Osteoprotegerin and Osteopontin Serum Levels are Associated with Vascular Function and Inflammation in Coronary Artery Disease Patients

2020 ◽  
Vol 18 (5) ◽  
pp. 523-530 ◽  
Author(s):  
Konstantinos Maniatis ◽  
Gerasimos Siasos ◽  
Evangelos Oikonomou ◽  
Manolis Vavuranakis ◽  
Marina Zaromytidou ◽  
...  

Background: Osteoprotegerin and osteopontin have recently emerged as key factors in both vascular remodelling and atherosclerosis progression. Interleukin-6 (IL-6) is an inflammatory cytokine with a key role in atherosclerosis. The relationship of osteoprotegerin, osteopontin, and IL-6 serum levels with endothelial function and arterial stiffness was evaluated in patients with coronary artery disease (CAD). Methods: We enrolled 219 patients with stable CAD and 112 control subjects. Osteoprotegerin, osteopontin and IL-6 serum levels were measured using an ELISA assay. Endothelial function was evaluated by flow-mediated dilation (FMD) in the brachial artery and carotid-femoral pulse wave velocity (PWV) was measured as an index of aortic stiffness. Results: There was no significant difference between control subjects and CAD patients according to age and sex. Compared with control subjects, CAD patients had significantly impaired FMD (p<0.001) and increased PWV (p=0.009). CAD patients also had significantly higher levels of osteoprotegerin (p<0.001), osteopontin (p<0.001) and IL-6 (p=0.03), compared with control subjects. Moreover, IL-6 levels were correlated with osteoprotegerin (r=0.17, p=0.01) and osteopontin (r=0.30, p<0.001) levels. FMD was correlated with osteoprotegerin levels independent of possible confounders [b coefficient= - 0.79, 95% CI (-1.54, -0.05), p=0.04]. Conclusion: CAD patients have increased osteoprotegerin, osteopontin and IL-6 levels. Moreover, there is a consistent association between osteoprotegerin and osteopontin serum levels, vascular function and inflammation in CAD patients. These findings suggest another possible mechanism linking osteoprotegerin and osteopontin serum levels with CAD progression through arterial wall stiffening and inflammation.

2021 ◽  
Author(s):  
Mina Mohammad-Rezaei ◽  
Reza Ahmadi ◽  
Ali Rafiei ◽  
Arsalan Khaledifar ◽  
Shohila Fatahi ◽  
...  

Abstract Coronary Artery Disease (CAD) is a chronic inflammatory disease caused by atherosclerosis and arteries become clogged due to plaque formation, fat accumulation, and various sorts of immune cells. IL-32 is a new proinflammatory cytokine, which enhances inflammation through inducing different inflammatory cytokines. The purpose of current research was to assess IL-32 serum levels in coronary artery disease subjects and its relationship with serum levels of IL-6 and TNF-α. Forty-two subjects diagnosed with CAD and thirty-nine control subjects were enrolled in the research. Serum levels of IL-6, TNF-α, and IL-32 were measured using the enzyme-linked immunosorbent assay (ELISA). IL-32, TNF-α, and IL-6 serum levels were significantly higher by 2.7, 3.48, and 3.2-fold in the CAD subjects than in control subjects, respectively. Moreover, no significant difference was found in TNF-α, IL-6 and IL-32 serum levels with the clogged arteries number in the CAD group. TNF-α and IL-32 serum levels in the CAD subjects with cardiac arterial stenosis in one major vessel were significantly increased than CAD subjects with cardiac arterial stenosis in more than one major vessels. ROC curve analysis revealed that serum levels of IL-32, TNF-α, and IL-6 showed good abilities in predicting CAD. Also, Multiple logistic regression analyses suggested that TNF-α, IL-6, and IL-32, serum levels of LDL and ox-LDL were independently related to the presence of CAD, while HDL serum levels were not. TNF-α, IL-32, and IL-6 showed an increase in CAD group and serum levels of these cytokines showed good abilities in predicting CAD. Our data suggested the involvement of TNF-α and IL-32 in the early stage of CAD.


2021 ◽  
Vol 10 (12) ◽  
pp. 2720
Author(s):  
Hyun-Woong Park ◽  
Min-Gyu Kang ◽  
Jong-Hwa Ahn ◽  
Jae-Seok Bae ◽  
Udaya S. Tantry ◽  
...  

