bi h thng (MPO/HOCl/chloramines).

Trong nghin cu Baldus v cng s cho thy MPO l protein vn chuyn t

bo. Khc vi H2O2 tit t bch cu c thi gian bn hy ngn, MPO gn kt

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mch mu c th tn ti trong thnh mch mt thi gian c ngha. MPO c

th dng H2O2 phng thch t bch cu v khng t bch cu tit ra. MPO c

th dng cht oxy ha H2O2 to ra t ng huyt cao khng t ngun gc

bch cu sn xut HOCl v dng chlorinate. Quan trng hn, cc dng

chlorinate v HOCl c ngun gc t MPO lm tng ROS gy ra tn thng

bng suy yu gin mch ph thuc ni mc.

S gia tng ROS nh H2O2 trong mch mu T v s hot ha, kt

dnh v s thm nhp bch cu vo thnh mch mu l mt thnh phn then

cht trong pht trin bin chng T [176].

Hnh 1.7. C ch MPO tng tc vi gc t do chn lc nh hng bt li

trong lp ni mc [88]

Nhiu c ch to ra ROS do tng glucose mu trong T nh c ch t

ng oxy ha, s hnh thnh cc AGEs v kch hot con ng polyol c th

VIM

NI MC

T BO C TRN MCH MU

32

gy stress oxy ha [163]. Bn cnh vic tng sn xut ROS ca ty th

trong iu kin glucose mu tng l nguyn nhn chnh gy bin chng lm

sng lin quan ti T v bo ph. Mt s nghin cu chng minh s gia

tng cc du ch im ca cc gc t do gy tn thng mch mu th hin s

suy yu trong phng th chng oxy ha ca chng [107].

1.4. CC PHNG TIN THM D TN THNG X VA NG

MCH CNH

Kho st ng mch cnh ngoi s bng hnh nh khng th thiu nhm

chn on bnh l x va ng mch cnh.

1.4.1. Siu m

1.4.1.1. Siu m ng mch cnh qua da

Kho st siu m h thng mch mu ng mch cnh cn hai k thut:

Siu m B- mode cho hnh nh mch mu v tn thng thnh mch vi u

d tn s cao ( 7,5 MHz); Siu m Doppler phn tch cc ch s huyt ng

hc ni mch.

B dy lp ni trung mc

Siu m B-mode miu t lp ni-trung mc nh cu trc hai ng.

Hnh 1.8. B dy lp ni trung mc ng mch cnh chung bn tri

dy 2,8mm [94]

o IMT ng mch cnh c s dng rng ri bao gm: Kim tra

yu t nguy c mi xut hin. nh gi hiu qu dng thuc iu tr cc

http://radiographics.rsna.org/content/25/6/1561/F15.expansion.html

33

yu t nguy c c th thay i ln tin trnh thay i thnh ng mch giai

on sm [64].

Nhc im: Thit b khng c chun ha, khc nhau v thc hin

cc trung tm khc nhau. Nhng kh khn khi o IMT l cht lng hnh nh

km, my khng ph hp, lch v gii phu ca bnh nhn kh nh c c

ngn, ch phn nhnh ng mch qu cao, mch mu quanh co hoc khng

nm phng c do bnh h hp hoc bnh tim.

Hnh thi hc mng x va

Dng B-mode nh gi. Mng ng nht dng si (mm) hoc calci

ha (cng) v c cu trc bn trong nh nhau vi b mt nhn. Mng khng

ng nht v mng lot khng n nh hoc d vn c kh nng thuyn tc.

Nhng mng c triu chng ny c calci thp hn nhng s lng xut huyt

trong mng v lipid ln hn v chng gim m. Mng bm gim m c kh

nng nhiu triu chng hn mng tng m [94].

Hnh 1.9. Hnh nh mng x va ng nht [94]

1.4.1.2. Siu m ni mch (Intravascular ultrsound, IVUS)

Nissen v cs bo co siu m ni mch vo nm 1991 [101]. IVUS dng

u d qua da lung vo lng mch ti v tr kho st bng h thng thng

lung rt nh v dy dn mng di hng dn cht cn quang.

http://radiographics.rsna.org/content/25/6/1561/F16.expansion.html

34

Hn ch v u im ca IVUS

y l mt k thut xm nhp, dng u d n v nhiu loi vi tn s

cao, chi ph cao nn s dng gii hn ch trung tm chuyn bit. Nguy c c

th xy ra khi thao tc thng lung bng tay v bt buc i qua tn thng

hp. Li ch cn chng minh l cn thit hn nguy c lin quan.

Vi s phn gii cao, IVUS tt hn siu m ngoi da chng minh dy

ni mc v mng bm; kho st c tnh ca mng cng tt hn nh phn

bit kiu mng bm l mng hoi t hay mng x [173]. IVUS dng

nh gi tn thng x va mch, phnh bc tch v ngay c cu trc gn

thnh mch.

Hnh 1.10. Cc lp ca thnh ng mch trong qua IVUS [173]

(a) lp ni mc, (b) lp trung mc,(c) lp ngoi mc, (P) mng bm.

