Carotid Plaque Inflammation Research Articles

Assessment of atherosclerotic plaque activity in patients with sleep apnea using hybrid positron emission tomography/magnetic resonance imaging (PET/MRI): a feasibility study

Evidence suggests that the inflammatory state of an atherosclerotic plaque is important in predicting future risk of plaque rupture. This study aims to investigate the feasibility of measuring plaque inflammation in patients with obstructive sleep apnea (OSA) utilizing advanced vascular imaging-hybrid positron-emission tomography/magnetic resonance imaging (PET/MRI) with fluorodeoxyglucose (FDG) tracer-before and after continuous positive airway pressure (CPAP). Patients with newly diagnosed moderate to severe OSA underwent baseline PET/MRI for assessment of vascular inflammation of the carotid arteries and thoracic aorta prior to initiation of CPAP. Those adherent to CPAP returned for repeat imaging after 3-6months of CPAP use. Atherosclerotic plaque activity, as measured by arterial wall FDG uptake, was calculated using target-to-background ratios (TBR) before and after CPAP. Five patients were recruited as part of a focused project. Mean age was 52years (80% male), and mean apnea-hypopnea index (AHI) was 33. Three patients were objectively adherent with CPAP. In the pre-CPAP phase, all patients had focal FDG uptake in the carotid arteries and aorta. After CPAP, there was an average reduction in TBR of 5.5% (TBRmean) and 6.2% (TBRmax) in carotid and aortic plaque inflammation, similar in magnitude to the reduction observed with statin therapy alone in non-OSA patients (previously reported by others). We demonstrate the feasibility of using hybrid PET/MRI to assess atherosclerotic plaque inflammation in patients with OSA before and after CPAP. Use of the vascular PET/MRI platform in patients with OSA may provide better insight into the role of OSA and its treatment in reducing atherosclerotic inflammation.

Cadmium, Carotid Atherosclerosis, and Incidence of Ischemic Stroke.

BackgroundExposure to cadmium has been associated with carotid plaques, inflammation in carotid plaques, and increased risk of ischemic stroke. This study examined the separate and interacting effects of blood cadmium levels and carotid plaques on the risk of incident ischemic stroke.Methods and ResultsCadmium levels were measured in 4156 subjects (39.2% men; mean±SD age 57.3±5.9 years) without history of stroke, from the Malmö Diet and Cancer cohort. The right carotid artery was examined using B‐mode ultrasound examination at baseline. Incidence of ischemic stroke was monitored over a mean follow‐up of 16.7 years. Carotid plaque was present in 34.5% of participants. Cadmium was significantly higher in subjects with plaque (mean±SD: 0.53±0.58 μg/L versus 0.42±0.49 μg/L; P<0.001). A total of 221 subjects had ischemic stroke during the follow‐up. Incidence of ischemic stroke was associated both with carotid plaque (hazard ratio 1.44, 95% confidence interval, 1.09–1.90, P=0.009) and cadmium (hazard ratio for quartile [Q] 4 versus Q1–3: 1.95, confidence interval, 1.33–2.85, P=0.001), after adjustment for risk factors. There was a significant interaction between cadmium and plaque with respect to risk of ischemic stroke (P=0.011). Adjusted for risk factors, subjects with plaque and cadmium in Q4 had a hazard ratio of 2.88 (confidence interval, 1.79–4.63) for ischemic stroke, compared with those without plaque and cadmium in Q1 to Q3.ConclusionsCadmium was associated with incidence of ischemic stroke, both independently and in synergistic interaction with carotid plaques. This supports the hypothesis that cadmium promotes vulnerability of carotid plaques, thereby increasing the risk of rupture and ischemic stroke.

Kinin B1 receptor as a novel, prognostic progression biomarker for carotid atherosclerotic plaques.

