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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 -
Systematic Reviews Jan 2024Coronary artery disease (CAD) remains one of the leading causes of mortality worldwide. We aimed to summarize what is currently known with regard to causal modifiable... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Coronary artery disease (CAD) remains one of the leading causes of mortality worldwide. We aimed to summarize what is currently known with regard to causal modifiable risk factors associated with CAD in populations of diverse ancestries through conducting a systematic review and meta-analysis of Mendelian randomization (MR) studies on CAD.
METHODS
The databases Embase, Medline, Cochrane Library and Web of Science were searched on the 19th and 20th of December 2022 for MR studies with CAD as a primary outcome; keywords of the search strategy included "coronary artery disease" and "mendelian randomization". Studies were included if they were published in the English language, included only human participants, employed Mendelian randomization as the primary methodology and studied CAD as the outcome of interest. The exclusion criteria resulted in the removal of studies that did not align with the predefined inclusion criteria, as well as studies which were systematic reviews themselves, and used the same exposure and outcome source as another study. An ancestry-specific meta-analysis was subsequently conducted on studies which investigated either body mass index, lipid traits, blood pressure or type 2 diabetes as an exposure variable. Assessment of publication bias and sensitivity analyses was conducted for risk of bias assessment in the included studies.
RESULTS
A total of 1781 studies were identified through the database searches after de-duplication was performed, with 47 studies included in the quantitative synthesis after eligibility screening. Approximately 80% of all included study participants for MR studies on CAD were of European descent irrespective of the exposure of interest, while no study included individuals of African ancestry. We found no evidence of differences in terms of direction of causation between ancestry groups; however, the strength of the respective relationships between each exposure and CAD were different, with this finding most evident when blood pressure was the exposure of interest.
CONCLUSIONS
Findings from this review suggest that patterns regarding the causational relationship between modifiable risk factors and CAD do not differ in terms of direction when compared across diverse ancestry populations. Differences in the observed strengths of the respective relationships however are indicative of the value of increasing representation in non-European populations, as novel genetic pathways or functional SNPs relating to CAD may be uncovered through a more global analysis.
SYSTEMATIC REVIEW REGISTRATION
The protocol for this systematic review was registered to the International Prospective Register of Systematic Reviews (PROSPERO) and is publicly available online (CRD42021272726).
Topics: Humans; Coronary Artery Disease; Diabetes Mellitus, Type 2; Mendelian Randomization Analysis; Risk Factors; Causality
PubMed: 38225600
DOI: 10.1186/s13643-023-02442-8 -
Journal of the American Heart... Jan 2024Despite the initial evidence supporting the utility of intravascular imaging to guide percutaneous coronary intervention (PCI), adoption remains low. Recent new trial... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Despite the initial evidence supporting the utility of intravascular imaging to guide percutaneous coronary intervention (PCI), adoption remains low. Recent new trial data have become available. An updated study-level meta-analysis comparing intravascular imaging to angiography to guide PCI was performed. This study aimed to evaluate the clinical outcomes of intravascular imaging-guided PCI compared with angiography-guided PCI.
METHODS AND RESULTS
A random-effects meta-analysis was performed on the basis of the intention-to-treat principle. The primary outcomes were major adverse cardiac events, cardiac death, and all-cause death. Mixed-effects meta-regression was performed to investigate the impact of complex PCI on the primary outcomes. A total of 16 trials with 7814 patients were included. The weighted mean follow-up duration was 28.8 months. Intravascular imaging led to a lower risk of major adverse cardiac events (relative risk [RR], 0.67 [95% CI, 0.55-0.82]; <0.001), cardiac death (RR, 0.49 [95% CI, 0.34-0.71]; <0.001), stent thrombosis (RR, 0.63 [95% CI, 0.40-0.99]; =0.046), target-lesion revascularization (RR, 0.67 [95% CI, 0.49-0.91]; =0.01), and target-vessel revascularization (RR, 0.60 [95% CI, 0.45-0.80]; <0.001). In complex lesion subsets, the point estimate for imaging-guided PCI compared with angiography-guided PCI for all-cause death was a RR of 0.75 (95% CI, 0.55-1.02; =0.07).
CONCLUSIONS
In patients undergoing PCI, intravascular imaging is associated with reductions in major adverse cardiac events, cardiac death, stent thrombosis, target-lesion revascularization, and target-vessel revascularization. The magnitude of benefit is large and consistent across all included studies. There may also be benefits in all-cause death, particularly in complex lesion subsets. These results support the use of intravascular imaging as standard of care and updates of clinical guidelines.
