Subclinical atherosclerosis underlies most cardiovascular diseases, manifesting before clinical symptoms and representing a key focus for early prevention strategies. Recent advancements highlight the importance of early detection and management of subclinical atherosclerosis. This review underscores that traditional risk factor levels considered safe, such as low-density lipoprotein cholesterol (LDL-C) and glycated haemoglobin (HbA1c), may still permit the development of atherosclerosis, suggesting a need for stricter thresholds. Early-life interventions are crucial, leveraging the brain's neuroplasticity to establish lifelong healthy habits. Preventive strategies should include more aggressive management of LDL-C and HbA1c from youth and persist into old age, supported by public health policies that promote healthy environments. Emphasising early education on cardiovascular health can fundamentally shift the trajectory of cardiovascular disease prevention and optimise long-term health outcomes.
Humans ; Atherosclerosis/diagnosis* ; Risk Factors ; Cardiovascular Diseases/prevention & control* ; Cholesterol, LDL/blood* ; Glycated Hemoglobin ; Cardiology/trends* ; Heart Disease Risk Factors

BACKGROUND: Epstein-Barr (EB) virus infection stimulates the production of vascular endothelial growth factor (VEGF), which contributes to the progression of angiogenesis. Angiogenesis plays an important role in the development of atherosclerosis. Since serum anti-early antigen EB virus IgG (EBV EA-IgG) titer is a sign of active EB virus infection, EBV EA-IgG titer could be associated with atherosclerosis. The number of minor (T) alleles in VEGF polymorphism rs3025039 has been reported to be inversely associated with serum VEGF concentration, suggesting that rs3025039 might have a strong influence on the association between EBV EA-IgG titer and atherosclerosis. By focusing on the role of VEGF in the development of atherosclerosis, this study aimed to investigate the association between active EB virus infection and atherosclerosis. METHODS: A cross-sectional study of 2,661 older Japanese individuals aged 60-89 years who participated in annual health check-ups during 2017-2019 was conducted. Logistic regression was used to evaluate the association between EBV EA-IgG titer and atherosclerosis in relation to rs3025039 genotype. The influence of rs3025039 (T) allele carrier status on the association between EBV EA-IgG titer and atherosclerosis was also evaluated by using logistic regression. RESULTS: Among rs3025039 CC-homozygotes, with the lowest EBV EA-IgG titer tertile as the reference, the multivariable odds ratio (95% confidence interval) was 1.11 (0.82, 1.50) for the medium tertile and 1.07 (0.78, 1.47) for the high tertile. Among rs3025039 (T) allele carriers, the corresponding values were 1.44 (0.88, 2.36) and 1.88 (1.15, 3.05), respectively. There was a significant interaction between rs3025039 (T) allele carrier status and the association between EBV EA-IgG titer and atherosclerosis (adjusted p = 0.0497). CONCLUSION EBV EA-IgG titer was significantly positively associated with atherosclerosis only among participants who are genetically less likely to have progressive angiogenesis. An angiogenesis-related genetic factor was revealed as a determinant of the association between EBV EA-IgG titer and atherosclerosis. These findings introduce a novel concept that could explain the association between viral infection and atherosclerosis.
Humans ; Aged ; Male ; Middle Aged ; Female ; Japan/epidemiology* ; Atherosclerosis/virology* ; Aged, 80 and over ; Vascular Endothelial Growth Factor A/genetics* ; Epstein-Barr Virus Infections/virology* ; Polymorphism, Single Nucleotide ; Cross-Sectional Studies ; Herpesvirus 4, Human ; Antigens, Viral/immunology* ; Antibodies, Viral/blood* ; Immunoglobulin G/blood* ; Genotype ; East Asian People

