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  • Ovid Technologies (Wolters Kluwer Health)  (12)
  • 1
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    Online Resource
    Abstract 12839: Integrated Multi-Omics and Single Nucleus Transcriptomics Highlight Enhanced Adaptive Immune Responses in Human Bicuspid Aortic Valve Stenosis
    Ovid Technologies (Wolters Kluwer Health) ; 2022
    In:  Circulation Vol. 146, No. Suppl_1 ( 2022-11-08)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 146, No. Suppl_1 ( 2022-11-08)
    Abstract: Introduction: Bicuspid aortic valve (BAV) is the most common congenital cardiac defect, occurring in 1.5% of humans. Due to unknown pathogenic mechanisms, over 70% of those with BAV develop calcific aortic valve disease (CAVD). These patients require valve replacement 25x more frequently and a decade earlier than those with a tricuspid aortic valve (TAV). Objective: Identify cellular and molecular drivers of accelerated disease in BAV-CAVD. Methods: Small RNA-seq, RNA-seq, and proteomics were performed on 70 human aortic valves (11 non-diseased TAVs; fibrotic and calcific stages of 32 TAVs and 27 BAVs excised for CAVD). Single nuclei RNA-seq (snRNA-seq) was completed on 54,608 nuclei from 13 additional human valves (4 non-diseased TAVs; 5 TAVs and 4 BAVs with CAVD). Results: 4,938 miRs, transcripts, and proteins were differentially enriched between stages of BAV- and TAV-CAVD (q 〈 0.05). Multi-omics data, CT-derived valve calcification, and 29 clinical parameters were integrated by latent factor analysis. Protein-protein interaction networks revealed significantly elevated adaptive immune responses in BAV-CAVD: T cell/B cell inflammatory activation was enhanced and SLIT-ROBO signaling disrupted in diseased BAVs. snRNA-seq identified 10 major cell types in human aortic valves: valvular interstitial cells (65% of cells; 3 states), endothelial cells (10%; 2), macrophages (13%), T cells (8%; 2), and B cells (3%; 2). CAVD drove differentiation of dual side-specific endothelial subpopulations, enrichment of CARMN/CACNA1C/ACTA2-high interstitial cells, and substantial immune cell accumulation. B cells were further enriched in BAV- vs. TAV-CAVD. Conclusions: Adaptive immunity underpins molecular differences in BAV- vs. TAV-CAVD and is a novel avenue for tailored pharmacotherapy. We potentiate targeting of key cellular subpopulations by defining the dissociation bias-free transcriptional and cellular diversity of human CAVD at single-cell resolution.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/circ.146.suppl_1.12839
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 1466401-X
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  • 2
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    Abstract 11618: Angiopoietin-2 is Associated With Capillary Leak and Complications After Cardiac Surgery
    Ovid Technologies (Wolters Kluwer Health) ; 2022
    In:  Circulation Vol. 146, No. Suppl_1 ( 2022-11-08)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 146, No. Suppl_1 ( 2022-11-08)
    Abstract: Introduction: Patients undergoing cardiac surgery are prone to numerous complications. Increased vascular permeability may be associated with morbidity and mortality due to hemodynamic instability, fluid overload, and edema formation. Hypothesis: Markers of endothelial injury and inflammation are associated with capillary leak (CLS), ultimately increasing the risk of perioperative complications. Methods: In a prospective, observational trial 405 cardiac surgery patients were evaluated using daily body impedance electrical analysis, ultrasound, sublingual intravital microscopy, and analysis of biomarkers. Multivariable models and machine