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Cytokine Feb 2023Interleukin-10 (IL-10) is an anti-inflammatory cytokine with potent deactivating properties on macrophages and T cells; and plays an important role in atherosclerotic... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Interleukin-10 (IL-10) is an anti-inflammatory cytokine with potent deactivating properties on macrophages and T cells; and plays an important role in atherosclerotic plaque maturation and rupture. A guanine (G) to adenine (A) substitution in the IL-10 gene at -1082 bp (rs1800896) has been associated with reduced in IL-10 production in vitro. Against this background, we tested the association of IL-10 -1082G/A with early or severe presentation of coronary artery disease (CAD) using a systematic review and updated meta-analysis of published association studies.
MATERIALS AND METHODS
Relevant studies were identified following a comprehensive online search on PubMed, EMBASE, MEDLINE, Scopus, Cochrane library and Web of Science databases and stratified into two subgroups based on mode of CAD presentation: early or severe and non-severe. Study level odds ratios (ORs) and their 95% confidence intervals (CI) were pooled using random effects employing a Z test.
RESULTS
A total of 24 studies were included for quantitative synthesis with a cumulative sample of 19,135 (11,143 cases / 7,992 controls). A significant association was derived for IL-10 -1082G/A and early or severe CAD via dominant, recessive, and allelic genetic model comparisons [OR 1.24 (95 % CI 1.02, 1.50), p = 0.03; OR 1.32 (95 % CI 1.03, 1.69), p = 0.03 and OR 1.18 (95 % CI 1.02, 1.36), p = 0.02 respectively]. In contrast, no significant association was seen for the pooled group or non-severe CAD subgroup (p = NS). Sensitivity analysis showed consistent results.
CONCLUSIONS
IL-10 -1082G/A appears to be associated with early or severe presentation of CAD. Further studies are warranted to confirm this association.
Topics: Humans; Coronary Artery Disease; Interleukin-10; Polymorphism, Single Nucleotide; Genetic Predisposition to Disease; Gene Expression
PubMed: 36463660
DOI: 10.1016/j.cyto.2022.156103 -
Stroke Feb 2023Over the last decades, several individual studies on sex differences in carotid atherosclerosis have been performed covering a wide range of plaque characteristics and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Over the last decades, several individual studies on sex differences in carotid atherosclerosis have been performed covering a wide range of plaque characteristics and including different populations. This systematic review and meta-analysis aims to summarize previously reported results on sex differences in carotid atherosclerosis and present a roadmap explaining next steps needed for implementing this knowledge in clinical practice.
METHODS
We systematically searched PubMed, Embase, Web of Science, Cochrane Central, and Google Scholar for eligible studies including both male and female participants reporting prevalence of imaging characteristics of carotid atherosclerosis and meta-analyzed these studies. Studies had to report at least the following: (1) calcifications; (2) lipid-rich necrotic core; (3) intraplaque hemorrhage; (4) thin-or-ruptured fibrous cap; (5) plaque ulceration; (6) degree of stenosis; (7) plaque size; or (8) plaque inflammation. We prespecified which imaging modalities had to be used per plaque characteristic and excluded ultrasonography.
RESULTS
We included 42 articles in our meta-analyses (ranging from 2 through 23 articles per plaque characteristic). Men had more frequently a larger plaque compared to women and, moreover, had more often plaques with calcifications (odds ratio=1.57 [95% CI, 1.23-2.02]), lipid-rich necrotic core (odds ratio=1.87 [95% CI, 1.36-2.57]), and intraplaque hemorrhage (odds ratio=2.52 [95% CI, 1.74-3.66]), or an ulcerated plaque (1.81 [95% CI, 1.30-2.51]). Furthermore, we found more pronounced sex differences for lipid-rich necrotic core in symptomatic opposed to asymptomatic participants.
CONCLUSIONS
In this systematic review and meta-analysis, we demonstrate convincing evidence for sex differences in carotid atherosclerosis. All kinds of plaque features-plaque size, composition, and morphology-were more common or larger in men compared to women. Our results highlight that sex is an important variable to include in both study design and clinical-decision making. Further investigation of sex-specific stroke risks with regard to plaque composition is warranted.
Topics: Female; Male; Humans; Carotid Stenosis; Sex Characteristics; Magnetic Resonance Imaging; Carotid Artery Diseases; Plaque, Atherosclerotic; Hemorrhage; Calcinosis; Necrosis; Lipids; Carotid Arteries; Risk Factors
PubMed: 36444718
DOI: 10.1161/STROKEAHA.122.041046 -
Frontiers in Cardiovascular Medicine 2022Several clinical trials have indicated that statins stabilize and reverse atherosclerotic plaque. However, different studies have provided inconsistent findings...