Topics: Humans; Coronary Artery Disease; Coronary Angiography; Percutaneous Coronary Intervention; Ultrasonography, Interventional; Randomized Controlled Trials as Topic; Thrombosis; Treatment Outcome; Death
PubMed: 38214263
DOI: 10.1161/JAHA.123.031111 -
Heart & Lung : the Journal of Critical... 2024An important component of secondary prevention of CVD (including HF) is comprehensive cardiac rehab, including exercise. Novel, individualised approaches are needed to... (Meta-Analysis)
Meta-Analysis
Physiological and psychological outcomes of high intensity interval training in patients with heart failure compared to moderate continuous training and usual care: A systematic review with meta analysis.
BACKGROUND
An important component of secondary prevention of CVD (including HF) is comprehensive cardiac rehab, including exercise. Novel, individualised approaches are needed to increase uptake and adherence to exercise programmes, one area offering potential is HIIT. HIIT has been shown to be both safe and effective for improving cardiovascular fitness in both coronary artery disease and HF patients.
OBJECTIVES
To provide a current and up to date evaluation of the physiological and psychological outcomes of HIIT in patients with HF compared to MCT and UC. Secondly to perform sub-group analyses comparing short and long HIIT protocols.
METHODS
A systematic review and meta-analysis of randomised controlled trials was undertaken. Medline, Embase, Scopus, CINAHL and SportDISCUS were searched up to July 2022. Trials were included if they carried out a HIIT intervention (defined at intensity ≥ 80% peak HR or ≥ 80% VO2) in HF patients (HFpEF or HFrEF) for at least 6 weeks. Comparator group was UC or MCT.
RESULTS
HIIT was shown to be superior to MCT and UC for improving VO (HIIT mean improvement 3.1 mL.kgmin). HITT was superior to MCT and UC for improving LVEF (HIIT mean improvement 5.7%). HIIT was superior to MCT and UC for improving HRQoL, using the MLHFQ (HIIT mean point change of -12.8). Subgroup analysis showed no difference between long and short HIIT.
CONCLUSION
HIIT improves VO, LVEF and HRQoL in patients with HF, the improvements seen in VO and LVEF are superior in HIIT compared to MCT and UC.
Topics: Humans; Heart Failure; Exercise Therapy; High-Intensity Interval Training; Stroke Volume; Coronary Artery Disease
PubMed: 38159428
DOI: 10.1016/j.hrtlng.2023.12.002 -
Schizophrenia Research Feb 2024Increasing evidence suggests an association between schizophrenia and atherosclerosis. We conducted a systematic review and meta-analysis of cell adhesion molecules,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Increasing evidence suggests an association between schizophrenia and atherosclerosis. We conducted a systematic review and meta-analysis of cell adhesion molecules, critically involved in early atherosclerosis, in schizophrenia.
METHODS
We searched electronic databases from inception to 11 November 2023 for case-control studies assessing vascular cell, VCAM-1, intercellular, ICAM-1, platelet endothelial cell, PECAM-1, neural cell, NCAM, and Down syndrome cell, DSCAM, adhesion molecules, selectins (E-, L-, and P-selectin), integrins, and cadherins in patients with schizophrenia and healthy controls. Risk of bias and certainty of evidence were assessed using the JBI checklist and GRADE, respectively.
RESULTS
In 19 eligible studies, there were non-significant between-group differences in the concentrations of cell adhesion molecules, barring higher P-selectin in patients with schizophrenia (standard mean difference, SMD = 2.05, 95 % CI 0.72 to 3.38, p = 0.003; I = 97.2 %, p<0.001; very low certainty of evidence). Limited or no information was available regarding PECAM-1, DSCAM, ESAM, integrins, and cadherins. In meta-regression and subgroup analysis, there were significant associations between the SMD of ICAM-1 and matrix used (plasma or serum) and pharmacological treatment of schizophrenia, and between the SMD of VCAM-1 and pharmacological treatment, but not with other study and patient characteristics.
CONCLUSIONS
The results of our systematic review and meta-analysis do not support a significant role of immunoglobulin-like adhesion molecules, selectins, integrins, or cadherins in mediating the associations between schizophrenia, atherosclerosis, and cardiovascular disease. Further studies are warranted to investigate these associations in patients with different cardiovascular risk and the effects of antipsychotic treatments on cell adhesion molecules and surrogate markers of atherosclerosis (PROSPERO registration number: CRD42023463916).
