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Sex and gender differences in coronary pathophysiology and ischaemic heart disease
(Oxford University Press (OUP), 2026-01-23)
Manfrini, Olivia
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Tousoulis, Dimitris
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Antoniades, Charalambos
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Badimon, Lina
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Bugiardini, Raffaele
Ischaemic heart disease shows important differences between men and women, requiring an understanding of sex and gender dissimilarities to improve outcomes. This Scientific Statement provides an updated review of the current knowledge from risk factors to prognosis. It discusses the unequal impact of certain traditional risk factors between men and women, along with additional factors, such as hormonal changes and treatments (including those for transgender people and cancer), pregnancy-related complications, and autoimmune diseases, which contribute to the sex-specific risk profiles. Moreover, it outlines functional and structural sex differences in the pathophysiology (e.g. coronary atheroma plaques and burden, coronary dissection, vasospasm, and microvascular disease) with women being more prone to microvascular disease and endothelial dysfunction, while paradoxically experiencing less severe myocardial ischaemia at similar levels of coronary stenosis. The document further addresses the evaluation of diagnostic tools, which often have a male-centric bias, resulting in underdiagnosis in women who also tend to receive less guideline-recommended treatment. Additionally, women can have different responses and side effects to various preventive and therapeutic treatments, potentially contributing to the worse prognosis documented in acute coronary syndromes with obstructive coronary artery disease, particularly at a young age. Considering all these sex and gender differences and the low enrolment of women in randomized controlled trials, questions arise regarding the optimal treatment for women. Addressing sex differences requires conducting sex-specific research to close the knowledge gap. Overall, the Scientific Statement highlights all relevant sex- and gender-specific dissimilarities to advance clinical practice and identify directions for future research to improve guideline recommendations for equitable care.
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Perivascular adipose tissue as a source of therapeutic targets and clinical biomarkers
(Oxford Academic, 2023-08-21)
Antoniades, Charalambos
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Tousoulis, Dimitris
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Fleming, Ingrid
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Duncker, Dirk J
Obesity is a modifiable cardiovascular risk factor, but adipose tissue (AT) depots in humans are anatomically, histologically, and functionally heterogeneous. For example, visceral AT is a pro-atherogenic secretory AT depot, while subcutaneous AT represents a more classical energy storage depot. Perivascular adipose tissue (PVAT) regulates vascular biology via paracrine cross-talk signals. In this position paper, the state-of-the-art knowledge of various AT depots is reviewed providing a consensus definition of PVAT around the coronary arteries, as the AT surrounding the artery up to a distance from its outer wall equal to the luminal diameter of the artery. Special focus is given to the interactions between PVAT and the vascular wall that render PVAT a potential therapeutic target in cardiovascular diseases. This Clinical Consensus Statement also discusses the role of PVAT as a clinically relevant source of diagnostic and prognostic biomarkers of vascular function, which may guide precision medicine in atherosclerosis, hypertension, heart failure, and other cardiovascular diseases. In this article, its role as a 'biosensor' of vascular inflammation is highlighted with description of recent imaging technologies that visualize PVAT in clinical practice, allowing non-invasive quantification of coronary inflammation and the related residual cardiovascular inflammatory risk, guiding deployment of therapeutic interventions. Finally, the current and future clinical applicability of artificial intelligence and machine learning technologies is reviewed that integrate PVAT information into prognostic models to provide clinically meaningful information in primary and secondary prevention.
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Mechanisms, therapeutic implications, and methodological challenges of gut microbiota and cardiovascular diseases: a position paper by the ESC Working Group on Coronary Pathophysiology and Microcirculation
(Oxford Journals, 2022-12-29)
Tousoulis, Dimitris
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Guzik, Tomasz
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Padro, Teresa
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Duncker, Dirk J
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De Luca, Giuseppe
The human gut microbiota is the microbial ecosystem in the small and large intestines of humans. It has been naturally preserved and evolved to play an important role in the function of the gastrointestinal tract and the physiology of its host, protecting from pathogen colonization, and participating in vitamin synthesis, the functions of the immune system, as well as glucose homeostasis and lipid metabolism, among others. Mounting evidence from animal and human studies indicates that the composition and metabolic profiles of the gut microbiota are linked to the pathogenesis of cardiovascular disease, particularly arterial hypertension, atherosclerosis, and heart failure. In this review article, we provide an overview of the function of the human gut microbiota, summarize, and critically address the evidence linking compositional and functional alterations of the gut microbiota with atherosclerosis and coronary artery disease and discuss the potential of strategies for therapeutically targeting the gut microbiota through various interventions.

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