Stroke caused by atherosclerosis remains a leading cause of morbidity and mortality worldwide, associated with carotid plaque rupture and inflammation progression. However, the inflammatory biomarkers which aid in predicting the future course of plaques are less detailed. The present study investigated the association between plaque vulnerable and inflammatory biomarkers using blood and plaque specimens. Carotid plaque specimens were obtained from 80 patients following stroke, 14 patients suffering from transient ischaemic attack and 17 asymptomatic patients that underwent carotid endarterectomy. To assess changes in plaque characteristics at histological levels, plaques were categorized by the time between the latest ischemic stroke and surgical intervention within 30, 30–90, 90–180 and over 180 days following stroke. Serum levels of inflammatory biomarkers interleukin (IL)-6, IL-10 and kinin B1 receptor (B1R) were measured by ELISA. Histological assessment of plaque was used to evaluate the plaque stability, progression and the inflammatory biomarker levels. Comparisons of histological characteristics demonstrated that plaques revealed an unstable phenotype following stroke within 30, 30–90 days and then remodeled into more stable plaques following stroke at 90–180 and over 180 days. By comparing the serum levels of inflammatory biomarkers, it was observed that IL-6 and B1R levels tended to decline whereas IL-10 levels increased in stroke patients from <30 days to over 180 days. Immunohistochemical analysis of IL-6, IL-10 and B1R demonstrated similar alterations in serum levels. Correlation analyses revealed that only B1R serum level was significantly correlated with histological level in patients with carotid atherosclerosis. The findings revealed that serum B1R levels may provide prognostic information and currently act as potential indicators for progression in atherosclerosis.

Letter by Chung and Kim Regarding Article, “Head-to-Head Comparison of Inflammation and Neovascularization in Human Carotid Plaques: Implications for the Imaging of Vulnerable Plaques”

We read with interest the recent published article by Demeure et al1 on the comparison of inflammation and neovascularization in carotid plaques. The authors had reported that inflammation and intraplaque neovascularization (IPN) confirmed by contrast echocardiography, known as 2 features of plaque vulnerability, were not systemically associated in carotid plaque. Furthermore, the presence of IPN was not related with patients’ symptoms, whereas inflammation was associated. In their study, intensity of contrast enhancement was highly correlated with the amount of neovessels confirmed by histology, which means imaging study was well validated. Inflammation and angiogenesis influence …

Assessment of Carotid Plaque Inflammation in Diabetic and Nondiabetic Patients—An Exploratory Ultrasmall Superparamagnetic Iron Oxide-Enhanced Magnetic Resonance Imaging Study

Ultrasmall superparamagnetic iron oxide (USPIO)-enhanced magnetic resonance (MR) imaging enables the identification of inflammation within the atheroma, predominantly by USPIO uptake by macrophages present in atherosclerotic tissue. Diabetic patients, however, may have dysfunctional macrophage activity, which may affect utilization of USPIO in identifying plaque inflammation in this patient cohort. Fifteen diabetic and fifteen nondiabetic patients underwent USPIO-enhanced carotid MR imaging using 1.5T MR system. Pre- and post-USPIO carotid MR images were manually coregistered. The percentage decrease in the signal intensity after USPIO administration was calculated as a relative measure of the USPIO uptake. Diabetic and nondiabetic patients had comparable demographics and comorbidities. The mean global, maximum quadrant, and maximum slice changes showing change in relative signal intensity as a result of USPIO administration were comparable for the two patient cohorts (P > .05). USPIO can identify inflammatory burden with carotid atheroma in both diabetic and nondiabetic patients.

Can Antibodies Protect Us Against Cardiovascular Disease?

Can Antibodies Protect Us Against Cardiovascular Disease?

Abstract 512: The Long Non-coding Rna MIAT Regulates Smooth Muscle Cell Proliferation and Macrophage Activity in Advanced Atherosclerotic Lesions

Background: Long noncoding RNAs (lncRNAs) have emerged as critical epigenetic regulators in various biological processes and diseases. Here we sought to identify and functionally characterize the lncRNA MIAT as a novel regulator in atherosclerotic plaque stability. Methods and results: We profiled RNA transcript expression in patients with advanced atherosclerotic lesions from the Biobank of Karolinska Endarterectomies (BiKE). By microarray analysis, lncRNA MIAT was identified as one of the most highly up-regulated non-coding RNAs in carotid plaques compared to iliac artery controls, which was confirmed by qRT-PCR and in situ hybridization. Additional in silico analysis indicated a substantial positive correlation of MIAT with markers of inflammation, apoptosis and matrix degradation in carotid plaques. Experimental knock-down of MIAT, utilizing site-specific antisense oligonucleotides (LNA-GapmeRs) not only markedly decreased proliferation and migration rates of cultured human carotid artery smooth muscle cells (hCASMCs), but also increased their levels of apoptosis. In addition, MIAT inhibition significantly impaired oxidized LDL (oxLDL) uptake of murine peritoneal as well as human monocyte-differentiated macrophages in vitro. In contrast, induction of MIAT expression by lipoprotein-a (LPa) treatment, displayed the opposite effect. Conditioned medium from macrophage cultures after MIAT knock-down substantially decreased hCASMC proliferation, indicating a potential involvement of MIAT in macrophage-SMC interactions during advanced stages of atherosclerosis. Conclusion: The lncRNA MIAT is a novel regulator of cellular processes in atherosclerosis and plaque stability, which influences SMC proliferation and apoptosis and interacts with disease-triggering macrophages.