1.4.2. Chp mch cng hng t (Magnetic resonance angiography, MRA)

u im v hn ch

MRA l k thut khng xm nhp v bnh nhn khng b phi nhim

cht phng x hoc cht cn quang iod, cho hnh nh 3 chiu ton b ng

mch cnh hoc ng mch t sng thn nn, hu ch xc nh hp

nng ng mch, tc mch v dng bng h.

MRA dng t trng mnh v sng radio to ra hnh nh nn d b

nh hng nhng iu kin lm cn tr dng mu phn lp. Khng chnh

Downloads/Documents/chuyende%20NCS/TLTK_CD3/51.Wilhelm_Schberle-Ultrasonography_in_Vascular_Diagnosis__A_Therapy-Oriented_Textbook_and_Atlas,_Second_Edition-Springer(2011).pdf

35

xc, cho nhiu nh nhng ngi mang kim loi. nh hng ca chuyn

ng. Dng mu chy chm v hn lon s mt tn hiu nn khng phn bit

tc hon ton hay gn tc [127].

Hnh 1.11. Chp MRA ca ng mch cnh trong [127]

A: ng mch cnh trong mt tn hiu hon ton (mi tn); B: ng

mch cnh bnh thng. C: ng mch cnh trong hp nng ch xut pht (mi

tn), mt mng x va c lot pha xa on hp (u mi tn).

1.4.3. Chp mch ct lp vi tnh (Computed tomographic angiography, CTA)

Ngy nay vi k thut v x l hnh nh nhanh, CTA tr thnh cng c

mnh chn on hnh nh mch mu thn kinh nht l trong tnh hung cp

cu i hi mt k thut hnh nh nhanh, thit thc gii p nhng cu hi

sng cn trn lm sng cho quyt nh iu tr r rng [126].

Hn ch v u im ca CTA

Khng cung cp cc d liu nh vn tc, hng chy. Vng vi ha

nng chm tia b cng i, gim chnh xc khi dng hnh. Nguy c c cho

thn hoc phn ng d ng do cht phng x v thuc cn quang [128].

CTA kh thi cho hnh nh ng mch cnh x va, kho st tun hon

ng mch cnh d dng v nhanh. CTA thun tin v nhanh hn DSA. CTA

o ng knh lng mch, b dy mng bm rt tt, c nhy 96-100% khi

dng siu m ni mch tham kho. Calci ha trong mng bm v cu trc

Downloads/Documents/chuyende%20NCS/TLTK_CD3/56.CTA.S45.full.pdf

36

gii phu mch mu d dng xc nh v tr v nhn dng mng XVM. CTA

gip theo di hnh nh y cho nghin cu tin cu, m t tt c tn

thng hp r rng tng t chp DSA. Gii phu mch mu phc tp khng

cn tr cht lng CTA v ti dng hnh c th to trong bt k hnh chiu

nu khng c xo nh t cu trc xung quanh [53].

Anderson v cng s chng minh chp n lt ct c nhy 89%,

c hiu 91% v chnh xc l 90% pht hin hp M cnh trn 50%

cn Josephson v cng s cho thy vi chp a lt ct cho nhy cao

(100%) nh gi hp ng mch cnh trn 70%.

Hnh 1.12. Hnh chp CTA ng mch cnh [53]

Vi ha ng mch cnh hai bn (mi tn); Hp ng mch cnh bn

phi (u mi tn)

1.4.4. Chp mch mu s ha xa nn (Digital subtraction angiography, DSA)

DSA l tiu chun vng chn on hnh nh mch mu.

Hn ch v u im ca chp mch mu

Chp DSA l k thut xm nhp, i hi c kinh nghim v iu kin l

tng, thc v kh nng hp tc ca ngi bnh cng nh cht lng nh.

Bnh nhn c theo di du hiu sinh tn v tnh trng thn kinh trong sut

qu trnh kho st v sau chp 12-24 gi. ng vo t ng mch i c

37

nguy c bin chng ti ch thp hn cc ng vo ng mch nch, cnh

chung. Chi ph v cc nguy c lin quan nh nhi mu no do thuyn tc

ng mch cnh v cht cn quang [117] l tr ngi ca chp DSA. Bin

chng t qu, xut hin

38

ph, suy thn hoc mang kim loi m v mt k thut CTA hoc MRA khng

y hoc khng th chp ng mch, khi nghin cu hnh nh khng xm

nhp cho kt qu mu thun nhau. DSA c s dng nh th thut ti thng

mch mu iu tr kt hp trin khai t stent [61].

