Coronary artery disease (CAD) risk factors

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Background

Coronary artery disease (CAD) risk factors CAD Risk factors Hypertension Insulin resistance /diabetes Dyslipidemia Smoking /Obesity Male gender/ Old age Atherosclerosis Arterial stiffness precedes atherosclerosis development Arterial stiffness as a surrogate end point for CAD Framingham Heart Study

Artery stiffness estimated by 2D speckle tracking technique Current clinical issue Development of accurate, simple and non invasive method Early diagnosis of arteriosclerosis in individuals without symptoms of overt atherosclerotic disease < 2D speckle tracking technique as a new diagnostic method> Estimate vascular tissue motion and deformation Strain and strain rate to be a useful parameter of arterial stiffness Arterial stiffness by 2D speckle tracking technique Simple Non invasive Angle independent In expensive Pressure dependent

Beta stiffness index (BSI) as a pressure independent arterial stiffness parameter Beta stiffness index Correction for the ratio of systolic and diastolic pressures Changes in arterial diameter during the cardiac cycle Good correlation with arterial stiffness -T. Hirai et, Stiffness of systemic arteries in patients with myocardial infarction, circulation, 1989 Arterial distensibility derived BSI Strain derived BSI BSI = ln SBP DBP Ds-Dd BSI = ln SBP DBP Peak strain(%) Ds 100 SBP : systolic blood pressure DBP : diastolic blood pressure -Yoshifumi Oishi, M.D, A novel approach to assess aortic stiffness related to changes in aging. Echocardiography, 2008 Ds : systolic diameter of CCA Dd : diastolic diameter of CCA

Aim of study To explore usefulness of common carotid artery(cca) strain derived beta stiffness index for the prediction of concurrent coronary artery disease in comparison with stiffness index derived from CCA distensibility, and conventional arterial stiffness parameters such as pulse wave velocity (PWV) and carotid intima-media thickness (IMT).

Method

Study population Total n=101 (age = 59±10yrs ) Coronary angiography in Inha university hospital Obstructive coronary artery disease (CAD) -> stenosis of more than 50% in at least one major epicardial coronary artery 9 patients were excluded : 7pts due to ABI<0.9 : 2 pts due to poor echo window CAD (N=46) non-cad (N=46) Exclusion criteria Previous PCI, STEMI & Non-STEMI Atrial fibrillation, Poor window for 2DE of CCA ABI <0.9

Echocardiographic baseline data Systolic function LVEF LV end systolic volume LV end diastolic volume - by biplane simpson s method Diastolic function Left atrium size - AP diameter on parasternal short axis view E/A ratio - by dividing mitral flow early diastolic velocity with mitral flow late diastolic velocity E/E ratio - by dividing mitral flow early diastolic velocity with mitral septal annular peak diastolic tissue velocity Vivid 7, GE Vingmed Ultrasound

Brachial-ankle pulse wave velocity & Carotid intima-media thickness VP 1000, Colin Waveform analyzer Vivid 7, GE Vingmed Ultrasound Brachial artery Distance Tansit time Tibial artery Brachial-ankle pulse wave velocity Automated waveform analyzer PWV = Distance / Transit time Mean bapwv Carotid intima-media thickness (IMT) 13 MHz probe Longitudinal axis image of Lt. CCA Semi-automated technique Far wall of Lt. CCA at 1.5cm from carotid bulb

Stiffness Index Beta 1 (BSI 1) as distensibility parameter of common carotid artery Vivid 7, GE Vingmed Ultrasound CCA distensibility by M-mode 2D longitudinal axis cine loop of Lt. CCA Peak systolic & diastolic inner diameter Brachial artery systolic and diastolic pressure Dd Ds B stiffness index 1 ( BSI 1 ) BSI 1= ln SBP DBP Ds-Dd SBP : systolic blood pressure DBP : diastolic blood pressure Ds : systolic diameter of CCA Ds Dd : diastolic diameter of CCA

