ASSESSMENT OF CARDIOVASCULAR RISK

M MOHSEN IBRAHIM , MD
CARDIOLOGY DEPARTMENT-CAIRO UNIVERSITY

The Complications of CAD Often Emerge without Warning

Adapted from Levy et al, Textbook of Cardiovascular Medicine, 1998

ASSESSMENT OF CARDIOVASCULAR RISK

50 Y/O woman Non-smoking BP: 170/100 mmHg Total cholesterol : 228 mg/dL HDL-C : 46 mg/dL Non-diabetic Chance of major CV event in the next 5 years : 6 % 60 Y/O male Smoker BP: 170/100 mmHg Total cholesterol : 228 mg/dL HDL-C : 38 mg/dL Non-diabetic Chance of major CV event in the next 5 years : 30 %

ASSESSMENT OF CARDIOVASCULAR RISK

DEFINITIONS Definition of Risk Risk Factors METHODS Risk Score Risk Charts IMPLICATIONS Initiation of Pharmacologic Therapy

ASSESSMENT OF CARDIOVASCULAR RISK

RISK OF WHAT ? ENDPOINTS

RISK OF WHAT ?
HARD END POINTS
TOTAL MORTALITY TOTAL CVD MORTALITY CORONARY MORTALITY FATAL MI SUDDEN CARDIAC DEATH NONFATAL MI RESUSCITATED CARDIAC ARREST STROKE

DEFINITION OF CORONARY HEART DISEASE - FRAMINGHAM

TOTAL CHD Angina pectoris Myocardial infarction recognized & unrecognized Unstable angina CHD death HARD CHD Myocardial infarction Unstable angina CHD death

RISK OF WHAT ?
SOFT END POINTS

UNSTABLE ANGINA CABG PTCA TOTAL DAYS OF HOSPITALIZATION WORSENING ANGINA TIME TO FIRST ISCHEMIC EVENT

RISK OF WHAT ?
SURROGATE END POINTS
CORONARY ART DISEASE PROGRESSION
Coronary angiography IVUS MRI UFCT (quantitative assessment of coronary calcium)

VASCULAR ENDOTHELIAL FUNCTION INFLAMMATORY MARKERS CAMs , hsCRP

RISK ESTIMATES
ABSOLUTE RISK Probability of developing CHD or CV death over given time period e.g. the next 10 years RELATIVE RISK The ratio of the absolute risk of a given patient (or group) to that of a lower risk group : - Average risk - Low risk

DEFINITION OF A LOWRISK STATE Framingham

SERUM TOTAL CHOLESTEROL 160 TO 199
mg/dl. LDL-C 100 TO 129 mg/dl

HDL-C >45 mg/dL IN MEN AND >55 mg/dL IN

WOMEN

BLOOD PRESSURE <120 mmHg SYSYOLIC AND

<80 mmHg DIASTOLIC

NONSMOKER NO DIABETES MELLITUS

CARDIOVASCULAR RISK FACTORS

CATEGORIES OF CARDIOVASCULAR RISK FACTORS

INDEPENDENT CAUSATIVE CONDITIONAL PREDISPOSING SUSCEPTIBILITY ESTABLISHED - EMERGING PROATHEROGENIC PROTHROMBOTIC

------------------------------------------------------------------------------------- MODIFIABLE NONMODIFIABLE

CARDIOVASCULAR RISK FACTORS

CHARACTERISTICS OF A MAJOR-CAUSATIVE RISK FACTOR

INDEPENDENCE OF CONTRIBUTION FROM OTHER RISK FACTORS QUANTITAVE CONTRIBUTION TO RISK

CARDIOVASCULAR RISK FACTORS

Independent / Established/Major
NON-MODIFIABLE Age Gender Family history Established CVD Dis MODIFIABLE Cigarette Smoking Hypertension Hypercholesterolemia Low HDL-Cholesterol Obesity Diabetes Mellitus Hypertriglyceridemia Sedentary Life-Style M M Ibrahim 2003

Dependent / Emerging/Novel
Homocysteine Lp (a) Small, dense LDL-Cholest Other lipid disorders Abnormalities in blood coagulation Plasma fibrinogen Coagulation factors: V, VII, VIII
Platelets abnormalities Impaired fibrinolysis: PAI-1

Inflammatory markers
C-Reactive protein Interlukin

Short stature Impaired glucose tolerance Increased oxidative stress Personality type Tachycardia Ethnic group S.creatinine

