Caduet (Dr. Ismahun Maret 2009)

7/27/2019 Caduet (Dr. Ismahun Maret 2009)

1/41

ChangingCardiovascular risk environment

andthe interpretation of current guidelines

Dr P. Ismahun SpJP, FIHA

Malang, 21 Maret 2009


2/41

Hypertension

Dyslipidemia

Diabetes

Mellitus Obesity

Risk Factors on Global CardiovascularDisease Burden

Smoking

Lp(a)

Homocystein

No exercise

Others (+ 200)


3/41

Hypertension

Dyslipidemia

Diabetes

Mellitus Obesity

Smoking

Lp(a)

Homocystein

No exercise

Others (+ 200)

Joint effects of Risk Factors on GlobalCardiovascular Disease Burden


4/41

Blood pressure and AtheromaLessons from veins

Veins dont develop atheroma even in peoplewith elevated Cholesterol low pressure system ;

Pulmonary Hypertension associated with

atheroma of pulmonary venous system ;

Venous grafts into coronary circulation (highpressure) develop atheroma ;

Pressure is permissive for the development of

atheroma ;

Logical to lower cholesterol and pressure toreduce the risk of developing atheroma.


5/41

Normal Prehypertension Hypertension

JNC 7 Categories

30

25

20

15

10

5

0

-5

-10

-15

-20

P < 0.001

P = 0.01

P = 0.039

Changei

nAtheromavolume(mm3)

Effect of Blood Pressure onProgression of Coronary Atheroma

J Am Coll Cardiol 2006;48: 833-8


6/41

Majority of US Hypertensive Patients Not at

SBP Goal of


7/41

NHANES = National Health and Nutrition Examination Survey; SBP = systolic blood pressure;

DBP = diastolic blood pressure.

Burt VL et al. Hypertension. 1995;26:60-69.Whyte JL et al. J Clin Hypertens. 2001;3:211-216.

NHANES III: Poor Systolic BP Control

Underlies Inadequate BP Control Overall

Only 34.3%

Reach SBP Goal

73% Reach DBP Goal

250

DBP(mm Hg)

50

100

150

200

140

0 50 100 150

9023.6% 10.7%

49.6% 16.1%SBP(mm Hg)


8/41

Coronary Disease by Usual SBP

Usual SBP (mm Hg)

HazardRatioand

95%CI

32.0

16.0

8.0

4.0

2.0

1.0

0.5

110 120 130 140 150 160

-10 mm Hg

70 years

60-69 years


9/41

2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 10.0 10.5 11.0

Men 30-59 years, Serum cholesterol (mmol/l)

25

20

15

10

5

0

Year 72778287

92

Serum cholesteroldistribution by study year,men aged 30 to 59 years inFinland

Jousilahti, P. et al. Circulation 1998;97:1087-1094

5 Mmol/l = 193 mg/dl

6 Mmol/l = 231.6 mg/dl


10/41

50

40

30

20

10

0

5.5

5

4.5

4

3.5

3

2.5

2

1.5

1

0.5

0

Serum Cholesterol CHD deaths Odds ratio

5.0 5.0-6.49 6.5-7.99 >8.0

Serum Cholesterol level (Mmol/l)

Distribution of serumcholesterol and

coronary heart disease(CHD) deaths of men inFinland, aged 30 to 59years (1972, 1977, and1982 cohorts combined)

and odds ratio of CHDmortality associatedwith serum cholesterol

Jousilahti, P. et al. Circulation

1998;97:1087-1094

5 Mmol/l = 193 mg/dl

6 Mmol/l = 231.6 mg/dl


11/41Chen Z,et al, BMJ, 1991;303:278-282

2.00

1.00

0.50

0.25

3.6 3.8 4.0 4.2 4.4 4.6 4.8

139 147 155 162 170 178 186

Mean Usual Cholesterol (mmol/L, mg/dL)

9

4

12

18

What is Normal Cholesterol ?

