Hyperuricemia is a metabolic disorder caused by abnormal purine metabolism or impaired uric acid excretion. Its prevalence has been increasing worldwide, particularly in the context of population aging and lifestyle changes. Consequently, hyperuricemia has emerged as a significant global public health concern [1, 2]. Accumulating evidence indicates that hyperuricemia is not only closely associated with the development of gout but is also significantly linked to the occurrence and progression of hypertension, diabetes, chronic kidney disease, and cardiovascular events [3]. Within the cardiovascular system, elevated uric acid levels may increase the risk of cardiovascular events through multiple pathophysiological mechanisms, including increased oxidative stress, inflammatory activation, endothelial dysfunction, and accelerated atherosclerosis [4].

Febuxostat is a selective xanthine oxidase inhibitor that effectively lowers serum uric acid levels by suppressing uric acid production. In recent years, it has been widely applied in the management of hyperuricemia and gout [5]. Compared with the conventional agent allopurinol, febuxostat has demonstrated certain advantages in renal protection and cardiovascular-related outcomes [5, 6]. However, according to a safety warning issued by the U.S. Food and Drug Administration, the cardiovascular safety of febuxostat in patients with hyperuricemia remains a matter of concern [7]. Several studies have suggested that febuxostat therapy may be associated with an increased risk of cardiovascular mortality, although findings remain inconsistent across different populations and follow-up periods [8, 9]. Therefore, exploring the relationship between febuxostat treatment and cardiovascular events in patients with hyperuricemia and developing a reliable risk prediction model for this population are of great clinical and scientific relevance.

In this study, patients with hyperuricemia who attended Quzhou Municipal People’s Hospital and received febuxostat therapy were enrolled as the study population. A 12-month follow-up period was conducted after treatment initiation to assess the occurrence of cardiovascular events. Potential risk factors were systematically evaluated using statistical modeling, and a cardiovascular event prediction model was constructed to provide evidence-based reference for clinical decision-making and facilitate early identification and intervention in high-risk patients.

The findings of this study demonstrated that the overall incidence of cardiovascular events within 12 months among patients with hyperuricemia receiving febuxostat therapy was 19.0%. Binary logistic regression analysis demonstrated that age, body mass index, and prior hypertension were independent risk factors for cardiovascular events. These findings indicate that traditional cardiovascular risk factors continue to exert a significant impact on patients with hyperuricemia, and that other potential contributors, such as triglyceride levels, body weight, and prior dyslipidemia, should not be overlooked in cardiovascular risk prediction.

Multivariate logistic regression analysis revealed that age was a statistically significant independent risk factor for cardiovascular events (OR = 1.05, 95% CI: 1.02–1.07). This association may be explained by age-related reductions in arterial elasticity, endothelial dysfunction, and the accumulation of chronic inflammatory processes, all of which contribute to increased cardiovascular risk [10, 11, 12]. Elevated BMI indicates obesity, which is closely associated with insulin resistance and dyslipidemia and may further exacerbate the metabolic disorders associated with hyperuricemia, thereby promoting cardiovascular damage [13, 14]. The increased cardiovascular risk observed in patients with prior hypertension is consistent with epidemiological evidence indicating that elevated blood pressure accelerates atherosclerosis and left ventricular hypertrophy, leading to a higher incidence of cardiovascular events [15, 16].

In the univariate analysis, elevated triglyceride levels were associated with cardiovascular events. Hypertriglyceridemia is a well-established risk factor for atherosclerosis and frequently coexists with hyperuricemia, and the two conditions may interact through shared metabolic pathways [17].

Previous studies have reported inconsistent findings regarding the cardiovascular risk associated with febuxostat compared with other urate-lowering therapies. For instance, Wang et al. [18] reported no significant difference in cardiovascular outcomes. Although the present study was not a prospective randomized controlled trial but rather a retrospective analysis based on follow-up data and medical records, the results suggest that, in a real-world clinical setting, febuxostat treatment does not fully mitigate the impact of traditional cardiovascular risk factors. This observation underscores the continued need for comprehensive cardiovascular risk stratification and management in patients receiving febuxostat therapy.

A major strength of this study is the development and validation of a cardiovascular event prediction model using multiple evaluation methods, including a nomogram, ROC curve analysis, and DCA, all of which demonstrated good discrimination and potential clinical utility. Notably, the model exhibited higher specificity than sensitivity, indicating reliable identification of low-risk individuals while exhibiting relatively limited ability to detect all potential high-risk cases. This performance characteristic should be carefully considered in clinical practice, as low predicted risk does not completely exclude the possibility of future cardiovascular events and should be interpreted alongside a comprehensive clinical assessment.

Several limitations of this study should be acknowledged. First, the single-center retrospective design may introduce selection bias. Second, the prediction model was specifically developed for patients with hyperuricemia receiving febuxostat, and its generalizability requires further validation in external cohorts; future studies should also compare this model with established cardiovascular risk scores to determine its incremental clinical value. Third, the absence of a parallel control group limits direct comparison of cardiovascular risk between febuxostat and other urate-lowering agents. Fourth, although the follow-up period was 12 months, potential misclassification of certain outcome events, such as deaths with complex etiologies, cannot be excluded, and longer-term follow-up is warranted. Fifth, biological indicators closely related to atherosclerosis, including systemic inflammatory indicators and imaging markers such as carotid intima-media thickness, were not included; incorporation of these variables in future prospective studies may further elucidate underlying mechanisms and optimize model performance. Finally, expansion of the sample size is necessary to enhance model stability and enable more robust analysis of subgroups.

The predictive model developed in this study demonstrated good predictive performance, confirming its potential clinical value as a cardiovascular risk assessment tool for patients with hyperuricemia. The model identified age, BMI, history of hypertension, and dyslipidemia as key independent predictors of cardiovascular events. Based on these findings, future research should prioritize external validation of the model and further evaluation of the long-term cardiovascular safety of febuxostat treatment through multicenter, prospective cohort studies, thereby providing higher-level evidence to support individualized clinical management.

• In this single-center retrospective cohort study, a predictive model incorporating age, history of hypertension, and BMI was developed and validated, demonstrating good discriminatory ability (AUC $\approx$ 0.78–0.80) for assessing cardiovascular event risk in patients with hyperuricemia receiving febuxostat therapy.

• In this retrospective cohort, age, BMI, and history of hypertension were identified as independent predictors of short-term cardiovascular events, suggesting that these traditional risk factors may remain relevant even in patients receiving urate-lowering therapy.

• The model showed good calibration and net clinical benefit in internal validation, indicating that it may serve as a useful adjunctive tool for cardiovascular risk stratification, though its generalizability requires further external validation.

The data used to support the findings of this study are available from the corresponding author upon request.

XJC and YXC designed the research study and wrote the first draft. YQC, WXX and YL performed the research. YQC, WXX and YL analyzed the data. All authors contributed to the important editorial changes in the manuscript. All authors read and approved the final manuscript. All authors have participated sufficiently in the work and agreed to be accountable for all aspects of the work.

This study was conducted in accordance with the principles of the Declaration of Helsinki, and the research protocol was approved by the Ethics Committee of Quzhou Municipal People’s Hospital (Ethics Approval No.: 2026-007). Written informed consent was obtained from all participants.

Not applicable.

This research received no external funding.

The authors declare no conflict of interest.