1.5. CC NGHIN CU V MYELOPEROXIDASE LIN QUAN N

TI

1.5.1. Nghin cu myeloperoxidase trong bnh l tim mch

Cc nghin cu dch t cho thy MPO lin quan vi bnh tim mch v

cc du ch im XVM bnh nhn XVM v bnh nhn au ngc cp

[148]. Nghin cu ct ngang ca Zhang v cng s (2001) v mi lin quan

gia MPO vi bnh ng mch vnh (MV) 158 bnh nhn c bnh MV

v 175 ngi chng cho thy nhm bnh MV c MPO cao hn so vi nhm

chng v MPO lin quan n nguy c tng bnh MV [177]. Nghin cu ca

Duzguncinar v cng s cho thy MPO tng bnh nhn bnh MV v

tng quan vi mc trm trng ca XVM. Trong nghin cu EPIC

(European prospective investigation into cancer and nutrition) v s lin quan

gia MV v MPO 1.138 bnh nhn khe mnh sau c bnh MV

trong 8 nm theo di so snh vi nhm chng 2.237 ngi, Meuvese v cng

s ghi nhn nng MPO cao nhm c bnh MV, MPO lin quan vi

nguy c pht trin bnh MV trong tng lai nhng ngi khe mnh, c

lp vi cc YTNC truyn thng [71], [125].

Ndrepepa (2008) nghin cu ct ngang gm 680 bnh nhn bnh MV

vi 382 bnh nhn c bnh MV n nh v 194 chng vi chp mch vnh

bnh thng, nng MPO bnh nhn bnh tim mch cao hn so vi nhm

chng. Hn na, nng MPO lin quan vi s hin din bnh MV.

Mocatta v cng s nghin cu 5 nm tt c nguyn nhn t vong 512 bnh

nhn vi NMCT thy rng bnh nhn c MPO tng trn mc trung bnh th

nguy c tng gp 2 ln tt c cc nguyn nhn gy t vong so vi bnh nhn

39

c MPO di mc trung bnh. Tc gi Dilshad Ahmed Khan v cng s cng

cho kt qu tng t [108]. Nng MPO cao cn l yu t tin on c lp

t vong trong bnh vin bnh nhn NMCT c ST chnh c chong tim

[111]. Baldus v cng s nghin cu CAPTURE gm 1.090 bnh nhn hi

chng mch vnh cp trong 6 thng theo di gi tr tin on ca MPO cho t

vong v NMCT cp. Bnh nhn c MPO tng th nguy c ti nhi mu hoc

t vong gp 2,25 ln. Mc thay i MPO khng tng ng vi Troponin T

[59]. Julia Searle cng cho rng MPO hu ch nh gi bnh mch vnh

cp bnh nhn ban u c troponin m tnh [149]. Marit Granr v cng s

cho thy o MPO thm ngoi troponin s gip chn on chnh xc bnh

mch vnh cp [92]. Nghin cu on h ca Esporcatte R v cng s 140

bnh nhn, c 49 (35%) c chn on b hi chng mch vnh cp, trong

13 bnh nhn (9,3%) c chn on NMCT khng c ST cao. im ct

MPO tt nht cho NMCT c xc nh l >100 pmol/l. Trong phn tch a

bin, MPO c chng minh l bin c lp duy nht chn on NMCT

cp vi t s nguy c (OR) 8,04 (p = 0,048). Nh vy bnh nhn cn au

ngc cp v khng c ST chnh, MPO cao l mt cng c quan trng tin

on yu t cho nhp vin [80]. W.H. Wilson Tang v cng s (2011) nghin

cu 1.895 bnh nhn c bnh MV theo di 3 nm cc bin c tim mch bt

li chnh (major adverse cardiovascular events -MACE) nh t vong, NMCT

cp, t qu th nhng bnh nhn c MPO>322pmol/l s tng nguy c b

MACE trong tng lai [158].

Mt nghin cu trong nc ca tc gi Nguyn Thanh nh v Hunh

Vn Minh nm 2011 v nng MPO huyt tng v mi lin quan vi mc

nng bnh nhn NMCT cp cho thy nng MPO tng nhm NMCT

cp hn so vi nhm chng (p = 0,01) v c s tng quan thun gia nng

MPO huyt tng vi mc nng ca bnh [16].

40

1.5.2. Nghin cu myeloperoxidase trong bnh l i tho ng

Wiersma JJ v cng s cho rng T tp 2 c lin kt vi RLCNNM

v XVM gia tng nhanh khi nghin cu so snh MPO huyt tng bnh

nhn T vi khng T c cn au tht ngc n nh v nh t 440 bnh

nhn c tuyn t cc phng khm tim mch ngoi tr, vi 268 bnh nhn

T tp 2 v 172 bnh nhn khng c T tp 2. Phn tch hi quy tuyn

tnh a bin iu chnh cho cc yu t nhiu. Kt qu: Nng MPO cao

bnh nhn T (trung bnh 141 pmol/l; khong t phn v 115-171 pmol/l)

hn so vi nhng bnh nhn khng T (trung bnh, 126 pmol/l; khong t

phn v 105-167 pmol/l) (p = 0,01). Nghin cu ny kt lun rng T tp 2

lin quan vi tng nh MPO, c lp ca cc bin khc trn lm sng. Mi

lin quan ny th hin tin trnh XVM bnh nhn T [172].