Use of somatostatin receptor PET to differentiate between high-risk and low-risk atherosclerotic lesions: a prospective clinical study

BackgroundInflammation drives atherosclerotic plaque rupture that underlies most myocardial infarctions and strokes. Upregulation of somatostatin receptor subtype-2 (SST2) occurs on the cell surface of activated macrophages, offering a potential imaging target for tracking vascular inflammation. We tested the hypothesis that SST2 PET-CT imaging with 68Ga-DOTATATE can detect high-risk carotid and coronary plaque inflammation. We then compared its efficacy with 18F-fludeoxyglucose (18F-FDG), which has limited use in coronary imaging. MethodsProspective sequential 68Ga-DOTATATE PET and 18F-FDG PET imaging, plus CT angiography, were performed in 42 patients with either a recent cardiovascular event (within 3 months of imaging) or stable atherosclerosis, and at least 30% carotid or coronary artery stenosis. Images were analysed, with investigators masked to clinical details, to derive median (IQR) maximum arterial tissue-to-background ratio (TBR). Arterial TBRs were statistically evaluated against clinical and biochemical data, as well as CT-derived plaque morphology. Findings70 carotid arteries and 230 coronary segments were included. 24 patients (57%) had a recent cardiovascular event. 68Ga-DOTATATE TBR (1·98 [1·67–2·14]) was higher in symptomatic carotid arteries than in contralateral arteries (1·77 [1·46–2·08], p=0·0031) and asymptomatic plaques (1·49 [1·36–1·66], p=0·0012). 18F-FDG TBR was also higher on the symptomatic side (1·68 [1·49–1·97] vs 1·51 [1·44–1·80], p=0·0081). The two PET tracers were moderately correlated (r=0·40, p=0·0007). Coronary SST2 signals were visible in all patients, but high myocardial muscle 18F-FDG uptake was prohibitive in 27 patients (64%). Culprit coronary arteries had higher 68Ga-DOTATATE TBR (2·91 [2·69–4·08]) than the highest non-culprit segment (2·61 [1·94–3·01], p=0·0078), stable stented (2·00 [1·51–2·70], p=0·0063), and calcified (1·64 [1·33–2·04], p<0·0001) plaques. SST2 signal from culprit and high-risk coronary arteries was correlated with total cholesterol (r=0·44, p=0·042). InterpretationWe have shown that measurement of vascular inflammation with SST2 PET is feasible and differentiates high-risk and low-risk carotid and coronary lesions. High target specificity, low myocardial binding, and lower cost owing to generator-production give advantage to 68Ga-DOTATATE over 18F-FDG for atherosclerosis imaging. Correlations with 18F-FDG TBR and serum cholesterol further support the vascular SST2 signal as a potential prognostic biomarker to identify patients most at risk of future cardiovascular events. FundingWellcome Trust.

Summary of clinical and laboratory data of study subjects with and without DCE-MRI plaque measurements in the AIM-HIGH clinical trial.

This brief data article summarizes the clinical risk factors and laboratory data of a group of subjects recruited for the AIM-HIGH trial (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides and Impact on Global Health Outcomes) and an associated magnetic resonance imaging (MRI) substudy. The sample is restricted to those on statin therapy at the time of enrollment and data are presented stratified by whether dynamic contrast enhanced MRI (DCE-MRI) markers of carotid plaque vascularity and inflammation were available or not. The data provided herein are directly related to the article “Longer Duration of Statin Therapy is Associated with Decreased Carotid Plaque Vascularity by Magnetic Resonance Imaging” [2].

Diabetes modifies the relationships among carotid plaque calcification, composition and inflammation.

