Cardiovascular risk environment and the interpretation of current guidelines

Dr P. Ismahun SpJP, FIHA

Changing

Malang, 21 Maret 2009

Risk Factors on Global Cardiovascular Disease Burden

Smoking Dyslipidemia Hypertension Lp(a) Others (+ 200) Diabetes Obesity Mellitus No Homocystein exercise

Joint effects of Risk Factors on Global

Cardiovascular Disease Burden
Smoking Dyslipidemia Hypertension Lp(a) Others (+ 200) Diabetes Obesity Mellitus No Homocystein exercise

Blood pressure and Atheroma Lessons from veins Veins dont develop atheroma even in people
Pulmonary Hypertension associated with
atheroma of pulmonary venous system ; pressure) develop atheroma ;

with elevated Cholesterol low pressure system ;

Venous grafts into coronary circulation (high Pressure is permissive for the development of
atheroma ;

Logical to lower cholesterol and pressure to

reduce the risk of developing atheroma.

Effect of Blood Pressure on Progression of Coronary Atheroma

Change in Atheroma volume (mm3)
30 25 20 P < 0.001

15
10 5 0 -5 -10 P = 0.039 -15 -20 Normal Prehypertension Hypertension P = 0.01

J Am Coll Cardiol 2006;48: 833-8

JNC 7 Categories

Majority of US Hypertensive Patients Not at SBP Goal of <140 mm Hg: Goal Gap
14.0
12.0 10.0

Population 8.0 (millions)

6.0 4.0 2.0 91100

< 140 mmHg

NOT MEETING GOAL

131140

0.0 8190

141150

151160

231240

121130

201210

191200

SBP Range (mm Hg) SBP = Systolic Blood Pressure Adapted from Whyte JL et al. J Clin Hypertens. 2001;3:211-216.

221230

241250

161170

171180

181190

101110

111120

211220

NHANES III: Poor Systolic BP Control Underlies Inadequate BP Control Overall

250

SBP (mm Hg)

200

49.6%

16.1%

150

140

Only 34.3% Reach SBP Goal

100

23.6%
50 0 50

90
100

10.7% DBP 150 (mm Hg)

73% Reach DBP Goal

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.

Coronary Disease by Usual SBP

-10 mm Hg 32.0 70 years 16.0 Hazard Ratio and 95% CI 60-69 years 8.0 4.0 2.0 1.0 0.5 110 120 130 140 150 160 Usual SBP (mm Hg)
425,325 participants were included in the Asia Pacific Cohort Studies Collaboration (APCSC).
APCSC. J Hypertens. 2003;21:707-716.

RRR=16% RRR=24% RRR=46%

<60 years

Burden of Disease

25

20

Serum cholesterol distribution by study year, men aged 30 to 59 years in Finland

Year

72 77 82 87 92

15

5 Mmol/l = 193 mg/dl 6 Mmol/l = 231.6 mg/dl

10

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)

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

50

Distribution of serum cholesterol and coronary heart disease (CHD) deaths of men in Finland, aged 30 to 59 years (1972, 1977, and 1982 cohorts combined) and odds ratio of CHD mortality associated with serum cholesterol

5 Mmol/l = 193 mg/dl 6 Mmol/l = 231.6 mg/dl

5.5

5
4.5 4 3.5

40

30 3 2.5 20 2

1.5
10 1 0.5 0 5.0 5.0-6.49 6.5-7.99 >8.0 Serum Cholesterol level (Mmol/l)
Serum Cholesterol CHD deaths Odds ratio

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

What is Normal Cholesterol ?

2.00

18
1.00 0.50

9 4

12

0.25

3.6 139

3.8 147

4.0 155

4.2 162

4.4 170

4.6 4.8 178 186

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

Relative risk of death (+) from CHD by quartiles of baseline total cholesterol in 9021 Chinese people with 8 13 years follow-up.
Chen Z,et al, BMJ, 1991;303:278-282

 What we define asnormalvalues for Blood Pressure and Cholesterol are based on usual values for our populationsthese are not normal values for a human being, they are the usual values of a human being at risk of dying prematurely from vascular disease
B. Williams, 2006

 The Population Burden of Cardiovascular Disease is in those people with modest elevations of multiple risk factors, NOT those with single, extreme elevations of single risk factors.

B. Williams, 2006

Increased Number of CV Events (MI) in Patients with Hypertension Plus Other CV Risk Factors
512 256 Odds Ratio (99% CI) 128 64 32 16 8 4 2 1 Risk Factors Smoking Diabetes HTN (1) (2) (3) Risk Ratio
2.9 (2.6-3.2) 2.4 (2.1-2.7) 1.9 (1.7-2.1)

HTN + 3 Risk Factors >20-Fold Increase OR from 1.9 (HTN only) to 42.3

HTN

Lipids (4)
3.3 (2.8-3.8)

1+2+3
13.0 (10.7-15.8)

All 4
42.3 (33.2-54.0)

+ Obes

+ PS

All RFs

68.5 182.9 333.7 (53.0-88.6) (132.6-252.2) (230.2-483.9)

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.

