scholarly journals Alternative C3 Complement System: Lipids and Atherosclerosis

2021 ◽  
Vol 22 (10) ◽  
pp. 5122
Author(s):  
Maisa Garcia-Arguinzonis ◽  
Elisa Diaz-Riera ◽  
Esther Peña ◽  
Rafael Escate ◽  
Oriol Juan-Babot ◽  
...  
Keyword(s):  
Cell Culture ◽  
Systems Biology ◽  
Complement System ◽  
Computed Tomographic Angiography ◽  
Lipid Lowering ◽  
Plaque Burden ◽  
Active Components ◽  
Differential Proteomics ◽  
Computed Tomographic ◽  
Atherosclerotic Process

Familial hypercholesterolemia (FH) is increasingly associated with inflammation, a phenotype that persists despite treatment with lipid lowering therapies. The alternative C3 complement system (C3), as a key inflammatory mediator, seems to be involved in the atherosclerotic process; however, the relationship between C3 and lipids during plaque progression remains unknown. The aim of the study was to investigate by a systems biology approach the role of C3 in relation to lipoprotein levels during atherosclerosis (AT) progression and to gain a better understanding on the effects of C3 products on the phenotype and function of human lipid-loaded vascular smooth muscle cells (VSMCs). By mass spectrometry and differential proteomics, we found the extracellular matrix (ECM) of human aortas to be enriched in active components of the C3 complement system, with a significantly different proteomic signature in AT segments. Thus, C3 products were more abundant in AT-ECM than in macroscopically normal segments. Furthermore, circulating C3 levels were significantly elevated in FH patients with subclinical coronary AT, evidenced by computed tomographic angiography. However, no correlation was identified between circulating C3 levels and the increase in plaque burden, indicating a local regulation of the C3 in AT arteries. In cell culture studies of human VSMCs, we evidenced the expression of C3, C3aR (anaphylatoxin receptor) and the integrin αMβ2 receptor for C3b/iC3b (RT-PCR and Western blot). C3mRNA was up-regulated in lipid-loaded human VSMCs, and C3 protein significantly increased in cell culture supernatants, indicating that the C3 products in the AT-ECM have a local vessel-wall niche. Interestingly, C3a and iC3b (C3 active fragments) have functional effects on VSMCs, significantly reversing the inhibition of VSMC migration induced by aggregated LDL and stimulating cell spreading, organization of F-actin stress fibers and attachment during the adhesion of lipid-loaded human VSMCs. This study, by using a systems biology approach, identified molecular processes involving the C3 complement system in vascular remodeling and in the progression of advanced human atherosclerotic lesions.

P6149Coronary computed tomographic angiography (CTA) for risk stratification in the diagnostic triage of patients undergoing liver transplantation (LT): A long-term outcome study

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
S Strobl ◽  
T Senoner ◽  
A Finkenstedt ◽  
G Widmann ◽  
F Plank ◽  
...  
Keyword(s):  
Risk Stratification ◽  
Calcium Score ◽  
Computed Tomographic Angiography ◽  
Plaque Burden ◽  
Computed Tomographic ◽  
All Cause Mortality ◽  
Stenosis Severity ◽  
Tomographic Angiography

Abstract Background Cardiovascular (CV) risk stratification in patients with end-stage liver disease (ESLD) prior to liver transplantation (LT) is crucial: CV-disease poses a major threat for posttransplant survival. Therefore, our purpose was to assess safety of coronary computed tomographic angiography (CTA) in patients prior to orthotopic LT over a long-term follow up period, and its value for CV risk stratification. Methods In this single center, retrospective observational study 458 patients underwent coronary calcium score (CCS) and coronary CTA for pre-LT risk stratification between 2005 and 2016. CTA was evaluated for 1) stenosis severity (CADRADS: 4-severe>70%/3-intermediate50–70%/2-mild<50%/1-minimal<25%/0=no CAD) 2) plaque burden (SIS, G-score), 3) high–risk plaque features (Napkin Ring Sign, low attenuation plaque, positive remodelling) and 4) Coronary Calcium Score. Primary endpoint was mortality (all-cause and cardiovascular), secondary endpoint major cardiovascular events (MACE). Results Finally 270 patients (79.3% males, age 61±8.5 years) who underwent orthotopic LT were included (mean follow-up 7.5 years±3.1, range 2–13). 87 (32.2%) had CCS zero and 60 (22.2%) CCS >300 Agatston Units (CCS 335.6 AU± 868.9). 248 patients underwent CTA after CCS. The majority had CAD (n=173, 72.3%) by CTA while only 75 (27.7%) had no CAD. 102 patients (38.8%) had minimal-or-mild stenosis<50% (CADRADS 1–2), 34 (12.9%) intermediate and 17 (6.5%) severe stenosis.Out of CCS 0 patients, 13 had non-calcified plaque. All-cause mortality rate was 46 (17.0%), with the majority of patients (43 (93.5%) experiencing non-cardiac death and 3 (6.5%) cardiovascular death due to 1 myocardial infarction and 2 cardiopulmonary failure. CADRADS predicted mortality (Kaplan Meir, p<0.001). On multivariate Cox Regression modell, SIS and G-score predicted all-cause mortality (HR 1.1:p=0.034; 95% CI: 0.649–0.983 and HR 1.1, p=0.029; 95% CI: 1.0–1.6), while Calcium Score did not. There were 6 MACE (3 STEMI, 3 NSTEMI). MACE rate was 0% in CADRADS 0 or 1, 1 in CADRADS-2 and increasing to 5 in CADRADS 3 and 4 groups. Coronary CTA for LT risk stratification Conclusion Cardiac CT is a reliable non-invasive modality for pre-LT assessment of CV-risk over a long-term period, with 0% MACE in patients with no CAD or minimal CAD. CTA allows for an improved CV-risk stratification by stenosis severity (CADRADS) and plaque burden as compared to calcium scoring.