learning (ML) were used to study the association of angiopoietin-2 (Ang-2) with extracellular water (ECW) as well as common complications after cardiac surgery. Results: Across all surgical groups, ECW increased postoperatively (20±6 preoperatively to 29±7L on POD2; P 〈 0.001). Concomitantly, the levels of Ang-2 rose, showing a strong correlation based on the time points of measurements (r=0.959, P =0.041). Inflammatory (IL-6, IL-8, CRP) and endothelial biomarkers (VE-Cadherin, syndecan-1, ICAM-1) suggestive of CLS were increased. After accounting for common risk factors of edema formation in cardiac surgery, we found a significant association of Ang-2 and ECW (Table 1). Furthermore, high Ang-2 patients showed an increased odds for developing acute kidney injury (OR 1.095 [1.032-1.169]; P =0.004), and high Ang-2 was associated with delayed extubation, longer time in the ICU, and a higher chance of prolonged dependence on vasoactive medication. ML predicted postoperative complications well if CLS was added to standard risk factors. Conclusions: CLS is a relevant problem after cardiac surgery. Ang-2 in combination with ECW shows promising potential to reliably anticipate CLS and postoperative complications after cardiac surgery.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/circ.146.suppl_1.11618
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 1466401-X
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  • 3
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    Genetic and Clinical Risk Prediction Model for Postoperative Atrial Fibrillation
    Ovid Technologies (Wolters Kluwer Health) ; 2015
    In:  Circulation: Arrhythmia and Electrophysiology Vol. 8, No. 1 ( 2015-02), p. 25-31
    Details
    In: Circulation: Arrhythmia and Electrophysiology, Ovid Technologies (Wolters Kluwer Health), Vol. 8, No. 1 ( 2015-02), p. 25-31
    Abstract: Postoperative atrial fibrillation (PoAF) is common after coronary artery bypass grafting. We previously showed that atrial fibrillation susceptibility single nucleotide polymorphisms (SNPs) at the chromosome 4q25 locus are associated with PoAF. Here, we tested the hypothesis that a combined clinical and genetic model incorporating atrial fibrillation risk SNPs would be superior to a clinical-only model. Methods and Results— We developed and externally validated clinical and clinical/genetic risk models for PoAF. The discovery and validation cohorts included 556 and 1164 patients, respectively. Clinical variables previously associated with PoAF and 13 SNPs at loci associated with atrial fibrillation in genome-wide association studies were considered. PoAF occurred in 30% and 29% of patients in the discovery and validation cohorts, respectively. In the discovery cohort, a logistic regression model with clinical factors had good discrimination, with an area under the receiver operator characteristic curve of 0.76. The addition of 10 SNPs to the clinical model did not improve discrimination (area under receiver operator characteristic curve, 0.78; P =0.14 for difference between the 2 models). In the validation cohort, the clinical model had good discrimination (area under the receiver operator characteristic curve, 0.69) and addition of genetic variables resulted in a marginal improvement in discrimination (area under receiver operator characteristic curve, 0.72; P 〈 0.0001). Conclusions— We developed and validated a model for the prediction of PoAF containing common clinical variables. Addition of atrial fibrillation susceptibility SNPs did not improve model performance. Tools to accurately predict PoAF are needed to risk stratify patients undergoing coronary artery bypass grafting and identify candidates for prophylactic therapies.
