NGHIEN CUtJ TINH TRANG SUY TIM VA NONG DO N-TERMINAL PRO B-TYPE NATRIURETIC PEPTIDE HUYET TU'ONG 6 BENH NHAN DANG L O C MAU CHU
KY
Hodng Bdi Bdo , Huynh Vdn Minh T6MTAT
Dat van de: Tang huylt dp thudng gap va se dua den hau qua suy tim d nhdm benh nhdn dang lgc mdu. N-Terminal Pro-B type Natriuretic Peptide (NT-ProBNP) - mpt ddu ehi dilm rat quan frpng cua suy tim - dugc xem la ylu to dy bao eho suy tim frong mong lai d benh nhdn suy than man giai doan cudi dang loc mau chu ky. Suy tim va cdc bien cd vi tim maeh la nhung nguyen nhan chfnh gay tu vong d nhdm benh nhan nay.
Mue tieu;
1. Khdo sdt tinh trgng suy tim a benh nhdn suy thgn mgn giai dogn cuoi dang loc mdu chu ky bdng than nhdn tgo.
2. Nghien cuu nong dg NT-ProBNP huyet tuang trudc khi lgc mdu vd tuang quan cda no vdi muc do suy tim a nhom binh nhdn ndy.
Doi tugng-phyong phap: Nhdm chiing 33 ngudi binh thudng va 30 benh nhan dang lgc mdu chu ky bang than nhan tao tai Benh vien tmng uang Hue. Danh gia suy tim theo NYHA. Dinh lugng ndng dp NT-ProBNP mau ngay tmdc khi lpc mdu.
Ket qua: Ty le suy tim d benh nhan dang lpc mdu; dd 1; 20%; dp 2: 23,3%; dp 3; 36,7% va dp 4: 20%. N6ng dp NT-ProBNP huyet tuang d benh nhdn dang lgc mdu rat cao va khac biet cd y nghTa thing ke so vdi nhdm chiing (10964±12504 pg/mL so vdi 59,86 ± 47,29 pg/mL;
p<0,0001). Ndng do NT-proBNP tang ddn theo mirc dp suy tim; d dp 1: 1369±74S; do 2:4994±
4579; dp 3:12310 ± 10971 va do 4; 25058 ± 15415 pg/ml. Cd tuang quan tiiuan chat chg giira ndng dp NT-Pro BNP huyet tucmg vdi miic do suy tim (r = -i- 0,641).
Ket luSn: C) benh nhdn dang lgc mau chu ky, suy tim rat thudng gap vd ndng dp NT-ProBNP huylt tuang tdng rat cao. Ndng do NT-ProBNP mang quan thuan vdi miie dp suy tim.
Tir khod: Suy than, IQC mdu ABSTRACT
HEART FAILURE AND SERUM N-TERMINAL PRO B-TYPE NATRIURETIC PEPTIDE (NT-ProBNP) CONCENTRATION IN HEMODIALYSIS PATIENTS Background: Hypertension is very common in hemodialysis (HD) patients and can resuU in heart failure (HF). N-Terminal Pro-B type Natriuretic Peptide (NT-ProBNP) - a marker of heart failure - is the good predictor of cardiovascular congestion and mortality in the future.
Cardiovascular events, especially HF are the main causes of mortality in HD patients.
Aims: 1. Study HF in HD patients. 2. Measure semm NT-ProBNP concentration before HD and look for the relationship between NT-ProBNP concenfration and HF.
Patients-Methods: 33 healtiiy adults in confrol group. 30 HD patients at Hue cenfral hospital.
HF classification by NYHA. Measure serum NT-ProBNP before dialysis.
Results: rate of heart failure: grade 1: 20%; grade 2; 23.3%; grade 3; 36.7% and grade 4;
20%. Serum NT-ProBNP concentration before HD is higher in HD patients tiian in confrols (10964±12504 pg/mL Vs 59.86 ± 47.29 pg/mL; p<0.0001). NT-proBNP in grade 1 of HF;
1369 ± 748; grade 2; 4994 ± 4579; grade 3; 12310+10971 and grade 4:25058 ± 15415 pgAnl. Semm NT- ProBNP concentration corelates to grade of HF (r = -»- 0.641).
Conclusion: in HD patients, HF is very common and semm NT-ProBNP concenfration is very high. NT-ProBNP concenfration corelates to grade of HF.
