The Phosphodiesterase Inhibitor Cilostazol Induces Regression of Carotid Atherosclerosis in Subjects With Type 2 Diabetes Mellitus Principal Results of the Diabetic Atherosclerosis Prevention by Cilostazol (DAPC) Study: A Randomized Trial

OBJECTIVE To analyze the associations of severity of fatty liver with oxidative stress, serum amyloid protein A (SAA), C-reactive protein (CRP) and degree of cerebral arteriosclerosis (CAS) in CAS patients with the complication of fatty liver, and to explore the predictive values of risk factors for these patients. METHODS A total of 200 patients diagnosed with CAS in our hospital from October 2016 to November 2018 were selected, including 90 cases with fatty liver (observation group) and 110 cases without fatty liver (control group), and there were 123 males and 77 females. The general clinical data, liver function, oxidative stress status, inflammatory factor levels, and degree of CAS were compared between the two groups, and their correlations and influencing factors were explored. RESULTS 1) There were no significant differences in the age, gender, and high-density lipoprotein (HDL) level between the observation group and control group (P>0.05). The body mass index (BMI), total cholesterol (TC), triglyceride (TG) and low-density lipoprotein (LDL) levels in the observation group were significantly higher than those in the control group. 2) The levels of liver function indexes, including alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transpeptidase (GGT), in the observation group were significantly higher than those in the control group, all (P<0.05). 3) In terms of the oxidative stress, the level of malondialdehyde (MDA) in the observation group was higher than that in the control group, while the levels of superoxide dismutase (SOD) and glutathione (GSH) in the observation group were obviously lower than in the control group, all (P<0.05). 4) The levels of inflammatory factors, including SAA, CRP and interleukin-6 (IL-6), in the observation group were much higher than those in the control group (P<0.05). 5) Observation group had higher whole blood low shear viscosity, whole blood high shear viscosity, and plasma viscosity than the control group (P<0.05). 6) ALT (r = 0.422, P = 0.000) and SAA (r = 0.828, P = 0.000) had positive correlations with the plasma viscosity, while GSH (r = -0.719, P<0.001) had a negative correlation with the plasma viscosity. CONCLUSION The liver function index levels, oxidative stress status, and inflammatory factor levels in CAS patients may affect the severity of arteriosclerosis and fatty liver.

Associations of severity of fatty liver with oxidative stress, SAA, CRP and degree of cerebral arteriosclerosis in cerebral arteriosclerosis patients who have fatty liver.

The study aimed to explore the correlations of the results of the high-frequency ultrasound evaluation of the brachial artery endothelial dilatation and carotid atherosclerosis with glucose and lipid metabolism, inflammatory cytokines, the severity of coronary artery disease (CAD) and vascular endothelial function in elderly patients. 78 elderly patients with CAD in Beijing Anzhen Hospital were selected. The high-frequency ultrasonography was carried out to observe the flow-mediated dilatation (FMD) and intima-media thickness (IMT) and to analyze their correlations with inflammatory cytokines [C-reactive protein (CRP) and plasminogen activator inhibitor (PAI-1)], endothelial function [nitric oxide (NO) and endothelin-1 (ET-1)], glycolipid metabolism [high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), triglyceride (TG) and fasting blood glucose (FBG)] and the severity of CAD. FMD, NO and HDL-C: patients with single-vesselCAD> those with double-vessel CAD>those with multi-vessel CAD. IMT, CRP, PAI-1, FBG, ET-1, TC and TG: patients with single-vesselCAD< those with double-vessel CAD <those with multi-vessel CAD (p<0.05). The FMD had negative correlations with CRP, PAI-1, FBG, ET-1, TC and TG and positive correlations with NO and HDL-C (p<0.05). The IMT was positively associated with CRP, PAI-1, FBG, ET-1, TC and TG and negatively related to NO and HDL-C (p<0.05). As the disease becomes severe, the endothelial dilatation of brachial arteries in elderly patients with CAD becomes weaker, and the risk of carotid atherosclerosis increases. 

/pdf/correlations-of-high-frequency-ultrasound-evaluation-of-3rydtqrb.pdf

Correlations of High-frequency Ultrasound Evaluation of Brachial Artery Endothelial Dilatation and Carotid Atherosclerosis with Glucose and Lipid Metabolism, Inflammatory Cytokines, Severity of Coronary Artery Disease and Vascular Endothelial Function in Elderly Patients

