Endothelial Microvesicles Circulating in Peripheral and Coronary Circulation Are Associated With Central Blood Pressure in Coronary Artery Disease

2019 ◽  
Vol 32 (12) ◽  
pp. 1199-1205 ◽  
Author(s):  
Eugenia Gkaliagkousi ◽  
Eleni Gavriilaki ◽  
Ioannis Vasileiadis ◽  
Barbara Nikolaidou ◽  
Efthalia Yiannaki ◽  
...  

Abstract BACKGROUND Endothelial microvesicles (EMVs) have emerged as markers of endothelial injury. However, little is known about their levels in the coronary circulation of acute coronary syndrome (ACS) and stable coronary artery disease (CAD). We hypothesized that ACS patients exhibit a more pronounced increase of EMVs both in the peripheral and coronary circulation when compared with CAD. We also investigated possible associations of EMVs with markers preclinical target organ damage. METHODS We enrolled consecutive eligible patients undergoing coronary angiography. Blood samples were collected from the stem of the left coronary artery and the femoral artery. ΕMVs were measured by a standardized flow cytometry protocol. Central systolic blood pressure (cSBP) was measured invasively and patients’ history was recorded. RESULTS CAD patients exhibited increased levels of EMVs compared with controls. When patients with ACS and stable CAD were compared, the former had significantly increased EMVs in both coronary and peripheral circulation. Importantly, both ACS and CAD patients exhibited increased levels of EMVs in the coronary circulation compared with periphery. In addition, EMVs were associated with cSBP. CONCLUSIONS EMVs emerge as novel markers of ongoing underlying vascular damage, further augmenting the vicious cycle of inflammation and thrombosis mainly in ACS but also in stable CAD.

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Paulo V Camargo ◽  
Raquel M Roman ◽  
Ana Paula W Rossini ◽  
Anderson Dedonelli ◽  
Steffan F Stella ◽  
...  

Background: The balance between pro-inflammatory cytokine IL-18 and anti-inflammatory cytokine IL-10 has been suggested to play a role in atherogenesis and in the prognosis of acute coronary syndrome (ACS). We hypothesized that stable coronary artery disease (CAD) patients have a pro-inflammatory profile prior to an acute event. Methods : A case-control study nested in a cohort of stable CAD patients was performed. Patients were consecutively included and blood samples collected at 3-months intervals. Cases were patients who presented any vascular event (death, ACS, ischemic stroke, peripheral arterial occlusion and revascularization) and controls were retrieved from a sequential list, in a 1:2 ratio, after 22 ± 9 months of follow-up. Serum hs-CRP, interleukin (IL)-10, IL-18 were measured in two serial samples, collected before the events. Results : Among 176 CAD patients, 42 developed a vascular event (cases) and 76 were selected to the control group. Serum levels of IL-18 were significantly higher among cases (411 ± 185 vs. 340 ± 133pg/ml; p = 0.037). Hs-CRP levels (5.4 vs. 5.1mg/l), IL-10 (7.4 vs. 7.2pg/ml), and IL-18/IL-10 ratio (66 vs. 61) were not different between cases and controls in both samples. Cox regression analysis showed that IL-18 levels (HR 1.75 (0.89 –3.5;p = 0.11) and IL-18/IL-10 ratio (HR 1.97; 1.0 –3.8) were predictors of worse prognosis (Figure ). Conclusion: In this study, IL-18 and IL-18/IL-10 ratio were associated with clinical outcomes and support the hypothesis that the balance between pro-inflammatory and anti-inflammatory cytokines may be an important determinant of vascular events in stable CAD patients.


2007 ◽  
Vol 98 (08) ◽  
pp. 413-419 ◽  
Author(s):  
Pal Soltesz ◽  
Katalin Veres ◽  
Renata Laczik ◽  
Henrietta Der ◽  
Istvan Csipo ◽  
...  

