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Antioxidants (Basel, Switzerland) Jul 2023The presence of a pro-oxidant state in patients with schizophrenia may account for the increased risk of atherosclerosis and cardiovascular disease in this group and... (Review)
Review
The presence of a pro-oxidant state in patients with schizophrenia may account for the increased risk of atherosclerosis and cardiovascular disease in this group and supports the potential utility of circulating biomarkers of oxidative stress for risk stratification and management. We investigated this issue by conducting a systematic review and meta-analysis of the association between the circulating concentrations of paraoxonase-1, an antioxidant calcium-dependent high-density lipoprotein (HDL)-associated esterase, with paraoxonase and arylesterase activity in schizophrenia. We searched electronic databases from inception to 31 May 2023 for studies investigating paraoxonase-1 in patients with schizophrenia and healthy controls and assessed the risk of bias and the certainty of evidence (PROSPERO registration number: CRD42023435442). Thirteen studies were identified for analysis. There were no significant between-group differences in paraoxonase (standard mean difference, SMD = 0.12, 95% CI -0.23 to 0.48, = 0.50; extremely low certainty of evidence) or arylesterase activity (SMD = -0.08, 95% CI -0.39 to 0.23, = 0.61; very low certainty of evidence). However, in meta-regression and subgroup analysis we observed significant associations between the SMD of paraoxonase and age ( = 0.003), HDL-cholesterol ( = 0.029), and study country ( = 0.04), and the SMD of arylesterase and age ( = 0.007), body mass index ( = 0.012), HDL-cholesterol ( = 0.002), and pharmacological treatment for schizophrenia ( < 0.001). In the absence of overall between-group differences, our systematic review and meta-analysis suggests that alterations in paraoxonase-1 may reflect a pro-oxidant state in specific subgroups of patients with schizophrenia that require further assessment in appropriately designed studies.
PubMed: 37627479
DOI: 10.3390/antiox12081484 -
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 -
Circulation Jan 2024Hypertrophic cardiomyopathy (HCM) is characterized by unexplained left ventricular hypertrophy and is classically caused by pathogenic or likely pathogenic variants... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Hypertrophic cardiomyopathy (HCM) is characterized by unexplained left ventricular hypertrophy and is classically caused by pathogenic or likely pathogenic variants (P/LP) in genes encoding sarcomere proteins. Not all subclinical variant carriers will manifest clinically overt disease because penetrance (proportion of sarcomere or sarcomere-related P/LP variant carriers who develop disease) is variable, age dependent, and not reliably predicted.
METHODS
A systematic search of the literature was performed. We used random-effects generalized linear mixed model meta-analyses to contrast the cross-sectional prevalence and penetrance of sarcomere or sarcomere-related genes in 2 different contexts: clinically-based studies on patients and families with HCM versus population or community-based studies. Longitudinal family/clinical studies were additionally analyzed to investigate the rate of phenotypic conversion from subclinical to overt HCM during follow-up.
RESULTS
In total, 455 full-text manuscripts and articles were assessed. In family/clinical studies, the prevalence of sarcomere variants in patients diagnosed with HCM was 34%. The penetrance across all genes in nonproband relatives carrying P/LP variants identified during cascade screening was 57% (95% CI, 52%-63%), and the mean age at HCM diagnosis was 38 years (95% CI, 36%-40%). Penetrance varied from ≈32% for (myosin light chain 3) to ≈55% for (myosin-binding protein C3), ≈60% for (troponin T2) and (troponin I3), and ≈65% for (myosin heavy chain 7). Population-based genetic studies demonstrate that P/LP sarcomere variants are present in the background population but at a low prevalence of <1%. The penetrance of HCM in incidentally identified P/LP variant carriers was also substantially lower at ≈11%, ranging from 0% in Atherosclerosis Risk in Communities to 18% in UK Biobank. In longitudinal family studies, the pooled phenotypic conversion across all genes was 15% over an average of ≈8 years of follow-up, starting from a mean of ≈16 years of age. However, short-term gene-specific phenotypic conversion varied between ≈12% for and ≈23% for .