Novel Risk Factors

fibrinogen sICAM-1 interleukin-6 hs-CRP hs-CRP + TC:HDL

1.0

2.0 4.0 6.0 Relative Risk of Future Myocardial Infarction

Ridker et al NEJM,2000

Ultra-Novel Risk Factors

2003
Plasma Myeloperoxidase Red Cell Glutathione Peroxidase 1 Activity

Red Cell Glutathione Peroxidase 1 Activity

Blankenberg et al. NEJM; October 23, 2003

PREVALENCE OF CONVENTIAL RISK FACTORS (%) IN CHD : MI/UA/PCI Women Men no 345 89 87869 66.1 29.5 23.2 39.6 55.9 15.4

Age (y)

59.9 41.6 15.3 34.1 38.4 19.4

Khot et al. JAMA- 2003

Current smoking Diabetes Hyperlipedemia Hypertension No risk factors

% 0f CAD are preventable by interfering with Cardiovascular Risk Factors

AHA Meeting , New Orleans - 2000

80

METHODS OF ASSSESSMENT OF RISK o Global Risk Score o Risk Charts

ASSESSMENT OF ABOLUTE RISK

METHODS
Calculate The Number Of Points For Each Risk Factor Estimate Global Risk Score ( Sum Of Points ) Consult Coronary/CV Risk Chart Assess 10-years Asolute Risk Level For CHD or CV event

GLOBAL RISK ASSESSMENT SCORING SYSTEMS FRAMINGHAM Scoring System

PROCAM Scoring System SCORE Project INDIANA Project

GLOBAL RISK ASSESSMENT SCORING

FRAMINGHAM RISK FACTORS
AGE ,y TOTAL CHOLESTEROL ( OR LDL-C ) , mg/dL HDL- C , mg/dL SYSTOLIC BLOOD PRESSURE , mmHg DIABETES SMOKER

FRAMINGHAM

S coring S ystem

Risk Factor Age, y <34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74

Risk Points Men Women -1 0 1 2 3 4 5 6 7 -9 -4 0 3 6 7 8 8 8

Risk Factor Systolic blood pressure, mm Hg <120 120 - 129 130 -139 140 - 159 >160

Risk Points Men Women 0 0 1 2 3 -3 0 1 2 3

Risk Factor

Risk Points Men Women

Risk Factor Total Cholesterol <160 169 -199 200 -239 240 -279 > 280

Risk Points Men Women

Diabetes

-3 0 1 2 3

-2 0 1 2 3

No Yes Smoker No

0 2

0 4

Yes

FRAMINGHAM

Scoring System

Global Risk Assessment Scoring

Risk Factor Men HDL Cholesterol , mg/dl <35 35-44 45-49 50-59 > 60 2 1 0 0 -2 5 2 1 0 -3 Risk Points Women

Source: Framingham Heart Study

Global Risk Assessment Scoring

Adjusted FRAMINGHAM

Scoring System

Plasma Glucose, mg/dl

Risk Points Men < 110 110-126 >126 0 1 2 Women 0 2 4

FRAMINGHAM

Scoring System

Global Risk Assessment Scoring

Adding up the points Age -----------------------------------------------------Cholesterol --------------------------------------------HDL-C -------------------------------------------------Blood pressure ----------------------------------------Diabetes ------------------------------------------------Smoker -------------------------------------------------Total points --------------------------------------------Source: Framingham Heart Study

FRAMINGHAM

Scoring System

Risk Corresponding to Total Points

Probability pts. 10 yrs
1 2 3 4 5 6 7 8 9 10 11 < 2% 2% 2% 2% 3% 3% 4% 4% 5% 6% 6%

Probability pts 10 yrs

12 13 14 15 16 17 18 19 20 21 22 7% 8% 9% 10% 12% 13% 14% 16% 18% 19% 21%

Probability pts 10 yrs

23 24 25 26 27 28 29 30 31 32 23% 25% 27% 29% 31% 33% 34% 39% 40% 44%

FRAMINGHAM

Scoring System

ASSESSMENT OF CARDIOVASCULAR RISK

Interaction With Other Risk Factors

Smoking increases risk x 2 3 Hypertension increases risk x 2 3 LVH increases risk x 2 LV strain pattern increases risk x 2 3 Diabetes increases risk x 1.5 2