Measurement of strain & strain rate of common carotid artery by 2D speckle tracking technique Vivid 7, GE Vingmed Ultrasound, Echopac 7.0.0 software Measurements of strain and strain rate Posterior wall (Far wall) 2D short axis cine loops of Lt. CCA with a 13MHz linear transducer Short axis of CCA posterior global peak strain At least three consecutive heart beats with average frame rate of 76 frames/sec Offline analysis using 2D strain software Region of interest (ROI) on cross sectional area of the CCA Wall Global & posterior wall (far wall) early peak strain rate during systolic phase late peak strain rate during diastolic phasee Circumferential strain & strain rate Global Posterior (far wall) Radial strain & strain rate Posterior (far wall)

Stiffness Index Beta 2 (BSI 2) estimated by strain variables of common carotid artery B stiffness index 2 (BSI 2) BSI 2 calculated by BSI 2 = ln SBP DBP Peak strain(%) Global circumferential strain Posterior circumferential strain Posterior radial strain 100 SBP : systolic blood pressure DBP : diastolic blood pressure Inter & intra-observer variability By analysis of 20 random patients Using a coefficients of variation (CV)

Result

Baseline characteristics CAD (n=46) Non- CAD (n=46) p- value Age (yr) 61.9 (10.8) 56.3 (8.6) p=0.007 DM n(%) 16 (34) 5 (10) p=0.006 Hypertension n(%) 29 (63) 28 (60) p=0.83 Hyperlipidemia n(%) 15 (32) 5 (10) p=0.01 Stroke n(%) 4 (8) 0 (0) p<0.001 Smoking n(%) 17 (37) 9 (20) 0.064 BMI (kg/m 2 ) 24.5 (2.7) 25.4 (2.9) p=0.129 EF(%) 62 (5.5) 67 (4.7) p=0.16 LVEDV (ml) 103 (20) 104 (19) p=0.8 LVESV (ml) 38 (9.05) 36 (8.4) p=0.053 LA dimension (mm) 3.6 (0.46) 3.6 (0.38) p=0.8 E/A 1. 2 (0.4) 1.4 (0.5) p=0.6 E/E 10 (3.26) 9.6 (2.4) p=0.19 CAD, coronary artery disease; DM, diabetes mellitus; BMI, body mass index; TG, triglyceride; LDL, low density lipoprotein; HDL, high density lipoprotein; EF, ejection fraction; LVEDV, left ventricular end diastolic volume; LVESV, left ventricular end systolic volume; E/E, the ratio f mitral flow peak early diastolic velocity (E) and mitral annular early diastolic tissue velocity ( E )

Strain & strain rate variables of common carotid artery between two groups Measured variables CAD (n=46) Non- CAD (n=46) p- value Circumferential variables Global strain (%) 3.11 (1.26) 3.56 (1.13) p=0.074 Global early strain rate (1/s) 0.44 (0.17) 0.47 (0.27) p=0.52 Global late strain rate (1/s) -0.18 (0.07) -0.02 (0.17) p=0.34 Posterior strain (%) 6.47 (2.91) 8.83 (3.22) p<0.001 Posterior early strain rate (1/s) 0.77 (0.30) 1.04 (0.39) p<0.001 Posterior late strain rate (1/s) -0.78 (0.24) -1.02 (0.78) p=0.45 Radial variables Posterior strain (%) -3.43 (3.22) -5.76 (5.30) p=0.012 Posterior early strain rate (1/s) -0.78 (0.64) -1.02 (0.78) p=0.11 Posterior late strain rate (1/s) 0.62 (0.34) 0.76 (0.39) p=0.084 All values as mean with SD; CCA, common carotid artery; CAD, coronary artery disease

The intra and inter observer variability for the measurement of strain and strain rate variables of common carotid artery Measured variables Intra observer CV(%) Inter-observer CV(%) Circumferential variables Global peak strain (%) 12.8 14.2 Global early strain rate (1/s) 10.4 11.6 Global late strain rate (1/s) 12.2 13.8 Posterior peak strain (%) 6.4 8.8 Posterior early strain rate (1/s) 5.8 6.2 Posterior late strain rate (1/s) 14.8 17.2 Radial variables Posterior peak strain (%) 28.5 32.1 Posterior early strain rate (1/s) 70.8 85.6 Posterior late strain rate (1/s) 148.5 195.4 CV, coefficient of variation

