TNG HUYT P NGI LN TUI

CP NHT IU TR
VI THUC CHN CALCI
PGS.TS. Nguyn c Cng Bnh Vin Thng Nht i hc y dc Tp H Ch Minh

I. TNG HUYT P NGI LN TUI

Tui th

Tui th ngy cng tng c tnh n 2030, ngi > 65 tui chim 20% dn s Hoa K.

Tui i v bnh tt

Tui cng cao cng tng t l bnh tt v mc nng ca bnh.

NGUYN NHN GY T VONG (US)

Other 18% COPD 3% Pneumonia 3% Accidents 5% CVD 50%

Cancer 21%

TNG HUYT P L MT TRONG NHNG YU T NGUY C QUAN TRNG NHT

BP > 140/90 mmHg is associated with:

277,000 deaths in 2003

BP, blood pressure; CHF, congestive heart failure; MI, myocardial infarction.
Rosamond W et al. Circulation. 2007;115:1-103.

Tnh hnh bnh tng huyt p ti Vit Nam

iu tra dch t: t l bnh THA gia tng nhanh trong cng ng. * 1960: 1% dn s trng thnh min Bc. * 1976: 1,9% dn s trng thnh min Bc. * 1992: 11,7% ngi ln c nc. * 1999: 16,05% ti ni & ngoi thnh H Ni. * 2002: 16,32% ngi 25 tui pha Bc VN. * 2008: 27,2% ngi 25 tui (iu tra ti 8 tnh/thnh ph VN)

II. THAY I HUYT P & H THNG TIM MCH THEO TUI

HUYT P

HA tm thu khuynh hng tng dn theo tui.

Tng 5-8 mm Hg cho mi thp nin sau tui 40-50.

HA tm trng tng nh n 60 tui, sau n nh v gim nh. (Generally increases 1 mm Hg per decade)

Nguy c xut hin tng huyt p khi > 65 tui

Risk of hypertension (%)

100 80 60 40 20 0 0 2 4 6 8 10 12 14 16 18 20 Years
Men Women

Residual lifetime risk of developing hypertension among people with blood pressure <140/90 mmHg

Vasan RS, et al. JAMA. 2002; 287:1003-1010. Copyright 2002, American Medical Association.

Vin cnh xut hin bnh tng HA

90% ngi > 55 tui s xut hin tng HA thi im no trong cuc i.

TNG HUYT P TM THU

Partners in Healthcare Education, LLC 2009

12

Nhp tim

Khng thay i khi nm ngh, gim t th ngi (gim p ng vi h giao cm) D b h HA t th Khi gng sc, nhp tim gim theo tui.

200 beats/min tui 20 140 beats/min tui 80

(Tn s tim c tinh theo tui = 220 tui)

Thay i h thng ng mch

Thnh ng mch dy v km n hi.

Tng HA Tng khng lc mch mu ngoi bin

p ng vi kch thch giao cm

Gim p ng vi cc kch thch bta giao cm.

Gim tn s tim ti a.

1 & 2 effect 2 effect

Gim kh nng gin mch ngoi bin.

Cung lng tim

Khng c s thay i quan trng theo tui trng thi ngh ngi, c th gim khi hot ng th lc.

C th do gim th tch cui tm trng tht tri do thnh tht tri dy v km n hi.

III. Y HC BNG CHNG

Phn b bnh tng huyt p theo tui

( NHANES III) ISH (SBP 140 mm Hg and DBP < 90 mm Hg) SDH (SBP 140 mm Hg and DBP 90 mm Hg) IDH (SBP < 140 mm Hg and DBP 90 mm Hg) 100 80 Frequency of hypertension 60 subtypes in all untreated 40 hypertensives (%) 20 0 <40 40-49 50-59 60-69 Age (y) 70-79 80+ 17% 16% 16% 20% 20%

ISH
11%

Franklin et al. Hypertension 2001;37: 869-874.

N Engl J Med 2007;357:789-96.

Tng huyt p tm thu v nguy c t vong do bnh l tim mch.

