A different perspective on studying stroke predictors: joint models for longitudinal and time-to-event data in a type 2 diabetes mellitus cohort

TL;DR

This study uses joint models to predict stroke or TIA in type 2 diabetes patients by combining longitudinal data and survival analysis.

Contribution

The novelty lies in using joint models to dynamically adjust stroke/TIA predictions based on changing patient data over time.

Findings

Age, atrial fibrillation, and systolic blood pressure were significant predictors in both sexes.

Renal function was a significant predictor only in women.

An increase in diastolic blood pressure may act as a protective factor in the cohort.

Abstract

Most predictive models rely on risk factors and clinical outcomes assessed simultaneously. This approach does not adequately reflect the progression of health conditions. By employing joint models of longitudinal and survival data, we can dynamically adjust prognosis predictions for individual patients. Our objective was to optimize the prediction of stroke or transient ischemic attack (TIA) via joint models that incorporate all available changes in the predictive variables.

A total of 3442 patients with type 2 diabetes mellitus (T2DM) and no history of stroke, TIA or myocardial infarction were followed for 12 years. Models were constructed independently for men and women. We used proportional hazards regression models to assess the effects of baseline characteristics (excluding longitudinal data) on the risk of stroke/TIA and linear mixed effects models to assess the effects of baseline characteristics on longitudinal data development over time. Both submodels were then combined into a joint model. To optimize the analysis, a univariate analysis was first performed for each longitudinal predictor to select the functional form that gave the best fit via the deviance information criterion. The variables were then entered into a multivariate model using pragmatic criteria, and if they improved the discriminatory ability of the model, the area under the curve (AUC) was used.

During the follow-up period, 303 patients (8.8%) experienced their first stroke/TIA. Age was identified as an independent predictor among males. Among females, age was positively associated with atrial fibrillation (AF). The final model for males included AF, systolic blood pressure (SBP), and diastolic blood pressure (DBP), with albuminuria and the glomerular filtration rate (GFR) as adjustment variables. For females, the model included AF, blood pressure (BP), and renal function (albuminuria and GFR), with HbA1c and LDL cholesterol as adjustment variables. Both models demonstrated an AUC greater than 0.70.

Age, AF, and SBP have been confirmed as significant predictive factors in both sexes, whereas renal function was significant only in women. Interestingly, an increase in DBP may serve as a protective factor in our cohort. These factors were particularly relevant in the last 3–7 years of follow-up.

The online version contains supplementary material available at 10.1186/s12933-025-02713-9.

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