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Atherosclerosis Jun 2024Atherosclerosis manifests itself differently in men and women with respect to plaque initiation, progression and plaque composition. The observed delay in plaque... (Review)
Review
Atherosclerosis manifests itself differently in men and women with respect to plaque initiation, progression and plaque composition. The observed delay in plaque progression in women is thought to be related to the hormonal status of women. Also features associated with the vulnerability of plaques to rupture seem to be less frequently present in women compared to men. Current invasive and non-invasive imaging modalities allow for visualization of plaque size, composition and high risk vulnerable plaque features. Moreover, image based modeling gives access to local shear stress and shear stress-related plaque growth. In this review, current knowledge on sex-related differences in plaque size, composition, high risk plaque features and shear stress related plaque growth in carotid and coronary arteries obtained from imaging are summarized.
PubMed: 38944895
DOI: 10.1016/j.atherosclerosis.2024.117616 -
Aging Jun 2024Cathepsin L (CTSL) has been implicated in aging and age-related diseases, such as cardiovascular diseases, specifically atherosclerosis. However, the underlying...
Cathepsin L (CTSL) has been implicated in aging and age-related diseases, such as cardiovascular diseases, specifically atherosclerosis. However, the underlying mechanism(s) is not well documented. Recently, we demonstrated a role of CUT-like homeobox 1 (CUX1) in regulating the p16-dependent cellular senescence in human endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) via its binding to an atherosclerosis-associated functional SNP (fSNP) rs1537371 on the locus. In this study, to determine if CTSL, which was reported to proteolytically activate CUX1, regulates cellular senescence via CUX1, we measured the expression of CTSL, together with CUX1 and p16, in human ECs and VSMCs undergoing senescence. We discovered that CUX1 is not a substrate that is cleaved by CTSL. Instead, CTSL is an upstream regulator that activates transcription indirectly in a process that requires the proteolytic activity of CTSL. Our findings suggest that there is a transcription factor in between CTSL and CUX1, and cleavage of this factor by CTSL can activate CUX1 transcription, inducing endothelial senescence. Thus, our findings provide new insights into the signal transduction pathway that leads to atherosclerosis-associated cellular senescence.
PubMed: 38944813
DOI: 10.18632/aging.205955 -
BMC Public Health Jun 2024The metabolic score for visceral fat (METS-VF) quantifies the cumulative burden of visceral and intra-abdominal adipose tissues. However, the relationship between the...
BACKGROUND
The metabolic score for visceral fat (METS-VF) quantifies the cumulative burden of visceral and intra-abdominal adipose tissues. However, the relationship between the METS-VF and carotid atherosclerosis (CAS) has not been extensively explored. Therefore, this study aimed to investigate the association between the METS-VF and CAS.
METHODS
This cross-sectional study enrolled 7089 Chinese adults who underwent physical examinations at the Zhenhai Lianhua Hospital, Zhejiang, China, in 2020. Multivariable logistic regression analysis was used to explore the linear relationship between METS-VF and CAS. Generalised additive models (GAM) were employed to evaluate potential nonlinear associations. The inflection points of METS-VF were determined using segmented logistic regression analysis optimised for maximum likelihood ratios and recursive algorithms.
RESULTS
Multivariable logistic regression analysis revealed a positive correlation between METS-VF and CAS (odds ratio [OR]: 1.824, 95% confidence interval [CI]: 1.753-1.899; P < 0.001). The GAM analysis confirmed a nonlinear association between them [effective degrees of freedom: 4.803, χ: 876.7, P < 0.001], with an inflection point at a METS-VF of 8.09 (P < 0.001 for log-likelihood ratio test). Below this inflection point, METS-VF exhibited a significant positive association with CAS risk (OR: 1.874, 95% CI: 1.796-1.954; P < 0.001). Conversely, no significant association was observed when METS-VF ≥ 8.09 (OR: 0.998, 95% CI: 0.786-1.268; P = 0.989).
CONCLUSIONS
METS-VF and CAS demonstrated a positive non-linear correlation, with the curve indicating a saturation effect at METS-VF = 8.09.