    Type of Medium: Online Resource
    ISSN: 1941-3149 , 1941-3084
    URL: Article
    DOI: 10.1161/CIRCEP.114.002300
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2015
    detail.hit.zdb_id: 2425487-3
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  • 4
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    Society of Cardiovascular Anesthesiologists/European Association of Cardiothoracic Anaesthetists Practice Advisory for the Management of Perioperative Atrial Fibrillation in Patients Undergoing Cardiac Surgery
    Ovid Technologies (Wolters Kluwer Health) ; 2019
    In:  Anesthesia & Analgesia Vol. 128, No. 1 ( 2019-01), p. 33-42
    Details
    In: Anesthesia & Analgesia, Ovid Technologies (Wolters Kluwer Health), Vol. 128, No. 1 ( 2019-01), p. 33-42
    Abstract: Postoperative atrial fibrillation (poAF) is the most common adverse event after cardiac surgery and is associated with increased morbidity, mortality, and hospital and intensive care unit length of stay. Despite progressive improvements in overall cardiac surgical operative mortality and postoperative morbidity, the incidence of poAF has remained unchanged at 30%–50%. A number of evidence-based recommendations regarding the perioperative management of atrial fibrillation (AF) have been released from leading cardiovascular societies in recent years; however, it is unknown how closely these guidelines are being followed by medical practitioners. In addition, many of these society recommendations are based on patient stratification into “normal” and “elevated” risk groups for AF, but criteria for that stratification have not been clearly defined. In an effort to improve the perioperative management of AF, the Society of Cardiovascular Anesthesiologists (SCA) Clinical Practice Improvement Committee developed a multidisciplinary Atrial Fibrillation Working Group that created a summary of current best practice based on a distillation of recent guidelines from professional societies involved in the care of cardiac surgical patients. An evidence-based set of survey questions was then generated to describe the current practice of perioperative AF management. Through collaboration with the European Association of Cardiothoracic Anaesthetists (EACTA), that survey was distributed to the combined memberships of both the SCA and EACTA, yielding 641 responses and resulting in the most comprehensive understanding to date of perioperative AF management in North America, Europe, and beyond. The survey data demonstrated the broad range of therapies utilized for the prevention and treatment of poAF, as well as a spectrum of adherence to published guidelines. With the goal of improving adherence, a graphical advisory tool was created with an easily accessible format that could be utilized for bedside management. Finally, given that no evidence-based threshold currently exists to differentiate patients at normal risk to develop poAF from those at elevated risk, the SCA/EACTA AF working group created a list of poAF risk factors using expert opinion and based on published risk score models for poAF. This approach allows stratification of patients into risk groups and facilitates adherence to the evidence-based recommendations summarized in the graphical advisory tool. It is our hope that these new additions to the clinical toolkit for the management of perioperative AF will improve the evidence-based care and outcomes of cardiac surgical patients worldwide.
    Type of Medium: Online Resource
    ISSN: 0003-2999
    URL: Article
    DOI: 10.1213/ANE.0000000000003865
    RVK:
    XA 22250
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2019
    detail.hit.zdb_id: 2018275-2
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  • 5
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    Abstract 10223: Tissue-Entrapped Extracellular Vesicles Modulate Divergent Mechanisms of Cardiovascular Calcification
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Circulation Vol. 144, No. Suppl_1 ( 2021-11-16)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 144, No. Suppl_1 ( 2021-11-16)
    Abstract: Introduction: Fewer than 50% of patients develop vascular and valvular calcification, implying differential pathogenesis. Tissue-entrapped extracellular vesicles (EVs) are implicated in mineralization but their contents and functions are unstudied. We investigated entrapped EV cargoes in human cardiovascular disease. Methods: Human carotid endarterectomy specimens and stenotic aortic valves were obtained from 53 patients. Disease stage-specific proteomics was performed on whole tissue (non-diseased/fibrotic/calcified areas). Tissue EVs were enriched by gradient fractionation then underwent proteomics and miRNA-seq. miR targets were predicted by TargetScan, pathway analyses utilized BioCarta/KEGG/Reactome, and protein-protein interaction networks employed STRING. Results: Disease progression drove significant convergence (p 〈 0.0001) of atherosclerotic plaque and valve proteomes (2,318 proteins). 548 and 158 proteins were exclusively altered (q 〈 0.05) by disease in plaques or valves, respectively. Vesicular GO terms increased 2.2x (p 〈 0.01) amongst proteins altered by disease in both tissues (202). Proteomics found 24 EV markers in the low-density fractions of plaques and valves, confirmed by electron microscopy and nanoparticle tracking. EV omics quantified 1,104 proteins and 123 miR cargoes. Networks of proteins and miR targets shared by plaque and valve EVs revealed common regulation of Rho GTPase and MAPK signaling. 179 proteins and 5 miRs were altered between plaque and valve EVs (q 〈 0.05); multi-omics integration found that EVs modulated cellular contraction and p53-mediated transcriptional regulation in plaques and valves, respectively. Conclusions: This first comparative proteomics study of human valves and arteries finds shared EV functionality in both diseases. Using novel means to examine tissue EV molecular cargoes, we also reveal critical divergent tissue-specific roles for EVs in mediating cardiovascular disease.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/circ.144.suppl_1.10223
