Cardiovascular Monosodium Urate Deposits Intensify MACE Risk in Gout

Christina Duftner, MD, PhD

Credit: EULVIC

A new investigation demonstrated a higher risk of major adverse cardiac events (MACE) among patients with dual-energy computed tomography (CT)-verified cardiovascular monosodium urate (MSU) deposits.¹

The risk of cardiovascular events in patients with gout and hyperuricemia is well-established, although the underlying mechanisms remain unclear—these findings may elaborate on this connection, as the presence of MSU deposits increased the risk of MACE by 4-fold.

“The higher prevalence of cardiac events in patients with cardiovascular monosodium urate deposit may facilitate risk stratification of gout patients, as classical cardiovascular risk scores or laboratory markers fail in their proper identification,” wrote the investigative team, led by Christina Duftner, MD, PhD and Gunter Weiss, MD, department of internal medicine, clinical division of internal medicine, Medical University Innsruch.

Gout originates from MSU depositions owing to persistent hyperuricemia and can induce immune responses via NLPR3 inflammasome activation during acute gout flares.² However, the effects are not limited to the acute phase of the disease, as recent evidence points to the role of gout in inducing an inflammatory environment which can promote atherosclerosis.

Patients with gout endure typical cardiovascular risk factors, but the reason for the higher risk has not been well-established—numerous data sets have suggested gout and hyperuricemia are independent risk factors for cardiovascular disease (CVD).³

Given the rising incidence of gout, and the subsequent increase in cardiovascular morbidity and mortality, Duftner and colleagues noted the importance of evaluating parameters putting individuals at risk.¹ The analysis sought to determine the relationship between cardiovascular MSU deposits and MACE risk in patients with gout and hyperuricemia.

The retrospective analysis involved patients with a clinical suspicion of gout, who underwent a dual-energy CT of the affected limb and thorax between June 2012 and December 2019. Clinical and laboratory factors were obtained from patient charts and investigators evaluated established cardiovascular risk factors, including dyslipidemia, hypertension, diabetes, and adiposity.

The medical history review identified the presence of MACE, with a median follow-up of 33 months, after the CT scan. From 295 identified patients, 189 were included in the study: 131 (69.3%) exhibited a final diagnosis of gout, 40 (21.2%) had hyperuricemia, and 18 (9.5%) were categorized as controls.

Cardiovascular MSU deposits were detected in 85 patients (45%), including 62 with gout and 22 with hyperuricemia. Those with detected cardiovascular MSU deposits were typically male (P = .016), older (P <.001), and exhibited higher C-reactive protein (P = .007), uric acid levels (P = .007), and calcium scores (P <.001), compared with patients without MSU deposits.

Overall, MACE was identified in 35 patients (18.5%) during the study observation period and these patients exhibited a higher coronary calcium score and CRP levels. A higher prevalence of MACE was observed among patients with cardiovascular MSU deposits (n = 22/85; 25.9%), compared with those without cardiovascular MSU (n = 13/104, 12.5%; odds ratio [OR], 2.4; P = .018). All 22 patients with MACE and cardiology MSU deposits demonstrated gout or hyperuricemia.

Dufner and colleagues indicated that, to the best of their knowledge, these are the first study data to demonstrate an association of cardiovascular MSU deposits with MACE. As a result, they called for larger, prospective studies to further evaluate and confirm the effects of cardiovascular MSU deposits.

“In summary, by demonstrating the increased risk for MACE in patients with cardiovascular MSU deposits, our results highlight the urgent need for improved management in these patients,” Duftner and colleagues wrote.

References

1. _{Held J, Schwabl C, Haschka D, et al. Major cardiovascular events in patients with cardiovascular monosodium urate deposits in atherosclerotic plaques. Rheumatology (Oxford). Published online April 23, 2024. doi:10.1093/rheumatology/keae240}
2. _{Cox P, Gupta S, Zhao SS, Hughes DM. The incidence and prevalence of cardiovascular diseases in gout: a systematic review and meta-analysis. Rheumatol Int. 2021;41(7):1209-1219. doi:10.1007/s00296-021-04876-6}
3. _{Cipolletta E, Tata LJ, Nakafero G, Avery AJ, Mamas MA, Abhishek A. Association Between Gout Flare and Subsequent Cardiovascular Events Among Patients With Gout. JAMA. 2022;328(5):440–450. doi:10.1001/jama.2022.11390}