Topics: Humans; Cross-Sectional Studies; Male; Female; Intra-Abdominal Fat; Middle Aged; China; Carotid Artery Diseases; Adult; Metabolic Syndrome; Aged; Risk Factors; Logistic Models
PubMed: 38943105
DOI: 10.1186/s12889-024-19186-2 -
Scientific Reports Jun 2024Circulating amyloid-beta 1-40 (Αb40) has pro-atherogenic properties and could serve as a biomarker in atherosclerotic cardiovascular disease (ASCVD). However, the...
Circulating amyloid-beta 1-40 (Αb40) has pro-atherogenic properties and could serve as a biomarker in atherosclerotic cardiovascular disease (ASCVD). However, the association of Ab40 levels with morphological characteristics reflecting atherosclerotic plaque echolucency and composition is not available. Carotid atherosclerosis was assessed in consecutively recruited individuals without ASCVD (n = 342) by ultrasonography. The primary endpoint was grey scale median (GSM) of intima-media complex (IMC) and plaques, analysed using dedicated software. Vascular markers were assessed at two time-points (median follow-up 35.5 months). In n = 56 patients undergoing carotid endarterectomy, histological plaque features were analysed. Plasma Αb40 levels were measured at baseline. Ab40 was associated with lower IMC GSM and plaque GSM and higher plaque area at baseline after multivariable adjustment. Increased Ab40 levels were also longitudinally associated with decreasing or persistently low IMC and plaque GSM after multivariable adjustment (p < 0.05). In the histological analysis, Ab40 levels were associated with lower incidence of calcified plaques and plaques without high-risk features. Ab40 levels are associated with ultrasonographic and histological markers of carotid wall composition both in the non-stenotic arterial wall and in severely stenotic plaques. These findings support experimental evidence linking Ab40 with plaque vulnerability, possibly mediating its established association with major adverse cardiovascular events.
Topics: Humans; Male; Female; Plaque, Atherosclerotic; Aged; Middle Aged; Biomarkers; Amyloid beta-Peptides; Carotid Arteries; Ultrasonography; Carotid Intima-Media Thickness; Carotid Artery Diseases; Endarterectomy, Carotid
PubMed: 38942831
DOI: 10.1038/s41598-024-64906-8 -
RMD Open Jun 2024The nature of the relationship between inflammation, cardiovascular (CV) risk factors and atherosclerosis in axial spondyloarthritis (axSpA) remains largely unknown and...
INTRODUCTION
The nature of the relationship between inflammation, cardiovascular (CV) risk factors and atherosclerosis in axial spondyloarthritis (axSpA) remains largely unknown and sex differences in this regard are yet to be assessed.
METHODS
Study including 611 men and 302 women from the Spanish multicentre AtheSpAin cohort to assess CV disease in axSpA. Data on CV disease risk factors were collected both at disease diagnosis and at enrolment, and data on disease activity, functional indices and carotid ultrasonography only at enrolment.
RESULTS
After a median disease duration of 9 years, patients of both sexes who at disease diagnosis had elevated acute phase reactants (APRs), more frequently had hypertension and obesity. The same occurred with dyslipidaemia in men and with diabetes mellitus in women. At enrolment, CV risk factors were independently associated with APR and with activity and functional indices, with various sex differences. C reactive protein (CRP) values were inversely associated with HDL-cholesterol in men (β coefficient: -1.2 (95% CI: -0.3 to -0.07) mg/dL, p=0.001), while erythrocyte sedimentation rate values were positively associated with triglycerides in women (β coefficient: 0.6 (95% CI: 0.04 to 1) mg/dL, p=0.035). Furthermore, only women showed an independent relationship between insulin resistance parameters and APR or disease activity. Both men and women with high-very high CV risk according to the Systematic Assessment of Coronary Risk Evaluation 2 and CRP levels higher than 3 mg/L at diagnosis of the disease presented carotid plaques significantly more frequently than those with normal CRP levels at disease diagnosis.
CONCLUSION
Inflammation is associated with atherosclerosis and CV disease in axSpA. A gender-driven effect is observed in this relationship.