SummaryThe aim was to measure the level of antibodies to oxidized LDL (oxLDL) and C-reactive protein (CRP) in the serum of patients with acute coronary syndrome (ACS). The results were correlated with data obtained from patients with stable coronary artery disease (stable CAD) and healthy controls.Thirty-three patients with ACS and 62 stable CAD patients were enrolled in the study. Fifty healthy individuals served as controls.The evaluation of anti-oxLDL autoantibodies was performed by ELISA, while CRP levels were measured by turbidimetry. The level of antibodies to oxLDL was significantly higher in both groups of patients with ACS and stable CAD compared to controls.The comparison between the acute and stable groups showed that anti-oxLDL levels were higher in the acute group,but because of high SD, the difference was not significant. By performing group analysis, anti-oxLDL levels were found to be significantly higher in ACS patients with unstable clinical state (circulatory insufficiency, malignant arrhythmias, recurring ischemic pain, need for urgent coronary intervention and death). CRP level in patients with ACS was significantly higher than in those with stable CAD. A positive correlation was found between anti-oxLDL antibodies and CRP levels both in patients with ACS and stable CAD. The association between the two biomarkers was stronger in the ACS group. In conclusion, our findings support the notion that the presence of antibodies to oxLDL, a plaquespecific antigen, plays a major role as a predictor of complicated manifestations of ACS.


2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Mark S Borja ◽  
Yumin He ◽  
Jacques Genest ◽  
Michael N Oda

Objective: The exchange of apolipoprotein A-I between lipid-associated and lipid-free states is a key step in reverse cholesterol transport and is representative of HDL’s functional status. Reduced HDL-apoA-I exchange (HAE) is associated with the presence of cardiovascular disease. To build on this observation, we investigated the hypothesis that HAE in a coronary artery disease-identified patient decreases with increased coronary artery disease instability. Method: HAE was measured by electron paramagnetic resonance spectroscopy (EPR), wherein nitroxide-labeled lipid-free apoA-I is introduced into apolipoprotein B-depleted plasma, incubated at 37°C and measured. When added to plasma, the nitroxide-labeled apoA-I specifically interacts with HDL and displaces resident apoA-I. The EPR spectrum reports the population of lipid-bound, spin labeled apoA-I, which is directly proportional to the amount of resident apoA-I displaced. The relative level of apoA-I displaced is representative of the plasticity of HDL and its ability to make lipid-poor apoA-I available for ABCA1-mediated cholesterol efflux. We measured HAE in the plasma of three groups: stable coronary artery disease (n=22), 3 months following acute coronary syndrome (n=19), and a control group with no history of coronary artery disease (n=15). Results: HAE was significantly lower in both the stable coronary artery disease and acute coronary syndrome groups, compared to the control group (P<0.001 and, P<0.0001, respectively). Remarkably, the ACS subjects also had significantly lower HAE compared to those with stable CAD (P<0.01). By comparing HAE to apoA-I and HDL-C levels, we observed that stable CAD and ACS subjects have lower HAE per milligram/deciliter of apoA-I, consistent with a qualitative deficiency in their apoA-I. Conclusions: HAE activity is a by-product of apoA-I qualitative status, which is inversely correlated with coronary artery disease stability.


Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1143
Author(s):  
Jeremy Yuvaraj ◽  
Andrew Lin ◽  
Nitesh Nerlekar ◽  
Ravi K. Munnur ◽  
James D. Cameron ◽  
...  

Background: High-risk plaques (HRP) detected on coronary computed tomography angiography (CTA) confer an increased risk of acute coronary syndrome (ACS). Pericoronary adipose tissue attenuation (PCAT) is a novel biomarker of coronary inflammation. This study aimed to evaluate the association of PCAT with HRP and subsequent ACS development in patients with stable coronary artery disease (CAD). Methods: Patients with stable CAD who underwent coronary CTA from 2011 to 2016 and had available outcome data were included. We studied 41 patients with HRP propensity matched to 41 controls without HRP (60 ± 10 years, 67% males). PCAT was assessed using semi-automated software on a per-patient basis in the proximal right coronary artery (PCATRCA) and a per-lesion basis (PCATLesion) around HRP in cases and the highest-grade stenosis lesions in controls. Results: PCATRCA and PCATLesion were higher in HRP patients than controls (PCATRCA: −80.7 ± 6.50 HU vs. −84.2 ± 8.09 HU, p = 0.03; PCATLesion: −79.6 ± 7.86 HU vs. −84.2 ± 10.3 HU, p = 0.04), and were also higher in men (PCATRCA: −80.5 ± 7.03 HU vs. −86.1 ± 7.08 HU, p < 0.001; PCATLesion: −79.6 ± 9.06 HU vs. −85.2 ± 7.96 HU, p = 0.02). Median time to ACS was 1.9 years, within a median follow-up of 5.3 years. PCATRCA alone was higher in HRP patients who subsequently presented with ACS (−76.8 ± 5.69 HU vs. −82.0 ± 6.32 HU, p = 0.03). In time-dependent analysis, ACS was associated with HRP and PCATRCA. Conclusions: PCAT attenuation is increased in stable CAD patients with HRP and is associated with subsequent ACS development. Further investigation is required to determine the clinical implications of these findings.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hack-Lyoung Kim ◽  
Jung Pyo Lee ◽  
Nathan Wong ◽  
Woo-Hyun Lim ◽  
Jae-Bin Seo ◽  
...  

