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Effects of Statin Plus Ezetimibe on Coronary Plaques in Acute Coronary Syndrome Patients with Diabetes Mellitus: Sub-Analysis of PRECISE-IVUS Trial.
Fujisue, K, Yamanaga, K, Nagamatsu, S, Shimomura, H, Yamashita, T, Nakao, K, Nakamura, S, Ishihara, M, Matsui, K, Sakaino, N, et al
Journal of atherosclerosis and thrombosis. 2021;(2):181-193
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Abstract
AIM: Coronary plaque regression is weak in acute coronary syndrome (ACS) patients with diabetes mellitus (DM). We evaluated whether dual lipid-lowering therapy (DLLT) with ezetimibe and atorvastatin attenuates coronary plaques in ACS patients with DM. METHODS The prospective, randomized controlled, multicenter PRECISE-IVUS (Plaque Regression with Cholesterol Absorption Inhibitor or Synthesis Inhibitor Evaluated by Intravascular Ultrasound) trial assigned 246 patients undergoing percutaneous coronary intervention to DLLT or atorvastatin monotherapy and evaluated IVUS-derived changes in percent atheroma volume (ΔPAV), at baseline and 9-12-month follow-up, in 126 ACS cases, including 25 DM patients. The atorvastatin dose was up-titrated to achieve low-density lipoprotein cholesterol (LDL-C) <70 mg/dL. RESULTS In DM patients, the monotherapy group (n=13) and the DLLT group (n=12) showed a similar prevalence of coronary risks and baseline lipid profiles. During the study, the change in LDL-C level was similar between DM and non-DM patients. Compared with non-DM patients, DM patients showed weaker regression of ΔPAV by DLLT than those who underwent monotherapy (DM: -2.77±3.47% vs. -0.77±2.51%, P=0.11; non-DM: -2.01±3.36% vs. -0.08±2.66%, P=0.008). The change in LDL-C level was not correlated with ΔPAV in non-DM patients, but there was significant correlation between the change in LDL-C level and ΔPAV in DM patients (r=0.52, P=0.008). CONCLUSIONS ACS patients with DM showed weaker coronary plaque regression than their counterparts. A significant correlation between the change in LDL-C level and ΔPAV in DM patients suggested that more intensive lipid-lowering therapy is required in ACS patients with DM.
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Randomized Comparison Between Everolimus-Eluting Bioresorbable Scaffold and Metallic Stent: Multimodality Imaging Through 3 Years.
Onuma, Y, Honda, Y, Asano, T, Shiomi, H, Kozuma, K, Ozaki, Y, Namiki, A, Yasuda, S, Ueno, T, Ando, K, et al
JACC. Cardiovascular interventions. 2020;(1):116-127
Abstract
OBJECTIVES The aim of this study was to investigate the vascular responses and fates of the scaffold after bioresorbable vascular scaffold (BVS) implantation using multimodality imaging. BACKGROUND Serial comprehensive image assessments after BVS implantation in the context of a randomized trial have not yet been reported. METHODS In the ABSORB Japan trial, 400 patients were randomized to a BVS (n = 266) or a cobalt-chromium everolimus-eluting stent (n = 134). Through 3 years, patients underwent serial angiography and intravascular ultrasound or optical coherence tomography (OCT). RESULTS Luminal dimension at 3 years was consistently smaller with the BVS than with the cobalt-chromium everolimus-eluting stent (mean angiographic minimal luminal diameter 2.04 ± 0.63 mm vs. 2.40 ± 0.56 mm, mean difference -0.37 mm [95% confidence interval: -0.50 to -0.24 mm]; p < 0.001), mainly because of smaller device area (6.13 ± 2.03 mm2 vs. 7.15 ± 2.16 mm2, mean difference -1.04 mm2 [95% confidence interval: -1.66 to -0.42 mm2]; p < 0.001), and larger neointimal area (2.10 ± 0.61 mm2 vs. 1.86 ± 0.64 mm2, mean difference 0.24 mm2 [95% confidence interval: 0.06 to 0.43 mm2]; p = 0.01) by OCT. BVS-treated vessels did not show previously reported favorable vessel responses, such as positive vessel remodeling, late luminal enlargement, and restoration of vasomotion, although the OCT-based healing score was on average zero (interquartile range: 0.00 to 0.00). At 3 years, intraluminal scaffold dismantling (ISD) was observed in 14% of BVS. On serial OCT, ISD was observed in 6 lesions at 2 years, where the struts had been fully apposed at post-procedure, while ISD was observed in 12 lesions at 3 years, where 8 lesions were free from ISD on 2-year OCT. In 5 cases of very late scaffold thrombosis, strut discontinuities were detected in all 4 cases with available OCT immediately before reintervention. CONCLUSIONS In this multimodality serial imaging study, luminal dimension at 3 years was smaller with the BVS than with the cobalt-chromium everolimus-eluting stent. ISD, suspected to be one of the mechanisms of very late BVS thrombosis, was observed in a substantial proportion of cases at 3 years, which developed between post-procedure and 2 years and even beyond 2 years. (AVJ-301 Clinical Trial: A Clinical Evaluation of AVJ-301 [Absorb™ BVS] in Japanese Population [ABSORB JAPAN]; NCT01844284).