SBP versus DBP in Risk of CHD Mortality
CHD Death Rate

100+ 9099 8089 Diastolic BP 7579 7074

160+ 140159 120139 <70 <120

(mm Hg)

Systolic BP (mm Hg)

Adapted from Neaton JD et al. Arch Intern Med. 1992;152:56-64. MRFIT = Multiple risk factor intervention trial. Risk factor changes and mortality results. Multiple Risk Factor Intervention Trial Research Group.

Tng huyt p tm thu n c gy tng nguy c bnh l tim mch v bnh thn.
Disease
Kidney failure (ESRD) Stroke Heart failure Peripheral vascular disease Myocardial infarction* Coronary artery disease

Relative Risk
2.8 2.7 1.5 1.8 = 1.6 1.5

ESRD = end-stage renal disease; SBP 165 mm Hg. *Men only. Adapted from Kannel WB. Am J Hypertens. 2000;13:3S-10S; Perry HM Jr et al. Hypertension. 1995;25(part 1):587-594; Klag MJ et al. N Engl J Med. 1996;334:13-18; Nielsen WB et al. Ugeskr Laeger. 1996;158:3779-3783; Neaton JD et al. Arch Intern Med. 1992;152:56-64.

LI IM KHI IU TR TNG HUYT P

BN < 60 tui (gim HA 10/5-6 mmHg)

Gim nguy c t qu 42% Gim nguy c xut hin bin c bnh MV 14%

BN > 60 tui (gim HA 15/6 mmHg)

Gim t vong ton b Gim t vong do bnh l TM Gim t qu Gim bnh l ng mch vnh
Lancet 1990;335:827-38

15% 36% 35% 18%

Arch Fam Med 1995;4:943-50

LI IM KHI IU TR T HUYT P MC TIU

BN > 60 tui
(SBP 160 mm Hg and DBP < 90 mm Hg)

Gim nguy c t qu 42% Gim nguy c xut hin bin c bnh l ng mch vnh 26%

Lancet 1997;350:757-64

H p l vn then cht
Meta-analysis of 61 prospective, observational studies* 1 million adults 12.7 million person-years

Gim 2 mm Hg HATTh trung bnh

Gim 7% nguy c t vong bnh tim thiu mu cc b Gim 10% nguy c t vong do t qu

*Epidemiologic studies, not clinical trials of HTN agents. BP, blood pressure; IHD, ischemic heart disease. Lewington S et al. Lancet 2002;360:1903-1913.

Mc HA mc tiu cn t n ty theo din tin bnh v tn thng c quan ch

*LV Hypertrophy, Angina, MI, PTCA, Bypass; Sroke or TIA, Peripheral Arterial Disease, retinopathy, carotid plaque, microalbuminurea

2007 Guidelines for the Management of Arterial Hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens. 2007;25(6):1105-87

NHNG TH NGHIM LM SNG

The Hypertension Optimal Treatment Study (HOT Study)

S lng bnh nhn tham gia NC

A total of 18.790 patients from 26 countries were randomised
Country/ randomised area Argentina Austria Belgium Canada Denmark East Asia Finland France Germany Great Britain Greece Hungary No. of randomised patients area 47 628 755 838 503 134 373 1.574 4.269 131 335 194 Country/ patients Israel Italy Mexico Norway South East Asia Spain Sweden Switzerland The Netherlands USA 411 2.702 49 432 71 806 492 797 603 2.646 No. of

Tiu ch chnh.
nh gi mi lin quan gia nhng bin c v
tim mch vi 3 tr s HA tm trng ch (< 90, < 85 v < 80 mm Hg) trong thi gian iu tr tng HA.

 Step 1

Cc bc iu tr tng HA trong NC HOT.