Relative risk of death (+) from CHD by quartiles of baseline total

cholesterol in 9021 Chinese people with 8 13 years follow-up.


12/41

What we define

asnormalvalues for BloodPressure and Cholesterol are basedon usual values for our

populationsthese are not normalvalues for a human being, they arethe usual values of a human being

at risk of dying prematurely fromvascular disease

B. Williams, 2006


13/41

The Population Burden ofCardiovascular Disease is in thosepeople with modest elevations ofmultiple risk factors, NOT thosewith single, extreme elevations ofsingle risk factors.

B. Williams, 2006


14/41

MI=myocardial infarction; PS=psychosocial.

Reproduced with permission from Yusuf S et al. Lancet. 2004;364:937-952.Please see prescribing information at the end of this slide presentation.

Increased Number of CV Events (MI) in Patients

with Hypertension Plus Other CV Risk Factors

OddsRatio(99%C

I)

512

256

128

64

32

16

8

4

2

1

2.9(2.6-3.2)

2.4(2.1-2.7)

1.9(1.7-2.1)

3.3(2.8-3.8)

13.0(10.7-15.8)

42.3(33.2-54.0)

68.5(53.0-88.6)

182.9(132.6-252.2)

333.7(230.2-483.9)

Smoking(1)

Diabetes(2)

HTN(3)

Lipids(4)

1+2+3 All 4 + Obes + PS All RFsRisk Factors

Risk Ratio

HTN + 3 RiskFactors

HTN >20-Fold Increase

OR from 1.9 (HTN only) to

42.3


15/41

Multiple CV Risk Factors in Addition toHypertension Result in a High CVD Risk

*Reference=nondiabetic, nonsmoker woman, aged 50 years with total cholesterol (TC)=4.0 mmol/L

and HDL-C=1.6 mmol/L.Jackson R et al. Lancet. 2005;365:434-441.

Increasing No. of Additional Risk Factors

0

5

10

15

20

25

30

35

40

45

50

5-YearCVDRis

kper100Peop

le

+ 60years

+ Diabetes+ Male+ HDL-

1 mmol/L

+ Smoker+ TC-7 mmol/L

Reference

3%6%

12%

18%

24%

33%

44%110

120

130

140

150

160

170

180

BP (mm Hg)

M H i P i H Addi i l


16/41

90.3%with 3 risk factors

Most Hypertensive Patients Have AdditionalRisk Factors

REACH Registry

81.8%HTN*

Bhatt DL et al. JAMA. 2006;295:180-189.

*140/90 mm Hg at baseline.

Risk factors include: treated diabetes mellitus, diabetic nephropathy, asymptomatic

carotid stenosis 70%, Systolic blood pressure [SBP], 150 mm Hg, treated

hypercholesterolaemia, current smoking, men 55 y, women 70 y.

N=67,888patients aged45 years orolder from 44countries

HTN=hypertension;

REACH=Reduction of

Atherothrombosis for

Continued Health.


17/41

Wong ND et al.Arch Intern Med2007; 167: 2431-2436.

NHANES :Prevalence ofhypertension, treated and controlled,

in patient subsets by comorbidity

Population subset HTNprevalence(%)

HTNtreated

(% of thosewith HTN)

HTNcontrolled

(% of thosewith HTN)

No CV comorbidities 23.1 66.5 64.6

HTN and dyslipidemia 51.8 68.0 49.3

HTN and diabetes 73.7 84.0 61.2a

HTN and CKD 81.8 65.9 42.2b

HTN and heart failure 71.4 83.4 48.8

a.`Rate based on treatment goal


18/41

1. Prospective Studies Collaboration, Lancet,2002;300:1903-1913; 2. Rodgers A et al,Pros Medicine, 2004;1; 3. Cholesterol Treatment Trials Collaborators, Lancet,2005.

Preventing Cardiovascular Disease

High BP and High Cholesterol are majorrisk factors for CHD and Stroke Most people who develop CHD or Strokedo not have very high BP or Cholesterol

values but their values are not normal,either !

