Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon, South Korea.
Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
RMD Open. 2024 Oct 8;10(4):e004552. doi: 10.1136/rmdopen-2024-004552.
Recent studies have reported that gout is associated with a risk of cardiovascular disease (CVD) later in life. However, the predictive value of genetic predisposition to gout combined with lifestyle habits for CVD risk remains unclear. This study aimed to examine the association between genetic predisposition to gout and lifestyle habits and the risk of developing CVD in two diverse prospective cohorts from different ancestries.
A total of 224 689 participants of European descent from the UK Biobank and 50 364 participants of East Asian descent from the Korean Genome and Epidemiology Study were included. The genetic risk for gout was assessed using a polygenic risk score (PRS) derived from a meta-genome-wide association study (n=444 533). The incident CVD risk was evaluated according to genetic risk, lifestyle and metabolic syndrome (MetS).
Individuals at high genetic risk for gout had a higher risk of incident CVD than those with low genetic risk across ancestry. Notably, a reduction in CVD risk by up to 62% (HR 0.38; 95% CI 0.31 to 0.46; p <0.001) was observed in individuals at both low and high genetic risk for gout when they maintained ideal MetS and favourable lifestyle habits.
Our findings indicate that a higher genetic risk of gout is significantly associated with an increased risk of CVD. Moreover, adherence to a favourable lifestyle can significantly reduce CVD risk, particularly in individuals with high genetic risk. These results underscore the potential of PRS-based risk assessment to improve clinical outcomes through tailored preventative strategies.
最近的研究报告称，痛风与晚年发生心血管疾病（CVD）的风险有关。然而，痛风遗传易感性与生活方式相结合对 CVD 风险的预测价值仍不清楚。本研究旨在检查痛风遗传易感性与生活方式在两个不同祖源的多样化前瞻性队列中与 CVD 风险发展之间的关联。
本研究共纳入了来自英国生物银行的 224689 名欧洲血统参与者和来自韩国基因组和流行病学研究的 50364 名东亚血统参与者。痛风的遗传风险使用来自全基因组关联研究的多基因风险评分（PRS）进行评估（n=444533）。根据遗传风险、生活方式和代谢综合征（MetS）评估新发 CVD 风险。
在不同祖源的人群中，痛风遗传风险高的个体发生 CVD 的风险高于遗传风险低的个体。值得注意的是，在痛风遗传风险低和高的个体中，当他们保持理想的 MetS 和有利的生活习惯时，CVD 风险可降低高达 62%（HR 0.38；95%CI 0.31 至 0.46；p<0.001）。
我们的研究结果表明，痛风的遗传风险较高与 CVD 风险增加显著相关。此外，坚持有利的生活方式可以显著降低 CVD 风险，尤其是在遗传风险较高的个体中。这些结果强调了基于 PRS 的风险评估通过量身定制的预防策略改善临床结局的潜力。
