European Heart Journal

Chronic cardiometabolic assaults during type 2 diabetes (T2D) and obesity induce a progenitor cell imbalance in the circulation characterized by overproduction and release of pro-inflammatory monocytes and granulocytes from the bone marrow alongside aberrant differentiation and mobilization of pro-vascular progenitor cells that generate downstream progeny for the coordination of blood vessel repair. This imbalance can be detected in the peripheral blood of individuals with established T2D and severe obesity using multiparametric flow cytometry analyses to discern pro-inflammatory vs. pro-angiogenic progenitor cell subsets identified by high aldehyde dehydrogenase activity, a conserved progenitor cell protective function, combined with lineage-restricted cell surface marker analyses. Recent evidence suggests that progenitor cell imbalance can be reversed by treatment with pharmacological agents or surgical interventions that reduce hyperglycaemia or excess adiposity. In this state-of-the-art review, we present current strategies to assess the progression of pro-vascular regenerative cell depletion in peripheral blood samples of individuals with T2D and obesity and we summarize novel clinical data that intervention using sodium-glucose co-transporter 2 inhibition or gastric bypass surgery can efficiently restore cell-mediated vascular repair mechanisms associated with profound cardiovascular benefits in recent outcome trials. Collectively, this thesis generates a compelling argument for early intervention using current pharmacological agents to prevent or restore imbalanced circulating progenitor content and maintain vascular regenerative cell trafficking to sites of ischaemic damage. This conceptual advancement may lead to the design of novel therapeutic approaches to prevent or reverse the devastating cardiovascular comorbidities currently associated with T2D and obesity.

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Importance of sex and gender in ischaemic stroke and carotid atherosclerotic disease

Karina Gasbarrino, Diana Di Iorio, Stella S Daskalopoulou

doi : 10.1093/eurheartj/ehab756

European Heart Journal, Volume 43, Issue 6, 7 February 2022, Pages 460â€“473

Stroke is a leading cause of death and disability worldwide. Women are disproportionately affected by stroke, exhibiting higher mortality and disability rates post-stroke than men. Clinical stroke research has historically included mostly men and studies were not properly designed to perform sex- and gender-based analyses, leading to under-appreciation of differences between men and women in stroke presentation, outcomes, and response to treatment. Reasons for these differences are likely multifactorial; some are due to gender-related factors (i.e. decreased social support, lack of stroke awareness), yet others result from biological differences between sexes. Unlike men, women often present with â€˜atypicalâ€™ stroke symptoms. Lack of awareness of â€˜atypicalâ€™ presentation has led to delays in hospital arrival, diagnosis, and treatment of women. Differences also extend to carotid atherosclerotic disease, a cause of stroke, where plaques isolated from women are undeniably different in morphology/composition compared to men. As a result, women may require different treatment than men, as evidenced by the fact that they derive less benefit from carotid revascularization than men but more benefit from medical management. Despite this, women are less likely than men to receive medical therapy for cardiovascular risk factor management. This review focuses on the importance of sex and gender in ischaemic stroke and carotid atherosclerotic disease, summarizing the current evidence with respect to (i) stroke incidence, mortality, awareness, and outcomes, (ii) carotid plaque prevalence, morphology and composition, and gene connectivity, (iii) the role of sex hormones and sex chromosomes in atherosclerosis and ischaemic stroke risk, and (iv) carotid disease management.

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Cardiovascular and kidney outcomes with finerenone in patients with type 2 diabetes and chronic kidney disease: the FIDELITY pooled analysis

Rajiv Agarwal, Gerasimos Filippatos, Bertram Pitt, Stefan D Anker, Peter Rossing, Amer Joseph, Peter Kolkhof, Christina Nowack, Martin Gebel, Luis M Ruilope, George L Bakris, FIDELIO-DKD and FIGARO-DKD investigators

doi : 10.1093/eurheartj/ehab777

European Heart Journal, Volume 43, Issue 6, 7 February 2022, Pages 474â€“484

The complementary studies FIDELIO-DKD and FIGARO-DKD in patients with type 2 diabetes and chronic kidney disease (CKD) examined cardiovascular and kidney outcomes in different, overlapping stages of CKD. The purpose of the FIDELITY analysis was to perform an individual patient-level prespecified pooled efficacy and safety analysis across a broad spectrum of CKD to provide more robust estimates of safety and efficacy of finerenone compared with placebo.