Treating only those people with significant

elevations of single risk factors will notprevent most CHD or strokes and will leave

most people at risk


19/41

34

21

17

13

12

23

12

810

6

18

11

9

6

6

17

8

8

6

4

14

56

3

3

142+

125-131


20/41

Class

WG-ASH Definition andClassification of Hypertension ( 2005 )

C.V.Class

B.P

ElevationC.V.D. Risk

Factor

Early Disease

Markers

Target Organ

Disease

Normal

Hypertension

Stage

1

Stage

2

Stage

3

Normal

or rareNone None

or fewNone None

Occasional /

Intermittent

> 120/80

Sustained

> 140/90

Marked &

Sustained

>140/90 &

>160/90

Early

Progre

ssive

Advan

ced

Several

Many

Many

Usually

present

Overtly

present

Overtly

present with

progression

None

Early signs

present

Overtly

present

with or without

CVD events

Writing Group of the American Society of Hypertension (WG-ASH) ; 2005


21/41

JNC 7 2003

WritingGroup of the

American

Society ofHypertension

(WG-ASH)2005

EuropeanSociety of

Hypertension2003

EuropeanSociety of

Hypertension /

EuropeanSociety ofCardiology(ESH/ESC)

2007

BritishHypertensionSociety (BHS)

NICE 2004

Update 2006( National

Institute for

health andClinical

Excellence)


22/41

Algorithm for Treatment of Hypertension(JNC 7 2003 )

Not at Goal Blood Pressure (100 mmHg)

2-drug combination for most(usually thiazide-type diuretic and

ACEI, or ARB, or BB, or CCB)

Stage 1 Hypertension(SBP 140159 or DBP 9099

mmHg)Thiazide-type diuretics for most.

May consider ACEI, ARB, BB, CCB,or combination.

Without CompellingIndications

Not at GoalBlood Pressure

Optimize dosages or add additionaldrugs

until goal blood pressure is achieved.

Consider consultation with hypertensionspecialist.


23/41

A : ACE inhibitor or

Angiotensin Receptor Blocker

B : Betablocker

C : Calcium Channel Blocker

D : Diuretic

Younger ( < 55 years )

and non Black

Older ( > 55 years )

or Black

A C or D

A ( or B ) + C or D

A ( or B ) + C + D

Add either Alpha blockeror Spironolactoneor other Diuretic

Step 1

Step 2

Step 3

Step 4Resistant Hypertension

NICE / BHS 2007


24/41

2004 PPS

Expert Panel on Detection, Evaluation, and Treatment ofHigh Blood Cholesterol in Adults. JAMA. 2001;285:2486-2497.

High240

Borderline high200239Desirable


25/41

2004 PPS


26/41


27/41

Assessing CVD risk: the effect of high blood pressure

2007 guidelines on hypertension of the European Society of Hypertension (ESH) and the EuropeanSociety of Cardiology (ESC) OD: subclinical organ damage, MS: metabolic syndrome.


