Research Centre, Montreal Heart Institute, Université de Montréal, Montreal, Quebec, Canada.
Research Centre, Montreal Heart Institute, Université de Montréal, Montreal, Quebec, Canada.
Am J Cardiol. 2023 Jan 1;186:11-16. doi: 10.1016/j.amjcard.2022.09.029. Epub 2022 Nov 3.
In aortic stenosis (AS), left ventricular (LV) remodeling often occurs before symptom onset, and early intervention may be beneficial. Risk stratification remains challenging and identification of biomarkers may be useful. We evaluated the association between growth differentiation factor-15 (GDF-15) and soluble suppression of tumorigenicity 2 (sST2) and known markers of poor prognosis in AS. Baseline plasma GDF-15 and sST2 levels were measured in 70 patients with moderate-severe AS (aortic valve area <1.5 cm) and preserved LV ejection fraction (>45%). Patients were categorized into "low GDF-15" versus "high GDF-15" and "low sST2" versus "high sST2" groups. Groups were compared for differences in cardiovascular risk factors, 6-minute walk test, 5 m gait speed, cognitive function (Montreal Cognitive Assessment), and echocardiographic parameters. Overall, 44% of patients were deemed asymptomatic by New York Heart Association class, 61% had severe AS (aortic valve area <1 cm) and all patients had preserved LV ejection fraction. GDF-15 levels were not predictive of AS severity. However, high GDF-15 (>1,050 pg/ml) was associated with LV dysfunction as shown by lower indexed stroke volume (p <0.01), worse LV global longitudinal strain (p = 0.04), greater mean E/e' (p = 0.02) and indexed left atrial volume (p <0.01). It was also associated with decreased functional capacity with shorter 6-minute walk test (p = 0.01) and slower 5 m gait speed (p = 0.02). Associations between sST2 levels and markers of poor prognosis were less compelling. In this study of patients with moderate to severe AS, elevated GDF-15 levels are associated with impaired functional capacity, poorer performance on fragility testing, and LV dysfunction. In conclusion, GDF-15 may integrate these markers of adverse outcomes into a single biomarker of poor prognosis.
在主动脉瓣狭窄（AS）中，左心室（LV）重构通常在症状出现之前发生，早期干预可能有益。风险分层仍然具有挑战性，生物标志物的识别可能有用。我们评估了生长分化因子-15（GDF-15）和可溶性肿瘤抑制物 2（sST2）与 AS 预后不良的已知标志物之间的相关性。在 70 例中重度 AS（主动脉瓣面积<1.5cm）和保留的 LV 射血分数（>45%）患者中测量了基线血浆 GDF-15 和 sST2 水平。将患者分为“低 GDF-15”与“高 GDF-15”和“低 sST2”与“高 sST2”组。比较两组间心血管危险因素、6 分钟步行试验、5 米步行速度、认知功能（蒙特利尔认知评估）和超声心动图参数的差异。总体而言，44%的患者按纽约心脏协会（NYHA）分级为无症状，61%的患者为严重 AS（主动脉瓣面积<1cm），所有患者均保留 LV 射血分数。GDF-15 水平不能预测 AS 的严重程度。然而，高 GDF-15（>1050pg/ml）与 LV 功能障碍相关，表现为较低的指数化 stroke volume（p<0.01）、较差的 LV 整体纵向应变（p=0.04）、较大的平均 E/e'（p=0.02）和指数化左心房容积（p<0.01）。它还与功能能力下降相关，6 分钟步行试验（p=0.01）和 5 米步行速度（p=0.02）更短。sST2 水平与预后不良标志物之间的相关性不那么明显。在这项对中重度 AS 患者的研究中，升高的 GDF-15 水平与功能能力受损、脆弱性测试表现较差和 LV 功能障碍相关。总之，GDF-15 可能将这些不良结局标志物整合到单一的预后不良生物标志物中。