5 mg felodipine

Step 2
Step 3 Step 4 Step 5

5 mg felodipine + low dose ACE inhibitor or -blocker

10 mg felodipine + low dose ACE inhibitor or -blocker 10 mg felodipine + high dose ACE inhibitor or -blocker 10 mg felodipine + high dose ACE inhibitor or -blocker + low dose alternative addition or HCT

HOT STUDY

c im dn s nghin cu (%)
DBP target group (mm Hg) 90 85 80 n=6 264 n=6 264 n=6 262

Previous treatment Smokers Previous MI Other previous CHD Previous stroke Diabetes mellitus

52.3 15.9 1.6 5.9 1.2 8.0

52.7 15.8 1.5 6.0 1.2 8.0

52.6 15.9 1.5 5.9 1.2 8.0

Thi gian theo di = 36 thng

Gim tr s HA tm thu ln thm khm cui cng.

mm Hg 90 mm Hg 0 -15 -20 -25 -30 DSBP
85 mm Hg 80 mm Hg

HOT STUDY

Gim 30% cc bin c tim mch khi t mc HA tm trng = 82,6mmHg.

105 0 5 10 15 20 100 95 90 85 Achieved DBP 80 mm Hg

Optimal DBP reduction in the HOT Study

25
30 % risk reduction

Gim 22% cc bin c tim mch khi t mc HA tm thu = 138,5mmHg.

170 0 5 10 15 20
Optimal SBP reduction in the HOT Study

160

150

140

130

Achieved SBP mm Hg

25
30 % risk reduction

HOT : Kt lun
Hiu qu h HA i km vi gim t l bin c
v tim mch.

Gim cc bin c tim mch nhiu nht khi iu

tr t c tr s HA ti u: HA tm thu # 139mmHg, v HA tm trng # 83mmHg.

Cu hi?

Ngi Chu c t c tiu ch chnh trong NC HOT hay khng? Mc HA ti u ca ngi Chu trong iu tr tng HA?

Dn s Chu trong nghin cu HOT

Global
S BN

Asian

18,790
47% (8,883) 53% (9,907) 61.5+7.5 years (50-80 years)

205
38% (78) 62% (127) 58.8+6.3 years (50-80 years)

N: Nam: Tui:

MC GIM HUYT P TRONG NGHIN CU HOT

90 0 -5 -10 85 80 mm Hg 90 85 80 mm Hg

0
-5 -10

Global patients Asian patients

-15
-15 -20 -25 -30 -20 -25 -30
p<0.0001 p<0.0001

-35
p<0.0001 -40

p<0.0001 p<0.01

DDBP mm Hg

DSBP mm Hg

p<0.0001

T l kim sot c HA mc tiu (Target < 90mmHg)

DBP (mmHg)

105

100
95 90
74% 80% 83% 85%

Global patients* Asian patients

86% 86%

85
80 75 0 0 3 6 12
89% 97% 97%

98%

97% 95%

24

36

Final
Follow-up (Month)

* Except for Asian patients

T l xut hin tc dng ph trong NC HOT

Patients who suffered side effect %
18 17.1 16 14 12 10 8.5 8 6 4 2 0 3M 6M 12M 18M 24M 30M 36M 42M 48M
ns ns p<0.001

***

Global patients* Asian patients

9.0
p<0.05

10.8

6.5

6.2

7.0

6.2 3.7
ns

p<0.01

*
2.6

4.9

4.3 ns 1.6

p<0.05

3.9

p<0.01

1.1

**

0.6

3.2 ns 1.1

2.5
ns

3.0

0 54M Final

**

Time of follow-up
* Except for Asian patients

KT LUN CA NC HOT - PLENDIL CHO BN NGI CHU

Hiu qu iu tr tng HA vi thuc c ch knh Ca (Plendil) tt hn nhm BN chu . BN Chu t xut hin tc dng ph.

Mc tiu nghin cu HOT - China

nh gi hiu qu iu tr tng HA trong 10 tun l bnh nhn tng HA nguyn pht ngi Trung Quc theo Protocol ca NC HOT. nh gi tnh an ton v kh nng dung np vi Plendil trong iu tr tng HA nguyn pht ngi Trung Quc.

Dn s nghin cu

Tui: 18 - 90

Tng HA v cn, SBP > 140mmHg v/hay DBP > 90mmHg

N khng mang thai hay cho con b. Khng s dng Plendil t nht 4 tun l.

