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Peter Libby - One of the best experts on this subject based on the ideXlab platform.
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targeted near infrared fluorescence imaging of atherosclerosis clinical and intracoronary evaluation of indocyanine green
Jacc-cardiovascular Imaging, 2016Co-Authors: Johan Verjans, Peter Libby, Eric A Osborn, Giovanni J Ughi, Marcella Calfon Press, Ehsan Hamidi, Antonios P Antoniadis, Michail I Papafaklis, Mark F Conrad, Peter H StoneAbstract:Abstract Objectives This study sought to determine whether indocyanine green (ICG)–enhanced near-infrared fluorescence (NIRF) imaging can illuminate high-risk histologic plaque features of human carotid atherosclerosis, and in coronary Atheroma of living swine, using intravascular NIRF-optical coherence tomography (OCT) imaging. Background New translatable imaging approaches are needed to identify high-risk biological signatures of Atheroma. ICG is a U.S. Food and Drug Administration–approved NIRF imaging agent that experimentally targets plaque macrophages and lipid in areas of enhanced endothelial permeability. However, it is unknown whether ICG can target Atheroma in patients. Methods Eight patients were enrolled in the BRIGHT-CEA (Indocyanine Green Fluorescence Uptake in Human Carotid Artery Plaque) trial. Five patients were injected intravenously with ICG 99 ± 25 min before clinically indicated carotid endarterectomy. Three saline-injected endarterectomy patients served as control subjects. Excised plaques underwent analysis by intravascular NIRF-OCT, reflectance imaging, microscopy, and histopathology. Next, following ICG intravenous injection, in vivo intracoronary NIRF-OCT and intravascular ultrasound imaged 3 Atheroma-bearing coronary arteries of a diabetic, cholesterol-fed swine. Results ICG was well tolerated; no adverse clinical events occurred up to 30 days post-injection. Multimodal NIRF imaging including intravascular NIRF-OCT revealed that ICG accumulated in all endarterectomy specimens. Plaques from saline-injected control patients exhibited minimal NIRF signal. In the swine experiment, intracoronary NIRF-OCT identified ICG uptake in all intravascular ultrasound–identified plaques in vivo. On detailed microscopic evaluation, ICG localized to plaque areas exhibiting impaired endothelial integrity, including disrupted fibrous caps, and within areas of neovascularization. Within human plaque areas of endothelial abnormality, ICG was spatially related to localized zones of plaque macrophages and lipid, and, notably, intraplaque hemorrhage. Conclusions This study demonstrates that ICG targets human plaques exhibiting endothelial abnormalities and provides new insights into its targeting mechanisms in clinical and experimental Atheroma. Intracoronary NIRF-OCT of ICG may offer a novel, clinically translatable approach to image pathobiological aspects of coronary atherosclerosis. (Indocyanine Green Fluorescence Uptake in Human Carotid Artery Plaque [BRIGHT-CEA]; NCT01873716)
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c reactive protein but not low density lipoprotein cholesterol levels associate with coronary Atheroma regression and cardiovascular events after maximally intensive statin therapy
Circulation, 2013Co-Authors: Rishi Puri, Peter Libby, Steven E Nissen, Mingyuan Shao, Christie M Ballantyne, P Barter, John M Chapman, Raimund Erbel, Joel S Raichlen, Kiyoko UnoAbstract:Background—Baseline C-reactive protein (CRP) levels predict major adverse cardiovascular events (MACE: death, myocardial infarction, stroke, coronary revascularization, and hospitalization for unstable angina). The association between changes in CRP levels with plaque progression and MACE in the setting of maximally intensive statin therapy is unknown. Methods and Results—The Study of Coronary Atheroma by Intravascular Ultrasound: Effect of Rosuvastatin Versus Atorvastatin (SATURN) used serial intravascular ultrasound measures of coronary Atheroma volume in patients treated with rosuvastatin 40 mg or atorvastatin 80 mg for 24 months. The treatment groups did not differ significantly in the change from baseline of percent Atheroma volume on intravascular ultrasound, CRP-modulating effects, or MACE rates, thus allowing for a (prespecified) post hoc analysis to test associations between the changes in CRP levels with coronary disease progression and MACE. Patients with nonincreasing CRP levels (n=621) had hi...