Kev words: Renal failure, hemodialysis ' Trudng D?i Hpc Y Dugc Hue
Dia chi Uen lac: TS.BS. Hoang Bui Bao DT: 0905405005 Email; [email protected]
DAT VAN DE
Suy tim la mdt frong nhiing bien chiing thudng gap va nang ne d nhirng benh nhan suy than man giai doan cudi dang lgc mau chu ky. Cac benh nhdn nay thudng ed cac yeu td dua den suy tim nhu tang huyet dp, thieu mau, rdi loan dien giai,... frong dd ldng huyet ap Id ylu td rdt quan frpng gan nhu thudng xuyen gdn lien vdi suy than man. Hau qua eua tdng huyet dp se dua din phi dai that frai va ddn din suy tim ve sau. Ngoai viec lam tang ty le hi vong, tW suy tim cdn lam giam chat lugng sdng d nhdm benh nhan nay va lam giam hieu qua dilu fri.
Hormone lgi nieu tam nhT (Atrial Natriuretic hormone) dugc De Bold va cdng sy bdt ddu nghien ciru tir ndm 1981, sau dd cdc tac gia khac da xdc nhdn Natriuretic Peptide la ddu chi diem cua suy tim vdi eae loai ANP, BNP, CNP va DNP cung cac thanh phan cua chung.
N-Terminal Pro-B type Natriuretic Peptide (NT-ProBNP) la dang duge diing nhilu nhdt de dy bao nguy ca suy tim cho benh nhan d nhieu nhdm ddi mgng benh ly khde nhau. BNP dugc tiet ra khi cd tang dp lyc len thanh tim. Trong nhiing benh nhan dang lgc mau ehu ky thi vifc qua tdi the tfch cung vdi kfch hoat he thdng renin-angiotensin-aldosterone la nhiing yeu tl quan frpng gay tang tiet BNP nay.
Theo Matthew A. Roberts va cgng sy thi NT-ProBNP cd vai frd frong viec dy bdo tii vong d nhiing benh nhan dang lgc mau chu ky. Ndng dp ciia NT-ProBNP mau d nhiing benh nhan nay thudng rat cao va lien quan tryc tiep den ty le tir vong'*'.
David M. Voss va cpng sy da phat hien n6ng dp eua ed ANP va BNP diu tdng rat cao d nhung benh nhan suy than man dang Ipc mdu bi qua tai the tfch vd tang huyet dp.
Trong suy than man giai doan cuoi, tang huyet dp hau nhu luon ludn cd vd ddy la nguyen nhan chfnh ciia phi dai that frai, hau qua sau cung la suy tim va ldm tang ty le tii' vong d nhdm benh nhan nay.
Muc tiSu nghien ciru
1. Khdo sdt tinh trang suy tim a benh nhdn suy thdn mgn giai dogn cudi dang loc mdu chu ky bdng than nhdn tgo.
2. Nghien cuu nong dg NT-ProBNP huyet tuang tru&c khi lgc mdu vd liin quan ciia nd vdi muc do suy tim a nhdm benh nhdn ndy.
DOI TUQNG VA PHUONG PHAP NGHIEN CUU 2.1. Doi tugng nghien cihi
30 benh nhdn suy than man giai doan cudi dang lpc mau chu ky bdng th^n nhdn tao tai Khoa Ndi Than - Benh vien tinng ucmg Hui. Chgn benh nhan STM do 2 nguyen nhdn viem cau than man yd do viem than be than man. Nhdm chiing gdm 33 ngudi, hodn todn khde manh, cd do tudi mong duong vdi nhdm nghien ciiu.
2.2.Phtnmg phap nghien cihi Thiet ke cdt ngang, md td.
Cdc budc tiln hanh;
Chan doan suy than man giai doan cudi bang ude tfnh miie lgc cdu than theo cdng thiie Clia Cockcroft-Gault.
Lgc mau chu ky bang than nhan tao, tiidi gian lgc mdu ft nhdt cho cdc ddi mgng ndy la 3 thang.
Phan do suy tim tiieo NYHA (hiep hdi tim mach NewYork).
Xet nghiem cdc chi sd sinh hda va huyet hge thong thudng.
Dinh lugng ndng do NT-ProBNP huylt mcmg d nhdm chirng va nhdm benh. Doi vdi nhdm chiing, Idy mau tinh mach, budi sdng, nhjn ddi. Ddi vdi cdc benh nhan dang lgc mau thi ldy mdu ngay tiudc khi lgc mdu. Xet nghiem tai khoa Sinh hoa, benh vien Tmng uong Hue.