CONCLUSIONS
The penetrance of P/LP variants is highly variable and influenced by currently undefined and context-dependent genetic and environmental factors. Additional longitudinal studies are needed to improve our understanding of true lifetime penetrance in families and in the community and to identify drivers of the transition from subclinical to overt HCM.
Topics: Humans; Adult; Penetrance; Mutation; Cross-Sectional Studies; Pedigree; Cardiomyopathy, Hypertrophic; Troponin T
PubMed: 37929589
DOI: 10.1161/CIRCULATIONAHA.123.065987 -
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 -
Journal of the American Heart... Nov 2023Intracranial atherosclerosis disease (ICAD) alters cerebrovascular hemodynamics and brain structural integrity. Multiple studies have evaluated the link between ICAD and...
BACKGROUND
Intracranial atherosclerosis disease (ICAD) alters cerebrovascular hemodynamics and brain structural integrity. Multiple studies have evaluated the link between ICAD and cognitive impairment, with mixed results. This study aims to systematically review and summarize the current evidence on this link.
METHODS AND RESULTS
PubMed, EMBASE, PsycInfo, and Web of Science were searched from 2000 to 2023 without language restriction. Cross-sectional and prospective cohort studies as well as postmortem studies were included. Studies containing data on the link between ICAD, defined as at least 50% stenosis in 1 intracranial vessel, and cognitive impairment and dementia were screened by 2 independent reviewers. A total of 22 (17 observational and 5 postmortem) unique studies, comprising 11 184 individuals (average age range, 59.8-87.6 years; 45.7% women; 36.5% Asian race), were included in the systematic review. Seven of 10 cross-sectional studies and 5 of 7 prospective studies showed a significant association between ICAD and cognitive impairment. In the pooled analysis, ICAD was associated with greater cognitive impairment (measure of association, 1.87 [95% CI, 1.49-2.35]). Meta-regression analyses did not show a significant impact of age, sex, and race. All postmortem studies showed that patients with Alzheimer disease and vascular dementia had a higher burden of ICAD compared with controls.
CONCLUSIONS
This study shows that ICAD is associated with cognitive impairment and dementia across age, sex, and race groups. Our findings may underscore the need to develop individualized dementia preventive care plans in patients with ICAD.
PubMed: 37955546
DOI: 10.1161/JAHA.123.032506 -
Current Oncology (Toronto, Ont.) Jul 2023Statins are widely used due to their ability to lower plasma cholesterol and offer protection from the effects of atherosclerosis. However, their role in urology and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Statins are widely used due to their ability to lower plasma cholesterol and offer protection from the effects of atherosclerosis. However, their role in urology and specifically bladder cancer remains unclear. We aimed to systematically address this issue in the literature and determine any possible effects of statin therapy on bladder cancer.
METHODS
We searched MEDLINE (PubMed) and Cochrane Library databases for records up to 26 March 2023, for studies evaluating the effects of statins on urinary bladder cancer (UBC). We included all randomized controlled trials (RCTs), cohorts, and case-control studies that were conducted on the adult population. PROSPERO registration number: CRD42023407795.
RESULTS
Database searches returned 2251 reports, and after thorough investigation and assessment for eligibility, 32 reports were included in the analysis. Of them, 4 were RCTs, 6 were case-control studies, and 22 were cohort studies. Our qualitative analysis demonstrated no association between statin administration and UBC local control, recurrence, survival, or mortality, or between statin administration and bacille Calmette-Guérin (BCG) immunotherapy effectiveness. A meta-analysis of 10 trials revealed a non-significant reduction of 11% in UBC risk among users compared with non-users in RCTs (RR: 0.89, 95% CI 0.68-1.16, = 0.37) and a non-significant increase of 32% of UBC risk among statin users compared with non-users in the analysis of the cohort studies (RR: 1.32, 95% CI 0.76-2.30, = 0.33).