28/41


29/41

Nondiabetic Men

180

160

SBP 140

120

100

180

160

SBP 140

120

100

180

160

SBP 140

120

100

180

160

SBP 140

120

100

180

160

SBP 140

120

100

180

160

SBP 140

120

100

3 4 5 6 7 8 9 10TC : HDL

3 4 5 6 7 8 9 10TC : HDL

3 4 5 6 7 8 9 10

TC : HDL

3 4 5 6 7 8 9 10

TC : HDL

Non smoker Smoker

Age under 50 years

Age 50 59 years

3 4 5 6 7 8 9 10

TC : HDL

3 4 5 6 7 8 9 10

TC : HDL

Age 60 years and over

CVD risk 20% over next 10 year

Copyright University

of Manchester

CVD risk over

next 10 years

30%

10% 20%

SBP = Systolic blood Pressure

TC : HDL = Total Cholesterol to

HDL Cholesterol ratio


30/41

Non smoker Smoker

Age under 50 years180

160

SBP 140

120100

180

160SBP 140

120

100

180

160

SBP 140

120

100

180

160

SBP 140

120100

180

160SBP 140

120

100

180

160

SBP 140

120

100

3 4 5 6 7 8 9 10

TC : HDL

3 4 5 6 7 8 9 10

TC : HDL

3 4 5 6 7 8 9 10

TC : HDL

3 4 5 6 7 8 9 10

TC : HDL

3 4 5 6 7 8 9 10TC : HDL

3 4 5 6 7 8 9 10TC : HDL

Age 50 59 years


Copyright University

of Manchester

CVD risk over

next 10 years

30%

10% 20%

SBP = Systolic blood Pressure

TC : HDL = Total Cholesterol to

HDL Cholesterol ratio

Nondiabetic Women

CVD risk 20% over next 10 year


31/41

180

160

SBP 140

120

100

180

160

SBP 140

120

100

180

160

SBP 140

120

100

180

160

SBP 140

120

100

180

160

SBP 140

120

100

180

160

SBP 140

120

100

3 4 5 6 7 8 9 10TC : HDL

3 4 5 6 7 8 9 10TC : HDL

3 4 5 6 7 8 9 10

TC : HDL

3 4 5 6 7 8 9 10

TC : HDL

Non smoker Smoker

Age under 50 years

Age 50 59 years

3 4 5 6 7 8 9 10

TC : HDL

3 4 5 6 7 8 9 10

TC : HDL


Nondiabetic Men

Chart for men and women

No chart for diabetesTreat diabetes as > 20% CVD risk

i.e. as coronary equivalents


32/41

Primary Prevention:> 20% CVD risk over 10 years:

Secondary Prevention:

Any Vascular disease or Target organ damage or Diabetes

Treat stage 1 hypertension (> 140/90 mmHg)Prescribe statin ( irrespective of baseline total Cholesterol )Target total Cholesterol


33/41

Most Hypertensive Patientsare at sufficient CVD risk to

benefit from a statin,irrespective of their baseline

cholesterol level

M lti l Ri k F t M t R lt


34/41

Multiple Risk Factor Management Resultsin Greater CVD Risk Reduction

Williams B. J Am Coll Cardiol. 2005;45:813-827. Reproduced with permission from Professor Bryan Williams.

Likelihood of a Major Cardiovascular Event in theNext 10 Years in 100 People Like You

Cardiovascular Events Expected

Without Drug Therapy



35/41

Cardiovascular Events Prevented

by Antihypertensive Therapy






36/41

Optimising Hypertension Management by Addition ofStatin Therapy May Reduce CV Events by Half

Events Prevented by

Antihypertensive TherapyEvents Prevented by

Adding Statin Therapy





37/41

2000 2001 2002 2003 2004 2005

Co-Prescribing of a Statin in Hypertension( England; n = 5,5 million )

%H

ypertens

ivePatientsC

o-prescribing

statin

35%

30%

25%

20%

15%

10%

5%

0%

B. Williams, 2006


38/41

2000 2001 2002 2003 2004 2005%H

ypertens

ivePatientsC

o-prescribingstatin

Co-Prescribing of a Statin in Hypertension

with Diabetes.( England; n = 5,5 million )

80%

70%

60%

50%

40%

30%

20%

10%

0%

B. Williams, 2006


39/41

Benefits of systems reform

UK changing trends

35% reduction in cardiovascular

mortality in 5 years ( 2000 2005 )

B. Williams, 2006


40/41

ConclusionCVD is preventable;

Available treatments ( especially BP

lowering and statins ) are very effective

at reducing CVD risk and mortality;

You do not need high BP and high

cholesterol to benefit from treatment

you only need high CVD risk;

CVD risk assessment should be simple;

The benefits of treatment are very large


41/41

Caduet (Dr. Ismahun Maret 2009)

Documents

Transcript of Caduet (Dr. Ismahun Maret 2009)