hypertension lecture prof zak (1)

UPDATE ON HYPERTENSION

Prof. Dr. M Zak Khalil,MD, FACP, FACC, FESC, MRCP (UK)

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

Prevalence of hypertension in China, Egypt, and USA

Prevalence of hypertension in USA

JAMA 2003; 190:199

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.

22.4

27.9

0

5

10

15

20

25

30

RuralUrban

Residence

Hypertension in Saudi Arabia



Hypertension is a silent killerUawareness = 58%

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

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

Consequences of Hypertension

Hypertension

Brain

Heart

Kidney End-stage renal disease

MI, heart failure,sudden death

Stroke, dementia

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.

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.

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

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

The circadian pattern of BP

Weber M.A. et al., Rev Cardiovasc Med 2004

24-hour BP levels

The circadian pattern of BP

Weber M.A. et al., Rev Cardiovasc Med 2004

Correlation with CV events (ISAM study)

SCD

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

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

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

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)

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

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

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

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

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

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

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

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%

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

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

hypertension lecture prof zak (1)

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