High-risk Coronary Plaque Research Articles

Serial optical coherence tomography assessment of coronary atherosclerosis and long-term clinical outcomes

Abstract Background The impact of high-risk coronary artery plaques identified using optical coherence tomography (OCT) on late luminal narrowing and clinical events remains poorly understood. Methods This multicenter prospective study included 176 patients who underwent percutaneous coronary intervention (PCI) and serial OCT at baseline and 1-year follow-up to investigate non-target regions with angiographically intermediate stenosis. The primary outcome measure was luminal narrowing within the matched regions of interest in the non-target regions over a 1-year period. The secondary outcome measures included all-cause death, cardiac death, nonfatal myocardial infarction, and ischemia-driven coronary artery revascularization within 3 years. Results At 1 year after PCI, the coronary artery lumen area in non-target regions significantly decreased from 6.06 (95% confidence interval [CI], 5.60–6.53) to 5.88 (95% CI, 5.41–6.35) mm2, with a difference of -0.18 (95% CI, -0.22 to -0.14 mm2; P<0.001). This decrease was pronounced in thin-cap fibroatheromas (TCFAs), thick-cap fibroatheromas, mixed plaques, and fibrous plaques. The prevalence of TCFAs decreased from 3.4% to 3.3% (P<0.001), whereas that of thick-cap fibroatheromas also decreased from 35% to 33% (P<0.001). Patients with TCFA had a significantly higher risk of ischemia-driven non-target vessel revascularization (hazard ratio [HR], 2.42; 95% CI, 1.03–5.71; P=0.04), primarily due to revascularization in the imaged region. The higher prevalence of fibroatheroma was associated with a numerically increased risk of imaged region revascularization (HR per 10%, 1.38; 95% CI, 0.97–1.97; P=0.07). The prevalence of coronary artery calcium significantly increased from 31% at baseline to 34% at 1-year follow-up (P<0.001), accompanied by a significant increase in calcium thickness and angle. Diabetes and current smoking habits were independently associated with increasing calcium prevalence. No significant association was observed between the prevalence of coronary artery calcium and clinical outcomes within 3 years. Conclusions Coronary artery lumen area significantly decreased over a 1-year interval, particularly in TCFAs, thick-cap fibroatheromas, mixed plaques, and fibrous plaques. Although no significant association was noted between coronary artery calcium prevalence and clinical outcomes within 3 years, the interaction between calcium progression and long-term clinical events necessitates further investigation.

Serial Optical Coherence Tomography Assessment of Coronary Atherosclerosis and Long-Term Clinical Outcomes.

The impact of high-risk coronary artery plaques identified using optical coherence tomography on late luminal narrowing and clinical events remains poorly understood. This multicenter prospective study included 176 patients who underwent percutaneous coronary intervention and serial optical coherence tomography at baseline and 1-year follow-up to investigate nontarget regions with angiographically intermediate stenosis. At 1 year after percutaneous coronary intervention, the coronary artery lumen area decreased significantly from 6.06 (95% CI, 5.60-6.53) mm2 to 5.88 (95% CI, 5.41-6.35) mm2 (difference, -0.18; 95% CI, -0.22 to -0.14 mm2; P<0.001), particularly in thin-cap fibroatheromas, thick-cap fibroatheromas, mixed plaques, and fibrous plaques. The prevalence of fibroatheroma decreased from 38% to 36% (P<0.001), whereas calcified plaque increased from 31% to 34% (P<0.001), accompanied by a significant increase in calcium thickness and angle. Diabetes and current smoking habits were independently associated with increasing calcium prevalence. Patients with thin-cap fibroatheroma had a significantly higher 3-year risk of ischemia-driven nontarget vessel revascularization (hazard ratio, 2.42 [95% CI, 1.03-5.71]; P=0.04), primarily due to revascularization in the imaged region. No significant association was observed between coronary artery calcium prevalence and clinical outcomes within 3 years. The coronary artery lumen area significantly decreased over a 1-year interval, particularly in thin-cap fibroatheromas, thick-cap fibroatheromas, mixed plaques, and fibrous plaques. Although thin-cap fibroatheroma prevalence was associated with higher risk of ischemia-driven nontarget vessel revascularization, no significant association was noted between coronary artery calcium prevalence and clinical outcomes within 3 years. The interaction between calcium progression and long-term clinical events necessitates further investigation. URL: https://www.umin.ac.jp/ctr/; Unique Identifier: UMIN000031937.