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relationship of antihypertensive treatment to plasma markers of vascular inflammation and remodeling in the comparison of amlodipine versus enalapril to limit occurrences of thrombosis study
American Heart Journal, 2012Co-Authors: Payman Zamani, Peter Libby, Stephen J Nicholls, Steven E Nissen, Peter Ganz, Santosh Sutradhar, Nader Rifai, Scott KinlayAbstract:Background Antihypertensive agents lower the risk of cardiovascular events, but whether they affect pathways important in inflammation and plaque remodeling in atherosclerosis is uncertain. We assessed whether 2 commonly used antihypertensive agents affected plasma biomarkers reflecting specific inflammatory and remodeling processes over 2 years in the Comparison of Amlodipine versus Enalapril to Limit Occurrences of Thrombosis (CAMELOT) study. Methods The study was a randomized controlled trial of 2 antihypertensives (amlodipine and enalapril) compared with placebo in patients with coronary artery disease and diastolic blood pressure less than 100 mm Hg. In 196 subjects who had baseline and 2-year intravascular coronary ultrasound examinations, we measured plasma interleukin 18, interleukin 1 receptor antagonist, matrix metalloproteinase 9, neopterin, and C-reactive protein. Results for both treatment groups were pooled and compared with placebo. Results Antihypertensive treatment with either agent significantly lowered diastolic blood pressure (−4.7 vs placebo 1.3 mm Hg, P = .002) and progression of coronary Atheroma (Δ percent Atheroma volume 0.6 vs placebo 2.1, P = .031). Antihypertensive therapy did not affect plasma biomarkers of inflammation or plaque remodeling in the 135 subjects with baseline and 2-year biomarker samples. Progression in percent Atheroma volume was significantly less in subjects taking statins at baseline (−2.5%, P = .0008). Conclusions In patients with coronary artery disease and well-controlled risk factors, antihypertensive therapy lowered blood pressure and progression of coronary atherosclerosis but did not affect plasma biomarkers of inflammation and remodeling. Antihypertensives may decrease Atheroma progression by mechanisms other than those reflected by these plasma biomarkers.
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indocyanine green enables near infrared fluorescence imaging of lipid rich inflamed atherosclerotic plaques
Science Translational Medicine, 2011Co-Authors: Claudio Vinegoni, Peter Libby, Ion Botnaru, Elena Aikawa, Marcella A Calfon, Yoshiko Iwamoto, Eduardo J Folco, Vasilis Ntziachristos, Ralph Weissleder, Farouc A JafferAbstract:New high-resolution molecular and structural imaging strategies are needed to visualize high-risk plaques that are likely to cause acute myocardial infarction, because current diagnostic methods do not reliably identify at-risk subjects. Although molecular imaging agents are available for low-resolution detection of atherosclerosis in large arteries, a lack of imaging agents coupled to high-resolution modalities has limited molecular imaging of atherosclerosis in the smaller coronary arteries. Here, we have demonstrated that indocyanine green (ICG), a Food and Drug Administration-approved near-infrared fluorescence (NIRF)-emitting compound, targets Atheromas within 20 min of injection and provides sufficient signal enhancement for in vivo detection of lipid-rich, inflamed, coronary-sized plaques in atherosclerotic rabbits. In vivo NIRF sensing was achieved with an intravascular wire in the aorta, a vessel of comparable caliber to human coronary arteries. Ex vivo fluorescence reflectance imaging showed high plaque target-to-background ratios in Atheroma-bearing rabbits injected with ICG compared to Atheroma-bearing rabbits injected with saline. In vitro studies using human macrophages established that ICG preferentially targets lipid-loaded macrophages. In an early clinical study of human Atheroma specimens from four patients, we found that ICG colocalized with plaque macrophages and lipids. The Atheroma-targeting capability of ICG has the potential to accelerate the clinical development of NIRF molecular imaging of high-risk plaques in humans.
