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  • 1
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    Online Resource
    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
    detail.hit.zdb_id: 2927603-2
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  • 2
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    Proteins in Preservation Fluid as Predictors of Delayed Graft Function in Kidneys from Donors after Circulatory Death
    Ovid Technologies (Wolters Kluwer Health) ; 2017
    In:  Clinical Journal of the American Society of Nephrology Vol. 12, No. 5 ( 2017-5), p. 817-824
    Details
    In: Clinical Journal of the American Society of Nephrology, Ovid Technologies (Wolters Kluwer Health), Vol. 12, No. 5 ( 2017-5), p. 817-824
    Abstract: Kidney transplantation is the preferred treatment for ESRD, and donor kidney shortage urges proper donor-recipient matching. Zero-hour biopsies provide predictive values for short- and long-term transplantation outcomes, but are invasive and may not reflect the entire organ. Alternative, more representative methods to predict transplantation outcome are required. We hypothesized that proteins accumulating in preservation fluid during cold ischemic storage can serve as biomarkers to predict post-transplantation graft function. Design, setting, participants, & measurements Levels of 158 proteins were measured in preservation fluids from kidneys donated after circulatory death (Maastricht category III) collected in two Dutch centers (University Medical Center Utrecht and Erasmus Medical Center Rotterdam) between 2013 and 2015. Five candidate biomarkers identified in a discovery set of eight kidneys with immediate function (IF) versus eight with delayed graft function (DGF) were subsequently analyzed in a verification set of 40 additional preservation fluids to establish a prediction model. Results Variables tested for their contribution to a prediction model included five proteins (leptin, periostin, GM-CSF, plasminogen activator inhibitor-1, and osteopontin) and two clinical parameters (recipient body mass index [BMI] and dialysis duration) that distinguished between IF and DGF in the discovery set. Stepwise multivariable logistic regression provided a prediction model on the basis of leptin and GM-CSF. Receiver operating characteristic analysis showed an area under the curve (AUC) of 0.87, and addition of recipient BMI generated a model with an AUC of 0.89, outperforming the Kidney Donor Risk Index and the DGF risk calculator, showing AUCs of 0.55 and 0.59, respectively. Conclusions We demonstrate that donor kidney preservation fluid harbors biomarkers that, together with information on recipient BMI, predict short-term post-transplantation kidney function. Our approach is safe, easy, and performs better than current prediction algorithms, which are only on the basis of clinical parameters. Podcast This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2017_05_05_Balkom.mp3
    Type of Medium: Online Resource
    ISSN: 1555-9041 , 1555-905X
    URL: Article
    DOI: 10.2215/CJN.10701016
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2017
    detail.hit.zdb_id: 2216582-4
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  • 3
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    Growth Differentiation Factor 15 Is Associated With Major Amputation and Mortality in Patients With Peripheral Artery Disease
    Ovid Technologies (Wolters Kluwer Health) ; 2017
    In:  Journal of the American Heart Association Vol. 6, No. 9 ( 2017-09-22)
    Details
    In: Journal of the American Heart Association, Ovid Technologies (Wolters Kluwer Health), Vol. 6, No. 9 ( 2017-09-22)
    Abstract: Peripheral artery disease ( PAD ) is one of the most common clinical presentations of atherosclerosis, and its prevalence is still increasing. Despite improvement of health care, morbidity and mortality risks remain high, including the risk of amputation. GDF15 (growth differentiation factor 15) is a member of the transforming growth factor family that is involved in apoptosis and inflammation; therefore, GDF 15 is a potential biomarker to identify patients at high risk of adverse clinical outcomes. Methods and Results Circulating GDF 15 levels were measured using a multiplex immunoassay in patients with critical limb ischemia and PAD from 2 different patient cohorts that included patients with clinically manifest PAD : the JUVENTAS (Rejuvenating Endothelial Progenitor Cells via Transcutaneous Intra‐Arterial Supplementation) trial (n=160, 67 major events; critical limb ischemia) and the Athero‐Express Biobank (n=386, 64 major events; PAD ). Kaplan–Meier curves demonstrated that high levels of GDF 15 were associated with increased risk of major events, defined as major amputation (at or above the ankle joint) and all‐cause mortality, in both cohorts (highest versus lowest, JUVENTAS : hazard ratio: 4.01 [95% confidence interval, 2.05–7.84; P 〈 0.0001]; Athero‐Express: hazard ratio: 3.27 [95% confidence interval, 1.64–6.54; P =0.0008]). In the JUVENTAS trial, this was more pronounced in women. Cox proportional multivariable regression models with median follow‐up of 3 years, corrected for common confounders, showed hazard ratios of 1.70 (95% confidence interval, 1.18–2.69; P =0.0053) and 1.57 (95% confidence interval, 1.02–2.41; P =0.041) per 2.78‐fold increase of GDF 15 in JUVENTAS and Athero‐Express, respectively. Conclusions High GDF 15 levels are associated with increased risk of major amputation and/or death in PAD patients. GDF 15 levels could be of additive value to identify patients who are at high risk of amputation or death and could help guide treatment choices.
