Assessment of carotid plaque neovascularization using quantitative analysis of contrast-enhanced ultrasound imaging is useful for risk stratification in patients with coronary artery disease.

BACKGROUND: Contrast-enhanced ultrasound (CEUS) of the carotid artery is a potential technique for imaging plaque neovascularization, a feature of unstable atherosclerotic plaques. This study examined whether assessment of intra-plaque neovascularization of the carotid artery using CEUS provides prognostic information in patients with coronary artery disease (CAD). METHODS: A total of 206 patients with stable CAD underwent a CEUS examination of the carotid artery and were followed up prospectively for <38 months or until a cardiac event (cardiac death, non-fatal myocardial infarction (MI), unstable angina pectoris (uAP) requiring unplanned coronary revascularization, or heart failure requiring hospitalization). The degree of contrast signals measured within the carotid plaque was quantified by calculating the mean gray scale level within the region of interest of the carotid plaque, expressed as plaque enhanced intensity. RESULTS: During the follow-up period, 31 events occurred (2 cardiac deaths, 7 non-fatal MIs, 16 uAP, and 6 heart failure). Multivariate Cox proportional hazard analysis showed that plaque enhanced intensity was a significant predictor of cardiac events independent of traditional risk factors (HR, 1.13; 95% CI, 1.05-1.21; p<0.001). The addition of the plaque enhanced intensity to traditional risk factors resulted in net reclassification improvement (NRI) and integrated discrimination improvement (IDI) (NRI 0.62, p=0.001; and IDI 0.106, p=0.002). CONCLUSIONS: The assessment of carotid plaque neovascularization using quantitative analysis of CEUS may be useful for risk stratification in patients with CAD.

Combined assessment of flow-mediated dilation of the brachial artery and brachial-ankle pulse wave velocity improves the prediction of future coronary events in patients with chronic coronary artery disease.

BACKGROUND AND PURPOSE: Measurement of either flow-mediated endothelium-dependent dilatation (FMD) of the brachial artery, brachial-ankle pulse wave velocity (baPWV), or intima-media thickness (IMT) of the carotid artery is useful for risk assessment of future cardiovascular events. This study examined whether combination of these vascular parameters may have an additive effect on the ability of traditional risk factors to predict coronary events in patients with chronic coronary artery disease (CAD). METHODS: Patients (n=923) with stable CAD had measurements of FMD, baPWV, and maximum IMT (maxIMT), and were prospectively followed up for <8.5 years or until a coronary event - cardiac death, non-fatal myocardial infarction (MI) or unstable angina pectoris (uAP) requiring unplanned coronary revascularization. RESULTS: During the follow-up period, 116 events occurred (29 cardiac deaths, 46 non-fatal MIs and 41 cases of uAP). A multivariate Cox proportional hazards analysis showed that FMD (HR 0.50, 95% CI 0.38-0.66) and baPWV (HR 1.52, 95% CI 1.27-1.82) but not maxIMT were significant predictors of coronary events. Based on the concordance statistics, the predictive value of traditional risk factors [area under the receiver operating characteristic curve (AUC), 0.67] was increased more by the addition of FMD and baPWV combined (AUC, 0.75) compared with the addition of either maxIMT, FMD, or baPWV alone, or the combination of maxIMT and FMD or maxIMT and baPWV (AUC, 0.67, 0.71, 0.71, 0.71 and 0.71, respectively). CONCLUSIONS: The combined addition of FMD and baPWV to the risk assessment algorithms may be useful for risk stratification of chronic CAD patients.

Echolucency of carotid plaque is useful for assessment of residual cardiovascular risk in patients with chronic coronary artery disease who achieve LDL-C goals on statin therapy.

