Background Exploring longitudinal associations of blood biomarkers with left atrial (LA) structure and function can enhance our understanding of atrial fibrillation (AF) etiopathogenesis. Methods We studied 532 participants of the PREDIMED-Plus trial, a multicenter randomized trial in overweight and obese adults with metabolic syndrome. At baseline, 3 and 5 years after randomization, participants underwent transthoracic echocardiography and provided blood for serum biomarker measurements [propeptide of procollagen type I (PICP), high-sensitivity (hs) troponin T (hsTnT), hs C-reactive protein (hsCRP), 3-nitrotyrosine (3-NT), and N-terminal propeptide of B-type natriuretic peptide (NT-proBNP)]. Outcomes of interest included LA peak systolic longitudinal strain (LA PSLS), LA volume index (LAVi), LA function index (LAFi), and LA stiffness index (LASi). We performed cross-sectional and longitudinal analyses to evaluate relationships between log-transformed biomarkers and echocardiographic measurements using multiple linear regression and mixed models. Results The participants in this analysis had a mean age of 65 (SD 4.8) years, and 40% were females. At baseline, increased NT-proBNP and hsTnT were associated with larger LAVi and worse LA function as measured by the LAFi, LASi, and LA PSLS. Longitudinally, higher NT-proBNP, but not higher hsTnT, was associated with increased LAVi and worsening LA function. Over 5 years, 1 unit increase in log(NT-proBNP) was associated with a steeper decline in LA PSLS (-0.19%, 95% CI -0.35%, -0.02%) and a greater increase in LAVi (0.28 mL/m2, 95% CI 0.10, 0.45) each year. PICP, hsCRP, and 3-NT did not show consistently significant associations with LA outcomes at baseline and through 5 years. Conclusion In an overweight and obese population, higher NT-proBNP was associated with LA volume enlargement and worsening LA function over 5 years. The implications of these findings for the prevention and prediction of AF warrant further investigation.

The authors have declared no competing interest.

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Research reported in this publication was supported by the National Heart, Lung, And Blood Institute of the National Institutes of Health under Award Number R01HL137338. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Linzi Li was supported by the American Heart Association Predoctoral Fellowship 23PRE1020888. The PREDIMED-Plus trial was supported by the official funding agency for biomedical research of the Spanish government, ISCIII, through the Fondo de Investigacion para la Salud (FIS), which is co-funded by the European Regional Development Fund (PI13/00673, PI13/00492, PI13/00272, PI13/01123, PI13/00462, PI13/00233, PI13/02184, PI13/00728, PI13/01090, PI13/01056, PI14/01722, PI14/0147, PI14/00636, PI14/00972, PI14/00618, PI14/00696, PI14/01206, PI14/01919, PI14/00853, PI14/01374, PI16/00473, PI16/00662, PI16/01873, PI16/01094, PI16/00501, PI16/00533, PI16/00381, PI16/00366, PI16/01522, PI16/01120, PI17/00764, PI17/01183, PI17/00855, PI17/01347, PI17/00525, PI17/01827, PI17/00532, PI17/00215, PI17/01441, PI17/00508, PI17/01732, PI17/00926, PI19/00957, PI19/00386, PI19/00309, PI19/01032, PI19/00576, PI19/00017, PI19/01226, PI19/00781, PI19/01560, PI19/01332), the European Research Council Advanced Research Grant 2013-2018 (340918), the Recercaixa grant 2013ACUP00194, grants from the Consejeria de Salud de la Junta de Andalucia (PI0458/2013; PS0358/2016, PI0137/2018), the PROMETEO/2017/017 grant from the Generalitat Valenciana, the SEMERGEN grant and FEDER funds (CB06/03).

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The PREDIMED-Plus study was approved by the ethics research committee of all study centers and this analysis was approved by the Institutional Review Board at Emory University. Participants provided written informed consent at each visit.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

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I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

Data collaboration for PREDIMED-Plus study is guided by the Data Sharing and Management guide. We follow a controlled data collaboration model, using anonymised (de-identified) study data only, for collaborating with approved researchers. Requests are considered by the PREDIMED-Plus Steering Committee. Please see https://www.predimedplus.com/en/project/#top for detail.

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