High-risk Coronary Atherosclerotic Plaques Research Articles

Management of Coronary VulnerablePlaque With Medical Therapyor LocalPreventive Percutaneous CoronaryIntervention.

Acute coronary syndromes (ACS) often result from the rupture or erosion of high-risk coronary atherosclerotic plaques (ie, vulnerable plaques). Advances in intracoronary imaging such as intravascular ultrasound, optical coherence tomography, or near-infrared spectroscopy have improved the identification of vulnerable plaques, characterized by large plaque burden, small minimal luminal area, thin fibrous cap, and large lipid content. Although pharmacology, including lipid-lowering agents, and intensive risk-factor control are pivotal for management of vulnerable plaques and secondary prevention, recurrent events tend to accrue despite intensive pharmacotherapy. Therefore, it has been hypothesized that local preventive percutaneous coronary intervention may passivate these vulnerable plaques, preventing the occurrence of plaque-related ACS. However, solid evidence is lacking on its use for treatment of non-flow-limiting vulnerable plaques. As such, the optimal management of vulnerable plaques has not been established. Herein, we have reviewed the diagnosis and management of vulnerable plaques, focusing on systematic pharmacology and focal treatments.

Biomarkers for identification of high-risk coronary plaques in patients with suspected coronary artery disease

Abstract Background Patients with atherosclerotic plaques containing high-risk features have an increased likelihood of events and a worse prognosis. Whether elevated levels of biomarkers of ischemia e.g. TnI and inflammation e.g. high sensitive C-reactive protein (hsCRP) are associated with the presence of high-risk coronary atherosclerotic plaques (HRP) evaluated on coronary computed tomography angiography (CCTA) is not well described. Objectives To assess the association between 1) TnI and 2) hsCRP and quantified coronary plaque burden, luminal diameter stenosis and HRP in symptomatic patients with low/intermediate pre-test probability of obstructive coronary artery disease (CAD) referred to CCTA evaluation. Methods On enrolled patients (n=1,615), CCTA were analysed using a semiautomatic software for coronary artery plaque characterization. Patients with high (>6 ng/L) and low (<3 ng/L) TnI as well as high (>2 mg/L) and low (<1 mg/L) hsCRP were identified. Associations of high levels of TnI and hsCRP compared to low levels were investigated for the following: high plaque burden (defined as having total plaque volume above the 75th percentile on CCTA), presence of significant stenosis (defined as ≥50% luminal diameter stenosis on CCTA), and presence of HRP (defined as having a plaque with at least two risk features on CCTA). Results TnI and hsCRP were both positively correlated with total plaque burden (TnI rs=0.14, p<0.001; hsCRP rs=0.08, p<0.001). In multivariate logistic regression analyses, high TnI was when compared to low TnI associated with presence of stenosis (OR 1.43, 95% confidence interval (CI) 1.03-1.99, p=0.034), the presence of HRP (OR 1.79, 95% CI: 1.17– 2.74, p=0.008) and further the subtypes of HRP including low attenuation plaque (OR 1.93, 95% CI: 1.24–3.00, p=0.003) and positive remodelling (OR 1.51, 95% CI: 1.07–2.13, p=0.018). For high hsCRP levels, only the presence of stenosis and the HRP-subtype napkin ring sign correlated significantly. Conclusion In patients with suspected CAD TnI and hsCRP are associated with the presence of HRP features. These findings suggest that inflammatory and particularly ischemic biomarkers might improve early risk stratification and potentially also affect patient management.

Association of serum cystatin C level with coronary atherosclerotic plaque burden: a comprehensive analysis of observational studies and genetic study