    Type of Medium: Online Resource
    ISSN: 2047-9980
    URL: Article
    DOI: 10.1161/JAHA.117.006225
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2017
    detail.hit.zdb_id: 2653953-6
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  • 4
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    High Levels of (Un)Switched Memory B Cells Are Associated With Better Outcome in Patients With Advanced Atherosclerotic Disease
    Ovid Technologies (Wolters Kluwer Health) ; 2017
    In:  Journal of the American Heart Association Vol. 6, No. 9 ( 2017-09-22)
    Details
    In: Journal of the American Heart Association, Ovid Technologies (Wolters Kluwer Health), Vol. 6, No. 9 ( 2017-09-22)
    Abstract: Atherosclerosis is an inflammatory lipid disorder and the main underlying pathology of acute ischemic events. Despite a vast amount of data from murine atherosclerosis models, evidence of B‐cell involvement in human atherosclerotic disease is limited. We therefore investigated the association of circulating B‐cell subtypes with the occurrence of secondary cardiovascular events in advanced atherosclerotic disease. Methods and Results This cohort study consists of 168 patients who were included in the Athero‐Express biobank between 2009 and 2011. Before surgery, peripheral blood mononuclear cells were isolated and stored in liquid nitrogen. After gentle thawing of the peripheral blood mononuclear cells, different B‐cell subtypes including naïve, (un)switched memory, and CD 27 + CD 43 + B1‐like B cells, were analyzed by flow cytometry. Univariable and multivariable Cox proportional hazard models were used to analyze associations between B‐cell subtypes, circulating antibodies and secondary cardiovascular manifestations during the 3‐year follow‐up period. Mean age was 70.1±9.6 years, males represented 62.8% of the population, and 54 patients had secondary manifestations during follow‐up. High numbers of unswitched memory cells were protective against secondary outcome (hazard ratio, 0.30 [95% CI , 0.13–0.69]; P 〈 0.01). Similar results were obtained for the switched memory cells that also showed to be protective against secondary outcome (hazard ratio, 0.33 [95% CI , 0.14–0.77]; P =0.01). Conclusions A high number of (un)switched memory B cells is associated with better outcome following carotid artery endarterectomy. These findings suggest a potential role for B‐cell subsets in prediction and prevention of secondary cardiovascular events in patients with atherosclerosis.