OBJECTIVES: In recent years, the role of remnant cholesterol (RC) in the development and progression of cardiovascular diseases has gained increasing attention. However, evidence on the association between RC and subclinical atherosclerosis is limited. This study aims to examine the relationship between RC and atherosclerotic plaques in single and multiple vascular territories. METHODS: This retrospective cross-sectional study used baseline data from participants enrolled between October 2022 and May 2024 in the National Key Research Program "Study on the Prevention and Control System of Risk Factors for Panvascular Diseases". Color Doppler ultrasonography was performed to detect plaques in 4 vascular territories: Bilateral carotid arteries, bilateral subclavian arteries, abdominal aorta, and iliac-femoral arteries. RC was calculated as total cholesterol minus the sum of low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C). Participants were categorized into quartiles (Q1-Q4) according to RC levels. The proportions of participants with ≥2 plaques in a single vascular territory and with plaques in ≥2 vascular territories were compared across RC quartiles. Multivariate ordinal Logistic regression was used to assess the association between RC and the number of plaques in a single vascular territory, as well as the risk of multiple vascular territory involvement. Additionally, the effects of LDL-C/RC concordance on plaque distribution were analyzed. RESULTS: A total of 3 539 participants were included, of whom 2 169 (61.29%) were male, with a age of (51.94±9.22) years. From Q1 to Q4, the proportion of participants with ≥2 plaques in a single vascular territory (bilateral carotid, subclavian, abdominal aorta, and iliac-femoral arteries), as well as those with plaques in ≥2 vascular territories, increased progressively. Compared with Q1, both Q3 and Q4 were significantly associated with higher plaque numbers in a single vascular territory (both P<0.05). When treated as a continuous variable, higher RC levels were associated with an increased risk of greater plaque numbers within a single vascular territory (all P<0.05). RC levels were also significantly associated with multiple vascular territory involvement: Compared with Q1, Q4 had a 1.015-fold higher risk [odds ratio (OR)=2.015, 95% confidence interval (CI) 1.669 to 2.433], and each 1 mmol/L increase in RC corresponded to a 0.160-fold increased risk (OR=1.160, 95% CI 1.073 to 1.271). In LDL-C/RC coordination analysis, compared with the low LDL-C/low RC group, the low LDL-C/high RC group was significantly associated with multiple vascular territory involvement (OR=1.576, 95% CI 1.220 to 2.036). CONCLUSIONS Elevated RC levels are closely associated with atherosclerotic plaques in both single and multiple vascular territories, even among individuals with normal LDL-C, suggesting that RC should be considered in clinical risk assessment and management of atherosclerosis.
Humans ; Plaque, Atherosclerotic/diagnostic imaging* ; Male ; Female ; Cross-Sectional Studies ; Middle Aged ; Retrospective Studies ; Cholesterol/blood* ; Cholesterol, LDL/blood* ; Aged ; Cholesterol, HDL/blood* ; Risk Factors ; Atherosclerosis ; Ultrasonography, Doppler, Color ; Femoral Artery/diagnostic imaging*

Exosomes are subtypes of extracellur vesicles containing a variety of cell-specific proteins, lipids and nucleic acids released during cell activation or apoptosis, and play the role of intercellur communication mediators in different physiological and pathological processes. With the development of research in recent years, the role of platelet-derived exosomes in cardiovascular diseases has attracted extensive attention. This paper reviews the role of platelet-derived exosomes in atherosclerotic thrombosis and the potential role of platelet-derived exosomes as biomarkers for the diagnosis and treatment of atherosclerotic thrombotic disease and the problems to be solved.
Apoptosis ; Atherosclerosis/pathology* ; Blood Platelets/pathology* ; Exosomes/pathology* ; Humans ; Thrombosis

