Major adverse cardiovascular events and mortality associated with ADHD and its treatment in adults with hypertension: a retrospective, multinational cohort study
Year: 2026
Type: article
Study design: Observational Study
Abstract: Background Adults with attention-deficit hyperactivity disorder (ADHD) have increased cardiometabolic risk. Hypertension increases the risk of major adverse cardiovascular events (MACE). We aimed to investigate whether ADHD is associated with MACE and all-cause mortality among adults with hypertension and assess medication safety among adults with ADHD and hypertension. Methods We conducted a retrospective, multinational cohort study across seven settings (Australia, England, Denmark, the Netherlands, Norway, Sweden, and the USA) using distributed network analyses with a common protocol. We included adults aged 18–90 years initiating first-line antihypertensive medications between Jan 1, 2010, and Dec 31, 2020 (depending on data availability); individuals with previous cardiovascular disease were excluded. Primary outcomes were incident MACE (composite of myocardial infarction, stroke, and cardiovascular death) and all-cause mortality. We estimated cause-specific hazard ratios (HRs) using Cox models with ADHD as a time-varying exposure. In a secondary analysis among adults with ADHD, we estimated HRs with ADHD medication use as a time-varying exposure. We pooled country-specific estimates using a random-effects meta-analysis. Findings Among 5 843 667 adults initiating first-line antihypertensives (2 980 617 [51·0%] were female and 2 863 050 [49·0%] were male; median follow-up ranged from 2·72 years [IQR 0·96–5·43] in the USA to 5·51 years [2·57–8·49] in Denmark), 113 397 (1·9%) had ADHD. Race and ethnicity data were not available. Unadjusted incidence rates among adults with and without ADHD were 9·8 (95% CI 9·5–10·2) per 1000 person-years and 11·1 (11·1–11·2) per 1000 person-years for MACE, and 8·6 (8·3–8·9) per 1000 person-years and 8·5 (8·4–8·5) per 1000 person-years for all-cause mortality, respectively. In pooled analyses, ADHD was associated with higher rates of MACE (HR 1·31 [95% CI 1·18–1·45]) and all-cause mortality (2·83 [2·07–3·87]) after adjusting for sex, age, and calendar year of first-line antihypertensive treatment initiation. In further controlled analyses, these associations attenuated after including psychiatric and cardiometabolic comorbidities and changed little after further including antihypertensive medication use during follow-up, indicating the relevance of comorbidity for prognosis. In pooled analyses among adults with ADHD, ADHD medication use was not associated with MACE (HR 1·00 [95% CI 0·85–1·17]) or all-cause mortality (0·96 [0·76–1·22]). Interpretation Among adults initiating antihypertensive treatment, ADHD marks a clinically vulnerable subgroup that might benefit from primary care combining routine hypertension care with adherence support and assessment and management of psychiatric and behavioural risk factors. Within the ADHD population, ADHD medication use was not associated with MACE, providing some reassurance regarding ADHD medication use in this population at increased cardiovascular risk under current clinical practice. Funding EU Horizon 2020 Research and Innovation Programme.
Source: The Lancet Primary Care
Authors: Yiling Zhou, Zihan Dong, Aske Astrup, Anders Engeland, Malcolm B Gillies, Astrid Lunde, Andrew S C Yuen, Yanli Zhang-James, Masako Araki, Isabell Brikell, Le Gao, Jan Haavik, Brian M D’Onofrio, Dina Sarsembayeva, Melissa Vos, Theresa Wimberley, Honghui Yao, Søren Dalsgaard, Stephen V Faraone, Kari Klungsøyr, Henrik Larsson, Kenneth K C Man, Sallie-Anne Pearson, Ian C K Wong, Helga Zoega, Zheng Chang, Ebba Du Rietz, Harold Snieder, Catharina A Hartman
Institutions: University Medical Center Groningen, University of Groningen, Karolinska Institutet, Aarhus University, Norwegian Institute of Public Health, University of Bergen, UNSW Sydney, National Health Service, University College Hospital, University College London Hospitals NHS Foundation Trust, UCL School of Pharmacy, University College London, SUNY Upstate Medical University, Xi'an Jiaotong University, University of Hong Kong, Haukeland University Hospital, Indiana University Bloomington, Indiana University, Second Xiangya Hospital of Central South University, University of Copenhagen, Mental Health Services, Copenhagen University Hospital, Örebro University, Macau University of Science and Technology, Aston University, University of Iceland
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $6,680
Funders: Jeanssons Stiftelser, Savvaerksejer Jeppe Juhl og Hustru Ovita Juhls Mindelegat, Supernus Pharmaceuticals, Upstate Foundation, Svenska Sällskapet för Medicinsk Forskning, China Scholarship Council, NordForsk, Greater Copenhagen Health Science Partners, National Institutes of Health, Horizon 2020 Framework Programme, National Health and Medical Research Council, National Institute of Mental Health, National Institute of Arthritis and Musculoskeletal and Skin Diseases
Awards: G1643414495, G2280845943, G3693693, G585089319, Discoveries in ADHD genomics: Help or hype in clinical settings?, G6339633103, Leveraging Nordic Opportunities to Transform Mental Health Care through Precision Medicine (PreciMENT), G7554036688, Polygenic and environmental contributions to ADHD trajectory and outcome from childhood through adolescence, Person-centered diagnostics and prediction for child dysregulatory psychopathology using novel phenotypes, SLE Treatment with N-acetylcysteine
OpenAlex ID: W7203827521