scholarly journals Soluble CD40 Levels in Plasma Are Associated with Cardiovascular Disease and in Carotid Plaques with a Vulnerable Phenotype

2021 ◽  
Vol 23 (3) ◽  
pp. 367-376
Author(s):  
Annelie Shami ◽  
Andreas Edsfeldt ◽  
Eva Bengtsson ◽  
Jan Nilsson ◽  
Angela C. Shore ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Carotid Plaque ◽  
Cardiovascular Events ◽  
Inflammatory Diseases ◽  
Tumor Necrosis Factor Receptor ◽  
Intima Media Thickness ◽  
Carotid Intima Media Thickness ◽  
Cd40 Ligand ◽  
Plaque Area ◽  
Stable Plaque

Background and Purpose CD40 and CD40 ligand (CD40L) are costimulatory molecules of the tumor necrosis factor receptor superfamily and well known for their involvement in inflammatory diseases: atherosclerotic mouse models with disrupted CD40 signalling develop lesions of reduced size with a more stable plaque profile. This study investigated the potential of plasma and intraplaque levels of CD40 and CD40L as markers for cardiovascular disease (CVD) in humans and their association with plaque stability.Methods Soluble CD40 and CD40L (sCD40L) were measured in plasma in 1,437 subjects from The SUrrogate markers for Micro- and Macro-vascular hard endpoints for Innovative diabetes Tools (SUMMIT) cohort. Intra-plaque levels of sCD40 and sCD40L were measured in atherosclerotic plaque homogenates from 199 subjects of the Carotid Plaque Imaging Project (CPIP) cohort. Results Both plasma sCD40 and sCD40L levels were elevated in individuals with prevalent stroke, while sCD40 levels also were higher in individuals with a prior acute myocardial infarction. Plasma levels of sCD40 correlated with carotid intima-media thickness and total carotid plaque area and were associated with risk of cardiovascular events over a 3-year follow-up period. Intra-plaque levels of sCD40 and sCD40L were associated with plaque components characteristic for plaque vulnerability and extracellular matrix remodelling.Conclusions Higher plasma sCD40 and sCD40L levels are associated with prevalent CVD. Plasma sCD40 levels also correlate with the severity of carotid atherosclerosis and predict future cardiovascular events, while intra-plaque levels correlate with a vulnerable plaque phenotype. Our findings thus demonstrate that elevated levels of sCD40 and sCD40L are markers of CVD.

Abstract 17791: Yield of Different Approaches for Screening for Cardiovascular Disease in Asymptomatic Diabetics

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Timothy W Churchill ◽  
Carlos H Rassi ◽  
Carlos A Fernandes Tavares ◽  
Mateus G Fahel ◽  
Fabricia P Rassi ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Coronary Artery ◽  
Coronary Stenosis ◽  
Carotid Plaque ◽  
Intima Media Thickness ◽  
Carotid Intima Media Thickness ◽  
Coronary Plaque ◽  
Carotid Ultrasound ◽  
Asymptomatic Subjects ◽  
A Prospective Study

Introduction: While diabetes has long been considered a coronary heart disease equivalent, there is increasing evidence to suggest that not all individuals with diabetes have cardiovascular disease, and it is unclear how best to risk stratify this population. We sought to compare the yield of testing for pre-clinical atherosclerosis with various approaches. Methods: A group of 98 asymptomatic subjects with type 2 diabetes mellitus (T2DM) without known coronary artery disease (CAD) were enrolled in a prospective study and underwent carotid ultrasound, exercise treadmill testing (ETT), coronary artery calcium (CAC) scoring, and coronary computed tomography angiography (CTA). CTA was used as the reference standard for CAD. Results: Of 98 subjects (average age 55±6, 64% female, 22 on insulin, mean A1c 7.3%), 43 (44%) had coronary plaque detectable on CTA, and 38 (39%) had CAC score > 0. By CTA, 16 (16%) had coronary stenosis ≥ 50%, including 3 subjects with CAC=0. Subjects with coronary plaque had greater prevalence of carotid plaque (58% vs. 38%, p=0.01) and greater carotid intima media thickness (0.80±0.20 mm vs. 0.70±0.11mm, p=0.02). However, 18 of the 55 subjects (33%) with normal CTA had carotid plaque. Eight subjects had a positive ETT, of whom 5 had ≥ 50% coronary stenosis and 2 had <50% stenosis, but there was no difference in METS achieved between subjects with and without plaque (8.2 vs. 8.7, p=0.19). Test characteristics of different imaging modalities for prediction of coronary plaque are shown in Figure 1. Conclusion: Among asymptomatic subjects with T2DM, a majority (56%) had no CAD by CTA. CAC was the most accurate screening modality for detection of CAD while ETT and carotid ultrasound had a limited sensitivity. Interestingly, 33% of subjects with normal CTA had carotid plaque. Further studies are needed to better characterize stroke risk in such patients and whether there is a role for screening for carotid plaque in diabetics without CAC or with normal CTA.