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
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  • 6
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    Abstract 13348: Single Nuclear RNA-seq of Human Thoracic Aortic Dissection Identifies Expansion of Vascular Smooth Muscle Cells With a Distinct Transcriptional Phenotype
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Circulation Vol. 144, No. Suppl_1 ( 2021-11-16)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 144, No. Suppl_1 ( 2021-11-16)
    Abstract: Introduction: Phenotypic switching of vascular cells is a complex process associated with vascular disorders, including thoracic aortic aneurysm (TAA). Vascular smooth muscle cells (VSMCs) appear to switch from a contractile to synthetic phenotype in TAA. Single nuclear RNA-seq (snRNA-seq) of normal human and TAA aortas may be used to characterize cell heterogeneity of normal aortas, population shifts in disease, and the transcriptional profile of VSMC phenotypic switching. Hypothesis: snRNA-seq of normal and TAA aortas will identify the cell heterogeneity and transcriptional profiles of TAA. Methods: We performed snRNA-seq of 5 aortas from 2 normal and 3 TAA patients. We used a 10X-CellBender pipeline for profiling and analysis. Results: snRNA-seq identified 6 major cell types. The majority were VSMCs, exhibiting 4 sub-populations in all specimens (a). Cell distribution comparisons showed VSMC1 (ELN, PKD1, FLNA high) and VSMC2 (PRKG1, PDE3A, PCDH7 high) to be differentially-enriched in controls and TAA samples, respectively (b,c). Gene set and trajectory analyses confirmed prior observations of phenotypic switching (d,e). Genes associated with switching in VSMCs included TAA genes (PRKG1, PKD1, FLNA) with concordance of expression and putative function of Mendelian variants (i-k). Cell junction and regulation of muscle contraction pathways drove trajectory. We further assessed cell-type heritability of vascular GWAS variants (h). These gene sets were differentially-regulated between control and TAA. The strongest association was between VSMC2 and ascending aortic size (h). Conclusions: In this study, we demonstrated a dissociation bias-free method for snRNA-Seq of human vasculature. We confirmed enrichment of synthetic VSMCs in TAA and implicate phenotypic switching as a pathologic mechanism. Our study identifies a cell type-specific transcriptional profile of aortopathy genes, which may drive TAA and represent therapeutic targets.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/circ.144.suppl_1.13348
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
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  • 7
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    Impact of Selection Bias on Estimation of Subsequent Event Risk
    Ovid Technologies (Wolters Kluwer Health) ; 2017
    In:  Circulation: Cardiovascular Genetics Vol. 10, No. 5 ( 2017-10)
    Details
    In: Circulation: Cardiovascular Genetics, Ovid Technologies (Wolters Kluwer Health), Vol. 10, No. 5 ( 2017-10)
    Abstract: Studies of recurrent or subsequent disease events may be susceptible to bias caused by selection of subjects who both experience and survive the primary indexing event. Currently, the magnitude of any selection bias, particularly for subsequent time-to-event analysis in genetic association studies, is unknown. Methods and Results— We used empirically inspired simulation studies to explore the impact of selection bias on the marginal hazard ratio for risk of subsequent events among those with established coronary heart disease. The extent of selection bias was determined by the magnitudes of genetic and nongenetic effects on the indexing (first) coronary heart disease event. Unless the genetic hazard ratio was unrealistically large ( 〉 1.6 per allele) and assuming the sum of all nongenetic hazard ratios was 〈 10, bias was usually 〈 10% (downward toward the null). Despite the low bias, the probability that a confidence interval included the true effect decreased (undercoverage) with increasing sample size because of increasing precision. Importantly, false-positive rates were not affected by selection bias. Conclusions— In most empirical settings, selection bias is expected to have a limited impact on genetic effect estimates of subsequent event risk. Nevertheless, because of undercoverage increasing with sample size, most confidence intervals will be over precise (not wide enough). When there is no effect modification by history of coronary heart disease, the false-positive rates of association tests will be close to nominal.