OBJECTIVE
Several clinical trials have indicated that statins stabilize and reverse atherosclerotic plaque. However, different studies have provided inconsistent findings regarding mechanisms and influencing factors of plaque regression under statin therapy. Apart from lipid-lowering effect, statins have pleiotropic effects including anti inflammation in humans. In this study, meta-analysis and meta-regression were used to determine the effects of statin medications on coronary plaque volume. Meanwhile, to assess whether statins promote plaque regression effect was related to their anti-inflammatory ability, the impact of CRP/hsCRP reduction during statin therapy on plaque regression was investigated.
METHODS
Up to June 15, 2022, a systematic PubMed, EMBASE, and Cochrane search was performed for randomized controlled trials that assessed treatment effect using total atheroma volume (TAV), percent atheroma volume (PAV), or plaque volume (PV). Only CRP/hsCRP and LDL-C values reported before and after treatment were considered.
RESULTS
12 studies (2,812 patients with heart and/or vascular disease) fulfilled the inclusion criteria and were included in the systematic review. A meta-analysis of 15 statin-treated arms reported a significant reduction in change of TAV/PV [standardized mean difference (SMD): -0.27, 95% confidence intervals (-CI): -0.42, -0.12, < 0.001], compared with the control arms. Another meta-analysis of 7 trials also found that patients in the intervention group had a significant reduction in change of PAV (SMD: -0.16, 95% CI: -0.29, -0.03, = 0.019), compared with those in the control group. Meta-regressionanalysis revealed that the percent change of CRP/hsCRP was significantly associated with SMD in change of TAV/PV after adjusting for percent change of LDL-C, age, gender and study duration. Meta-regression analysis showed that percent change of CRP/hsCRP statistically influenced SMD in change of PAV, when percent change of CRP/hsCRP was included separately. However, the percent change of CRP/hsCRP was not significantly associated with SMD of PAV change after adjusting for all covariates.
CONCLUSION
In conclusion, statin therapy is beneficial for plaque regression. Statins promote plaque regression, which might be associated to their anti-inflammatory ability.
PubMed: 36440015
DOI: 10.3389/fcvm.2022.989527 -
Frontiers in Pharmacology 2022This meta-analysis aimed at evaluating the effectiveness and safety of Chinese medicine (TCM), which nourished qi, promoted blood circulation, and expelled phlegm...
Effectiveness and safety of treating carotid atherosclerotic plaques with the method of nourishing qi, promoting blood circulation and expelling phlegm: A systematic review and meta-analysis.
This meta-analysis aimed at evaluating the effectiveness and safety of Chinese medicine (TCM), which nourished qi, promoted blood circulation, and expelled phlegm (YQHXZT), in treating carotid atherosclerosis (CAS) from an immunological perspective. The incidence of CAS has been increasing and tends to be younger. Although western medicine is effective, there are some limitations. TCM has certain advantages over the multichannel and multitarget treatment strategies in slowing down the process of CAS. However, there is no comprehensive review in this field. Nine databases were searched from January, 2012, to September, 2022. After applying the inclusion and exclusion criteria to the RCTs, research quality evaluation and data extraction were conducted, and a meta-analysis of the articles was performed. The GRADE was used to assess the quality of the evidence. Fourteen RCTs involving 1,191 patients were identified. The results indicated that the experimental group was more effective in improving carotid intima-media thickness (CIMT)[SMD = -0.97, 95%CI(-.30,-0.65), < 0.00001], reducing carotid plaque area [SMD = -1.98, 95%CI(-3.06,-0.89), = 0.0003], lowering hs-CRP [SMD = -1.33, 95%CI(-1.59,-1.06), < 0.00001] and LDL-C levels [SMD = -0.60, 95%CI(-0.83,-0.38), < 0.00001]. Moreover, the experimental group was superior to peak systolic blood flow velocity (PSV) [SMD = -0.37, 95%CI(-0.59,-0.16), = 0.0007], clinical efficacy [RR = 1.64, 95% CI (1.39, 1.94), < 0.00001] and plaque area efficacy [RR = 1.36, 95% CI (1.22, 1.52), < 0.0001]. The adverse reactions were not statistically significant in the two groups [RD = -0.01, 95% CI (-0.04.0.01), = 0.17]. The results of grade evaluation suggested that the outcome indicators LDL-C, hs-CRP, plaque area efficacy, PSV, and adverse events were moderate. CIMT, plaque reduction area, and TCM clinical efficacy were low-quality. The combination of YQHXZT can alleviate the process of CAS by inhibiting the thickening of CIMT, reducing plaque area and lowering hs-CRP and LDL-C levels. The mechanism may possibly be related to reducing lipid deposition and inhibiting the inflammatory response. Besides, the combination did not increase the risk of adverse effects. However, more well-designed RCTs are needed in the future. CRD42022360529, https://www.crd.york.ac.uk/prospero/.