CONCLUSIONS
Our results provide strong evidence to support the neutral effect of statins on UBC local control, recurrence, survival, and mortality, and on BCG immunotherapy. Our meta-analysis revealed a non-significant effect on UBC risk among statin users when compared with non-users, indicating no statin effect on UBC incidence and overall prognosis.
Topics: Adult; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; BCG Vaccine; Incidence; Prognosis; Urinary Bladder Neoplasms
PubMed: 37504348
DOI: 10.3390/curroncol30070488 -
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 -
Journal of the American Heart... Dec 2023Carotid intima-media thickness (cIMT) has been widely used as a predictor of future cardiovascular disease (CVD); however, various definitions of cIMT exist. This study... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Carotid intima-media thickness (cIMT) has been widely used as a predictor of future cardiovascular disease (CVD); however, various definitions of cIMT exist. This study provides a systematic review and meta-analysis of the associations between different cIMT definitions and CVD.
METHODS AND RESULTS
A systematic review of the different cIMT definitions used in prospective cohort studies was performed. The relationships between cIMT of different definitions (common carotid artery IMT [CCA-IMT], internal carotid artery IMT [ICA-IMT], combined segments [combined-IMT], mean CCA-IMT, and maximum CCA-IMT) with future stroke, myocardial infarction (MI), and CVD events were analyzed using random effects models. Among 2287 articles, 18 articles (14 studies) with >10 different cIMT definitions were identified and included in our meta-analysis. After adjusting for age and sex, a 1-SD increase in CCA-IMT was associated with future stroke (hazard ratio [HR], 1.32 [95% CI, 1.27-1.38]), MI (HR, 1.27 [95% CI, 1.22-1.33]), and CVD events (HR, 1.28 [95% CI, 1.19-1.37]). A 1-SD increase in ICA-IMT was related to future stroke (HR, 1.25 [95% CI, 1.11-1.42]) and CVD events (HR, 1.25 [95% CI, 1.04-1.50]) but not MI (HR, 1.26 [95% CI, 0.98-1.61]). A 1-SD increase in combined-IMT was associated with future stroke (HR, 1.30 [95% CI, 1.08-1.57]) and CVD events (HR, 1.36 [95% CI, 1.23-1.49]). Maximum CCA-IMT was more strongly related than mean CCA-IMT with risk of MI, and both measures were similarly associated with stroke and CVD events.
CONCLUSIONS
Combined-IMT is more strongly associated with CVD events compared with single-segment cIMT definitions. Maximum CCA-IMT shows a stronger association with MI than mean CCA-IMT. Further research is warranted to validate our findings and to standardize the cIMT measurement protocol, as well as to explore underlying mechanisms.
Topics: Humans; Carotid Intima-Media Thickness; Cardiovascular Diseases; Prospective Studies; Carotid Artery, Common; Stroke; Myocardial Infarction; Risk Factors
PubMed: 38014663
DOI: 10.1161/JAHA.123.031217 -
Journal of the American Heart... Aug 2023Background Sodium-glucose cotransporter-2 (SGLT2) inhibitors reduce atherosclerotic cardiovascular disease (ASCVD) events in patients with prior ASCVD and type 2... (Meta-Analysis)
Meta-Analysis
Background Sodium-glucose cotransporter-2 (SGLT2) inhibitors reduce atherosclerotic cardiovascular disease (ASCVD) events in patients with prior ASCVD and type 2 diabetes; however, this benefit is uncertain in patients without established ASCVD. Methods and Results Large-scale cardiovascular outcome randomized controlled trials or their prespecified subgroup analyses were selected, evaluating SGLT2 inhibitors versus placebo for primary prevention of ASCVD (inception, March 2023). The primary outcome was atherosclerotic major adverse cardiovascular events (MACEs), which was a composite of cardiovascular mortality, myocardial infarction, and stroke. The secondary outcomes were individual components of MACEs and all-cause mortality. The outcomes