Incremental Predictive Value of Vascular Assessments Combined with the

Framingham Risk Score for Prediction of Coronary Events in Subjects of Low

Intermediate Risk

Kui-Kai Lau,1 Yap-Hang Chan,1 Kai-Hang Yiu, MBBS,1 Sidney Tam, MD,2

Sheung-Wai Li, MBBS,3 Chu-Pak Lau, MD,1 Hung-Fat Tse, MD,PhD.1

1Cardiology Division, The University of Hong Kong,2Department of Clinical Biochemistry Unit, Queen Mary Hospital, and

3Department of Medicine, Tung Wah Hospital, Hong Kong, China.

Background• In the past, clinical prediction of cardiovascular

disease has mainly relied on evaluating its risk factors.

• Various risk scores have been developed to improve the prediction of coronary risk.

• The Framingham Risk Score (FRS) is one of the most common scoring systems – subjects are stratified into low, intermediate or high risk of developing a future coronary event.

Background• However, a large and heterogeneous

population of subjects are stratified into low-intermediate risk category by using the FRS.

• The decision to initiate primary prevention in such subjects remain unclear.

• Additional methods for risk stratification of cardiovascular disease are therefore needed in such subjects.

Background • Previous studies have already shown that

coronary artery calcium score has incremental benefit in risk stratification when used with the FRS.

• However, measurement of the coronary artery calcium score may not be readily accessible in the primary care setting.

• The incremental benefits of markers obtained from vascular ultrasonography has yet to be investigated.

Objectives

To investigate the potential added benefits of non-invasive vascular sonographic

assessments (brachial endothelial function, carotid IMT, carotid plaque) in conjunction with FRS for coronary risk

prediction.

Methodology

Vascular Markers

Flow mediated dilatation (FMD)

Carotid-Intima Media Thickness (IMT)

Carotid plaque

CAD

N = 70

•Low-Intermediate risk of coronary event

•Symptomatic significant CAD with a recent

history of acute coronary syndrome

Age & sex matched

2:1

Controls

N = 35

•CT Ca Score<10

•No history of CVD

•No history of DM

Brachial Artery Flow Mediated Dilatation

(BAD(BADhyperaemiahyperaemia – BAD – BAD at restat rest) ) BADBADat restat rest

== X 100X 100FMD%FMD%

Carotid Intima-Media Thickness and Plaque Detection

Intima-Media Thickness (IMT)

• Defined as distance between the blood-intima interface and media-adventitia interface

• Measurements from near and far wall of the left and right common carotid, carotid bifurcation and internal carotid artery were taken

• Mean maximum IMT was used for analysis

Carotid Plaque

Endoluminal protrusion of 1.5mm ≧or 2 times adjacent IMT

Blood-intima interface

Media-adventitia interface

IMT

Carotid Plaque

Clinical Characteristics of Study Population

1.035 (100)70 (100)Males, n (%)

<0.0011 (3)55 (79)Lipid lowering therapy, n (%)

<0.00110 (29)62 (89)Anti-hypertensives, n (%)

0.101 (3)9 (13)Family history of cardiovascular disease, n (%)

0.2715 (43)38 (54)Smoking, n (%)

1.00 (0)0 (0)Diabetes, n (%)

0.00219 (54)58 (83)Hypercholesterolemia, n (%)

0.0019 (26)42 (60)Hypertension, n (%)

0.1224.0 3.125.1 3.3Body-Mass Index, kg/m2

0.1159.5 8.962.4 8.5Age, years

P Value

Controls (N=35)

CAD (N=70)Characteristic

Vascular Assessments of Study Population

0.00814 (40)47 (67)Carotid plaque (%)

0.320.96 0.141.01 0.28mmIMT (mm)

0.0035.18 2.69 3.56 2.41FMD (%)

P Value

Controls(N=35)

CAD(N=70)

Correlations between FRS and Vascular Markersr= 0.314, p=0.001

r= -0.246, p=0.016

r= -0.226, p=0.026

Diagnostic Values of FRS & Vascular Markers According to Specified Cut-off Values

54.580.768.669.7-0.0000.69FRS + mmIMT 1.05

47.380.974.356.7 2.500.0070.66FRS

83.3

82.3

81.2

81.4

80.0

77.0

79.1

PPV

71.4

68.6

62.9

68.6

82.9

60.0

60.0

SP

60.081.5 4.750.0010.70FMD, %

66.781.0-0.0000.75FRS + FMD 4.75 + Carotid Plaque

61.075.8-0.0000.73FRS + Carotid plaque + mmIMT 1.05

66.783.6-0.0000.72FRS + Carotid Plaque

61.576.2-0.0000.78FRS + FMD 4.75

39.234.8 1.050.4920.54mm IMT, mm

47.767.1-0.0330.64Carotid plaque

NPVSNCut-off values

P Value

AUCMarker

FRS, AUC=0.66

FRS + Carotid plaque, AUC=0.72 (P=0.008 vs. FRS)

FRS + FMD ≤4.75%, AUC=0.78 (P=0.007 vs. FRS)

1-Specificity

Sen

siti

vity

0.0 0.2 0.4 0.6 0.8 1.0

0.0

0.2

0.4

0.6

0.8

1.0

Incremental Benefit of Vascular Markers in Addition to FRS for Coronary Risk Prediction

Univariate and Multivariate Predictors of an Acute Coronary Event

0.0014.33 (1.77-10.62)Hypertension

0.0034.80 (1.67-13.65)0.0005.28 (2.20-12.68)Hypercholesterolemia

0.271.58 (0.70-3.59)Smoking

0.0093.07 (1.32-7.10)Carotid plaque

0.0662.58 (0.94-7.07)mmIMT 1.05mm

<0.0017.97 (2.69-23.59)<0.0016.63 (2.64-16.66)FMD 4.75%

0.0341.45 (1.03-2.05)0.0061.50 (1.13-2.00)FRS

P Value

OR (95% CI)P

ValueOR (95% CI)

MultivariableUnivariableRisk Variables

Conclusions• In subjects with low-intermediate risk of

developing a coronary event, detection of an impaired FMD response or presence of carotid plaque provides incremental value when used with the FRS for risk stratification.

• Larger scaled prospective studies are required to confirm the benefit of using such markers in coronary risk stratification and cardiovascular disease prevention.

Limitations of Study• This was a retrospective study which

consisted of a small number of patients • Only male Chinese subjects were

recruited, thus our results might not be applicable to women or other ethnic groups