scholarly journals Characteristics of Coronary Artery Disease in Patients with Subclinical Hypothyroidism: Evaluation Using Coronary Artery Computed Tomography Angiography

2021 ◽  
Author(s):  
Xin-zhu Zhou ◽  
Rui Shi ◽  
Jin Wang ◽  
Ke Shi ◽  
Xi Liu ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Subclinical Hypothyroidism ◽  
Linear Regression Analysis ◽  
Coronary Plaque ◽  
Computed Tomographic Angiography ◽  
Plaque Burden ◽  
Computed Tomographic ◽  
Luminal Narrowing ◽  
Artery Disease

Abstract Background: Subclinical hypothyroidism (SCH) has recently been acknowledged as an independent risk factor for coronary artery disease (CAD). However, the characteristics of CAD in patients with SCH are not fully understood. This study aims to evaluate the features of CAD in patients with SCH using coronary computed tomographic angiography (CCTA).Materials and Methods: From 1 April, 2018 to 30 June, 2020, 234 consecutive SCH patients with coronary plaques identified on CCTA were included retrospectively. They were further subdivided into different degree of SCH groups (mild SCH vs. moderate SCH vs. severe SCH: 143 vs 62 vs 28) and different gender groups (men with SCH vs. women with SCH:116 vs 118). The distributions and types of plaques, luminal narrowing, segment involvement scores (SIS) and segment stenosis scores (SSS) were evaluated and compared among the different groups.Results: Patients with severe SCH had fewer calcified plaques (0.7 ± 0.9 vs. 2.0 ± 1.9, p < 0.001) and more non-calcified plaques (0.9 ± 1.0 vs. 0.3 ± 0.5, p < 0.001) than those with mild SCH. As the SCH condition worsened, the proportion of non-calcified plaques significantly increased. Whereas there were no significant discrepancies in SIS and SSS among patients with different grades of SCH (all p > 0.05). Men with SCH had higher SIS (3.9 ± 2.3 vs. 3.0 ± 2.3, p = 0.004) and SSS (7.8 ± 5.4 vs. 5.4 ± 3.0, p = 0.002) than women. Multivariate logistic and linear regression analysis demonstrated that grades of SCH (Moderate SCH, odds ratio [OR]: 2.11; 95% CI 1.03–4.34, p = 0.042; severe SCH, OR: 10.00; 95% CI 3.82–26.20, p < 0.001, taken mild SCH as a reference) was independently associated with the presence of non-calcified plaques, whereas sex (B: 1.67; 95% CI 0.27–3.10, p = 0.009) was independently associated with SSS. Conclusions: Severe SCH is associated with non-calcified plaques, and men with SCH have higher total plaque burden than women. We suggest that it is important to evaluate for coronary plaque in SCH patients, especially those with severe SCH and men with SCH.

scholarly journals A New Approach in Risk Stratification by Coronary CT Angiography

Scientifica ◽  
2014 ◽  
Vol 2014 ◽  
pp. 1-10
Author(s):  
Rine Nakanishi ◽  
Matthew J. Budoff
Keyword(s):  
Risk Stratification ◽  
Invasive Coronary Angiography ◽  
Coronary Plaque ◽  
Computed Tomographic Angiography ◽  
Plaque Burden ◽  
Cardiovascular Risks ◽  
Computed Tomographic ◽  
Coronary Ct ◽  
Hemodynamic Information ◽  
Tomographic Angiography