    Type of Medium: Online Resource
    ISSN: 2047-9980
    URL: Article
    DOI: 10.1161/JAHA.117.005747
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2017
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  • 5
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    Apparent therapy-resistant hypertension as risk factor for the development of type 2 diabetes mellitus
    Ovid Technologies (Wolters Kluwer Health) ; 2020
    In:  Journal of Hypertension Vol. 38, No. 1 ( 2020-01), p. 45-51
    Details
    In: Journal of Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 38, No. 1 ( 2020-01), p. 45-51
    Type of Medium: Online Resource
    ISSN: 0263-6352
    URL: Article
    DOI: 10.1097/HJH.0000000000002227
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
    detail.hit.zdb_id: 2017684-3
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  • 6
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    Microanatomy of the Human Atherosclerotic Plaque by Single-Cell Transcriptomics
    Ovid Technologies (Wolters Kluwer Health) ; 2020
    In:  Circulation Research Vol. 127, No. 11 ( 2020-11-06), p. 1437-1455
    Details
    In: Circulation Research, Ovid Technologies (Wolters Kluwer Health), Vol. 127, No. 11 ( 2020-11-06), p. 1437-1455
    Abstract: Atherosclerotic lesions are known for their cellular heterogeneity, yet the molecular complexity within the cells of human plaques has not been fully assessed. Objective: Using single-cell transcriptomics and chromatin accessibility, we gained a better understanding of the pathophysiology underlying human atherosclerosis. Methods and Results: We performed single-cell RNA and single-cell ATAC sequencing on human carotid atherosclerotic plaques to define the cells at play and determine their transcriptomic and epigenomic characteristics. We identified 14 distinct cell populations including endothelial cells, smooth muscle cells, mast cells, B cells, myeloid cells, and T cells and identified multiple cellular activation states and suggested cellular interconversions. Within the endothelial cell population, we defined subsets with angiogenic capacity plus clear signs of endothelial to mesenchymal transition. CD4 + and CD8 + T cells showed activation-based subclasses, each with a gradual decline from a cytotoxic to a more quiescent phenotype. Myeloid cells included 2 populations of proinflammatory macrophages showing IL (interleukin) 1B or TNF (tumor necrosis factor) expression as well as a foam cell-like population expressing TREM2 (triggering receptor expressed on myeloid cells 2) and displaying a fibrosis-promoting phenotype. ATACseq data identified specific transcription factors associated with the myeloid subpopulation and T cell cytokine profiles underlying mutual activation between both cell types. Finally, cardiovascular disease susceptibility genes identified using public genome-wide association studies data were particularly enriched in lesional macrophages, endothelial, and smooth muscle cells. Conclusions: This study provides a transcriptome-based cellular landscape of human atherosclerotic plaques and highlights cellular plasticity and intercellular communication at the site of disease. This detailed definition of cell communities at play in atherosclerosis will facilitate cell-based mapping of novel interventional targets with direct functional relevance for the treatment of human disease.
    Type of Medium: Online Resource
    ISSN: 0009-7330 , 1524-4571
    URL: Article
    DOI: 10.1161/CIRCRESAHA.120.316770
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
    detail.hit.zdb_id: 1467838-X
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  • 7
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    Female Gene Networks Are Expressed in Myofibroblast-Like Smooth Muscle Cells in Vulnerable Atherosclerotic Plaques
    Ovid Technologies (Wolters Kluwer Health) ; 2023
    In:  Arteriosclerosis, Thrombosis, and Vascular Biology Vol. 43, No. 10 ( 2023-10), p. 1836-1850
    Details
    In: Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 43, No. 10 ( 2023-10), p. 1836-1850
    Abstract: Women presenting with coronary artery disease more often present with fibrous atherosclerotic plaques, which are currently understudied. Phenotypically modulated smooth muscle cells (SMCs) contribute to atherosclerosis in women. How these phenotypically modulated SMCs shape female versus male plaques is unknown. METHODS: Gene regulatory networks were created using RNAseq gene expression data from human carotid atherosclerotic plaques. The networks were prioritized based on sex bias, relevance for smooth muscle biology, and coronary artery disease genetic enrichment. Network expression was linked to histologically determined plaque phenotypes. In addition, their expression in plaque cell types was studied at single-cell resolution using single-cell RNAseq. Finally, their relevance for disease progression was studied in female and male Apoe −/− mice fed a Western diet for 18 and 30 weeks. RESULTS: Here, we identify multiple sex-stratified gene regulatory networks from human carotid atherosclerotic plaques. Prioritization of the female networks identified 2 main SMC gene regulatory networks in late-stage atherosclerosis. Single-cell RNA sequencing mapped these female networks to 2 SMC phenotypes: a phenotypically modulated myofibroblast-like SMC network and a contractile SMC network. The myofibroblast-like network was mostly expressed in plaques that were vulnerable in women. Finally, the mice ortholog of key driver gene MFGE8 (milk fat globule EGF and factor V/VIII domain containing) showed retained expression in advanced plaques from female mice but was downregulated in male mice during atherosclerosis progression. CONCLUSIONS: Female atherosclerosis is characterized by gene regulatory networks that are active in fibrous vulnerable plaques rich in myofibroblast-like SMCs.