Background and AimsEpidemiological studies show that high circulating cystatin C is associated with risk of cardiovascular disease (CVD), independent of creatinine-based renal function measurements. However, the relationship between serum cystatin C level and coronary atherosclerotic plaque burden is limited. We aimed to evaluate the relationship between circulating cystatin C and coronary atherosclerotic plaque burden.MethodsThis study was a cross-sectional study based on China community population. Measurements of plaque burden were based on the segment-involvement score (SIS) and segment stenosis score (SSS), which derived from the Coronary Artery Tree Model Depicting Coronary Artery Plaque Scores. Logistic regression model was used to demonstrate the association between cystatin C level and coronary artery plaque burden. Mendelian randomization (MR) analyses were conducted to assess the causal effect of cystatin C level on coronary atherosclerosis risk.ResultsA total of 3,043 objects were included in the present study. The odds risks (OR) of severe plaque burden in the highest serum cystatin C levels (OR: 2.50; Cl:1.59–3.91; P < 0.001) and medium-level cystatin C levels (OR: 1.86; 95% Cl: 1.21–2.88; P = 0.005) were significantly higher after fulled adjusted confounders compared with the lowest levels of serum cystatin C by SSS. The MR analysis showed that genetic predicted cystatin C levels was associated with an increased risk of coronary atherosclerosis (OR, 1.004; 95% CI, 1.002–1.006, P < 0.001) .ConclusionElevated serum cystatin C levels were associated with coronary atherosclerotic plaque burden. Cystatin C levels had a causal effect on an increased risk of coronary atherosclerosis at the genetic level.What is already known on this topic?Coronary artery disease is currently the most common cardiovascular disease and the leading global cause of mortality. Previous studies reported that higher serum cystatin C levels were associated with an increased risk for future cardiovascular events, independent of the normal creatinine levels or estimated glomerular filtration rate (eGFR) values. The presence of high-risk coronary atherosclerotic plaque burden is associated with increased risk of cardiovascular events. However, the association between serum cystatin C and coronary atherosclerotic plaque burden is not very clear.What this study adds?Our study demonstrated that the elevated serum cystatin C levels were associated with coronary atherosclerotic plaque burden. In addition, we found that serum cystatin C levels had a causal effect on an increased risk of coronary atherosclerosis at the genetic level.How this study might affect research, practice or policy?Current research finds that serum cystatin C levels were associated with coronary atherosclerosis. The metabolic pathway of cystatin C could be a target for new therapies against CAD.

Hepatic fat as a novel marker for high-risk coronary atherosclerotic plaque features in familial hypercholesterolaemia

Background & aimsHepatic steatosis has been associated with increased risk of coronary artery disease. Individuals with familial hypercholesterolaemia have accelerated but variable progression of coronary artery disease. We investigated whether hepatic steatosis is associated with novel coronary atherosclerosis biomarkers in adults with heterozygous familial hypercholesterolaemia, using comprehensive coronary computed tomographic angiography. MethodsWe conducted a cross-sectional study of 213 asymptomatic patients with familial hypercholesterolaemia (median age 54.0 years, 59 % female) who underwent coronary computed tomographic angiography for cardiovascular risk assessment in an outpatient clinic. High-risk plaque features, plaque volume and pericoronary adipose tissue attenuation were assessed. From concurrently captured upper abdominal images, severity of hepatic steatosis was computed, as liver minus spleen computed tomography attenuation and stratified into quartiles. ResultsOf 213 familial hypercholesterolaemia patients, 59 % had coronary artery calcium, 36 % obstructive coronary artery disease (≥50 % stenosis) and 77 % high-risk plaque features. Increasing hepatic steatosis was associated with higher calcium scores, more high-risk plaque features and presence of obstructive coronary artery disease. Hepatic steatosis was associated with the presence of high-risk plaque features (OR: 1.48; 95 % CI: 1.09–2.00; p = 0.01), particularly in the proximal coronary segments (OR: 1.52; 95 % CI: 1.18–1.96; p = 0.001). Associations persisted on multivariable logistic regression analysis adjusting for cardiometabolic factors, obstructive coronary artery disease and calcium score. Hepatic steatosis was associated with higher plaque volumes (Q4: 499 mm3 vs Q1: 414 mm3, p = 0.02), involving mainly low attenuation and noncalcified plaques (both p = 0.03). No differences in pericoronary adipose tissue attenuation were observed. ConclusionsHepatic steatosis is associated with multiple indices of advanced coronary atherosclerosis in familial hypercholesterolaemia patients, particularly high-risk plaque features, independent of conventional cardiovascular risk factors and markers. This may involve specific mechanisms related to hepatic steatosis.Clinical trial number: N/A.