To evaluate the effect of clopidogrel vs. aspirin monotherapy on vascular function and hemostatic measurement. Background: Monotherapy with P2Y12 receptor inhibitor vs. aspirin can be a useful alterative to optimize clinical efficacy and safety in high-risk patients with coronary artery disease (CAD). Methods: We performed a randomized, open-label, two-period crossover study in stented patients receiving at least 6-month of dual antiplatelet therapy (DAPT). Thirty CAD patients with moderate-to-high ischemic risk were randomly assigned to receive either 75 mg of clopidogrel or 100 mg of aspirin daily for 4 weeks, and were crossed over to the other strategy for 4 weeks. Vascular function was evaluated with reactive hyperemia-peripheral arterial tonometry (RH-PAT) and brachial-ankle pulse wave velocity (baPWV). Hemostatic profiles were measured with VerifyNow and thromboelastography (TEG). The primary endpoint was the reactive hyperemia index (RHI) during clopidogrel or aspirin monotherapy. Results: Clopidogrel vs. aspirin monotherapy was associated with better endothelial function (RHI: 2.11 ± 0.77% vs. 1.87 ± 0.72%, p = 0.045), lower platelet reactivity (130 ± 64 vs. 214 ± 50 P2Y12 reaction unit [PRU], p < 0.001) and prolonged reaction time (TEG R: 5.5 ± 1.2 vs. 5.1 ± 1.1 min, p = 0.037). In multivariate analysis, normal endothelial function (RHI ≥ 2.1) was significantly associated with clot kinetics (TEG angle ≤ 68 degree) and ‘PRU ≤ 132’. ‘PRU ≤ 132’ was achieved in 46.2% vs. 3.8% during clopidogrel administration vs. aspirin monotherapy (odds ratio 21.4, 95% confidence interval 2.7 to 170.1, p < 0.001). Conclusions: In CAD patients, clopidogrel vs. aspirin monotherapy was associated with better endothelial function, greater platelet inhibition and lower coagulation activity, suggesting pleiotropic effects of clopidogrel on endothelial function and hemostatic profiles.


2020 ◽  
Vol 16 (4) ◽  
pp. 508-513
Author(s):  
Farshad K. Birgani ◽  
Majid M. Shahi ◽  
Bahman Cheraghian ◽  
Habib Haybar

Background: Coronary artery disease (CAD) is one of the most common cardiovascular diseases that can lead to mortality, inability, and lower productivity levels. Objective: The aim of this study was to determine the relationship between serum vitamin D level and cardiovascular risk factors and the severity of CAD after determining and eliminating the confounding effects of dietary patterns in male patients undergoing angiography. Methods: This descriptive-analytic study was carried out on 132 men undergoing angiography during 2017 and 2018. To this end, food frequency questionnaire (FFQ) and physical activity questionnaire (PAQ) were completed for the patients. Fasting blood sugar (FBS), triglyceride, total cholesterol, HDL-C, LDL-C and vitamin D levels were also investigated. Results: Serum vitamin D levels significantly decreased with an increase in CAD severity (p=0.001). Also, low serum levels led to the highest severity of CAD (p=0.005). However, there was no significant difference between patients with vitamin D deficiency with different degrees of CAD (p=0.084). Also, the highest percentage of individuals with normal serum levels of vitamin D was observed in the group without any blocked blood arteries (normal) (p=0.023). Conclusion: This study shows an inverse relationship between serum 25(OH) D level and the severity of CAD. Our data show that vitamin D plays an important role in preventing CAD. These findings could help design prospective studies and clinical trials on a wider scale to investigate the effects of vitamin D interventions in preventing the development of CAD.


2013 ◽  
Vol 111 (7) ◽  
pp. 1245-1252 ◽  
Author(s):  
Patrick Horn ◽  
Nicolas Amabile ◽  
Franca S. Angeli ◽  
Roberto Sansone ◽  
Berthold Stegemann ◽  
...  

