Effect of diabetes mellitus on coronary plaque characteristics and progression by serial Coronary Computed Tomography Angiography (CCTA)

Background Diabetes Mellitus (DM) is a major risk factor for coronary artery disease (CAD) and associated poor outcomes. There is a higher incidence of major adverse cardiac events in patients with DM than those without DM. Coronary plaque characteristics measured by CCTA are correlated with adverse cardiovascular (CV) outcomes. Purpose We sought to evaluate coronary plaque characteristics as well as rates of progression of coronary plaque burden as measured by serial CCTA in patients with DM and those without DM. Methods The study population included a total of 403 participants (mean age 61.4±11.4 years, 53% men; median scan interval 1.5 years) who were prospectively enrolled in serial CCTA trials. We identified 212 participants with DM and 191 participants without DM, who had undergone serial CCTA. Coronary Plaque volumes were measured and characterized as low attenuation plaque (LAP), total non-calcified plaque (TNCP) and total plaque (TP) using semi-automated plaque analysis software (Qangio medis). Multivariate linear regression was used to examine the effect of DM on coronary plaque progression. Results Patients with DM had greater rates of progression of normalized TP volume (median change in annualized plaque (IQR): 39.1 (9.9–114.4) in DM vs 23.5 (4.1–63.8) mm3 in non-DM, p=0.001), TNCP volume (21.6 (3.3–60.8) in DM vs 8.7 (0.1–35.6) mm3 in non-DM, p=0.003) and LAP volumes (0.7 (−0.6 to 7.8) in DM vs 0.1 (−0.4 to 1.9) mm3 in non-DM, p=0.04). After adjusting for relevant risk factors and baseline plaque, the annualized rates of progression were higher in patients with DM by 28% for TP (p=0.004), 27% for TNCP (p=0.011), 23% for fibrous plaque (p=0.026) and by 42% LAP (p=0.050), compared to those without DM. Conclusion Patients with DM have significantly higher rates of coronary plaque progression, including vulnerable LAP, than those without DM. Our findings reveal differences in rates, burden and characteristics of coronary plaque progression in patients with DM vs those without DM. These results provide mechanistic understanding of natural history of coronary atherosclerosis in this vulnerable population, that could explain the increased risk of CV events among patients with DM. Coronary atherosclerotic phenotyping by CCTA could serve as a potential surrogate measure for risk stratification and evaluation in clinical trials to examine therapeutic strategies in this vulnerable population. FUNDunding Acknowledgement Type of funding sources: None.

Downregulation of miR-29b is associated with Peyronie’s disease

Background: Peyronie’s disease (PD) is characterized by the formation of fibrous plaque in tunica albuginea, causing several problems in patients. The etiology of this disease is not fully understood, and there are few effective treatments. To better understand the molecular pathways of PD, we studied miR-29b, a microRNA that could be involved with this illness. MicroRNAs are endogenous molecules that act by inhibiting messenger RNA. MiR-29b regulates 11 of 20 collagen genes and the TGF-β1 gene, which are related to PD progression. Methods: We compared miR-29b expression in 11 patients with PD and 14 patients without PD (control group). For the patients with PD, we utilized samples from the fibrous plaque ( n = 9), from the tunica albuginea ( n = 11), and from the corpus cavernosum ( n = 8). For the control group, we utilized samples from the tunica albuginea ( n = 14) and from the corpus cavernosum ( n = 10). MiR-29b expression was determined by q-PCR. Results: We found a downregulation of miR-29b in the fibrous plaque, tunica albuginea and corpus cavernosum of patients with PD in comparison with the control group ( p = 0.0484, p = 0.0025, and p = 0.0016, respectively). Conclusion: Although our study has a small sample, we showed for the first time an evidence that the downregulation of miR-29b is associated with PD.

Discordance in the diagnostic assessment of vulnerable plaques between radiofrequency intravascular ultrasound versus optical coherence tomography among patients with acute myocardial infarction: insights from the IBIS-4 study