Gim HDL v tng stress oxy ha l c trng ca T tp 2. MPO l

mt enzyme oxy ha mt phn lin kt vi HDL v gy ri lon chc nng

HDL, MPO l yu t nguy c c lp cho bnh tim mch. Paraoxonase-1 l

mt enzyme HDL-lin kt bo v chng li bnh tim mch v gim bnh

T. Jornayvaz FR v cng s (2009) nghin cu v nng MPO trong

huyt tng v paraoxonase-1 bnh nhn T tp 2 v bnh nhn khng c

T, c v khng c bnh tim mch. Kt qu: Nng MPO huyt tng

tng ng k cc nhm bnh nhn c v khng c T c bnh mch vnh.

Phn tch a bin cho thy MPO huyt tng l mt yu t nguy c c lp

thc y ri lon chc nng HDL v lm tng nguy c tim mch [103].

Trong nghin cu ca Leonard P. Vander Zwan v cng s (2009) ghi

nhn nng MPO l du ch im lin quan n qu trnh vim nhim v

stress oxy ha khi o nng MPO 230 bnh nhn c nng glucose bnh

thng v 386 bnh nhn c glucose bt thng cho thy bnh nhn c

chuyn ha glucose mu bt thng th nng MPO tng [166].

41

Fabio R Tavora v cng s (2009) nghin cu 61 bnh nhn v mng x

va cp, 15 bnh nhn v cp, 15 trng hp v c t chc, 31 va ng

mch c bao mng v 28 x va ng mch t 72 bnh nhn t t do bnh

ng mch vnh bng k thut sinh ha m min dch v sinh ha m. Kt

qu t bo dng tnh vi MPO hin din nhiu hn tc mch hon ton so

khng hon ton gy v mng x va (p=0,006) v s lng nhiu hn

bnh nhn T so vi khng T (p=0,002) [160].

Elena Moldoveanu v cng s nghin cu mi lin quan gia

lipoprotein-phospholipase 2, MPO v paraxonase nhng enzyme ny lin

quan ti tin trin ri lon chc nng ni mc bnh nhn T tp 2 t 100

bnh nhn T: 50 khng c bnh mch vnh (nhm 1); 50 c bnh mch

vnh (nhm 2) v 46 ngi chng khe mnh. Kt qu cho thy lipoprotein-

phospholipase 2 cao nhm 2 hn nhm 1 v nhm chng. Paraxonase

nhm 1 thp hn nhm chng v thp nht nhm 2. MPO cao bnh nhn

T hn nhm chng [131].

Heilman K v cng s xem nhng thay i chc nng, cu trc ca

ng mch vi du ch im sinh ha mi ca x va mch l MPO t 30

bnh nhn T, thi gian mc bnh 5,43,4 nm c xt nghim MPO

v o IMT ng mch cnh so vi 30 ngi chng. Kt qu bnh T c

MPO tng (p=0,006), IMT tng (p=0,005) so vi nhm chng [97].

Cho n nay, ti Vit Nam cc nghin cu v MPO cn rt t. Chng ti

cha tm thy nghin cu no trong nc cp n enzyme ny bnh nhn

T ni chung cng nh bnh nhn T tp 2 ni ring.

42

Chng 2

I TNG V PHNG PHP NGHIN CU

2.1. I TNG NGHIN CU

i tng nghin cu gm nhng bnh nhn T tp 2 ang iu tr ti

khoa ni Bnh vin a khoa Trung tm Tin Giang v c nhm tham chiu l

nhng ngi khe mnh khng b T.

2.1.1. Nhm bnh i tho ng tp 2

2.1.1.1. Tiu chun chn on i tho ng

Chng ti dng tiu chun chn on ca ADA nm 2010 [46], [47].

T c chn on khi c t nht 1 trong 4 tiu chun sau:

+ Nng HbA1C 6,5% v/hoc

+ Nng glucose huyt tng lc i (t nht sau 8 gi khng n) 7

mmol/L (126mg/dL), v/ hoc

+ Nng glucose huyt tng 2 gi sau lm nghim php dung np

glucose 11,1 mmol/L (200mg/dL), v/hoc

+ Nng glucose huyt tng bt k 11,1mmol/L (200mg/dL ) km

triu chng lm sng c in nh tiu nhiu, ung nhiu, st cn.

Chn on c xc nh khi thc hin li xt nghim ln th hai

nhng ngi c ng huyt bt thng (HbA1C, glucose huyt tng lc

i, glucose huyt tng sau 2 gi) vn t tiu chun chn on.

Trong nghin cu ny, chng ti da vo 2 tiu chun (glucose huyt

tng i hoc glucose huyt tng bt k) trong 4 tiu chun trn.

2.1.1.2. Tiu chun chn on i tho ng tp 2

- Chn on T tp 2 da theo tiu chun ca Lin on T th gii

v T chc Y t Th gii 2005 [12], [51].

+ Tui thng pht hin bnh >30.

+ Khi pht chm, thng khng triu chng.

43

+ Lm sng thng gp ngi bo ph, c tin s gia nh bnh

T tp 2.

+ Nhim toan ceton him gp.

+ Insulin mu: tng, bnh thng hoc gim nh.

Trong nghin cu ny chng ti chn bnh nhn i tho ng tp 2

c chn on trc ang iu tr bng thuc vin h ng huyt c

hoc khng c kt hp vi insulin.