    Type of Medium: Online Resource
    ISSN: 1079-5642 , 1524-4636
    URL: Article
    DOI: 10.1161/ATVBAHA.123.319325
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
    detail.hit.zdb_id: 1494427-3
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  • 8
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    Short-Term Double Layer Mesh Stent Patency for Emergent or Elective Carotid Artery Stenting : A Single Center Experience
    Ovid Technologies (Wolters Kluwer Health) ; 2019
    In:  Stroke Vol. 50, No. 7 ( 2019-07), p. 1898-1901
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 50, No. 7 ( 2019-07), p. 1898-1901
    Abstract: Novel double layer micromesh stents have recently been introduced for treatment of patients with significant carotid stenosis. Strict evaluation of safety and patency of such novel devices is required both in elective and in emergency interventions. We report a single center experience with double layer mesh stents for carotid artery revascularization. Methods— Consecutive patients who underwent carotid artery stenting with a double layer mesh stent between June 2015 and September 2018 in our tertiary vascular referral center were included. Treatment indications were emergent carotid artery stenting for intracranial or extracranial carotid stenosis in patients undergoing intraarterial thrombectomy for acute ischemic stroke in the anterior circulation, or elective carotid artery stenting for significant symptomatic or asymptomatic stenosis. End points were postprocedural thrombotic stent occlusion and procedural stroke or death. Results— Fifty-four patients were included; 27 were treated for acute stroke with intracranial and extracranial (tandem) lesions and 27 for elective stenting. Follow-up imaging was available for 9/27 (33%) patients with acute stroke, and 19/27 (70%) electively treated patients. Five stent occlusions occurred, of which 2 were symptomatic with clinical deterioration within one day. Another patient deteriorated on postprocedural day one, but imaging of the carotids was not performed, and the stent turned out occluded on the 30-day duplex. All stent occlusions occurred in patients treated for acute stroke. Conclusions— This study suggests that occlusion of novel double layer mesh stents occurs in a considerable proportion of carotid artery stenting procedures performed in the emergency setting for acute stroke, with occlusion-related symptoms in half the cases. Future prospective studies should clarify the role of double layer mesh stents in this high-risk patient population.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/STROKEAHA.118.024586
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2019
    detail.hit.zdb_id: 1467823-8
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  • 9
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    Genetic Susceptibility Loci for Cardiovascular Disease and Their Impact on Atherosclerotic Plaques
    Ovid Technologies (Wolters Kluwer Health) ; 2018
    In:  Circulation: Genomic and Precision Medicine Vol. 11, No. 9 ( 2018-09)
    Details
    In: Circulation: Genomic and Precision Medicine, Ovid Technologies (Wolters Kluwer Health), Vol. 11, No. 9 ( 2018-09)
    Type of Medium: Online Resource
    ISSN: 2574-8300 , 2574-8300
    URL: Article
    DOI: 10.1161/CIRCGEN.118.002115
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2018
    detail.hit.zdb_id: 2927603-2
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  • 10
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    Response by de Vries et al to Letter Regarding Article, “Short-Term Double Layer Mesh Stent Patency for Emergent or Elective Carotid Artery Stenting: A Single Center Experience”
    Ovid Technologies (Wolters Kluwer Health) ; 2019
    In:  Stroke Vol. 50, No. 12 ( 2019-12)
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 50, No. 12 ( 2019-12)
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/STROKEAHA.119.027656
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2019
    detail.hit.zdb_id: 1467823-8
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