    Type of Medium: Online Resource
    ISSN: 1942-325X , 1942-3268
    URL: Article
    DOI: 10.1161/CIRCGENETICS.116.001616
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2017
    detail.hit.zdb_id: 2927603-2
    detail.hit.zdb_id: 2457085-0
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  • 8
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    Subsequent Event Risk in Individuals With Established Coronary Heart Disease : Design and Rationale of the GENIUS-CHD Consortium
    Ovid Technologies (Wolters Kluwer Health) ; 2019
    In:  Circulation: Genomic and Precision Medicine Vol. 12, No. 4 ( 2019-04)
    Details
    In: Circulation: Genomic and Precision Medicine, Ovid Technologies (Wolters Kluwer Health), Vol. 12, No. 4 ( 2019-04)
    Abstract: The Genetics of Subsequent Coronary Heart Disease (GENIUS-CHD) consortium was established to facilitate discovery and validation of genetic variants and biomarkers for risk of subsequent CHD events, in individuals with established CHD. Methods: The consortium currently includes 57 studies from 18 countries, recruiting 185 614 participants with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. All studies collected biological samples and followed-up study participants prospectively for subsequent events. Results: Enrollment into the individual studies took place between 1985 to present day with a duration of follow-up ranging from 9 months to 15 years. Within each study, participants with CHD are predominantly of self-reported European descent (38%–100%), mostly male (44%–91%) with mean ages at recruitment ranging from 40 to 75 years. Initial feasibility analyses, using a federated analysis approach, yielded expected associations between age (hazard ratio, 1.15; 95% CI, 1.14–1.16) per 5-year increase, male sex (hazard ratio, 1.17; 95% CI, 1.13–1.21) and smoking (hazard ratio, 1.43; 95% CI, 1.35–1.51) with risk of subsequent CHD death or myocardial infarction and differing associations with other individual and composite cardiovascular endpoints. Conclusions: GENIUS-CHD is a global collaboration seeking to elucidate genetic and nongenetic determinants of subsequent event risk in individuals with established CHD, to improve residual risk prediction and identify novel drug targets for secondary prevention. Initial analyses demonstrate the feasibility and reliability of a federated analysis approach. The consortium now plans to initiate and test novel hypotheses as well as supporting replication and validation analyses for other investigators.