2.1.1.3. Tiu chun loi tr

- Bnh nhn ang b cc bin chng nng ca T nh hn m tng

ng mu, iu tr cc bnh ni khoa nng c hn m, nhi mu c tim,

bnh phi mn tnh nng, vim khp dng thp, bnh nhn tn thng

thnkhng cho php thc hin cc k thut thm d.

- Khng ng tham gia nghin cu.

2.1.2. Nhm chng tham chiu

tham chiu gi tr trung bnh nng MPO i tng T tp 2

so vi khng T, i tng c tham chiu l nhng ngi n khm

sc khe ti khoa Khm Bnh, bnh vin a khoa Trung tm Tin Giang,

khng mc cc bnh l nh hng n tng nng MPO.

- Tnh nguyn tham gia nghin cu.

2.1.3. a im v thi gian nghin cu

Tt c cc i tng tham gia nghin cu c thm khm lm sng

v thc hin cn lm sng ti Bnh vin a khoa Trung tm Tin Giang.

Ring xt nghim nh lng nng MPO huyt tng c thc

hin ti Bnh vin Trung ng Hu.

Thi gian nghin cu t thng 01 nm 2011 n thng 12 nm 2013.

2.2. PHNG PHP NGHIN CU

2.2.1. Thit k nghin cu

Phng php nghin cu l m t, ct ngang c nhm chng tham

chiu nng MPO.

44

2.2.2. Cch thc chn mu

C mu: theo cng thc tnh c mu tnh gi tr trung bnh nng

MPO gia 2 nhm:

1

21

22

ES

ES

CN

Trong

- 1: nng MPO trung bnh ca nhm tham chiu.

1= 130,9 pmol/l.

Kt qu gi tr trung bnh MPO nhm tham chiu ly t gi tr trung

bnh nhm chng ca nghin cu Shetty [151].

- 2: nng MPO trung bnh ca nhm bnh.

2=178,3pmol/l.

Kt qu gi tr trung bnh MPO ly t gi tr trung bnh MPO nhm

T tp 2 t nghin cu ca Shetty [151].

- 1: lch chun ca nhm tham chiu.

lch chun 1=61,7 ly t nghin cu ca Shetty [151].

- C:19,84 (ng vi =0,01; =0,05).

Kt qu tnh ton s n c mu cn thit cho mi nhm l 67.

Thc t mu nghin cu ca chng ti gm 2 nhm:

Nhm bnh T tp 2 gm 81 bnh nhn.

Nhm chng tham chiu gm 67 ngi.

45

2.2.3. Cc bin s nghin cu

Tt c cc i tng T c nghin cu cc tham s bao gm:

2.2.3.1. Yu t nguy c truyn thng

- Tui: Tnh theo nm sinh dng lch ca bnh nhn.

Da vo cc khuyn co nguy c tim mch tui 55 t [85], [121].

Chng ti chia tui c chia thnh 3 nhm: nhm 1:

46

mc tiu kim sot HA da vo ADA 2014, bnh nhn T mc tiu kim

sot l HA

47

2.2.3.2. Yu t nguy c khng truyn thng

- Vng bng (VB)

+ Phng php tin hnh: Bnh nhn ng thng, 2 bn chn dng 10

cm, th u, dng thc dy (n v tnh l cm) o VB vo cui k th ra.

Vng bng o ngang qua trung im gia xng sn cui v mo chu (i

vi ngi qu bo ph). Sai s khng qu 0,5cm.

+ nh gi kt qu: Ch s VB c nh gi theo tiu chun ca Lin

on i tho ng Quc t nm 2005 dnh cho ngi Chu , VB c

xem l c nguy c khi nam 90cm v n 80cm [129].

- Ch s khi c th (BMI)

+ Phng php tin hnh: Cn t v tr cn bng. i tng trong t

th ng thng thoi mi, mt nhn v pha trc, 2 gt chn st mt sau ca

cn chm li thnh hnh ch V. i chn trn, khng i m, khng mang bt

c vt g, ch mc o qun mng. m bo 4 im trn c th chm vo thc

o l vng chm, xng b vai, mng v gt chn.

o cn nng c th. Kt qu tnh bng kg, sai s khng qu 100g.

o chiu cao c th bng thc o chiu cao gn lin vi cn. Bnh

nhn ng trong t th nh o cn nng. Ngi o ko ke gn sn trn thc

o ln cho qu u, h xung n chm nh u. Kt qu tnh bng n v m,

sai s khng qu 10mm [1].

+ n v dng: Cn nng (CN)= kg; Chiu cao (CC)= m.

+ Tnh ch s khi c th (BMI) theo cng thc: BMI= 2mCCkgCN

+ nh gi kt qu theo tiu chun phn bo ph ca WHO p dng

cho ngi Chu - Thi Bnh Dng [129].

