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 • 60 Y/O male
• Non-smoking • Smoker
• BP: 170/100 mmHg • BP: 170/100 mmHg
• Total cholesterol : 228 • Total cholesterol : 228
mg/dL mg/dL
• HDL-C : 46 mg/dL • HDL-C : 38 mg/dL
• Non-diabetic • Non-diabetic

• Chance of major CV event • Chance of major CV event

in the next 5 years : 6 % 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
¾ Angina pectoris
¾ Myocardial infarction –recognized & unrecognized
¾ Unstable angina
¾ CHD death

• HARD CHD
¾ Myocardial infarction
¾ Unstable angina
¾ 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 LOW-
RISK 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

0 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
Age (y) 66.1 59.9
Current smoking 29.5 41.6
Diabetes 23.2 15.3
Hyperlipedemia 39.6 34.1
Hypertension 55.9 38.4
No risk factors 15.4 19.4
Khot et al. JAMA- 2003
“80 % 0f CAD are preventable by
interfering with Cardiovascular Risk
Factors”

AHA Meeting , New Orleans - 2000

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

METHODS

¾ Calculate The Number Of Points For Each

Risk Factor
¾ Estimate Global Risk Score ( Sum Of Points )
¾ Consult Coronary/CV Risk Chart
¾ 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 Scoring System

Risk Factor Risk Points

Men Women Risk Points
Age, y Risk Factor
Men Women
<34 -1 -9 Systolic blood pressure, mm Hg
35-39 0 -4
40-44 1 0 <120 0 -3
45-49 2 3
50-54 3 6 120 - 129 0 0
55-59 4 7 130 -139 1 1
60-64 5 8
65-69 6 8 140 - 159 2 2
70-74 7 8 >160 3 3

Risk Factor Risk Points

Risk Factor Risk Points
Men Women
Men Women
Total Cholesterol Diabetes
<160 -3 -2
No 0 0
169-199 0 0
200-239 1 1 Yes 2 4
240-279 2 2
Smoker
> 280 3 3
No 0 0

Yes 2 2
 FRAMINGHAM Scoring System

Global Risk Assessment Scoring

Risk Factor Risk Points

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

Source: Framingham Heart Study

Global Risk Assessment Scoring
Adjusted FRAMINGHAM Scoring System
Plasma Glucose, mg/dl

Risk Points

Men Women

< 110 0 0

110-126 1 2

>126 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 Probability Probability
pts. 10 yrs pts 10 yrs pts 10 yrs

≤1 < 2% 12 7% 23 23%
2 2% 13 8% 24 25%
3 2% 14 9% 25 27%
4 2% 15 10% 26 29%
5 3% 16 12% 27 31%
6 3% 17 13% 28 33%
7 4% 18 14% 29 34%
8 4% 19 16% 30 39%
9 5% 20 18% 31 40%
10 6% 21 19% 32 44%
11 6% 22 21%
 FRAMINGHAM Scoring System

ASSESSMENT OF CARDIOVASCULAR RISK

Interaction With Other Risk
Factors

¾ Smoking increases risk x 2 → 3

¾ Hypertension increases risk x 2 → 3
¾ LVH increases risk x 2
¾ LV strain pattern increases risk x 2 → 3
¾ 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 Hypertension
25.5% (185/100mmHg)
18.3% 17.7%
41.9%
33.3% 32.5%
Hyperlipidaemia
(TC:HDL=8)
24.5%
all risk factors + diabetes = 47.9%
 Risk Categorization
Typical 10 year risk of stroke or myocardial infarction

Low risk = < 15 percent

Medium risk = 15-20 percent

High risk = 20-30 percent

Very high risk > 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 Hypertension
13.8% (185/100mmHg)
5.0% 7.8%
14.1%
5.1% 8.0%
Hyperlipidaemia
(TC:HDL=8)
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 , • HDL cholesterol,
35-39 0 mg/dl
40-44 6 <35 11
45-49 11 35-44 8
50-54 16 45-54 5
55-59 21 >=55 0
60-65 26
• LDL cholesterol, • Triglycerides, mg/dl AcuteCoronaryEvents
mg/dl <100 0
<100 0 100-149 2 Mean Estimated Risk
100-129 5 150-199 3
PROCAM Score In 10 y
130-159 10 >=200 4
(%)
160-189 14
>=190 20
0-20 0.7
21-29 1.6
29-37 3.3
• D iabetes m ellitus
38-44 6.8
N0 0
• Systolic blood 45-53 13.5
Y ES 6
pressure, m m H g 54-61 26.3
<120 0
• M I in fam ily history 120-129 2 >61 49.9
No 0 130-139 3
Y es 4 140-159 5
• S m o ker >=160 8
No 0
Y es 8
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
48.6 BEFORE 40
50 AT 40 Y
AT 70 Y
40 34.9
31.7
% Lloid-Jones et al
30 24.2 Lancet-1999

20

10 1.2 0.2
0
MEN WOMEN
 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 –clinical-
atherosclerotic 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 : 4-
fold 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 Asymptomatic
• Established CHD • Diabetes mellitus
• Carotid art disease • Multiple major risk factors
• Peripheral art disease (3 or more - absolute risk >
• Abdominal aortic 20% in 10 ys)
aneurysm • Very high level single risk
factor
 RISK FACTORS

0-1 MULTIPLE

CHD RISK SCORE

NO SCORING

10-Y RISK OF CHD

LEVEL OF RISK FACTOR

HIGH INTERMEDIATE LOW

>20% 10-20% <10%
 INITIATION OF DRUG THERAPY
SINGLE vs MULTIPLE RISK FACTORS

LDL-C 160-189 mg/dL >/= 190 mg/dL

SBP 160 - 180 mmHg > 180 mmHg

DBP 100 - 110 mmHg > 110 mmHg

+
Other Risk •Severe single risk
factors factor
•Multiple RFs
CHD 10-y risk Approaches 10 %
 RISK CATEGORIZATION – NEED FOR
PHARMACOLOGIC INTERVENTION

RISK HIGH MODERATE LOW

CATEGORY
CHD Risk in 10 >20% 10-20% <10%
years

•CHD Multiple Risk 0-1 Risk Factor

•CHD Risk Factors - 2+ – No need for

Equivalents risk scoring

DRUG +++ 0 - +++ 0

THERAPY
+ - +++ 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

CLINICAL
ASYMPTOMATIC
CVDCVDCVD

HIGH RISK INTERMEDIATE LOW RISK

RISK

INITIATE DRUG THERAPY ?NONINVASIVE TESTING FOLLOW UP

MYOCARDIAL ISCHEMIA SUBCLINICAL ASO

STRESS ECG Ankle/Brachial BP Index

Carotid B mode US-IMT
STRESS ECHO
EBCT-Coronary Ca score
PERFUSION IMAGING
CRP, Endothelial function
ASSESSMENT OF CARDIOVASCULAR
RISK

In Asymptomatic Patient, To Treat Or Not To Treat

That’s 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