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effect of very high intensity statin therapy on regression of coronary atherosclerosis the asteroid trial
JAMA, 2006Co-Authors: Steven E Nissen, Peter Libby, Stephen J Nicholls, Ilke Sipahi, Christie M Ballantyne, Raimund Erbel, Joel S Raichlen, Jean Davignon, Jean Charles Fruchart, Jeanclaude TardifAbstract:ContextPrior intravascular ultrasound (IVUS) trials have demonstrated slowing or halting of atherosclerosis progression with statin therapy but have not shown convincing evidence of regression using percent Atheroma volume (PAV), the most rigorous IVUS measure of disease progression and regression.ObjectiveTo assess whether very intensive statin therapy could regress coronary atherosclerosis as determined by IVUS imaging.Design and SettingProspective, open-label blinded end-points trial (A Study to Evaluate the Effect of Rosuvastatin on Intravascular Ultrasound-Derived Coronary Atheroma Burden [ASTEROID]) was performed at 53 community and tertiary care centers in the United States, Canada, Europe, and Australia. A motorized IVUS pullback was used to assess coronary Atheroma burden at baseline and after 24 months of treatment. Each pair of baseline and follow-up IVUS assessments was analyzed in a blinded fashion.PatientsBetween November 2002 and October 2003, 507 patients had a baseline IVUS examination and received at least 1 dose of study drug. After 24 months, 349 patients had evaluable serial IVUS examinations.InterventionAll patients received intensive statin therapy with rosuvastatin, 40 mg/d.Main Outcome MeasuresTwo primary efficacy parameters were prespecified: the change in PAV and the change in nominal Atheroma volume in the 10-mm subsegment with the greatest disease severity at baseline. A secondary efficacy variable, change in normalized total Atheroma volume for the entire artery, was also prespecified.ResultsThe mean (SD) baseline low-density lipoprotein cholesterol (LDL-C) level of 130.4 (34.3) mg/dL declined to 60.8 (20.0) mg/dL, a mean reduction of 53.2% (P<.001). Mean (SD) high-density lipoprotein cholesterol (HDL-C) level at baseline was 43.1 (11.1) mg/dL, increasing to 49.0 (12.6) mg/dL, an increase of 14.7% (P<.001). The mean (SD) change in PAV for the entire vessel was −0.98% (3.15%), with a median of −0.79% (97.5% CI, −1.21% to −0.53%) (P<.001 vs baseline). The mean (SD) change in Atheroma volume in the most diseased 10-mm subsegment was −6.1 (10.1) mm3, with a median of −5.6 mm3 (97.5% CI, −6.8 to −4.0 mm3) (P<.001 vs baseline). Change in total Atheroma volume showed a 6.8% median reduction; with a mean (SD) reduction of −14.7 (25.7) mm3, with a median of −12.5 mm3 (95% CI, −15.1 to −10.5 mm3) (P<.001 vs baseline). Adverse events were infrequent and similar to other statin trials.ConclusionsVery high-intensity statin therapy using rosuvastatin 40 mg/d achieved an average LDL-C of 60.8 mg/dL and increased HDL-C by 14.7%, resulting in significant regression of atherosclerosis for all 3 prespecified IVUS measures of disease burden. Treatment to LDL-C levels below currently accepted guidelines, when accompanied by significant HDL-C increases, can regress atherosclerosis in coronary disease patients. Further studies are needed to determine the effect of the observed changes on clinical outcome.Trial RegistrationClinicalTrials.gov Identifier: NCT00240318Published online March 13, 2006 (doi:10.1001/jama.295.13.jpc60002).
Giampiero Bricca - One of the best experts on this subject based on the ideXlab platform.
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8d 07 gene expression analysis and bioinformatics revealed potential transcription factors associated with renin angiotensin aldosterone system in Atheroma
Journal of Hypertension, 2015Co-Authors: Ali Nehme, Claudio Cerutti, Kazem Zibara, Giampiero BriccaAbstract:Abstract The implication of the renin-angiotensin-aldosterone system (RAAS) in Atheroma development is well described. However, a complete view of the local RAAS in Atheroma is still missing. In this study we aimed to reveal the organization of RAAS in Atheroma at the transcriptomic level and identify the transcriptional regulators behind it. Extended RAAS (extRAAS) was defined as the set of 37 genes coding for classical and novel RAAS participants (Figure 1). Five microarray datasets containing overall 590 samples representing carotid and peripheral Atheroma were downloaded from the GEO database. Correlation-based hierarchical clustering (R software) of extRAAS genes within each dataset allowed the identification of modules of co-expressed genes. Reproducible co-expression modules across datasets were then extracted. Transcription factors (TFs) having common binding sites (TFBSs) in the promoters of coordinated genes were identified using the Genomatix database tools and analyzed for their correlation with extRAAS genes in the microarray datasets. Expression data revealed the expressed extRAAS components and their relative abundance displaying the favored pathways in Atheroma. Three co-expression modules with more than 80% reproducibility across datasets were extracted. Two of them (M1 and M2) contained genes coding for angiotensin metabolizing enzymes involved in different pathways: M1 included ACE, MME, RNPEP, and DPP3, in addition to 7 other genes; and M2 included CMA1, CTSG, and CPA3. The third module (M3) contained genes coding for receptors known to be implicated in Atheroma (AGTR1, MR, GR, LNPEP, EGFR and GPER). M1 and M3 were negatively correlated in 3 of 5 datasets. We identified 19 TFs that have enriched TFBSs in the promoters of genes of M1, and two for M3, but none was found for M2. Among the extracted TFs, ELF1, MAX, and IRF5 showed significant positive correlations with peptidase-coding genes from M1 and negative correlations with receptors-coding genes from M3 (p
