-
The Cochrane Database of Systematic... Dec 2021Peripheral arterial disease (PAD) is a manifestation of systemic atherosclerosis. Intermittent claudication is a symptomatic form of PAD that is characterized by pain in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Peripheral arterial disease (PAD) is a manifestation of systemic atherosclerosis. Intermittent claudication is a symptomatic form of PAD that is characterized by pain in the lower limbs caused by chronic occlusive arterial disease. This pain develops in a limb during exercise and is relieved with rest. Propionyl-L-carnitine (PLC) is a drug that may alleviate the symptoms of PAD through a metabolic pathway, thereby improving exercise performance.
OBJECTIVES
The objective of this review is to determine whether propionyl-L-carnitine is efficacious compared with placebo, other drugs, or other interventions used for treatment of intermittent claudication (e.g. exercise, endovascular intervention, surgery) in increasing pain-free and maximum walking distance for people with stable intermittent claudication, Fontaine stage II.
SEARCH METHODS
The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL databases and the World Health Organization International Clinical Trials Registry Platform and the ClinicalTrials.gov trials register to July 7, 2021. We undertook reference checking and contact with study authors and pharmaceutical companies to identify additional unpublished and ongoing studies.
SELECTION CRITERIA
Double-blind randomized controlled trials (RCTs) in people with intermittent claudication (Fontaine stage II) receiving PLC compared with placebo or another intervention. Outcomes included pain-free walking performance (initial claudication distance - ICD) and maximal walking performance (absolute claudication distance - ACD), analyzed by standardized treadmill exercise test, as well as ankle brachial index (ABI), quality of life, progression of disease, and adverse events.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected trials, extracted data, and evaluated trials for risk of bias. We contacted study authors for additional information. We resolved any disagreements by consensus. We performed fixed-effect model meta-analyses with mean differences (MDs) and 95% confidence intervals (CIs). We graded the certainty of evidence according to GRADE.
MAIN RESULTS
We included 12 studies in this review with a total number of 1423 randomized participants. A majority of the included studies assessed PLC versus placebo (11 studies, 1395 participants), and one study assessed PLC versus L-carnitine (1 study, 26 participants). We identified no RCTs that assessed PLC versus any other medication, exercise, endovascular intervention, or surgery. Participants received PLC 1 grams to 2 grams orally (9 studies) or intravenously (3 studies) per day or placebo. For the comparison PLC versus placebo, there was a high level of both clinical and statistical heterogeneity due to study size, participants coming from different countries and centres, the combination of participants with and without diabetes, and use of different treadmill protocols. We found a high proportion of drug company-backed studies. The overall certainty of the evidence was moderate. For PLC compared with placebo, improvement in maximal walking performance (ACD) was greater for PLC than for placebo, with a mean difference in absolute improvement of 50.86 meters (95% CI 50.34 to 51.38; 9 studies, 1121 participants), or a 26% relative improvement (95% CI 23% to 28%). Improvement in pain-free walking distance (ICD) was also greater for PLC than for placebo, with a mean difference in absolute improvement of 32.98 meters (95% CI 32.60 to 33.37; 9 studies, 1151 participants), or a 31% relative improvement (95% CI 28% to 34%). Improvement in ABI was greater for PLC than for placebo, with a mean difference in improvement of 0.09 (95% CI 0.08 to 0.09; 4 studies, 369 participants). Quality of life improvement was greater with PLC (MD 0.06, 95% CI 0.05 to 0.07; 1 study, 126 participants). Progression of disease and adverse events including nausea, gastric intolerance, and flu-like symptoms did not differ greatly between PLC and placebo. For the comparison of PLC with L-carnitine, the certainty of evidence was low because this included a single, very small, cross-over study. Mean improvement in ACD was slightly greater for PLC compared to L-carnitine, with a mean difference in absolute improvement of 20.00 meters (95% CI 0.47 to 39.53; 1 study, 14 participants) or a 16% relative improvement (95% CI 0.4% to 31.6%). We found no evidence of a clear difference in the ICD (absolute improvement 4.00 meters, 95% CI -9.86 to 17.86; 1 study, 14 participants); or a 3% relative improvement (95% CI -7.4% to 13.4%). None of the other outcomes of this review were reported in this study.
AUTHORS' CONCLUSIONS
When PLC was compared with placebo, improvement in walking distance was mild to moderate and safety profiles were similar, with moderate overall certainty of evidence. Although In clinical practice, PLC might be considered as an alternative or an adjuvant to standard treatment when such therapies are found to be contraindicated or ineffective, we found no RCT evidence comparing PLC with standard treatment to directly support such use.
