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期刊来源：Nat Med

原文链接：https://doi.org/10.1038/s41591-024-03039-x

摘要内容如下：

尽管心肺适应性（CRF）对代谢、心血管、肺和神经健康具有广泛的影响，但CRF测量的可行性和可重复性方面的挑战阻碍了其在临床决策中的应用。在这里，我们将四个国际队列中的14，145名个体的蛋白质组图谱与CRF联系起来，使用不同的CRF确定方法来建立、验证和表征蛋白质组CRF评分。在英国生物库（UK Biobank）的一个约22，000人的队列中，蛋白质组CRF评分与全因死亡率风险降低相关（未调整的风险比为0.50（95%置信区间0.48-0.52）/1s.d.增加）。蛋白质组CRF评分也与多系统疾病风险相关，并提供临床风险因素之外的风险重新分类和区分，以及调节某些疾病的高多基因风险。最后，我们观察了接受20周运动训练计划的个体的蛋白质组CRF评分的动态性，以及该评分与训练对CRF的影响程度之间的关联，表明该评分可能用于个性化的运动建议。这些结果表明，基于群体的蛋白质组学提供了CRF的生物学相关分子读数，这些读数可增加遗传风险，具有潜在的可修改性和临床可译性。

英文原文如下：

Abstracts

Despite the wide effects of cardiorespiratory fitness (CRF) on metabolic, cardiovascular, pulmonary and neurological health, challenges in the feasibility and reproducibility of CRF measurements have impeded its use for clinical decision-making. Here we link proteomic profiles to CRF in 14,145 individuals across four international cohorts with diverse CRF ascertainment methods to establish, validate and characterize a proteomic CRF score. In a cohort of around 22,000 individuals in the UK Biobank, a proteomic CRF score was associated with a reduced risk of all-cause mortality (unadjusted hazard ratio 0.50 (95% confidence interval 0.48-0.52) per 1 s.d. increase). The proteomic CRF score was also associated with multisystem disease risk and provided risk reclassification and discrimination beyond clinical risk factors, as well as modulating high polygenic risk of certain diseases. Finally, we observed dynamicity of the proteomic CRF score in individuals who undertook a 20-week exercise training program and an association of the score with the degree of the effect of training on CRF, suggesting potential use of the score for personalization of exercise recommendations. These results indicate that population-based proteomics provides biologically relevant molecular readouts of CRF that are additive to genetic risk, potentially modifiable and clinically translatable.

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