identification of subjects at high risk for cardiovascular disease

Identification of subjects at high

risk for cardiovascular disease

Lars RydénKarolinska InstitutetStockholm, Sweden

Introductory remarksWhy detect

To prevent premature developmentof cardiovascular disease

Vartiainen et al. BMJ 1994;309:445

1975 1980 1985 1990-70

-60

-50

-40

-30

-20

-10

0

Pro

po

rtio

nat

e re

du

ctio

n

Smoking

Cholesterol

Predicted bythe threefactors combined

Blood pressure

ObservedMortality

Enhanced bytherapeutic success

Cardiovascular Disease PreventionImpact of prevention vs. treatment - the landmark Finnish example

Cardiovascular Disease PreventionImpact prevention vs. treatment - CHD deaths in the US 1980 - 2000

(New Engl J Med 2007: 356:2388)

Cardiovascular Disease PreventionFour pillars for success

Epidemiological informationPopulation based, trustworthy and updatedMortality not enough, morbidity important

Epidemiology on Cardiovascular DiseaseInformation from the ESC and EHN collaborating on the European Heart Health Charter

Epidemiology of Cardiovascular DiseaseTrends in mortality and morbidity

CVD the major contributor to an almost 20 yeardifference in life expectancy across Europe

Epidemiology of Cardiovascular DiseaseCardiovascular mortality across Europe (<65 years)

Diabetes in EuropeActual in 2007

Million withdiabetes 48 and IGT 63

(IDF Diabetes Atlas 3rd edition 2006)

Diabetes in EuropePrognosis for 2026

Million withdiabetes 56 and IGT 71


DiabetesHospital days spent and costs of complications


(Source: IDF 1999)

Annual costs

/patient

(€)

6000

5000

4000

3000

2000

1000

0

No Micro

Macro

Macro

+

Micro

Vascular complicatons

Total 736 mill €

4.5% of health care expenditures

(Henriksson et al 2000 J Intern Med; 248:387)

UK

Neuropathy

Other Eye disease

Acutecompli-cations

Cardiovasculardisease

Kidneydisease

Cardiovascular Disease Prevention (CVD)Four pillars for success

Epidemiological informationPopulation based, trustworthy and updated

Mortality not enough, morbidity important

Risk assessement toolsConsidering total riskRisk enginesRisk asessement tools

Population High risk Secondary

10-year risk

Pro

port

ion

High risk:Covering a few at

high risk falling ill

Low risk:Covering mostof those falling ill

Population distribution of cardiovascular (CV) risk

Primary

Cardiovascular Disease Prevention (CVD)Three strategies

WHO Technical Report Series 678, Geneva, 1982

1994 First Joint Task Force recommendations

1998 Second Joint Task Force recommendations

2003 Third Joint Task Force guidelines

Guidelines for CVDThe European version

2007 Fourth Joint Task Force guidelines

2011 Fifth under way

• ID of (vulnerable)

plaques

•MR/MSCRT

•ECG

•Stress test

•Echocardiogram

Lab examinations

• Lipids

• Glucose

•Case history

•Length/weight

•Waist circumf

•Blood pressure

Assessment of CV RiskClassic and Emerging Methods

Pyörälä K et al. Atherosclerosis. 1994;110:121-161.

CVD is multifactorial in origin

Risk factors interact synergistically

Physicians see people, not isolated risk

factors

Cornerstone in

Cardiovascular Disease Prevention

The Concept of Total Risk Assessment

About diabetes and cardiovascular risk

INTERHEART

(Yusuf et al. Lancet 2004; 364:937)

Odds R

atio (

99%

CI)

2.9 2.4 1.9 3.3 13.0 42.3 68.5 182.9 333.7

Of importance

….the rapid increase in

Odds Ratio by a combination of

risk factors…

Common in diabetes

The Concept of Total Risk Assessment

Usually multiple risk factors behind atherosclerosis

causing CVD

These risk factors interact, sometimes multiplicatively

The aim is to reduce total risk

If a target cannot be reached with one risk factor, total

risk can still be reduced by trying harder with other

Why stress assessment of total CVD risk

Objectives with CVD prevention

1 To assist people at low risk of CVD to maintain this state lifelong and help those at increased risk to reduce it

2 To achieve the “healthy characteristics” No smoking

Healthy food choices

Physical activity: 30 min of moderate activity/day

BMI <25 kg/m2 + avoidance of central obesity

BP <140/90 mmHg

Total cholesterol <5 mmol/L

LDL cholesterol <3 mmol/L

Blood glucose <6mmo/L

3 To achieve rigorous risk factor control in high risk subjects, especially in known CVD or diabetes

Blood pressure under 130/80 mmHg if feasible

Total cholesterol <4.5 mmol/L; option <4 mmol/L

LDL cholesterol <2.5 mmol/L; option <2mmol/L

Fasting blood glucose <6 mmol/L and HbA1c <6.5%

4 To consider cardioprotective drug therapy in high risk subjects especially those with atherosclerotic CVD

Objectives with CVD prevention

CVD Risk

Continuum

Obesity

DM

Prediabetes

Ethnicity

Age and sex

Smoking

Physical

inactivity

Hypertension

Hyper-

lipidemia

Metabolic

syndrome

Family

history

Need for

prevention of

CVD

Consider Total CV Risk

Variable Total CV risk during 10 years

Absolute risk (%) 1 10

Adj RR (%) 30 30

NNT (n) 333 33

NNT to side effects !!! -

Randomized trials show that statins cause a RR reduction of −30%

(outcome when applied to 2 different risk patterns)

