Background:Increased left ventricular (LV) mass is associated with adverse cardiovascular events including heart failure (HF). Both increased LV mass and HF disproportionately affect Black individuals. To understand the underlying mechanisms, we undertook a proteomic screen in a Black cohort and compared the findings to results from a White cohort.Methods:We measured 1305 plasma proteins using the SomaScan platform in 1772 Black participants (mean age, 56 years; 62% women) in JHS (Jackson Heart Study) with LV mass assessed by 2-dimensional echocardiography. Incident HF was assessed in 1600 participants. We then compared protein associations in JHS to those observed in White participants from FHS (Framingham Heart Study; mean age, 54 years; 56% women).Results:In JHS, there were 110 proteins associated with LV mass and 13 proteins associated with incident HF hospitalization with false discovery rate <5% after multivariable adjustment. Several proteins showed expected associations with both LV mass and HF, including NT-proBNP (N-terminal pro-B-type natriuretic peptide; β=0.04; P=2×10⁻⁸; hazard ratio, 1.48; P=0.0001). The strongest association with LV mass was novel: LKHA4 (leukotriene-A4 hydrolase; β=0.05; P=5×10⁻¹⁵). This association was confirmed on an alternate proteomics platform and further supported by related metabolomic data. Fractalkine/CX3CL1 (C-X3-C Motif Chemokine Ligand 1) showed a novel association with incident HF (hazard ratio, 1.32; P=0.0002). While established biomarkers such as cystatin C and NT-proBNP showed consistent associations in Black and White individuals, LKHA4 and fractalkine were significantly different between the two groups.Conclusions:We identified several novel biological pathways specific to Black adults hypothesized to contribute to the pathophysiologic cascade of LV hypertrophy and incident HF including LKHA4 and fractalkine.

中文翻译：

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黑人和白人群体的多组学分析揭示了针对黑人成年人的左心室肥大和心力衰竭事件的新候选途径

背景：左心室 (LV) 质量增加与包括心力衰竭 (HF) 在内的不良心血管事件相关。增加的 LV 质量和 HF 不成比例地影响黑人个体。为了了解潜在机制，我们在一个黑人队列中进行了蛋白质组学筛选，并将结果与​​来自白人队列的结果进行了比较。方法：我们使用 SomaScan 平台测量了 1772 名黑人参与者（平均年龄 56 岁；62%）的 1305 种血浆蛋白女性）在 JHS（杰克逊心脏研究）中，通过二维超声心动图评估 LV 质量。在 1600 名参与者中评估了事件 HF。然后，我们将 JHS 中的蛋白质关联与 FHS 的白人参与者中观察到的蛋白质关联进行了比较（弗雷明汉心脏研究；平均年龄，54 岁；56% 的女性）。结果：在 JHS，多变量调整后，有 110 种蛋白质与 LV 质量相关，13 种蛋白质与心衰住院相关，错误发现率 <5%。几种蛋白质显示出与 LV 质量和 HF 的预期关联，包括 NT-proBNP（N 端 pro-B 型利钠肽；β=0.04；P =2×10 ^-8；风险比，1.48；P = 0.0001)。与 LV 质量最强的关联是新的：LKHA4（白三烯-A4 水解酶；β=0.05；P =5×10 ^-15）。这种关联在替代蛋白质组学平台上得到证实，并得到相关代谢组学数据的进一步支持。Fractalkine/CX3CL1（C-X3-C Motif 趋化因子配体 1）显示出与 HF 事件的新关联（风险比，1.32；P=0.0002)。虽然已建立的生物标志物（如 胱抑素 C 和 NT-proBNP）在黑人和白人个体中显示出一致的关联，但 LKHA4 和 fractalkine 在两组之间存在显着差异。结论：我们确定了几种新的针对黑人成年人的新生物学途径，这些途径假设有助于病理生理级联反应LV 肥大和偶发性 HF，包括 LKHA4 和 fractalkine。