Hypertension lecture prof zak (1)
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UPDATE ON HYPERTENSION
Prof. Dr. M Zak Khalil,MD, FACP, FACC, FESC, MRCP (UK)
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Case 1
40 y.o. white male was found to have Bp (158/92) on pre-employment physical exam.
A) ARB B) ACE I C) B blocker D) Diuretic E) Calcium Ch blocker F) None of the above
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Prevalence of hypertension in China, Egypt, and USA
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Prevalence of hypertension in USA
JAMA 2003; 190:199
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FemaleMale
23.9
28.7
0
5
10
15
20
25
30
% p
reva
lenc
e
Saudis
Hypertension
Al Nozha et al, S Med J, 2007.
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22.4
27.9
0
5
10
15
20
25
30
RuralUrban
Residence
Hypertension in Saudi Arabia
Al Nozha et al, S Med J, 2007.
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Al Nozha et al, S Med J, 2007.
Hypertension is a silent killerUawareness = 58%
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JNC 7
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ESC & ESH Guidelines 2007
Category Systolic DiastolicOptimal <120 <80Normal 120-129 80-84High normal 130-139 85-89Grade 1 140-159 90-99Grade 2 160-179 100-109Grade 3 ≥180 ≥110Isolated sys ≥140 <90
European Heart Journal (2007) 28, 1462-1536
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ESC/ESH 2007Bp (mmHg) with different measurement
SBP DBPOffice or clinic 140 90
24-hour 125 -130 80
Day 130 – 135 85
Night 120 70
Home 130-135 85
European Heart Journal 2007
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Consequences of Hypertension
Hypertension
Brain
Heart
Kidney End-stage renal disease
MI, heart failure,sudden death
Stroke, dementia
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Framingham Heart Study - Risk of Cardiovascular Events by Hypertensive Status in Patients Aged 35-64 Years; 36-Year Follow-Up
9.5
3.3 2.45
2 3.5 2.1
45.4
21.3
12.4
6.29.9
7.3
13.9
6.3
22.7
0
10
20
30
40
50
Men Women Men Women Men Women Men Women
NormotensiveHypertensive
Risk Ratio 2.0 2.2 3.8 2.6 2.0 3.7 4.0 3.0Excess Risk 22.7 11.8 9.1 3.8 4.9 5.3 10.4 4.2
Coronary Disease Stroke Peripheral ArteryDisease
Cardiac Failure
Bie
nnia
l Age
-Adj
uste
d R
ate
per 1
000
Kannel WB JAMA 1996;275(24):1571-1576.
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Hea
lth S
tatu
s/Q
OL
Time, years
NormotensiveElevated Blood Pressure
Left Ventricular Dysfunction
Heart Failure
Low
erH
ighe
r
Death
Renal Impairment
Decline in Glomerular Filtration Rate
Kidney Failure
Vascular Hypertrophy
Stroke
Consequences of Hypertension
Am Heart J. 1991;121:1244–1263.
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0
5
10
15
20
0 100 200 300
5 Ye
ar R
isk
(%)
Stroke
Myocardial Infarction
Systolic Blood Pressure (mmHg)
Differing influence of hypertension onabsolute and relative risk of stroke and MI
Brown, M.J. Lancet 2000; 355: 659 - 660
20 40 60 80 120 140 160 180 220 240 260 280
Normotensives Hypertensives
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MI and Stroke in Hypertension Trials
N Engl J Med 2003
0
1
2
3
4
5
6
7
8
STOP-1SHEP
STONE
SYST-EUR
SYST-CHIN
AHOT
CAPPP
STOP-2NIC
S
NORDIL
INSIGHT
Perc
enta
ge o
f pat
ient
s w
ith e
vent Stroke
Myocardial Infarction
LIFEANBP2
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The circadian pattern of BP
Weber M.A. et al., Rev Cardiovasc Med 2004
24-hour BP levels
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The circadian pattern of BP
Weber M.A. et al., Rev Cardiovasc Med 2004
Correlation with CV events (ISAM study)
SCD
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Proteinuria: predicting cardiovascular events and survival in diabetes
A: U-Prot <150 mg/L B: U-Prot 150–300 mg/L C: U-Prot >300 mg/L
Incidence (%)
Survival
Months
A
B
COverall p<0.001
1.0
0.9
0.8
0.7
0.6
0.5
00 10 30 50 70 90 Stroke Coronary
Events
0
10
20
30
40
Overallp<0.001
Overallp<0.001
U-Prot=concentration of urinary protein
Miettinen et al. Stroke 1996; 27: 2033–9
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What level of blood pressure shouldbe achieved?