were reported as random-effect relative risk (RR) with a 95% CI. This analysis, comprising 23 987 patients enrolled in 5 randomized controlled trials with a mean follow-up duration of ≈135 weeks, found no significant reduction in atherosclerotic MACEs with SGLT2 inhibitors in comparison to placebo (RR, 0.85 [95% CI, 0.71-1.01]; =0.07; I=44). There were no significant differences in cardiovascular mortality (RR, 0.93 [95% CI, 0.77-1.14]; =0.50; I=0), myocardial infarction (RR, 0.88 [95% CI, 0.69-1.11]; =0.28; I=23), and stroke (RR, 0.84 [95% CI, 0.62-1.16]; =0.29; I=46). SGLT2 inhibitors significantly improved all-cause mortality (RR, 0.85 [95% CI, 0.72-1.0]; =0.04; I=23). On subgroup analyses, the use of SGLT2 inhibitors led to significant reductions in MACEs (RR, 0.74 [95% CI, 0.61-0.89]; =0.001), myocardial infarction (RR, 0.67 [95% CI, 0.47-0.97]; =0.03), and stroke (RR, 0.61 [95% CI, 0.41-0.91]; =0.01) primarily in patients with chronic kidney disease along with type 2 diabetes, whereas these benefits were not observed in patients with type 2 diabetes without chronic kidney disease. Conclusions SGLT2 inhibitors significantly reduced atherosclerotic MACEs in subjects having both chronic kidney disease and type 2 diabetes without established ASCVD.
Topics: Humans; Atherosclerosis; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Myocardial Infarction; Primary Prevention; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic; Sodium-Glucose Transporter 2 Inhibitors; Stroke
PubMed: 37581396
DOI: 10.1161/JAHA.123.030578 -
Medicina (Kaunas, Lithuania) Nov 2023: Lipid-lowering agents such as ezetimibe are recommended in uncontrolled hyperlipidemia for primary and secondary prevention of cardiovascular disease. Carotid... (Meta-Analysis)
Meta-Analysis
Effect of Combination Therapy with Ezetimibe and Statins versus Statin Monotherapy on Carotid Intima-Media Thickness: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
: Lipid-lowering agents such as ezetimibe are recommended in uncontrolled hyperlipidemia for primary and secondary prevention of cardiovascular disease. Carotid intima-media thickness (CIMT) is a surrogate marker of atherosclerosis and a predictor of cardiovascular and cerebral events. The effects of ezetimibe on CIMT have been inconsistently reported. The aim of this meta-analysis is to compare the effects of ezetimibe/statin and statin alone therapies on CIMT reduction. : The PubMed, Embase, and Cochrane library databases were searched for randomized controlled trials (RCTs) published prior to 26 January 2023 with the MeSH keywords 'Ezetimibe' and 'Carotid Intima-Media Thickness'. The results were presented as standard mean difference (SMD) with 95% confidence intervals using the random-effect model method, and heterogeneity was assessed. Subgroup, meta-regression, and sensitivity analyses were conducted. : Five RCTs with 642 participants were included. CIMT reduction was not significantly different between the ezetimibe/statin and statin alone groups. However, in subgroup analyses, CIMT in the ezetimibe/statin group was significantly reduced in patients with non-familial hypercholesterolemia (SMD: -0.34 mm and = 0.002) and in patients with secondary prevention (SMD: -0.38 mm and = 0.002). The low-density lipoprotein cholesterol level was significantly reduced in the ezetimibe/statin group (SMD: -0.58 mg/dL and < 0.001). : The effect of ezetimibe on CIMT reduction was shown in non-familial hypercholesterolemia and secondary prevention. These results suggest that the efficacy of ezetimibe may vary with potential CIMT reduction benefits in certain subpopulations.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Ezetimibe; Carotid Intima-Media Thickness; Hypercholesterolemia; Anticholesteremic Agents; Azetidines; Cholesterol, LDL; Randomized Controlled Trials as Topic; Drug Therapy, Combination
PubMed: 38004029
DOI: 10.3390/medicina59111980