For a decade, coronary computed tomographic angiography (CCTA) has been used as a promising noninvasive modality for the assessment of coronary artery disease (CAD) as well as cardiovascular risks. CCTA can provide more information incorporating the presence, extent, and severity of CAD; coronary plaque burden; and characteristics that highly correlate with those on invasive coronary angiography. Moreover, recent techniques of CCTA allow assessing hemodynamic significance of CAD. CCTA may be potentially used as a substitute for other invasive or noninvasive modalities. This review summarizes risk stratification by anatomical and hemodynamic information of CAD, coronary plaque characteristics, and burden observed on CCTA.

scholarly journals Characteristics of coronary artery disease in patients with subclinical hypothyroidism: evaluation using coronary artery computed tomography angiography

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xin-zhu Zhou ◽  
Rui Shi ◽  
Jin Wang ◽  
Ke Shi ◽  
Xi Liu ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Subclinical Hypothyroidism ◽  
Linear Regression Analysis ◽  
Coronary Plaque ◽  
Computed Tomographic Angiography ◽  
Plaque Burden ◽  
Computed Tomographic ◽  
Luminal Narrowing ◽  
Artery Disease

Abstract Background Subclinical hypothyroidism (SCH) has recently been acknowledged as an independent risk factor for coronary artery disease (CAD). However, the characteristics of CAD in patients with SCH are not fully understood. This study aims to evaluate the features of CAD in patients with SCH using coronary computed tomographic angiography (CCTA). Materials and methods From 1 April, 2018 to 30 June, 2020, 234 consecutive SCH patients with coronary plaques identified on CCTA were included retrospectively. They were further subdivided into different degree of SCH groups (mild SCH vs. moderate SCH vs. severe SCH: 143 vs 62 vs 28) and different gender groups (men with SCH vs. women with SCH:116 vs 118). The distributions and types of plaques, luminal narrowing, segment involvement scores (SIS) and segment stenosis scores (SSS) were evaluated and compared among the different groups. Results Patients with severe SCH had fewer calcified plaques (0.7 ± 0.9 vs. 2.0 ± 1.9, p < 0.001) and more non-calcified plaques (0.9 ± 1.0 vs. 0.3 ± 0.5, p < 0.001) than those with mild SCH. As the SCH condition worsened, the proportion of non-calcified plaques significantly increased. Whereas there were no significant discrepancies in SIS and SSS among patients with different grades of SCH (all p > 0.05). Men with SCH had higher SIS (3.9 ± 2.3 vs. 3.0 ± 2.3, p = 0.004) and SSS (7.8 ± 5.4 vs. 5.4 ± 3.0, p = 0.002) than women. Multivariate logistic and linear regression analysis demonstrated that grades of SCH (Moderate SCH, odds ratio [OR] 2.11; 95% CI 1.03–4.34, p = 0.042; severe SCH, OR: 10.00; 95% CI 3.82–26.20, p < 0.001, taken mild SCH as a reference) was independently associated with the presence of non-calcified plaques, whereas sex (B: 1.67; 95% CI 0.27–3.10, p = 0.009) was independently associated with SSS. Conclusions Severe SCH is associated with non-calcified plaques, and men with SCH have higher total plaque burden than women. We suggest that it is important to evaluate for coronary plaque in SCH patients, especially those with severe SCH and men with SCH.

scholarly journals Quantitative Evaluation of Coronary Plaque Progression by Computed Tomographic Angiography

2017 ◽  
Vol 44 (5) ◽  
pp. 312-319
Author(s):  
Xiujian Liu ◽  
Guanghui Wu ◽  
Chuangye Xu ◽  
Yuna He ◽  
Lixia Shu ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Right Coronary Artery ◽  
Computed Tomographic Angiography ◽  
Plaque Burden ◽  
Plaque Volume ◽  
Computed Tomographic ◽  
Luminal Area ◽  
The Right ◽  
Tomographic Angiography

Understanding plaque formation in patients at risk for coronary artery disease—the leading cause of morbidity and death in the world—enables physicians to better determine whether and how to treat these individuals. We used computed tomographic angiography to quantitatively evaluate the progression of nonculprit coronary plaques along the full length of the right coronary artery in 21 patients with acute coronary syndrome. Each right coronary artery was analyzed in sequential, 3-mm-long segments, and the minimum luminal area, plaque burden, and plaque volume within each segment were evaluated at baseline and at 12-month follow-up. Serial remodeling of the right coronary artery was also evaluated. In total, 625 arterial segments were analyzed. At 12-month follow-up, the plaque burden had increased slightly by 0.34% (interquartile range [IQR], −4.32% to 6.35%; P=0.02), and the plaque volume was not significantly changed (0.33 mm3; IQR, −3.05 to 3.54; P=0.213). The minimum luminal area decreased 0.05 mm2 (IQR, −1.33 to 0.87 mm2; P=0.012), and this was accompanied by vessel reduction, as evidenced by negative remodeling in 43% of the 625 segments. We conclude that serial computed tomographic angiography can be used to quantitatively evaluate the morphologic progression of coronary plaques.

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