The study, published in Nature Mental Health by an interdisciplinary team led by Yiling Zhou and Douwe Postmus of the University of Groningen’s University Medical Center, together with colleagues in nephrology, psychiatry and endocrinology, is among the first to map the long-term cardiorenal illness trajectories of newly treated hypertensive patients according to ADHD status. Rather than asking a single question such as whether ADHD raises the risk of one event, the team used multistate modeling to trace how patients move through a sequence of health states: from apparently healthy hypertensive treatment, to the onset of complications such as heart failure hospitalization or chronic kidney disease, and ultimately, in some cases, to cardiorenal death.

This trajectory-based approach matters because hypertension is rarely a one-act story. Standard cardiovascular risk tools typically estimate the probability of a first event, but clinicians and patients also care deeply about what happens afterward: whether a person who survives a stroke or develops kidney disease faces elevated risk of dying from a cardiorenal cause. By modeling the entire pathway, the researchers could distinguish between transitions, asking, for example, not only whether adults with ADHD were more likely to develop heart failure, but whether, once heart failure appeared, they were more likely to die from it.

The scale of the analysis lends its findings unusual statistical weight. The cohort included 706,414 adults aged 18 to 90 who initiated antihypertensive medications between 2007 and 2021, with no prior cardiovascular disease or chronic kidney disease recorded. Just over half, 52.2 percent, were women. Within this population, 10,689 individuals had a documented ADHD diagnosis. The data came from Dutch national registers held by Statistics Netherlands, linking medication dispensing, hospital records and cause of death at the level of individual citizens, an infrastructure that permits follow-up across nearly the entire population rather than a select insured sample.

The headline results are stark. After adjusting for age, sex, comorbidities, medication class, lifestyle-related factors and other covariates, adults with ADHD had a 46 percent higher rate of hospitalization for heart failure after starting antihypertensive treatment, with a hazard ratio of 1.46 and a 95 percent confidence interval of 1.12 to 1.90. Their adjusted rate of stroke was 19 percent higher, with a hazard ratio of 1.19. These are not marginal signals confined to subgroups; they persisted across a large, unselected nationwide population followed for years after treatment initiation.

Perhaps more troubling are the findings on what happens after complications emerge. Once hospitalized for heart failure, adults with ADHD showed a 79 percent higher adjusted rate of subsequent cardiorenal death compared with adults without ADHD, a hazard ratio of 1.79. After the onset of chronic kidney disease, their rate of cardiorenal death was more than two and a half times higher, with a hazard ratio of 2.57. Put together, the ten-year trajectories that pass through heart failure or kidney disease and end in cardiorenal death were consistently more common among patients with ADHD than among otherwise comparable hypertensive patients without the diagnosis.

Why should ADHD, a neurodevelopmental condition most often associated with inattention, impulsivity and hyperactivity, shape the course of cardiovascular and kidney disease so profoundly? The study was not designed to isolate mechanisms, but the authors and related literature point to several converging explanations. One candidate is medication adherence. A companion multinational cohort study cited by the team found that adults with ADHD are less likely to adhere to antihypertensive treatment, and interruptions in therapy blunt the very protection these drugs are meant to provide. ADHD medications themselves, particularly stimulants, have also been scrutinized for cardiovascular effects, although the new analysis focused on newly treated hypertension and adjusted for a range of factors, leaving the contribution of ADHD pharmacotherapy an open question.

Broader biological and social pathways likely contribute as well. Recent genetically informed research has documented familial co-aggregation and shared heritability between neurodevelopmental conditions and cardiometabolic disease, hinting at shared physiological roots. Adults with ADHD also carry higher burdens of obesity, smoking, sleep problems and other somatic conditions across the lifecourse, and they frequently encounter barriers in healthcare systems, from fragmented follow-up to challenges in self-management of chronic therapy. Heart failure and chronic kidney disease, in particular, demand sustained engagement: daily medication regimens, fluid and dietary vigilance, and prompt recognition of worsening symptoms. Where engagement falters, outcomes deteriorate.

