Spontaneous admission hypothermia as a multifactorial indicator of early in-hospital mortality risk in acute myocardial infarction: advanced 3PM approach to the benefits of patients

Rationale and purpose Elevated body temperature (BT) is a common manifestation in patients with acute myocardial infarction (AMI), indicating infection or recurrent myocardial infarction. However, the significance of admission hypothermia for early in-hospital mortality risk remains unclear. From the perspective of Predictive, Preventive, and Personalized Medicine (3PM), this study evaluated the prognostic significance and potential clinical utility of admission hypothermia in patients with AMI. We further explored the clinical significance of admission hypothermia for accurate risk stratification, targeted prevention, and optimized personalized therapy within the 3PM framework, facilitating a paradigm shift from reactive to advanced proactive 3PM-oriented healthcare strategies. Working hypothesis and methods We hypothesized that spontaneous admission hypothermia is a multifactorial indicator for identifying high-risk AMI patients, facilitating early risk prediction, targeted prevention, and personalized management to reduce early in-hospital mortality within the 3PM framework. In this retrospective multicenter cohort study, data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database served as the primary cohort, and data from the electronic intensive care unit collaborative research database (eICU-CRD) were used for external validation. Adult intensive care unit patients with AMI were included. The non-linear relationship between admission BT and 14-day in-hospital all-cause mortality was evaluated using restricted cubic splines (RCS). An optimal BT cut-off was determined using Youden’s index. Inverse probability of treatment weighting (IPTW) and a time-split Cox proportional hazards regression model were used to assess the independent and time-varying prognostic value of admission hypothermia. Subgroup analyses were performed to assess effect modification across clinical strata. Results A total of 5,316 patients in the primary cohort and 3,973 in the validation cohort were included. RCS analysis showed a linear association between admission BT and increased mortality. Using the Youden’s index, an optimal BT cut-off of 36.2 °C was identified. Admission hypothermia (< 36.2 °C) was independently associated with a higher risk of 14-day mortality in the primary cohort (adjusted HR, 1.56; 95% CI, 1.27–1.91; P < 0.001). This association remained robust after IPTW adjustment (HR, 1.35; 95% CI, 1.11–1.64; P = 0.002) and was successfully externally validated (adjusted HR, 2.02; 95% CI, 1.35–3.03; P < 0.001). Time-split models revealed a prominent time-varying effect, with excess mortality risk occurring predominantly within the first 7 days of admission (HR, 1.67; 95% CI, 1.33–2.11; P < 0.001). Subgroup analyses indicated that the prognostic impact of hypothermia was more pronounced in younger patients (< 65 years), those with hyperlactatemia, and those with ST-segment elevation myocardial infarction. The increased mortality risk associated with hypothermia was neutralized in patients who underwent timely revascularization. Conclusions and expert recommendations in the framework of 3PM Within the 3PM paradigm, admission BT enables early identification of high-risk patients, supports timely, targeted preventive interventions, including hemodynamic regulation and myocardial revascularization, and facilitates personalized risk stratification for tailored therapeutic strategies. These findings underscore that admission hypothermia serves as a convenient, non-invasive multifactorial indicator that optimizes early risk evaluation and guides 3PM clinical management for this high-risk population.