Cc bc nghin cu
1st step Plendil 5mg *

2nd step

Plendil 5mg + Betaloc 25mg BID /Low dose of ACEI *

3rd step 4th step

Plendil 10mg + Betaloc 25mg BID/Low dose of ACEI * Plendil 10mg + Betaloc 50mg BID/High dose of ACEI
*

5th step

Plendil 10mg + Betaloc 50mg BID/High dose of ACEI + Low dose of other anti-hypertensive drugs (-blocker/ACEI)/Diuretic

* Target DBP < 90mmHg after 2 weeks treatment.

Dn s nghin cu
Repeated data

321 Data sum 58,289

Qualified data 56,438 Unqualified data Intention-to-treat population (ITT)

53,040

(age, gender or baseline BP missing)

1,530

KT QU

KT QU

TC DNG PH

AE = Ankle Edema

HOT China: Kt lun

Cc bc iu tr tng HA trong NC HOT ph hp vi bnh tng HA nguyn pht ngi Trung Quc. Cc bc iu tr c tnh an ton, hiu qu v dung np tt. Kt hp thuc liu thp gia cc nhm thuc nh Plendil + Betaloc / ACEI khng lm tng thm hiu qu h HA nhng lm gim c tc dng ph khi tng liu thuc trong ch iu tr 1 thuc Bnh nhn tng HA nguyn pht ngi Trung Quc c kim sot HA an ton v hiu qu hn.

The Felodipine Event Reduction (FEVER) Study

A Randomized Long-Term Placebo-Controlled Trial in Chinese Hypertensive Patients Design and Principal Results

Lisheng Liu, Yuqing Zhang, Guozhang Liu, Wei Li, Xuezhong Zhang and Alberto Zanchetti for the FEVER Study Group (Beijing, China and Milan, Italy)

1338 Z

FEVER: MC TIU
1. So snh hiu qu trn bin c v bnh l tim mch ca Plendil liu thp 5mg/ngy vi placebo BN tng HA c iu tr bng thuc li tiu liu thp (HCTZ 12,5mg/ngy).

2. So snh hiu qu h HA tch cc t c mc HA mc tiu theo cc khuyn co.

1340 Z

FEVER: Inclusion Criteria

50-79 tui, c nam v n i tng < 60 tui: c t nht 1 bin c tim mch nh NMCT, t qu, au tht ngc, suy tim, bnh ng mch ngoi vi, cn thieesyu mu no thong qua hoc c 2 yu t nguy c tim mch (nam, ht thuc l, TC > 5.7 mmol/l, tiu ng, LVH (voltage), proteinuria > +, BMI > 27 kg/m2) i tng > 60 tui: c t nht mt bin c tim mch hoc mt yu t nguy c. Khm sng lc: Bnh nhn iu tr: SBP/DBP < 210/115 mmHg : Bnh nhn cha iu tr : SBP 160-210 mmHg hoc DBP 95-115 mmHg Chn ngu nhin: SBP 140-180 or DBP 90-100 mmHg, sau 6 tun dng HCTZ 12.5 mg/ngy (ct thuc dng trc y)
1342 Z

Giam tai bien mach mau nao

10

Ty le benh nhan xay ra bien co (%)

HR = 0.732, 95% CI: 0.601-0.891, p = 0.0019

Xanh: Placebo Chm: Plendil

-26.8%

12

18

24

30

36

42

48

54

60

(the FEVER Study Group)

Theo doi (thang)

Giam tong bien co tim mach

15

Ty le benh nhan xay ra bien co (%)

HR = 0.726, 95% CI: 0.612-0.860, p = 0.0002

12

Xanh: Placebo Chm: Plendil -27.4%

12

18

24

30

36

42

48

54

60

(the FEVER Study Group)

Theo doi (thang)

Giam bien co mach vanh

4 Ty le benh nhan xay ra bien co (%) HR = 0.675, 95% CI: 0.491-0.927, p = 0.0153 3

Xanh: Placebo Chm: Plendil

-32.5%

12

18

24

30

36

42

48

54

60

(the FEVER Study Group)

Theo doi (thang)

Giam t vong do nguyen nhan tim mach

4 Ty le benh nhan xay ra bien co (%) HR = 0.668, 95% CI: 0.489-0.912, p = 0.0112 3

Xanh: Placebo Chm: Plendil

-33.2%

12

18

24

30

36

42

48

54

60

(the FEVER Study Group)

