Highlight
– In a linked national administrative dataset of 931,133 patients with acute myocardial infarction (AMI), frailty assessed using a secondary care administrative records frailty index was associated with higher 1‑year all‑cause mortality across all age groups.
– The adjusted hazard ratio (aHR) for 1‑year mortality for severely frail versus fit patients was highest in the youngest group: 6.69 (95% CI 5.76–7.76) for patients <55 years, 4.33 (95% CI 4.11–4.57) for ages 55–74, and 2.31 (95% CI 2.23–2.39) for ≥75 years.
– Interaction testing indicated the relative prognostic impact of severe frailty was significantly larger in younger patients compared with older patients (3.51‑fold higher relative risk; P < .001).
Background — why this matters
Frailty describes reduced physiological reserve and increased vulnerability to stressors. It is commonly conceptualized as an accumulation of deficits (diseases, impairments) or as a phenotype of low reserves (weight loss, exhaustion, slowness). Frailty is well documented as a major determinant of outcomes in older adults with cardiovascular disease, including after acute myocardial infarction (AMI). However, frailty assessment has traditionally been targeted to older populations, and its prevalence, prognostic importance, and implications in younger adults with AMI are less clear.
Understanding the age‑modified prognostic value of frailty has clinical implications: it may change triage, secondary prevention intensity, rehabilitation planning, and shared decision making across the adult age spectrum. The study by Mohiaddin and colleagues (Eur Heart J. 2025) provides large-scale contemporary evidence on this question using administrative data from England and Wales.
Study design
This was a population‑based epidemiological analysis using linked national administrative records from England and Wales. The cohort included 931,133 patients admitted with AMI. Patients were stratified into three prespecified age groups: <55 years (young), 55–74 years (middle), and ≥75 years (older).
Frailty was quantified using a Secondary Care Administrative Records Frailty index (an index constructed from coded diagnoses, procedures, and recorded deficits in secondary care records), and patients were categorised as fit, mild, moderate, or severe frailty. The primary outcome was all‑cause mortality at 1 year. Secondary outcomes included cardiovascular events and bleeding‑related events. Models were adjusted for relevant covariates (the summary paper reports adjusted hazard ratios, but specific covariates are not reproduced here; see the primary publication for model covariates and modelling strategy).
Key results
Cohort and frailty prevalence
The analysis included 931,133 AMI patients. Overall, 13% of patients were classified as severely frail. Frailty was present across age groups but enriched in older patients as expected.
Primary outcome — 1‑year all‑cause mortality
Severe frailty was strongly associated with 1‑year mortality in all age groups after multivariable adjustment. Adjusted hazard ratios (aHR) for severe frailty versus fit were:
- Age <55 years: aHR 6.69 (95% CI 5.76–7.76)
- Age 55–74 years: aHR 4.33 (95% CI 4.11–4.57)
- Age ≥75 years: aHR 2.31 (95% CI 2.23–2.39)
These estimates indicate that, after adjusting for measured confounders, severely frail younger patients had nearly seven times the hazard of death within 1 year compared with fit younger patients, whereas the relative hazard was smaller but still significant in older patients.
Age × frailty interaction
The statistical interaction between age category and frailty indicated that the relative effect of severe frailty (versus fit) was greater in younger than older patients. Specifically, younger patients with severe frailty had a 3.51‑fold (95% CI 3.11–3.96) higher relative risk of 1‑year death compared with older patients with severe frailty (P < .001 for interaction).
Secondary outcomes
Although the summary focused on mortality, the authors also examined cardiovascular and bleeding events. Frailty was associated with elevated risks of cardiovascular events and bleeding, generally following a similar pattern to mortality (greater relative associations in younger patients). For detailed event rates, absolute risks, and subgroup analyses, readers should consult the full paper.
Interpreting the findings — clinical and epidemiological perspectives
These results demonstrate three key points:
- Frailty is not exclusive to older adults and is measurable in younger AMI patients using administrative records.
- Frailty is a robust independent predictor of adverse outcomes after AMI across the adult age spectrum.
- The relative prognostic impact of frailty is largest in younger patients.
The strong relative effect in younger adults requires careful interpretation. Relative measures (hazard ratios) compare risk between frail and fit patients within the same age group; younger fit patients have low baseline mortality, so the same absolute increment in risk translates into a larger relative hazard. Older adults have higher baseline risks, meaning the same absolute risk difference yields a smaller relative hazard. Thus, while the relative risk increment is larger in younger patients, absolute risks of death remain highest in older, frail patients. Both relative and absolute risks are clinically important: the former highlights how much frailty changes prognosis for a given age, and the latter informs clinical prioritisation and resource allocation.