BACKGROUND: Ultrasound assessment of either intima-media thickness (IMT) or plaque echolucency of the carotid artery provides prognostic information on coronary events. This study examined the hypothesis that IMT and plaque echolucency of the carotid artery may remain useful for prediction of coronary events in patients with coronary artery disease (CAD) after achievement of LDL-C goals on statin therapy. METHODS AND RESULTS: Ultrasound assessment of carotid maximum IMT (maxIMT) and plaque echolucency with integrated backscatter (IBS) analysis was performed in 357 chronic CAD patients with LDL-C <100mg/dl on statin therapy. All patients were prospectively followed up until the occurrence of one of the following coronary events: cardiac death, non-fatal myocardial infarction, or unstable angina pectoris requiring unplanned revascularization. During a mean follow-up of 32±18 months, 33 coronary events occurred. On multivariate Cox proportional hazards analysis, plaque echolucency (lower IBS value) was a significant predictor of coronary events (HR, 0.44; 95% CI: 0.29-0.73; P=0.009), whereas maxIMT was not. The addition of plaque echolucency to traditional risk factors improved net reclassification improvement (NRI) and integrated discrimination improvement (IDI; NRI, 0.59; P=0.0013; and IDI, 0.075; P=0.0009). CONCLUSIONS: Measurement of echolucency of the carotid artery was useful for assessment of residual coronary risk in CAD patients after LDL-C goal attainment on statin treatment.

Ultrasound assessment of brachial endothelial vasomotor function in addition to carotid plaque echolucency for predicting cardiovascular events in patients with coronary artery disease.

BACKGROUND: Single assessment of either flow-mediated vasodilatation of the brachial artery (FMD) or carotid plaque echolucency provides prognostic information for both cerebrovascular and coronary events. OBJECTIVES: This study tested the hypothesis that combined assessment using carotid plaque echolucency and FMD may have an additive effect when predicting cardiovascular events in patients with coronary artery disease (CAD). METHODS: Ultrasound assessment of carotid plaque echolucency with integrated backscatter (IBS) analysis (calibrated IBS=intima-media IBS value-adventitia IBS) and FMD was performed in 547 consecutive patients with CAD. All the study patients were followed up prospectively for a period of ≤ 60 months until the occurrence of one of the following cardiovascular events: cardiac death, non-fatal myocardial infarction, unstable angina requiring coronary revascularization, or ischemic stroke. RESULTS: During a mean follow-up period of 52 ± 10 months, 69 cardiovascular events occurred. A multivariate Cox proportional hazard model after 1000 bootstrapped resampling demonstrated that calibrated IBS and FMD were significant, independent predictors of future cardiovascular events after adjustment for known risk factors (calibrated IBS, HR 0.88, 95% CI 0.83-0.93; FMD, HR 0.76, 95% CI 0.68-0.85). The c-statistics, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) analyses showed that the combination of calibrated IBS and FMD values had a greater incremental effect on the predictive value of known risk factors for cardiovascular events. CONCLUSIONS: Combined assessment of brachial endothelial function and carotid plaque echolucency is an independent predictor of cardiovascular events and improves risk prediction when added to known risks.

Predictive value of serial assessment of endothelial function in chronic heart failure.

BACKGROUND: It remains undefined whether reversibility of endothelial dysfunction after optimized therapies for heart failure (HF) provides prognostic information in patients with HF. This study examined whether changes in endothelial vasomotor function after therapies for HF may predict future outcomes in patients with stable HF. METHODS: This study included 245 patients with stable chronic ischemic HF and an impaired flow-mediated dilation (FMD) of the brachial artery (FMD <5.5%). Measurement of FMD was repeated after 6 months for individualized and optimized therapy for HF and atherosclerotic risk factors. Patients were followed for 36 months or until the occurrence of cardiac death or hospitalization with decompensated HF. RESULTS: FMD was persistently impaired (<5.5%) in 130 (53%) patients after 6 months of the optimized therapy, whereas it improved (FMD ≥5.5%) in the remaining 115 (47%) patients. During follow-up, an event occurred in 26 (20%) patients with persistently impaired FMD and in 7 (6%) patients with improved FMD (p<0.01). Multivariate Cox hazards analysis showed that persistent impairment of FMD was an independent predictor of cardiac events (hazard ratio 3.0, 95% CI 1.3-6.9, p=0.013). Persistently impaired FMD had a significantly incremental effect on the predictability of brain natriuretic peptide levels for cardiac events. Baseline FMD before the therapy for HF and atherosclerotic risk factors had no significant prognostic information. CONCLUSIONS: Persistent endothelial vasomotor dysfunction despite therapies for HF and atherosclerotic risk factors was a predictor of cardiac events in patients with chronic ischemic HF.