Theo doi (thang)

FEVER: Endpoint Analysis (first time occurrence in each category)

Per 1000 patient-years Felodipine Stroke Fatal Non-fatal All CV events All cardiac events All cause death CV death Coronary events Heart failure New onset diabetes Cancer 11.2 2.1 9.1 15.2 4.6 7.1 4.6 4.5 1.1 3.6 2.6 Placeb o 15.9 3.1 12.7 21.2 6.6 9.6 6.4 6.2 1.7 3.5 3.9
0.4

Hazard Ratio (95% CI)

0.72 0.70 0.72 0.72 0.66 0.70 0.68 0.68 0.76 1.03 0.60
0.6
0.8 1.0 1.5 2.0

Felodipine better
1355 Z

Placebo better

FEVER: KT LUN
BN tng HA ngi Trung Quc iu tr bng HCTZ (12.5 mg/d) v Felodipine liu thp 5mg/ngy gim c HA nhiu hn (SBP/DBP # 4/2 mmHg) v gim quan trng cc bin c t qu (28%), bin c v bnh tim mnh (28%), bin c v bnh ng mch vnh (32%), gim t vong do tt c cc nguyn nhn (30%), gim t vong do bnh l tim mch (17%). iu tr kt hp liu thp UC knh Ca v HCTZ cho kt qu tt hn n tr liu HCTZ liu thp. iu tr vi liu thp ch c 1% xut hin bnh l T mi mc.
1362 Z

IV. NHNG KHUYN CO IU TR TNG HUYT P

BHS IV, 2004 and Update of the NICE Hypertension Guideline, 2006

BHS Guidelines for the management of hypertension

ESH
Compelling and possible indications, contraindications, and cautions for the major classes of antihypertensive drugs
Class of drug Beta-blockers Compelling indications MI, Angina Possible indications Heart failure Caution Heart failure, PVD, Diabetes (except with CHD) Combination with betablockade Compelling contraindications Asthma/COPD, Heart block

CCBs (dihydropyridine) CCBs (rate limiting)

Elderly, ISH Angina

Angina Elderly

Heart block Heart failure Gout

Thiazide/thiazide- Elderly like diuretics ISH Heart failure 2 o stroke prevention

Combination between some classes of antihypertensive drugs

Thiazide diuretics

2007 ESH/ESC Guidelines

-blockers

AT1-receptor antagonists

-blockers ACE inhibitors

J Hypertens. 2007;25:1105-1187.

Calcium antagonists

JNC 7.

Bnh nhn ln tui

Tng HA v cn ph bin nht:

Nn bt u iu tr bng thay i li sng. Nn khi u dng thuc vi liu thp. HA mc tiu < 140/90 mm Hg. Nhm thuc c ch knh Ca l mt trong nhng thuc chn la u tin.

Hng dn iu tr tng HA theo Hi Tng HA Canada 2010

Hng dn iu tr tng HA theo Hi Tng HA Canada 2010

V. KT LUN

Tng huyt p ngi ln tui rt thng gp. Thng l tng huyt p tm thu n c. Tng huyt p tm thu cng gy ra nhng bin c v tim mch trm trng v t vong. iu tr tt tng HA tm thu lm gim quan trng t xut v cc bin chng tng HA. Nhm thuc c ch knh calci dihydropyridines tc dng ko di (nh Felodipine - Plendil) c vai tr quan trng trong kim sot tt HA ngi ln tui.

Chn thnh cm n s ch ca Qu v

T L NHP VIN V T VONG V BNH L TIM MCH

Number of Total 858 1280 731 1040 1044 Admissions Age > 65 562 (65.5%) 685 (53.5%) 519 (71.0%) 805 (77.4%) 758 (72.6%) Deaths Age > 65 63 (81.2%) 12 (85.7%) 11 (73.3%) 38 (92.7%) 47 (74.6%)

Acute MI Coronary disease Arrhythmias Heart failure Cerebrovascular Dz (numbers in thousands)

> 65 yo 13% population

National Hospital Discharge Survey, 2000.