Computed Tomography Angiography Identified High-Risk Coronary Plaques: From Diagnosis to Prognosis and Future Management.

CT angiography has become, in recent years, a main evaluating modality for patients with coronary artery disease (CAD). Recent advancements in the field have allowed us to identity not only the presence of obstructive disease but also the characteristics of identified lesions. High-risk coronary atherosclerotic plaques are identified in CT angiographies via a number of specific characteristics and may provide prognostic and therapeutic implications, aiming to prevent future ischemic events via optimizing medical treatment or providing coronary interventions. In light of new evidence evaluating the safety and efficacy of intervening in high-risk plaques, even in non-flow-limiting disease, we aim to provide a comprehensive review of the diagnostic algorithms and implications of plaque vulnerability in CT angiography, identify any differences with invasive imaging, analyze prognostic factors and potential future therapeutic options in such patients, as well as discuss new frontiers, including intervening in non-flow-limiting stenoses and the role of CT angiography in patient stratification.

Aggravating effect of abnormal low-density protein cholesterol level on coronary atherosclerotic plaque in type 2 diabetes mellitus patients assessed by coronary computed tomography angiography

BackgroundThe abnormal low-density protein cholesterol (LDL-C) level in the development of atherosclerosis is often comorbid in individuals with type 2 diabetes mellitus(T2DM). This study aimed to investigate the aggravating effect of abnormal LDL-C levels on coronary artery plaques assessed by coronary computed tomography angiography (CCTA) in T2DM.Materials and methodsThis study collected 3439 T2DM patients from September 2011 to February 2022. Comparative analysis of differences in coronary plaque characteristics was performed for the patients between the normal LDL-C level group and the abnormal LDL-C level group. Factors with P < 0.1 in the univariable linear regression analyses were included in the multivariable linear stepwise regression.ResultsA total of 2820 eligible T2DM patients were included and identified as the normal LDL-C level group (n = 973) and the abnormal LDL-C level group (n = 1847). Compared with the normal LDL-C level group, both on a per-patient basis and per-segment basis, patients with abnormal LDL-C level showed more calcified plaques, partially calcified plaques, low attenuation plaques, positive remodellings, and spotty calcifications. Multivessel obstructive disease (MVD), nonobstructive stenosis (NOS), obstructive stenosis (OS), plaque involvement degree (PID), segment stenosis score (SSS), and segment involvement scores (SIS) were likely higher in the abnormal LDL-C level group than that in the normal LDL-C level group (P < 0.001). In multivariable linear stepwise regression, the abnormal LDL-C level was validated as an independent positive correlation with high-risk coronary plaques and the degree and extent of stenosis caused by plaques (low attenuation plaque: β = 0.116; positive remodelling: β = 0.138; spotty calcification: β = 0.091; NOS: β = 0.427; OS: β = 0.659: SIS: β = 1.114; SSS: β = 2.987; PID: β = 2.716, all P value < 0.001).ConclusionsAbnormal LDL-C levels aggravate atherosclerotic cardiovascular disease (ASCVD) in patients with T2DM. Clinical attention deserves to be caught by the tailored identification of cardiovascular risk categories in T2DM individuals and the achievement of the corresponding LDL-C treatment goal.

Lipoprotein(a) and Coronary Plaque in Asymptomatic Individuals: The Miami Heart Study at Baptist Health South Florida.