Topics: Ankle Brachial Index; Carnitine; Humans; Intermittent Claudication; Peripheral Arterial Disease; Randomized Controlled Trials as Topic; Walking
PubMed: 34954832
DOI: 10.1002/14651858.CD010117.pub2 -
The Japanese Dental Science Review Dec 2023The mechanisms modulated by periodontal pathogens in atherosclerosis are not fully understood. Aim: to perform an integrative analysis of gene and protein expression... (Review)
Review
UNLABELLED
The mechanisms modulated by periodontal pathogens in atherosclerosis are not fully understood. Aim: to perform an integrative analysis of gene and protein expression modulated by periodontal pathogens in cells and animal models for atherosclerosis.
METHODS
Cochrane, PRISMA and AMSTAR2 guidelines for systematic reviews were followed. Data search was conducted in Pub-med, LILACS and Science Direct databases. Gene and protein expression data were collected from the included papers to perform an overrepresentation analysis using the Reactome Pathway Analysis tool and the KEGG database.
RESULTS
Thirty-two papers were included in the review, they analyzed the effect of , , , , , and or/and their virulent factors on gene and protein expression in human cells and animal models of atherosclerosis. Some of the modulated pathways include the immune system, programmed cell death, cellular responses to external stimuli, transport of small molecules, and signal transduction (p < 0.05). Those pathways are known to be involved in different stages of atherosclerosis progression.
CONCLUSION
Based on the performed analysis, it is possible to state that periodontal pathogens have the potential to be a contributing factor for atherosclerosis even in absence of a high-fat diet or high shear stress.
PubMed: 36654677
DOI: 10.1016/j.jdsr.2022.12.001 -
F1000Research 2022Rheumatoid arthritis (RA) is a highly prevalent, chronic inflammatory condition of the synovial joints that affects approximately 1% of the global population. The...
Rheumatoid arthritis (RA) is a highly prevalent, chronic inflammatory condition of the synovial joints that affects approximately 1% of the global population. The pathogenesis of RA is predominantly inflammatory in nature, thereby accelerating the co-occurrence of other immunoinflammatory conditions such as atherosclerosis. Apart from traditional cardiovascular risk factors, RA patients possess a multitude of other factors that predispose them to early atherosclerotic disease. The aim of this systematic review is to assess the prevalence of premature atherosclerosis in RA patients and elucidate the role that proinflammatory cytokines, RA-related autoantibodies, and endothelial dysfunction play in the pathophysiology of RA-mediated atherosclerosis. We also discussed novel biomarkers that can be used to predict early atherosclerosis in RA and current guidelines used to treat RA. This review followed the PRISMA guidelines to select and analyze relevant articles. A literature search for articles was performed on February 25, 2022, through three research databases including PubMed, ProQuest, and ScienceDirect. The query used to identify relevant publications was "Rheumatoid arthritis and atherosclerosis" and the search duration was set from 2012-2022. Relevant articles were selected based on the inclusion and exclusion criteria. Our initial search generated 21,235 articles. We narrowed our search according to the inclusion and exclusion criteria. After assessing eligibility based on the full content of the articles, 73 articles were ultimately chosen for this review. There is an increased prevalence of accelerated atherosclerosis among RA patients. We found evidence to explain the role of proinflammatory cytokines, RA-related autoantibodies, and endothelial dysfunction in the pathophysiology RA-mediated atherosclerosis. Therapies targeting either the inflammatory load or traditional CV risk-factors seem to improve vascular outcomes in RA patients. Novel markers of atherosclerosis in RA may be useful in predicting premature atherosclerosis and serve as new targets for therapeutic intervention.
Topics: Humans; Atherosclerosis; Arthritis, Rheumatoid; Risk Factors; Cytokines; Autoantibodies
PubMed: 36249997
DOI: 10.12688/f1000research.112921.2 -
Atherosclerosis Feb 2021The role of inflammation in atherosclerosis development and expression in different arterial territories is unclear. Soluble CD40 ligand (sCD40L) mediates inflammation... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
The role of inflammation in atherosclerosis development and expression in different arterial territories is unclear. Soluble CD40 ligand (sCD40L) mediates inflammation and atherogenesis. Through a systematic review and meta-analysis, we assessed whether sCD40L was dysregulated in stable atherosclerosis, irrespective of the diseased arterial territory, and whether this dysregulation differed according to the specific territory.