P1535Clinical impact of carotid plaque score rather than carotid intima-media thickness on atherosclerotic cardiovascular disease

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
H Tada ◽  
T Nakagawa ◽  
H Okada ◽  
T Nakahashi ◽  
M Mori ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Carotid Plaque ◽  
Intima Media Thickness ◽  
Carotid Intima Media Thickness ◽  
Plaque Burden ◽  
Atherosclerotic Cardiovascular Disease ◽  
Plaque Score ◽  
Media Thickness

Abstract Background Carotid intima-media thickness (cIMT) assessed by ultrasound has been widely accepted as a surrogate marker of atherosclerotic cardiovascular disease. On the other hand, carotid plaque score (cPS) reflecting throughout the carotid artery plaque burden may be better marker. Methods We retrospectively examined 2,035 patients who underwent carotid ultrasonography between January 2006 and December 2015 at our University Hospital. Median follow-up period was 4 years. We used Cox models that adjusted for established risk factors of ASCVD, including age, gender, hypertension, diabetes, smoking, and serum lipids to assess the association of cIMT as well as cPS with major adverse cardiac events (MACE). MACE was defined as all-cause mortality or rehospitalization for a cardiovascular-related illness Results During follow-up, 243 participants experienced MACE. After adjustment for established risk factors, cPS was associated with MACE (hazard ratio [HR] = 3.38 for top quintile vs. bottom quintile of cPS; 95% confidence interval [CI] 1.82 to 6.27; P-trend = 1.4×10–8), while cIMT was not (HR = 0.88, P=0.57). Addition of the cPS to established risk factors significantly improved risk discrimination (C-index 0.726 vs. 0.746; P=0.017) Conclusion As a marker, cPS, rather than cIMT can identify 20% of individuals who are at more than three-fold increased risk for MACE. Targeting diagnostic or therapeutic interventions to this subset may prove clinically useful.

Correlation of Waist to Calf Circumference Ratio and Carotid Intima Media Thickness in Diabetes Mellitus

2020 ◽  
Vol 16 ◽  
Author(s):  
Harish A Rao ◽  
Prakash Harischandra ◽  
Srikanth Yadav
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Risk Factor ◽  
Carotid Atherosclerosis ◽  
Intima Media Thickness ◽  
Carotid Intima Media Thickness ◽  
Calf Circumference ◽  
Media Thickness

Introduction: Diabetes mellitus is a well-known risk factor for cardiovascular disease, because of the accelerated process of atherosclerosis. Obesity is an established risk factor and has gained immense importance in recent studies as an important risk factor for clinical cardiovascular disease, yet the fundamental component stays unclear. Calf circumference is another form for lean mass and peripheral subcutaneous fat and is inversely associated with occurrence of carotid plaques (CP). Multiplicative and opposite effects of both Calf Circumference (CC) and Waist Circumference (WC) in event of CP suggest that the two measures should be taken into account commonly while assessing vascular risk profile. Aim & Objective: To ascertain if waist to calf circumference ratio (WCR) is a marker of Carotid atherosclerosis in patients with type 2 diabetes mellitus. To asses s the correlation between waist to calf circumference ratio and carotid intima media thickness (CIMT ) in patients with Type 2 diabetes. Materials and methods: A cross sectional study at Hospital affiliated to Kasturba Medical college Mangalore from Sept 2016 to Sept 2018 . Method of study: Patients with type 2 DM as per ADA criteria, age >18years are recruited for the study. Results and discussion: In our study with 150 population 25 patients had carotid atherosclerosis and 20 patients had CIMT>1.1. The waist circumference in patients with CA is in the range of 93.07 and 99.85 & the CC in patients with CA is in the range of 29.49 to 31.25. The WCR in patients with CA is in the range of 3.12 to 3.26. The difference was statistically significant with a p value of <0.05. In our study it was found that WC and WCR correlated well with carotid atherosclerosis, and surprisingly calf circumference also correlated with carotid atherosclerosis but not as significant as both WC and WCR. Conclusion: To conclude, in our population based study of 150 subjects we found that carotid atherosclerosis is significantly more in people with increased waist calf circumference ratio. WCR may be a new, useful and practical anthropometric index that facilitates the early identification of diabetic subjects with high risk for cardiovascular disease. Validation of this finding in individual populations is required. Future studies should test the association of calf circumference with carotid intima media thickness and carotid plaques using better measures than ultrasound such as magnetic resonance imaging. Further research focusing on underlying mechanisms in the role of lean mass and peripheral fat mass is required.

