Sex–specific associations between frailty and long-term outcomes in patients with acute myocardial infarction: a national population-based study

Background: Frailty and female sex are both recognised independent predictors of adverse outcomes after acute myocardial infarction (AMI). While females presenting with AMI are known to have a higher burden of frailty than males, it is unknown whether this fully explains sex-based disparities in outcomes, or if the prognostic impact of frailty itself differs between the sexes. Methods: We conducted a retrospective national cohort study using data from the Myocardial Ischaemia National Audit Project (MINAP), linked to hospital admission and mortality registries in England and Wales between 2005 and 2019. Frailty was assessed using the Secondary Care Administrative Records Frailty (SCARF) index and categorised as fit, mild, moderate, or severe. Multivariable Cox proportional hazards models were used with a primary outcome of all-cause mortality at 1-year. Findings: Of 931,133 patients with AMI, 317,967 (34.1%) were female. Frailty was more prevalent in females than in males (severe frailty: 53,065 [16.7%] vs. 64,018 [10.4%]). Males received more intensive therapeutic care across all frailty levels. After multivariable adjustment, the relationship between severe frailty and 1-year all-cause mortality was 26% greater in males than in females (relative hazard ratio [rHR]: 1.26, 95% CI 1.19-1.32, P-interaction <0.001). This corresponded to an adjusted absolute risk difference of 1.19% (95% CI 0.58%-1.79%). Interpretation: In this national AMI cohort, while frailty was more prevalent in females, its association with 1-year mortality was significantly greater in males. This sex-specific effect of frailty challenges current risk-assessment paradigms and underscores the need for sex-informed care pathways. Funding: National Institute for Health and Care Research and British Heart Foundation Centre of Research Excellence, Leicester.