Thay i tim

Dy thnh tm tht tri km tng huyt p.

nng ln khi c

Ph i tm tht tri c th gy chm th gin trong thi k tm trng. Gin nh tri th pht sau ph i tm tht tri.

Sites of Clinical Centers of FEVER

JNC 7.

Algorithm for Treatment of Hypertension

Lifestyle Modifications

Not at Goal Blood Pressure (<140/90 mmHg) (<130/80 mmHg for those with diabetes or chronic kidney disease)

Initial Drug Choices

Without Compelling Indications

With Compelling Indications

Stage 1 Hypertension
(SBP 140159 or DBP 9099 mmHg) Thiazide-type diuretics for most. May consider ACEI, ARB, BB, CCB, or combination.

Stage 2 Hypertension
(SBP >160 or DBP >100 mmHg) 2-drug combination for most (usually thiazide-type diuretic and ACEI, or ARB, or BB, or CCB)

Drug(s) for the compelling indications

Other antihypertensive drugs (diuretics, ACEI, ARB, BB, CCB) as needed.

Not at Goal Blood Pressure Optimize dosages or add additional drugs until goal blood pressure is achieved. Consider consultation with hypertension specialist.

FEVER: TIU CH NGHIN CU

Chnh:
Ph :
t qu (fatal and nonfatal)
1) Total cardiovascular events (composite of CV death, non-fatal stroke, non-fatal MI, dissecting aortic aneurysm, HF requiring treatment, PTCA, CABG, interventions for PAD, s. creatinine > 355 mol/l) 2) Total cardiac events (composite of death by CHD, non-fatal MI, death by HF, HF requiring treatment, PTCA, CABG) 3) Death by any cause (composite of CV death and non-CV death) 4) Any of the event categories in composite outcomes a) fatal stroke, b) non-fatal stroke, c) CHD events (fatal and nonfatal MI and sudden death), d) HF, e) CV death, f) renal failure 5) New onset diabetes (FBG > 7.0 mmol/l or treatment) 6) Cancer

1345 Z

FEVER: TIU CH NGHIN CU

Chnh:
Ph :
t qu (fatal and nonfatal)
1) Total cardiovascular events (composite of CV death, non-fatal stroke, non-fatal MI, dissecting aortic aneurysm, HF requiring treatment, PTCA, CABG, interventions for PAD, s. creatinine > 355 mol/l) 2) Total cardiac events (composite of death by CHD, non-fatal MI, death by HF, HF requiring treatment, PTCA, CABG) 3) Death by any cause (composite of CV death and non-CV death) 4) Any of the event categories in composite outcomes a) fatal stroke, b) non-fatal stroke, c) CHD events (fatal and nonfatal MI and sudden death), d) HF, e) CV death, f) renal failure 5) New onset diabetes (FBG > 7.0 mmol/l or treatment) 6) Cancer

1345 Z

FEVER: THIT K V S NC
+ Felodipine 5 mg/d HCTZ 12.5 mg/d + Placebo

visits weeks

1 -6

2 -4

3 -2

4 0

5 1

6 2

7 3

8 4

9 5

10 11 12 6 9 12

16 24

20 36

24 48

28 60 months

Add-on diuretic or other agents (not CA) if BP > 160/90 mmHg, at investigators discretion Screening Randomization

1344 Z

FEVER: TIU CH NGHIN CU

Chnh:
Ph :
t qu (fatal and nonfatal)
1) Total cardiovascular events (composite of CV death, non-fatal stroke, non-fatal MI, dissecting aortic aneurysm, HF requiring treatment, PTCA, CABG, interventions for PAD, s. creatinine > 355 mol/l) 2) Total cardiac events (composite of death by CHD, non-fatal MI, death by HF, HF requiring treatment, PTCA, CABG) 3) Death by any cause (composite of CV death and non-CV death) 4) Any of the event categories in composite outcomes a) fatal stroke, b) non-fatal stroke, c) CHD events (fatal and nonfatal MI and sudden death), d) HF, e) CV death, f) renal failure 5) New onset diabetes (FBG > 7.0 mmol/l or treatment) 6) Cancer

1345 Z