The clinical implications are hard to ignore. Current hypertension guidelines stratify patients by age, blood pressure severity and comorbidity, but ADHD rarely appears in the risk calculators that guide treatment intensity and follow-up schedules. The new findings suggest it should. A newly diagnosed hypertensive patient with ADHD may warrant closer monitoring of blood pressure control, more deliberate selection of antihypertensive agents, proactive screening for early heart and kidney involvement, and targeted support for medication persistence. The researchers emphasize that their results describe elevated risks and trajectories in an observational setting; they do not establish that ADHD causes worse outcomes, and residual confounding cannot be excluded. Still, the consistency of elevated hazard ratios across multiple transitions, from first complication to death, argues that ADHD belongs in the conversation about cardiorenal risk management.

For the study’s authors, the multistate framework is as much a message as the numbers themselves. Illness after hypertension unfolds as a chain of events, and each link in that chain represents a moment where intensified care could change the trajectory. The analysis code has been released publicly, and the underlying microdata remain accessible to accredited researchers through Statistics Netherlands under strict legal safeguards. As populations age and hypertension remains the leading modifiable risk factor for death worldwide, the study adds a new and sobering dimension to the growing evidence that mental health conditions cast long physical shadows, and that treating blood pressure alone may not be enough to equalize the odds for the one in twenty adults living with ADHD.

Subject of Research: Long-term cardiorenal illness trajectories after antihypertensive medication initiation in adults with and without ADHD

Article Title: Long-term cardiorenal illness trajectories after initiation of antihypertensive medications in adults with and without ADHD: a nationwide cohort study

Article References: Long-term cardiorenal illness trajectories after initiation of antihypertensive medications in adults with and without ADHD: a nationwide cohort study. (n.d.). https://doi.org/10.1038/s44220-026-00718-1

Image Credits: AI Generated

DOI: 10.1038/s44220-026-00718-1

Keywords: ADHD, hypertension, antihypertensive medications, heart failure, chronic kidney disease, stroke, cardiorenal death, multistate modeling, nationwide cohort study, medication adherence, cardiovascular risk, epidemiology

The research team, led by Jesper N. Bech of the University Clinic in Nephrology and Hypertension at Gødstrup Hospital and Aarhus University in Denmark, together with colleagues from the United Kingdom, the United States, Germany, Spain, Israel, and Denmark, extracted data from de-identified electronic medical records, insurance claims, and national health registries covering the years 2018 through 2023, and through 2024 for Denmark. Their study population comprised 64,501 adults with diagnosed hypertension who had been maintained on a stable two-drug regimen and then initiated a third antihypertensive medication, a step that clinicians interpret as treatment intensification in patients whose blood pressure remains above goal. The third medication fell into one of six commonly prescribed classes: angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, calcium channel blockers, beta-blockers, diuretics, or mineralocorticoid receptor antagonists.

The headline result is stark. Across countries and drug classes, between 54 percent and 100 percent of patients had discontinued their third medication within 12 months of starting it, and between 67 percent and 100 percent had done so within 24 months. In most countries, the median time to discontinuation was remarkably short, ranging from just 0.1 to 0.5 years, meaning that half of patients in many cohorts had abandoned the new drug within roughly two to six months. Denmark stood out as the exception, with discontinuation rates of 54 to 67 percent at one year and median persistence of 0.5 to 0.8 years, a difference the investigators suggest may partly reflect differences in how Danish physicians prescribe and dispense medications, with prescriptions commonly issued for 100 days or more.

Adherence told a similarly sobering story. The researchers measured adherence using the proportion of days covered, a pharmacoepidemiological standard that tracks how much of a follow-up period a patient actually has medication available based on prescription fills and dispensations. Median adherence to the third drug declined steadily over time, and the proportion of patients achieving the conventional threshold of more than 80 percent adherence at six months was 66 to 79 percent in Denmark but only 8 to 52 percent elsewhere. By 24 months, the picture in most countries had deteriorated further. Notably, adherence and persistence patterns were broadly similar across the six drug classes within each country, suggesting that the problem is less about which particular medication is chosen and more about systemic factors governing how patients engage with complex multidrug regimens.

The blood pressure outcomes raise equally difficult questions. Among the subset of patients with recorded blood pressure measurements at 12 months, only 23 to 50 percent in the United States, 35 to 66 percent in the United Kingdom, 42 to 55 percent in Germany, 57 to 70 percent in Spain, 63 to 89 percent in Israel, and 35 to 71 percent in Denmark had blood pressure below their country-specific target, which was 130/80 mmHg in the United States and 140/90 mmHg everywhere else. Median reductions in systolic blood pressure over the first year were modest, ranging from essentially zero for some drug classes in some countries to around 14 mmHg for calcium channel blockers at best. At 24 months, many patients showed no meaningful improvement, and some experienced worsening systolic pressures relative to baseline.