Elevated levels of lipoprotein(a) (Lp(a)) are independently associated with an increased risk of atherosclerotic cardiovascular disease events. However, the mechanisms driving this association are poorly understood. We aimed to evaluate the association between Lp(a) and coronary plaque characteristics in a contemporary US cohort without clinical atherosclerotic cardiovascular disease, undergoing coronary computed tomography angiography, the noninvasive gold standard for the assessment of coronary atherosclerosis. We used baseline data from the Miami Heart Study-a community-based, prospective cohort study-which included asymptomatic adults aged 40 to 65 years evaluated using coronary computed tomography angiography. Those taking any lipid-lowering therapies were excluded. Elevated Lp(a) was defined as ≥125 nmol/L. Outcomes included any plaque, coronary artery calcium score >0, maximal stenosis ≥50%, presence of any high-risk plaque feature (positive remodeling, spotty calcification, low-attenuation plaque, napkin ring), and the presence of ≥2 high-risk plaque features. Among 1795 participants (median age, 52 years; 54.3% women; 49.6% Hispanic), 291 (16.2%) had Lp(a) ≥125 nmol/L. In unadjusted analyses, individuals with Lp(a) ≥125 nmol/L had a higher prevalence of all outcomes compared with Lp(a) <125 nmol/L, although differences were only statistically significant for the presence of any coronary plaque and ≥2 high-risk features. In multivariable models, elevated Lp(a) was independently associated with the presence of any coronary plaque (odds ratio, 1.40, [95% CI, 1.05-1.86]) and with ≥2 high-risk features (odds ratio, 3.94, [95% CI, 1.82-8.52]), although only 35 participants had this finding. Among participants with a coronary artery calcium score of 0 (n=1200), those with Lp(a) ≥125 nmol/L had a significantly higher percentage of any plaque compared with those with Lp(a) <125 nmol/L (24.2% versus 14.2%; P<0.001). In this contemporary analysis, elevated Lp(a) was independently associated with the presence of coronary plaque. Larger studies are needed to confirm the strong association observed with the presence of multiple high-risk coronary plaque features.

Management of Coronary VulnerablePlaque With Medical Therapyor LocalPreventive Percutaneous CoronaryIntervention.

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

High-risk coronary plaque of sudden cardiac death victims: postmortem CT angiographic features and histopathologic findings

High-risk coronary plaques (HRP) are characterized in clinical radiological imaging by the presence of low plaque attenuation, a napkin-ring sign (NRS), spotty calcifications (SC) and a positive remodeling index (RI). To evaluate if these signs are detectable in postmortem imaging by a multi-phase postmortem CT angiography (MPMCTA), a retrospective study of a series of autopsy well-documented coronary plaques related to sudden cardiac death (SCD) was performed. Then correlations between histological and radiological findings were described. Fourty SCD cases due to acute coronary syndrome based on clinical history and confirmed at autopsy were selected (28 men and 12 women, age 53.3 ± 10.9). The culprit lesion was mainly situated in the proximal segments of coronary arteries, in the right coronary artery in 23 cases (57.5%), the left anterior descending artery in 13 cases (32.5%), the circumflex artery in 3 cases (7.5%) and in one case in the left main stem. MPMCTA showed a positive RI (≥ 1.1) in 75% of cases with a mean RI 1.39 ± 0.71. RI values were lower in cases with fibrotic plaques. NRS was observed in 40% of cases, low attenuation plaque in 46.3%, and SC in 48.7% of cases. There were significant correlations of the radiological presence of NRS for fibrolipid composition of the plaque (p-value 0.007), severe intraplaque inflammation (p-value 0.017), severe adventitial inflammation (p-value 0.021) and an increased vasa vasorum (p-value 0.012). A significant correlation (p-value 0.002) was observed between the presence of SC at radiological examination and the presence of punctuate/fragmented calcification at histology. In addition, in 58.3% of cases, plaque enhancement was observed, which correlated with plaque inflammation and the fibrolipid composition of the plaque. The coronary artery calcium score was 314 (± 455). There was a poor agreement between stenosis of the lumen at histology versus radiology. Our study shows that the various radiological signs of HRP can be detected in all plaques by MPMCTA, but individually only to a variable extent; plaque enhancement appeared as a new sign of vulnerability. In the postmortem approach, these radiological markers of HRP, should always be applied in combination, which can be useful for developing a predictive model for diagnosing coronary SCD.