2.3. Phan tich so lieu Excel 2003 va Epi 6.
K E T Q U A
598
Bang 1 Phdn bo tudi - gidi d nhdm chiins vd nhdm benh
Nhom chirng
Nbom benh nhan
Chis6 So benl nhan Ty le % Tuoi (nam) So benl nhan Ty le % Tuoi (nam)
P r^—^
Chung 33 100%
39,18 ± 6,6 30 100%
40,3 ± 13,3
>0,05 17 51,5%
42,5 + 10,9
23 76,7%
39,6 ± 12,9 0,05
Nir 16 48,5%
35,6 ± 11,6 7 23,3 % 42,7 + 15,3
>0,05
>
n,05
>
0,05
Nhan xet; Khdng ed sy khac biet ve tudi giira nhdm benh va nhdm chiing, giira 2 gidi nam va ntr (p > 0,05).
Bar Gd suy tim Do 1 Do 2 Do
3 Do
4 g 1.1 y 1 Cbung n
6 7 11
6
%
20%
23,3%
36,7%
20%
i suy i m c a c VCTM(17)
• .
3 3 7 5
%
17,65%
17,65%
41,18%
29,41%
^lai do in a be VTBTM(13)
n 3 4 4 1
%
23,1%
30,8%
30,8%
7,7%
Nhan xet: Suy tim giai doan 3 va 4 theo NYHA la kha cao 17/30 benh nhan chiem 56,7%.
Bang 3: Ket qua nong do NT-proBNP huyet tuan
So benh nhan
Chi so Nh6m chimg
BNP tmoc loc mau (pg/mL)
59,86 47,29
; a nhom benh va nh6m chiing
10964,1+12503,913473,9±13105,910200,3±12515,3
< 0,0001
Nam
>0,05
Nhan xet: - Nong do BNP truoc loc mau a benh nhan suy than man rat cao.
- Khong CO su khac biet giiia nam va nQ ve chi so NT-ProBNP huyet tuong.
- Co su kh^c biet rat lon giira nong do NT-proBNP huyet tuang o nhom benh va nh6m chung (p<0,0001).
- Gia tri NT-proBNP huyet tuong thip nhat trong nhom benh ciia nghign ciiu nay la 475,7 pg/mL, gip 8 lan so vod gia tri binh thuemg.
Bang 4. Kk qua NT - proBNP theo dp suy tim
So
ST do I
ST do II
STd§
IU ST do
rv
NT-proBNP (pg/ml)
1369±]4994±| 12310± I 25058 + 748 4579 10971 15415
p I <aor ^
Nhan xet: Nong do NT - proBNP tang dan theo miic do suy tim tren lam sang (p < 0,01) Bieu do 1: Tuong quan giua n6ng dp NT-proBNP voi hnyet ap tam thu
tao
JLU
TuvngquanglOvNTptoBKPvMHATT limiHji) i = - 0 1 K
„ . .
inWO 20000 30000 40
J
Nhdn xet: khdng cd Wong quan giira NT-proBNP vdi chi so huyet dp tam thu Bilu do 2: Tuang quan giiia NT-proBNP vdi chi sd huyet dp tdm tiuong
m g l O i NT.proBNP vdi KAItr
Nhdn xet: khdng xd tucmg quan giua NT-proBNP vdi chi sd huyet ap tam trucmg Bieu dd 3: Tuang quan giita NT-proBNP vdi mirc do suy lim
T u o n g quan g i » i NT-proSNP v6> m r c 66 suy dm
Nhan x6t: cd mdi mang quan thuan giiia nong dp NT-proBNP huyet mong vdi miic do suy tim.
BAN LUAN
C) nhdm benh nhan dang loc mdu tang huyet dp la van de thudng xuyen vd khd giai quyet. Mac dil da duge dung phdi hgp nhieu thudc vdi lieu lugng cao nhung viee kiem soat huyet dp d nhdm benh nhan dang lgc mau vdn khd khan hon d nhung benh nhan tang huyet dp khac. Day ehinh la nguyen nhan eua phi dai thdt trai, eua suy tim ve sau d benh nhdn dang lpc mdu. Ngoai tang huyet ap, ed nhieu yeu td khde gdp phan gdy suy tim d nhdm benh nhan nay nhu thieu mau man ti'nh, cau ndi ddng tmh mach, roi loan dien giai (tang Kali mdu, toan mau man tfnh, ...) Han che suy tim d nhdm benh nhdn dang lgc mdu can phai phoi hgp dong bd nhieu bien phap va khdng ch^ tdt huyet dp van la vdn dk quan trgng nhdt.