INFLUENCE OF RISK FACTORS ON RISK OF CHD

59 year old man, non-smoker, BP 140/85mmHg, TC:HDL = 4 10 year risk of CHD event = 11.9%
Smoking

25.5%

Hypertension
(185/100mmHg)

18.3% 33.3%

41.9%
32.5%
(TC:HDL=8)

17.7%

Hyperlipidaemia

24.5%
all risk factors + diabetes = 47.9%

Risk Categorization
Typical 10 year risk of stroke or myocardial infarction

Low risk Medium risk High risk Very high risk

= < 15 percent = 15-20 percent = 20-30 percent > 30 percent

INFLUENCE OF RISK FACTORS ON RISK OF STROKE

59 year old man, non-smoker, BP 140/85mmHg, TC:HDL = 4 10 year risk of stroke = 2.8%
Smoking

13.8%

Hypertension
(185/100mmHg)

5.0% 5.1%

14.1%
8.0%
(TC:HDL=8)

7.8%

Hyperlipidaemia

2.8%
all risk factors + diabetes = 21.7%

FRAMINGHAM GLOBAL RISK ASSESSMENT SCORING

LIMITATIONS
DOES NOT ACCOUNT FOR OTHER ESTABLISHED MAJOR RISK FACTORS e g Hypertriglyceridemia, Obesity, Physical Inactivity , Family History DOES NOT ACCOUNT FOR SEVERE ABNORMALITIES OF RISK FACTORS ABSOLUTE RISK IN TYPE 2 DIABETES EXCEEDS FRAMINGHAM SCORE ?APPLICATION TO OTHER POPULATIONS

PROCAM Scoring System - 2002

GLOBAL RISK ASSESSMENT SCORING

GLOBAL RISK ASSESSMENT SCORING

PROCAM Scoring System

Prospective Cardiovascular Munster Study -5389 men aged 35 65 years -10 years follow-up -Major coronary event : . Sudden cardiac death . Definite fatal or nonfatal MI

PROCAM Scoring System

Age ,
35-39 0 40-44 6 45-49 11 50-54 16 55-59 21 60-65 26 LDL cholesterol, mg/dl <100 0 100-129 5 130-159 10 160-189 14 >=190 20 HDL cholesterol, mg/dl <35 11 35-44 8 45-54 5 >=55 0 Triglycerides, mg/dl <100 0 100-149 2 150-199 3 >=200 4

AuteCro E nts c o nary ve

PROCAM Score 0-20 21-29 29-37 38-44 45-53 54-61 >61
M Estimated Risk ean In 10 y (% )

D iabetes m ellitus
N0 Y ES 0 6

Systolic blood pressure, m m H g

<120 120-129 130-139 140-159 >=160 0 2 3 5 8

M I in fam ily history

No Y es 0 4 0 8

0.7 1.6 3.3 6.8 13.5 26.3 49.9

S m o ker
No Y es

SCORE Project - 2003

GLOBAL RISK ASSESSMENT SCORING

GLOBAL RISK ASSESSMENT SCORING

SCORE Project - 2003

Ten year risk of fatal cardiovascular disease 205 178 persons Separate estimation equations were calculated for CHD and for non-CHD and for high risk and low risk regions of Europe Two estimation models based upon: Total cholesterol and TC/HDL-C ratio High risk if 10-year risk of fatal CVD is more than 5% Conroy et al. Eu Heart J : 2003

Framingham vs SCORE
Framingham
Based on 5000 Americans Predicts coronary event Includes nonfatal events Cannot be adjusted for national variations

SCORE
Based on >200,000 Europeans Predicts CVD Restricted to fatal events Can be customized using national mortality statistics

INDIANA Project -

2001
GLOBAL RISK ASSESSMENT SCORING

INDIANA Project - 2001

47 088 men and women from eight randomised controlled trials 5.2 years (mean) follow-up Risk score developed from 11 factors 5 years risk of death from CV disease, fatal CHD, fatal stroke and all cause mortality

INDIANA Projct Scoring for Predicting Risk of Death from CVD, Pococket al. 2001

INDIANA Project Scoring for Predicting Risk of Death from CVD,

INDIANA Project Scoring for Predicting Risk of Death from CVD, Pococket al. 2001

INDIANA Project Scoring for Predicting Risk of Death from CVD, Pococket al. 2001

GLOBAL RISK ASSESSMENT SCORING

Age is a particularly strong risk factor Male sex carries an increased risk. Sex difference narrows with age Median age specific score for men is similar to the median score for women 10 years older Smoking contributes more in women and in younger age groups Total cholesterol is more important in men than in women Total cholesterol and SBP have similar predictive strength in men Diabetes has more effect in women than in men

