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Joint modelling of individual trajectories, within-individual variability and a later outcome: systolic blood pressure through childhood and left ventricular mass in early adulthood
George Leckie
Alun D. Hughes
Jon Heron
Kate Tilling
Richard M.A. Parker
David M. Phillippo
Laura D. Howe
Harvey Goldstein
Novel Coronavirus
Acceso Abierto
Within-individual variability of repeatedly-measured exposures may predict later outcomes: e.g. blood pressure (BP) variability (BPV) is an independent cardiovascular risk factor above and beyond mean BP. Since two-stage methods, known to introduce bias, are typically used to investigate such associations, we introduce a joint modelling approach, examining associations of both mean BP and BPV across childhood to left ventricular mass (indexed to height; LVMI) in early adulthood with data from the UK's Avon Longitudinal Study of Parents and Children (ALSPAC) cohort. Using multilevel models, we allow BPV to vary between individuals (a "random effect") as well as to depend on covariates (allowing for heteroscedasticity). We further distinguish within-clinic variability ("measurement error") from visit-to-visit BPV. BPV was predicted to be greater at older ages, at higher bodyweights, and in females, and was positively correlated with mean BP. BPV had a positive association with LVMI (10% increase in SD(BP) was predicted to increase LVMI by mean = 0.42% (95% credible interval: -0.47%, 1.38%)), but this association became negative (mean = -1.56%, 95% credible interval: -5.01%, 0.44%)) once the effect of mean BP on LVMI was adjusted for. This joint modelling approach offers a flexible method of relating repeatedly-measured exposures to later outcomes. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement R.M.A.P. was funded by the UK’s Medical Research Council (MRC) grant MR/N027485/1 awarded to investigator K.T. This work was also supported by the following grants: the MRC and the University of Bristol support the MRC Integrative Epidemiology Unit (MC_UU_00011/3); A.D.H. received support from the Wellcome Trust (086676/7/08/Z) and the British Heart Foundation (PG/06/145 & CS/15/6/31468) and works in a unit that receives support from the MRC (Programme Code MC_UU_12019/1); D.M.P. was funded by MRC grant MR/P015298/1; the UK Medical Research Council and Wellcome (Grant ref: 102215/2/13/2) and the University of Bristol provide core support for ALSPAC. This publication is the work of the authors and they will serve as guarantors for the contents of this paper. A comprehensive list of grants funding is available on the ALSPAC website ( ### Author Declarations All relevant ethical guidelines have been followed and any necessary IRB and/or ethics committee approvals have been obtained. Yes All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes Any clinical trials involved have been registered with an ICMJE-approved registry such as and the trial ID is included in the manuscript. Not Applicable I have followed all appropriate research reporting guidelines and uploaded the relevant Equator, ICMJE or other checklist(s) as supplementary files, if applicable. Not Applicable Data are available following relevant procedures for data access from Avon Longitudinal Study of Parents and Children (ALSPAC,; computing code to fit models to simulated data is provided in Appendix 3 of the Supplementary Materials.
Cold Spring Harbor Laboratory Press
Appears in Collections:Artículos científicos

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