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Hauptverfasser: Courcoul, Léonie, Tzourio, Christophe, Woodward, Mark, Barbieri, Antoine, Jacqmin-Gadda, Hélène
Format: Preprint
Veröffentlicht: 2023
Schlagworte:
Online-Zugang:https://arxiv.org/abs/2306.16785
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author Courcoul, Léonie
Tzourio, Christophe
Woodward, Mark
Barbieri, Antoine
Jacqmin-Gadda, Hélène
author_facet Courcoul, Léonie
Tzourio, Christophe
Woodward, Mark
Barbieri, Antoine
Jacqmin-Gadda, Hélène
contents Given the high incidence of cardio and cerebrovascular diseases (CVD), and its association with morbidity and mortality, its prevention is a major public health issue. A high level of blood pressure is a well-known risk factor for these events and an increasing number of studies suggest that blood pressure variability may also be an independent risk factor. However, these studies suffer from significant methodological weaknesses. In this work we propose a new location-scale joint model for the repeated measures of a marker and competing events. This joint model combines a mixed model including a subject-specific and time-dependent residual variance modeled through random effects, and cause-specific proportional intensity models for the competing events. The risk of events may depend simultaneously on the current value of the variance, as well as, the current value and the current slope of the marker trajectory. The model is estimated by maximizing the likelihood function using the Marquardt-Levenberg algorithm. The estimation procedure is implemented in a R-package and is validated through a simulation study. This model is applied to study the association between blood pressure variability and the risk of CVD and death from other causes. Using data from a large clinical trial on the secondary prevention of stroke, we find that the current individual variability of blood pressure is associated with the risk of CVD and death. Moreover, the comparison with a model without heterogeneous variance shows the importance of taking into account this variability in the goodness-of-fit and for dynamic predictions.
format Preprint
id arxiv_https___arxiv_org_abs_2306_16785
institution arXiv
publishDate 2023
record_format arxiv
spellingShingle A location-scale joint model for studying the link between the time-dependent subject-specific variability of blood pressure and competing events
Courcoul, Léonie
Tzourio, Christophe
Woodward, Mark
Barbieri, Antoine
Jacqmin-Gadda, Hélène
Methodology
Given the high incidence of cardio and cerebrovascular diseases (CVD), and its association with morbidity and mortality, its prevention is a major public health issue. A high level of blood pressure is a well-known risk factor for these events and an increasing number of studies suggest that blood pressure variability may also be an independent risk factor. However, these studies suffer from significant methodological weaknesses. In this work we propose a new location-scale joint model for the repeated measures of a marker and competing events. This joint model combines a mixed model including a subject-specific and time-dependent residual variance modeled through random effects, and cause-specific proportional intensity models for the competing events. The risk of events may depend simultaneously on the current value of the variance, as well as, the current value and the current slope of the marker trajectory. The model is estimated by maximizing the likelihood function using the Marquardt-Levenberg algorithm. The estimation procedure is implemented in a R-package and is validated through a simulation study. This model is applied to study the association between blood pressure variability and the risk of CVD and death from other causes. Using data from a large clinical trial on the secondary prevention of stroke, we find that the current individual variability of blood pressure is associated with the risk of CVD and death. Moreover, the comparison with a model without heterogeneous variance shows the importance of taking into account this variability in the goodness-of-fit and for dynamic predictions.
title A location-scale joint model for studying the link between the time-dependent subject-specific variability of blood pressure and competing events
topic Methodology
url https://arxiv.org/abs/2306.16785