Multivariate longitudinal data for survival analysis of cardiovascular event prediction in young adults: insights from a comparative explainable study

Hieu T. Nguyen, Henrique D. Vasconcellos, Kimberley Keck, Jared P. Reis, Cora E. Lewis, Steven Sidney, Donald M. Lloyd-Jones, Pamela J. Schreiner, Eliseo Guallar, Colin O. Wu, João A.C. Lima, Bharath Ambale-Venkatesh

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Background: Multivariate longitudinal data are under-utilized for survival analysis compared to cross-sectional data (CS - data collected once across cohort). Particularly in cardiovascular risk prediction, despite available methods of longitudinal data analysis, the value of longitudinal information has not been established in terms of improved predictive accuracy and clinical applicability. Methods: We investigated the value of longitudinal data over and above the use of cross-sectional data via 6 distinct modeling strategies from statistics, machine learning, and deep learning that incorporate repeated measures for survival analysis of the time-to-cardiovascular event in the Coronary Artery Risk Development in Young Adults (CARDIA) cohort. We then examined and compared the use of model-specific interpretability methods (Random Survival Forest Variable Importance) and model-agnostic methods (SHapley Additive exPlanation (SHAP) and Temporal Importance Model Explanation (TIME)) in cardiovascular risk prediction using the top-performing models. Results: In a cohort of 3539 participants, longitudinal information from 35 variables that were repeatedly collected in 6 exam visits over 15 years improved subsequent long-term (17 years after) risk prediction by up to 8.3% in C-index compared to using baseline data (0.78 vs. 0.72), and up to approximately 4% compared to using the last observed CS data (0.75). Time-varying AUC was also higher in models using longitudinal data (0.86–0.87 at 5 years, 0.79–0.81 at 10 years) than using baseline or last observed CS data (0.80–0.86 at 5 years, 0.73–0.77 at 10 years). Comparative model interpretability analysis revealed the impact of longitudinal variables on model prediction on both the individual and global scales among different modeling strategies, as well as identifying the best time windows and best timing within that window for event prediction. The best strategy to incorporate longitudinal data for accuracy was time series massive feature extraction, and the easiest interpretable strategy was trajectory clustering. Conclusion: Our analysis demonstrates the added value of longitudinal data in predictive accuracy and epidemiological utility in cardiovascular risk survival analysis in young adults via a unified, scalable framework that compares model performance and explainability. The framework can be extended to a larger number of variables and other longitudinal modeling methods. Trial registration: Identifier: NCT00005130, Registration Date: 26/05/2000.

Original languageEnglish (US)
Article number23
JournalBMC Medical Research Methodology
Issue number1
StatePublished - Dec 2023

Bibliographical note

Funding Information:
The Coronary Artery Risk Development in Young Adults Study (CARDIA) is conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with the University of Alabama at Birmingham (HHSN268201800005I & HHSN268201800007I), Northwestern University (HHSN268201800003I), University of Minnesota (HHSN268201800006I), and Kaiser Foundation Research Institute (HHSN268201800004I). This manuscript has been reviewed by CARDIA for scientific content.

Funding Information:
This manuscript has been reviewed by CARDIA for scientific content. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the U.S. Department of Health and Human Services.

Publisher Copyright:
© 2023, The Author(s).


  • Explainable AI
  • Longitudinal data
  • Personalized medicine
  • Repeated measures
  • Risk prediction
  • SHAP
  • Survival analysis
  • TIME
  • Time-varying covariates

PubMed: MeSH publication types

  • Clinical Study
  • Journal Article
  • Research Support, N.I.H., Extramural


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