Multiple CV Risk Factors in Addition to Hypertension Result in a High CVD Risk

5-Year CVD Risk per 100 People 50 45 40 35 30 25
BP (mm Hg) 110 120 130 140 150 160

44% 33% 24% 18% 12% 6%

20 15
10

170
180

5
0

3%
Reference

+ TC+ Smoker + HDL7 mmol/L 1 mmol/L

+ Male + Diabetes

+ 60 years

Increasing No. of Additional Risk Factors

*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.

Most Hypertensive Patients Have Additional Risk Factors REACH Registry

N=67,888 patients aged 45 years or older from 44 countries
HTN=hypertension; REACH=Reduction of Atherothrombosis for Continued Health.

81.8% HTN* 90.3%

with 3 risk factors

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

NHANES :Prevalence of

hypertension, treated and controlled, in patient subsets by comorbidity

Population subset HTN HTN prevalence treated (%) (% of those with HTN)
23.1 51.8 66.5 68.0

HTN controlled (% of those with HTN)

64.6 49.3

No CV comorbidities HTN and dyslipidemia

HTN and diabetes

HTN and CKD HTN and heart failure

73.7
81.8 71.4

84.0
65.9 83.4

61.2a
42.2b 48.8

a.`Rate based on treatment goal <130/80 mm Hg = 35.3%

b. `Rate based on treatment goal <130/80 mm Hg = 23.2% HTN=hypertension Wong ND et al. Arch Intern Med 2007; 167: 2431-2436. CKD=chronic kidney disease

Preventing Cardiovascular Disease

High BP and High Cholesterol are major

risk factors for CHD and Stroke

Most people who develop CHD or Stroke

Treating only those people with significant
elevations of single risk factors will not prevent most CHD or strokes and will leave most people at risk
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.

do not have very high BP or Cholesterol values but their values are not normal, either !

Potential Benefit of Blood Pressure and Cholesterol Lowering on Death (per 10,000 Patient-Years)
34

Blood Pressure Lowering

17

21 12

23

Cholesterol Lowering
18 17

13 12 6
245+

10 6

8 9 6 6 4 3
<182

11 8 8 6 5

14

221-244 203-220 182-202

142+ 132-141 3 125-131 118-124 <118

Adapted from Neaton JD et al. Arch Intern Med. 1992;152:56-64.

WG-ASH Definition and Classification of Hypertension ( 2005 )

Class

Class

B.P Elevation Normal or rare

C.V.D.

Normal

None

Risk Factor C.V. None or few

Early Disease Markers

Target Organ Disease

None

None

Hypertension
Stage 1 Stage 2 Occasional / Intermittent > 120/80 Sustained > 140/90 Marked & Sustained >140/90 & >160/90

Early
Progre ssive Advan ced

Several

Usually present Overtly present

None
Early signs present

Many

Stage 3

Many

Overtly Overtly present present with with or without progression CVD events

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

JNC 7

2003

European Society of Hypertension 2003

British Hypertension Society (BHS) NICE 2004

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

European Society of Hypertension / European Society of Cardiology (ESH/ESC) 2007

Update 2006 ( National Institute for health and Clinical Excellence)

Algorithm for Treatment of Hypertension (JNC 7 2003 )

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
Stage 1 Hypertension Stage 2 Hypertension

With Compelling Indications

Drug(s) for the compelling indications
Other antihypertensive drugs (diuretics, ACEI, ARB, BB, CCB) as needed.

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

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

Not at Goal Blood Pressure

Optimize dosages or add additional drugs until goal blood pressure is achieved. Consider consultation with hypertension specialist.

NICE / BHS 2007

Younger ( < 55 years ) and non Black Older ( > 55 years ) or Black C or D

Step 1

Step 2
Step 3 Step 4 Resistant Hypertension
A : ACE inhibitor or Angiotensin Receptor Blocker B : Betablocker

A ( or B ) + C or D

A ( or B ) + C + D Add either Alpha blocker or Spironolactone or other Diuretic

C : Calcium Channel Blocker D : Diuretic

2004 PPS

ATP III: LDL-C, HDL-C, TC Classification

LDL-C (mg/dL) <100 100129 130159 160189 190 HDL-C (mg/dL) <40 60 TC (mg/dL) <200 200239 240
Optimal Above, near optimal Borderline high High Very high Low High

Desirable Borderline high High

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

2004 PPS

ATP III: Risk Categories, LDL-C Goals

Risk Category CHD and CHD risk equivalents (10-year risk >20%)

LDL-C Goal (mg/dL) <100 <130 <160

2 risk factors (10-year risk 20%)

01 risk factor*

*Almost all people with 01 risk factor have a 10-year risk <10%; thus, Framingham risk calculations are not necessary.
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 2001;285:2486-2497.