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8d 07 gene expression analysis and bioinformatics revealed potential transcription factors associated with renin angiotensin aldosterone system in Atheroma
Journal of Hypertension, 2015Co-Authors: Ali Nehme, Claudio Cerutti, Kazem Zibara, Giampiero BriccaAbstract:Abstract The implication of the renin-angiotensin-aldosterone system (RAAS) in Atheroma development is well described. However, a complete view of the local RAAS in Atheroma is still missing. In this study we aimed to reveal the organization of RAAS in Atheroma at the transcriptomic level and identify the transcriptional regulators behind it. Extended RAAS (extRAAS) was defined as the set of 37 genes coding for classical and novel RAAS participants (Figure 1). Five microarray datasets containing overall 590 samples representing carotid and peripheral Atheroma were downloaded from the GEO database. Correlation-based hierarchical clustering (R software) of extRAAS genes within each dataset allowed the identification of modules of co-expressed genes. Reproducible co-expression modules across datasets were then extracted. Transcription factors (TFs) having common binding sites (TFBSs) in the promoters of coordinated genes were identified using the Genomatix database tools and analyzed for their correlation with extRAAS genes in the microarray datasets. Expression data revealed the expressed extRAAS components and their relative abundance displaying the favored pathways in Atheroma. Three co-expression modules with more than 80% reproducibility across datasets were extracted. Two of them (M1 and M2) contained genes coding for angiotensin metabolizing enzymes involved in different pathways: M1 included ACE, MME, RNPEP, and DPP3, in addition to 7 other genes; and M2 included CMA1, CTSG, and CPA3. The third module (M3) contained genes coding for receptors known to be implicated in Atheroma (AGTR1, MR, GR, LNPEP, EGFR and GPER). M1 and M3 were negatively correlated in 3 of 5 datasets. We identified 19 TFs that have enriched TFBSs in the promoters of genes of M1, and two for M3, but none was found for M2. Among the extracted TFs, ELF1, MAX, and IRF5 showed significant positive correlations with peptidase-coding genes from M1 and negative correlations with receptors-coding genes from M3 (p
Steven E Nissen - One of the best experts on this subject based on the ideXlab platform.
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effects of aliskiren in diabetic and non diabetic patients with coronary artery disease insights from aquarius
Atherosclerosis, 2015Co-Authors: Steven E Nissen, Rishi Puri, Venu Menon, Mingyuan Shao, George L Bakris, John J P Kastelein, Bryan Williams, Juergen Armbrecht, Patrick BrunelAbstract:Abstract Background Aliskiren previously was found to have potentially harmful effects in diabetic individuals prescribed concomitant angiotensin converting enzyme inhibitors (ACEI) or angiotenisn receptor antagonists (ARB). We explored potential effects of aliskiren on coronary Atheroma progression and major adverse cardiovascular events (MACE: death/non-fatal MI/non-fatal stroke/hospitalization for heart failure/hospitalization for ACS/arterial revascularization) in patients with and without diabetes mellitus (DM). Methods AQUARIUS employed serial intravascular ultrasound measures of coronary Atheroma volume in coronary artery disease patients randomized to receive daily aliskiren 300 mg or placebo for 104 weeks. This post hoc analysis compared changes in plaque volume [percent Atheroma volume (PAV) and total Atheroma volume (TAV)] and MACE in patients with (n = 115) and without (n = 343) DM stratified by treatment allocation. Results In multivariable propensity-weighted analyses, which included controlling for baseline and concomitant ACEI/ARB therapy and duration of aliskiren therapy, aliskiren-treated non-DM patients demonstrated the greatest PAV and TAV regression, whereas aliskiren-treated DM patients demonstrated the greatest TAV progression and greater PAV. Aliskiren-treated non-DM patients appeared at significantly lower risk of MACE compared with their aliskiren-treated DM counterparts [HR 95% CI 0.28 (0.10, 0.80)]. Statistical interactions were noted between DM status and treatment allocation for both changes in PAV (p Conclusions Aliskiren appears to be relatively anti-atherosclerotic in non-diabetic patients. Due to the limited number MACE and low numbers of diabetic patients in AQUARIUS, the pro-atherosclerotic effects of aliskiren in this population are inconclusive, and these results should be thus considered hypothesis generating. Further outcome studies are required in non-diabetic patients to confirm the possible favorable effects of aliskiren.
