ASSESSMENT OF ASSESSMENT OF CARDIOVASCULAR RISKCARDIOVASCULAR RISK

M MOHSEN IBRAHIM , MDCARDIOLOGY DEPARTMENT-CAIRO UNIVERSITY

Adapted from Levy et al, Textbook of Cardiovascular Medicine, 19Adapted from Levy et al, Textbook of Cardiovascular Medicine, 1998 98

The Complications of CAD Often Emerge without The Complications of CAD Often Emerge without WarningWarning

• 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

• DEFINITIONSDefinition of RiskRisk Factors

• METHODSRisk ScoreRisk Charts

• IMPLICATIONSInitiation of Pharmacologic Therapy

ASSESSMENT OF CARDIOVASCULAR RISK

RISK OF WHAT ?

ENDPOINTS

ASSESSMENT OF CARDIOVASCULAR RISK

RISK OF WHAT ?

HARD END POINTSHARD 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 CHDAngina pectorisMyocardial infarction –recognized & unrecognizedUnstable anginaCHD death

• HARD CHDMyocardial infarctionUnstable anginaCHD death

RISK OF WHAT ?SOFTSOFT END POINTSEND POINTS

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

RISK OF WHAT ?

SURROGATE END POINTSSURROGATE END POINTS

• CORONARY ART DISEASE PROGRESSIONCoronary angiographyIVUSMRIUFCT (quantitative assessment of coronary calcium)

• VASCULAR ENDOTHELIAL FUNCTION

• INFLAMMATORY MARKERSCAMs , hsCRP

RISK ESTIMATES

• ABSOLUTE RISKProbability of developing CHD or CV death over

given time period e.g. the next 10 years

• RELATIVE RISKThe 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 STATEFramingham

• 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 CARDIOVASCULAR RISK FACTORSFACTORS

• INDEPENDENT – CAUSATIVE

• CONDITIONAL

• PREDISPOSING

• SUSCEPTIBILITY

• ESTABLISHED - EMERGING

• PROATHEROGENIC – PROTHROMBOTIC

--------------------------------------------------------------------------------------

• MODIFIABLE – NONMODIFIABLE

CATEGORIES OF CATEGORIES OF CARDIOVASCULAR RISK FACTORSCARDIOVASCULAR RISK FACTORS

CARDIOVASCULAR RISK FACTORS

CHARACTERISTICS OFA MAJOR-CAUSATIVE RISK FACTOR

• INDEPENDENCE OF CONTRIBUTION FROM OTHER RISK FACTORS

• QUANTITAVE CONTRIBUTION TO RISK

•Age •Gender•Family history•Established CVD Dis

•Cigarette Smoking•Hypertension•Hypercholesterolemia•Low HDL-Cholesterol•Obesity•Diabetes Mellitus•Hypertriglyceridemia•Sedentary Life-Style

MODIFIABLE

NON-MODIFIABLE •↑ 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

Independent / Established/Major Dependent / Emerging/Novel

CARDIOVASCULAR RISK FACTORSCARDIOVASCULAR RISK FACTORS

M M Ibrahim 2003

Relative Risk of Future Myocardial Infarction

0 1.0 2.0 4.0 6.0

fibrinogen

sICAM-1

interleukin-6

hs-CRP

hs-CRP + TC:HDL

Novel Risk Factors

Ridker et al NEJM,2000

• Plasma Myeloperoxidase

• Red Cell Glutathione Peroxidase 1 Activity

Ultra-Novel Risk Factors2003

•Red Cell Glutathione Peroxidase 1 ActivityBlankenberg et al. NEJM; October 23, 2003

PREVALENCE OF CONVENTIAL RISK FACTORS (%) IN CHD : MI/UA/PCI

Women Menno 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 19.4Khot et al. JAMA- 2003

“80 % 0f CAD are preventable by interfering with Cardiovascular Risk Factors”