170Lipoprotein subclasses associated with high-risk coronary atherosclerotic plaque: insights from the PROMISE clinical trial

Abstract Background Greater than half of major adverse cardiovascular events (MACE) occur in individuals with non-obstructive coronary artery disease (CAD) and may be related to the presence of high-risk coronary atherosclerotic plaque (HRP). HRP can be detected by coronary computed tomographic angiography (CTA) and is associated with increased MACE risk. Biomarkers associated with HRP may therefore aid in risk stratification in individuals with chest pain and provide insight into the biology of HRP. Purpose To determine whether nuclear magnetic resonance (NMR)-measured lipoprotein particles are associated with HRP independent of risk factors. Methods This study included 1755 stable symptomatic outpatients enrolled in the PROMISE trial who had coronary CTA performed. Thirty-seven lipoprotein particle parameters were measured in plasma using NMR. Principal components analysis was used to reduce the number of correlated lipoproteins into a smaller number of uncorrelated factors. HRP cases (N=277) were defined as presence of HRP features (positive remodeling, low CT attenuation or napkin-ring sign) with or without obstructive CAD; controls had no HRP and no obstructive CAD (N=1478). Multivariable logistic regression models adjusting for age, sex, diabetes, hypertension, BMI, smoking status and statin use were used to test for association of lipoprotein factors with HRP case/control status; lipoproteins loaded within significant factors (p&lt;0.05) were tested individually. Finally, because event rates in PROMISE were too low, we used a separate study (CATHGEN, a study of individuals undergoing coronary angiography; N=8707) to test for association of lipoproteins with MACE using multivariable Cox proportional hazard models. Results HRP cases were less likely to be female than controls (36.8% vs. 56.6%) and were more likely to have diabetes (23.5% vs 19.6%), but were of similar age (60.1 vs 60.4 years [SD±8]) and with similar statin use (45.2% vs 44.4%). In multivariable models, two lipoprotein factors were associated with HRP: an HDL factor (OR 1.29 [95% CI, 1.10–1.52], p=0.002) and a triglyceride (TG) factor (OR 1.19 [1.03–1.36], p=0.01). Within these two factors, H6P (a large HDL subclass; OR 0.67 [0.54–0.82], p&lt;0.001), HDL size (OR 0.78 [0.66–0.92], p=0.003) and small TG-rich lipoproteins (OR 1.22 [1.07–1.39], p=0.002) were associated with HRP. H6P (HR 1.1 [1.07–1.13], p&lt;0.0001) and HDL size (HR 1.28 [1.24–1.32], p&lt;0.0001) were also associated with time to death or MI in CATHGEN, but in the opposite direction. Conclusions In a cohort of low-risk patients from the PROMISE trial, large HDL and small TG particles were associated with CTA-defined HRP independent of risk factors. Large HDL particles were also associated with incident MACE in a separate high-risk cohort. The discordant direction of association of HDL subclasses with HRP and MACE is likely due to underlying HDL biology and requires further study. Acknowledgement/Funding The PROMISE trial was funded by the National Heart, Lung, and Blood Institute (grants R01HL098237, R01HL098236, R01HL98305, and R01HL098235)

Dual Antiplatelet Therapy To Inhibit Myocardial Injury In Patients With High-risk Coronary Artery Plaque: A Randomised Controlled Trial

Introduction: High-risk coronary atherosclerotic plaque is associated with higher plasma troponin concentrations suggesting ongoing myocardial injury that may be a target for dual antiplatelet therapy. To determine whether ticagrelor reduces high-sensitivity troponin I concentrations in patients with established coronary artery disease and high-risk coronary plaque.

High-Risk Coronary Atherosclerotic Plaque Assessment by Coronary Computed Tomography Angiography—Should We Use It?