Suy tim rat tiiudng gap d nhdm benh nhan dang lpc mau chu ky, ti-ong nghien cun nay, ty le suy tim d 2 giai doan 3 va 4 theo phan do eua NYHA la kha eao 17/30 benh nhan chilm 600
joj h. Dieu nay nhdn manh tan quan trgng ciia viec chan doan, dieu tri va du phdng suy tim trong nhdm benh nhdn dang lgc mdu. Stelvinken P. va cgng su nhdn manh vai ti^d cua cdc bien CO tim mgch va nguy ca tim mach eao d nhdm benh nhdn nay va khuyen eao phai ehan doan sam, nham dieu tri sdm de ngdn ngira xay ra cae rdi loan tim maeh, mdt trong nhirng nguyen nhan hang ddu gay tii vong cho nhdm benh nhan dang lgc mdu'"*.
Ket qua ndng do NT-ProBNP huyet mcmg d nhdm benh nhan dang lpc mdu trong nghien cihi nay la rdt cao so vdi binh tiiudng: 10964,1±12503,9 pg/mL. Ndng dp NT-ProBNP huyet mang d nhdm chirng chi la 59,86 ± 47,29 pg/mL khde biet nhau rdt cd y nghTa th6ng ke {p<0,0001), tuy nhien trong boi eanh cua benh nhan suy than man dang lpc mdu chu ky bdng tiian nhan tao thi ed nhi8u ly do de nong dp chat nay tang eao nhu:
Ap lye len thanh tdm that cua benh nhan suy than man dang lpc mdu bang than nhdn tao luon ludn cao do cac nguyen nhan tdng huy6t dp, li nude muoi vi than giam lgc vd ti-ong khi lgc mdu thi ap lue ndy lai thay ddi mdt cdch dot ngdt. Ddy la y§u td chinh kich thi'ch tang tiet BNP va Yee-Moon Wang Angela da xem day la mdt ykn id du bdo dgc lap cho ckc yfikn c6 tim mach va hs vong cho nhdm benh nhdn nay'^'.
NT-ProBNP hi li lai trong mau vi khdng thai dugc qua dudng tieu.
Toe dp gidng hda ciia chat nay gidm di trong benh cdnh hpi chirng tang Ure mdu.
D6i vdi lgc mdu chu ky dung phuang phdp lgc thdng thudng, vdi mdng lpc ed ti'nh thdm thap, thi NT-Pro BNP khdng duge Ipe qua mang lgc, do vay ndng d§ NT-Pro BNP khdng gidm sau khi lgc mau'''^\
Chinh vi vay ndng dp NT-ProBNP huy€t tuang duge quan sat lu6n lu6n rdt eao. Cde tac gia Matthew A. Roberts va cpng su'''*, Orlando M. Gutierrez vd cgng su cOng ghi nhan nhiing gid trj cao cua NT-ProBNP mau tuong tu nhu vdy*^'. Theo cdc tdc gia nay thi nong do NT-ProBNP mdu cao nhu vay lien quan true tiep den viec tang ty le tii vong d benh nhan dang lpc mdu chu ky do lam gia tang cac bien cd tim mach - mot trong nhimg nguySn nhan gay tir vong hang ddu d benh nhan suy than man giai doan cuoi.
CJ nghien euu nay, 100% benh nhan deu cd ndng do NT-proBNP cao han binh thudng nhiSu ldn. Gia tri NT-proBNP huyet tuong trong nhdm benh thdp nhat la 475,7 pg/mL, gap 8 lan so vdi gid tri binh thudng. Nhu vay rd rang tit ed eae benh nhan dang lpc mdu deu ed nguy CO rat cao cua suy tim vd gia tang cae bien ed ve tim maeh.
Khdng nhiing vdi benh nhdn lpc mau bang than nhdn tao, cdc benh nhan dang tham phan phuc mac cung cd ndng dp NT-ProBNP mdu rat eao vd tdc gia Angela Yee-Moon Wang eung xem ddy Id y8u td du bdo nguy co ddc lap cua tinh trang suy tim sung huyet, eua tinh trang tu vong d nhdm dan^ tham phdn phiic mac*^l Rd rang, vdi eae nghien ciru gan day, cac tac gia nude ngoai dang de cap den tam quan trgng cua su lien he giiia ndng do NT-ProBNP mau vdi cdc bien ed tim mach, suy tim sung huyet va ty le tu vong d nhdm benh nhan suy than man giai doan cudi. Ban than cua NT-ProBNP kh6ng gay dpc cho tim, ma NT-ProBNP chinh la sdn pham cua tinh trang tang ganh eho tim gdy ra, nghTa Id chat nay la hau qua eua nhirng r6i loan tim maeh trong suy than man va dd chinh la ddu chi diem cho tinh trang nang ne sau nay''*'
CJ bang 4, chiing tdi thu dugc ket qua cua NT-proBNP theo timg giai doan cua suy tim, ndng dp chdt nay tdng dan rat rd ret theo miic do ndng cua suy tim. Su khac biet 4 nhdm nay ed y nghTa thdng ke (p<0,01) va theo do, Wong quan gifla ndng d6 NT-proBNP vdi miic dp suy tim d bi^u dd 3 eung the hien ro chieu hudng nay. Mac dii tuong quan nay chi cd gia tri mong d6i vi miic dp suy tim la 1 bien rdi chii kh6ng phai la bien lien tuc.
