Open Access

REVIEW

Gout as a systemic cardio-inflammatory disease: molecular and clinical links between hyperuricaemia and cardiovascular remodelling

Rajallectchumy Subramaniam, Nelli Giribabu^*, Naguib Salleh^*

Department of Physiology, Faculty of Medicine, Universiti Malaya, Lembah Pantai, Kuala Lumpur, Malaysia

* Corresponding Authors: Nelli Giribabu. Email: ; Naguib Salleh. Email:

European Cytokine Network 2026, 37(3), 293-318. https://doi.org/10.32604/ecn.2026.080872

Received 17 February 2026; Accepted 25 August 2026; Issue published 28 September 2026

Abstract

This narrative review summarises epidemiological associations and evaluates proposed mechanisms linking gout and hyperuricaemia with cardiovascular dysfunction and remodelling. Gout is a crystal arthropathy that is increasingly recognised as also carrying systemic cardio-inflammatory features. Hyperuricaemia and monosodium urate (MSU) crystals trigger Toll-like receptor 4/nuclear factor-kappa B (TLR4/NF-κB) and NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome signalling, driving IL-1β, IL-6, and TNF-α release together with xanthine oxidase (XO)–derived oxidative stress. Experimental studies in hyperuricaemia and non-gout cardiovascular models suggest that these cascades contribute to endothelial dysfunction and promote cardiac fibroblasts through TGF-β/Smad, JAK2/STAT3/HMGCS2, and Wnt/β-catenin pathways, promoting extracellular matrix (ECM) deposition and progressive cardiac remodelling. Population studies consistently associate gout with atrial fibrillation, ischaemic heart disease, stroke, and heart failure after adjustment for multiple cardiovascular risk factors. Multi-omics analyses of gout have identified the candidate hub genes CXCL8, PTGS2 and IL10 in gout. Separately, and by extrapolation rather than from gout-derived myocardial tissue, single-cell analysis of end-stage heart failure has implicated macrophage programmed cell-death pathways including ferroptosis and anoikis in cardiac remodelling, while experimental hyperuricaemia has implicated polyamine depletion and lumican suppression in mitochondrial dysfunction and ECM dysregulation. These latter findings are hypothesis-generating and have not been validated in patients with gout. Clinically, a single prospective observational study reported that guideline-concordant treatment combining a xanthine oxidase inhibitor (XOI) with colchicine improved flow-mediated dilation and reduced serum IL-1β, IL-6 and high-sensitivity C-reactive protein (hsCRP); no randomised cardiovascular outcome trial of this combination has been undertaken. In summary, gout is best regarded at present as a clinically important marker of increased cardiovascular risk rather than as an established independent causal exposure.

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Keywords

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