AimsBiomarkers associated with asymptomatic ventricular dysfunction might improve risk stratification and identify pathways leading to heart failure (HF). We explored the association between proteomic biomarkers and left ventricular hypertrophy (LVH), diastolic dysfunction (DD) and incident HF in three population‐based cohorts.Methods and resultsA chip was used to measure 92 protein biomarkers in blood samples from >1500 Malmö Preventive Project (MPP) participants, of whom 514 had LVH (34%), 462 had DD (32.4%) and, over a median follow‐up of 13 (11–14) years, 130 developed HF (7.7%). Findings were confirmed in the STANISLAS (n > 1500, 238 participants with LVH, 76 with DD) and HOMAGE case‐control (562 cases of incident HF, 871 controls) cohorts. In multivariable logistic or Cox regression analyses adjusted for age, sex and cardiovascular risk factors, N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) was associated with LVH, DD and incident HF in all cohorts: MPP (LVH odds ratio [OR] [95% confidence interval] 1.48 [1.28–1.71]; DD OR 1.71 [1.53–1.92]; HF HR 1.98 [1.66–2.36]); STANISLAS (LVH OR 1.20 [1.02–1.41]; DD OR 1.46 [1.12–1.90]); HOMAGE (HF HR 1.85 [1.62–2.12]). Galectin‐4, growth differentiation factor 15 and suppression of tumorigenicity‐2 were associated with incident HF in MPP and HOMAGE. A pathway enrichment analysis suggested that inflammation and viral infection were related to incident HF.ConclusionIn conclusion, our study reinforces the role of NT‐proBNP as a key biomarker for asymptomatic cardiac dysfunction and incident HF, consistent with its established use in clinical practice. This underscores the value of NT‐proBNP for identifying patients at high risk for HF, and provides insights into pathways leading to HF and potential therapeutic targets.

中文翻译：

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三个流行病学代表性队列中进展为心力衰竭的蛋白质组学生物标志物和通路分析


Aims与无症状心室功能障碍相关的生物标志物可能会改善风险分层并确定导致心力衰竭 （HF） 的途径。我们在三个基于人群的队列中探讨了蛋白质组学生物标志物与左心室肥大 （LVH） 、舒张功能障碍 （DD） 和新发 HF 之间的关联。方法和结果使用芯片测量 >1500 名马尔默预防项目 （MPP） 参与者血液样本中的 92 种蛋白质生物标志物，其中 514 名患有 LVH （34%），462 名患有 DD （32.4%），在中位随访 13 （11-14） 年期间，130 名患上了 HF （7.7%）。在 STANISLAS （n > 1500,238 名 LVH 参与者，76 名 DD 参与者）和 HOMAGE 病例对照 （562 例 HF 新发病例，871 名对照）队列中证实了研究结果。在针对年龄、性别和心血管危险因素调整的多变量 logistic 或 Cox 回归分析中，在所有队列中，N 末端 B 型利钠肽前体 （NT-proBNP） 与 LVH、DD 和新发 HF 相关：MPP（LVH 比值比 [OR] [95% 置信区间] 1.48 [1.28–1.71];DD OR 1.71 [1.53–1.92];HF HR 1.98 [1.66–2.36]）;斯坦尼斯拉斯 （LVH OR 1.20 [1.02–1.41];DD OR 1.46 [1.12–1.90]）;致敬 （HF HR 1.85 [1.62–2.12]）。半乳糖凝集素-4 、生长分化因子 15 和致瘤性抑制-2 与 MPP 和 HOMAGE 中发生 HF 相关。通路富集分析表明，炎症和病毒感染与心力衰竭的发生有关。结论总之，我们的研究加强了 NT-proBNP 作为无症状心功能不全和新发 HF 的关键生物标志物的作用，与其在临床实践中的既定用途一致。 这强调了 NT-proBNP 在识别 HF 高危患者方面的价值，并为导致 HF 的途径和潜在治疗靶点提供了见解。