AbstractThe role of ST2 in stable coronary artery disease (CAD) has not yet been well defined. This study was performed to investigate baseline serum soluble ST2 (sST2) level can predict clinical outcomes in patients with stable CAD. A total of 388 consecutive patients with suspected CAD (65 years and 63.7% male) in stable condition referred for elective invasive coronary angiography (ICA) was prospectively recruited. Major adverse cardiovascular event (MACE), including cardiac death, non-fatal myocardial infarction, coronary revascularization (90 days after ICA), and ischemic stroke during clinical follow-up was assessed. Most of the patients (88.0%) had significant CAD (stenosis ≥ 50%). During median follow-up of 834 days, there was 29 case of MACE (7.5%). The serum sST2 level was significantly higher in patients with MACE than those without (47.3 versus 30.6 ng/ml, P < 0.001). In multiple Cox regression model, higher sST2 level (≥ 26.8 ng/ml) was an independent predictor of MACE even after controlling potential confounders (hazard ratio, 13.7; 95% confidence interval 1.80–104.60; P = 0.011). The elevated level of baseline sST2 is associated with an increased risk of adverse clinical events in stable CAD patients. Studies with larger sample size are needed to confirm our findings.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Bayi Xu ◽  
Zhixia Xu ◽  
Yequn Chen ◽  
Nan Lu ◽  
Zhouwu Shu ◽  
...  

Abstract Background Both DNA genotype and methylation of antisense non-coding RNA in the INK4 locus (ANRIL) have been robustly associated with coronary artery disease (CAD), but the interdependent mechanisms of genotype and methylation remain unclear. Methods Eighteen tag single nucleotide polymorphisms (SNPs) of ANRIL were genotyped in a matched case–control study (cases 503 and controls 503). DNA methylation of ANRIL and the INK4/ARF locus (p14ARF, p15INK4b and p16INK4a) was measured using pyrosequencing in the same set of samples (cases 100 and controls 100). Results Polymorphisms of ANRIL (rs1004638, rs1333048 and rs1333050) were significantly associated with CAD (p < 0.05). The incidence of CAD, multi-vessel disease, and modified Gensini scores demonstrated a strong, direct association with ANRIL gene dosage (p < 0.05). There was no significant association between ANRIL polymorphisms and myocardial infarction/acute coronary syndrome (MI/ACS) (p > 0.05). Methylation levels of ANRIL were similar between the two studied groups (p > 0.05), but were different in the rs1004638 genotype, with AA and AT genotype having a higher level of ANRIL methylation (pos4, p = 0.006; pos8, p = 0.019). Further Spearman analyses indicated that methylation levels of ANRIL were positively associated with systolic blood pressure (pos6, r = 0.248, p = 0.013), diastolic blood pressure (pos3, r = 0.213, p = 0.034; pos6, r = 0.220, p = 0.028), and triglyceride (pos4, r = 0.253, p = 0.013), and negatively associated with high-density lipoprotein cholesterol (pos2, r = − 0.243, p = 0.017). Additionally, we identified 12 transcription factor binding sites (TFBS) within the methylated ANRIL region, and functional annotation indicated these TFBS were associated with basal transcription. Methylation at the INK4/ARF locus was not associated with ANRIL genotype. Conclusions These results indicate that ANRIL genotype (tag SNPs rs1004638, rs1333048 and rs1333050) mainly affects coronary atherosclerosis, but not MI/ACS. There may be allele-related DNA methylation and allele-related binding of transcription factors within the ANRIL promoter.