BHS 2004<140/85 mm Hg (<130/80 for diabetics)1
ESH/ESC 2003 + 2007<140/80 mm Hg (<130/80 for diabetics)2
JNC 7: 2003<140/90 mm Hg (<130/80 for diabetics)3
1. Williams et al. J Hum Hypertens 2004;18:139–85 2. Guidelines committee. J Hypertens 2003;21:1011–53
3. Chobanian et al. Hypertension 2003;42:1206–52
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AASK MAP <92
Target BP (mm Hg)
Multiple antihypertensive agents are needed to achieve target BP
No. of antihypertensive agents1
UKPDS DBP <85
ABCD DBP <75
MDRD MAP <92
HOT DBP <80
Trial 2 3 4
DBP, diastolic blood pressure; MAP, mean arterial pressure; SBP, systolic blood pressure.Bakris GL et al. Am J Kidney Dis. 2000;36:646-661.Lewis EJ et al. N Engl J Med. 2001;345:851-860.Cushman WC et al. J Clin Hypertens. 2002;4:393-404.
IDNT SBP <135/DBP <85
ALLHAT SBP <140/DBP <90
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Value of excellent vs. good blood pressure control in NIDDM(144/82 vs. 154/87mmHg)
0
10
20
30
40
0 1 2 3 4 5 6 7 89
Pat
ient
s W
ith E
vent
s (%
) Less tight controlTight control
Years From Randomisation
UKPDS, BMJ 1998;317:703-713.
Reduction in risk with tight control 32% (95% CI 6% to 51%) (P=0.019)
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LIFE Trial: Blood-Pressure Reductions
0 6 12 18 24 30 36 42 48 54
Study Month
40
50
60
70
80
90
100
110
120
130
140
150
160
170
180
Systolic
Diastolic
Mean Arterialmm
Hg
Atenolol 145.4 mmHg
Losartan 144.1 mmHg
Atenolol 80.9 mmHgLosartan 81.3 mmHg
Dahlöf B et al Lancet 2002;359:995-1003.
Atenolol 102.4 mmHgLosartan 102.2 mmHg
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SBP Control in Trials *
Mancia and Grassi, J Hypert 2002
FACET
Micro HOPE
CAPPP
INSIGHT
HOT
VALUE
STOP-2
UKPDS
LIFE
RENAAL
IDNT
IRMA
ABCD130
140
150
160
170
180
190
200mmHg
120
Diabetics
B T
ALLHAT 1
HOPE
PROGRESS
CAPPP
INSIGHT
NORDIL
HOT
STONE
STOP-2
LIFE
ALLHAT 2
ANBP2
INVEST
SCOPE
ASCOT
VALUE
All patients
130
140
150
160
170
180
190
200mmHg
B T
* Most patients under ≥ 2 drugs
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USA
27
Canada
13
England
6
France
24
Adapted from G. Mancia / L. Adapted from G. Mancia / L. RuilopeRuilope
<140/90 mmHg
MarquesMarques--Vidal P et al. J Vidal P et al. J Hum HypertensHum Hypertens19971997
Percentages of Patients whose Hypertension is Controlled
Percentages of Patients whose Percentages of Patients whose Hypertension is ControlledHypertension is Controlled
Finland Spain
20
Germany Scotland
<160/95 mmHgAustralia
19
India
9
20.5
17.522.5
> 65 years
USA:USA: JNC VI. JNC VI. Arch Intern MedArch Intern Med19971997Canada:Canada: Joffres Joffres et al. et al. AmAmJ J HypertensHypertens2001 2001
England:England: Colhoun et al. J Hypertens 1998Colhoun et al. J Hypertens 1998France:France: Chamontin et Chamontin et al. al. AmAmJ J HypertensHypertens19981998
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Limitations of Clinical Trials
• Mostly high risk / elderly patients:i.e. younger / low risk patients are not represented