The aim of this paper was to observe the effect of Di'ao Xinxuekang(DXXK) on TLR4/MyD88/NF-κB signaling pathway in atherosclerotic rats, and to explore its anti-atherosclerotic mechanism. Sixty SD rats were randomly divided into normal group, model group, atorvastatin group(4.0 mg·kg~(-1)), and DXXK groups(100, 30, 10 mg·kg~(-1)), with 10 rats in each group. The atherosclerosis model was induced by high fat diet plus vitamin D_2. Experimental drugs were administered intragastrically once daily for 8 weeks starting from the 9 th week. Biochemical analyzers were used to detect levels of triglyceride(TG), total cholesterol(TC), low-density lipoprotein cholesterol(LDL-C) and high-density lipoprotein cholesterol(HDL-C) in blood lipid. The levels of serum tumor necrosis factor(TNF)-α, interleukin(IL)-6 and IL-1β were detected by ELISA. Pathological changes of aortic tissues were observed by using Sudan Ⅳ and HE staining. The mRNA and protein expressions of TLR4, MyD88 and NF-κB p65 in aortic tissues were detected by RT-PCR and Western blot, respectively. As compared with the model group, TC, TG, and LDL-C levels in serum were significantly decreased, HDL-C content was significantly increased, and levels of TNF-α, IL-6, and IL-1β in serum were significantly decreased in atorvastatin group and DXXK high and middle dose groups. Aortic lesions in atorvastatin group and DXXK group were significantly improved, and the mRNA and protein expressions of TLR4, MyD88, NF-κB p65 in the aorta were decreased. DXXK has a preventive and therapeutic effect on atherosclerosis in rats, and its mechanism may be related to inhibiting inflammatory reaction by regulating TLR4/MyD88/NF-κB signal transduction, thereby inhibiting the progression of atherosclerosis.
Animals ; Aorta/pathology* ; Atherosclerosis/drug therapy* ; Atorvastatin ; Drugs, Chinese Herbal/pharmacology* ; Interleukin-6/blood* ; Interleukin-8/blood* ; Lipids/blood* ; Myeloid Differentiation Factor 88/metabolism* ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; Toll-Like Receptor 4/metabolism* ; Transcription Factor RelA/metabolism* ; Tumor Necrosis Factor-alpha/blood*

This paper describes how to develop a practical new type of atherosclerosis detection device, which can realize real-time measurement and analysis of human atherosclerosis. According to the mechanism of human atherosclerosis, the design objectives of the system are formulated to determine the construction of the platform. The system calculates the pulse wave velocity by measuring the pulse wave of human fingers and toes, adds four blood pressure measurements to the system design, calculates the ankle-brachial index, and comprehensively measures and analyses the degree of human arteriosclerosis.
Ankle ; Atherosclerosis ; Blood Flow Velocity ; Blood Pressure ; Brachial Artery ; Humans ; Pulse Wave Analysis

PURPOSE: Cigarette smoking (CS) is one of the major risk factors of cerebral atherosclerotic disease, however, its level of contribution to extracranial and intracranial atherosclerotic stenosis (ECAS and ICAS) was not fully revealed yet. The purpose of our study was to assess the association of CS to cerebral atherosclerosis along with other risk factors. MATERIALS AND METHODS: All consecutive patients who were angiographically confirmed with severe symptomatic cerebral atherosclerotic disease between January 2002 and December 2012 were included in this study. Multivariate logistic regression analyses were performed to identify risk factors for ECAS and ICAS. Thereafter, CS group were compared to non-CS group in the entire study population and in a propensity-score matched population with two different age-subgroups. RESULTS: Of 1709 enrolled patients, 794 (46.5%) had extracranial (EC) lesions and the other 915 (53.5%) had intracranial (IC) lesions. CS group had more EC lesions (55.8% vs. 35.3%, P<0.001) whereas young age group (<50 years) had more IC lesion (84.5% vs. 47.6%, P<0.001). In multivariate analysis, seven variables including CS, male, old age, coronary heart disease, higher erythrocyte sedimentation rate, multiple lesions, and anterior lesion were independently associated with ECAS. In the propensity-score matched CS group had significant more EC lesion compared to non-CS group (65.7% vs. 47.9%) only in the old age subgroup. CONCLUSION: In contrast to a significant association between CS and severe symptomatic ECAS shown in old population, young patients did not show this association and showed relatively higher preference of ICAS.
Atherosclerosis ; Blood Sedimentation ; Cerebrovascular Circulation ; Constriction, Pathologic ; Coronary Disease ; Humans ; Intracranial Arteriosclerosis ; Logistic Models ; Male ; Multivariate Analysis ; Risk Factors ; Smoking ; Tobacco Products