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impact of baseline lipoprotein and c reactive protein levels on coronary Atheroma regression following high intensity statin therapy
American Journal of Cardiology, 2014Co-Authors: Rishi Puri, Murat E Tuzcu, Kiyoko Uno, Steven E Nissen, Mingyuan Shao, Yu Kataoka, Samir R Kapadia, Stephen J NichollsAbstract:Guidelines now recommend high-intensity statin therapy in all patients with proven atherosclerotic disease. Yet the impact of baseline lipoprotein and C-reactive protein (CRP) levels on measures of disease regression to this therapy are unknown. The aim of this study was to test the hypothesis that high-intensity statin therapy causes equivalent degrees of coronary Atheroma regression irrespective of baseline lipoprotein and CRP levels. In 8 prospective randomized trials using serial coronary intravascular ultrasound, 1,881 patients who maintained or switched to 18- to 24 months of high-intensity statin therapy (rosuvastatin 40 mg or atorvastatin 80 mg) were stratified according to baseline lipoprotein and CRP levels. Changes in coronary percentage Atheroma volume (PAV) and total Atheroma volume (TAV) were evaluated. High-intensity statin therapy produced significant reductions from baseline in low-density lipoprotein cholesterol by 38.4%, non–high-density lipoprotein (HDL) cholesterol by 33.6%, triglycerides by 13.1%, and CRP by 33.3%, while increasing HDL cholesterol by 11.7% (p 3 (p
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c reactive protein but not low density lipoprotein cholesterol levels associate with coronary Atheroma regression and cardiovascular events after maximally intensive statin therapy
Circulation, 2013Co-Authors: Rishi Puri, Peter Libby, Steven E Nissen, Mingyuan Shao, Christie M Ballantyne, P Barter, John M Chapman, Raimund Erbel, Joel S Raichlen, Kiyoko UnoAbstract:Background—Baseline C-reactive protein (CRP) levels predict major adverse cardiovascular events (MACE: death, myocardial infarction, stroke, coronary revascularization, and hospitalization for unstable angina). The association between changes in CRP levels with plaque progression and MACE in the setting of maximally intensive statin therapy is unknown. Methods and Results—The Study of Coronary Atheroma by Intravascular Ultrasound: Effect of Rosuvastatin Versus Atorvastatin (SATURN) used serial intravascular ultrasound measures of coronary Atheroma volume in patients treated with rosuvastatin 40 mg or atorvastatin 80 mg for 24 months. The treatment groups did not differ significantly in the change from baseline of percent Atheroma volume on intravascular ultrasound, CRP-modulating effects, or MACE rates, thus allowing for a (prespecified) post hoc analysis to test associations between the changes in CRP levels with coronary disease progression and MACE. Patients with nonincreasing CRP levels (n=621) had hi...
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relationship of antihypertensive treatment to plasma markers of vascular inflammation and remodeling in the comparison of amlodipine versus enalapril to limit occurrences of thrombosis study
American Heart Journal, 2012Co-Authors: Payman Zamani, Peter Libby, Stephen J Nicholls, Steven E Nissen, Peter Ganz, Santosh Sutradhar, Nader Rifai, Scott KinlayAbstract:Background Antihypertensive agents lower the risk of cardiovascular events, but whether they affect pathways important in inflammation and plaque remodeling in atherosclerosis is uncertain. We assessed whether 2 commonly used antihypertensive agents affected plasma biomarkers reflecting specific inflammatory and remodeling processes over 2 years in the Comparison of Amlodipine versus Enalapril to Limit Occurrences of Thrombosis (CAMELOT) study. Methods The study was a randomized controlled trial of 2 antihypertensives (amlodipine and enalapril) compared with placebo in patients with coronary artery disease and diastolic blood pressure less than 100 mm Hg. In 196 subjects who had baseline and 2-year intravascular coronary ultrasound examinations, we measured plasma interleukin 18, interleukin 1 receptor antagonist, matrix metalloproteinase 9, neopterin, and C-reactive protein. Results for both treatment groups were pooled and compared with placebo. Results Antihypertensive treatment with either agent significantly lowered diastolic blood pressure (−4.7 vs placebo 1.3 mm Hg, P = .002) and progression of coronary Atheroma (Δ percent Atheroma volume 0.6 vs placebo 2.1, P = .031). Antihypertensive therapy did not affect plasma biomarkers of inflammation or plaque remodeling in the 135 subjects with baseline and 2-year biomarker samples. Progression in percent Atheroma volume was significantly less in subjects taking statins at baseline (−2.5%, P = .0008). Conclusions In patients with coronary artery disease and well-controlled risk factors, antihypertensive therapy lowered blood pressure and progression of coronary atherosclerosis but did not affect plasma biomarkers of inflammation and remodeling. Antihypertensives may decrease Atheroma progression by mechanisms other than those reflected by these plasma biomarkers.
