BACKGROUND:Coarctation of the aorta (CoA) often leads to hypertension posttreatment. Evidence is lacking for the current >20 mm Hg peak-to-peak blood pressure (BP) gradient (BPGpp) guideline, which can cause aortic thickening, stiffening, and dysfunction. This study sought to find the BPGpp severity and duration that avoid persistent dysfunction in a preclinical model and test if predictors translate to hypertension status in patients with CoA.METHODS:Rabbits (n=75; 5–12/group) were exposed to mild, intermediate, or severe CoA (≤12, 13–19, ≥20 mm Hg BPGpp) for ≈1, 3, or 22 weeks using dissolvable and permanent sutures with thickening, stiffening, contraction, and endothelial function evaluated via multivariate regression. Relevance to patients with CoA (n=239; age, 0.01–46 years; median 3.7 months) was tested by retrospective review of predictors (preoperative BPGpp, surgical age, etc.) versus follow-up hypertension status.RESULTS:CoA duration and severity were predictive of aortic remodeling and active dysfunction in rabbits, and hypertension in patients with CoA. Interaction between patient age and BPGpp at surgery contributed significantly to hypertension, similar to rabbits, suggesting preclinical findings translate to patients. Machine learning decision tree analysis uncovered that preoperative BPGpp and surgical age predict risk of hypertension along with residual postoperative BPGpp.CONCLUSIONS:These findings suggest the current BPGpp threshold determined decades ago is likely too high to prevent adverse coarctation-induced aortic remodeling. The results and decision tree analysis provide a foundation for revising CoA treatment guidelines considering the interaction between CoA severity and duration to limit the risk of hypertension.

中文翻译：

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缩窄持续时间和严重程度可预测临床前模型中高血压前兆的风险和患者的高血压状态

背景：主动脉缩窄（CoA）常常导致治疗后高血压。目前缺乏证据支持 >20 mm Hg 峰峰值血压 (BP) 梯度 (BPGpp) 指南，这可能导致主动脉增厚、僵硬和功能障碍。本研究旨在寻找避免临床前模型中持续功能障碍的 BPGpp 严重程度和持续时间，并测试预测因子是否转化为 CoA 患者的高血压状态。方法：兔子（n=75；5-12/组）暴露于轻度、使用可溶解和永久缝线进行中度或重度 CoA（≤12、13-19、≥20 mm Hg BPGpp）约 1、3 或 22 周，并通过多元回归评估增厚、僵硬、收缩和内皮功能。通过预测因素（术前 BPGpp、手术年龄等）与随访高血压状态的回顾性审查来测试与 CoA 患者（n=239；年龄，0.01-46 岁；中位 3.7 个月）的相关性。 结果：CoA 持续时间和严重程度可预测家兔的主动脉重塑和活动性功能障碍，以及 CoA 患者的高血压。与兔子相似，患者年龄和手术时 BPGpp 之间的相互作用对高血压有显着影响，这表明临床前发现也适用于患者。机器学习决策树分析发现，术前 BPGpp 和手术年龄可预测高血压风险以及术后残余 BPGpp。结论：这些研究结果表明，几十年前确定的当前 BPGpp 阈值可能过高，无法防止不良缩窄引起的主动脉重塑。结果和决策树分析为修订 CoA 治疗指南提供了基础，考虑到 CoA 严重程度和持续时间之间的相互作用，以限制高血压风险。