Long-term cardiorenal illness trajectories after initiation of antihypertensive medications in adults with and without ADHD: a nationwide cohort study – Nature Mental Health

long-term-cardiorenal-illness-trajectories-after-initiation-of-antihypertensive-medications-in-adults-with-and-without-adhd:-a-nationwide-cohort-study-–-nature-mental-health

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Abstract

Adults with attention deficit hyperactivity disorder (ADHD) have a higher prevalence and incidence of hypertension, but whether long-term cardiorenal trajectories after the initiation of antihypertensive medications differ by ADHD status is unclear. Here, in this nationwide retrospective cohort study using Dutch register data, we included 706,414 new users (52.2% female, aged 18–90 years) of antihypertensive medications without prior cardiovascular disease or chronic kidney disease (CKD); 10,689 had ADHD. Multistate modelling was used to characterize long-term cardiorenal illness trajectories and compare transition-specific rates between adults with and without ADHD. Adults with ADHD had higher adjusted rates of heart failure hospitalization (HHF; hazard ratio (HR), 1.46; 95% confidence interval (CI), 1.12–1.90) and stroke (HR, 1.19; 95% CI, 1.03–1.38) after antihypertensive medication initiation. They also had higher adjusted rates of cardiorenal death after HHF (HR, 1.79; 95% CI, 1.01–3.17) or CKD (HR, 2.57; 95% CI, 1.33–4.97) onset. Ten-year trajectories through HHF or CKD to cardiorenal death were more common in adults with ADHD.

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Data availability

This study was approved by Statistics Netherlands (CBS) under project agreement 9205 microdata services research. The data contain de-identified individual-level administrative and healthcare information and are subject to legal restrictions under the Dutch Statistics Act and General Data Protection Regulation. Statistics Netherlands (CBS) acts as the data controller and imposes strict conditions on data access. Access to CBS microdata is granted only to researchers affiliated with accredited institutions following formal approval by CBS and is provided exclusively through the secure CBS Remote Access environment. The data cannot be downloaded or made publicly available. Under certain conditions, these microdata are accessible for statistical and scientific research. For further information, please contact microdata@cbs.nl.

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References

  1. Faraone, S. V. et al. Attention-deficit/hyperactivity disorder. Nat. Rev. Dis. Primers 10, 11 (2024).

    Article  PubMed  Google Scholar 

  2. Faraone, S. V. et al. The World Federation of ADHD International Consensus Statement: 208 evidence-based conclusions about the disorder. Neurosci. Biobehav. Rev. 128, 789–818 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  3. Libutzki, B., Neukirch, B., Reif, A. & Hartman, C. A. Somatic burden of attention-deficit/hyperactivity disorder across the lifecourse. Acta Psychiatr. Scand. 150, 105–117 (2024).

    Article  PubMed  Google Scholar 

  4. Li, L. et al. Attention-deficit/hyperactivity disorder as a risk factor for cardiovascular diseases: a nationwide population-based cohort study. World Psychiatry 21, 452–459 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  5. Li, L. et al. Attention-deficit/hyperactivity disorder is associated with increased risk of cardiovascular diseases: a systematic review and meta-analysis. JCPP Adv. 3, e12158 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  6. Du Rietz, E. et al. Mapping phenotypic and aetiological associations between ADHD and physical conditions in adulthood in Sweden: a genetically informed register study. Lancet Psychiat. 8, 774–783 (2021).

    Article  Google Scholar 

  7. Zhou, B., Perel, P., Mensah, G. A. & Ezzati, M. Global epidemiology, health burden and effective interventions for elevated blood pressure and hypertension. Nat. Rev. Cardiol. 18, 785–802 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  8. Olsen, M. H. et al. A call to action and a lifecourse strategy to address the global burden of raised blood pressure on current and future generations: the Lancet Commission on hypertension. Lancet 388, 2665–2712 (2016).

    Article  PubMed  Google Scholar 

  9. Campbell, N. R. C. et al. 2021. World Health Organization guideline on pharmacological treatment of hypertension: policy implications for the region of the Americas. Lancet Reg. Health Am. 9, 100219 (2022).

