Dr. Felix Nunura Heart Institute of the Caribbean (HIC)

UTJ Adjunct Associate Professor of Medicine

CARDIAC RISK EVALUATION:Searching for the vulnerable

patient

September, 2012

Screening for the Risk Factors for the disease

Screening for the

disease

The Disease: Atheroesclerosis

Types of Cardiovascular Disease

What do you think about this patient ?

23 points, 22 % CV Risk

What do you think about this patient..?

18 points, > 30 % CV Risk

The risk of develop CV disease ( CHD or Stroke) in the next 10 years in percent (%) can be calculated

with the help of the Framingham Risk Score

Gender, Age, Total-C , HDL-C, SBP, Smoking status

Systematic COronary Risk Evaluation (SCORE): based on gender, age, total cholesterol, systolic blood pressure and smoking status.

Roques F, Michel P, Goldstone AR, Nashef SA. The logistic EuroSCORE. Eur Heart J. 2003 May;24(9):882-3

Effects of any treatment (to lower cholesterol / lower blood pressure) that reduced the risk of CVD in 50 %

100ptes

With20%CV

Risk 20

80

Treatment10

80

10

Will develop CHD or Stroke in the next 10 years

Will not develop CHD or Stroke in the next 10 years

1994 4S 2002 PROSPER 1995 WOSCOPS 2002 ALLHAT-LLA 1996 CARE 2002 ASCOT-LLA 1998 AFCAPS/TEXCAPS 2004 PROVE-IT 1998 LIPID 2004 A to Z 2001 MIRACL 2005 TNT 2002 HPS 2005 IDEAL

2008 JUPITER

Study populations:Primary prevention

Acute coronary syndromes (Secondary prevention)Chronic Coronary heart disease (Secondary prevention)

*Trials with clinical outcomes

HMG-CoA Reductase Inhibitor:STATINSHMG-CoA Reductase Inhibitor:STATINSChronological Order of Event Driven Chronological Order of Event Driven

TrialsTrials

Efficacy of antihypertensive treatmentEfficacy of antihypertensive treatment: Duration and homogeneity of the efficacy of antihypertensive drugs are currently quantified by computation of the smoothness index (SI) from ambulatory blood

pressure monitoring (ABPM) recordings.

The smoothness index (SI) identifies the occurrence of a balanced 24 h

blood pressure reduction with treatment and correlates with the

favourable effects of treatment on left ventricular hypertrophy better than the commonly used trough : peak

ratio.

According to the standard definition, the SI is calculated as the ratio

between the mean hourly reductions and the standard deviation of these

reductions. (American Journal of Hypertension 2005; 18, 24A )

General Cardiovascular Risk Profile for Use in Primary Care

The Framingham Heart Study

Ralph B. D’Agostino, Sr, PhD; Ramachandran S. Vasan, MD; Michael J. Pencina, PhD; Philip A. Wolf, MD; Mark Cobain, PhD; Joseph M. Massaro, PhD; William B. Kannel, MD

Circulation. 2008;117:743-753.

Background

• Framingham risk score effective, but only predicts CHD risk .

• CV diseases share common risk factors

• …a way to predict risk for all CVD events

JAMA. 2007;298(7):776-785Circulation. 2008;117:743-753.

Sexmale (m) or female

(f) fAge years 30Systolic Blood Pressure mmHg 125.0Treatment for Hypertension yes (y) or no (n) nSmoking yes (y) or no (n) nDiabetes yes (y) or no (n) nBody Mass Index kg/m² 22.5  

Your 10-Year Risk (The risk score shown is derived on the

basis of an equation. Other print products, use a point-based system to calculate a

risk score that approximates the equation-based one.)

1.1%

Sex male (m) or female (f) fAge years 24Systolic Blood Pressure mmHg 125.0Treatment for Hypertension yes (y) or no (n) nSmoking yes (y) or no (n) nDiabetes yes (y) or no (n) nHDL mg/dL 45Total Cholesterol mg/dL 180 

Your 10-Year Risk (The risk score shown is derived on the basis of an equation. Other print

products, use a point-based system to calculate a risk score that

approximates the equation-based one.)

0.8%

The 10 years General CV Risk ScoreCirculation. 2008;117:743-753.

