The relationship between serum uric acid (SUA) levels and cardiovascular disease is intricate and influenced by multiple factors. The association between elevated SUA levels and increased risk of cardiovascular disease remains uncertain, as it is not yet clear whether this association is independent of other known risk factors. Among the various risk factors associated with cardiovascular disease, left ventricular hypertrophy (LVH) has been identified as a significant contributor to increased risk and complications [1]. Previous research has explored the relationship between SUA levels and LVH [2]. It has been found that SUA is independently associated with left ventricular mass index (LVMI), and the combination of hyperuricemia with LVH has been identified as an independent predictor of cardiovascular mortality [3,4]. A specific cutoff point of 5.6 mg/dl SUA has been identified as a predictor of larger left ventricular sizes in patients with essential hypertension [5]. Collectively, these studies indicating a strong association between SUA and LVH, suggesting that SUA may serve as a valuable biomarker for these conditions.

Interestingly, a previous study discovered that in patients with chronic kidney disease, there was a correlation between SUA levels and LVMI and LVH in women, but no such association was observed in men [6]. In contrast, SUA was found to be associated with LVH in male cardiac patients, independent of serum parathyroid hormone levels [2]. A study conducted on Caucasian hypertensive women and men did not find any independent association between SUA and left ventricular mass [7]. However, another study on essential hypertension revealed that SUA was independently associated with LVMI in both men and women, with a stronger association observed in women [8]. Therefore, it remains unclear whether the association between SUA and LVH differs between sexes.

In this particular scenario, Gherbesi et al. conducted a comprehensive meta-analysis of echocardiographic studies to examine the gender-specific evidence regarding the relationship between SUA levels and LVH as assessed by echocardiography [9]. The researchers employed MeSH terms and combined search items, including ‘uric acid’, ‘hyperuricemia’, ’left ventricular mass’, ‘left ventricular hypertrophy’, ’echocardiography’, ‘female’, and ‘male’, to identify relevant studies. Ultimately, six studies comprising 2791 normotensive and hypertensive individuals were included in the analysis. In the findings, there was a positive correlation observed between increasing SUA levels and age, body mass index (BMI), and systolic blood pressure (SBP) in women, while no such association was found in men. Additionally, a meta-analysis conducted to compare LVMI between individuals with low and high SUA levels revealed a higher pooled LVMI in the high SUA group among women, but not among men. Based on these findings, the authors concluded that hyperuricemia is indicative of a higher likelihood of increased LVMI in women but not in men. However, the authors also concluded that the current findings do not provide evidence for a separate role of SUA in the process of left ventricular (LV) remodeling in women. This is due to the fact that hyperuricemia in the combined female population was found to be associated with older age, higher BMI, and SBP.

This study represents an inaugural systematic meta-analysis examining sex-specific evidence of the correlation between SUA and LVH. The findings presented in this article are of the utmost importance in clinical practice. First, it is noteworthy that SUA is significantly associated with age, BMI, and SBP in women, whereas no such association was observed in men. The findings of this study indicate that SUA level has the potential to serve as a comprehensive indicator of cardiovascular risk in women. It is important to consider that the clinical significance of uric acid levels as a risk factor for cardiovascular disease may not be as pronounced in men as in women. Second, a notable association between elevated SUA level and LVMI was observed in women, whereas no such relationship was observed in men. This finding is of great significance, as previous reports have not consistently identified sex differences. However, through a systematic meta-analysis, a significant relationship was discovered in women, whereas no such relationship was observed in men. This study revealed a notable correlation between LVMI and SUA levels, which is closely associated with the prognosis of cardiovascular disease, specifically in women. Therefore, SUA may serve as a potential prognostic factor for cardiovascular disease in women. However, its significance in men remains inconclusive. Although definitive conclusions cannot be drawn from this study regarding the potential of SUA as a therapeutic target, the findings strongly indicate the importance of monitoring SUA levels over time in the management of cardiovascular disease in women.

In contrast, as the authors have also discussed, the current findings do not provide evidence that SUA plays an independent role in LV remodeling in women. This study found a significant association between SUA levels and age, BMI, and SBP in women. Additionally, age, BMI, and SBP were found to have an impact on the development of LVH. The adequacy of the number of women included in this meta-analysis is still a subject of controversy. To address these concerns, it would be necessary to conduct a prospective study specifically focusing on women to investigate the association between SUA intervention and the occurrence of LVH and cardiovascular events.

Several studies have identified a correlation between elevated SUA levels and the occurrence of cardiovascular disease [10–12]. It has been observed that patients with hypertension, insulin resistance, obesity, and cardiovascular disease often exhibit increased SUA levels [13]. Furthermore, higher SUA levels have been linked to a greater incidence of diabetes, hypertension, and chronic kidney disease [13]. However, there is an ongoing debate regarding whether elevated SUA levels independently predict cardiovascular risk [13]. A comprehensive cohort study demonstrated that elevated SUA levels were associated with heightened systemic inflammation, preclinical atherosclerosis, and future cardiovascular events [13]. Conversely, another study conducted in China found that individuals without risk factors for cardiac diseases had a lower risk of cardiovascular disease when their SUA levels were within the average range [14]. Despite the association between elevated SUA levels and cardiovascular disease, it remains uncertain whether targeting SUA levels therapeutically can effectively mitigate the progression of cardiovascular disease [11]. Nonetheless, maintaining SUA levels below the normal range may be a potential therapeutic approach. In the context of severe gout, there is a correlation with cardiovascular mortality [15]. Hence, additional investigation is required to ascertain the potential efficacy of reducing SUA levels as a therapeutic intervention for cardiovascular diseases.

Previous studies have examined sex disparities in the correlation between SUA levels and cardiovascular risk. A study conducted on Chinese patients with type 2 diabetes revealed gender disparities in the correlation between SUA levels and arteriosclerotic cardiovascular risk [16]. Similarly, another study discovered a U-shaped association between SUA levels and cardiovascular outcomes in male patients with coronary artery disease following stent implantation [17]. Furthermore, a dose-response meta-analysis of prospective studies demonstrated a significant positive relationship between SUA levels and the risk of cardiovascular disease mortality, with a more pronounced association observed in women than in men [18]. In the context of patients with chronic kidney disease. A study found that SUA was linked to cardiac hypertrophy, with notable differences between sexes [6]. A comprehensive review article concluded that elevated SUA levels were independently and significantly associated with the risk of cardiovascular mortality [19]. Collectively, these studies suggest the existence of sex differences in the association between SUA levels and cardiovascular risk, with some studies indicating stronger associations in women than men. Further investigations are required to gain a more comprehensive understanding.

In conclusion, a systematic meta-analysis conducted by Gherbesi et al. demonstrated a significant association between SUA levels and age, BMI, and SBP. Furthermore, the study findings indicated that elevated SUA levels were predictive of increased LVMI in women, but not in men. SUA has been identified as a potential prognostic factor for cardiovascular disease in women; however, its impact on men remains inconclusive.

ACKNOWLEDGEMENTS

There is no previous presentation of the whole of the work.

There is no funding received for this work from any of the following organizations: National Institutes of Health (NIH); Wellcome Trust; Howard Hughes Medical Institute (HHMI); and other(s).

Conflicts of interest

There are no conflicts of interest.

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