METHODS
Systematic literature searches were performed in MEDLINE, Cochrane Library, Web of Science, and Embase for studies reporting circulating sCD40L levels in individuals with and without stable atherosclerosis. sCD40L levels were compared using random-effects meta-analysis, weighted by the inverse variance method (study protocol: PROSPERO CRD42020181392).
RESULTS
Fifty-four studies (59 estimates) including 7705 patients and 7841 controls were analyzed. sCD40L levels were found to be increased in patients with atherosclerosis, irrespective of the territory (standardized mean difference [SMD] 0.43, 95% CI 0.29-0.57; 59 estimates; χ heterogeneity p < 0.001; I = 92%). SMD was greatest in carotid atherosclerosis (SMD 0.58, 95% CI 0.30-0.86; 17 estimates), followed by coronary (SMD 0.43, 95% CI 0.24-0.62; 33 estimates), lower extremity (SMD 0.26, 95% CI -0.02-0.54; 7 estimates), and renal atherosclerosis (SMD -0.07, 95% CI -2.77-2.64; 2 estimates) (χ heterogeneity p < 0.001; I ≥ 80% for all). Subgroup analysis revealed that sCD40L levels were increased in clinical, but not subclinical, atherosclerosis.
CONCLUSIONS
sCD40L levels were increased in stable atherosclerosis, particularly in the carotid and coronary territories. These novel data support sCD40L as a marker of systemic atherosclerosis, possibly with differential roles in specific territories.
Topics: Atherosclerosis; Biomarkers; CD40 Ligand; Carotid Artery Diseases; Humans; Inflammation
PubMed: 33494009
DOI: 10.1016/j.atherosclerosis.2020.12.011 -
Inflammation Research : Official... Mar 2024The availability of robust biomarkers of endothelial activation might enhance the identification of subclinical atherosclerosis in rheumatoid arthritis (RA). We... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The availability of robust biomarkers of endothelial activation might enhance the identification of subclinical atherosclerosis in rheumatoid arthritis (RA). We investigated this issue by conducting a systematic review and meta-analysis of cell adhesion molecules in RA patients.
METHODS
We searched electronic databases from inception to 31 July 2023 for case-control studies assessing the circulating concentrations of immunoglobulin-like adhesion molecules (vascular cell, VCAM-1, intercellular, ICAM-1, and platelet endothelial cell, PECAM-1, adhesion molecule-1) and selectins (E, L, and P selectin) in RA patients and healthy controls. Risk of bias and certainty of evidence were assessed using the JBI checklist and GRADE, respectively.
RESULTS
In 39 studies, compared to controls, RA patients had significantly higher concentrations of ICAM-1 (standard mean difference, SMD = 0.81, 95% CI 0.62-1.00, p < 0.001; I = 83.0%, p < 0.001), VCAM-1 (SMD = 1.17, 95% CI 0.73-1.61, p < 0.001; I = 95.8%, p < 0.001), PECAM-1 (SMD = 0.82, 95% CI 0.57-1.08, p < 0.001; I = 0.0%, p = 0.90), E-selectin (SMD = 0.64, 95% CI 0.42-0.86, p < 0.001; I = 75.0%, p < 0.001), and P-selectin (SMD = 1.06, 95% CI 0.50-1.60, p < 0.001; I = 84.8%, p < 0.001), but not L-selectin. In meta-regression and subgroup analysis, significant associations were observed between the effect size and use of glucocorticoids (ICAM-1), erythrocyte sedimentation rate (VCAM-1), study continent (VCAM-1, E-selectin, and P-selectin), and matrix assessed (P-selectin).
CONCLUSIONS
The results of our study support a significant role of cell adhesion molecules in mediating the interplay between RA and atherosclerosis. Further studies are warranted to determine whether the routine use of these biomarkers can facilitate the detection and management of early atherosclerosis in this patient group. PROSPERO Registration Number: CRD42023466662.
