The relationship shown between gout and cardiovascular disease indicates that gout could be one of a series of inflammatory conditions that increase the risk of cardiac disease (for example, rheumatoid arthritis). The prevalence of rheumatoid arthritis was higher in the gout group (2.7%) than in the non-gout population (2.3%), as observed in our study.

On the other hand, it is also possible that this link we observed was due to specific effects of elevated uric acid levels [7]. The molecular signaling pathways involved need to be further deciphered. The association we have shown between gout and all major cardiac diseases suggests that there is a risk modifier, the treatment of which could help prevent these diseases [8]. However, no clear protective effect of, e.g., allopurinol for the prevention of cardiovascular endpoints has yet been demonstrated in gout patients [9]. Although initial evidence suggested that cardiovascular patients might benefit from allopurinol even in the absence of gout, an important new study has shown that patients with ischemic heart disease, for example, do not benefit from taking allopurinol [10].

Our study lends support to the findings of McDowell et al. that elevated uric acid (UA) levels, which are associated with gout, increase the risk of cardiovascular disease. Elevated uric acid levels contribute to oxidative stress and vascular dysfunction, thereby establishing a link between gout and adverse cardiovascular outcomes [11]. Although reducing uric acid (UA) levels via sodium-glucose co-transporter 2 (SGLT2) inhibitors such as dapagliflozin has demonstrated benefits, UA appears to be more of a marker of disease severity than a direct risk factor [12]. Further research should be conducted to gain a more detailed understanding of the comorbidities associated with gout and to investigate alternative treatments that target oxidative stress, with the aim of improving the management of cardiovascular risk in patients with gout.

Better knowledge of the molecular and genetic links between gout and cardiovascular disease may also help explain the sex-related differences we found. These appear to be disease-specific: While there is a stronger association between gout and disease risk in women, as consistent with previous studies in CHD [13], the risk for the other cardiac diseases is higher in men.

The observed sex-related differences in the association between gout and cardiovascular events may be attributed to a number of biological, hormonal, and behavioral factors. Hormonal differences, such as the protective effects of estrogen against cardiovascular disease in premenopausal women, may be a significant contributing factor. Following menopause, a decline in estrogen levels may elevate the risk of cardiovascular disease in women, potentially modifying the influence of gout [13, 14]. It is postulated that males with elevated testosterone levels may exhibit augmented uric acid production, thereby contributing to a higher prevalence of gout and an elevated risk of cardiovascular disease. Additionally, biological differences in uric acid metabolism and higher baseline uric acid levels in men may contribute to the stronger observed association between gout and cardiovascular events in men [14, 15].

Behavioral and lifestyle factors, such as diet, alcohol consumption, and physical activity, differ between men and women and may modify the impact of gout on cardiovascular health.

It is crucial to distinguish between risk factors and risk modifiers in the context of our study. In the context of disease development, risk factors are defined as variables that directly increase the likelihood of a particular disease occurring. For example, hypertension, smoking, and high cholesterol are well-established risk factors for cardiovascular disease, as they directly contribute to the pathophysiology of the condition.

Conversely, risk modifiers impact the influence of these risk factors on disease outcomes. In our study, gout serves as a risk modifier. While gout itself may not directly cause cardiovascular events, its presence can exacerbate the effects of existing cardiovascular risk factors, leading to an increased likelihood of adverse cardiovascular outcomes. This distinction is crucial for understanding the role of gout in the context of cardiovascular health and for developing targeted management strategies for patients with gout.

Our study relates more to the overarching aspect of the relationship between gout and cardiovascular disease in general. Understanding the association between gout and cardiovascular risk has significant implications for clinical practice. If gout is identified as a risk modifier for cardiovascular events, healthcare providers can better monitor and manage cardiovascular risk factors in patients with gout. This could lead to improved patient outcomes through more targeted and effective management strategies.