Mechanistic plausibility
Frailty captures multimorbidity, chronic inflammation, sarcopenia, cognitive and functional impairment, and reduced physiological reserve. In younger individuals who develop frailty, these deficits often reflect a higher burden of premature multimorbidity, social vulnerability, or severe comorbidity (e.g., advanced chronic diseases, severe chronic inflammatory conditions, substance misuse). When AMI occurs on this background, the ability to withstand ischaemic injury, invasive procedures, or complications is reduced, leading to worse outcomes. Administrative frailty indices aggregate coded deficits and may reflect these processes at scale.
Strengths and limitations
Strengths of the study include very large, population‑level sample size, inclusion of contemporary AMI cases, and use of linked administrative datasets enabling near‑complete follow‑up.
Limitations to consider:
- Frailty was measured using an administrative records index rather than bedside phenotypic or performance measures (e.g., gait speed, grip strength) or comprehensive geriatric assessment. Administrative indices are validated for population surveillance but may misclassify individual frailty status.
- Residual confounding is possible; administrative data lack some clinical granularity (left ventricular function, frailty phenotypes, socioeconomic detail, lifestyle factors) and may incompletely capture acuity or treatment decisions.
- Cause–effect relationships cannot be definitively established in an observational dataset; frailty may be a marker of both biological vulnerability and decisions about care intensity (treatment selection bias).
- Generalisability outside England and Wales, and across different healthcare systems, requires confirmation.
Clinical implications and practical recommendations
1) Broaden frailty screening: These results support routine frailty assessment in adults with AMI irrespective of chronological age to identify high‑risk patients who may benefit from tailored management.
2) Individualised care planning: For younger patients identified as frail, consider early multidisciplinary involvement (cardiology, geriatrics or internal medicine, rehabilitation, social work) to optimise secondary prevention, medication reconciliation, and post‑discharge support.
3) Treatment decisions: Frailty should inform — but not automatically contraindicate — invasive strategies. Shared decision making that accounts for frailty, comorbidity, expected recovery trajectory, and patient goals is essential.
4) Secondary prevention and rehabilitation: Frail patients may benefit from targeted cardiac rehabilitation programmes that incorporate strength training, nutritional support, and management of polypharmacy. Implementation trials are needed to identify optimal interventions across ages.
Research and policy priorities
– Validate administrative frailty indices against performance‑based and clinical frailty measures in AMI cohorts across age groups.
– Prospectively test frailty‑guided care pathways and evaluate whether targeted interventions (multidisciplinary rehabilitation, comprehensive geriatric assessment, tailored antithrombotic regimens) improve outcomes.
– Explore mechanisms underlying premature frailty in younger adults — social determinants, chronic inflammation, multimorbidity profiles — to identify upstream prevention opportunities.
– Consider incorporating frailty metrics into risk scores and quality metrics for AMI care and post‑hospitalisation follow‑up.
Conclusions
Mohiaddin and colleagues provide compelling, population‑level evidence that frailty is an independent and clinically meaningful predictor of poor outcomes after AMI across the adult lifespan, with the largest relative prognostic effect observed in younger patients. These findings challenge the age‑limited use of frailty assessment and argue for broader, systematic consideration of frailty in AMI care pathways, risk communication, and research.
Funding and clinicaltrials.gov
Funding and trial registration details were not provided in the summary. Readers should consult the original article for funding declarations, conflict of interest statements, and any trial registration information.
Selected references
1. Mohiaddin H, Sze S, Damluji AA, et al. Frailty and long‑term outcomes in younger patients with acute myocardial infarction. Eur Heart J. 2025 Nov 25:ehaf876. doi:10.1093/eurheartj/ehaf876. Epub ahead of print. PMID: 41288370.
2. Clegg A, Young J, Iliffe S, Rikkert MO, Rockwood K. Frailty in elderly people. Lancet. 2013 Mar 2;381(9868):752–762. doi:10.1016/S0140‑6736(12)62167‑9.
3. 2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST‑segment elevation. Eur Heart J. 2020;41(3):349–399. (European Society of Cardiology guideline documents and updates.)
Author note
This article synthesises and interprets results from a large administrative data analysis to inform clinicians, researchers, and policymakers. For granular methods, adjusted covariates, and subgroup results, consult the original manuscript.