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Use of High-Risk Coronary Atherosclerotic Plaque Detection for Risk Stratification of Patients With Stable Chest Pain

Coronary computed tomographic angiography (coronary CTA) can characterize coronary artery disease, including high-risk plaque. A noninvasive method of identifying high-risk plaque before major adverse cardiovascular events (MACE) could provide practice-changing optimizations in coronary artery disease care. To determine whether high-risk plaque detected by coronary CTA was associated with incident MACE independently of significant stenosis (SS) and cardiovascular risk factors. This prespecified nested observational cohort study was part of the Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE) trial. All stable, symptomatic outpatients in this trial who required noninvasive cardiovascular testing and received coronary CTA were included and followed up for a median of 25 months. Core laboratory assessment of coronary CTA for SS and high-risk plaque (eg, positive remodeling, low computed tomographic attenuation, or napkin-ring sign). The primary end point was an adjudicated composite of MACE (defined as death, myocardial infarction, or unstable angina). The study included 4415 patients, of whom 2296 (52%) were women, with a mean age of 60.5 years, a median atherosclerotic cardiovascular disease (ASCVD) risk score of 11, and a MACE rate of 3% (131 events). A total of 676 patients (15.3%) had high-risk plaques, and 276 (6.3%) had SS. The presence of high-risk plaque was associated with a higher MACE rate (6.4% vs 2.4%; hazard ratio, 2.73; 95% CI, 1.89-3.93). This association persisted after adjustment for ASCVD risk score and SS (adjusted hazard ratio [aHR], 1.72; 95% CI, 1.13-2.62). Adding high-risk plaque to the ASCVD risk score and SS assessment led to a significant continuous net reclassification improvement (0.34; 95% CI, 0.02-0.51). Presence of high-risk plaque increased MACE risk among patients with nonobstructive coronary artery disease relative to patients without high-risk plaque (aHR, 4.31 vs 2.64; 95% CI, 2.25-8.26 vs 1.49-4.69). There were no significant differences in MACE in patients with SS and high-risk plaque as opposed to those with SS but not high-risk plaque (aHR, 8.68 vs. 9.31; 95% CI, 4.25-17.73 vs 4.21-20.61). High-risk plaque was a stronger predictor of MACE in women (aHR, 2.41; 95% CI, 1.25-4.64) vs men (aHR, 1.40; 95% CI, 0.81-2.39) and younger patients (aHR, 2.33; 95% CI, 1.20-4.51) vs older ones (aHR, 1.36; 95% CI, 0.77-2.39). High-risk plaque found by coronary CTA was associated with a future MACE in a large US population of outpatients with stable chest pain. High-risk plaque may be an additional risk stratification tool, especially in patients with nonobstructive coronary artery disease, younger patients, and women. The importance of findings is limited by low absolute MACE rates and low positive predictive value of high-risk plaque. clinicaltrials.gov Indentifier: NCT01174550.

P534Radiomic features of high risk coronary atherosclerotic plaques in coronary CT angiography

P534Radiomic features of high risk coronary atherosclerotic plaques in coronary CT angiography

High-risk carotid plaques identified by CT-angiogram can predict acute myocardial infarction.

Prior studies identified the incremental value of non-invasive imaging by CT-angiogram (CTA) to detect high-risk coronary atherosclerotic plaques. Due to their superficial locations, larger calibers and motion-free imaging, the carotid arteries provide the best anatomic access for the non-invasive characterization of atherosclerotic plaques. We aim to assess the ability of predicting obstructive coronary artery disease (CAD) or acute myocardial infarction (MI) based on high-risk carotid plaque features identified by CTA. We retrospectively examined carotid CTAs of 492 patients that presented with acute stroke to characterize the atherosclerotic plaques of the carotid arteries and examined development of acute MI and obstructive CAD within 12-months. Carotid lesions were defined in terms of calcifications (large or speckled), presence of low-attenuation plaques, positive remodeling, and presence of napkin ring sign. Adjusted relative risks were calculated for each plaque features. Patients with speckled (<3mm) calcifications and/or larger calcifications on CTA had a higher risk of developing an MI and/or obstructive CAD within 1 year compared to patients without (adjusted RR of 7.51, 95%CI 1.26-73.42, P = 0.001). Patients with low-attenuation plaques on CTA had a higher risk of developing an MI and/or obstructive CAD within 1 year than patients without (adjusted RR of 2.73, 95%CI 1.19-8.50, P = 0.021). Presence of carotid calcifications and low-attenuation plaques also portended higher sensitivity (100 and 79.17%, respectively) for the development of acute MI. Presence of carotid calcifications and low-attenuation plaques can predict the risk of developing acute MI and/or obstructive CAD within 12-months. Given their high sensitivity, their absence can reliably exclude 12-month events.