Perhaps most striking was what the medication data revealed about dosing behavior. When the investigators plotted daily dose categories and discontinuation across the first 365 days after the index prescription, they found that up-titration to higher doses was uncommon. Patients overwhelmingly started on low or usual doses and stayed there, even as a substantial proportion remained above their blood pressure targets. In some cases, prescriptions fell below licensed doses altogether: at least half of patients receiving the mineralocorticoid receptor antagonist spironolactone in the UK, USA, and Spain were dispensed 25 mg or less, below the 50 mg threshold generally considered the licensed starting dose for hypertension, and a similar pattern appeared for eplerenone. The authors interpret this combination of low starting doses, minimal up-titration, and high discontinuation as a signature of therapeutic inertia, the well-documented clinical phenomenon in which providers fail to intensify treatment despite evidence that a patient’s condition remains uncontrolled.

The clinical stakes of this gap are considerable. Hypertension is the leading modifiable risk factor for cardiovascular and renal disease worldwide, and meta-analyses indicate that every 10 mmHg reduction in systolic blood pressure lowers the risk of major cardiovascular events by roughly 20 percent. Yet globally, only about one in five people with hypertension achieves guideline-recommended blood pressure control. Patients who require multiple medications and still fail to reach target face elevated risks of stroke, ischemic heart disease, heart failure, chronic kidney disease, diabetes, and death. The EnligHTN analysis also showed that many of these patients carried substantial comorbid disease at baseline: the prevalence of heart failure ranged from 2 to 56 percent across cohorts, chronic kidney disease from 14 to 84 percent, and type 2 diabetes from 8 to 38 percent, conditions that complicate blood pressure management both biologically and pharmacologically.

The authors are careful to note important limitations. Discontinuation was inferred from prescribing and dispensing records rather than direct measurement of medication intake, so the estimates reflect loss of observed treatment continuity rather than definitive proof that patients stopped taking their pills; gaps may also reflect clinician-directed strategy changes or incomplete data capture. Blood pressure measurements were missing for a majority of patients at follow-up, ranging from 50 to 90 percent at the 12- and 24-month time points, so control rates describe only those patients with documented monitoring and may not generalize to the full cohort. The setting in which readings were taken could not always be determined, leaving open the possibility of white-coat or pseudo-resistant effects, and some prescribed doses may have been intended for indications other than hypertension.

Even with those caveats, the scale and consistency of the findings across six distinct healthcare systems carry a clear message. High discontinuation, suboptimal adherence, and therapeutic inertia converge to leave many patients with harder-to-control hypertension undertreated and unprotected. The study’s authors argue that the field needs two parallel advances: adherence-focused strategies that reduce pill burden and support patients in staying on therapy, and new classes of antihypertensive agents that are better tolerated and more effective at targeting the underlying pathophysiology in patients who do not respond adequately to existing drugs. With newer pharmacological options entering the hypertension landscape, the real-world treatment patterns documented by EnligHTN provide a crucial benchmark against which any genuine improvement in persistence, adherence, and blood pressure control will have to be measured.

Subject of Research: Real-world antihypertensive medication adherence, discontinuation, and blood pressure control in patients with harder-to-control hypertension

Article Title: Antihypertensive Medication Patterns in Patients with Hypertension that is Harder to Control: Insights from the EnligHTN Study

Article References: Bech, J. N., McCormack, T., Bhalla, V., Ben Dor, N. R., Segura, J., Hougaard Christiansen, S., Andersen, I. T., Erhard, C., Rhodes, K. M., Norris, T., Coto, E., & Weil, J. (2026). Antihypertensive Medication Patterns in Patients with Hypertension that is Harder to Control: Insights from the EnligHTN Study. Advances in Therapy. https://doi.org/10.1007/s12325-026-03771-5

Image Credits: AI Generated

DOI: 10.1007/s12325-026-03771-5

Keywords: hypertension, antihypertensive medications, medication adherence, blood pressure control, treatment discontinuation, therapeutic inertia, EnligHTN study, real-world evidence, observational cohort study, treatment persistence, cardiovascular risk, polypharmacy