Diabetes is traditionally associated with vascular calcification, but the molecular mechanisms are largely unknown. We herein explored the relationships among carotid plaque calcification, composition and gene expression, and how these are modified by diabetes. We collected carotid endoarterectomy specimen from 59 patients, of whom 23 had diabetes. We analysed histology with pentachromic staining, calcification with Alizarin red and Von Kossa's staining, chemical calcium extraction and quantification, as well as gene expression by quantitative PCR. We detected no differences in the extent of plaque calcification and in plaque composition between diabetic and non-diabetic patients. In non-diabetic plaques, calcium content was directly correlated with the area occupied by muscle/fibrinoid tissue and inversely correlated with collagen, but such correlations were not seen in plaques from diabetic patients. While consistent correlations were found between calcium content and RUNX2 (direct), as well as Osteopontin (inverse), diabetes modified the association between plaque calcification and inflammatory gene expression. Only in diabetic plaques, calcium content was inversely correlated with MCP1 and IL1b, whereas the direct correlation with TNF-alpha expression seen in non-diabetic plaques was lost in diabetes. Though plaque composition and calcification were not quantitatively affected, diabetes modified the relationships between plaque calcium, composition and inflammation. These results suggest that the mechanisms and the clinical significance of atherosclerotic calcification in diabetic may be different than in non-diabetic patients.

Evaluation of carotid plaque inflammation in patients with active rheumatoid arthritis using 18F-fluorodeoxyglucose PET-CT and MRI: a pilot study

BackgroundRheumatoid arthritis is associated with a 50% increased risk in cardiovascular mortality. Inflammation is thought to accelerate atherosclerosis and might also lead to an inflammatory rupture-prone plaque phenotype. We tested the hypothesis that patients with active rheumatoid arthritis also have carotid plaque inflammation and that plaque inflammation correlates with clinical and serological markers of inflammation. MethodsPatients with active rheumatoid arthritis, defined as the Disease Activity Score in 28 joints (DAS28) score of more than 3·2, were recruited to a single centre study in the UK. Patients with carotid plaque on ultrasound underwent carotid MRI followed by 18F-fluorodeoxyglucose (18F-FDG) PET-CT. Scans were co-registered and analysed by a physicist, masked to clinical information. The maximum standardised uptake values (SUVmax) were measured in the plaque area. The association of SUV with DAS28, C-reactive protein, and CD4+CD28– T-cell frequency was tested with non-parametric statistics. Ethics approval and informed consent were obtained. FindingsScans were done in 13 patients, nine of whom were women. Median age was 60 years (IQR 57–65), disease duration was 11 years (6–25), and DAS28 score was 4·52 (4·32–5·13). None had a history or symptoms of clinical cardiovascular disease or took statins. All plaques caused less than 70% stenosis, and tracer uptake in plaque was seen on PET in all 13 patients. Median SUVmax was 2·18 (IQR 2·00–2·65), and all cases had an SUVmax greater than 1·6 (the threshold for defining carotid plaque inflammation). There was a significant association with SUVmax and C-reactive protein (r=0·58, p=0·04) and quartiles of CD4+CD28– T-cell frequency (p=0·045), but not with low-density lipoprotein concentrations (r=-0·49, p=0·09) or DAS28 score (r=0·38, p=0·20). No association was found with age (r=0·13, p=0·69) or sex (p=0·64). InterpretationIn this small pilot study, plaque inflammation was seen in all patients and correlated with C-reactive protein. Whether this finding represents simultaneous joint and plaque inflammation, which might improve on treatment of joint disease, remains to be determined. CD4+CD28– T-cells are known to predict cardiovascular events in patients with angina. Their association with plaque inflammation in this study suggests a possible role in cardiovascular risk prediction in rheumatoid arthritis. Larger studies are warranted to investigate these findings further. FundingNorth West England MRC Clinical Pharmacology and Therapeutics Clinical Research Fellowship, National Institute for Health Research, AstraZeneca-University of Manchester Strategic Alliance Fund.