Evaluation of fractional flow reserve and atherosclerotic plaque characteristics on coronary non-contrast T1-weighted magnetic resonance imaging

Background and aimsThe relationship between high-risk coronary plaque characteristics regardless of the severity of lesion stenosis and myocardial ischemia remains unsettled. High-intensity plaques (HIPs) on non-contrast T1-weighted magnetic resonance imaging (T1WI) have been characterized as high-risk coronary plaques. We sought to elucidate whether the presence of coronary HIPs on T1WI influences fractional flow reserve (FFR) in the distal segment of the vessel. MethodsWe retrospectively analyzed 281 vessels in 231 patients with chronic coronary syndrome who underwent invasive FFR measurement and coronary T1WI using a multicenter registry. The plaque-to-myocardial signal intensity ratio (PMR) of the most stenotic lesion was evaluated; a coronary plaque with PMR ≥1.4 was defined as a HIP. ResultsThe median PMR of coronary plaques on T1WI in vessels with FFR ≤0.80 was significantly higher than that of plaques with FFR >0.80 (1.17 [interquartile range (IQR): 0.99–1.44] vs. 0.97 [IQR: 0.85–1.09]; p < 0.001). Multivariable analysis showed that an increase in PMR of the most stenotic segment was associated with lower FFR (beta-coefficient, −0.050; p < 0.001). The presence of coronary HIPs was an independent predictor of FFR ≤0.80 (odds ratio (OR), 6.18; 95% confidence interval (CI), 1.93–19.77; p = 0.002). Even after adjusting for plaque composition characteristics based on computed tomography angiography, the presence of coronary HIPs was an independent predictor of FFR ≤0.80 (OR, 4.48; 95% CI, 1.19–16.80; p = 0.026). ConclusionsCoronary plaques with high PMR are associated with low FFR in the corresponding vessel, indicating that plaque morphology might influence myocardial ischemia severity.

Diet and Lifestyle Intervention-Induced Pattern of Weight Loss Related to Reduction in Low-Attenuation Coronary Plaque Burden.

Despite extensive research on body weight and cardiovascular risk, the mechanistic relationship between weight loss and coronary plaque modification has not been adequately addressed. This study aimed to determine the association between body composition dynamics and low-attenuation coronary plaque (LAP) burden. Eighty-nine participants (40% women, 60 ± 7.7 years) of the Dietary Intervention to Stop Coronary Atherosclerosis in Computed Tomography (DISCO-CT) study with non-obstructive atherosclerosis with nonobstructive atherosclerosis confirmed in computed tomography angiography (CCTA), a randomized (1:1), prospective, single-center study were included into the analysis. Patients were randomly assigned to either experimental arm (intensive diet and lifestyle intervention atop optimal medical therapy, n = 45) or control arm (optimal medical therapy alone, n = 44) over 66.8 ± 13.7 weeks. Changes (∆) in body mass (BM) and body composition parameters, including total body fat (TBF), skeletal muscle mass (SMM), and fat-to-muscle ratio (FMR), measured with bioimpedance analyzer were compared with CCTA-measured ∆LAP. Coronary plaque analysis was performed using the 2 × 192 dual-energy scanner (Somatom Force, Siemens, Germany), while quantitative coronary plaque measurements were performed using a semi-automated plaque analysis software system (QAngioCT v3.1.3.13, Medis Medical Imaging Systems, Leiden, The Netherlands). Significant intergroup differences were found for ∆BM (-3.6 ± 4.9 kg in the experimental vs. -1.4 ± 2.9 kg in the control group, p = 0.015), ∆TBF (-3.4 ± 4.8% in the experimental vs. 1.1 ± 5.5% in the control arm, p < 0.001), ∆SMM (1.9 ± 2.8% in the experimental vs. -0.7 ± 3.2% in the control arm, p < 0.001), and FMR [-12.9 (-21.2; -4.3)% in the experimental vs. 3.1 (-5.3; 10.7)% in the control arm, p < 0.001]. ∆LAP did not differ significantly between the study arms; however, in the whole study population, ∆LAP was positively correlated with ∆BM, ∆TBF, and ∆FMR (r = 0.45, p < 0.001; r = 0.300, p = 0.004; r = 0.233, p = 0.028, respectively), and negatively with ∆SMM (r = -0.285, p = 0.007). Multivariate linear regression analysis revealed the association of ∆LAP with ∆BM, ∆TBF, and ∆FMR. The study intervention resulted in BM reduction characterized by fat loss, skeletal muscle gain, and increased FMR. This weight loss pattern may lead to a reduction in high-risk coronary plaque. Compared to a simple weight control, tracking body composition changes over time can provide valuable information on adverse coronary plaque modification.