Topics: Humans; Male; Female; Atherosclerosis; Middle Aged; Inflammation; Adult; Heart Disease Risk Factors; Sex Factors; Axial Spondyloarthritis; Risk Factors; Biomarkers; Cardiovascular Diseases; C-Reactive Protein
PubMed: 38942590
DOI: 10.1136/rmdopen-2024-004187 -
Computer Methods and Programs in... Jun 2024In this work, the analysis of the importance of hemodynamic updates on a mechanobiological model of atheroma plaque formation is proposed.
BACKGROUND AND OBJECTIVE
In this work, the analysis of the importance of hemodynamic updates on a mechanobiological model of atheroma plaque formation is proposed.
METHODS
For that, we use an idealized and axisymmetric model of carotid artery. In addition, the behavior of endothelial cells depending on hemodynamical changes is analyzed too. A total of three computational simulations are carried out and their results are compared: an uncoupled model and two models that consider the opposite behavior of endothelial cells caused by hemodynamic changes. The model considers transient blood flow using the Navier-Stokes equation. Plasma flow across the endothelium is determined with Darcy's law and the Kedem-Katchalsky equations, considering the three-pore model, which is also employed for the flow of substances across the endothelium. The behavior of the considered substances in the arterial wall is modeled with convection-diffusion-reaction equations, and the arterial wall is modeled as a hyperelastic Yeoh's material.
RESULTS
Significant variations are noted in both the morphology and stenosis ratio of the plaques when comparing the uncoupled model to the two models incorporating updates for geometry and hemodynamic stimuli. Besides, the phenomenon of double-stenosis is naturally reproduced in the models that consider both geometric and hemodynamical changes due to plaque growth, whereas it cannot be predicted in the uncoupled model.
CONCLUSIONS
The findings indicate that integrating the plaque growth model with geometric and hemodynamic settings is essential in determining the ultimate shape and dimensions of the carotid plaque.
PubMed: 38941860
DOI: 10.1016/j.cmpb.2024.108296 -
Turkish Journal of Ophthalmology Jun 2024The triglyceride-glucose (TyG) index is a sign of atherosclerosis in cardiovascular diseases. The TyG index is thought to have clinical significance for the assessment... (Observational Study)
Observational Study
OBJECTIVES
The triglyceride-glucose (TyG) index is a sign of atherosclerosis in cardiovascular diseases. The TyG index is thought to have clinical significance for the assessment of vascular damage. In this study we aimed to demonstrate the connection between the TyG index and retinal vein occlusion (RVO).
MATERIALS AND METHODS
This case-control observational study involved 492 participants aged 40-90, admitted to the ophthalmology outpatient clinic of our hospital. TyG index was calculated using the formula: ln(fasting TG [mg/dL] × fasting plasma glucose [mg/dL]/2).
RESULTS
The RVO group included 387 patients (181 women and 206 men) and the control group included 115 patients (61 women and 54 men). The average patient age was 62.9±11.1 years in the RVO group and 56.7±8.7 years in the control group. The TyG index was higher in the RVO group (8.9±0.7) than in the control group (8.8±0.6). This difference was statistically significant (p=0.04). The correlation was statistically significant when evaluated according to age and sex by multivariate logistic regression analysis (odds ratio: 1.45, confidence interval: 1.03- 2.02, p=0.03).
CONCLUSION
The TyG index is a novel atherogenicity index that is derived from routine blood tests and can be used to determine the risk of RVO in at-risk individuals with a simple calculation. Therefore, the TyG index could help as a reliable guide to identify individuals at RVO with high risk and initiate early intervention.