2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Dinaldo Oliveira ◽  
Elaine Heide ◽  
Maira Pita ◽  
Danielle A Oliveira ◽  
Ricardo Pontes ◽  
...  

Introduction: The role of the immune and inflammatory pathways in patients with coronary artery disease (CAD) is important but not complete understood. The aim of this study was to evaluate concentrations of the interleukins 17 (IL 17) according to severity of coronary stenosis in patients with stable CAD Hypothesis: There is no association between severity of coronary stenosis and IL 17 in patients with stable CAD. Methods: This is a cross-sectional, prospective, analytical study, conducted from january to september, 2013. We included 40 patients (P) with stable CAD, CCS III or IV, ischemic myocardial scintigraphy, who had not been subjected to any kind of myocardial revascularization and with coronary stenosis ≥ 50% according to current coronary angiography. There were 20 healthy volunteers (C), to take up comparison of concentrations of IL 17. Interleukins were evaluated in serum of patients and after 48 hours of cells in culture with and without stimulus. IL 17 A concentrations were expressed in pg / ml. Coronary stenosis were classified as severe (> 70%) [SS] and intermediate (50 - 69%) [MS] according to coronary angiography. Results: Stenosis ≥ 50% were found in the anterior descending artery in 31 patients, in the left circumflex artery in 19 patients, and in the right coronary artery in 24 patients. No cases of stenosis were observed in the left main. Eighteen patients (45%) had single-artery disease, 8 patients (20%) had two-artery disease, and 14 patients (35%) had multiarterial disease. The comparison between the groups showed: IL 17: Serum: P with SS = 3.91 (3.91 -- 72.27) vs P with MS = 3.91 (3.91 -- 3.91) vs C = 3.91 (3.91 -- 28.8), p = 0.53; culture 48 hours without stimulus: P with SS = 3.91 (3.91 -- 3.91) vs P with MS = 3.91 (3.91 -- 86.8) vs C = 3.91 (3.91 -- 53.3), p = 0.55; culture 48 hours with stimulus: P with SS = 241.8 (3.91 -- 2200) vs P with MS = 217.5 (3.91 -- 1346) vs C = 154.3 (3.91 -- 1353), p = 0.7. Conclusions: There were no differences in concentrations of IL 17 according to severity of coronary stenosis, does not matter in serum or cell in culture. In conclusion, there was no association between severity of coronary stenosis and IL 17 in patients with stable CAD


2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Dinaldo Oliveira ◽  
Maira R Pitta ◽  
Ivan R Pitta ◽  
Elayne Heide ◽  
Viviane R Gomes ◽  
...  