PubMed: 36438842
DOI: 10.3389/fphar.2022.1059737 -
Cureus Oct 2022Coronary artery disease (CAD) is one of the leading causes of death worldwide. Atherosclerosis begins in childhood as fatty streaks, progresses with age, and lifestyle... (Review)
Review
Coronary artery disease (CAD) is one of the leading causes of death worldwide. Atherosclerosis begins in childhood as fatty streaks, progresses with age, and lifestyle influences the progression of atherosclerotic plaque. Over time, with significant narrowing of the blood vessels, blood flow into the coronary arteries is compromised, resulting in various symptoms of coronary heart disease. Many drugs are used in clinical practice to prevent atherosclerotic cardiovascular events in patients with CAD. This review aims to investigate the efficacy and safety of a non-statin novel lipid-lowering drug, bempedoic acid (BDA), an adenosine triphosphate (ATP) citrate lyase inhibitor, in lowering serum low-density lipoprotein cholesterol (LDL-C) levels among patients with CAD. BDA is a new drug that recently got approval for clinical use. Following its discovery, BDA has been researched in order to investigate its role in the treatment of hypercholesterolemia. A search for studies was conducted using databases such as PubMed, PMC, ScienceDirect, and Google Scholar up until April 30, 2022. This systematic review has followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A total of 11 studies were finalized to explore the role of BDA alone or as an adjunct in lowering serum LDL-C levels in high-risk patients under maximally tolerated statins, statin-intolerant groups, or treatment with other lipid-lowering drugs. These studies are three randomized controlled trials (RCTs), one pre-proof RCT, two systematic reviews and meta-analyses, and five narrative review articles. This review included 8465 participants from recently conducted RCTs and systematic reviews. Another 14014 participants, enrolled for the Cholesterol Lowering via Bempedoic Acid, an Adenosine Triphosphate-Citrate Lyase-Inhibiting Regimen (CLEAR) Outcomes clinical trial, were also included. BDA in combination with ezetimibe showed good evidence of LDL-C lowering effect. Patients on maximally tolerated statin failing to achieve desired LDL-C when treated in combination with BDA showed a significant decrement in serum LDL-C levels, high sensitivity C-reactive protein (HsCRP), and triglyceride. BDA use showed no adverse side effects. The most common side effect seen in several trials was the rise in serum uric acid level. When treating patients with BDA, baseline uric acid levels should be obtained and regular monitoring of uric acid should be done. The CLEAR Outcomes trial, scheduled to be completed by December 2022, will provide further information on BDA. BDA appears to be a promising alternative to currently available secondary lipid-lowering agents.
PubMed: 36348882
DOI: 10.7759/cureus.29891 -
Journal of Stroke and Cerebrovascular... Dec 2022To compare the difference in the risk of stroke for four kinds of carotid artery plaque and carotid artery stenosis. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To compare the difference in the risk of stroke for four kinds of carotid artery plaque and carotid artery stenosis.
METHODS
Literature was collected by searching the PubMed, Embase, Cochrane library and Ovid databases up to June 2022, using the free search terms "carotid plaque" and "stroke". Meta-analysis was performed on the selected articles using Stata16 to analyse the relationship of stroke risk factors.
RESULTS
A total of 11 studies including 6661 participants were included. Meta-analysis results showed that the incidence of stroke was statistically significantly different between IPH (intraplaque haemorrhage) plaques and LRNC (lipid-rich necrotic core) plaques (RR: 1.27, 95% CI: 1.04-1.55, P < 0.05) and IPH plaques and calcification plaques (RR: 2.99, 95% CI: 1.74-5.14, P < 0.0001). Furthermore, there was a statistically significant difference between TRFC (thinned or ruptured fibrous caps) plaques and carotid artery stenosis (RR: 10.84, 95% CI: 5.60-20.98, P < 0.0001) and calcification plaques and carotid artery stenosis (RR: 0.83, 95% CI: 0.75-0.92, P < 0.0001). However, there was no statistically significant difference between the IPH and carotid artery stenosis (RR: 1.55, 95% CI: 0.68-3.52, P > 0.05), LRNC and TRFC (RR: 0.80, 95% CI: 0.11-5.82, P > 0.05), LRNC and calcification (RR: 1.81, 95% CI: 0.90-3.66, P > 0.05) and LRNC and carotid artery stenosis (RR: 1.40, 95% CI: 0.69-2.81, P > 0.05).