Increased arterial inflammation relates to high-risk coronary plaque morphology in HIV-infected patients.

Mechanisms predisposing HIV-infected patients to increased cardiovascular disease (CVD) risk remain unclear. To determine the interrelationship between arterial inflammation and high-risk coronary plaque morphology in HIV-infected patients with subclinical coronary atherosclerosis. Forty-one HIV-infected patients on stable antiretroviral therapy without known CVD but with atherosclerotic plaque on coronary CT angiography were evaluated with F-FDG-PET. Patients were stratified into 2 groups based on relative degree of arterial inflammation [aortic target-to-background ratio (TBR)]. High-risk coronary atherosclerotic plaque morphology features were compared between groups. HIV-infected patients with higher and lower TBRs were similar with respect to traditional CVD risk parameters. Among HIV-infected patients with higher TBR, an increased percentage of patients demonstrated at least 1 low-attenuation coronary atherosclerotic plaque (40% vs. 10%, P = 0.02) and at least 1 coronary atherosclerotic plaque with both low attenuation and positive remodeling (35% vs. 10%, P = 0.04). Moreover, in the higher TBR group, both the number of low-attenuation plaques per patient (P = 0.02) and the number of vulnerability features in the most vulnerable plaque (P = 0.02) were increased. TBR grouping remained significantly related to the number of low-attenuation plaques/subject (β = 0.35, P = 0.004), controlling for age, gender, low-density lipoprotein, duration of HIV, and CD4. These data demonstrate a relationship between arterial inflammation on F-FDG-PET and high-risk coronary atherosclerotic plaque features among HIV-infected patients with subclinical coronary atherosclerosis. Further studies are needed to determine whether arterial inflammation and related high-risk coronary morphology increase the risk of clinical CVD events in the HIV population.

Molecular imaging of coronary atherosclerosis; predictive of an acute myocardial infarction?