Carotid Plaque Inflammation Assessed with 18F-FDG PET/CT is Higher in Symptomatic Compared with Asymptomatic Patients

Carotid artery plaque inflammation is thought to be an important marker of plaque vulnerability and increased stroke risk. The main aim of this study was to assess the level of agreement between 2-deoxy-2-[(18)F] fluoro-D-glucose (18F-FDG) uptake on PET (positron emission tomography) scan in carotid plaques, with cerebrovascular symptoms, carotid plaque ultrasound echogenicity and histological assessments of plaque inflammation. Thirty-six patients with ≥70% carotid stenosis scheduled for carotid endarterectomy underwent a Colour Duplex ultrasound, (18)F-FDG PET/CT and blood tests less than 24 h prior to surgery. Plaques were defined as symptomatic when associated with ipsilateral cerebral ischemic symptoms within 30 days prior to inclusion. Plaques were assessed histologically following endarterectomy. The level of agreement between (18)F-FDG uptake (mean SUVmax and SUVmax ), and target-to-background ratio, symptoms, plaque echolucency, and histological evidence of inflammation was assessed. The amount of (18)F-FDG uptake in plaques and the amount of inflammation on histological assessment were significantly correlated (r = 0·521, P = 0·003). (18)F-FDG uptake was significantly higher in symptomatic plaques with median SUVmax 1·75 (1·26-2·04) in symptomatic, and 1·43 (1·15-2·28) in asymptomatic patients (P = 0·03). (18)F-FDG uptake was also positively correlated with echolucency on Doppler ultrasound (P = 0·03). (18)F-FDG uptake on PET/CT correlated with histological assessments of inflammation and was higher in patients with symptomatic compared with asymptomatic carotid artery plaques. These results support the use of (18)F-FDG PET/CT in the detection inflammation in carotid atherosclerosis, which may be of help in the detection of vulnerable plaques.

Carotid inflammation on 18F-fluorodeoxyglucose positron emission tomography associates with recurrent ischemic lesions

BackgroundInflammation plays an important role in the development of ischemic stroke. We hypothesized that inflammation of carotid atherosclerosis, as measured by 18F-fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET), associates with the early recurrent ischemic lesions (ERILs). MethodsThis prospective study included patients with symptomatic carotid atherosclerosis. ERILs were defined as newly developed ischemic lesions in the territory of symptomatic internal carotid artery stenosis, as detected by follow-up diffusion-weighted imaging (DWI). The patients with and without ERILs were compared in terms of risk factors, inflammatory markers, and FDG uptake on PET. ResultsOf the 21 patients, 8 had ERILs (38.1%). Compared to the patients without ERILs, those with ERILs had higher FDG uptake (maximum standardized uptake value, 3.07±0.79 vs. 2.17±0.68, p=0.013) and were more likely to have irregular carotid plaques (100% vs. 38.5%, p=0.007). Inflammatory markers were not different between the two groups, and also did not correlate with FDG uptake. ConclusionsIncreased carotid plaque inflammation, as measured by FDG uptake on PET, may be a useful marker for identifying patients with symptomatic carotid atherosclerosis who are at risk of recurrence.

Insights from a thermography-based method suggesting higher carotid inflammation in patients with diabetes mellitus and coronary artery disease

AimDiabetes mellitus (DM) is an independent risk factor for stroke. In a DM population, carotid atheromatosis is a major cause of stroke. The role of carotid plaque inflammation remains conflicting. Microwave radiometry (MWR) is a new non-invasive method allowing in vivo measurement of the temperature of tissues, so reflecting inflammation. The aim of this prospective study was to evaluate the impact of DM on carotid artery inflammation in patients with documented coronary artery disease (CAD). MethodsConsecutive patients (n=300) with significant CAD were evaluated by: (1) ultrasound study of both carotid arteries; and (2) the temperature difference (ΔT) along each carotid artery on MWR. ΔT≥0.90°C was considered high ΔT. Vessel- and patient-based analyses were performed to determine the impact of DM on morphological and functional characteristics of carotid arteries. ResultsOut of 300 patients, 113 (37.7%) had DM. Patients with DM had similar carotid plaque thickness compared with patients without DM in both vessel- and patient-based analyses. In contrast, patients with DM exhibited higher ΔT values in both vessel- and patient-based analyses. On multivariate logistic regression analysis, DM was an independent predictor of high ΔT both unilaterally and bilaterally (OR: 1.66, 95% CI: 1.06–2.58, P=0.03 and OR: 1.96, 95% CI: 1.01–3.81, P=0.05, respectively). ConclusionIn patients with CAD, DM was an independent predictor of local carotid plaque inflammatory activation. Whether or not the assessment of functional plaque characteristics by MWR can be an additional prognostic tool independent of structural factors now needs to be further investigated.

