Background/Purpose: Asymptomatic hyperuricemia and gout are two clinical conditions associated with a high risk of cardiovascular events and mortality. Recent data suggest that the number of patients presenting with gout, under the age of 40 years (early-onset), is increasing, and these early-onset patients may have different clinical signs and co-morbidities from those who present with gout at a later age. A coronary Event Risk Tool (CERT) based on the measurement of selected plasma ceramides is reliable and predictive for cardiovascular disease-related events and death with prognostic performance beyond traditional risk factors¹. As our recent study demonstrated systematic lipidome dysregulation in patients with gout and hyperuricemia², the question emerged whether altered lipidomic profiles can assess the cardiovascular disease (CVD) risk in gout and hyperuricemia.

Methods: Our cohort, previously reported, consisted of plasma samples from 94 patients with asymptomatic hyperuricemia (77% ≤ 40 years), 196 patients with gout (59% ≤  40 years), and a control group of 53 normouricemic individuals². We reanalyzed lipid extracts using a targeted LC-MS method³. The CERT score was calculated using an established methodology that transforms ceramide concentrations to a 12-point scale. The CERT score of 10-12 (high risk) compared to 0-2 (low risk) is associated with a 4.3/4.2/6.0-fold increase in CVD-related death (5.1/11.4/9.4% risk in 13/5/1 years) when comparing primary prevention/coronary artery disease patients/acute coronary syndrome patients, respectively. All participants were fully informed about the study’s goals, written informed consent was obtained before enrolment, and all procedures were performed following the Declaration of Helsinki.

Results: We observed a significant increase in the CERT score in gout patients and in hyperuricemic patients compared to controls. There was also a gradual increase in the median CERT score with increasing age (P< 0.0001). The increased and high-risk CERT score (≥7) was 2-fold and 5.5-fold more frequent in hyperuricemic and gout patients, respectively, relative to controls. Our data also show an increase of the C-reactive protein as median values of 0.8/1.6/3.4 mg/ml in controls/hyperuricemia/gout, respectively, consistent with the association of chronic inflammation and cardiovascular risk in rheumatic diseases.

Conclusion: A significantly higher CERT score was found in patients with gout and hyperuricemia (even in early-onset ≤ 40 years), suggesting a strong correlation with an increased risk of CVD (P< 0.0001).  Prediction tools incorporating the CERT score could be proposed for cardiovascular disease risk stratification in patients with hyperuricemia and gout, but its use in practice needs further evaluation.

References:

1. Laaksonen R, et al. Eur Heart J 2016; 37: 1967-76.

2. Kvasnička A, et al. Arthritis Res Ther 2023; 25: 234.

3. Kauhanen D, et al. Anal Bioanal Chem 2016; 408: 3475-83.

Funded by: Ministry of Health, Czech Republic, NU22-01-00465 and MH CZ: DRO (FNOL 00098892).

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