Increased prevalence of high-risk coronary plaques in metabolic dysfunction associated steatotic liver disease patients: A meta-analysis.

Metabolic dysfunction associated steatotic liver disease (MASLD) is associated with an increased risk of coronary artery disease. Computed Tomography Coronary Angiography (CTCA) can assess both the extent and the features of coronary plaques. We aimed to gather evidence about the prevalence and features of coronary plaques among MASLD patients. PubMed, Scopus, and Google Scholar databases were searched for randomized controlled trials and adjusted observational studies assessing the prevalence and features of coronary plaques by means of CTCA in MASLD patients as compared with a control group. The prevalence of coronary stenosis (defined as >30% and >50% diameter of stenosis), of increasing coronary artery calcium (CAC) score and of high-risk features (namely low-attenuation plaques, napkin ring sign, spotty calcification and positive remodelling) in MASLD patients were the endpoints of interest. Twenty-four observational studies were included. MASLD was associated with an increased prevalence of critical coronary stenosis compared with controls (odds ratio [OR] 1.54, 95%CI 1.23-1.93). Increased values of CAC score were observed in MASLD patients (OR 1.35, 95%CI 1.02-1.78 and OR 2.26, 95%CI 1.57-3.23 for CAC score 0-100 and >100, respectively). An increased risk of 'high-risk' coronary plaques was observed in MASLD patients (OR 2.13, 95%CI 1.42-3.19). As high-risk features plaques, a higher prevalence of positive remodelling and spotty calcification characterize MASLD patients (OR 2.92, 95%CI 1.79-4.77 and OR 2.96, 95%CI 1.22-7.20). Patients with MASLD are at increased risk of developing critical coronary stenosis and coronary plaques characterized by high-risk features as detected by CTCA.

Proteomics associated with coronary high-risk plaques by optical coherence tomography.

Biomarkers are widely used for the diagnosis and monitoring of cardiovascular disease. However, markers for coronary high-risk plaques have not been identified.The aim of this study was to identify proteins specific to coronary high-risk plaques.Fifty-one patients (71.2 ± 11.1 years, male: 66.7%) who underwent intracoronary optical coherence tomography imaging and provided blood specimens for proteomic analysis were prospectively enrolled. A total of 1470 plasma proteins were analyzed per patient using the Olink® Explore 1536 Reagent Kit.In patients with thin-cap fibroatheroma, the protein expression of Calretinin (CALB2), Corticoliberin (CRH) and Alkaline phosphatase, placental type (ALPP) were significantly increased, while the expression of Neuroplastin (NPTN), Folate receptor gamma (FOLR3) and Serpin A12 (SERPINA12) were significantly decreased. In patients with macrophage infiltration, the protein expressions of Fatty acid-binding protein, intestinal (FABP2), and Fibroblast growth factor 21 (FGF21) were significantly decreased. In patients with lipid-rich plaques, the protein expression of Interleukin-17C (IL17C) was significantly increased, while the expression of Fc receptor-like protein 3 (FCRL3) was significantly decreased.These proteins might be useful markers in identifying patients with coronary high-risk plaques. Clinical Trial Registration: https://www.umin.ac.jp/ctr/ , UMIN000041692.

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

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

Triglyceride levels predict high-risk coronary artery plaque progression in asymptomatic patients with type 2 diabetes and normal LDL cholesterol