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lowering the triglyceride high density lipoprotein cholesterol ratio is associated with the beneficial impact of pioglitazone on progression of coronary atherosclerosis in diabetic patients insights from the periscope pioglitazone effect on regressio
Journal of the American College of Cardiology, 2011Co-Authors: Stephen J Nicholls, Murat E Tuzcu, Kathy Wolski, Ozgur Bayturan, Andrea Lavoie, Kiyoko Uno, Stuart Kupfer, Alfonso Perez, Richard W Nesto, Steven E NissenAbstract:Objectives The purpose of this study was to determine the factors associated with the favorable effect of pioglitazone on Atheroma progression. Background Diabetes mellitus is associated with accelerated coronary Atheroma progression. Pioglitazone slowed progression compared with glimepiride in this population. Methods In all, 360 diabetic patients with coronary artery disease were treated with pioglitazone or glimepiride for 18 months in the PERISCOPE (Pioglitazone Effect on Regression of Intravascular Sonographic Coronary Obstruction Prospective Evaluation) study. Coronary Atheroma progression was evaluated by serial intravascular ultrasound. The relationship between changes in biochemical parameters, percent Atheroma volume, and total Atheroma volume was investigated. Results Pioglitazone-treated patients demonstrated greater increases in high-density lipoprotein cholesterol (HDL-C) and reductions in glycated hemoglobin, triglycerides, and C-reactive protein. Significant correlations were observed between changes in percent Atheroma volume and triglycerides (r = 0.15, p = 0.04), triglyceride/HDL-C ratio (r = 0.16, p = 0.03), and glycated hemoglobin (r = 0.16, p = 0.03) with pioglitazone, and changes in low-density lipoprotein cholesterol (r = −0.15, p = 0.05), apolipoprotein B (r = −0.16, p = 0.04), and apolipoprotein A-I (r = −0.20, p = 0.01) with glimepiride. Substantial Atheroma regression, compared to progression, was associated with greater relative increases in HDL-C (14.2% vs. 7.8%, p = 0.04), relative decreases in triglycerides (−13.3% vs. −1.9%, p = 0.045), triglyceride/HDL-C ratio (−22.5 vs. −9.9%, p = 0.05), and decrease in glycated hemoglobin (−0.6% vs. −0.3%, p = 0.01). Multivariable analysis revealed that pioglitazone-induced effects on triglyceride/HDL-C were associated with changes in percent Atheroma volume (p = 0.03) and total Atheroma volume (p = 0.02). Conclusions Favorable effects of pioglitazone on the triglyceride/HDL-C ratio correlated with delayed Atheroma progression in diabetic patients. This finding highlights the potential importance of targeting atherogenic dyslipidemia in diabetic patients with coronary artery disease.
Jonathan R Weirmccall - One of the best experts on this subject based on the ideXlab platform.