We aimed to evaluate the diagnostic agreement between radiofrequency (RF) intravascular ultrasound (IVUS) and optical coherence tomography (OCT) for thin-cap fibroatheroma (TCFA) in non-infarct-related coronary arteries (non-IRA) in patients with ST-segment elevation myocardial infarction (STEMI). In the Integrated Biomarker Imaging Study (IBIS-4), 103 STEMI patients underwent OCT and RF-IVUS imaging of non-IRA after successful primary percutaneous coronary intervention and at 13-month follow-up. A coronary lesion was defined as a segment with ≥ 3 consecutive frames (≈1.2 mm) with plaque burden ≥ 40% as assessed by grayscale IVUS. RF-IVUS-derived TCFA was defined as a lesion with > 10% confluent necrotic core abutting to the lumen in > 10% of the circumference. OCT-TCFA was defined by a minimum cap thickness < 65 μm. The two modalities were matched based on anatomical landmarks using a dedicated matching software. Using grayscale IVUS, we identified 276 lesions at baseline (N = 146) and follow-up (N = 130). Using RF-IVUS, 208 lesions (75.4%) were classified as TCFA. Among them, OCT identified 14 (6.7%) TCFA, 60 (28.8%) thick-cap fibroatheroma (ThCFA), and 134 (64.4%) non-fibroatheroma. All OCT-TCFA (n = 14) were confirmed as RF-TCFA. The concordance rate between RF-IVUS and OCT for TCFA diagnosis was 29.7%. The reasons for discordance were: OCT-ThCFA (25.8%); OCT-fibrous plaque (34.0%); attenuation due to calcium (23.2%); attenuation due to macrophage (10.3%); no significant attenuation (6.7%). There was a notable discordance in the diagnostic assessment of TCFA between RF-IVUS and OCT. The majority of RF-derived TCFA were not categorized as fibroatheroma using OCT, while all OCT-TCFA were classified as TCFA by RF-IVUS.ClinicalTrials.gov Identifier NCT00962416.

Peyronie’s Disease: Clinical Image

Peyronie's disease (PD) is characterized by fibrous plaque deposit in the tunica albuginea of corpus cavernosum in middle-aged and older men. It is a rare disorder with limited numbers of reported cases in literature, a prevalence rate of 3.2% was reported in Europe and a lesser prevalence of 0.6% was reported in Japan.

Abstract 15473: Effect of Statins on Coronary Plaque Progression Assessed by Serial Coronary Computed Tomography Angiography

Introduction: Statins stabilize coronary plaques and reduce clinical events. However, it is unclear how statins change the total plaque burden and plaque morphology. Hypothesis: We aimed at investigating whether statin users have less coronary plaque progression compared to non-statins users. Methods: We identified 243 subjects undergoing serial computed tomography angiography, 163 taking statins and 80 who are not. Coronary plaque (total, calcified, non-calcified including fibrous, fibrous-fatty and low-attenuation plaque (LAP)) volume was measured using semi-automated plaque software (Qangio, Medis) and its change overtime between statins users and non-statins users was evaluated using Analysis of Covariance (ANCOVA) modeling adjusted for age, gender, diabetic status, presence of hypertension, past smoking use, and baseline plaque levels. Results: Subjects on statin therapy had higher body mass index, were more likely to be diabetic, had hyperlipidemia, and were past smokers. Median coronary artery calcium score was significantly lower in the statin group; p<0.034. Driven primarily by changes in fibrous plaque, those on statin therapy showed 25% less total plaque (P=0.013) and 31% less total non-calcified plaque (P=0.006) at follow-up than non-statin users. Conclusions: The current study indicates that statin use is associated with less progression of total plaque and total non-calcified plaque burden.

Morphological characteristics of plaque erosion with noncritical coronary stenosis: an optical coherence tomography study

Background Plaque erosion is a frequent and important mechanism of acute coronary thrombosis only secondary to plaque rupture. Recent studies suggested plaque erosion with noncritical stenosis could be treated conservatively that distinct from those with critical stenosis. However, characteristics of plaque erosions with different coronary stenosis remain unknown. Purpose The present study aimed to investigate morphological features of plaque erosions with different coronary stenosis using optical coherence tomography (OCT). Methods Consecutive ST-segment elevated myocardial infarction (STEMI) patients with OCT images of culprit lesion between August 2014 and December 2017 were enrolled and 348 cases presented with plaque erosion identified by OCT. Based on the severity of lumen area stenosis [calculated by (1-minimal lumen area/reference lumen area) * 100%], all culprit plaque erosions were divided into three groups: Group A (area stenosis&lt;50%, n=50, 14.4%); Group B (50%≤area stenosis&lt;75%, n=146, 42.0%); Group C (area stenosis≥75%, n=152, 43.7%). Clinical characteristics, lesion features detected by coronary angiography and OCT were compared among three groups. Results Of all 348 STEMI patients with plaque erosions, patients in Group A were youngest (p=0.008) and had the lowest frequency of hypertension (p=0.029) as compared with those in Group B and C. Angiographic analysis showed 72.0% of plaque erosions in Group A located in LAD, while 67.8% in Group B and 53.9% in Group C (p=0.039). OCT findings (Figure 1-A) showed the prevalence of fibrous plaque was significantly highest in Group A than those in Group B and C (82.0% vs. 54.8% vs. 34.9%, p&lt;0.001), whereas lipid rich plaque was most frequent in Group C (16.0% vs. 43.8% vs. 62.5%, p&lt;0.001). The prevalence of macrophage (p&lt;0.001), microvessel (p=0.009) and cholesterol crystals (p&lt;0.001) increased gradually from plaque erosion with lumen area stenosis &lt;50% to 50–75% to ≥75%. Notably, compared with Group B and C, nearby bifurcation was most common in Group A (72.0% vs. 67.1% vs. 55.3%, p=0.036). Multivariable regression analyses (Figure 1-B) showed fibrous plaque and nearby bifurcation were independently associated with plaque erosion with noncritical stenosis (area stenosis&lt;75%). Conclusion 56.3% plaque erosion in STEMI patients presented with noncritical stenosis, having distinct morphological features from erosion with critical stenosis. Fibrous plaque and nearby bifurcation were independently associated with the presence of noncritically stenotic plaque erosion, remaining a desire to tailor treatment therapy to individual patients. Figure 1 Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): National Key R&D Program of China