Current evidence suggests that regenerative v. degenerative endothelial responses can be integrated in a clinical endothelial phenotype, reflecting the net result between damage from risk factors and endogenous repair capacity. We have previously shown that a cocoa flavanol (CF) intervention can improve endothelial function and increase the regenerative capacity of the endothelium by mobilising circulating angiogenic cells in patients with coronary artery disease (CAD). The aim of the present study was to investigate whether CF can lower the levels of circulating endothelial microparticles (EMP), markers of endothelial integrity, along with improvements in endothelial function. The levels of EMP in the frozen plasma samples of CAD patients were measured along with endothelial function (flow-mediated vasodilation, FMD); n 16, FMD data published previously), and these data were compared with those of young (n 12) and age-matched (n 12) healthy control subjects. The CAD patients exhibited significantly increased levels of EMP along with impaired FMD when compared with the healthy control subjects. The levels of CD144+ and CD31+/41− EMP were inversely correlated with FMD (r − 0·67, P= 0·01 and r − 0·59, P= 0·01, respectively). In these CAD patients, the levels of EMP were measured after they had consumed a drink containing 375 mg of CF (high-CF intervention, HiFI) or 9 mg of CF (macro- and micronutrient-matched low-CF control, LoFl) twice daily over a 30-d period in a randomised, double-blind, cross-over study. After 1 month of HiFI, the levels of CD31+/41− and CD144+ EMP decreased ( − 25 and − 23 %, respectively), but not after LoFl. Our data show that flavanols lower the levels of EMP along with higher endothelial function, lending evidence to the novel concept that flavanols may improve endothelial integrity.


2012 ◽  
Vol 59 (13) ◽  
pp. E2066
Author(s):  
Konstantinos Maniatis ◽  
Gerasimos Siasos ◽  
Dimitris Tousoulis ◽  
Evangelos Oikonomou ◽  
Marina Zaromitidou ◽  
...  

BMJ Open ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. e037340
Author(s):  
Jing-Lu Jin ◽  
Ye-Xuan Cao ◽  
Li-Guo Wu ◽  
Xiang-Dong You ◽  
Na Guo ◽  
...  

ObjectiveThe aim of the study was to investigate the impacts of triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) dyslipidaemia on prognosis in coronary artery disease (CAD) patients with different glucose metabolism status.DesignAn observational cohort study.Setting/participantsA total of 3057 patients with stable CAD were consecutively enrolled and divided into three groups according to different glucose metabolism status. Atherogenic dyslipidaemia (AD) was defined as TG ≥1.7 mmol/L and HDL-C <1.0 mmol/L for men or <1.3 mmol/L for women. The patients were further classified into six subgroups by status of AD. All subjects were followed up for the cardiovascular events (CVEs).Primary outcome measuresThe primary endpoints were cardiovascular mortality, non-fatal myocardial infarction and non-fatal stroke.ResultsDuring a median follow-up of 6.1 years, 308 (10.1%) CVEs occurred. No significant difference in the occurrence of CVEs was observed between normal glucose regulation (NGR) and pre-diabetes (pre-DM) groups (HR: 1.25, 95% CI 0.89 to 1.76) while DM group presented 1.45-fold higher risk of CVEs (HR: 1.45, 95% CI 1.02 to 2.05). When the participants were categorised according to combined status of two parameters, the cardiovascular risk was significantly elevated in pre-DM or DM plus AD group compared with the NGR plus non-AD group (HR: 1.76, 95% CI 1.10 to 2.80 and HR: 1.87, 95% CI 1.17 to 2.98).ConclusionsThe present study suggested that the presence of AD might affect the prognosis in patients with DM or pre-DM and stable CAD.


Author(s):  
Fatemeh Khaki-Khatibi

Background: Coronary Artery Disease (CAD) is a major cause of mortality in most countries. Many risk factors such as high blood pressure, hyperlipidemia, diabetes, age, sex, obesity, smoking, and family history play a role in CAD. The aim of this study was to evaluate the concentration of Total Sialic Acid (TSA) and Lipid Profiles (LP) with the Severity of the Vessel in patients with non-smoker and diabetic CAD, so that by measuring these parameters, effective help for diagnosis and prevention for healthy people Prone to CAD, and also control the treatment of patients. Methods: In this study, 200 individual including 160 patient and 40 control group were considered. All patient groups were non-smokers and diabetic. Patients were divided into 4 groups according to the results of angiography: Patients with Normal angiography (n = 40) with one eclipse (n = 40), patients with double stenosis (n = 40) and patients with eclipse Three vessels (n = 40). The control group was chosen from people who had no history of CAD and other diseases. The lipid profile was measured by standard methods and serum total sialic acid was measured by ELISA method. Results: There was no significant difference between the two groups in age and sex, but there was a significant difference in family history (p<0.05). There was a significant difference in serum glucose level between the patient and the control group (p<0.05), Also hs-CRP serum levels were normal in two patient and control groups. Serum levels of cholesterol, triglyceride and LDL in patient group were significantly higher than that of the control group but HDL serum level was adverse (p <0.05), Also TSA serum level in the patient group was significantly higher than the control group (p<0.05). Conclusion: Serum Total Sialic Acid level in non-smoker and diabetic CAD patients has a significant increase compared to the control group. It seems that the above biochemical parameters contribute significantly to the development and progression of atherosclerosis and CAD, by which timely measurements of these parameters in healthy individual probably can be helpful in preventing and improving CAD and controlling the treatment of patients.