Topics: Humans; Intercellular Adhesion Molecule-1; Vascular Cell Adhesion Molecule-1; Platelet Endothelial Cell Adhesion Molecule-1; E-Selectin; P-Selectin; Cell Adhesion Molecules; Arthritis, Rheumatoid; Biomarkers; Atherosclerosis
PubMed: 38240792
DOI: 10.1007/s00011-023-01837-6 -
Cureus Oct 2023With the advent of modern antiretroviral therapy (ART), human immunodeficiency virus (HIV) infection has been modified into a chronic manageable condition, prolonging... (Review)
Review
With the advent of modern antiretroviral therapy (ART), human immunodeficiency virus (HIV) infection has been modified into a chronic manageable condition, prolonging the lifespan of people living with HIV (PLHIV). This has resulted in an increased non-AIDS-related morbidity in the HIV-infected population. Our aim is to study the role of contemporary ART in tackling the risk of atherosclerosis and cardiovascular disease (CVD) in PLHIV. We searched through the databases of PubMed, PubMed Central, and Cochrane Library for pertinent articles using the medical subject headings (MeSH) "HIV infection", "Atherosclerosis", and "Antiretroviral agents". The articles published in the past five years were retrieved, screened for relevance, and assessed for quality before being included in the review. This review was performed following the PRISMA 2020 guidelines. The results indicate that the incidence of dyslipidemia with integrase strand transfer inhibitors (INSTIs) is greater than with non-nucleoside reverse transcriptase inhibitors (NNRTIs) and lesser than with protease inhibitors (PIs). INSTIs are indispensably associated with weight gain and obesity. High triglyceride (TG) and oxidized low-density lipoproteins to low-density lipoproteins (oxLDL/LDL) ratio levels and low high-density lipoprotein (HDL) levels are seen in patients taking PIs. A higher incidence of hypertension and metabolic syndrome (MetS) was noticed with INSTIs compared to NNRTIs. PI intake for >5 years increases the risk of subclinical atherosclerosis. Increased risk of myocardial infarction with INSTIs was observed in a study, while another study reported decreased risk. HIV infection independently increases the risk for atherosclerosis and CVD. Although contemporary ART decreases this enhanced risk, it inherently increases the risk for abnormal lipid profile, MetS, weight gain, and obesity. Further research into the risk of atherosclerosis and CVD with newer ART drugs is essential for decoding the underlying mechanisms and preventing adverse cardiac outcomes in PLHIV.
PubMed: 38021858
DOI: 10.7759/cureus.47730 -
Drug Development Research Dec 2022Diosgenin, a steroidal saponin, is a natural product found in many plants. Diosgenin has a wide range of pharmacological activities, and has been used to treat cancer,... (Review)
Review
Diosgenin, a steroidal saponin, is a natural product found in many plants. Diosgenin has a wide range of pharmacological activities, and has been used to treat cancer, nervous system diseases, inflammation, and infections. Numerous studies have shown that diosgenin has potential therapeutic value for lipid metabolism diseases via various pathways and mechanisms, such as controlling lipid synthesis, absorption, and inhibition of oxidative stress. These mechanisms and pathways have provided ideas for researchers to develop related drugs. In this review, we focus on data from animal and clinical studies, summarizing the toxicity of diosgenin, its pharmacological mechanism, recent research advances, and the related mechanisms of diosgenin as a drug for the treatment of lipid metabolism, especially in obesity, hyperlipidemia, nonalcoholic fatty liver disease, atherosclerosis, and diabetes. This systematic review will briefly describe the advantages of diosgenin as a potential therapeutic drug and seek to enhance our understanding of the pharmacological mechanism, recipe-construction, and the development of novel therapeutics against lipid metabolism diseases.
Topics: Animals; Diosgenin; Lipid Metabolism; Oxidative Stress; Antioxidants; Inflammation
PubMed: 36126194
DOI: 10.1002/ddr.21991 -
Helicobacter Feb 2022In recent years, many studies have tried to prove whether Helicobacter pylori (H. pylori) can promote the progression of atherosclerosis (AS), but the reported results... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
In recent years, many studies have tried to prove whether Helicobacter pylori (H. pylori) can promote the progression of atherosclerosis (AS), but the reported results are conflicting. Carotid intima-media thickness (CIMT), flow-mediated dilation (FMD), or pulse wave velocity (PWV) are the most commonly used indicators to evaluate the progress of AS. So, we collected and evaluated these three indicators to provide evidence-based medicine for the clinic.
MATERIALS AND METHODS
We included and evaluated studies on H. pylori infection and CIMT, FMD, or PWV from PubMed, Cochrane trials, and Embase databases before September 1, 2021, and language restrictions: English. Research types include cross-sectional studies, cohort studies, and case-control studies. The MINORS scale was used to evaluate the quality of these studies. For all studies, we choose a random-effects model and calculate the weighted mean difference (WMD) for analysis, and all our analyses use STATA software.
