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一种基于模拟的框架,用于对高血压患者降压治疗后的个性化血压轨迹进行建模和预测。

A simulation-based framework for modeling and prediction of personalized blood pressure trajectories in hypertensive patients after antihypertensive treatment.

作者信息

Hunsdieck Berit, Mielke Johanna, Ickstadt Katja, Elçi Eren

机构信息

Bayer AG, Research & Early Development, Division Pharmaceuticals, Wuppertal, Germany.

Department of Statistics, TU Dortmund University, Dortmund, Germany.

出版信息

PLoS One. 2025 Apr 10;20(4):e0318549. doi: 10.1371/journal.pone.0318549. eCollection 2025.

Abstract

Hypertension, a leading global cause of death, poses challenges in stabilizing blood pressure within target values despite various therapeutic options, often necessitating multiple therapy adjustments and delayed impact assessments. Recently, the first wrist-based wearable blood pressure measurement devices were introduced which allow for a continuous assessment of blood pressure trajectories. This enables the development of statistical methodology for prediction of saturated steady-state of blood pressure under treatment-and thus allowing physicians to adjust the therapy earlier. As a prerequisite for the evaluation of such models and algorithms, it is necessary to simulate reliable and realistic hypothetical patient trajectories under treatment with antihypertensive medication. In this paper, we propose a simulation framework for blood pressure profiles through Pharmacokinetic-Pharmacodynamic modeling, which incorporates individual daily rhythms, patient characteristics, and medication effects. We also propose and evaluate two models for steady-state prediction under antihypertensive therapy, a Gaussian process and a non-linear mixed effect model. When only one day of measurements is available, the Gaussian process is preferred, but in real-world situations with more data, the non-linear mixed effect model is favored. It effectively reduces RMSE and bias in noisy data, outperforming the Gaussian process regardless of sample size.

摘要

高血压是全球主要的死亡原因之一,尽管有多种治疗选择,但在将血压稳定在目标值方面仍面临挑战,通常需要多次调整治疗方案并延迟疗效评估。最近,首批基于手腕的可穿戴血压测量设备问世,可对血压轨迹进行连续评估。这有助于开发统计方法,以预测治疗下血压的饱和稳态,从而使医生能够更早地调整治疗方案。作为评估此类模型和算法的前提条件,有必要模拟使用抗高血压药物治疗时可靠且现实的假设患者轨迹。在本文中,我们通过药代动力学-药效学建模提出了一个血压曲线模拟框架,该框架纳入了个体日常节律、患者特征和药物作用。我们还提出并评估了两种抗高血压治疗下稳态预测模型,即高斯过程模型和非线性混合效应模型。当只有一天的测量数据时,高斯过程模型更受青睐,但在有更多数据的实际情况中,非线性混合效应模型更具优势。它能有效降低噪声数据中的均方根误差(RMSE)和偏差,无论样本量大小,其表现均优于高斯过程模型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d665/11984981/b27cc478f162/pone.0318549.g001.jpg

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