Topics: Humans; Female; Male; Middle Aged; Retinal Vein Occlusion; Triglycerides; Aged; Blood Glucose; Atherosclerosis; Adult; Case-Control Studies; Risk Factors; Biomarkers; Aged, 80 and over; Retrospective Studies
PubMed: 38940357
DOI: 10.4274/tjo.galenos.2024.69841 -
Frontiers in Bioscience (Landmark... May 2024Epigenetics refers to heritable changes in gene expression and function that impact nuclear processes associated with chromatin, all without altering DNA sequences.... (Review)
Review
Epigenetics refers to heritable changes in gene expression and function that impact nuclear processes associated with chromatin, all without altering DNA sequences. These epigenetic patterns, being heritable traits, are vital biological mechanisms that intricately regulate gene expression and heredity. The application of chemical labeling and single-cell resolution mapping strategies has significantly facilitated large-scale epigenetic modifications in nucleic acids over recent years. Notably, epigenetic modifications can induce heritable phenotypic changes, regulate cell differentiation, influence cell-specific gene expression, parentally imprint genes, activate the X chromosome, and stabilize genome structure. Given their reversibility and susceptibility to environmental factors, epigenetic modifications have gained prominence in disease diagnosis, significantly impacting clinical medicine research. Recent studies have uncovered strong links between epigenetic modifications and the pathogenesis of metabolic cardiovascular diseases, including congenital heart disease, heart failure, cardiomyopathy, hypertension, and atherosclerosis. In this review, we provide an overview of the progress in epigenetic research within the context of cardiovascular diseases, encompassing their pathogenesis, prevention, diagnosis, and treatment. Furthermore, we shed light on the potential prospects of nucleic acid epigenetic modifications as a promising avenue in clinical medicine and biomedical applications.
Topics: Humans; Epigenesis, Genetic; Cardiovascular Diseases; DNA Methylation; Animals
PubMed: 38940023
DOI: 10.31083/j.fbl2906205 -
Exploration (Beijing, China) Jun 2024Atherosclerosis, a chronic disease associated with metabolism, poses a significant risk to human well-being. Currently, existing treatments for atherosclerosis lack... (Review)
Review
Atherosclerosis, a chronic disease associated with metabolism, poses a significant risk to human well-being. Currently, existing treatments for atherosclerosis lack sufficient efficiency, while the utilization of surface-modified nanoparticles holds the potential to deliver highly effective therapeutic outcomes. These nanoparticles can target and bind to specific receptors that are abnormally over-expressed in atherosclerotic conditions. This paper reviews recent research (2018-present) advances in various ligand-modified nanoparticle systems targeting atherosclerosis by specifically targeting signature molecules in the hope of precise treatment at the molecular level and concludes with a discussion of the challenges and prospects in this field. The intention of this review is to inspire novel concepts for the design and advancement of targeted nanomedicines tailored specifically for the treatment of atherosclerosis.
PubMed: 38939861
DOI: 10.1002/EXP.20230090 -
JACC. Advances Apr 2024Cost-effectiveness of testing for coronary artery calcium (CAC) relative to other treatment strategies is not established in Canada.
BACKGROUND
Cost-effectiveness of testing for coronary artery calcium (CAC) relative to other treatment strategies is not established in Canada.
OBJECTIVES
The purpose of this study was to evaluate the cost-effectiveness of using CAC score-guided statin treatment compared with universal statin therapy among intermediate-risk, primary prevention patients eligible for statins.
METHODS
A state transition, microsimulation model used data from Canadian sources and the Multi-Ethnic Study of Atherosclerosis to simulate clinical and economic consequences of cardiovascular disease from a Canadian publicly funded health care system perspective. In the CAC score-guided treatment arm, statins were started when CAC ≥1. Outcome of interest was the incremental cost-effectiveness ratio at 5 and 10 years; an incremental cost-effectiveness ratio <$50,000 per quality-adjusted life year (QALY) gained was considered cost-effective. Sensitivity analyses examined uncertainty in model parameters.
RESULTS
Compared with universal statin treatment at 5 and 10 years, CAC score-guided statin treatment was projected to increase mean costs by $326 (95% CI: $325-$326) and $172 (95% CI: $169-$175), increase mean QALYs by 0.01 (95% CI: 0.01-0.01) and 0.02 (95% CI: 0.02-0.02), and cost $54,492 (95% CI: $52,342-$56,816) and $8,118 (95% CI: $7,968-$8,279) per QALY gained, respectively. The model was most sensitive to statin cost, CAC testing cost, adherence to statin monitoring, and disutility associated with daily statin use. At 5 years, CAC score-guided statin treatment was cost-effective when CAC test costs ranged from $80 to $160 in different scenarios.
CONCLUSIONS
CAC score-guided statin initiation in comparison to universal statin treatment was borderline cost-neutral at 5 years and cost-effective at 10 years in statin-eligible Canadian patients at intermediate cardiovascular disease risk.
PubMed: 38939688
DOI: 10.1016/j.jacadv.2024.100886