Coronary atherosclerosis is a leading cause of cardiovascular morbidity and mortality worldwide. Plaque complications occur most commonly from plaque rupture, and also from plaque erosion and calcified nodule formation. Over the past years, advanced structural, metabolic and molecular imaging technologies have emerged and offer new windows into atherosclerosis pathophysiology [1–4]. Molecular imaging complements traditional structural plaque imaging through the use of targeted probes that identify specific molecules and/or biological processes in vivo [5]. Preclinical atherosclerosis molecular imaging has successfully identified nearly all established high-risk plaque characteristics including inflammation, thrombosis, neo-vessel formation, apoptosis, and haemorrhage. However, clinical translation of molecular imaging has been slow compared with the rapid growth within the field. Currently, clinical atherosclerosis molecular imaging is dominated by non-invasive PET metabolism/inflammation plaque imaging with fluorine 18 (18F)-fluorodeoxyglucose (FDG). For the past two decades, 18F FDG has been the only fluorine-18 radioligand approved by the US Food and Drug Administration (FDA) for PET imaging. Coronary FDG PET is challenging, in part owing to the small size of coronary vessels and cardiac motion artefacts, but also because of the intense FDG uptake of the adjacent highly metabolic myocardium that obscures the coronary FDG signal. However, with dietary myocardial suppression protocols, detection of FDG PET signal in the left main and proximal coronary artery beds is sometimes achievable. Recently, non-invasive coronary FDG PET activity has been investigated in the stented culprit lesions of 20 subjects with acute coronary syndromes (ACS) versus seven non-ACS subjects within 1 week of stent placement [6]. Using a predetermined FDG target to background ratio of 2.0 or greater to identify FDG-positive lesions, the ACS patients correlated positively with elevated stent FDG signal. However, coronary FDG signal was interpretable in only 50 % of ACS patients, implying the need for further improvements in coronary FDG PET. Apart from 18F FDG coronary imaging, clinically available approaches such as sodium 18F-fluoride (NaF) for PET are emerging. Coronary calcification is a hallmark of advanced atheroma that can be detected with non-invasive NaF PET, which has been used for the past 3 decades to detect cancer bone metastases. As opposed to FDG, background myocardial uptake of NaF is negligible, and therefore NaF can determine coronary osteogenic activity. In a study by Dweck et al. from the University of Edinburgh [7], NaF PET molecular imaging identified sites of active coronary calcification non-invasively by PET and may be a new therapeutic target. The NaF signal was elevated in proportion to coronary CT calcium scores in 119 subjects, except in those with the highest calcium scores that may represent end-stage calcified plaques. From the same research group, Joshi et al. [8] recently (Lancet November 2013) studied coronary plaque imaging using two different radioactive tracers: 18F-NaF and 18F-FDG. The Scottish study included 40 patients with acute myocardial infarction (AMI) and 40 patients with stable angina. All patients underwent PET-CT, invasive coronary angiography, CT coronary angiography, and CT calcium scoring. Among the 40 patients with AMI, 18F-NaF PET uptake was 34 % higher in the culprit ruptured plaque compared with non-culprit plaques. Nearly all patients (93 %) had increased 18F-NaF uptake in the culprit plaque. With 18F-FDG, however, no differences in uptake between culprit and non-culprit plaques were observed. Among the 40 patients with stable angina, 45 % had plaques with increased 18F-NaF uptake. These plaques were mostly non-obstructive at coronary angiography and contained more high-risk features on intravascular ultrasound compared with plaques without tracer uptake. Consequently, 18F-NaF PET may become an effective tool for predicting an AMI, which would have a great impact for patients with coronary atherosclerosis. Early detection of the atherosclerotic ‘danger zones’ could include immediate instalment of drugs such as statins or aspirin, drastic changes in lifestyle and even inserting stents into the affected coronary artery. The use of 18F-NaF PET-CT offers the first non-invasive imaging method to identify and localise ruptured and high-risk coronary plaques. A next step is to show that increased 18F-NaF predicts future adverse clinical events. Further studies are therefore needed to evaluate whether the detection of risky plaques before rather than after an AMI has the potential to save lives. To summarise, the addition of newer molecular imaging tools such as NaF PET-CT will continue to strengthen our understanding of the in vivo biology of high-risk plaques [9, 10]. They are increasingly being translated into clinical use, and in combination with structural imaging they provide more comprehensive information to build risk-prediction tools. Ongoing efforts to improve non-invasive coronary imaging strategies must be pursued. Overall, with continued advances in molecular and structural atherosclerosis imaging, high-risk coronary atherosclerotic plaques will be brightened as never before. The recent study in the Lancet at least suggests that molecular imaging using PET-CT scanning may provide an answer in identifying ‘ticking time bomb’ patients at risk of an AMI.

18F-fluoride positron emission tomography for identification of ruptured and high-risk coronary atherosclerotic plaques: a prospective clinical trial