CONCLUSION
IPH was associated with a higher incidence of stroke compared to LRNC and calcification plaques and TRFC has a higher risk of stroke than calcification plaques and carotid stenosis. This evidence suggests that IPH and TRFC may play an important role in predicting stroke.
Topics: Humans; Carotid Stenosis; Carotid Arteries; Plaque, Atherosclerotic; Stroke; Risk Factors; Magnetic Resonance Imaging
PubMed: 36334373
DOI: 10.1016/j.jstrokecerebrovasdis.2022.106857 -
Journal of Ultrasound in Medicine :... Feb 2023The aim of this meta-analysis was to evaluate the diagnostic value of contrast-enhanced ultrasound (CEUS) and high-resolution magnetic resonance imaging (HR-MRI) in... (Meta-Analysis)
Meta-Analysis
Diagnostic Performance of Contrast-Enhanced Ultrasound and High-Resolution Magnetic Resonance Imaging for Carotid Atherosclerotic Plaques: A Systematic Review and Meta-Analysis.
OBJECTIVES
The aim of this meta-analysis was to evaluate the diagnostic value of contrast-enhanced ultrasound (CEUS) and high-resolution magnetic resonance imaging (HR-MRI) in patients with carotid vulnerable plaques.
METHODS
A systematic review was conducted in PubMed, Embase, Cochrane Library, and Web of Science using the search terms carotid artery, atherosclerotic plaque, CEUS, contrast-enhanced ultrasound, HR-MRI, and high-resolution magnetic resonance. Studies published since the establishment of the library until December 2021 were retrieved. The statistical analyses were performed with Meta-DiSc version 1.4. Beyond that, the potential sources of heterogeneity for CEUS and HR-MRI were explored.
RESULTS
Nine articles were included in this study. For CEUS, the pooled sensitivity and specificity for detecting carotid vulnerable plaques 91% (95% confidence interval [CI]: 84%, 95%) and 67% (95% CI: 54%, 79%), respectively. For HR-MRI, the pooled sensitivity and specificity were 78% (95% CI: 72%, 83%) and 65% (95% CI, 56%, 73%), respectively. The area under the summary receiver operating characteristic curve for CEUS and HR-MRI were 0.9218 and 0.8129, respectively. However, the difference in diagnostic accuracy between CEUS and HR-MRI diagnostic accuracy was not statistically significant.
CONCLUSIONS
The study shows that the sensitivity of CEUS was higher than that of HR-MRI, and the specificity was similar to HR-MRI. CEUS and HR-MRI provide a similar diagnostic yield in detecting a vulnerable plaque. Thus, CEUS may be a useful tool for the diagnosis of carotid vulnerable plaques.
Topics: Humans; Plaque, Atherosclerotic; Contrast Media; Carotid Arteries; Ultrasonography; Magnetic Resonance Imaging
PubMed: 36321389
DOI: 10.1002/jum.16122 -
Dementia and Geriatric Cognitive... 2022Extracranial carotid atherosclerosis has been variably associated with dementia. Prior studies have focused on the association of carotid intima media thickness or... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Extracranial carotid atherosclerosis has been variably associated with dementia. Prior studies have focused on the association of carotid intima media thickness or carotid stenosis; however, there is evidence that carotid plaque may contribute to dementia, perhaps via microembolic phenomena.
OBJECTIVES
We sought to evaluate the role of carotid plaque in contributing to cognitive impairment by performing a systematic review and meta-analysis to summarize the association between extracranial carotid plaque and cognitive dysfunction and dementia.
METHODS
We performed a comprehensive literature search evaluating the association of extracranial carotid plaque with cognition. We included studies measuring carotid plaque on ultrasound, computed tomography, or MR and also evaluated cognition through neuropsychological testing. Meta-analyses with assessment of study heterogeneity and publication bias were performed. Results were presented in a forest plot and summarized using a random-effects model.
RESULTS
After screening 1,674 studies, we included 40 for systematic review and 16 and 7 studies for two meta-analyses with a total of 19,029 and 27,325 patients, respectively. We found a positive relationship between the presence of extracranial carotid plaque and cognitive dysfunction with a pooled random-effects odds ratio (OR) of 1.83 (95% CI, 1.50, 2.24) and a pooled random-effects hazard ratio (HR) of 1.47 (95% CI, 1.15, 1.89), respectively. A sensitivity analysis of only longitudinal studies found a persistent positive association. Measures of heterogeneity showed moderate heterogeneity in each meta-analysis, respectively (I-squared statistic = 57% and 70%).