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Coronary 18F-Fluoride Uptake and Progression of Coronary Artery Calcification.
Doris, MK, Meah, MN, Moss, AJ, Andrews, JPM, Bing, R, Gillen, R, Weir, N, Syed, M, Daghem, M, Shah, A, et al
Circulation. Cardiovascular imaging. 2020;(12):e011438
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Abstract
Background Positron emission tomography (PET) using 18F-sodium fluoride (18F-fluoride) to detect microcalcification may provide insight into disease activity in coronary atherosclerosis. This study aimed to investigate the relationship between 18F-fluoride uptake and progression of coronary calcification in patients with clinically stable coronary artery disease. Methods Patients with established multivessel coronary atherosclerosis underwent 18F-fluoride PET-computed tomography angiography and computed tomography calcium scoring, with repeat computed tomography angiography and calcium scoring at one year. Coronary PET uptake was analyzed qualitatively and semiquantitatively in diseased vessels by measuring maximum tissue-to-background ratio. Coronary calcification was quantified by measuring calcium score, mass, and volume. Results In a total of 183 participants (median age 66 years, 80% male), 116 (63%) patients had increased 18F-fluoride uptake in at least one vessel. Individuals with increased 18F-fluoride uptake demonstrated more rapid progression of calcification compared with those without uptake (change in calcium score, 97 [39-166] versus 35 [7-93] AU; P<0.0001). Indeed, the calcium score only increased in coronary segments with 18F-fluoride uptake (from 95 [30-209] to 148 [61-289] AU; P<0.001) and remained unchanged in segments without 18F-fluoride uptake (from 46 [16-113] to 49 [20-115] AU; P=0.329). Baseline coronary 18F-fluoride maximum tissue-to-background ratio correlated with 1-year change in calcium score, calcium volume, and calcium mass (Spearman ρ=0.37, 0.38, and 0.46, respectively; P<0.0001 for all). At the segmental level, baseline 18F-fluoride activity was an independent predictor of calcium score at 12 months (P<0.001). However, at the patient level, this was not independent of age, sex, and baseline calcium score (P=0.50). Conclusions Coronary 18F-fluoride uptake identifies both patients and individual coronary segments with more rapid progression of coronary calcification, providing important insights into disease activity within the coronary circulation. At the individual patient level, total calcium score remains an important marker of disease burden and progression. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02110303.
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Impact of iodine concentration and iodine delivery rate on contrast enhancement in coronary CT angiography: a randomized multicenter trial (CT-CON).
Rengo, M, Dharampal, A, Lubbers, M, Kock, M, Wildberger, JE, Das, M, Niezen, A, van Tilborg, F, Kofflard, M, Laghi, A, et al
European radiology. 2019;(11):6109-6118
Abstract
OBJECTIVE To compare the effect of contrast medium iodine concentration on contrast enhancement, heart rate, and injection pressure when injected at a constant iodine delivery rate in coronary CT angiography (CTA). METHODS One thousand twenty-four patients scheduled for coronary CTA were prospectively randomized to receive one of four contrast media: iopromide 300 mg I/ml, iohexol 350 mg I/ml, iopromide 370 mg I/ml, or iomeprol 400 mg I/ml. Contrast media were delivered at an equivalent iodine delivery rate of 2.0 g I/s. Intracoronary attenuation was measured and compared (per vessel and per segment). Heart rate before and after contrast media injection was documented. Injection pressure was recorded (n = 403) during contrast medium injection and compared between groups. RESULTS Intracoronary attenuation values were similar for the different contrast groups. The mean attenuation over all segments ranged between 384 HU for 350 mg I/ml and 395 HU for 400 mg I/ml (p = 0.079). Dose-length product (p = 0.8424), signal-to-noise ratio (all p > 0.05), time to peak (p = 0.324), and changes in heart rate (p = 0.974) were comparable between groups. The peak pressures differed: 197.4 psi for 300 mg I/ml (viscosity 4.6 mPa s), 229.8 psi for 350 mg I/ml (10.4 mPa s), 216.1 psi for 370 mg I/ml (9.5 mPa s), and 243.7 psi for 400 mg I/ml (12.6 mPa s) (p < 0.0001). CONCLUSION Intravascular attenuation and changes in heart rate are independent of iodine concentration when contrast media are injected at the same iodine delivery rate. Differences in injection pressures are associated with the viscosity of the contrast media. KEY POINTS • The contrast enhancement in coronary CT angiography is independent of the iodine concentration when contrast media are injected at body temperature (37 °C) with the same iodine delivery rate. • Iodine concentration does not influence the change in heart rate when contrast media are injected at identical iodine delivery rates. • For a fixed iodine delivery rate and contrast temperature, the viscosity of the contrast medium affects the injection pressure.