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common carotid intima media thickness and ankle brachial pressure index correlate with local but not global Atheroma burden
2016Co-Authors: Jonathan R Weirmccall, Faisel Khan, Matthew Lambert, Carly L Adamson, Michael Gardner, Stephen J Gandy, Prasad Guntur Ramkumar, J J F Belch, Allan D Struthers, Petra RauchhausAbstract:Background: Common carotid intima media thickness (CIMT) and ankle brachial pressure index (ABPI) are used as surrogate marker of atherosclerosis, and have been shown to correlate with arterial stiffness, however their correlation with global atherosclerotic burden has not been previously assessed. We compare CIMT and ABPI with Atheroma burden as measured by whole body magnetic resonance angiography (WB-MRA). Methods: 50 patients with symptomatic peripheral arterial disease were recruited. CIMT was measured using ultrasound while rest and exercise ABPI were performed. WB-MRA was performed in a 1.5T MRI scanner using 4 volume acquisitions with a divided dose of intravenous gadolinium gadoterate meglumine (Dotarem, Guerbet, FR). The WB-MRA data was divided into 31 anatomical arterial segments with each scored according to degree of luminal narrowing: 0 = normal, 1 =, 50%, 2 = 50–70%, 3 = 70–99%, 4 = vessel occlusion. The segment scores were summed and from this a standardized Atheroma score was calculated. Results: The atherosclerotic burden was high with a standardised Atheroma score of 39.5611. Common CIMT showed a positive correlation with the whole body Atheroma score (b 0.32, p = 0.045), however this was due to its strong correlation with the neck and thoracic segments (b 0.42 p = 0.01) with no correlation with the rest of the body. ABPI correlated with the whole body Atheroma score (b 20.39, p = 0.012), which was due to a strong correlation with the ilio-femoral vessels with no correlation with the thoracic or neck vessels. On multiple linear regression, no correlation between CIMT and global Atheroma burden was present (b 0.13 p = 0.45), while the correlation between ABPI and Atheroma burden persisted (b 2 0.45 p = 0.005). Conclusion: ABPI but not CIMT correlates with global Atheroma burden as measured by whole body contrast enhanced magnetic resonance angiography in a population with symptomatic peripheral arterial disease. However this is primarily due to a strong correlation with ilio-femoral Atheroma burden. Citation: Weir-McCall JR, Khan F, Lambert MA, Adamson CL, Gardner M, et al. (2014) Common Carotid Intima Media Thickness and Ankle-Brachial Pressure Index Correlate with Local but Not Global Atheroma Burden: A Cross Sectional Study Using Whole Body Magnetic Resonance Angiography. PLoS ONE 9(6): e99190. doi:10.1371/journal.pone.0099190 Editor: Angelo Scuteri, INRCA, Italy Received February 5, 2014; Accepted May 12, 2014; Published June 16, 2014 Copyright: 2014 Weir-McCall et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: Funding for the study was provided by Wyeth TMRC. JRWM is supported by the Wellcome Trust through the Scottish Translational Medicine and Therapeutics Initiative (Grant no. WT 085664) in the form of a Clinical Research Fellowship. The authors have declared that no competing interests exist. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: j.weirmccall@dundee.ac.uk
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common carotid intima media thickness and ankle brachial pressure index correlate with local but not global Atheroma burden a cross sectional study using whole body magnetic resonance angiography
PLOS ONE, 2014Co-Authors: Jonathan R Weirmccall, Faisel Khan, Matthew Lambert, Carly L Adamson, Michael Gardner, Stephen J Gandy, Prasad Guntur Ramkumar, J J F Belch, Allan D StruthersAbstract:Background: Common carotid intima media thickness (CIMT) and ankle brachial pressure index (ABPI) are used as surrogate marker of atherosclerosis, and have been shown to correlate with arterial stiffness, however their correlation with global atherosclerotic burden has not been previously assessed. We compare CIMT and ABPI with Atheroma burden as measured by whole body magnetic resonance angiography (WB-MRA). Methods: 50 patients with symptomatic peripheral arterial disease were recruited. CIMT was measured using ultrasound while rest and exercise ABPI were performed. WB-MRA was performed in a 1.5T MRI scanner using 4 volume acquisitions with a divided dose of intravenous gadolinium gadoterate meglumine (Dotarem, Guerbet, FR). The WB-MRA data was divided into 31 anatomical arterial segments with each scored according to degree of luminal narrowing: 0=normal, 1= , 50%, 2=50–70%, 3=70–99%, 4=vessel occlusion. The segment scores were summed and from this a standardized Atheroma score was calculated. Results: The atherosclerotic burden was high with a standardised Atheroma score of 39.5611. Common CIMT showed a positive correlation with the whole body Atheroma score (b 0.32, p=0.045), however this was due to its strong correlation with the neck and thoracic segments (b 0.42 p=0.01) with no correlation with the rest of the body. ABPI correlated with the whole body Atheroma score (b 20.39, p=0.012), which was due to a strong correlation with the ilio-femoral vessels with no correlation with the thoracic or neck vessels. On multiple linear regression, no correlation between CIMT and global Atheroma burden was present (b 0.13 p=0.45), while the correlation between ABPI and Atheroma burden persisted (b 2 0.45 p=0.005). Conclusion: ABPI but not CIMT correlates with global Atheroma burden as measured by whole body contrast enhanced magnetic resonance angiography in a population with symptomatic peripheral arterial disease. However this is primarily due to a strong correlation with ilio-femoral Atheroma burden.