• Short durations (4 – 5 years):i.e. the extra 20 – 30 years are not studied
• Multiple combined primary end points:i.e. single end point as a beneficial effect, can not be concluded
• Limitations of meta-analysis:i.e.: by definition, they are post-hoc analysis
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Facts that we now know:
• Antihypertensive Rx = Less CV morbidity & mortality
• The benefits extend to isolated systolic hypertension
• The beneficial effect is present across men & women in various ethnic groups
• 30 -40% risk reduction in stroke
• 20% risk reduction in coronary events
• Large reduction in heart failure
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25
Biochemical Results –Fasting Glucose – mg/dL
100.5 (19.5)*103.1 (27.7)104.4 (28.5)4 Years
Diabetes Incidence (follow-up fasting glucose 126 mg/dL)
Among baseline nondiabetics with baseline <126 mg/dL
Total
4 Years
Baseline
4 YearsBaseline
8.1%*9.8%*11.6%
93.3 (11.8)93.0 (11.4)93.1 (11.7)
121.5 (51.3)*123.7 (52.0)126.3 (55.6)
122.9 (56.1)123.1 (57.0)123.5 (58.3)
LisinoprilAmlodipineChlorthalidone
*p<.05 compared to chlorthalidone
ALLHAT
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Intention-to-Treat
LIFE: New Onset Diabetes
Losartan
Atenolol
Endp
oint
Rat
e
Study Day 0 180 360 540 720 900 1080 1260 1440 1620 1800 19800.00
0.01
0.02
0.03
0.04
0.05
0.06
0.07
0.08
0.09
0.10
Adjusted Risk Reduction 25%, p<0.001Unadjusted Risk Reduction 25%, p<0.001
7 B Dahlof et al. Lancet 2002;359:995-1003
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CAPPP
ACEIvs
Conv
STOP-2
ACEIvs
Conv
ALLHAT
ACEIvsD
HOPE
ACEIvsPL
STOP-2
CAvs
Conv
INSIGHT
CAvsD
ALLHAT
CAvsD
STOP-2
ACEIvsCA
LIFE
ARBvsBB
SCOPE
ARBvs
Conv
CHARM
ARBvsPL
INVEST
CAvs
Conv
SOLVDT
ACEIvsPL
ASCOT
CAvs
Conv
VALUE
ARBvsCA
-14
-4
-40-34
-74
-2
-16
-23 -25
-2
-33
-25-20 -21 -23
-80
-70
-60
-50
-40
-30
-20
-10
0
-30*
-16**
*=2 yrs, **=4 yrs
New DM in antihypertensive drug trials%
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Choosing drugs for patients newly diagnosed with hypertension
< 55 years > 55 years or black patients at any age
A* C or D
A* + C or A* + D
A* + C + D
Consider 4th line drug:Further diuretic therapy orAlpha blocker or Beta blocker
A = ACE inhibitor (* consider ARB if ACE intolerant)C = calcium channel blocker D = thiazide type diuretic
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Conclusions• Hypertension is the commonest cause of major
morbidity, but less than a quarter of patients are adequately treated.
• A reduction in cardiovascular disease mortality and morbidity can be achieved through improved treatment and control of hypertension.
• A greater choice of drugs are available for hypertension than for other chronic diseases
• Rational choice of single and combination drugs facilitated by understanding their effects on the renin system, but systematic trial and error may still be necessary
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