Lifetime Risks of Cardiovascular DiseaseJarett D. Berry, M.D., Alan Dyer, Ph.D., Xuan Cai, M.S., Daniel B. Garside, B.S., Hongyan Ning, M.D., Avis Thomas, M.S., Philip Greenland, M.D., Linda Van Horn, R.D., Ph.D., Russell P. Tracy, Ph.D., and Donald M. Lloyd-Jones, M.D.

N Engl J Med 2012; 366:321-329January 26, 2012

BackgroundThe lifetime risks of cardiovascular disease have not been reported across the age spectrum in black adults and white

adults.Conclusions

Differences in risk-factor burden translate into marked differences in the lifetime risk of cardiovascular disease, and

these differences are consistent across race and birth cohorts. (Funded by the National Heart, Lung, and Blood

Institute.)

What do you think about this patient ?

Lifetime Risk50 %

What do you think about this patient ?

Lifetime Risk69 %

Future CV Risk Prediction: Concept of Lifetime Risk

Lloyd-Jones et al. Circulation 2006; 113: 791-798

Framingham Heart Study: Optimization of RFs in asymptomatic 50 year-olds associated with low lifetime CVD risk

OptimalTotal chol <180BP <120/80NonsmokerNon diabetic

Not optimalTotal chol 180-200BP 120-140/80-90

Elevated RFTotal chol 200-240SBP 140-160/90-100

Major RFTotal chol >240BP >160/90SmokerDiabetic

Other issues:Low

H D L

Diabetes

Metabolic Syndrome

Inflammation

HsCRP

Triglycerides

Stress

Niacin in Patients with Low HDL Cholesterol Levels Receiving Intensive

Statin Therapy

The AIM-HIGH InvestigatorsN Engl J Med 2011; 365:2255-2267

In patients with established cardiovascular disease, residual cardiovascular risk persists despite the achievement of target low-density lipoprotein (LDL) cholesterol levels with statin therapy. It is unclear

whether extended-release niacin added to simvastatin to raise low levels of high-density lipoprotein (HDL)

cholesterol is superior to simvastatin alone in reducing such residual risk.

AIM-HIGH : AIM-HIGH : The trial was stopped after a mean follow-up period of 3 years owing to a lack of

efficacy.

• Among patients with atherosclerotic cardiovascular disease and LDL cholesterol levels of less than 70 mg per deciliter (1.81 mmol per liter), there was no incremental clinical benefit from the addition of niacin to statin therapy during a 36-month follow-up period, despite significant improvements in HDL cholesterol and triglyceride levels.

• (Funded by the National Heart, Lung, and Blood Institute and Abbott Laboratories)

The “Super-Sizing” of America

“This year, Americans will spend more money on fast food than on higher education…”

Eric Schlosser. Eric Schlosser. Fast Food Nation: The Dark Side of the All-American MealFast Food Nation: The Dark Side of the All-American Meal..Harper Collins. 2002.Harper Collins. 2002.

Haffner SM, Lehto S, Ronnemaa T, et al: N Engl J Med 339:229–234, 1998

Diabetes is a “cardiovascular disease risk equivalent”

► Optimal fasting triglyceride levels, defined as 100 mg/dL, as a parameter of metabolic health, and ► Non-fasting triglyceride levels can be used to screen for those with high fasting triglyceride levels. Normal non-fasting < 200 mg/dL

AHA Scientific Statement on Triglycerides and CVD

This statement suggests the following new designations:

Miller M et al. Circulation. 2011;123 published online Apr 18, 2011; DOI: 10.1161

Systemic inflammation

Eur Heart J 2010 (31) 3: 290-297

Current Opinion 2012; 142:w13502

Ps: Psychosocial stress as a risk factor

Many times the traditional risk factor based screening fails in identifying the Vulnerable Patient.

-

Sir Winston Churchill, 91 Sir Winston Churchill, 91 Jim Fixx, 53Jim Fixx, 53 Who Has More Cardiovascular Risk Who Has More Cardiovascular Risk

Factors?Factors?