The relationship between residual cholesterol risk and plaque characteristics in patients with acute coronary syndrome evaluated by optical coherence tomography

Background It has been demonstrated that high sensitive-C reactive protein (hs-CRP) and low density lipoprotein cholesterol (LDL-C) are independently associated with major adverse cardiovascular events (MACEs). Whether the level of LDL has impact on plaque characteristics in acute coronary syndrome (ACS) patients with normal hs-CRP are still unknown. Methods We retrospectively enrolled ACS patients with the level of hs-CRP&lt;2mg/L on admission from 1st January, 2017 to 31st December,2017, from our hospital. All patients underwent pre-intervention optical coherence tomography (OCT) to evaluate the plaque characteristics. Residual cholesterol risk (RCR) was defined as LDL-C≥1.8mmol/L, while hs-CRP&lt;2mg/L. According to the level of baseline LDL-C, patients were divided into RCR group and non-RCR group. Results A total of 90 patients (94 vessels) were included, with 50 patients in RCR group and 40 patients in non-RCR group. Compared with non-RCR group, patients in RCR group had higher levels of total cholesterol (4.39±0.89 vs 3.05±0.48, p=0.000), LDL-C (2.56±0.57 vs 1.54±0.22, p=0.000), triglycerides (1.11±1.12 vs 1.02±0.74, p=0.003). Patients in RCR group were younger (54.0±11.04 vs 58.4±9.59, p=0.049) and had higher rate of multivessel disease (6.0% vs 2.5%, p=0.028) than those in non-RCR group. With regard to plaque characteristics, fibrous plaque (0.0% vs 12.5%, p=0.003) was less seen and atherosclerotic plaque (79.6% vs 50.0%, p=0.028) was more seen in RCR group. In addition, patients in RCR group had significantly higher rate of plaque rupture than that in non-RCR group (24.1% vs 5%, p=0.008). To be noticed, cholesterol crystal and thin-cap fibroatheroma (TCFA) were more commonly in RCR group, though the difference was not statistical. Conclusion Patients with RCR have a great extent of plaque rupture, indicating more vulnerable plaque phenotype. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): China Youth Clinical Research Foundation-VG Foundation

High-risk plaque regression after intensive dietary intervention in patients with non-obstructive coronary artery disease: a randomised computed tomography angiography study (DISCO-CT)

Background Lifestyle and diet modification are the forefront in the management of coronary artery disease (CAD), however, there is no data whether they may stop progression of atheroslcerosis. Some coronary plaque characteristics are known to increase the risk of future cardiovascular events independently of coronary stenosis severity. These plaques are characterized by the presence of lipids and necrotic elements, and can be identified with coronary computed tomography angiography (CTA). Purpose To study the effect of intensive dietary intervention on changes in atherosclerotic plaque volume and composition. Methods We enrolled 89 patients (41% women, mean age 60±7.7 years) with nonobstructive coronary lesions (&lt;70% stenosis) identified by CTA (2x192-multislice scanner, temporal resolution 66 ms), qualified to medical treatment. All participants were subjected to optimal medical therapy (OMT). Patients were randomised (1:1) to either A) OMT with regular follow-up (after 1, 3, 6, 9 and 12 months) by a dietitian to stick to Dietary Approaches to Stop Hypertension (DASH) model, or B) routine management, ie. OMT alone. CTA was repeated in all patients after the mean time of 66.9±13.7 weeks. An experienced observer blinded to the allocated treatment group and other clinical data evaluated all of the scans. The outcome was change in total plaque volume, percent plaque volume and plaque composition, assessed with a dedicated software system. Based on tissue attenuation ranges in Hounsfield units (HU), the following components of atheroma were distinguished: dense calcium (&gt;351 HU), fibrous plaque (151 to 350 HU), and fibrofatty plaque plus necrotic core (−100 to 150 HU), regarded as the vulnerable plaque component. Results Total plaque volume did not change significantly in any group (p=0.41; Figure 1A). Percent atheroma volume increased in the control arm vs. no significant change in the experimental arm, with no significant intergroup difference (p=0.79; Figure 1B). Vulnerable plaque component decreased in both subgroups, by 52.9±82.2 mm3 in the experimental vs. 20.8±58.5 mm3 in the control arm, and there was a significant difference in the reductions between the groups (p=0.04; Figure 1C). Fibrous plaque volume and dense calcium volume did not change significantly in any group (+9.5±117.8 mm3 in the experimental vs. +7.6±92.1 mm3 in the control arm, p=0.93, and +33±68.9 mm3 vs. +30.2±52.5 mm3, p=0.78, respectively). Conclusions Intensive diet intervention atop OMT can stop the progression of atherosclerosis and lead to a significant reduction in vulnerable plaque component compared to OMT alone. Figure 1 Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): Institute of Cardiology in Warsaw, Poland