scholarly journals Plasma expression of microRNA-425-5p and microRNA-451a as biomarkers of cardiovascular disease in rheumatoid arthritis patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Delia Taverner ◽  
Dídac Llop ◽  
Roser Rosales ◽  
Raimon Ferré ◽  
Luis Masana ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Cardiovascular Disease ◽  
Pulse Wave Velocity ◽  
Wave Velocity ◽  
Pulse Wave ◽  
Disease Risk ◽  
Intima Media Thickness ◽  
Carotid Intima Media Thickness ◽  
Media Thickness ◽  
Epigenetic Biomarkers

AbstractTo validate in a cohort of 214 rheumatoid arthritis patients a panel of 10 plasmatic microRNAs, which we previously identified and that can facilitate earlier diagnosis of cardiovascular disease in rheumatoid arthritis patients. We identified 10 plasma miRs that were downregulated in male rheumatoid arthritis patients and in patients with acute myocardial infarction compared to controls suggesting that these microRNAs could be epigenetic biomarkers for cardiovascular disease in rheumatoid arthritis patients. Six of those microRNAs were validated in independent plasma samples from 214 rheumatoid arthritis patients and levels of expression were associated with surrogate markers of cardiovascular disease (carotid intima-media thickness, plaque formation, pulse wave velocity and distensibility) and with prior cardiovascular disease. Multivariate analyses adjusted for traditional confounders and treatments showed that decreased expression of microRNA-425-5p in men and decreased expression of microRNA-451 in women were significantly associated with increased (β = 0.072; p = 0.017) and decreased carotid intima-media thickness (β = −0.05; p = 0.013), respectively. MicroRNA-425-5p and microRNA-451 also increased the accuracy to discriminate patients with pathological carotid intima-media thickness by 1.8% (p = 0.036) in men and 3.5% (p = 0.027) in women, respectively. In addition, microRNA-425-5p increased the accuracy to discriminate male patients with prior cardiovascular disease by 3% (p = 0.008). Additionally, decreased expression of microRNA-451 was significantly associated with decreased pulse wave velocity (β = −0.72; p = 0.035) in overall rheumatoid arthritis population. Distensibility showed no significant association with expression levels of the microRNAs studied. We provide evidence of a possible role of microRNA-425-5p and microRNA-451 as useful epigenetic biomarkers to assess cardiovascular disease risk in patients with rheumatoid arthritis.

scholarly journals Meta-analysis of epigenome-wide association studies of carotid intima-media thickness

2021 ◽  
Author(s):  
Eliana Portilla-Fernández ◽  
Shih-Jen Hwang ◽  
Rory Wilson ◽  
Jane Maddock ◽  
W. David Hill ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Dna Methylation ◽  
Cardiovascular Risk ◽  
Cardiovascular Risk Factors ◽  
Association Studies ◽  
Subclinical Atherosclerosis ◽  
Intima Media Thickness ◽  
Carotid Intima Media Thickness ◽  
Media Thickness

AbstractCommon carotid intima-media thickness (cIMT) is an index of subclinical atherosclerosis that is associated with ischemic stroke and coronary artery disease (CAD). We undertook a cross-sectional epigenome-wide association study (EWAS) of measures of cIMT in 6400 individuals. Mendelian randomization analysis was applied to investigate the potential causal role of DNA methylation in the link between atherosclerotic cardiovascular risk factors and cIMT or clinical cardiovascular disease. The CpG site cg05575921 was associated with cIMT (beta = −0.0264, p value = 3.5 × 10–8) in the discovery panel and was replicated in replication panel (beta = −0.07, p value = 0.005). This CpG is located at chr5:81649347 in the intron 3 of the aryl hydrocarbon receptor repressor gene (AHRR). Our results indicate that DNA methylation at cg05575921 might be in the pathway between smoking, cIMT and stroke. Moreover, in a region-based analysis, 34 differentially methylated regions (DMRs) were identified of which a DMR upstream of ALOX12 showed the strongest association with cIMT (p value = 1.4 × 10–13). In conclusion, our study suggests that DNA methylation may play a role in the link between cardiovascular risk factors, cIMT and clinical cardiovascular disease.

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