Assessment of carotid plaque echolucency in addition to plaque size increases the predictive value of carotid ultrasound for coronary events in patients with coronary artery disease and mild carotid atherosclerosis.

OBJECTIVES: This study examined whether combined ultrasound assessment of plaque size and echolucency in the carotid artery had an additive effect for predicting coronary events in patients with coronary artery disease (CAD). Ultrasound assessment of either plaque size or echolucency of carotid artery provides prognostic information on coronary events. Combined assessment of plaque size and echolucency of carotid artery has the advantage of obtaining both structural and compositional information in the same artery in a single session. METHODS AND RESULTS: Ultrasound assessment of carotid plaque maximum intima-media thickness (plaque-IMTmax) and echolucency with integrated backscatter analysis was performed in 413 patients with CAD and carotid plaque. All study patients were followed up prospectively for 54 months or until the occurrence of a coronary event. During the follow-up period, 49 coronary events occurred including 2 cardiac deaths, 10 non-fatal acute myocardial infarctions and 37 recurrent and refractory unstable angina. Multivariate Cox hazards analysis showed plaque-IMTmax alone (HR 2.01, 95%CI 1.30-3.10), plaque echogenicity alone (HR 0.86, 95%CI 0.80-0.91) and combination of high plaque-IMTmax and low echogenicity on categorical data (HR 2.56, 95%CI 1.39-4.74) were independent predictors of coronary events. Analysis using c-statistics showed that plaque-IMTmax and plaque echolucency in combination had a significant incremental effect on the predictive value of the conventional risk factors for coronary events. CONCLUSIONS: Combined ultrasound assessment of carotid plaque size and echolucency has an additive value for prediction of coronary events. Further studies need to evaluate the clinical utility of both ultrasound measurements for risk stratification in CAD.

Measurement of the platelet retention rate in a column of collagen-coated beads is useful for the assessment of efficacy of antiplatelet therapy.

INTRODUCTION: A simple, validated method to measure platelet function is unavailable for bedside use. Measurement of platelet retention rate using a column of collagen-coated beads and whole blood is a new, simple assay that reflects platelet aggregation. This study was aimed to examine the utility of this assay to assess efficacy of antiplatelet drug therapy. METHODS: Citrated whole blood (1.5 ml) in a syringe was passed through a polyvinyl tube packed with collagen-coated beads for 40 seconds using a syringe pump. Platelet retention rate in the column was calculated from platelet counts in blood before and after passage. An increase in the retention rate reflects an increase in platelet activity. This new platelet retention assay and the traditional optical aggregometry assay were performed in 331 patients with stable coronary artery disease (CAD). RESULTS: The retention rate was significantly reduced in patients taking dual antiplatelet therapy (aspirin plus clopidogrel or ticlopidine) compared with aspirin alone. There was a significant linear correlation between the platelet retention rate and platelet aggregability measured by the traditional method (r=0.44, p<0.001). In multivariate Cox proportional hazards analysis, higher platelet retention rate was an independent predictor of future cardiovascular events in patients on dual antiplatelet therapy (hazard ratio 3.9, 95% CI 1.6 to 9.5, p=0.003). CONCLUSIONS: Measurement of the platelet retention rate in a column of collagen-coated beads may be useful for monitoring the efficacy of antiplatelet drug therapy in patients with CAD.