Ali Nehme - One of the best experts on this subject based on the ideXlab platform.
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8d 07 gene expression analysis and bioinformatics revealed potential transcription factors associated with renin angiotensin aldosterone system in Atheroma
Journal of Hypertension, 2015Co-Authors: Ali Nehme, Claudio Cerutti, Kazem Zibara, Giampiero BriccaAbstract:Abstract The implication of the renin-angiotensin-aldosterone system (RAAS) in Atheroma development is well described. However, a complete view of the local RAAS in Atheroma is still missing. In this study we aimed to reveal the organization of RAAS in Atheroma at the transcriptomic level and identify the transcriptional regulators behind it. Extended RAAS (extRAAS) was defined as the set of 37 genes coding for classical and novel RAAS participants (Figure 1). Five microarray datasets containing overall 590 samples representing carotid and peripheral Atheroma were downloaded from the GEO database. Correlation-based hierarchical clustering (R software) of extRAAS genes within each dataset allowed the identification of modules of co-expressed genes. Reproducible co-expression modules across datasets were then extracted. Transcription factors (TFs) having common binding sites (TFBSs) in the promoters of coordinated genes were identified using the Genomatix database tools and analyzed for their correlation with extRAAS genes in the microarray datasets. Expression data revealed the expressed extRAAS components and their relative abundance displaying the favored pathways in Atheroma. Three co-expression modules with more than 80% reproducibility across datasets were extracted. Two of them (M1 and M2) contained genes coding for angiotensin metabolizing enzymes involved in different pathways: M1 included ACE, MME, RNPEP, and DPP3, in addition to 7 other genes; and M2 included CMA1, CTSG, and CPA3. The third module (M3) contained genes coding for receptors known to be implicated in Atheroma (AGTR1, MR, GR, LNPEP, EGFR and GPER). M1 and M3 were negatively correlated in 3 of 5 datasets. We identified 19 TFs that have enriched TFBSs in the promoters of genes of M1, and two for M3, but none was found for M2. Among the extracted TFs, ELF1, MAX, and IRF5 showed significant positive correlations with peptidase-coding genes from M1 and negative correlations with receptors-coding genes from M3 (p
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8d 07 gene expression analysis and bioinformatics revealed potential transcription factors associated with renin angiotensin aldosterone system in Atheroma
Journal of Hypertension, 2015Co-Authors: Ali Nehme, Claudio Cerutti, Kazem Zibara, Giampiero BriccaAbstract:Abstract The implication of the renin-angiotensin-aldosterone system (RAAS) in Atheroma development is well described. However, a complete view of the local RAAS in Atheroma is still missing. In this study we aimed to reveal the organization of RAAS in Atheroma at the transcriptomic level and identify the transcriptional regulators behind it. Extended RAAS (extRAAS) was defined as the set of 37 genes coding for classical and novel RAAS participants (Figure 1). Five microarray datasets containing overall 590 samples representing carotid and peripheral Atheroma were downloaded from the GEO database. Correlation-based hierarchical clustering (R software) of extRAAS genes within each dataset allowed the identification of modules of co-expressed genes. Reproducible co-expression modules across datasets were then extracted. Transcription factors (TFs) having common binding sites (TFBSs) in the promoters of coordinated genes were identified using the Genomatix database tools and analyzed for their correlation with extRAAS genes in the microarray datasets. Expression data revealed the expressed extRAAS components and their relative abundance displaying the favored pathways in Atheroma. Three co-expression modules with more than 80% reproducibility across datasets were extracted. Two of them (M1 and M2) contained genes coding for angiotensin metabolizing enzymes involved in different pathways: M1 included ACE, MME, RNPEP, and DPP3, in addition to 7 other genes; and M2 included CMA1, CTSG, and CPA3. The third module (M3) contained genes coding for receptors known to be implicated in Atheroma (AGTR1, MR, GR, LNPEP, EGFR and GPER). M1 and M3 were negatively correlated in 3 of 5 datasets. We identified 19 TFs that have enriched TFBSs in the promoters of genes of M1, and two for M3, but none was found for M2. Among the extracted TFs, ELF1, MAX, and IRF5 showed significant positive correlations with peptidase-coding genes from M1 and negative correlations with receptors-coding genes from M3 (p