Topics: Humans; Atherosclerosis; Cadherins; Cell Adhesion Molecules; E-Selectin; Integrins; Intercellular Adhesion Molecule-1; P-Selectin; Platelet Endothelial Cell Adhesion Molecule-1; Schizophrenia; Selectins; Vascular Cell Adhesion Molecule-1
PubMed: 38150848
DOI: 10.1016/j.schres.2023.12.025 -
Genes Dec 2023Myocardial bridging (MB) is a congenital coronary artery anomaly that has limited molecular disease state characterization. Though a large portion of individuals may be... (Review)
Review
BACKGROUND
Myocardial bridging (MB) is a congenital coronary artery anomaly that has limited molecular disease state characterization. Though a large portion of individuals may be asymptomatic, the myocardial ischemia caused by this anomaly can lead to angina, acute coronary syndrome, coronary artery disease, and sudden cardiac death in patients.
OBJECTIVE
This study aims to summarize and consolidate the current literature regarding the genomic associations of myocardial bridge development and, in doing so, prompt further investigation into the molecular basis of myocardial bridge development.
METHODS
We performed a systematic literature review of myocardial bridging using the key search terms "Myocardial Bridging" AND ("Gene" OR "Allelic Variants" OR "Genomic") in the databases of PubMed, CINAHL, EMBASE, and Cochran. We then performed a detailed review of the resulting abstracts and a full-text screening, summarizing these findings in this report.
RESULTS
In total, we identified eight articles discussing the associated genomics behind MB development. Studies included review articles, case reports and genomic studies that led to the discussion of several genes: (E434K), (I1175M), and ; , , (A1157G), and (A714T); (A862V); (E31D); and (R2313Q), and to the discussion of miRNAs (miR-29b, miR-151-3p, miR-126, miR-503-3p, and miR-645).
CONCLUSIONS
Our study is the first to summarize the genes and molecular regulators related to myocardial bridges as they exist in the current literature. This work concludes that definitive evidence is lacking, warranting much broader genetic and genomic studies.
Topics: Humans; Myocardial Bridging; Coronary Artery Disease; MicroRNAs; Genomics
PubMed: 38136997
DOI: 10.3390/genes14122175 -
European Radiology Jul 2024Coronary artery calcifications (CACs) indicate the presence of coronary artery disease. CAC can be found on thoracic computed tomography (CT) conducted for non-cardiac... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Coronary artery calcifications (CACs) indicate the presence of coronary artery disease. CAC can be found on thoracic computed tomography (CT) conducted for non-cardiac reasons. This systematic review and meta-analysis of non-gated thoracic CT aims to assess the clinical impact and prevalence of CAC.
METHODS
Online databases were searched for articles assessing prevalence, demographic characteristics, accuracy and prognosis of incidental CAC on non-gated thoracic CT. Meta-analysis was performed using a random effects model.
RESULTS
A total of 108 studies (113,406 patients) were included (38% female). Prevalence of CAC ranged from 2.7 to 100% (pooled prevalence 52%, 95% confidence interval [CI] 46-58%). Patients with CAC were older (pooled standardised mean difference 0.88, 95% CI 0.65-1.11, p < 0.001), and more likely to be male (pooled odds ratio [OR] 1.95, 95% CI 1.55-2.45, p < 0.001), with diabetes (pooled OR 2.63, 95% CI 1.95-3.54, p < 0.001), hypercholesterolaemia (pooled OR 2.28, 95% CI 1.33-3.93, p < 0.01) and hypertension (pooled OR 3.89, 95% CI 2.26-6.70, p < 0.001), but not higher body mass index or smoking. Non-gated CT assessment of CAC had excellent agreement with electrocardiogram-gated CT (pooled correlation coefficient 0.96, 95% CI 0.92-0.98, p < 0.001). In 51,582 patients, followed-up for 51.6 ± 27.4 months, patients with CAC had increased all cause mortality (pooled relative risk [RR] 2.13, 95% CI 1.57-2.90, p = 0.004) and major adverse cardiovascular events (pooled RR 2.91, 95% CI 2.26-3.93, p < 0.001). When CAC was present on CT, it was reported in between 18.6% and 93% of reports.
CONCLUSION
CAC is a common, but underreported, finding on non-gated CT with important prognostic implications.
CLINICAL RELEVANCE STATEMENT
Coronary artery calcium is an important prognostic indicator of cardiovascular disease. It can be assessed on non-gated thoracic CT and is a commonly underreported finding. This represents a significant population where there is a potential missed opportunity for lifestyle modification recommendations and preventative therapies. This study aims to highlight the importance of reporting incidental coronary artery calcium on non-gated thoracic CT.