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Decrease in oxidized high-density lipoprotein is associated with slowed progression of coronary artery calcification: Subanalysis of a prospective multicenter study.
Miki, T, Miyoshi, T, Kotani, K, Kohno, K, Asonuma, H, Sakuragi, S, Koyama, Y, Nakamura, K, Ito, H
Atherosclerosis. 2019;:1-6
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Abstract
BACKGROUND AND AIMS Oxidized high-density lipoprotein (oxHDL) is characterized by reduced anti-inflammatory properties compared with HDL. However, the role of oxHDL in the pathogenesis of coronary artery calcification (CAC), a marker of subclinical atherosclerosis, remains unclear. We prospectively investigated the association between the change in oxHDL and progression of CAC in a substudy of a multicenter study. METHODS In the principal study, patients with a CAC score of 1-999 were treated with pitavastatin with/without eicosapentaenoic acid. Measurement of CAC with multidetector-row computed tomography and a blood test were performed at baseline and at the 1-year follow-up. In the principal study, the increase in CAC did not differ among treatment groups. In this substudy, patients were divided into two groups: CAC progression (change in Agatston score of >0) and no CAC progression. RESULTS In total, 140 patients were analyzed. The oxHDL level significantly decreased from 167 (132-246) at baseline to 122 (103-149) after treatment (median [25th-75th percentile], U/ml) (p < 0.001). The annual change in CAC was significantly positively associated with changes in oxHDL (r = 0.17, p = 0.04), triglycerides (r = 0.17, p = 0.04), and high-sensitivity C-reactive protein (r = 0.22, p = 0.01) but was not associated with changes in low-density lipoprotein cholesterol or HDL-cholesterol. Multiple logistic analysis demonstrated that the decrease in oxHDL per 10 U/ml was independently associated with CAC progression (odds ratio, 0.95; 95% confidence interval, 0.90-0.99; p = 0.04). CONCLUSIONS The decrease in oxHDL is associated with the attenuation of CAC progression, suggesting that oxHDL is a potential target for atherosclerosis prevention.
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Impact of Water- and Lipid-Soluble Statins on Nonculprit Lesions in Patients with Acute Coronary Syndrome.
Ishikawa, Y, Itoh, T, Satoh, M, Fusazaki, T, Sugawara, S, Nakajima, S, Nakamura, M, Morino, Y
International heart journal. 2018;(1):27-34
Abstract
Statins can be differentiated into two types, based on their solubility, which have potentially differing effects on the coronary artery wall. However, suspected differences in statins' effects on plaque composition have not been systemically investigated.Sixty-seven patients with acute coronary syndrome (ACS) were randomly assigned to either atorvastatin (10 mg/day) or rosuvastatin (2.5 mg/day). Intravascular ultrasound (IVUS) and integrated backscatter (IB)-IVUS, an established tool to quantify each plaque's components, were performed immediately after emergent percutaneous coronary intervention (PCI). Follow-up IVUS was performed between 6 and 12 months after PCI. Serial changes in serum lipid profiles and plaque composition volumes were compared between the two groups.Thirty-five patients were eligible for serial IB-IVUS analyses. The mean low-density lipoprotein-cholesterol level significantly decreased in the atorvastatin and rosuvastatin groups (P < 0.001); plaque volumes were also significantly reduced from 82.0 ± 46.2 to 74.9 ± 41.3 mm3 (P = 0.01) and from 74.7 ± 35.3 to 67.7 ± 27.0 mm3 (P = 0.02), respectively. IB-IVUS revealed a significant reduction in fibrous volume from 33.8 ± 20.0 to 27.5 ± 14.9 mm3 (P < 0.01) and from 29.6 ± 13.6 to 24.8 ± 7.6 mm3 (P < 0.05), respectively; however, significant changes were not noted in the volume of the lipid pool for the atorvastatin group and the rosuvastatin group, respectively.Water- and lipid-soluble statins may be similarly effective in reducing coronary plaques in patients with ACS as judged qualitatively and quantitatively. Further study is needed to determine whether differences between water- and lipid-soluble statins affect plaque components.
