The Effects of Statin Dose, Lipophilicity, and Combination of Statins plus Ezetimibe on Circulating Oxidized Low-Density Lipoprotein Levels: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Elevated plasma low-density lipoprotein cholesterol (LDL-C) is the main risk factor for atherosclerotic cardiovascular disease (ASCVD). Statins are the drugs of choice for decreasing LDL-C and are used for the prevention and management of ASCVD. Guidelines recommend that subjects with high and very high ASCVD risk should be treated with high-intensity statins or a combination of high-intensity statins and ezetimibe. The lipophilicity or hydrophilicity (solubility) of statins is considered to be important for at least some of their LDL-C lowering independent pleiotropic effects. Oxidative modification of LDL (ox-LDL) is considered to be the most important atherogenic modification of LDL and is supposed to play a crucial role in atherogenesis and ASCVD outcomes. OBJECTIVE: The aim of this systematic review and meta-analysis was to find out what are the effects of statin intensity, lipophilicity, and combination of statins plus ezetimibe on ox-LDL. METHODS: PubMed, Scopus, Embase, and Web of Science were searched from inception to February 5, 2021, for randomized controlled trials (RCTs). Two independent and blinded authors evaluated eligibility by screening the titles and abstracts of the studies. Risk of bias in the studies included in this meta-analysis was evaluated according to the Cochrane instructions. Meta-analysis was performed using Comprehensive Meta-Analysis (CMA) V2 software. Evaluation of funnel plot, Begg's rank correlation, and Egger's weighted regression tests were used to assess the presence of publication bias. RESULTS: Among the 1427 published studies identified by a systematic databases search, 20 RCTs were finally included in the systematic review and meta-analysis. A total of 1874 patients are included in this meta-analysis. This meta-analysis suggests that high-intensity statin treatment is associated with a significant decrease in circulating concentrations of ox-LDL when compared with low-to-moderate treatment (SMD: -0.675, 95% CI: -0.994, -0.357, p < 0.001; I 2: 55.93%). There was no difference concerning ox-LDL concentration between treatments with hydrophilic and lipophilic statins (SMD: -0.129, 95% CI: -0.330, -0.071, p = 0.206; I 2: 45.3%), but there was a significant reduction in circulating concentrations of ox-LDL associated with statin plus ezetimibe combination therapy when compared with statin monotherapy (SMD: -0.220, 95% CI: -0.369, -0.071, p = 0.004; I 2: 0%). CONCLUSION: High-dose statin or combination of statins with ezetmibe reduces plasma ox-LDL in comparison low-to-moderate intensity statin therapy alone. Statin lipophilicity is not associated with reduction in ox-LDL plasma concentrations.

Diagnostic Value of Non-invasive Liver Function Tests in Liver Fibrosis and Changes in These Parameters Post-metabolic Surgery.

PURPOSE: This study aimed to ascertain the diagnostic accuracy of non-invasive liver function tests in liver fibrosis and assess their changes after metabolic surgery. MATERIALS AND METHODS: 1005 individuals with severe obesity who were referred for metabolic surgery were analysed. All participants had blood samples taken for liver enzymes and lipid profile. In addition, hepatic indexes, including AAR, APRI, NFS and Fibrosis-4 (FIB4), were checked. Furthermore, all participants underwent two-dimensional shear wave elastography (2D-SWE). All investigations were repeated 6-8 months after metabolic surgery. The receiver operating characteristic (ROC) curve and the area under the ROC curve was utilised to determine the optimal cut-off values for baseline study parameters. Logistic regression was applied to predict the relationship between study parameters-as predictors-and change in 2D-SWE. RESULTS: AST/ALT (AAR) was the most sensitive (79%) pre-operative non-invasive serological marker for detecting liver fibrosis, whereas NAFLD Fibrosis Score (NFS) was the most specific (84%). AST/upper limit of the normal AST range × 100/platelets (× 109/L) (APRI) showed a positive correlation with 2D-SWE post-metabolic surgery (p-value = 0.021). Regression analysis from both adjusted and unadjusted models showed that baseline AAR was a predictor of postoperative liver status in terms of hepatic fibrosis. CONCLUSION: AAR has a high sensitivity, whereas NFS exhibits a high specificity in diagnosing liver fibrosis. The authors recommend using both investigations in conjunction with 2D-SWE to increase the likelihood of detecting liver fibrosis.

Effects of curcumin on low-density lipoprotein oxidation: From experimental studies to clinical practice.

Atherosclerosis is the most frequent cause of death globally. Oxidized low-density lipoprotein (ox-LDL) has an essential role in the formation of atherosclerotic plaques and foamy macrophages. Ox-LDL increases the uptake of cholesterol by macrophages and is the major cause of blood flow disruption. Ox-LDL is produced during oxidative stress and treatment with antioxidants could inhibit the production and function of ox-LDL. Curcumin is a potent antioxidant and has a strong track record in the treatment of numerous diseases. Recent studies indicate that Curcumin exerts a lipid-lowering effect, and can modulate the formation of atherosclerotic plaque. The current review focuses upon the role of Curcumin in oxidation of LDL and foam cell formation in atherosclerotic lesions.

The Effects of Statin Therapy on Oxidized LDL and Its Antibodies: A Systematic Review and Meta-Analysis.

Background: Elevated serum low-density lipoproteins (LDL), the substrate for the formation of atherogenic oxidized LDLs (oxLDL), are a causal factor for atherosclerotic cardiovascular disease (ASCVD). Statins are well known to decrease LDL particle concentration and reduce ASCVD morbidity and mortality. Objective: To perform a meta-analysis of the effects of statins (i.e., type, dose, and duration of treatment) on serum levels of oxLDL and on immunoglobulin M (IgM) and immunoglobulin G (IgG) antibody levels against oxLDL. Methods: PubMed, Scopus, Embase, and Web of Science were searched up to February 5th, 2021, for randomized controlled trials (RCT) evaluating the effect of statins on oxLDL and anti-oxLDL antibody levels. Meta-analysis was performed using Comprehensive Meta-Analysis (CMA) V2 software. To evaluate the influence of each study on the overall effect size, a sensitivity analysis was performed using the leave-one-out method. Evaluation of the funnel plot, Begg's rank correlation, and Egger's weighted regression tests was used to assess the presence of publication bias in the meta-analysis. Results: A total of 28 RCTs including 4019 subjects were finally included in the meta-analysis. The results indicated a significant decrease in circulating concentrations of oxLDL after treatment with statins (SMD: -2.150, 95% CI: -2.640, -1.697, p < 0.001). Subgroup analysis found no significant effect of the intensity of statin treatment or statin lipophilicity on the reduction of circulating concentrations of oxLDL. An additional meta-analysis of 3 trials showed that statins did not change the serum levels of IgM and IgG antibodies to oxLDL. Conclusion: Statin therapy decreases serum oxLDL concentrations but does not affect circulating levels of anti-oxLDL antibodies.