Abstract Background Type 2 diabetes mellitus (T2D) is associated with an increased risk of coronary artery disease (CAD) and a significant residual risk remains despite management of conventional risk factors. Purpose The purpose of the present study was to assess the association of triglycerides and high-risk plaque progression in patients with asymptomatic T2D without known CAD. Methods Asymptomatic patients with T2D and no history of CAD were studied with serial computed tomography angiography with an inter-scan interval of 13 ± 0.8 months. The total atheroma volume (TAV), and plaque composition (dense calcium, fibrous, fibrous-fatty, and necrotic core plaque) were assessed at baseline and at follow-up. Lipid status was assessed at baseline and after a one-year follow-up. Patients were divided into two groups depending on progression in triglyceride (TG) levels (TG+) and regression of TG levels (TG-). Results Of the 261 patients who were enrolled, 209 patients (157 men and 52 women) were included in the final analysis. Based on changes in TG levels, 107 patients were categorized as (TG+) and 102 patients were categorized as (TG-). The mean age was 62 ± 10 years, and the mean diabetes duration was 11 ± 8 years. At baseline, 76 % of the patients received lipid-lowering treatment, and low-density lipoprotein (LDL) cholesterol was 2.0 ± 0.8 mmol/L. A significantly higher progression of TAV was observed in patients with TG+ compared to TG- (50.2 ± 144.3 vs. -28.5 ± 176.9 mm3, P&amp;lt;0.001). This observation was primarily driven by an increase of fibrous fatty plaque (8.6 ± 41.2 vs. -12.8 ± 39.2 mm3, P&amp;lt;0.001) and necrotic core plaque (-3.9 ± 51.4 vs. -23.7 ± 71.8 mm3, P=0.002). Furthermore, an increase in TG levels predicted rapid plaque progression independent of LDL and other risk factors (OR 1.36, 95% CI; 1.02 – 1.81, P=0.04). Conclusion Changes in TG levels are associated with the progression of total and high-risk plaque volumes in asymptomatic patients with T2D and well-controlled LDL cholesterol.Low attenuation plaque vs. triglycerides

Abstract 12257: The Relationship Between Histological Features of Epicardial Adipose Tissue and Aortic Valve Calcification Assessed on Computed Tomography

Background: It has been hypothesized that epicardial adipose tissue (EAT) biologically contributes to the pathogenesis of cardiac diseases. However, it remains unclear how EAT correlates with the progression of aortic valve calcification (AVC). We evaluated if histological features of EAT are specifically related to AVC assessed on computed tomography (CT). Methods: We enrolled 35 patients undergoing cardiac CT examination before elective cardiac surgery (coronary artery bypass graft [CABG] and/or cardiac valve surgery), in which AVC was detected on CT. Each patient was evaluated with EAT volume, coronary calcium score (CCS), AVC score, and the presence of high-risk coronary plaque (HRP) on CT. During each cardiac surgery, histological samples for immunohistochemistry were obtained from EATs adjacent to the left anterior descending and right coronary arteries. Each patient was assessed with the numbers of CD-68 + and CD-11c + individual macrophages and osteocalcin + individual cells in a total of 6 random high-power fields (x400) of EAT samples. Results: In the histological findings of EAT, osteocalcin + cells showed a weak correlation with CD-68 + macrophages ( r = 0.40, p = 0.016) and a moderate correlation with CD-11c + macrophages ( r = 0.60, p = 0.0001). The AVC score on CT correlated with CD-11c + macrophages and osteocalcin + cells in EAT (Fig 1), whereas CCS had no correlation with such histological findings. On multivariate analysis adjusted for age, sex, CABG vs. non-CABG, EAT volume, CCS, and the presence of HRP, the AVC score independently correlated with increased CD-11c + macrophages (β = 0.58; p = 0.0036) and osteocalcin + cells (β = 0.59; p = 0.0021) in EAT. Fig 2 shows representative cases with different levels of AVC and EAT histology. Conclusions: The inflammatory and osteogenic activity in EAT significantly correlate with the progression of AVC, which may indicate a specific contribution of EAT to aortic valve degeneration through biological activities.

Association of oxidized ApoB and oxidized ApoA-I with high-risk coronary plaque features in cardiovascular disease.

Oxidized apolipoprotein B (oxLDL) and oxidized ApoA-I (oxHDL) are proatherogenic. Their prognostic value for assessing high-risk plaques by coronary computed tomography angiography (CCTA) is missing. In a prospective, observational study, 306 participants with cardiovascular disease (CVD) had extensive lipoprotein profiling. Proteomics analysis was performed on isolated oxHDL, and atherosclerotic plaque assessment was accomplished by quantitative CCTA. Patients were predominantly White, overweight men (58.5%) on statin therapy (43.5%). Increase in LDL-C, ApoB, small dense LDL-C (P < 0.001 for all), triglycerides (P = 0.03), and lower HDL function were observed in the high oxLDL group. High oxLDL associated with necrotic burden (NB; β = 0.20; P < 0.0001) and fibrofatty burden (FFB; β = 0.15; P = 0.001) after multivariate adjustment. Low oxHDL had a significant reverse association with these plaque characteristics. Plasma oxHDL levels better predicted NB and FFB after adjustment (OR, 2.22; 95% CI, 1.27-3.88, and OR, 2.80; 95% CI, 1.71-4.58) compared with oxLDL and HDL-C. Interestingly, oxHDL associated with fibrous burden (FB) change over 3.3 years (β = 0.535; P = 0.033) when compared with oxLDL. Combined Met136 mono-oxidation and Trp132 dioxidation of HDL showed evident association with coronary artery calcium score (r = 0.786; P < 0.001) and FB (r = 0.539; P = 0.012) in high oxHDL, whereas Met136 mono-oxidation significantly associated with vulnerable plaque in low oxHDL. Our findings suggest that the investigated oxidized lipids are associated with high-risk coronary plaque features and progression over time in patients with CVD. gov NCT01621594. National Heart, Lung, and Blood Institute at the NIH Intramural Research Program.