KEY POINTS
• Coronary artery calcification is a common finding on non-gated thoracic CT and can be reliably identified compared to gated-CT. • Coronary artery calcification on thoracic CT is associated with an increased risk of all cause mortality and major adverse cardiovascsular events. • Coronary artery calcification is frequently not reported on non-gated thoracic CT.
Topics: Humans; Coronary Artery Disease; Prevalence; Tomography, X-Ray Computed; Vascular Calcification; Radiography, Thoracic; Male; Female
PubMed: 38133672
DOI: 10.1007/s00330-023-10439-z -
Frontiers in Bioengineering and... 2023Brucellosis, the most common bacterial zoonosis, poses a serious threat to public health in endemic regions. Cardiovascular complications of brucellosis, mostly...
Brucellosis, the most common bacterial zoonosis, poses a serious threat to public health in endemic regions. Cardiovascular complications of brucellosis, mostly pericarditis or endocarditis, are the leading cause of brucellosis-related death. Complications involving the aorta and iliac arteries are extremely rare but can be life-threatening. Our objective was to identify and review all reported cases of aortic and iliac involvement in brucellosis to provide a deep, up-to-date understanding of the clinical characteristics and management of the disease. Online searches in PubMed, Web of Science, China National Knowledge Infrastructure, and the Chinese Wanfang database were conducted to collect articles reporting cases of brucellosis with aortic and iliac artery involvement. All data in terms of patient demographics, diagnostic methods, clinical manifestations, and treatment regimens and outcomes were extracted and analyzed in this systematic review. A total of 79 articles were identified, reporting a total of 130 cases of brucellosis with aortic and iliac artery involvement. Of the 130 cases, 110 (84.5%) were male individuals and 100 (76.9%) were over 50 years old. The patients had an overall mortality rate of 12.3%. The abdominal aorta was most commonly involved, followed by the ascending aorta, iliac artery, and descending thoracic aorta. Arteriosclerosis, hypertension, and smoking were the most common comorbidities. There were 71 patients (54.6%) who presented with systemic symptoms of infection at the time of admission. Endovascular therapy was performed in 56 patients (43.1%), with an overall mortality rate of 3.6%. Open surgery was performed in 52 patients (40.0%), with an overall mortality rate of 15.4%. Aortic and iliac involvement in brucellosis is extremely rare but can be life-threatening. Its occurrence appears to be associated with the male gender, an older age, arteriosclerosis, and smoking. Although the number of reported cases in developing countries has increased significantly in recent years, its incidence in these countries may still be underestimated. Early diagnosis and therapeutic intervention are critical in improving patient outcomes. Endovascular therapy has become a preferred surgical treatment in recent years, and yet, its long-term complications remain to be assessed.
PubMed: 38098968
DOI: 10.3389/fbioe.2023.1326246 -
Frontiers in Endocrinology 2023Insulin resistance (IR), a risk factor for cardiovascular diseases, has garnered significant attention in scientific research. Several studies have investigated the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Insulin resistance (IR), a risk factor for cardiovascular diseases, has garnered significant attention in scientific research. Several studies have investigated the correlation between IR and coronary artery calcification (CAC), yielding varying results. In light of this, we conducted a systematic review to investigate the association between IR as evaluated by the homeostasis model assessment (HOMA-IR) and CAC.
METHODS
A comprehensive search was conducted to identify relevant studies in PubMed, Embase, Scopus, and Web of Science databases. In addition, preprint servers such as Research Square, BioRxiv, and MedRxiv were manually searched. The collected data were analyzed using either fixed or random effects models, depending on the heterogeneity observed among the studies. The assessment of the body of evidence was performed using the GRADE approach to determine its quality.
RESULTS
The current research incorporated 15 studies with 60,649 subjects. The analysis revealed that a higher category of HOMA-IR was associated with a greater prevalence of CAC in comparison to the lowest HOMA-IR category, with an OR of 1.13 (95% CI: 1.06-1.20, I = 29%, P < 0.001). A similar result was reached when HOMA-IR was analyzed as a continuous variable (OR: 1.27, 95% CI: 1.14-1.41, I = 54%, P < 0.001). In terms of CAC progression, a pooled analysis of two cohort studies disclosed a significant association between increased HOMA-IR levels and CAC progression, with an OR of 1.44 (95% CI: 1.04-2.01, I = 21%, P < 0.05). It is important to note that the strength of the evidence was rated as low for the prevalence of CAC and very low for the progression of CAC.