48

Bng 2.1. Phn bo ph p dng cho ngi Chu - Thi Bnh Dng

BMI (kg/m2) Phn

< 18,5

18,5-22,9

23,0-24,9

25,0-29,9

30,0

Gy

Bnh thng

Tha cn

Bo ph 1

Bo ph 2

- Glucose mu lc i: Cho bnh nhn nhn i qua m ti thiu 10

gi. Ly ng mu sng hm sau, trc n sng, lm xt nghim ti khoa

sinh ho Bnh vin a khoa Trung tm Tin Giang.

n v tnh l mmol/L.

nh gi iu tr: Theo ADA 2014, ng mu lc i t 3,9-7,2

mmol/L (70-130 mg/dL) gi l c kim sot tt [47].

- HbA1C: L loi huyt sc t c glycosyl ha, sn phm to

thnh glucose hoc dn xut phosphoryl ca glucose ln gc valin ca u

N tn ca chui ca huyt sc t A. Bnh nhn c ly mu vo bui

sng hm sau cng mu mu vi lm ng mu lc i. Lm xt nghim

ti khoa sinh ha bnh vin.

n v tnh l %. nh gi iu tr: Theo ADA 2014, HbA1C < 7% gi

l T kim sot tt [47].

- CRP: n v tnh l mg/L. loi nhng trng hp CRP tng do

bnh l vim cp, chng ti ch chn nhng trng hp c CRP20mg/L.

nh gi nguy c tim mch qua nng CRP huyt thanh theo

AHA/CDC 2003 [43], [138].

+ CRP < 1mg/L: nguy c tim mch thp.

+ CRP = 1-3mg/L: nguy c tim mch trung bnh.

+ CRP > 3mg/L: nguy c tim mch cao.

49

- Fibrinogen huyt tng: Nng fibrinogen huyt tng (mg/l) c

o khoa xt nghim ti bnh vin ly mu nghin cu.

Ly mu tnh mch, thng l mt trong khy tay hay trn mt mu

bn tay.

Bnh thng theo chun my l: 200 - 400 mg/dl.

- Bch cu trung tnh: Bng my m ti khoa xt nghim ti bnh

vin ly mu nghin cu. Gi tr bnh thng ca bch cu chun theo my

l: 5.000-10.000 bch cu/ mm3 (5-10 G/L)

- o b dy lp trung ni mc ng mch cnh (IMT): My siu m

Mylab 50 Xvision ca hng Esaote, u d tn s 7,5 MHz c gn h thng

my vi tnh, tnh ton cc thng s t ng theo chng trnh. o IMT da

theo hng dn ca ASE 2008 [155].

+ T th bnh nhn: Nm nga, u quay 45 v pha i din

bn khm.

Hnh 2.1. V tr t u d o IMT ng mch cnh [155]

+ V tr o: Trc ch chia i ca ng mch cnh chung 10 mm.

+ Cch ly hnh nh b dy lp ni trung mc: Hnh nh cu trc thnh

ng mch qua siu m 2D, ct dc gm 3 lp. Lp ni mc (intima) v lp

ngoi (adventitia) to ra 2 ng hi m (echogenic) song song v chen gia

l lp gia (media) khng hi m.

50

Trn siu m c th thy ng trong cng tng i r l lp ni mc,

ng en k tip l lp gia v ng trng ngoi cng l lp ngoi ca

ng mch.

B dy lp ni trung mc ng mch cnh chung trn siu m c tnh

t bt u ca lp ni mc pha trong lng mch, l lp hi m u tin,

ngang qua vng gim hi m n bt u ca lp ngoi mc (ranh gii ca

lp ngoi - trung mc), lp hi m th hai [178].

o khong cch t im trn b mt lp ni mc pha lng mch thng

gc tng xng n im nm trn ranh gii lp ngoi - trung mc.

o t nht 3 im khc nhau v tr kho st, b dy lp IMT c tnh

theo cng thc:

R = yin

i

n1

1

R: L b dy trung bnh cng lp IMT ti v tr kho st. n v biu th mm.

n: S im kho st.

yi: B dy lp ni trung mc ti im i.

n v biu th l mm.

+ nh gi IMT ng mch cnh chung theo hng dn ca Hi Tng

huyt p Chu u/ Hi Tim mch Chu u nm 2007 [121], [123], [143].

IMT 50% so vi b

dy ca on thnh mch k cn, khu tr, nh vo lng mch hoc khi

IMT 1,5mm.

51

Hnh 2.2. Cch o b dy lp ni trung mc (IMT)

- in tim: Cho bnh nhn nm nga, bc l ngc, 2 tay xui dc

thn mnh, 2 chn dui thng, ci b cc trang sc c tnh dn in. Bi

kem dn in, mc cc in cc cc chi v trc tim theo quy nh ca Hi

Tim mch Hoa K. Tin hnh o 12 chuyn o thng dng.

Tc my o l 25mm/giy, bin l ng k ngang mi

1mV=1mm, thi gian l ng k dc mi 1mm=0,04 giy (my ci

chng trnh t ng ha).