Insulin resistance is associated with high-risk coronary artery plaque composition in asymptomatic men between 65 and 75 years and no diabetes: A DANCAVAS cross-sectional sub-study

Background and aimsInsulin resistance (IR) and pre-diabetes are associated with an increased risk of cardiovascular disease (CVD). We aimed to investigate vulnerable plaque composition in relation to IR and pre-diabetes in asymptomatic non-diabetic men. MethodsAll participants underwent a contrast-enhanced coronary computed tomography angiography (CCTA) to evaluate coronary artery plaque burden and plaque composition (necrotic core, dense calcium, fibrotic and fibrous-fatty volume). Homeostasis model assessment of IR (HOMA-IR) was used, and participants were stratified into tertiles. Participants underwent a standard oral glucose tolerance test (OGTT) and were categorized into 2 groups (normal glucose tolerance (NGT) or pre-diabetes). A multivariable linear regression model was used to evaluate the association between vulnerable plaque composition and IR or glycemic group. ResultsFour-hundred-and-fifty non-diabetic men without known CAD were included. The mean age was 70 ± 3 years. Participants in the higher HOMA-IR tertile (H-IR) had higher median necrotic plaque volume compared to the lower HOMA-IR tertile (L-IR) (18.2 vs. 11.0 mm3, p = 0.02). H-IR tertile (β 0.37 [95% CI 0.10–0.65], p = 0.008), pack-years (β 0.07 [95% CI 0.007–0.14], p = 0.03) and total atheroma volume (TAV) (β 0.47 [95% CI 0.36–0.57], p < 0.001) remained associated with necrotic plaque volume in the multivariable linear regression model. ConclusionsIR was associated with necrotic plaque volume in asymptomatic men without diabetes. Thus, even in asymptomatic men without diabetes, IR seems to have an incremental effect on necrotic plaque volume and vulnerable plaque composition.

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

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

Coronary Plaque Characteristics Associated With Major Adverse Cardiovascular Events in Atherosclerotic Patients and Lesions: A Systematic Review and Meta-Analysis

BackgroundThe clinical value of high-risk coronary plaque characteristics (CPCs) to inform intensified medical therapy or revascularization of non–flow-limiting lesions remains uncertain. ObjectivesThe authors performed a systematic review and meta-analysis to study the prognostic impact of CPCs on patient-level and lesion-level major cardiovascular adverse events (MACE). MethodsThirty studies (21 retrospective, 9 prospective) with 30,369 patients evaluating the association of CPCs with MACE were included. CPCs included high plaque burden, low minimal lumen area, thin cap fibroatheroma, high lipid core burden index, low-attenuation plaque, spotty calcification, napkin ring sign, and positive remodeling. ResultsCPCs were evaluated with the use of intracoronary modalities in 9 studies (optical coherence tomography in 4 studies, intravascular ultrasound imaging in 3 studies, and near-infrared spectroscopy intravascular ultrasound imaging in 2 studies) and by means of coronary computed tomographic angiography in 21 studies. CPCs significantly predicted patient-level and lesion-level MACE in both unadjusted and adjusted analyses. For most CPCs, accuracy for MACE was modest to good at the patient level and moderate to good at the lesion level. Plaques with more than 1 CPC had the highest accuracy for lesion-level MACE (AUC: 0.87). Because the MACE rate was low, estimated positive predictive values for lesion-level MACE were modest. Results were mostly consistent across imaging modalities and clinical presentations, and in studies with prevailing hard outcomes. ConclusionsCharacterization of CPCs identifies high-risk atherosclerotic plaques that place lesions and patients at risk for future MACE, albeit with modest sensitivity and positive predictive value (Coronary Plaque Characteristics Associated With Major Adverse Cardiovascular Events Among Atherosclerotic Patients and Lesions; CRD42021251810)