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Randomized trial evaluating the effect of aged garlic extract with supplements versus placebo on adipose tissue surrogates for coronary atherosclerosis progression.
Zeb, I, Ahmadi, N, Flores, F, Budoff, MJ
Coronary artery disease. 2018;(4):325-328
Abstract
AIMS: Increased epicardial adipose tissue (EAT), pericardial adipose tissue (PAT), periaortic adipose tissue (PaAT), and subcutaneous adipose tissue (SAT) are mediators of metabolic risk, and are associated with the severity of coronary artery calcium (CAC). Aged garlic extract (AGE) has been shown to reduce the progression of coronary atherosclerosis. This study evaluates the effect of AGE with supplements (AGE+S) on EAT, PAT, SAT, and PaAT. METHODS Sixty asymptomatic participants participated in a randomized trial evaluating the effect of AGE+S versus placebo on coronary atherosclerosis progression, and underwent CAC at baseline and after 12 months of treatment. EAT, PAT, PaAT, and SAT volumes were measured on CAC scans. PAT was calculated as: intrathoracic adipose tissue-EAT. SAT was defined as the volume of fat depot anterior to the sternum and posterior to the vertebra. PaAT was defined as fat depot around the descending aorta. RESULTS At 1 year, the increase in EAT, PAT, PaAT, and SAT was significantly lower in the AGE+S as compared with the placebo group (P<0.05). The odds ratios of increase in EAT, PAT, PaAT, and SAT were 0.63 [95% confidence interval (CI): 0.43-0.90], 0.72 (95% CI: 0.45-0.93), 0.81 (95% CI: 0.65-0.98), and 0.87 (CI: 0.52-0.98), respectively, compared with the placebo group, which even remained significant (all P<0.05) after adjustment for cardiovascular risk factors and statin therapy and BMI. CONCLUSION This study shows that AGE+S is associated with favorable effects on reducing the progression rate of adipose tissue volumes.
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Pathologic Intimal Thickening Plaque Phenotype: Not as Innocent as Previously Thought. A Serial 3D Intravascular Ultrasound Virtual Histology Study.
Kovarnik, T, Chen, Z, Wahle, A, Zhang, L, Skalicka, H, Kral, A, Lopez, JJ, Horak, J, Sonka, M, Linhart, A
Revista espanola de cardiologia (English ed.). 2017;(1):25-33
Abstract
INTRODUCTION AND OBJECTIVES Pathologic intimal thickening (PIT) has been considered a benign plaque phenotype. We report plaque phenotypic changes in a baseline/follow-up intravascular ultrasound-based virtual histology study. METHODS A total of 61 patients with stable coronary artery disease were analyzed from the HEAVEN trial (89 patients randomized between routine statin therapy vs atorvastatin 80mg and ezetimibe 10mg) with serial intravascular ultrasound imaging of nonculprit vessels. We compared changes in 693 baseline and follow-up 5-mm long segments in a novel risk score, Liverpool Active Plaque Score (LAPS), plaque parameters, and plaque composition. RESULTS The PIT showed the highest increase of risk score and, with fibrous plaque, also the LAPS. Necrotic core (NC) abutting to the lumen increased in PIT (22 ± 51.7; P = .0001) and in fibrous plaque (17.9 ± 42.6; P = .004) but decreased in thin cap fibroatheroma (TCFA) (15.14 ± 52.2; P = .001). The PIT was the most likely of all nonthin cap fibroatheroma plaque types to transform into TCFA at follow-up (11% of all TCFA found during follow-up and 35.9% of newly-developed TCFA), but showed (together with fibrous plaque) the lowest stability during lipid-lowering therapy (24.7% of PIT remained PIT and 24.5% of fibrous plaque remained fibrous plaque). CONCLUSIONS Over the 1-year follow-up, PIT was the most dynamic of the plaque phenotypes and was associated with an increase of risk score and LAPS (together with fibrous plaque), NC percentage (together with fibrous plaque) and NC abutting to the lumen, despite a small reduction of plaque volume during lipid-lowering therapy. The PIT was the main source for new TCFA segments.