RISK OF DEVELOPING CORONARY HEART DISEASE

LIFETIME RISK

Framingham
60 50 40 % 30 20 10 0 MEN WOMEN 1.2 0.2 48.6 34.9 BEFORE 40 AT 40 Y AT 70 Y 31.7
Lloid-Jones et al 24.2 Lancet-1999

HIGH RISK INDIVIDUAL

Probability of Developing a Fatal or Nonfatal MI =>20% in next 10 years CHD Risk Equivalent

Three or more major risk factors High risk score Established clinicalatherosclerotic disease Very high level single risk factor

CHD RISK EQUIVALENTS

DIABETES CLINICAL ASO DISEASE
Abdominal Aortic Aneurysm Peripheral Arterial Disease Carotid Arterial Disease

MULTIPLE RISK FACTORS ( CHD Risk in 10-y >20%)

CLINICAL ASO DISEASE Risk Comparison with General Population

MI : 5-7 fold of increased risk of recurrent MI Cerebrovascular disease : 2-3 fold increased risk of MI Peripheral vascular disease : 4fold increased risk of MI

ASSESSMENT OF CARDIOVASCULAR RISK

IMPLICATIONS

IMPLICATIONS
IDENTIFCATION OF HIGH RISK INDIVIDUALS

Intensive Life Style Modification Need To Initiate Pharmacologic Intervention Extent Of Risk Factors Correction

INDICATIONS FOR NON-INVASIVE TESTING

HIGH RISK INDIVIDUAL

Probability of Developing a Fatal or Nonfatal MI >20% in next 10 years CHD Risk Equivalent

Symptomatic
Established CHD Carotid art disease Peripheral art disease Abdominal aortic aneurysm

Asymptomatic
Diabetes mellitus Multiple major risk factors (3 or more - absolute risk > 20% in 10 ys) Very high level single risk factor

RISK FACTORS
0-1
NO SCORING 10-Y RISK OF CHD LEVEL OF RISK FACTOR HIGH >20% INTERMEDIATE 10-20%
LOW <10%

MULTIPLE
CHD RISK SCORE

INITIATION OF DRUG THERAPY

SINGLE vs MULTIPLE RISK FACTORS
LDL-C SBP DBP
Other Risk factors CHD 10-y risk

160-189 mg/dL 160 - 180 mmHg 100 - 110 mmHg +

Severe single risk factor Multiple RFs Approaches 10 %

>/= 190 mg/dL > 180 mmHg > 110 mmHg

RISK CATEGORIZATION NEED FOR

PHARMACOLOGIC INTERVENTION

RISK CATEGORY
CHD Risk in 10 years

HIGH

MODERATE

LOW

>20%
CHD CHD Risk Equivalents

10-20%
Multiple Risk Factors - 2+

<10%
0-1 Risk Factor No need for risk scoring

DRUG THERAPY

+++

0 - +++

+ - +++ Intesity of pharmacologic intervention and risk factors reduction

ELEVATED LDL CHOLESTEROL Pharmacologic Therapy

In Absence of Other Risk Factors

LDL cholesterol >220 mg/dl Always Necessary

LDL cholesterol >=190 mg/dl

Should be considered Except : -Young men (<35 y} -Premenopausal women

RISK ASSESSMENT OFFICE

ASYMPTOMATIC
INTERMEDIATE RISK

CLINICAL CVDCVDCVD
HIGH RISK
INITIATE DRUG THERAPY

LOW RISK
FOLLOW UP

?NONINVASIVE TESTING

MYOCARDIAL ISCHEMIA STRESS ECG STRESS ECHO PERFUSION IMAGING

SUBCLINICAL ASO

Ankle/Brachial BP Index Carotid B mode US-IMT EBCT-Coronary Ca score CRP, Endothelial function

ASSESSMENT OF CARDIOVASCULAR RISK

In Asymptomatic Patient, To Treat Or Not To Treat Thats The Question . Whether To Initiate Drug Therapy Is Cost Effective . Whether Drug Therapy Should Be Intensive

Risk Assessment Can Answer Many Questions

In Many Times Clinical Judgement Is the Choice, But When Symptomatic There Is No Choice but Secondary Prevention