Longitudinal association of epicardial and thoracic adipose tissues with coronary and cardiac characteristics in psoriasis

Backgrounds: Psoriasis is a disease of systemic inflammation associated with increased cardiometabolic risk. Epicardial adipose tissue (EAT) and thoracic adipose tissue (TAT) are contributing factors for atherosclerosis and cardiac dysfunction. We strove to assess the longitudinal impact of the EAT and TAT on coronary and cardiac characteristics in psoriasis. MethodsThe study consisted of 301 patients with baseline coronary computed tomography angiography (CTA), of which 139 had four-year follow up scans. EAT and TAT volumes from non-contrast computed tomography scans were quantified by an automated segmentation framework. Coronary plaque characteristics and left ventricular (LV) mass were quantified by CTA. ResultsWhen stratified by baseline EAT and TAT volume quartiles, a stepwise significant increase in cardiometabolic parameters was observed. EAT and TAT volumes associated with fibro-fatty burden (FFB) (TAT: ρ = 0.394, P < 0.001; EAT: ρ = 0.459, P < 0.001) in adjusted models. Only EAT had a significant four-year time-dependent association with FFB in fully adjusted models (β = 0.307 P = 0.003), whereas only TAT volume associated with myocardial injury in fully adjusted models (TAT: OR = 1.57 95 % CI = (1.00–2.60); EAT: OR = 1.46 95 % CI = (0.91–2.45). Higher quartiles of EAT and TAT had increased LV mass and developed strong correlation (TAT: ρ = 0.370, P < 0.001; EAT: ρ = 0.512, P < 0.001). ConclusionsOur study is the first to explore how both EAT and TAT volumes associate with increased cardiometabolic risk profile in an inflamed psoriasis cohorts and highlight the need for further studies on its use as a potential prognostic tool for high-risk coronary plaques and cardiac dysfunction.

Identification of noncalcified coronary plaque characteristics using machine learning radiomic analysis of non-contrast high-resolution computed tomography.

Novel imaging and analysis techniques may offer the ability to detect noncalcified or high-risk coronary plaques on a non-contrast computer tomography (CT) scan, advancing cardiovascular diagnostics. We aimed to explore whether machine learning (ML) radiomic analysis of low-dose high-resolution non-contrast electrocardiographically (ECG) gated cardiac CT scan allows for the identification of noncalcified coronary plaque characteristics. We prospectively enrolled 125 patients with noncalcified plaques and adverse plaque characteristics (APC) and 25 controls without visible atherosclerosis on coronary CT angiography (CCTA). All patients underwent non-contrast CT exam before CCTA. Four hundred and nineteen radiomic features were calculated to identify the presence of any coronary artery disease (CAD), obstructive CAD (stenosis >50%), plaque with ≥2 APC, degree of calcification, and specific APCs. ML models were trained on a training set (917 segmentations) and tested (validation) on a separate set (292 segmentations). Among the radiomic features, 88.3% were associated with a plaque, 0.9% with obstructive CAD, and 76.4% with the presence of at least two APCs. Overall, 80.2%, 88.5%, and 36.5%, of features were associated with calcified, partially calcified, and noncalcified plaques, respectively. Regarding APCs, 61.1%, 61.8%, 84.2%, and 61.3% of features were associated with low attenuation (LAP), napkin-ring sign (NRS), spotty calcification (SC), and positive remodeling (PR), respectively. ML models outperformed conventional methods for the presence of plaque obstructive stenosis, and the presence of 2 APCs, as well as for noncalcified plaques and partially calcified plaques, but not for calcified plaques. ML models also significantly outperformed identification of LAP and PR, but neither NRS nor SC. Radiomic analysis of non-contrast cardiac CT exams may allow for the identification of specific noncalcified coronary plaque characteristics displaying the potential for future clinical applications.