    Type of Medium: Online Resource
    ISSN: 2574-8300
    URL: Article
    DOI: 10.1161/CIRCGEN.119.002470
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2019
    detail.hit.zdb_id: 2927603-2
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  • 9
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    Association of Chromosome 9p21 With Subsequent Coronary Heart Disease Events : A GENIUS-CHD Study of Individual Participant Data
    Ovid Technologies (Wolters Kluwer Health) ; 2019
    In:  Circulation: Genomic and Precision Medicine Vol. 12, No. 4 ( 2019-04)
    Details
    In: Circulation: Genomic and Precision Medicine, Ovid Technologies (Wolters Kluwer Health), Vol. 12, No. 4 ( 2019-04)
    Abstract: Genetic variation at chromosome 9p21 is a recognized risk factor for coronary heart disease (CHD). However, its effect on disease progression and subsequent events is unclear, raising questions about its value for stratification of residual risk. Methods: A variant at chromosome 9p21 (rs1333049) was tested for association with subsequent events during follow-up in 103 357 Europeans with established CHD at baseline from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) Consortium (73.1% male, mean age 62.9 years). The primary outcome, subsequent CHD death or myocardial infarction (CHD death/myocardial infarction), occurred in 13 040 of the 93 115 participants with available outcome data. Effect estimates were compared with case/control risk obtained from the CARDIoGRAMplusC4D consortium (Coronary Artery Disease Genome-wide Replication and Meta-analysis [CARDIoGRAM] plus The Coronary Artery Disease [C4D] Genetics) including 47 222 CHD cases and 122 264 controls free of CHD. Results: Meta-analyses revealed no significant association between chromosome 9p21 and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline (GENIUS-CHD odds ratio, 1.02; 95% CI, 0.99–1.05). This contrasted with a strong association in CARDIoGRAMPlusC4D odds ratio 1.20; 95% CI, 1.18–1.22; P for interaction 〈 0.001 compared with the GENIUS-CHD estimate. Similarly, no clear associations were identified for additional subsequent outcomes, including all-cause death, although we found a modest positive association between chromosome 9p21 and subsequent revascularization (odds ratio, 1.07; 95% CI, 1.04–1.09). Conclusions: In contrast to studies comparing individuals with CHD to disease-free controls, we found no clear association between genetic variation at chromosome 9p21 and risk of subsequent acute CHD events when all individuals had CHD at baseline. However, the association with subsequent revascularization may support the postulated mechanism of chromosome 9p21 for promoting atheroma development.
    Type of Medium: Online Resource
    ISSN: 2574-8300
    URL: Article
    DOI: 10.1161/CIRCGEN.119.002471
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2019
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  • 10
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    Association of Factor V Leiden With Subsequent Atherothrombotic Events : A GENIUS-CHD Study of Individual Participant Data
    Ovid Technologies (Wolters Kluwer Health) ; 2020
    In:  Circulation Vol. 142, No. 6 ( 2020-08-11), p. 546-555
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 142, No. 6 ( 2020-08-11), p. 546-555
    Abstract: Studies examining the role of factor V Leiden among patients at higher risk of atherothrombotic events, such as those with established coronary heart disease (CHD), are lacking. Given that coagulation is involved in the thrombus formation stage on atherosclerotic plaque rupture, we hypothesized that factor V Leiden may be a stronger risk factor for atherothrombotic events in patients with established CHD. Methods: We performed an individual-level meta-analysis including 25 prospective studies (18 cohorts, 3 case-cohorts, 4 randomized trials) from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) consortium involving patients with established CHD at baseline. Participating studies genotyped factor V Leiden status and shared risk estimates for the outcomes of interest using a centrally developed statistical code with harmonized definitions across studies. Cox proportional hazards regression models were used to obtain age- and sex-adjusted estimates. The obtained estimates were pooled using fixed-effect meta-analysis. The primary outcome was composite of myocardial infarction and CHD death. Secondary outcomes included any stroke, ischemic stroke, coronary revascularization, cardiovascular mortality, and all-cause mortality. Results: The studies included 69 681 individuals of whom 3190 (4.6%) were either heterozygous or homozygous (n=47) carriers of factor V Leiden. Median follow-up per study ranged from 1.0 to 10.6 years. A total of 20 studies with 61 147 participants and 6849 events contributed to analyses of the primary outcome. Factor V Leiden was not associated with the combined outcome of myocardial infarction and CHD death (hazard ratio, 1.03 [95% CI, 0.92–1.16]; I 2 =28%; P -heterogeneity=0.12). Subgroup analysis according to baseline characteristics or strata of traditional cardiovascular risk factors did not show relevant differences. Similarly, risk estimates for the secondary outcomes including stroke, coronary revascularization, cardiovascular mortality, and all-cause mortality were also close to identity. Conclusions: Factor V Leiden was not associated with increased risk of subsequent atherothrombotic events and mortality in high-risk participants with established and treated CHD. Routine assessment of factor V Leiden status is unlikely to improve atherothrombotic events risk stratification in this population.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/CIRCULATIONAHA.119.045526
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
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