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Effect of treatment with 5-lipoxygenase inhibitor VIA-2291 (atreleuton) on coronary plaque progression: a serial CT angiography study.
Matsumoto, S, Ibrahim, R, Grégoire, JC, L'Allier, PL, Pressacco, J, Tardif, JC, Budoff, MJ
Clinical cardiology. 2017;(4):210-215
Abstract
BACKGROUND Inflammation has a key role in the process of atherosclerosis. Production of leukotrienes by 5-lipoxygenase has been linked to atherosclerotic plaques and cardiovascular events. HYPOTHESIS In this study, a selective 5-LO inhibitor will slow plaque progression using serial cardiac computed tomographic angiography (CCTA). METHODS Patients with recent acute coronary syndrome (ACS) were prospectively assigned to one of 3 VIA-2291 doses (25 mg, 50 mg, 100 mg) or placebo by oral administration. All groups underwent CCTA at baseline and at 6 months' follow-up. Plaque types such as low-attenuation plaque (LAP), fibro-fatty tissue (FF), fibro-calcified plaque (FC), and dense calcium plaque (DC) were measured based upon predefined density threshold, and changes from baseline CCTA were analyzed. RESULTS The final analysis included 54 patients (age, 56 ± 9 years; 85.1% male) with CCTA at baseline and 24 weeks. Evaluating on treatment VIA-2291 (all 3 doses, n = 37) demonstrated significant reductions in plaque progression compared with placebo (n = 17). VIA-2291 significantly reduced LAP (5.9 ± 20.7 mm3 vs -9.7 ± 33.3 mm3 ), FF (11.1 mm3 ± 13.3 mm3 vs -0.9 ± 2.7 mm3 ), and FC (-0.1 ± 6.22 mm3 vs -14.3 ± 6.2 mm3 ; all P < 0.05) and retarded the progression of DC (3.9 ± 3.2 mm3 vs 0.2 ± 0.4 mm3 ) compared with placebo. CONCLUSIONS VIA-2291 resulted in slowed plaque progression compared with placebo across different plaque subtypes in patients with recent ACS (http://ClinicalTrials.gov NCT00358826).
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Sex Differences in the Performance of Cardiac Computed Tomography Compared With Functional Testing in Evaluating Stable Chest Pain: Subanalysis of the Multicenter, Randomized CRESCENT Trial (Calcium Imaging and Selective CT Angiography in Comparison to Functional Testing for Suspected Coronary Artery Disease).
Lubbers, M, Coenen, A, Bruning, T, Galema, T, Akkerhuis, J, Krenning, B, Musters, P, Ouhlous, M, Liem, A, Niezen, A, et al
Circulation. Cardiovascular imaging. 2017;(2)
Abstract
BACKGROUND Cardiac computed tomography (CT) represents an alternative diagnostic strategy for women with suspected coronary artery disease, with potential benefits in terms of effectiveness and cost-efficiency. METHODS AND RESULTS The CRESCENT trial (Calcium Imaging and Selective CT Angiography in Comparison to Functional Testing for Suspected Coronary Artery Disease) prospectively randomized 350 patients with stable angina (55% women; aged 55±10 years), mostly with an intermediate coronary artery disease probability, between cardiac CT and functional testing. The tiered cardiac CT protocol included a calcium scan followed by CT angiography if the Agatston calcium score was between 1 and 400. Patients with test-specific contraindications were not excluded from study participation. Sex differences were studied as a prespecified subanalysis. Enrolled women presented more frequently with atypical chest pain and had a lower pretest probability of coronary artery disease compared with men. Independently of these differences, cardiac CT led in both sexes to a fast final diagnosis when compared with functional testing, although the effect was larger in women (P interaction=0.01). The reduced need for further testing after CT, compared with functional testing, was most evident in women (P interaction=0.009). However, no sex interaction was observed with respect to changes in angina and quality of life, cumulative diagnostic costs, and applied radiation dose (all P interactions≥0.097). CONCLUSIONS Cardiac CT is more efficient in women than in men in terms of time to reach the final diagnosis and downstream testing. However, overall clinical outcome showed no significant difference between women and men after 1 year. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01393028.