Existing Guidelines (Status Quo):• Screen for Risk Factors of Atherosclerosis• Treat Risk Factors of Atherosclerosis

Goal of “ new” Guidelines:• Screen for Atherosclerosis (the Disease)

regardless of, Risk Factors• Treat based on the Severity of the Disease

and its Risk Factors

ATHEROESCLEROSIS: Risk Factor screen Vs the disease

screen

Slide 31

Atherosclerosis begins early :Usefulness and Prognostic Implications of Surrogate Markers

in Atherosclerosis

Risk factors

Surrogatemarkers

Arterial vascular symptoms

Clinical events (MI,

suddendeath)

Autopsy

LateEarly

Adapted from Crouse JR III. J Lipid Res. 2006;47:1677–1699; Nissen S. Am J Cardiol. 2001;87(suppl):15A–20A.

Importance of Subclinical Disease Detection

• Atherosclerosis begins early• can be detected prior to a cardiac event

• Most MI’s -previously <40% stenosis • plaque rupture and thrombus (blood clot)!

• Stress tests only detects flow-limiting stenoses (blockages)

• Subclinical disease measures • target patients for “aggressive primary prevention”

Evaluating coronary vasoreactivity

Eur. Heart J 2010 (31) 7, 777-783

012345678

<0.5 0.5-1.0

1.0-2.0

2.0-3.0

3.0-4.0

4.0-5.0

5.0-10.0

10.0-20.0

>20.0

Crude RRs Risks Adjusted for FRS

RR

of f

utur

e C

ardi

o. E

vent

s

Low risk Mod. risk High risk

hsCRPmg/L

Ridker PM, et al. Circulation 2004;109:1955-9.

Higher CRP levels predict increased risk for heart disease

From: Coronary Artery Calcium Scanning Should be Used for Primary Prevention: Title and subTitle BreakPros J Am Coll Cardiol Img. 2012;5(1):111-118. doi:10.1016/j.jcmg.2011.11.007

Coronary Artery CalciumCoronary Artery Calcium

No CalcificationNo Calcification Severe Severe CalcificationCalcification

Left Main

LAD

LCX

AortaAorta

LALA

PAPA

Left Main

LAD

Measurement of CAC may be reasonable for cardiovascular risk assessment persons at low to intermediate risk (6% to 10% 10-year

risk).

Direct in vivo measurement of thickness of carotid artery wall by B-mode ultrasound – “arterial biopsy”Vessel wall thickness correlates with status of atherosclerosis and cardiovascular events

Atherosclerosis is a systemic disorderDisease in carotid artery is predictive of disease in other vascular beds

Measurement of CA IMT

Adapted from Crouse JR III. J Lipid Res. 2006;47:1677–1699; Espeland MA, et al. Curr Controll Trials Cardiovasc Med. 2005;6:3; Kastelein JJP, et al. Am Heart J. 2005;149:234–239. .

A well-established marker of atherosclerotic disease

CA IMT Measured by B-Mode Ultrasound

Slide 41

Rotterdam StudyCA IMT Strongly Predictive of MI

*Adjusted for age and genderAdapted from van der Meer I, et al. Circulation. 2004;109:1089–1094.

1

1.682.05

2.91

0

1

2

3

<0.88 0.88–<0.99 0.99–<1.12 ≥1.12

CA IMT, mm

Haz

ard

Rat

io*

(n=1277) (n=1279) (n=1287) (n=1273)

ACCF/ACR/AIUM/ASE/ASN/ICAVL/SCAI/SCCT/SIR/SVM/SVS

2012 Appropriate Use Criteria for Peripheral Vascular Ultrasound and Physiological

Testing

Part I: Arterial Ultrasound and Physiological Testing:.. it is uncertain if Carotid Ultrasound should be used in patient with

intermediate Frammingham Risk Score…

J. Am. Coll. Cardiol. published online Jun 11, 2012;

Current: “Sick care” to “Health care”

Can a Polipill prevent CVD ?

Systematic COronary Risk Evaluation (SCORE): based on gender, age, total cholesterol, systolic blood pressure and smoking status.

Roques F, Michel P, Goldstone AR, Nashef SA. The logistic EuroSCORE. Eur Heart J. 2003 May;24(9):882-3

Can the combination Therapy (SPAA) for Cholesterol and Blood Pressure Reduce the 10-year Calculated Risk of

Coronary Heart Disease, Fatal Cardiovascular Disease ?

Zamorano and Edwards, Integrated Blood pressure Control 2011,4:55-71