A Need to Adapt Prevention to Total

Individual Cardiovascular Risk

Total CV risk is high or very high in subjects with:

Established CVD

DM

Markedly elevated single risk factors

- Total cholesterol 8 mmol/L, LDL cholesterol 6 mmol/L

- SBP 180 mm Hg and/or DBP 110 mm Hg

Pronounced family history of CVD at young age

In all other subjects, total CV risk should be estimated with a risk score model.

De Backer et al. Eur Heart J. 2003;24:1601-1610.

Assessment of Total CV Risk

General rule according to European Guidelines

LDL, low-density lipoprotein; SBP, systolic blood pressure; DBP, diastolic BP.

Framingham-based risk equation (USA)1

Systematic Coronary Risk Evaluation

(SCORE; Europe)2

PREDICT (New Zealand)3

Joint British Societies’ coronary risk prediction4

HeartScore (Europe)5

1. Wilson PWF et al. Circulation 1998;97:1837–7

2. Conroy RM et al. Eur Heart J 2003;24:987–1003

3. Bannink L et al. N Z Med J 2006;119:U2313

4. British Cardiac Society et al. Heart 1998;80(Suppl 2):1–29

5. European Society of Cardiology. http://www.heartscore.org/ (Accessed 19 August 2009)

Identification of people at riskRisk assessement tools used in Western populations

Kannel WB, McGee D, Gordon T

A general cardiovascular risk profile:

the Framingham StudyAm J Cardiol.1976;38:46

Assessment of Total CV RiskFramingham Heart Disease Risk Calculator

Assessment of Total CV RiskFramingham Heart Disease Risk Calculator

HDL, high-density lipoprotein. NCEP guidelines. JAMA. 2001;285:2486-2497.

SBP

mm Hg Untreated Treated

<120 0 0

120-129 0 1

130-139 1 2

140-159 1 2

>160 2 3

Points

Step 4: Systolic Blood Pressure

HDL-C

(mg/dL) Points

>60 –1

50-59 0

40-49 1

<40 2

Step 3: HDL-CTC

(mg/dL) Age 20-39 Age 40-49 Age 50-59 Age 60-69 Age 70-79

<160 0 0 0 0 0

160-199 4 3 2 1 0

200-239 7 5 3 1 0

240-279 9 6 4 2 1

>280 11 8 5 3 1

Points

Step 2: Total Cholesterol

Years Points

20-34 –9

35-39 –4

40-44 0

45-49 3

50-54 6

55-59 8

60-64 10

65-69 11

70-74 12

75-79 13

Step 1: Age

Category: Points

Age

Total-C

HDL-C

SBP

Smoking status

Point Total:

Step 6: Adding Points

Point Total 10-Year Risk

<0 <1%

0 1%

1 1%

2 1%

3 1%

4 1%

5 2%

6 2%

7 3%

8 4%

9 5%

10 6%

11 8%

12 10%

13 12%

14 16%

15 20%

16 25%

>17 >30%

Step 7: CHD Risk

20-39 40-49 50-59 60-69 70-79

Nonsmoker 0 0 0 0 0

Smoker 8 5 3 1 1

Step 5: Smoking Status

Points at Age

Characteristics

A rather small US populationfor fatal/nonfatal CHDincludes:

• Sex and age

• Total & HDL cholesterol

• Smoking

• Systolic blood pressure

http://www.nhlbi.nih.gov

Assessment of Total CV RiskFramingham Heart Disease Risk Calculator: Online Access

Highest risk: >20% or a history of heart disease or DM

High risk: 10%-20% and 2 risk factors

Moderate risk: <10% and 2 risk factors

Low risk: 1 risk factor

Screening tools from Western populations may

not be accurate in AP populations

Background epidemiology of CVD and risk factors may

differ affect risk calculations

AP: Asia-Pacific; NCEP ATP: National Cholesterol Education Programme Adult Treatment Panel

1. Tan C-E, et al. Diabetes Care 2004;27:1182-1186.

2. Asia Pacific Cohort Studies Collaboration, et al. J Epidemiol Community Health 2007;61:115-121.

– NCEP ATP III criteria underestimates the at-risk AP

population1

– Framingham-based CV risk calculators overestimates

the risk in Asian populations2

Identification of people at riskRisk assessement and ethnicity

20

15

10

5

0

CV

even

t (%

)

1 2 3 4 5 6 7 8 9 10

CV

even

t (%

)

1 2 3 4 5 6 7 8 9 10

Deciles of predicted risk based

on Framingham equation


on Framingham equation

Observed Predicted

Men Women

Bias = +276% Bias = +102%

20

15

10

5

0

CV: cardiovascular

APCSC. J Epidemiol Community Health 2007;61:115–21.