CONCLUSION
The presence of extracranial carotid plaque is significantly associated with cognitive dysfunction and dementia in both cross-sectional and longitudinal analyses. After further confirmation, our results support carotid plaque being a potentially modifiable risk factor in the development of dementia.
Topics: Humans; Carotid Stenosis; Carotid Intima-Media Thickness; Cross-Sectional Studies; Cognitive Dysfunction; Plaque, Atherosclerotic; Risk Factors; Dementia
PubMed: 36316004
DOI: 10.1159/000526822 -
Brain Circulation 2022Carotid stenosis is an important contributor to ischemic stroke risk with resultant significant impact on neurological disability and death in adults and with worldwide... (Review)
Review
Carotid stenosis is an important contributor to ischemic stroke risk with resultant significant impact on neurological disability and death in adults and with worldwide implications. Management of carotid stenosis is impacted by whether there are associated symptoms along with the degree of stenosis. Understanding of the pathogenesis of carotid atherosclerosis or stenosis is important in management of carotid stenosis. Atherosclerotic plaque formation is a chronic insidious process with a number of potential contributors to the formation of such a plaque. The definition of atherosclerosis is not simply limited to abnormal deposition of lipid but also includes a chronic, complex, inflammatory process. Molecularly, in atherosclerosis, there is decreasing nitric oxide (NO) bioavailability, activity and/or expression of endothelial NO synthase, or increasing degradation of NO secondary to enhanced superoxide production. These above changes cause endothelial dysfunction leading to formation of foam cell followed by formation on lipid plaque. After lipid plaque formation, stable or unstable atherosclerotic plaque is formed depending on the calcium deposition over the lipid plaque. It continues to be clearly established that carotid intervention for symptomatic high-grade carotid stenosis is best managed with intervention either by carotid endarterectomy or carotid stenting. However, asymptomatic carotid stenosis is the subject of considerable controversy in terms of optimal management. This review of carotid atherosclerosis is an attempt to incorporate the information provided by more recent studies on pathogenesis and management which may help in the decision-making process for optimal management for protection against stroke.
PubMed: 36267431
DOI: 10.4103/bc.bc_36_22 -
Medicine Oct 2022The additive effects of ezetimibe, evolocumab or alirocumab on lipid level, plaque volume, and plaque composition using intravascular ultrasound (IVUS) remain unclear. (Meta-Analysis)
Meta-Analysis
BACKGROUND
The additive effects of ezetimibe, evolocumab or alirocumab on lipid level, plaque volume, and plaque composition using intravascular ultrasound (IVUS) remain unclear.
METHODS
According to the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement, we performed a systematic review and meta-analysis of trials assessing the effects of ezetimibe, evolocumab, and alirocumab on coronary atherosclerosis using IVUS. The primary outcome was change in total atheroma volume (TAV), and the secondary outcomes were changes and differences in plaque composition and lipid content.
RESULTS
Data were collected from 9 trials, involving 917 patients who received ezetimibe, evolocumab or alirocumab in addition to a statin and 919 patients who received statins alone. The pooled estimate demonstrated a significant reduction in TAV with the addition of ezetimibe and favorable effects of evolocumab and alirocumab on TAV. Subgroup analysis also supported favorable effects of evolocumab and alirocumab on TAV, according to baseline TAV, gender, type 2 diabetes mellitus, and prior stain use. Addition of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor to statin therapy resulted in significant reductions in low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TG), but not in high-density lipoprotein cholesterol (HDL-C). The pooled estimate also showed significant favorable effects of ezetimibe on LDL-C, TC, and TG, but an insignificant effect on HDL-C. Patients who received ezetimibe showed similar changes in the necrotic core, fibro-fatty plaque, fibrous plaque, and dense calcification compared with patients not treated with ezetimibe.
CONCLUSIONS
The addition of ezetimibe to statin therapy may further reduce plaque and lipid burdens but may not modify plaque composition. Although current evidence supports a similar impact from the addition of PCSK9 inhibitors to statin therapy, more evidence is needed to confirm such an effect.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Anticholesteremic Agents; Cholesterol, HDL; Cholesterol, LDL; Diabetes Mellitus, Type 2; Ezetimibe; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; PCSK9 Inhibitors; Plaque, Atherosclerotic; Proprotein Convertase 9; Subtilisins; Triglycerides; Ultrasonography, Interventional
PubMed: 36254013
DOI: 10.1097/MD.0000000000031199