CONCLUSION
There is evidence to suggest that a relatively high HOMA-IR may be linked with an increased prevalence and progression of CAC.
Topics: Humans; Insulin Resistance; Coronary Artery Disease; Risk Factors; Hyperinsulinism; Homeostasis
PubMed: 38089605
DOI: 10.3389/fendo.2023.1271857 -
PloS One 2023Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of mortality worldwide. Atherosclerosis occurs due to accumulation of low-density lipoprotein... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of mortality worldwide. Atherosclerosis occurs due to accumulation of low-density lipoprotein cholesterol (LDL-c) in the arterial system. Thus, lipid lowering therapy is essential for both primary and secondary prevention. Proprotein convertase subtilisn/kexin type 9 (PCSK9) inhibitors (Evolocumab, Alirocumab) and small interfering RNA (siRNA) therapy (Inclisiran) have been demonstrated to lower LDL-c and ASCVD events in conjunction with maximally tolerated statin therapy. However, the degree of LDL-c reduction and the impact on reducing major adverse cardiac events, including their impact on mortality, remains unclear.
OBJECTIVE
The purpose of this study is to examine the effects of PCSK9 inhibitors and small interfering RNA (siRNA) therapy on LDL-c reduction and major adverse cardiac events (MACE) and mortality by conducting a meta-analysis of randomized controlled trials.
METHODS
Using Pubmed, Embase, Cochrane Library and clinicaltrials.gov until April 2023, we extracted randomized controlled trials (RCTs) of PCSK9 inhibitors (Evolocumab, Alirocumab) and siRNA therapy (Inclisiran) for lipid lowering and risk of MACE. Using random-effects models, we pooled the relative risks and 95% CIs and weighted least-squares mean difference in LDL-c levels. We estimated odds ratios with 95% CIs among MACE subtypes and all-cause mortality. Fixed-effect model was used, and heterogeneity was assessed using the I2 statistic.
RESULTS
In all, 54 studies with 87,669 participants (142,262 person-years) met criteria for inclusion. LDL-c percent change was reported in 47 studies (n = 62,634) evaluating two PCSK9 inhibitors and siRNA therapy. Of those, 21 studies (n = 41,361) included treatment with Evolocumab (140mg), 22 (n = 11,751) included Alirocumab (75mg), and 4 studies (n = 9,522) included Inclisiran (284mg and 300mg). Compared with placebo, after a median of 24 weeks (IQR 12-52), Evolocumab reduced LDL-c by -61.09% (95% CI: -64.81, -57.38, p<0.01) and Alirocumab reduced LDL-c by -46.35% (95% CI: -51.75, -41.13, p<0.01). Inclisiran 284mg reduced LDL-c by -54.83% (95% CI: -59.04, -50.62, p = 0.05) and Inclisiran 300mg reduced LDL-c by -43.11% (95% CI: -52.42, -33.80, p = 0.01). After a median of 8 months (IQR 6-15), Evolocumab reduced the risk of myocardial infarction (MI), OR 0.72 (95% CI: 0.64, 0.81, p<0.01), coronary revascularization, 0.77 (95% CI: 0.70, 0.84, p<0.01), stroke, 0.79 (95% CI: 0.66, 0.94, p = 0.01) and overall MACE 0.85 (95% CI: 0.80, 0.89, p<0.01). Alirocumab reduced MI, 0.57 (0.38, 0.86, p = 0.01), cardiovascular mortality 0.35 (95% CI: 0.16, 0.77, p = 0.01), all-cause mortality 0.60 (95% CI: 0.43, 0.84, p<0.01), and overall MACE 0.35 (0.16, 0.77, p = 0.01).
CONCLUSION
PCSK9 inhibitors (Evolocumab, Alirocumab) and siRNA therapy (Inclisiran) significantly reduced LDL-c by >40% in high-risk individuals. Additionally, both Alirocumab and Evolocumab reduced the risk of MACE, and Alirocumab reduced cardiovascular and all-cause mortality.
Topics: Humans; PCSK9 Inhibitors; Cholesterol, LDL; Myocardial Infarction; Proprotein Convertase 9; Atherosclerosis; Heart Disease Risk Factors; RNA, Small Interfering; Anticholesteremic Agents; Cardiovascular Diseases; Hydroxymethylglutaryl-CoA Reductase Inhibitors
PubMed: 38055686
DOI: 10.1371/journal.pone.0295359