The Framingham risk engine overestimates

the CVD risk in Asian populations

Observed and predicted CV event rate according to

deciles of predicted risk in Chinese patients

Development of new risk assessment equations

Recalibration/modification of existing equations

or definitions

Resources for risk factor screening are limited

in many AP countries

- Reliable and inexpensive risk tools are needed

Identification of people at riskRisk assessement and ethnicity


The Asia Pacific Cohort Studies CollaborationAPCSC

Objective

To compare ”low-information” equations

(age, systolic blood pressure, cholesterol,

smoking habits)

from the Framingham Study with

those derived from Asian cohorts…

Identification of people at riskRisk assessement in the Asian-Pacific region

Pools data from longitudinal studies with

information on CVD in the Asia Pacific region

Comprises data on >650,000 participants

44 separate cohort studies in mainland China, Hong

Kong, Taiwan, Japan, South Korea, Singapore,

Thailand, New Zealand and Australia

Is one of largest databases worldwide

Identification of people at riskRisk assessement in the Asian-Pacific region


8

6

4

2

0

CV

even

t (%

)

1 2 3 4 5 6 7 8 9 10

8

6

4

2

0C

V e

ven

t (%

)

1 2 3 4 5 6 7 8 9 10


on other Asian equation


on other Asian equation

Men Women

Bias = +11% Bias = +10%

Observed Predicted



A new CVD equation for Asian populations


6

5

4

3

2

1

0

CV

even

t (%

)

1 2 3 4 5 6 7 8 9 10

CV

even

t (%

)

1 2 3 4 5 6 7 8 9 10

Deciles of predicted risk

based on the recalibrated

Framingham equation

Men Women

Bias = –2% Bias = +4%

Deciles of predicted risk

based on the recalibrated

Framingham equation

6

5

4

3

2

1

0

Observed Predicted

Recalibration of the Framingham risk

calculator for an Asian population




European Cohort Studies (n = 12) Some with multiple sub-studies

Mainly population based

Some figures: About 250,000 people

Follow-up 3 million person years

Cardiovascular fatalities >7000

Assessment of Total CV RiskSystematic Coronary Risk Evaluation (SCORE)

Eur Heart J 2007; 28: 2375 – 2414Executive summary


European: 10 year risk for fatal CVD; high vs. low risk populations

A 10-year risk of CVD death >5%

considered as a high or at least increased risk

Eur Heart J 2007; 28: 2375 – 2414Executive summary


Risk estimation using SCORE qualifiers

● To be used with knowledge and judgement

● Risk overestimated with a falling and underestimated if rising CVD mortality

● Risk appears lower for women. This is misleading

- charts show that their risk is deferred by 10 years

● Risk may be higher than indicated in the chart in

The sedentary or obese

Those with a strong family history

The socially deprived

Diabetes - risk x 4-5 in women and x 3 in men


Relative risk chart

For younger persons who despite a low total risk may have a several times higher risk in relation to others in

the same age group

Assessment of the Risk for DiabetesOral Glucose Tolerance Test (OGTT) in CAD

DM

IGT

IFG

Normal

OGTT OGTTFPGWHO FPGADA0

20

40

60

80

100

%

WHO 1999 criterion(FPG < 6.1 mmol/l)

ADA 2003 criterion(FPG < 5.6 mmol/l)

% of all with OGTT

(Bartnik et al Heart 2007; 93:72)

8% 5%

21%27%

5% 8%

8%

Finnish Diabetes

Risk Score (FINDRISC)

to address 10-year risk

of type 2 DM (T2DM) in

adults

Assessment of the Risk for DiabetesFINDRISC

Available at: www.diabetes

Assessment of Total CV Risk in diabetesThe UKPDS Risk engine

Risk Engine

according to

United Kingdom

Prospective Diabetes

Study (UKPDS)

Available at

www.dtu.ox.ac.uk/index.php?maindoc=/riskengine/

Education

Guidelines

Surveys

Research

From evidence to clinical practice

0 smoking

3 km of daily walking

5 portions of fruit & vegetables/day

<140/90 mm Hg blood pressure

<5.0 mmol/L total cholesterol

<3.0 mmol/L LDL-cholesterol

0 diabetes

European phone number to health

0 3 5 140 90 5 3 0

If high risk

130/80

4.0

2.0

Characteristics of healthy people

Conclusions

CVD Risk

Continuum

Obesity

DM

Prediabetes

Ethnicity

Age and sex

Smoking

Physical

inactivity

Hypertension

Hyper-

lipidemia

Metabolic

syndrome

Family

history

Need for

prevention of

cardiovascular disease

Prevention of CVD should be based on total CV risk

rather than be split on primary and secondary

prevention

Risk calculators (ex. Framingham, SCORE UKPDS)

help in assessing total risk but must be adapted to

local populations

DM is an independent risk factor for CVD

The risk of CV events increases dramatically with

concomitant risk factors

Identification of subjects at high

risk for cardiovascular disease

Time for questions

identification of subjects at high risk for cardiovascular disease

Documents