Introduction Carotid atherosclerosis is a well-established biomarker associated with future cardiovascular disease and stroke. We explored the influence of sex on the relationship between metabolic syndrome (MetS) and its components with carotid intima-media thickness (CIMT) among a low-income population in China, which has a high incidence of stroke. Methods This population-based study recruited participants aged ≥45 years from rural areas of Tianjin, China between April 2014 and January 2015. Anthropometric characteristics and biochemical profiles were measured. CIMT was assessed using ultrasonography. Diagnosis of MetS and its components was made using the modified International Diabetes Federation criteria for the Asian population. A multivariate linear regression model was used to evaluate the effects of sex on the relationship between the presence of MetS and its components and CIMT. Results A total of 3583 individuals (men, 41.4%; women, 58.6%) were included in the analyses. MetS was prevalent in 54.5% (men, 42.3%; women, 63.2%) of the participants. Mean CIMT was 0.57 ± 0.09 mm. In the multivariate analysis, for both sexes, CIMT increased significantly when MetS was present compared with when it was not (both P < 0.001). A common trend was observed in both sexes, in that CIMT increased as the number of MetS components increased, with β (95% confidence interval [CI]) = 0.021 (0.000, 0.042) for men and 0.014 (0.002, 0.026) for women (both P < 0.05). Of the five MetS components, elevated blood pressure was an independent risk factor for increased CIMT in both sexes (men: β = 0.013; 95% CI: 0.003, 0.023; P = 0.008; women: β = 0.024; 95% CI: 0.016, 0.033; P < 0.001). Moreover, abdominal obesity was also an independent risk factor for increased CIMT in men (β = 0.013; 95% CI: 0.003, 0.023; P = 0.008) but not in women. Conclusion The presence and number of components of MetS were associated with CIMT in both men and women. Sex differences were found in the impact of individual components of MetS on CIMT. Early identification and management of MetS according to sex-specific risk of MetS should be considered to reduce the prevalence and burden of carotid atherosclerosis in rural China, which has a high incidence of stroke, a known consequence of carotid atherosclerosis.

/pdf/sex-specific-differences-in-the-association-between-3nu682ab83.pdf

Sex -Specific Differences in the Association Between Metabolic Syndrome and Carotid Intima-Media Thickness Among a Low-Income Population in China: A Cross-Sectional Study.

Although statins, ezetimibe, and PCSK9 inhibitors effectively reduce LDL-C levels and mitigate CHD risk, some residual risks persist. Probucol, a lipid-lowering agent with potent antioxidant properties, is prescribed in Asia for dyslipidemia treatment, ASCVD prevention, and xanthoma improvement. Its use was discontinued in Western countries due to concerns over HDL-C reduction and QT prolongation; however, recent research supports its therapeutic benefits. Probucol decreases HDL-C by promoting RCT through CETP and SR-BI activation while also enhancing HDL’s antioxidative function by elevating PON1 activity and lowering oxidized HDL levels. Studies on FH patients and those undergoing coronary revascularization indicate its role in secondary CV prevention. An integrated analysis of the PROSPECTIVE and IMPACT on IMT studies has suggested that, despite reducing HDL-C, probucol may offer protective effects against CHD. Potential applications of probucol for other diseases and recent advances of nanoparticle-based probucol delivery systems for the treatment of atherosclerosis and inflammation are also discussed. 

Impact of probucol on xanthoma reduction and its role in cardiovascular event prevention in familial hypercholesterolemia patients

Background Atherosclerosis is one of the main mechanisms of stroke and cardiovascular diseases and is associated with increased risk of recurrent stroke and cardiovascular events. Intima-medial thickness (IMT) is a well-known surrogate marker of atherosclerosis and has been used to predict stroke and cardiovascular events. However, the clinical significance of IMT and IMT change in stroke has not been investigated in well-designed studies. The PreventIon of CArdiovascular events in iSchemic Stroke patients with high risk of cerebral hemOrrhage—Intima-Media Thickness (PICASSO-IMT) sub-study is designed to investigate the effects of cilostazol, probucol, or both on IMT in patients with stroke. Methods PICASSO-IMT is a prospective sub-study of the PICASSO study designed to measure IMT and plaque score at 1, 13, 25, 37, and 49 months after randomization. Results The primary outcome is the change in mean carotid IMT, which is defined as the mean of the far-wall IMTs of the right and left common carotid arteries, between baseline and 13 months after randomization. Conclusion PICASSO-IMT will provide the largest IMT data set in a stroke population and will provide valuable information about the clinical significance of IMT in patients with ischemic stroke.

Design and Rationale of the Intima-Medial Thickness Sub-Study of the PreventIon of CArdiovascular Events in iSchemic Stroke Patients with High Risk of Cerebral hemOrrhage (PICASSO-IMT) Study.

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Design and Rationale of the Intima-Medial Thickness Sub-Study of the PreventIon of CArdiovascular Events in iSchemic Stroke Patients with High Risk of Cerebral hemOrrhage (PICASSO-IMT) Study.