Maloberti Alessandro, Colombo Valentina, Daus Francesca, De Censi Lorenzo, Abrignani Maurizio Giuseppe, Temporelli Pier Luigi, Binaghi Giulio, Colivicchi Furio, Grimaldi Massimo, Gabrielli Domenico, Borghi Claudio, Oliva Fabrizio
School of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy; Cardiology 4, Cardio Center, ASST GOM Niguarda Ca' Granda, Milan, Italy.
School of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy.
Nutr Metab Cardiovasc Dis. 2025 Mar;35(3):103792. doi: 10.1016/j.numecd.2024.103792. Epub 2024 Nov 16.
The most frequent consequence of elevated uric acid (UA) levels is the development of gout and urate kidney disease. Besides these effects, several studies have investigated the association between hyperuricemia and cardiovascular (CV) disease. High serum UA has been identified as an important determinant of all-cause and CV mortality and CV events (acute and chronic coronary syndrome, stroke and peripheral artery disease). Despite the high number of publications on this topic, there are two questions that are still unanswered: do we need a specific CV cut-off of serum UA to better refine the CV risk? Is urate lowering treatment (ULT) able to reduce CV risk in asymptomatic patients? In this review, we will focus on these two points.
Although no doubt exists that the relationship between CV events starts at lower levels than the actually used cut-off, different papers found dissimilar cut-offs. Furthermore, heterogeneity is present depending on the specific CV events evaluated and none of the found cut-off have been tested in external populations (in order to confirm its discriminatory capacity). Furthermore, only few randomized clinical trials on the role of hypouricemic agents in reducing the CV risk have been published giving heterogeneous results. The last published one (ALL-HEART) has strong limitations, that we will deeply discuss.
A definitive answer to the two questions is impossible with the actually published paper but, over identifying current gaps in knowledge we try to individuate how they can be overruled.
尿酸(UA)水平升高最常见的后果是痛风和尿酸盐肾病的发生。除了这些影响外,多项研究还探讨了高尿酸血症与心血管(CV)疾病之间的关联。高血清尿酸已被确定为全因死亡率、心血管死亡率以及心血管事件(急性和慢性冠状动脉综合征、中风和外周动脉疾病)的重要决定因素。尽管关于该主题的出版物数量众多,但仍有两个问题尚未得到解答:我们是否需要一个特定的心血管疾病血清尿酸临界值来更好地细化心血管疾病风险?尿酸降低治疗(ULT)能否降低无症状患者的心血管疾病风险?在本综述中,我们将聚焦于这两点。
尽管毫无疑问心血管事件之间的关系始于低于实际使用的临界值水平,但不同的论文发现了不同的临界值。此外,根据所评估的特定心血管事件存在异质性,并且所发现的临界值均未在外部人群中进行测试(以确认其区分能力)。此外,关于降尿酸药物在降低心血管疾病风险方面作用的随机临床试验仅有少数发表,结果也各不相同。最近发表的一项研究(ALL - HEART)存在严重局限性,我们将深入讨论。
就目前已发表的论文而言,无法对这两个问题给出明确答案,但在识别当前知识空白的过程中,我们试图找出如何能够克服这些问题。