Serum lipids associated with inflammation-related PET-FDG uptake in symptomatic carotid plaque.

We hypothesized that serum lipids, which experimental data suggest may be key initiators of carotid plaque inflammation, would be associated with plaque inflammation on (18)fluorodeoxyglucose (FDG)-PET in patients with acutely symptomatic carotid stenosis. In this cohort study, consecutive patients with acute symptomatic internal carotid artery (ICA) stenosis (≥50%) underwent carotid PET-CT. We quantified plaque FDG uptake as follows: (1) average maximum standardized uptake values (SUVmax) across 10 regions of interest (ROI); (2) highest single ROI SUV measure (SUVROImax); (3) averaged mean SUV across 10 ROIs (SUVmean). Sixty-one patients were included. Plaque inflammatory FDG SUVmax was associated with increasing tertiles of low-density lipoprotein (LDL) (trend p = 0.004), total cholesterol (p = 0.009), and triglycerides (p = 0.01), and with lower high-density lipoprotein (HDL) (p = 0.005). When analyzed as a continuous variable, LDL was associated with symptomatic ICA SUVmean (Spearman rho 0.44, p = 0.009), SUVROImax (rho 0.33, p = 0.01), and SUVmax (rho 0.35, p = 0.06). Total cholesterol was associated with SUVmean (rho 0.33, p = 0.009), with trends for SUVmax (rho 0.24, p = 0.059) and SUVROImax (rho 0.23, p = 0.08). Triglycerides were associated with SUVmax (rho 0.32, p = 0.01) and SUVROImax (rho 0.35, p = 0.005). HDL was associated with lower SUVmax (rho -0.37, p = 0.004) and SUVROImax (rho -0.44, p = 0.0004). On multivariable linear regression analysis adjusting for age, sex, degree of carotid stenosis, statins, and smoking, LDL (p = 0.008) and total cholesterol (p = 0.04) were independently associated with SUVmax. Serum LDL and total cholesterol were associated with acutely symptomatic carotid plaque FDG uptake, supporting experimental data suggesting lipids may promote plaque inflammation, mediating rupture and clinical events.

Predictors of change in carotid atherosclerotic plaque inflammation and burden as measured by 18-FDG-PET and MRI, respectively, in the dal-PLAQUE study

Baseline predictors of response to treatment of patients with coronary heart disease (CHD) with respect to vascular inflammation and atherosclerotic plaque burden are poorly understood. From post hoc analysis of the dal-PLAQUE study (NCT00655473), 18F-fluorodeoxyglucose-positron emission tomography (18-FDG-PET) imaging and carotid black blood magnetic resonance imaging (MRI) were used to track changes in these vascular parameters. Baseline demographics, imaging, and biomarkers were collected/measured in 130 patients with CHD or CHD risk-equivalents, and imaging follow-up at 6 months (PET) and 24 months (MRI) was performed. Using stepwise linear regression, predictors of change in carotid plaque inflammation by PET [target-to-background ratio (TBR), n = 92] and plaque burden by MRI [wall area (WA) and total vessel area (TVA), n = 89] were determined. Variables with p < 0.05 in multivariable models were considered independently significant. Interleukin-6, systolic blood pressure and standard deviation of wall thickness (WT) at baseline were independently positively associated with 18-FDG uptake (mean of maximum [MeanMax] TBR change over 6 months). Mean of mean TBR, phospholipase A2, apolipoprotein A-I, and high-sensitivity C-reactive protein at baseline were independently negatively associated with MeanMax TBR change over 6 months. Mean WT and plasminogen activator inhibitor-1 (PAI-1) activity at baseline, and age, were independently associated with change in WA over 24 months. For TVA changes; mean WA and PAI-1 activity at baseline, age, and female gender were independent predictors. These findings may help determine patients most suitable for clinical trials employing plaque inflammation or burden changes as endpoints.