    PubMed  PubMed Central  Google Scholar 

  10. Williams, B. et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Cardiology (ESC) and the European Society of Hypertension (ESH). Eur. Heart J. 39, 3021–3104 (2018).

    Article  PubMed  Google Scholar 

  11. Abbasi, K. How to model life’s trajectory from major diagnosis to death. BMJ 384, q568 (2024).

    Article  Google Scholar 

  12. Murray, S. A. et al. Using illness trajectories to inform person centred, advance care planning. BMJ 384, e067896 (2024).

    Article  PubMed  Google Scholar 

  13. Andersen, P. K. & Ravn, H. Models for Multi-State Survival Data: Rates, Risks, and Pseudo-Values 1st edn (Chapman and Hall/CRC, 2023).

  14. Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int. 105, S117–S314 (2024).

  15. Visseren, F. L. J. et al. 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice. Eur. Heart J. 42, 3227–3337 (2021).

    Article  PubMed  Google Scholar 

  16. McDonagh, T. A. et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur. Heart J. 42, 3599–3726 (2021).

    Article  PubMed  Google Scholar 

  17. Cai, R., Wu, X., Li, C. & Chao, J. Prediction models for cardiovascular disease risk in the hypertensive population: a systematic review. J. Hypertens. 38, 1632–1639 (2020).

    Article  PubMed  Google Scholar 

  18. Camanni, G. et al. ‘Being disabled’ as an exclusion criterion for clinical trials: a scoping review. BMJ Glob. Health 8, e013473 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  19. Azizi, Z. et al. Challenge of optimizing medical therapy in heart failure: unlocking the potential of digital health and patient engagement. J. Am. Heart Assoc. 13, e030952 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  20. Schrauben, S. J. et al. A qualitative study of facilitators and barriers to self-management of CKD. Kidney Int. Rep. 7, 46–55 (2022).

    Article  PubMed  Google Scholar 

  21. Larsson, H. How can we improve the management of individuals with attention deficit hyperactivity disorders and co-occurring cardiometabolic disease? Expert Rev. Cardiovasc. Ther. 21, 725–728 (2023).

    Article  PubMed  Google Scholar 

  22. Yao, H. et al. ADHD and adherence to antihypertensive medication treatment: a multinational cohort study. BMC Med. 24, 122 (2026).

    Article  PubMed  PubMed Central  Google Scholar 

  23. Theodoratou, M. Communication issues in co-occurring ADHD and autism spectrum disorders. Evaluative approaches and targeted interventions: mini review. Postep. Psychiatr. Neurol. 33, 188–195 (2024).

    PubMed  PubMed Central  Google Scholar 

  24. Kendall, M. et al. Outcomes, experiences and palliative care in major stroke: a multicentre, mixed-method, longitudinal study. CMAJ 190, E238–E246 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  25. Holt, A. et al. Long-term cardiovascular risk associated with treatment of attention-deficit/hyperactivity disorder in adults. J. Am. Coll. Cardiol. 83, 1870–1882 (2024).

    Article  PubMed  Google Scholar 

  26. Goodman, D. W., Cortese, S. & Faraone, S. V. Why is ADHD so difficult to diagnose in older adults? Expert Rev. Neurother. 24, 941–944 (2024).

    Article  PubMed  Google Scholar 

  27. Gillies, M. B. et al. Medicine utilization studies in Australian individual-level dispensing data: a blinded, multi-center replicated analysis. Pharmacoepidemiol. Drug Saf. 33, e5776 (2024).

    Article  PubMed  Google Scholar 

  28. Brikell, I. et al. ADHD medication discontinuation and persistence across the lifespan: a retrospective observational study using population-based databases. Lancet Psychiat. 11, 16–26 (2024).

