While frailty is more common in women with acute myocardial infarction (MI), its association with mortality and adverse outcomes appears stronger in men, according to a large national study.

Led by the University of Leicester, UK, and published in The Lancet Regional Health Europe, the study used linked data from the Myocardial Ischaemia National Audit Project to examine whether sex influences the relationship between frailty and adverse outcomes following acute MI.

The retrospective cohort included 931,133 adults admitted with acute MI between 2005 and 2019. Of these patients, 613,166 (65.9%) were men and 317,967 (34.1%) were women. Mortality data were available through linkage with national registries, allowing outcomes to be assessed up to one year after the index event.

Frailty was assessed using the Secondary Care Administrative Records Frailty (SCARF) index – a validated tool based on 31 health deficits identified via diagnostic coding. Patients were categorised into four groups: fit, mild-, moderate- and severe frailty.

Severe frailty was present in 16.7% of women compared with 10.4% of men, while a larger proportion of men were categorised as fit (33.7% vs 21.3%). Women were also older across all categories.

Frailty, mortality and adverse events after acute MI

The primary outcome was all-cause mortality at one year. Secondary outcomes included cardiovascular death, major adverse cardiovascular events, heart failure readmission, reinfarction and bleeding.

After adjusting for multiple variables, the hazard ratio (HR) for one-year mortality in men rose from 1.72 (95% CI 1.65–1.78) for mild frailty to 3.19 (95% CI 3.04–3.34) for severe frailty, compared with fit individuals.

In women, the corresponding HRs ranged from 1.50 (95% CI 1.43–1.57) to 2.66 (95% CI 2.51–2.82), respectively.

Formal interaction testing indicated that the association between severe frailty and one-year mortality after acute MI was 26% greater in men than in women (relative HR 1.26; 95% CI 1.19–1.32; P-interaction <0.001).

A similar pattern was observed for other outcomes, including major adverse cardiovascular events and heart failure readmission. The stronger association between frailty and adverse outcomes in men was also consistent across both ST-elevation MI and non-ST-elevation MI.

Although women were more frequently frail, men within the same clinical category had a higher prevalence of atherosclerosis-related comorbidities, such as diabetes, and were more likely to present with acute complications, including cardiac arrest.

‘Sex–frailty paradox’ and implications for clinical practice

The study also observed differences in treatment patterns. Men were more likely to receive invasive coronary angiography and percutaneous coronary intervention, and overall quality-of-care scores were slightly higher among men.

Despite receiving more intensive guideline-directed therapy, frail men faced a greater relative increase in mortality risk. This was described as a ‘sex–frailty paradox’, wherein frailty is more common among women but seems more strongly linked to adverse outcomes in men.

Despite several limitations – including the observational design, the possibility of unmeasured confounding factors such as socioeconomic status or functional capacity, and reliance on hospital coding data within the SCARF index that may lead to misclassification of frailty – the authors concluded that incorporating both frailty and sex into routine risk assessment could improve risk stratification following acute MI.

Challenging current risk assessments

Commenting on the potential for significant clinical implications, joint study lead, Dr Muhammad Rashid, honorary consultant interventional cardiologist and senior clinical research fellow at the University of Leicester’s Department of Cardiovascular Sciences and the NIHR Leicester Biomedical Research Centre, said the findings challenge ‘current risk assessments, which often treat frailty as a uniform predictor’.

He added: ‘[This] needs to evolve so that acute MI male care pathways are enhanced beyond cardio-metabolic management and prioritised cardiac rehabilitation, while equitable delivery of established, life-saving therapies should be established for females.

‘The development and validation of new sex-specific frailty assessment tools should therefore be a priority for future research as such tools may be better suited to identifying high-risk individuals and guiding targeted interventions for the most vulnerable patients.’

Reference
Mohiaddin H et al. Sex-specific associations between frailty and long-term outcomes in patients with acute myocardial infarction: a national population-based study. Lancet Reg Health Eur 2026;64:101612.