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Bringing FIDELITY to the estimate of treatment effects of finerenone in chronic kidney disease due to type 2 diabetes

Carly Adamson, Pardeep S Jhund

doi : 10.1093/eurheartj/ehab827

European Heart Journal, Volume 43, Issue 6, 7 February 2022, Pages 485â€“487

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Tubulin-folding cofactor E deficiency promotes vascular dysfunction by increased endoplasmic reticulum stress

Panagiotis Efentakis, Michael Molitor, Sabine Kossmann, Magdalena L Bochenek, Johannes Wild, Jeremy Lagrange, Stefanie Finger, Rebecca Jung, Susanne Karbach, Katrin SchÃ¤fer, Andreas Schulz, Philipp Wild, Thomas MÃ¼nzel, Philip Wenzel

doi : 10.1093/eurheartj/ehab222

European Heart Journal, Volume 43, Issue 6, 7 February 2022, Pages 488â€“500

Assessment of endothelial function in humans by measuring flow-mediated dilation (FMD) risk-stratifies individuals with established cardiovascular disease, whereas its predictive value is limited in primary prevention. We therefore aimed to establish and evaluate novel markers of FMD at the population level.

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Identification of a novel therapeutic target in vascular dysfunction: a showcase of reverse and forward translational research linking bench to bedside

Hiroshi Iwata, Tohru Minamino

doi : 10.1093/eurheartj/ehab263

European Heart Journal, Volume 43, Issue 6, 7 February 2022, Pages 501â€“503

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Matrix metalloproteinase-2 on activated platelets triggers endothelial PAR-1 initiating atherosclerosis

Stefania Momi, Emanuela Falcinelli, Eleonora Petito, Giulia Ciarrocca Taranta, Alice Ossoli, Paolo Gresele

doi : 10.1093/eurheartj/ehab631

European Heart Journal, Volume 43, Issue 6, 7 February 2022, Pages 504â€“514

Platelets participate in atherogenesis with mechanisms not yet fully clarified. Vascular wall MMP-2 is involved in the arterial remodelling accompanying atherosclerosis. Platelets contain and release MMP-2 but no informations are available on its role in atherosclerotic lesion formation.

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Platelet-derived MMP-2 in the prevention of plaque formation: how many strokes is par?

Judith M E M Cosemans

doi : 10.1093/eurheartj/ehab665

European Heart Journal, Volume 43, Issue 6, 7 February 2022, Pages 515â€“517

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Propionate attenuates atherosclerosis by immune-dependent regulation of intestinal cholesterol metabolism

Arash Haghikia, Friederike Zimmermann, Paul Schumann, Andrzej Jasina, Johann Roessler, David Schmidt, Philipp Heinze, Johannes Kaisler, Vanasa Nageswaran, Annette Aigner, Uta Ceglarek, Roodline Cineus, Ahmed N Hegazy, Emiel P C van der Vorst, Yvonne DÃ¶ring, Christopher M Strauch, Ina Nemet, Valentina Tremaroli, Chinmay Dwibedi, Nicolle KrÃ¤nkel, David M Leistner, Markus M Heimesaat, Stefan Bereswill, Geraldine Rauch, Ute Seeland, Oliver Soehnlein, Dominik N MÃ¼ller, Ralf Gold, Fredrik BÃ¤ckhed, Stanley L Hazen, Aiden Haghikia, Ulf Landmesser

doi : 10.1093/eurheartj/ehab644

European Heart Journal, Volume 43, Issue 6, 7 February 2022, Pages 518â€“533

Atherosclerotic cardiovascular disease (ACVD) is a major cause of mortality and morbidity worldwide, and increased low-density lipoproteins (LDLs) play a critical role in development and progression of atherosclerosis. Here, we examined for the first time gut immunomodulatory effects of the microbiota-derived metabolite propionic acid (PA) on intestinal cholesterol metabolism.

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