Department of Medical Sciences (L.L., R.Z., S.G., J.S.), Uppsala University, Sweden.
Department of Surgical Sciences (O.T., K.M.), Uppsala University, Sweden.
Circ Genom Precis Med. 2023 Dec;16(6):e004233. doi: 10.1161/CIRCGEN.123.004233. Epub 2023 Nov 28.
Proteomic profiling could potentially disclose new pathophysiological pathways for cardiovascular diseases (CVD) and improve prediction at the individual level. We therefore aimed to study the plasma protein profile associated with the incidence of different CVDs.
Plasma levels of 245 proteins suspected to be linked to CVD or metabolism were measured in 4 Swedish prospective population-based cohorts (SIMPLER [Swedish Infrastructure for Medical Population-Based Life-Course and Environmental Research], ULSAM (Uppsala Longitudinal Study of Adult Men), EpiHealth, and POEM [Prospective Investigation of Obesity, Energy Production, and Metabolism]) comprising 11 869 individuals, free of CVD diagnoses at baseline. Our primary CVD outcome was defined by a combined end point that included either incident myocardial infarction, stroke, or heart failure.
Using a discovery/validation approach, 42 proteins were associated with our primary composite end point occurring in 1163 subjects. In separate meta-analyses for each of the 3 CVD outcomes, 49 proteins were related to myocardial infarction, 34 to ischemic stroke, and 109 to heart failure. Thirteen proteins were related to all 3 outcomes. Of those, urokinase plasminogen activator surface receptor, adrenomedullin, and KIM-1 (kidney injury molecule 1) were also related to several markers of subclinical CVD in Prospective Investigation of Obesity, Energy production and Metabolism, reflecting myocardial or arterial pathologies. In prediction analysis, a lasso selection of 11 proteins in ULSAM improved the discrimination of CVD by 3.3% (<0.0001) in SIMPLER when added to traditional risk factors.
Protein profiling in multiple samples disclosed several new proteins to be associated with subsequent myocardial infarction, stroke, and heart failure, suggesting common pathophysiological pathways for these diseases. KIM-1, urokinase plasminogen activator surface receptor, and adrenomedullin were novel early markers of CVD. A selection of 11 proteins improved the discrimination of CVD.
蛋白质组学分析可能揭示心血管疾病（CVD）新的病理生理途径，并改善个体水平的预测。因此，我们旨在研究与不同 CVD 发病相关的血浆蛋白谱。
在 4 个瑞典前瞻性人群为基础的队列（SIMPLER[瑞典人口为基础的生活过程和环境医学研究的基础设施]、ULSAM（乌普萨拉男性纵向研究）、EpiHealth 和 POEM[肥胖症、能量产生和代谢的前瞻性研究]）中，测量了 245 种疑似与 CVD 或代谢相关的蛋白质的血浆水平，共纳入了 11869 名无 CVD 诊断的个体。我们的主要 CVD 结局定义为一个复合终点，包括新发心肌梗死、卒中和心力衰竭。
使用发现/验证方法，在 1163 例患者中，有 42 种蛋白质与我们的主要复合终点相关。在针对 3 种 CVD 结局的单独荟萃分析中，有 49 种蛋白质与心肌梗死相关，34 种与缺血性卒中和 109 种与心力衰竭相关。有 13 种蛋白质与所有 3 种结局相关。其中，尿激酶型纤溶酶原激活物表面受体、肾上腺髓质素和 KIM-1（肾损伤分子 1）与肥胖症、能量产生和代谢的前瞻性研究中的几种亚临床 CVD 标志物相关，反映了心肌或动脉的病理变化。在预测分析中，ULSAM 中的 11 种蛋白质的lasso 选择在 SIMPLER 中添加到传统危险因素后，提高了 CVD 的区分度 3.3%（<0.0001）。
在多个样本中的蛋白质谱分析揭示了几种与随后的心肌梗死、卒中和心力衰竭相关的新蛋白质，表明这些疾病存在共同的病理生理途径。KIM-1、尿激酶型纤溶酶原激活物表面受体和肾上腺髓质素是 CVD 的新型早期标志物。11 种蛋白质的选择提高了 CVD 的区分度。