    Article  Google Scholar 

  29. Pouwels, K. B., Voorham, J., Hak, E. & Denig, P. Identification of major cardiovascular events in patients with diabetes using primary care data. BMC Health Serv. Res. 16, 110 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  30. Steenhuis, D., de Vos, S., Bos, J. H. J. & Hak, E. Risk factors for drug-treated major adverse cardio-cerebrovascular events in patients on primary preventive statin therapy: a retrospective cohort study. Prev. Med. Rep. 34, 102258 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  31. Steenhuis, D., Li, X., Feenstra, T. L. & Hak, E. Validation of medication proxies for the identification of hospitalizations for major adverse cerebro-cardiovascular events. Clin. Epidemiol. 17, 327–336 (2025).

    Article  PubMed  PubMed Central  Google Scholar 

  32. Li, Y. et al. Familial co-aggregation and shared heritability between neurodevelopmental problems and cardiometabolic conditions. Nat. Ment. Health 3, 1545–1554 (2025).

    Article  Google Scholar 

  33. Hrzic, R., Clemens, T., Westra, D. & Brand, H. Comparability in cross-national health research using insurance claims data: the cases of Germany and the Netherlands. Gesundheitswesen 82, S83–S90 (2020).

    Article  PubMed  Google Scholar 

  34. Suchard, M. A. et al. Comprehensive comparative effectiveness and safety of first-line antihypertensive drug classes: a systematic, multinational, large-scale analysis. Lancet 394, 1816–1826 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  35. Iacobelli, S. & Carstensen, B. Multiple time scales in multi-state models. Stat. Med. 32, 5315–5327 (2013).

    Article  PubMed  Google Scholar 

  36. Greenland, S., Mansournia, M. A. & Altman, D. G. Sparse data bias: a problem hiding in plain sight. BMJ 352, i1981 (2016).

    Article  PubMed  Google Scholar 

  37. King, G., Tomz, M. & Wittenberg, J. Making the most of statistical analyses: improving interpretation and presentation. Am. J. Pol. Sci. 44, 341–355 (2000).

    Article  Google Scholar 

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Acknowledgements

We acknowledge the services of microdata, Statistics Netherlands and all the study participants. We thank Q. Shi from the University of Groningen for his assistance with statistical analysis and interpretation.

Funding

This project received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 965381. This publication reflects only the authors’ view, and the European Commission is not responsible for any use that may be made of the information it contains. Y.Z. was supported by a joint scholarship from the China Scholarship Council and the University of Groningen. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

Author information

Author notes

  1. These authors jointly supervised this work: Harold Snieder, Catharina A. Hartman.

Authors and Affiliations

  1. Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands

    Yiling Zhou, Douwe Postmus & Harold Snieder

  2. Department of Endocrinology and Metabolism, MAGIC China Center, West China Hospital of Sichuan University, Chengdu, China

    Sheyu Li

  3. Expertisecentrum Fier, Leeuwarden, the Netherlands

    Anne van Lammeren

  4. Division of Nephrology, Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands

    Casper F. M. Franssen

  5. Interdisciplinary Center Psychopathology and Emotion Regulation, Department of Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands

    Catharina A. Hartman

Authors

  1. Yiling Zhou
  2. Douwe Postmus
  3. Sheyu Li
  4. Anne van Lammeren
  5. Casper F. M. Franssen
  6. Harold Snieder
  7. Catharina A. Hartman

Contributions

Y.Z.: conceptualization, study design, methodology, formal analysis, interpretation, writing—original draft, and writing—editing. D.P.: methodology, interpretation and writing—review and editing. S.L.: interpretation and writing—review and editing. A.v.L.: interpretation and writing—review and editing. C.F.M.F.: interpretation and writing—review and editing. H.S.: conceptualization, study design, interpretation, writing—review and editing, and supervision. C.A.H.: conceptualization, study design, interpretation, writing—review and editing, and supervision. All authors contributed to the interpretation, review and editing of the paper and approved the submission of the final version.

Corresponding authors

Correspondence to Yiling Zhou or Catharina A. Hartman.

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The authors declare no competing interests.

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Nature Mental Health thanks Howaida Elmowafi and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Zhou, Y., Postmus, D., Li, S. et al. Long-term cardiorenal illness trajectories after initiation of antihypertensive medications in adults with and without ADHD: a nationwide cohort study. Nat. Mental Health (2026). https://doi.org/10.1038/s44220-026-00718-1

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