RESULTS
Meta-analysis shows that H. pylori infection can significantly increase CIMT (WMD = 0.059, 95% CI: 0.039, 0.079, p < 0.001). Based on subgroup analysis, we found that the relationship between the two is more significant in the young and middle-aged people younger than 60 years old and people without cardiovascular disease. In addition, we also found an association between H. pylori infection and FMD (WMD = -3.873, 95% CI: -5.684, -2.062, p < 0.001), but it is a pity that there are few literatures that meet the standards. Finally, We concluded that H. pylori infection can significantly increase PWV (WMD = 88.033, 95%CI: 67.297,108.768. I = 99.63%, p < 0.001). In the subgroup analysis, we also found that this correlation is similar to CIMT, and it is more significant in the young and middle-aged population under 60 and those without cardiovascular disease. We also found in the sub-analysis that there was a significant increase in CIMT in CagA-positive individuals in H. pylori-infected patients (WMD = 0.16, 95%CI: 0.02, 0.29. p = 0.03).
CONCLUSION
Helicobacter pylori infection can promote the process of AS, especially in people under the age of 60 and people without cardiovascular risk factors, and we hope that our meta-analysis can provide ideas for the early prevention of AS.
Topics: Atherosclerosis; Carotid Intima-Media Thickness; Cross-Sectional Studies; Helicobacter Infections; Helicobacter pylori; Humans; Middle Aged; Pulse Wave Analysis; Risk Factors
PubMed: 34841620
DOI: 10.1111/hel.12865 -
Expert Review of Clinical Pharmacology May 2022Statins might prevent cell adhesion to the endothelium, a key step in atherosclerosis. We conducted a systematic review and meta-analysis of the effect of statins on... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Statins might prevent cell adhesion to the endothelium, a key step in atherosclerosis. We conducted a systematic review and meta-analysis of the effect of statins on soluble vascular (sVCAM-1) and intercellular (sICAM-1) adhesion molecule 1.
METHODS
A systematic literature search was conducted in PubMed, Web of Science, and Scopus, from inception to July 2021. Risk of bias and certainty of evidence were assessed using the Joanna Briggs Institute Critical Appraisal Checklist for analytical studies and GRADE, respectively.
RESULTS
Statins significantly reduced both sVCAM-1 (standard mean difference, SMD = -0.28, 95% CI -0.44 to -0.12, p = 0.001; 46 treatment arms; low certainty of evidence) and sICAM-1 (SMD = -0.75, 95% CI -1.00 to -0.50, p < 0.001; 61 treatment arms; moderate certainty of evidence) concentrations. In sensitivity analysis, the SMD values were not modified when individual studies were sequentially removed. There were significant associations between SMD and publication year and, for sICAM-1, statin-induced changes in HDL-cholesterol. In subgroup analysis, the lowering effect was significant with lipophilic, but not hydrophilic, statins, and similar, for sICAM-1, in participants with or without clinically overt atherosclerosis.
CONCLUSIONS
Statins significantly lower sVCAM-1/sICAM-1. Prospective studies are required to determine whether this mediates their atheroprotective effects (PROSPERO registration number: CRD42021276825).
Topics: Atherosclerosis; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Intercellular Adhesion Molecule-1; Prospective Studies; Vascular Cell Adhesion Molecule-1
PubMed: 35485866
DOI: 10.1080/17512433.2022.2072294 -
Biomedicines Jan 2023Accumulating evidence considers psoriasis a systemic inflammatory disorder that is associated with comorbidities such as psoriatic arthritis, cardiovascular disease, and... (Review)
Review
Accumulating evidence considers psoriasis a systemic inflammatory disorder that is associated with comorbidities such as psoriatic arthritis, cardiovascular disease, and metabolic syndrome. Although the precise pathogenetic links between psoriasis and atherosclerosis warrants further investigation, it is believed that chronic systemic inflammation along with the T helper (Th)-1 and Th17 polarization are associated with endothelial dysfunction and subsequent acceleration of atherosclerosis. Considering the above, several studies have evaluated if optimal control of the inflammation in psoriasis by inhibiting interleukins targeting the Interleukin (IL)-23/Th17 axis could subsequently reduce the atherosclerotic process during anti-psoriatic treatment by using a variety of surrogate markers of subclinical atherosclerosis. This systematic review summarizes current knowledge on the pathogenetic mechanisms and diagnostic evaluation of atherosclerosis in the context of psoriasis and provides a systematic review of the literature on the impact of treatment with biologics targeting the IL-23/Th17 axis on subclinical atherosclerosis in patients with plaque psoriasis and/or psoriatic arthritis.
PubMed: 36830855
DOI: 10.3390/biomedicines11020318