Cch o QT v nh gi kt qu: Ly QT tiu biu V2 hay V4, nhng

nu kh khn (nh T dt, kh c) th ly D2. Trng hp c sng U qu

cao chng tip vo sn sng T lm d nhm vi vi phn ui ca sng T

nn lm khong QT di ra mt cch sai lm. Trng hp ny phi so snh

QT nhiu chuyn o. V QT ca mt nht bp ph thuc rt nhiu vo

tn s tim tc thi trc n nn khi o QT bao gi cng phi o khong

RR trc n. Khng nn o QT 3-4 phc b lin tip lin sau mt ngoi

tm thu v lc tnh dn truyn c bn ca c tim b ngoi tm thu tm

thi lm bin i, lm QT cng b bin i theo.

Phn tch on QT, tnh QTc theo cng thc Bazett: QTc = QT/ RR

(ms) [115]. Thi gian QTc l dng cng thc ton hc chuyn thi gian

52

QT thc t thnh thi gian QT ca mt chu chuyn tim c tn s khong 60

ln/pht, xem n c nm trong gii hn bnh thng hay khng.

QTc 440 ms c xem l bnh l [115].

+ Ch s Sokolow-Lyon: nh gi dy tht tri, chng ti da vo

ch s Sokolow- Lyon c WHO cng nhn: SV1+RV5 hoc RV6 35

mm. Hoc RV5 hay RV6 >26 mm.

+ Thiu mu cc b c tim: Tiu chun chn on thiu mu c tim di

ni mc:

ST chnh xung1mm ti im J.

ST chnh xung dng, v sng T dng hay o ngc hng vi QRS.

ST chnh xung ti thi im J t 1-2mm, theo sau bi s chch ln ca

ST nhng vn di ng ng in 1mm v ko di 0,08 giy.

ST o ngc, su, i xng: Thiu mu di thng tm mc.

Tiu chun chn on nhi mu c tim mn: Q rng sng R cng

chuyn o.

- Siu m tim: Thc hin ti phng siu m tim ti bnh vin ly mu.

Sau khi gii thch r v cuc thm khm, cho bnh nhn nm ngh 5-10

pht, kim tra my, mc cc in cc o in tm cng lc.

Bnh nhn nm nghing tri mt gc khong 45o, ci b trang sc

c tnh dn in, bc l ngc, bi gel siu m, ngi khm ngi bn phi

bnh nhn.

Dng u d sector in t 3,5 MHz. Tin hnh siu m tun t bng siu

m 2 bnh din, siu m 1 bnh din, siu m Doppler xung v lin tc. hn

ch nh hng ca h hp ln ph Doppler nn o cui k th ra, tt c cc

thng s siu m tim c o trn 3 chu chuyn tim lin tip c mc in tm

ng thi. Kt qu cui cng l trung bnh cng ca cc gi tr ny.

53

Cc php o trn siu m TM v 2D: t u d lin sn 2-3 cnh c

tri, kho st ton b tim qua siu m 2D mt ct cnh c trc dc, sau cc

thng s trn siu m TM. Chng ti s dng 2 nht ct: nht ct qua tht ghi

di b t do ca van 2 l v nht ct qua ng mch ch o theo khuyn co

ca Hi siu m tim Hoa K (2005).

+ ng knh tht tri cui tm trng (LVDd): o khi u ca phc

b QRS, t b di vch lin tht ti b trn ca thnh sau tht tri. Bnh

thng LVDd: 39-56 mm.

+ ng knh tht tri cui tm thu (LVDs): o t nh vn ng ra sau

ca vch lin tht ti b trn ca thnh sau tht tri. Bnh thng 22-43 mm.

+ Chiu dy vch lin tht cui tm trng (IVSd): o khi u ca

phc b QRS, t b trn ti b di ca vch lin tht. Bnh thng 6-11mm.

+ Chiu dy vch lin tht cui tm thu (IVSs), bnh thng 9-15 mm.

Chiu dy thnh sau tht tri cui tm thu (LVPWs), bnh thng 13-20mm.

+ Chiu dy thnh sau tht tri cui tm trng (LVPWd): o khi u

ca phc b QRS, t b trn thnh sau ti lp thng tm mc thnh sau.

Bnh thng 8-12 mm.

T cc ch s o c trn tnh c ch s khi c tht tri, chc nng

tm thu tht tri.

(1) Ch s khi c tht tri (LVMI)

Ch s khi c tht tri tnh theo cng thc c lp sn trn my t cc

ch s o c trn [147], [175].

LVMI(g/m2 ) = LVM (g)/BSA(m2)

Trong : LVM: khi c tht tri v BSA: din tch da c th

BSA = cn nng0,425(kg) x chiu cao 0,725(cm) x 71,84 x 10-10

LVM(g)= 0,8[1,04(LVDd+IVSd+ PWd)3 LVDd3] + 0,6

54

Theo tiu chun ca Hi siu m Hoa K (ASE- American Society of

Echocardiography) 2005, chn on ph i tht tri khi: LVMI >115 (g/m2)

i vi nam, LVMI > 95(g/m2) i vi n [147].

(2) Phn sut tng mu (EF):

c tnh theo cng thc sau: EF=(Vd Vs)/Vd

Trong : Vd v Dd l th tch v ng knh tht tri tm trng.Vs v

Ds l th tch v ng knh tht tri tm thu.