2013 ◽  
Vol 61 (10) ◽  
pp. E1187
Author(s):  
Konstantinos Maniatis ◽  
Gerasimos Siasos ◽  
Dimitris Tousoulis ◽  
Evangelos Oikonomou ◽  
Marina Zaromitidou ◽  
...  

2019 ◽  
Vol 46 (04) ◽  
pp. 446-456
Author(s):  
Mads Lamm Larsen ◽  
Erik Lerkevang Grove ◽  
Steen Dalby Kristensen ◽  
Anne-Mette Hvas

AbstractThe trade-off between the benefits and harm of long-term (> 12 months) treatment with P2Y12 inhibitors in patients with coronary artery disease (CAD) after percutaneous coronary intervention (PCI) remains controversial. This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. PubMed and Embase were searched without time restrictions to identify randomized controlled trials comparing > 12-month P2Y12 inhibition versus ≤ 12-month treatment in patients with acute coronary syndrome (ACS) or stable CAD undergoing PCI. A qualitative assessment was performed using the assessment tool from the National Heart, Lung, and Blood Institute of the National Institutes of Health. We performed a meta-analysis of the following endpoints: primary outcome (primarily major cardiovascular events), all-cause death, and major bleeding. Eight trials, comprising 40,218 patients, were included. Five studies were rated “good,” two studies “fair,” and one study “poor.” The meta-analysis showed that > 12-month P2Y12 inhibition significantly reduced the primary outcomes compared with ≤ 12-month treatment (hazard ratio [HR]: 0.85; 95% confidence interval (CI): 0.75–0.97; p = 0.01). No significant difference was demonstrated between groups in all-cause death (HR: 1.02; 95% CI: 0.76–1.36; p = 0.91) or major bleedings (HR: 1.26; 95% CI: 0.93–1.70; p = 0.14). I 2 test showed low to moderate heterogeneity among the included studies (21.6–62.3%). This systematic review and meta-analysis therefore demonstrates a reduction in major cardiovascular events during extended P2Y12-inhibitor treatment beyond 12 months compared with ≤ 12 months in patients with ACS or stable CAD undergoing PCI. There was no significant difference in all-cause death or major bleedings.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Benjamin C. Hofeld ◽  
Venkata K. Puppala ◽  
Sudhi Tyagi ◽  
Kwang Woo Ahn ◽  
Amberly Anger ◽  
...  

AbstractRecent trials demonstrate that systemic anti-inflammatory therapy reduces cardiovascular events in coronary artery disease (CAD) patients. We recently demonstrated Lactobacillus plantarum 299v (Lp299v) supplementation improved vascular endothelial function in men with stable CAD. Whether this favorable effect is in part due to anti-inflammatory action remains unknown. Testing this hypothesis, we exposed plasma obtained before and after Lp299v supplementation from these subjects to a healthy donor’s PBMCs and measured differences in the PBMC transciptome, performed gene ontological analyses, and compared Lp299v-induced transcriptome changes with changes in vascular function. Daily alcohol users (DAUs) (n = 4) had a significantly different response to Lp299v and were separated from the main analyses. Non-DAUs- (n = 15) showed improved brachial flow-mediated dilation (FMD) and reduced circulating IL-8, IL-12, and leptin. 997 genes were significantly changed. I.I.com decreased (1.01 ± 0.74 vs. 0.22 ± 0.51; P < 0.0001), indicating strong anti-inflammatory effects. Pathway analyses revealed downregulation of IL-1β, interferon-stimulated pathways, and toll-like receptor signaling, and an increase in regulator T-cell (Treg) activity. Reductions in GBP1, JAK2, and TRAIL expression correlated with improved FMD. In non-DAU men with stable CAD, post-Lp299v supplementation plasma induced anti-inflammatory transcriptome changes in human PBMCs that could benefit CAD patients. Future studies should delineate changes in circulating metabolites responsible for these effects.


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