Yee-Moon Wang Angela va cpng su cung ghi nhan ndng dp NT-proBNP tang cao la y6u to du bdo cho suy tim va cdc bien eb tim mach ve sau'*'. Matthew A. Roberts va cpng su ghi nhdn la khi n6ng dp NT-Pro BNP cang tang thi nguy ca ve cac biSn c6 tim mach ve sau cang ldn'"'. Ma day chinh la mot trong nhung nguyen nhan hang dau gay tii vong cho benh nhan dang lpc mau. Ket qud d bieu dd 1 va bieu d6 2 kh6ng thay cd tuong quan giua NT-
proBNP vdi cac chi sd huyet dp tam thu ldn tam tiuong, dieu nay cd thk do dnh hudng cua viec di^u tii cac thuoc huyet dp tren nhiing benh nhan nay, mat khac ehi sd huyit dp thudng khdng dn dinh tren benh nhan dang lpc mdu lam anh hudng den su phan ti'ch do mong quan.
Hon nu'a NT-proBNP dugc kieh thfch tang ti8t khdng phai do tang huylt dp ma la do tang dp luc len thanh tam thdt, di6u nay con bi anh hudng bdi mpt sd yeu td khac ngodi huylt dp.
KETLUAN
Qua nghien ciiu su tuong quan giua nong dp NT-ProBNP huyet mong va chi sd khdi ca thdt trai d 30 benh nhdn suy thdn man giai doan cudi dang lgc mau chu ky bang than nhan tao, ehiing tdi ed ket luan sau:
1. Suy tim rdt thudng gap d nhdm benh nhan dang lgc mau chu ky, ty Ie suy tim d nhdm benh nhdn nay la do 1: 20%; dp 2: 23,3%; dp 3: 36,7% va dp 4: 20%. Suy tim do 3 va do 4 chiem den 56,7 % so benh nhdn dugc nghien eiiu.
2. N6ng dp NT-ProBNP huyet tuong trudc khi Igc mau d benh nhan suy than man giai doan cudi dang lgc mau chu ky la rdt eao 10964+12504 pg/mL, khac biet rd so vdi nhdm chirng (59,86 ± 47,29 pg/mL; p<0,0001). Ndng dp NT-proBNP tang dan theo mue dp suy tim:
d d p 1: 1369 ± 748; dp 2:4994 ±4579; dp 3:12310 ±l{)971vd dp 4: 25058 ± 15415 pgtol. Co tuang quan thuan chat ehe giua n6ng dp NT-Pro BNP huyet mang va miic do suy tim tren lara sdng (r = + 0,641)."
TAI LIEU THAM KHAO
1. Hans Gunther Waht el al (2004). Elimination of the cardiac natriuretic peptide (BNP) and N-terminal pro BNP by hemodialysis. Clinical Chemistry 50, No 6: 1071-1074.
2. Matthew A. Roberts et al (2008). B-type Natriuretic peptides strongly predict mortality in patients who are treated with long-term dialysis. Clin J Am Soc Nephrol 3: 1057-1065.
3. Orlando M. Gutierrez et al (2008). N-terminal Pro-B-type Natriuretic peptide (NT-Pro BNP) concentrations in hemodialysis patients: prognostic value of baseline and folow-up measurements. Clinical Chemistry 54: 8: 1339-1348.
4., Stelvinken P. et al (2008). Emerging biomarkers for evaluating cardiovascular risk in the chronic kidney disease patients: how do new pieces fit into the uremic puzzle. Clin J Am Soc Nephrol 3: 505-521.
5. Vd Van Van, Hoang Biii Bao, Huynh Van Minh (2009). Nghien ciiu ndng do N-Terminal B-type Natriuretic peptide huyet tuang tiudc va sau lpc mdu d benh nhdn suy than man giai doan cudi. Tgp chiy hoc thuc hdnh. Bg Y te, sd 658-1-659, trang 534-538.
6. Yee-Moon Wang A. et al (2007). N-terminal Pro-Brain Natriuretic peptide: an independent risk predictor of cardiovascular congestion, mortality and adverse cardiovascular outcomes in chronic peritoneal dialysis patients. J Am Soc Nephrol 18:
321-330.
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