Cardiovascular disease is the leading cause of morbidity and mortality worldwide. Early detection of subclinical atherosclerosis is important for reduction of cardiovascular risk. However, the current diagnostic strategy, which focuses on traditional risk factors or the use of risk scoring, is unsatisfactory. Arterial walls thicken and stiffen with age, a process known as arteriosclerosis. There is a close interaction between arterial stiffness and atherosclerosis. Increased luminal pressure and shear stress caused by arterial stiffening result in endothelial dysfunction, accelerate the formation of atheromas, and stimulate excessive collagen production and deposition in the arterial wall. Carotid intima-media thickness (CIMT) has been shown to predict cardiovascular risk in many large studies. However, there is controversy regarding the value of CIMT for prediction of cardiovascular risk because of differences in study design, specifically with respect to CIMT measurements. Pulse wave velocity (PWV) is the most widely used measure of arterial stiffness; measurement of PWV is simple, non-invasive, and reproducible. Many clinical studies and meta-analyses have shown that PWV has predictive value in cardiovascular disease beyond traditional risk factors, both in the general population and in patients with various diseases. Brachial pressure has been a poor surrogate for aortic pressure for more than 50 years. However, recent studies have shown a closer relationship between central blood pressure and intermediate cardiovascular phenotypes or cardiovascular target organ damage, compared to the respective relationships with brachial blood pressure. Considering the non-invasiveness and ability to collect multiple types of clinical data, measurement of CIMT, PWV, and central blood pressure may be useful to identify patients at high risk for development of cardiovascular disease.
Arterial Pressure ; Arteriosclerosis ; Atherosclerosis ; Blood Pressure ; Cardiovascular Diseases ; Carotid Intima-Media Thickness ; Collagen ; Humans ; Mortality ; Phenobarbital ; Phenotype ; Plaque, Atherosclerotic ; Pulse Wave Analysis ; Risk Factors ; Vascular Stiffness

BACKGROUND: Endothelial dysfunction, the initial pathogenic factor in atherosclerosis, can be alleviated via transient limb ischemia. We observed the effects of regular transient limb ischemia (RTLI) on atherosclerosis in hypercholesterolemic rabbits. METHODS: Twenty-eight rabbits were randomized to control, cholesterol, sham, ischemia groups (n = 7 each) between October 2010 and March 2011. They were fed a normal diet in the control group and hypercholesterolemic diet in other groups for 12 weeks. Six cycles of RTLI were performed once per day on the ischemia group. Serum samples were prepared to measure the total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) before the experiment (W0), at the end of weeks 4, 8, 12 (W4, W8, W12). The whole aorta was harvested at W12 and stained using Sudan IV to identify the plaque. The plaque area was measured using Image J. Results were analyzed by analysis of variance or rank sum test. RESULTS: Concentrations of TC in the cholesterol group were higher than those in the control group at W4 (29.60 [23.75, 39.30] vs. 1.00 [0.80, 1.55], Z = -2.745, P = 0.006), W8 (41.78 [28.08, 47.37] vs. 0.35 [0.10, 0.68], Z = -2.739, P = 0.006), W12 (48.32 [40.04, 48.95] vs. 0.61 [0.50, 0.86], Z = -2.739, P = 0.006). Similar results were obtained for HDL-C and LDL-C. Serum concentrations of TC, HDL-C, and LDL-C in the hypercholesterolemic groups had no differences (all P > 0.05). The percentage of plaque area in the cholesterol group was higher than that in the control group (47.22 ± 23.89% vs. 0, Z = -2.986, P = 0.003). Square root of the percentage of plaque area was smaller in the ischemia group than that in the cholesterol (0.44 ± 0.13 vs. 0.67 ± 0.18, P = 0.014) or sham groups (0.44 ± 0.13 vs. 0.61 ± 0.12, P = 0.049). CONCLUSION In hypercholesterolemic rabbits, RTLI might prevent atherosclerosis progression by reducing the percentage of plaque area.
Animals ; Atherosclerosis ; blood ; prevention & control ; Cholesterol ; blood ; Cholesterol, HDL ; blood ; Cholesterol, LDL ; blood ; Extremities ; pathology ; Hypercholesterolemia ; blood ; Ischemic Attack, Transient ; blood ; Ischemic Postconditioning ; methods ; Male ; Rabbits ; Triglycerides ; blood