AHA Meeting , New Orleans - 2000

METHODS OF ASSSESSMENT OF RISKo Global Risk Scoreo Risk Charts

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

ASSESSMENT OF

GLOBAL RISK ASSESSMENT SCORING SYSTEMS

• FRAMINGHAM Scoring System

• PROCAM Scoring System

• SCORE Project

• INDIANA Project

GLOBAL RISK ASSESSMENT SCORINGFRAMINGHAM RISK FACTORS

• AGE ,y

• TOTAL CHOLESTEROL ( OR LDL-C ) , mg/dL

• HDL- C , mg/dL

• SYSTOLIC BLOOD PRESSURE , mmHg

• DIABETES

• SMOKER

Risk PointsRisk FactorMen Women

Age, y<34 -1 -935-39 0 -440-44 1 045-49 2 350-54 3 655-59 4 760-64 5 865-69 6 870-74 7 8

FRAMINGHAM Scoring System

Risk PointsRisk FactorMen Women

Total Cholesterol<160 -3 -2169-199 0 0200-239 1 1240-279 2 2> 280 3 3

Risk PointsRisk FactorMen Women

Systolic blood pressure, mm Hg

<120 0 -3

120- 129 0 0

130 -139 1 1

140 -159 2 2

>160 3 3

Diabetes

No 0 0

Yes 2 4

Smoker

No 0 0

Yes 2 2

Risk Factor Risk Points

Men Women

Global Risk Assessment Scoring

Risk PointsRisk FactorMen 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

FRAMINGHAM Scoring System

Adjusted FRAMINGHAM Scoring SystemPlasma Glucose, mg/dl

Global Risk Assessment Scoring

42>126

21110-126

00< 110

WomenMen

Risk Points

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

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

ASSESSMENT OF CARDIOVASCULAR RISK

FRAMINGHAM Scoring System

all risk factors + diabetes = 47.9%all risk factors + diabetes = 47.9%

Smoking Smoking HypertensionHypertension(185/100mmHg)(185/100mmHg)

HyperlipidaemiaHyperlipidaemia(TC:HDL=8)(TC:HDL=8)

17.7%17.7%18.3%18.3%

24.5%24.5%

33.3%33.3% 32.5%32.5%

25.5%25.5%

5959 year old man, nonyear old man, non--smoker, BP 140/85mmHg, smoker, BP 140/85mmHg, TC:HDL = 4 TC:HDL = 4

10 year risk of CHD event = 11.9%10 year risk of CHD event = 11.9%

41.9%41.9%

INFLUENCE OF RISK FACTORS ON RISK OF CHD

Risk Categorization

Low risk = < 15 percent

Medium risk = 15-20 percent

High risk = 20-30 percent

Very high risk > 30 percent

Typical 10 year risk of stroke or myocardial infarction

all risk factors + diabetes = 21.7%all risk factors + diabetes = 21.7%

Smoking Smoking HypertensionHypertension(185/100mmHg)(185/100mmHg)

HyperlipidaemiaHyperlipidaemia(TC:HDL=8)(TC:HDL=8)

7.8%7.8%5.0%5.0%

2.8%2.8%

5.1%5.1% 8.0%8.0%

13.8%13.8%

5959 year old man, nonyear old man, non--smoker, BP 140/85mmHg, smoker, BP 140/85mmHg, TC:HDL = 4 TC:HDL = 4

10 year risk of stroke = 2.8%10 year risk of stroke = 2.8%

14.1%14.1%

INFLUENCE OF RISK FACTORS ON RISK OF STROKE

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

FRAMINGHAM GLOBAL RISK ASSESSMENT SCORING

PROCAM Scoring System - 2002

GLOBAL RISK ASSESSMENT SCORING

•PROCAM Scoring SystemProspective Cardiovascular Munster Study

-5389 men aged 35 – 65 years

-10 years follow-up

-Major coronary event :