Introduction: The role of the immune and inflammatory pathways in coronary artery disease (CAD) is important but not complete understood. The aim of this study was to evaluate expressions of the interleukins 17th and 22th in patients with stable coronary artery disease. Hypothesis: Interleukins 17th and 22th are not increased in stable CAD. Methods: This is a cross-sectional, prospective, analytical study, conducted from August to December 2012. We included 40 patients (P) with stable CAD, CCS III or IV, ischemic myocardial scintigraphy, who had not been subjected to any kind of myocardial revascularization and with coronary stenosis equal or major than 50% according to current coronary angiography. There were 20 healthy volunteers (C), to take up comparison of expression of interleukins (IL). We evaluated the levels of IL 17th and 22th of the patients and controls. Interleukins were evaluated in serum of patients and after 48 hours of cells in culture with and without stimulus. IL concentrations were expressed in pg / ml. Statistical analysis was performed using the Mann-Whitney or Student t test. P ≤ 0,05 was considered statistically significant. Results: There were 26 men and 14 women in the group of the patients and 12 men and 8 women in the controls. The age was similar between the groups (63.2 ± 8.9 years vs 57.9 ± 9.4, p = ns). The comparison between the groups showed: Interleukin 17th: Serum: P = 3.9 (972.2 -- 2.93) vs C = 3.90 (28.8 -- 1.74), p = 0.5; culture 48 hours without stimulus: P = 3.90 (3.90 -- 3.90) vs C = 6.37 (3.90 - 11), p = 0.8; culture 48 hours with stimulus: P = 302.42 (2200 -- 3.90) vs C = 815 (1353 -- 3.90), p = 0.06. Interleukin 22th: Serum: P = 15.62 (64.72 -- 15.62) vs C = 15.62 (121 -- 15.62), p = 0.2; Culture 48 hours without stimulus: P = 11 (128.93 -- 7.81) vs C = 7.81 (7.81 -- 7.81), P = 0.8; Culture 48 hours with stimulus: P = 135 (2486.7 -- 7, 81) vs C = 322.86 (1319.11 -- 7.81), p = 0.4. Conclusions: There were no differences in concentrations of interleukins, but the trend of higher expression of the IL 17th in the controls after cell culture with stimulus. In conclusion, in patients with stable CAD the interleukins 17th and 22th did not exhibit increased concentrations.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A Darmon ◽  
G Ducrocq ◽  
A Jasilek ◽  
J M Juliard ◽  
E Sorbets ◽  
...  

Abstract Background The COMPASS trial demonstrated that a combination of rivaroxaban and aspirin improved cardiovascular (CV) outcomes in high-risk patients with either peripheral artery disease (PAD) or stable coronary artery disease (CAD) compared with aspirin alone, at the price of increased bleeding. A previous analysis of the REACH Registry reported an eligibility rate of 52.9% within a population with stable vascular disease. However, most of cardiologists actually treat patients with stable CAD, rather than PAD. Data regarding eligibility to COMPASS in CAD patients from real life practice are scarce. Purpose We aimed to describe the proportion of patients eligible to COMPASS within the CLARIFY Registry. Additionally, we aimed to describe their management and outcomes, comparing patients excluded from the trial (COMPASS Excluded), patients eligible for the trial (COMPASS Eligible), and patients who did not meet the “enrichment criteria” for enrolment (COMPASS Not Included). Methods We used the CLARIFY Registry, an international observational registry of more than 30.000 patients with stable CAD. In accordance with COMPASS exclusion criteria, patients with a REACH bleeding risk score >10, heart failure (HF), severe renal insufficiency, need for dual antiplatelet therapy (DAPT), or anticoagulant (AC) therapy were excluded. Then, COMPASS inclusion criteria were applied: CAD patients had to be 65 years or more, or, if younger, have documented atherosclerosis (PAD or revascularization involving at least two vascular beds) or at least two enrichment criteria (current smoker, diabetes mellitus, GFR <60 mL/min, or non lacunar ischemic stroke).The ischemic outcome was a composite of CV death, MI, or stroke and bleeding outcome was a composite of bleeding leading to either admission or transfusion, or haemorrhagic stroke. Results Among 15.185 patients with comprehensive data allowing precise assessment of eligibility, 43.1% (n=6.540) had at least one exclusion criteria (COMPASS-Excluded), 23.1% (n=3.503) did not have enrichment criteria (COMPASS-Not Included) and 33.9% (n=5.142) were eligible. The vast majority of excluded patients were excluded due to high bleeding risk (62.7% needing DAPT, and 52.7% for high REACH bleeding risk score). The rates (100 patients/year) of ischemic and bleeding outcome were 2.3 [2.1–2.5] and 0.5 [0.4–0.6] respectively for COMPASS-Eligible, 3.0 [2.8–3.2] and 0.6 [0.5–0.7] for COMPASS-Excluded and 1.2 [1.0–1.4] and 0.2 [0.2–0.3] for COMPASS-Not Included. Ischemic and bleeding events Conclusion In a large contemporary registry of stable CAD patients, approximately one of three patients was potentially eligible for adjunction of low-dose rivaroxaban to aspirin. This group is at particularly high risk of ischemic outcome. Patients with exclusion criteria for COMPASS had the worse ischemic and bleeding outcomes and represent a group in need of improved therapy. Acknowledgement/Funding None


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