An investigation into the critical role of fibre orientation in the ultimate tensile strength and stiffness of human carotid plaque caps

The development and subsequent rupture of atherosclerotic plaques in human carotid arteries is a major cause of ischemic stroke. Mechanical characterization of atherosclerotic plaques can aid our understanding of this rupture risk. Despite this however, experimental studies on human atherosclerotic carotid plaques, and fibrous plaque caps in particular, are very limited. This study aims to provide further insights into atherosclerotic plaque rupture by mechanically testing human fibrous plaque caps, the region of the atherosclerotic lesion most often attributed the highest risk of rupture. The results obtained highlight the variability in the ultimate tensile stress, strain and stiffness experienced in atherosclerotic plaque caps. By pre-screening all samples using small angle light scattering (SALS) to determine the dominant fibre direction in the tissue, along with supporting histological analysis, this work suggests that the collagen fibre alignment in the circumferential direction plays the most dominant role for determining plaque structural stability. The work presented in this study could provide the basis for new diagnostic approaches to be developed, which non-invasively identify carotid plaques at greatest risk of rupture.Graphical Abstract

Effect of icosapent ethyl on progression of coronary atherosclerosis in patients with elevated triglycerides on statin therapy: a prospective, placebo-controlled randomized trial (EVAPORATE): interim results

Aims Though statin therapy is known to slow coronary atherosclerosis progression and reduce cardiovascular (CV) events, significant CV risk still remains. In the REDUCE-IT study, icosapent ethyl (IPE) added to statin therapy reduced initial CV events by 25% and total CV events by 30%, but its effects on coronary atherosclerosis progression have not yet been fully investigated. Therefore, this study is to determine whether IPE 4 g/day will result in a greater change from baseline in plaque volume measured by serial multidetector computed tomography than placebo in statin-treated patients. Methods and results EVAPORATE is a randomized, double-blind, placebo-controlled trial. Patients had to have coronary atherosclerosis by coronary computed tomographic angiography (CCTA) (≥1 angiographic stenoses with ≥20% narrowing), on stable statin therapy with low-density lipoprotein cholesterol levels 40–115 mg/dL, and persistently high triglyceride levels (135–499 mg/dL). Patients underwent an interim scan at 9 months and were followed for an additional 9 months with CCTA at 0, 9, and 18 months. Here, we present the protocol-specified interim efficacy results. A total of 80 patients were enrolled, with 67 completing the 9-month visit and having interpretable CCTA at baseline and at 9 months (age = 57 ± 6 years, male = 36, 63%). At the 9-month interim analysis, there was no significant change in low attenuation plaque (LAP) between active and placebo groups (74% vs. 94%, P = 0.469). However, there was slowing of total non-calcified plaque (sum of LAP, fibrofatty, and fibrous plaque) (35% vs. 43%, P = 0.010), total plaque (non-calcified + calcified plaque) (15% vs. 26%, P = 0.0004), fibrous plaque (17% vs. 40%, P = 0.011), and calcified plaque (−1% vs. 9%, P = 0.001), after adjustment by baseline plaque, age, sex, diabetes, baseline triglyceride levels, and statin use. Conclusion EVAPORATE is the first study using CCTA to evaluate the effects of IPE as an adjunct to statin therapy on atherosclerotic plaque characteristics in a high-risk CV population with persistently high triglyceride levels. It provides important mechanistic data in regards to the reduction in CV events in the REDUCE-IT clinical trial. ClinicalTrials. govIdentifier NCT029226027.