. Sudden cardiac death

. Definite fatal or nonfatal MI

GLOBAL RISK ASSESSMENT SCORING

• Age , 35-39 040-44 645-49 11 50-54 1655-59 2160-65 26

• LDL cholesterol, mg/dl

<100 0100-129 5130-159 10160-189 14>=190 20

• HDL cholesterol, mg/dl<35 1135-44 845-54 5>=55 0

• Triglycerides, mg/dl<100 0100-149 2150-199 3>=200 4

• Systolic blood pressure, m m H g<120 0120-129 2130-139 3140-159 5>=160 8

• Diabetes m ellitusN 0 0Y ES 6

• M I in fam ily historyN o 0Y es 4

• Sm okerN o 0

Y es 8

Acute Coronary Events

PROCAM ScoreMean Estimated Risk

In 10 y(%)

0-20 0.721-29 1.629-37 3.338-44 6.845-53 13.554-61 26.3>61 49.9

PROCAM Scoring System

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

• 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 Project - 2001

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

• 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

GLOBAL RISK ASSESSMENT SCORING

0.21.2

31.7

48.6

24.2

34.9

0

10

20

30

40

50

60

MEN WOMEN

%

BEFORE 40AT 40 YAT 70 Y

RISK OF DEVELOPING CORONARY HEART DISEASE

LIFETIME RISK

Framingham

Lloid-Jones et al Lancet-1999

HIGH RISK INDIVIDUALProbability 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 DISEASERisk 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

IMPLICATIONSIMPLICATIONS

ASSESSMENT OF CARDIOVASCULAR RISK

• IDENTIFCATION OF HIGH RISK INDIVIDUALS

• Intensive Life Style Modification

• Need To Initiate Pharmacologic Intervention

• Extent Of Risk Factors Correction

• INDICATIONS FOR NON-INVASIVE TESTING

IMPLICATIONS

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

HIGH RISK INDIVIDUALProbability of Developing a Fatal or Nonfatal MI

>20% in next 10 yearsCHD Risk Equivalent

RISK FACTORS

0 - 1 MULTIPLE

NO SCORING

LEVEL OF RISK FACTOR

CHD RISK SCORE

10-Y RISK OF CHD

HIGH>20%

INTERMEDIATE10-20%

LOW<10%

INITIATION OF DRUG THERAPYSINGLE vs MULTIPLE RISK FACTORS

Approaches 10 %CHD 10-y risk

•Severe single risk factor•Multiple RFs

Other Risk factors

> 110 mmHg100 - 110 mmHg+

DBP

> 180 mmHg160 - 180 mmHgSBP

>/= 190 mg/dL160-189 mg/dLLDL-C

RISK CATEGORIZATION – NEED FOR PHARMACOLOGIC INTERVENTION

00 - ++++++DRUG

THERAPY

0-1 Risk Factor

– No need for

risk scoring

Multiple Risk

Factors - 2+

•CHD

•CHD Risk

Equivalents

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

years

LOWMODERATEHIGHRISK

CATEGORY

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

ELEVATED LDL CHOLESTEROLPharmacologic Therapy

In Absence of Other Risk Factors

LDL cholesterol >220 mg/dl Always Necessary

LDL cholesterol >=190 mg/dl Should be consideredExcept :-Young men (<35 y}-Premenopausal women

RISK ASSESSMENT OFFICE

CLINICAL CVDCVDCVD

ASYMPTOMATIC

HIGH RISK INTERMEDIATE RISK

LOW RISK

INITIATE DRUG THERAPY ?NONINVASIVE TESTING FOLLOW UP

MYOCARDIAL ISCHEMIA SUBCLINICAL ASO

STRESS ECG

STRESS ECHO

PERFUSION IMAGING

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

That’s The Question .

Whether To Initiate Drug Therapy Is Cost Effective .

Whether Drug Therapy Should Be Intensive

Risk Assessment Can Answer Many QuestionsIn Many Times Clinical Judgement Is the Choice,

But When Symptomatic There Is No Choice

but Secondary Prevention