Vd = 7x LVDd3/2,4 x LVDd

Vs = 7x LVDs3/ 2,4 x LVDs

+ nh gi ri lon chc nng tm thu tht tri theo ASE (2005) [116]

Chc nng tm thu gim nng: EF < 30%

Chc nng tm thu gim va: 30% EF 44%

Chc nng tm thu gim nh: 45% EF 54%

Chc nng tm thu bnh thng: 55% EF < 80%

- nh lng nng enzyme myeloperoxidase huyt tng

ARCHITECT MPO l mt xt nghim theo k thut in ha pht quang

vi ht, nh lng nng MPO huyt tng trn h thng my xt nghim

min dch t ng ARCHITECT ca hng Abbott [44], c ch chy cp

cu, c thc hin ti khoa sinh ha BV TW Hu.

n v biu th: pmol/l

Phng php: CMIA, Sandwich.

La chn khng th: khng th gn v khng th pht tn hiu ngun gc

chut n dng.

Loi mu bnh phm: Huyt tng vi cht chng ng EDTA.

Xt nghim ARCHITECT MPO ang pht trin l xt nghim min dch

gm 2 bc xc nh s hin din MPO ca ngi trong huyt tng bng

cch s dng k thut ha pht quang min dch t ng (chemiluminescent

55

automated immunoassay CMIA) xt nghim vi cc giao thc linh hot, c

gi l CHEMIFLEX. C th c thc hin ch thng xuyn hoc STAT.

Trong bc u tin, mu cha MPO v khng MPO mng thun t

phn vi th c kt hp. MPO hin din trong mu th lin kt vi cc

khng MPO mng phn vi th.

Bc th hai sau khi ra, khng MPO acridinium lin hp c dn

nhn v chuyn sang bc tip theo.

Tip theo mt bc v ra khc, pre - trigger v dung dch trigger

c thm vo hn hp phn ng.

Kt qu phn ng pht quang ha hc c o l n v nh sng tng

i (relative light units - RLUs). Mt mi lin quan trc tip tn ti gia s

lng ca MPO trong mu th v cc RLUs pht hin bi cc h thng quang

hc ARCHITECT. Nng ca MPO c c lin quan n mt ng

cong tiu chun thnh lp vi nng MPO chun c bit trc.

Khong o: 0-10000 pmol/l

Thi gian ra kt qu u tin: 18 pht

Nng MPO thc hin trong 149 mu khe mnh, nng trung bnh

l 190 pmol/l. Mt nghin cu khc thc hin 400 mu. Nng trung bnh l

285,5 pmol/l (95%) [44].

Cch thu thp, bo qun v vn chuyn mu: Mu sau khi c ly t

bnh nhn c b vo tup c cha cht chng ng EDTA, y np, dn

nhn, ghi y thng tin bnh nhn, chuyn n phng xt nghim t th

ng thng. Ti phng xt nghim sau khi mu c tip nhn s c quay

ly tm tch huyt tng sau c bo qun trong nhit thch hp

(khong -180C) v m bo mu c duy tr nhit thch hp trong sut

thi gian vn chuyn n ni xt nghim.

56

2.2.4. Phng php thu thp v x l s liu

2.2.4.1. Phng php thu thp s liu

Cc s liu lm sng, cn lm sng v nhng thng tin khc c ghi

nhn vo phiu nghin cu chung.

2.2.4.2. Phng php x l s liu

- X l s liu trn my vi tnh bng phn mm thng k SPSS 16.0.

- Gi tr cc ch s nh lng c trnh by di dng trung bnh

lch chun (SD).

Cch tnh tr s trung bnh:

n

n

ixn

X1

1

Trong x l tr s ca c th, n l tng s cc trng hp.

lch chun (SD): 1

)(1

2

n

xx

SD

n

i

i

- nh gi s khc bit gia 2 gi tr trung bnh bng kim nh t-test.

t =

ba

p

ba

nnS

XX

11

)(

X : Trung bnh mu. S: phng sai

- Cc ch s nh tnh c trnh by di dng t l phn trm (%).

Dng cng thc kim nh Z so snh hai t l ca hai tng th.

Z =

)11

)(1( 00BA

BA

nnPP

PP

P A = A

A

n

X; P B =

B

B

n

X ; P 0 =

BA

BA

nn

XX

- nh gi s khc bit c ngha thng k khi p < 0,05 [135].

- nh gi s tng quan theo h s tng quan Pearson (r) [112].

57

r =

n

i

n

i

ii

n

i

ii

yyxx

yyxx

1 1

22

1

)()(

))((

+ r > 0: tng quan thun.

+ r < 0: tng quan nghch.

- Thit lp ng cong ROC bng phn mm SPSS 16.0.

Din tch di ng cong ROC c nh gi nh sau:

+ Din tch di ng cong < 0,6: Khng c gi tr d bo.

+ Din tch di ng cong t 0,6-0,7: C gi tr d bo trung bnh.

+ Din tch di ng cong t