The objective of this study was to examine the relationship between serum uric acid levels and the occurrence of pulmonary embolism. The findings demonstrated that elevated uric acid levels independently increased the risk of pulmonary embolism, a correlation that persisted even after adjusting for various potential confounding factors. And, upon stratifying the subjects by age, notable differences in SUA were observed between patients with and without pulmonary embolism in both the elderly (≥ 60 years) and non-elderly (< 60 years) cohorts. Interestingly, uric acid levels exhibited a significant association with pulmonary embolism solely in the elderly population following adjustments for multiple confounders. In addition, there is an interaction between age and uric acid, which increases the risk of pulmonary embolism.

Previous studies have shown that uric acid is strongly associated with the onset and recurrence of pulmonary embolism and that high levels of serum uric acid may be a potential risk factor for pulmonary embolism [12, 15, 18], which is consistent with our findings. To our knowledge, our study represents the first attempt to explore the impact of uric acid on pulmonary embolism occurrence across different age groups. In a case-control analysis involving 368 hospitalized patients who underwent CTPA, we systematically screened numerous suspected risk factors and observed significantly higher uric acid levels in patients with pulmonary embolism compared to those without (325.11 ± 137.02 vs. 298.26 ± 110.54, P = 0.039). Furthermore, following adjustment for multiple confounding variables, multifactorial logistic regression analysis demonstrated that uric acid served as an independent risk factor for pulmonary embolism (OR = 1.002, 95% CI 1.000-1.005, p = 0.042).

After stratifying by age, elevated uric acid levels remained significant among elderly patients with pulmonary embolism. Upon adjusting for multiple confounders, heightened uric acid levels emerged as an independent risk factor for pulmonary embolism development in the elderly (OR = 1.003, 95% CI 1.001–1.005, P = 0.008). Previous studies have consistently linked gout or elevated uric acid levels with venous thrombosis in the elderly [19,20,21]. Our findings are consistent with this.

The current study reveals a robust association between elevated uric acid levels and pulmonary embolism, shedding light on further investigations into their causal relationship. Recent years have witnessed a notable surge in pulmonary embolism incidence among the elderly, leading to increased utilization of late-stage resources, including long-term care facilities and home health services, among afflicted individuals in this demographic [22]. Unfortunately, elderly patients with acute pulmonary embolism often face poor prognoses [23], exacerbated by financial constraints [24]. Our study identified high uric acid levels as an independent risk factor for pulmonary embolism in the elderly, suggesting the potential for proactive interventions to mitigate its incidence and improve survival and quality of life in this population. Given the elderly population’s susceptibility to various cardiovascular ailments, diagnosing pulmonary embolism based solely on symptoms can be challenging, resulting in delayed diagnosis and worse outcomes [25]. Clarifying the link between uric acid and pulmonary embolism risk in the elderly may facilitate early detection and intervention, thereby enhancing prognosis. Moreover, it may inspire novel strategies for pulmonary embolism prevention.

The pathogenesis linking uric acid and pulmonary embolism remains unclear, but most findings suggest that elevated uric acid levels activate inflammatory pathways, potentially associating SUA with PE. High uric acid levels correlate strongly with inflammatory factors like interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-ɑ (TNF-ɑ), and C-reactive protein (CRP) [26]. Moreover, uric acid promotes cyclooxygenase-2 (COX-2) and reactive oxygen species (ROS) production, fostering inflammation and vascular smooth muscle cell proliferation [27]. Subsequently, inflammation disrupts the coagulation system by boosting coagulation, reducing anticoagulation activity, inhibiting fibrinolysis, and inducing endothelial dysfunction [28]. Studies have identified that activated endothelial cells contribute to coagulation by affecting TMEM16 proteins (TMEM16F and TMEM16E), which externalize phosphatidylserine in the vessel wall [29]. Research has further explored uric acid’s role in this pathway, revealing that elevated uric acid induces phosphatidylserine exposure and particle release, thereby enhancing the procoagulant activity of erythrocytes and vascular endothelial cells via TMEM16F activation, thus promoting thrombosis [30, 31]. Moreover, the procoagulant activity of particles increases with age [32]. Consequently, we hypothesize that the serum uric acid level’s role in promoting thrombosis through this pathway may be more pronounced in the elderly. Furthermore, experiments treating mouse and human umbilical vein endothelial cells with serum uric acid levels revealed that it inhibits myocyte enhancer factor (MEF2C) expression by upregulating let-7c expression, activating the NF-κB pathway, and ultimately leading to thrombosis [33].

There are several limitations to our study. Firstly, the serum uric acid level was assessed upon initial hospital admission, and the diagnosis of pulmonary embolism was made concurrently, preventing the determination of the sequence linking high uric acid levels to the onset of pulmonary embolism. As a result, we can only make preliminary etiological assumptions and cannot definitively establish a causal relationship between the two. Further prospective studies are required to verify this causal relationship. Secondly, the sample size of our study is relatively small and limited in scope, potentially contributing to a smaller odds ratio (OR). Thus, larger sample sizes in prospective studies are necessary for further validation. Additionally, certain potential confounding factors associated with pulmonary embolism, such as body mass index, blood pressure and CRP, were not included in the study due to high levels of missing data. Finally, because the mechanism of pulmonary embolism is complex, the reasons are diverse. Therefore, at the individual level, the change of uric acid level may have different effects on the occurrence of pulmonary embolism.