The use of non-invasive imaging to identify ruptured or high-risk coronary atherosclerotic plaques would represent a major clinical advance for prevention and treatment of coronary artery disease. We used combined PET and CT to identify ruptured and high-risk atherosclerotic plaques using the radioactive tracers (18)F-sodium fluoride ((18)F-NaF) and (18)F-fluorodeoxyglucose ((18)F-FDG). In this prospective clinical trial, patients with myocardial infarction (n=40) and stable angina (n=40) underwent (18)F-NaF and (18)F-FDG PET-CT, and invasive coronary angiography. (18)F-NaF uptake was compared with histology in carotid endarterectomy specimens from patients with symptomatic carotid disease, and with intravascular ultrasound in patients with stable angina. The primary endpoint was the comparison of (18)F-fluoride tissue-to-background ratios of culprit and non-culprit coronary plaques of patients with acute myocardial infarction. In 37 (93%) patients with myocardial infarction, the highest coronary (18)F-NaF uptake was seen in the culprit plaque (median maximum tissue-to-background ratio: culprit 1·66 [IQR 1·40-2·25] vs highest non-culprit 1·24 [1·06-1·38], p<0·0001). By contrast, coronary (18)F-FDG uptake was commonly obscured by myocardial uptake and where discernible, there were no differences between culprit and non-culprit plaques (1·71 [1·40-2·13] vs 1·58 [1·28-2·01], p=0·34). Marked (18)F-NaF uptake occurred at the site of all carotid plaque ruptures and was associated with histological evidence of active calcification, macrophage infiltration, apoptosis, and necrosis. 18 (45%) patients with stable angina had plaques with focal (18)F-NaF uptake (maximum tissue-to-background ratio 1·90 [IQR 1·61-2·17]) that were associated with more high-risk features on intravascular ultrasound than those without uptake: positive remodelling (remodelling index 1·12 [1·09-1·19] vs 1·01 [0·94-1·06]; p=0·0004), microcalcification (73% vs 21%, p=0·002), and necrotic core (25% [21-29] vs 18% [14-22], p=0·001). (18)F-NaF PET-CT is the first non-invasive imaging method to identify and localise ruptured and high-risk coronary plaque. Future studies are needed to establish whether this method can improve the management and treatment of patients with coronary artery disease. Chief Scientist Office Scotland and British Heart Foundation.

Attenuation of inflammation and expansive remodeling by Valsartan alone or in combination with Simvastatin in high-risk coronary atherosclerotic plaques

Aims We investigated the role of Valsartan (V) alone or in combination with Simvastatin (S) on coronary atherosclerosis and vascular remodeling, and tested the hypothesis that V or V/S attenuate the pro-inflammatory effect of low endothelial shear stress (ESS). Methods Twenty-four diabetic, hyperlipidemic swine were allocated into Early ( n = 12) and Late ( n = 12) groups. In each group animals were treated with Placebo ( n = 4), V ( n = 4) and V/S ( n = 4) and followed for 8 weeks in the Early group and 30 weeks in the Late group. Blood pressure, serum cholesterol and glucose were similar across the treatment subgroups. ESS was calculated in plaque-free subsegments of interest ( n = 109) in the Late group at week 23. Coronary arteries of this group were harvested at week 30, and the subsegments of interest were identified, and analyzed histopathologically. Results V alone or with S reduced the severity of inflammation in high-risk plaques. Both regimens attenuated the severity of enzymatic degradation of the arterial wall, reducing the severity of expansive remodeling. V alone or with S attenuated the pro-inflammatory effect of low ESS. Conclusions V alone or with S exerts a beneficial effect of reducing and stabilizing high-risk plaque characteristics independent of a blood pressure- and lipid-lowering effect.

Prediction of the Localization of High-Risk Coronary Atherosclerotic Plaques on the Basis of Low Endothelial Shear Stress

Low endothelial shear stress (ESS) promotes the development of atherosclerosis; however, its role in the progression of atherosclerotic plaques and evolution to inflamed high-risk plaques has not been studied. Our hypothesis was that the lowest values of ESS are responsible for the development of high-risk coronary atherosclerotic plaques associated with excessive expansive remodeling. Twenty-four swine, treated with streptozotocin to induce diabetes and fed a high-fat diet, were allocated into early (n=12) and late (n=12) atherosclerosis groups. Intima-media thickness was assessed by intravascular ultrasound in the coronary arteries at weeks 4 and 8 in the early group and weeks 23 and 30 in the late group. Plaques started to develop after week 8, leading to marked heterogeneity in plaque severity at week 30. ESS was calculated in plaque-free subsegments of interest (n=142) in the late group at week 23. Coronary arteries (n=31) of this group were harvested at week 30, and the subsegments of interest were identified and analyzed histopathologically. Low ESS was an independent predictor of the development of high-risk plaques, characterized by intense lipid accumulation, inflammation, thin fibrous cap, severe internal elastic lamina degradation, and excessive expansive remodeling. The severity of high-risk plaque characteristics at week 30 was significantly correlated with the magnitude of low ESS at week 23. The magnitude of low ESS determines the complexity and heterogeneity of atherosclerotic lesions and predicts the development of high-risk plaque.