Carotid IMT, PWV, BSI1 and three kinds of strain derived BSI 2s between two groups p<0.001 6.5 7.9 ±2 ±1.5 1.6 ±0.2 p=0.004 1.4 ±0.2 p=0.003 6.1 ±1.9 4.1 ±1.2 p=0.028 21 ±11 17 ±6 p=0.002 10 ±4.5 7 ±3.6 28 ±29 p=0.062 18 ±24 All values as mean with SD; IMT, intima-media thickness; PWV, pulse wave velocity; BSI, beta stiffness index; G cir, global cicumferential straion; P cir, posterior circurmferential strain; P rad, posterior radial strain

Uni and multivariate regression analysis of IMT, PWV, BSI1 and BSI 2s in predicting concurrent CAD Parameters Univariate analysis Multivariate analysis Odds ratio (95% CI) p-value Odds ratio (95% CI) p-value Carotid IMT 1.65 (1.21-2.24) 0.001 1.48 (1.08-2.04) 0.014 ba PWV 1.002 (1.001-1.004) 0.006 1.002 (1.000-1.004) 0.048 BSI 1 1.56 (1.14-2.15) 0.005 1.32 (0.93-1.88) 0.045 BSI 2 Global circumferential strain 1.065 (1.002-1.13) 0.04 1.04 (0.978-1.121) 0.18 Posterior circumferential strain 1.18 (1.05-1.33) 0.004 1.15 (1.01-1.31) 0.025 CI, confidence interval; IMT, intima-media thickness; ba PWV, brachio-ankle pulse wave velocity; BSI, beta stiffness index

Correlations of posterior circumferential strain derived BSI 2 with BSI 1, PWV and IMT r=0.49, p<0.001 r=0.40,p=0.001 r=0.36, p=0.001

Receiver operating characteristic curves of posterior circumferential strain derived BSI2, BSI 1, PWV and IMT in predicting concurrent CAD Parameters AUC (95%CI) Cut off value Sensitivity(%) Specificity(%) BSI 1 0.661 (0.55-0.79) 5.4 65 60 BSI 2 by posterior circumferential strain 0.70 (0.56-0.81) 7.25 74 61 ba PWV (m/s) 0.677 (0.56-0.81) 1.51 74 63 Carotid IMT (mm) 0.73 (0.63-0.83) 0.64 73 60

Summary Among CCA strain derived stiffness indices, only posterior circumferential strain derived stiffness index, BSI 2 was found to be independent determinant of concurrent CAD by multivariate analysis adjusted with age, DM, stroke, hyperlipidemia. Posterior circumferential strain derived BSI 2 showed significant association with CCA distensibility derived BSI 1 as well as carotid IMT and bapwv. With ROC curve analysis, area under the curve (AUC) of BSI 2 was found to be comparable to those of BSI 1, carotid IMT and bapwv in predicting concurrent coronary artery disease.

Conclusions Posterior circumferential strain derived BSI2 of CCA was found to be comparable to other conventional parameters for arterial stiffness in predicting concurrent coronary artery disease

Study limitations Cross sectional study Small population Selection bias

Thank you

Atherosclerosis Vs Arteriosclerosis Atherosclerosis Arteriosclerosis Anatomic location focal diffuse Vascular physiology artheroma elasticity, stiffness Vascular location Intima media Parameter carotid IMT PWV, central BP, augmentation index Nichols WW, O Rourke MF. McDonald s Blood flow in Arteries

Novel indicators of arterial stiffness and atherosclerosis Pulse wave velocity (PWV) Non-invasive, simple and robust Pressure dependent Inaccurate results in patients with metabolic syndrome, obesity and peripheral artery disease Arterial distensibility Non-invasive, direct measurement of arterial stiffness Angle dependent Limited precision of diameter measurement Carotid intima-media thickness (IMT) Non-invasive, simple Depending on the focal atherosclerosis Stephane Laurent, Expert consensus doucument on arterila stifness, European Heart Jounal 2006