Assessing CVD risk: the effect of high blood pressure

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

Non smoker Smoker Age under 50 years

180 160 SBP 140 120 100
3 4 5 6 7 8 9 10 TC : HDL

Nondiabetic Men
CVD risk <10% over next 10 year CVD risk 10-20% over next 10 y. CVD risk >20% over next 10 year

180 160 SBP 140 120 100

3 4 5 6 7 8 9 10 TC : HDL

Age 50 59 years
180 160 SBP 140 120 100

180 160 SBP 140 120 100

3 4 5 6 7 8 9 10 TC : HDL

CVD risk over next 10 years 30% 10% 20% SBP = Systolic blood Pressure TC : HDL = Total Cholesterol to HDL Cholesterol ratio

3 4 5 6 7 8 9 10 TC : HDL

Age 60 years and over

180 160 SBP 140 120 100
3 4 5 6 7 8 9 10 TC : HDL

180 160 SBP 140 120 100

3 4 5 6 7 8 9 10 TC : HDL

Copyright University of Manchester

Non smoker Smoker Age under 50 years

180 160 SBP 140 120 100
3 4 5 6 7 8 9 10 TC : HDL

Nondiabetic Women
CVD risk <10% over next 10 year CVD risk 10-20% over next 10 y. CVD risk >20% over next 10 year

180 160 SBP 140 120 100

Age 50 59 years
180 160 SBP 140 120 100

3 4 5 6 7 8 9 10 TC : HDL

180 160 SBP 140 120 100

3 4 5 6 7 8 9 10 TC : HDL

CVD risk over next 10 years 30% 10% 20% SBP = Systolic blood Pressure TC : HDL = Total Cholesterol to HDL Cholesterol ratio

3 4 5 6 7 8 9 10 TC : HDL

Age 60 years and over

180 160 SBP 140 120 100
3 4 5 6 7 8 9 10 TC : HDL

180 160 SBP 140 120 100

3 4 5 6 7 8 9 10 TC : HDL

Copyright University of Manchester

Non smoker Smoker Age under 50 years

180 160 SBP 140 120 100
3 4 5 6 7 8 9 10 TC : HDL

Nondiabetic Men

180 160 SBP 140 120 100

3 4 5 6 7 8 9 10 TC : HDL

Chart for men women Age 50and 59 years

180 160 SBP 140 120 100 180 160 SBP 140 120 100

No chart for diabetes Treat diabetes as > 20% CVD risk

i.e. as coronary equivalents 3 4 5 6 7 8 9 10 3 4 5 6 7 8 9 10
TC : HDL TC : HDL

Age 60 years and over

180 160 SBP 140 120 100
3 4 5 6 7 8 9 10 TC : HDL

180 160 SBP 140 120 100

3 4 5 6 7 8 9 10 TC : HDL

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 <4,0 mmol/l or 25% reduction Prescribe Aspirin 75 mg od Do not prescribe vitamin waste of money.

Most Hypertensive Patients are at sufficient CVD risk to benefit from a statin, irrespective of their baseline cholesterol level

Multiple Risk Factor Management Results in Greater CVD Risk Reduction

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

Cardiovascular Events Expected Without Drug Therapy

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

Multiple Risk Factor Management Results in Greater CVD Risk Reduction

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

Cardiovascular Events Prevented by Antihypertensive Therapy

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

Multiple Risk Factor Management Results in Greater CVD Risk Reduction

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

Optimising Hypertension Management by Addition of Statin Therapy May Reduce CV Events by Half

Events Prevented by Antihypertensive Therapy

Events Prevented by Adding Statin Therapy

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

Co-Prescribing of a Statin in Hypertension

% Hypertensive Patients Co-prescribing statin ( England; n = 5,5 million )
35% 30% 25% 20% 15% 10%

5%
0% 2000
B. Williams, 2006

2001

2002

2003

2004

2005

% Hypertensive Patients Co-prescribing statin

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

80% 70% 60%

50%
40% 30%

20%
10% 0% 2000
B. Williams, 2006

2001

2002

2003

2004

2005

Benefits of systems reform UK changing trends

35% reduction in cardiovascular mortality in 5 years ( 2000 2005 )

B. Williams, 2006

CVD is preventable; Available treatments ( especially BP

lowering and statins ) are very effective at reducing CVD risk and mortality;

Conclusion

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