Combined 18 F-FDG PET-CT and DCE-MRI to Assess Inflammation and Microvascularization in Atherosclerotic Plaques

Hallmarks of vulnerable atherosclerotic plaques are inflammation that can be assessed with 18fluorine-fluorodeoxyglucose positron emission tomography/computed tomography, and increased neovascularization that can be evaluated by dynamic contrast-enhanced-MRI. It remains unclear whether these parameters are correlated or represent independent imaging parameters. This study determines whether there is a correlation between inflammation and neovascularization in atherosclerotic carotid plaques. A total of 58 patients with transient ischemic attack or minor stroke in the carotid territory and ipsilateral carotid artery stenosis of 30% to 69% were included. All patients underwent positron emission tomography/computed tomography and dynamic contrast-enhanced-MRI of the carotid plaque. 18Fluorine-fluorodeoxyglucose standard uptake values with target/background ratio were determined. Neovascularization was quantified by the mean (leakage) volume transfer constant Ktrans. Spearman rank correlation coefficients between target/background ratio and Ktrans were calculated. Images suitable for further analysis were obtained in 49 patients. A weak but significant positive correlation between target/background ratio and mean Ktrans (Spearman ρ=0.30 [P=0.035]) and 75th percentile Ktrans (Spearman ρ=0.29 [P=0.041]) was found. There is a weak but significant positive correlation between inflammation on positron emission tomography/computed tomography and neovascularization as assessed with dynamic contrast-enhanced-MRI. Future studies should investigate which imaging modality has the highest predictive value for recurrent stroke, as these are not interchangeable. http://www.clinicaltrials.gov. Unique identifier: NCT00451529.

Relationship of Serum Inflammatory Biomarkers With Plaque Inflammation Assessed by FDG PET/CT: The dal-PLAQUE Study

This study sought to longitudinally investigate the relationship between a broad spectrum of serum inflammatory biomarkers and plaque inflammation assessed by (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT).Both plaque inflammation and serum biomarkers of inflammation are associated with atherothrombotic events; however, the relationship between them is unclear.We conducted a post hoc analysis of the dal-PLAQUE (A Randomized Placebo-Controlled Study of the Effect of RO4607381 on Progression or Regression of Atherosclerotic Plaque in Patients With Coronary Heart Disease [CHD] Including Patients With Other CHD Risk Factors), a randomized, placebo-controlled study of dalcetrapib, a cholesteryl ester transfer protein inhibitor, in 130 patients with coronary heart disease, or coronary heart disease risk equivalents on stable lipid-lowering therapy. Baseline and change after 3-month follow-up in inflammatory biomarker levels and baseline and change after 3-month follow-up in aorta and carotid (18)F-FDG PET/CT (mean maximum target-to-background ratio of the most diseased segment [TBRmds]) were analyzed.Baseline myeloperoxidase positively correlated with baseline carotid TBRmds (rho = 0.25, p = 0.02). This correlation remained at the 3-month follow-up and was independent of traditional cardiovascular disease risk factors. Baseline lipoprotein-associated phospholipase A2 mass correlated with aorta TBRmds (rho = 0.21, p = 0.03). However, this correlation disappeared at the 3-month follow-up and was not independent of cardiovascular disease risk factors. There was no association between change from baseline in myeloperoxidase or lipoprotein-associated phospholipase A2 mass and change from baseline in aorta and carotid TBRmds. Baseline and change from baseline in high sensitivity C-reactive protein, interleukin 6, soluble P-selectin, soluble E-selectin, soluble intracellular adhesion molecule 1, soluble vascular cell adhesion molecule 1, and matrix-metalloproteinase 3 and 9 did not correlate with baseline or change from baseline in carotid or aorta TBRmds.Our data show that, in patients with coronary heart disease or at high risk of coronary heart disease on stable lipid-lowering therapy, circulating myeloperoxidase levels are associated with carotid plaque inflammation. (A Randomized, Placebo-controlled Study of the Effect of RO4607381 on Progression or Regression of Atherosclerotic Plaque in Patients With Coronary Heart Disease [CHD] Including Patients With Other CHD Risk Factors [dal-PLAQUE]; NCT00655473).

Carotid plaque inflammation in patients with acute coronary syndrome assessed by 18f-fluorodeoxyglucose positron emission tomography

Carotid plaque inflammation in patients with acute coronary syndrome assessed by 18f-fluorodeoxyglucose positron emission tomography

Carotid plaque inflammation as a marker for the presence of severe coronary artery disease in patients evaluated for chest pain

Carotid plaque inflammation as a marker for the presence of severe coronary artery disease in patients evaluated for chest pain