OBJECTIVE: To determine the effects of hawthorn extract on serum lipid levels, pathological changes in aortic atherosclerosis plaque, inflammatory factors, and apoptosis-related protein and mRNA expression in apolipoprotein E gene knockout (ApoE) mice. METHODS: Thirty-six ApoE mice were fed with a high-fat diet starting at the age of 8 weeks. Mice were randomly divided into 3 groups by a random number table including model group, hawthorn extract group, and simvastatin group, 12 mice in each group. Twelve 8-week-old C57BL/6 mice were fed a basic diet and served as control. The mice in the control and model groups were administered 0.2 mL saline daily, the mice in the hawthorn extract and simvastatin groups were administered with 50 mg/kg hawthorn extract or 5 mg/kg simvastatin daily for 16 weeks. After 16 weeks, plasma lipids including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were determined by an enzymatic assay. Aortic atherosclerotic lesions were observed by light microscopy, scanning and transmission electron microscopy, respectively. Plasma levels of monocyte chemoattractant protein-1 (MCP-1), interleukin-1β (IL-1β), adiponectin (APN), and hypersensitive C-reactive protein (hs-CRP) were measured by enzyme-linked immunosorbent assay (ELISA). Protein and mRNA expressions of Bax and Bcl-2 in the aorta were assessed by Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR), respectively. RESULTS: Compared to the control group, the plasma levels of TC, TG and LDL-C were significantly increased and HDL-C were significantly decreased in the model group (P<0.01). Compared to the model group, treatment with hawthorn extract significantly decreased the plasma levels of TC, TG, and LDL-C and increased the plasma level of HDL-C in ApoE mice (P<0.01). The levels of MCP-1, IL-1ß, and hs-CRP in the model group were significantly increased and APN was significantly decreased compared with the control group (P<0.01). Compared to the model group, treatment with hawthorn extract decreased the levels of MCP-1, IL-1ß, and hs-CRP and increased the APN level (P<0.01). Compared to the control group, the protein and mRNA expression of Bax in the model group were significantly increased and the expression of Bcl-2 was significantly decreased (P<0.01). Hawthorn extract also reduced the protein and mRNA expression of Bax and increased the Bcl-2 expression in the aorta (P<0.01). CONCLUSION Hawthorn extract has anti-atherosclerosis and stabilizing unstable plaque effects. The mechanism may be related to the inflflammation and apoptosis signaling pathways.
Animals ; Aorta ; pathology ; ultrastructure ; Apoptosis ; drug effects ; Atherosclerosis ; blood ; complications ; drug therapy ; Crataegus ; chemistry ; Inflammation ; blood ; complications ; drug therapy ; Inflammation Mediators ; metabolism ; Lipids ; blood ; Male ; Mice, Inbred C57BL ; Plant Extracts ; pharmacology ; therapeutic use ; RNA, Messenger ; genetics ; metabolism ; bcl-2-Associated X Protein ; metabolism