Acute-phase HOMA2-IR and in-hospital cardiovascular complications in patients with acute coronary syndrome without known diabetes.

Background: Insulin resistance measured during acute coronary syndrome (ACS) may reflect pre-existing metabolic vulnerability as well as the response to acute illness. We examined its association with cardiovascular complications arising during the index hospitalization in patients with ACS and no known diabetes. Methods: In this single-center prospective cohort, 252 patients with ACS and an admission HbA1c <6.5% had fasting glucose and insulin measured 24-48 hours after admission. Insulin resistance was defined by a HOMA2-IR threshold of ≥1.35 prespecified from independent healthy controls. The composite MACE outcome comprised five prespecified complications occurring between sampling and discharge or death. Logistic and modified Poisson regression were adjusted for age, sex, body mass index, smoking, and hypertension. Results: Insulin resistance was present in 137 patients (54.4%), and the composite MACE occurred in 57 (22.6%): 28.5% with versus 15.7% without insulin resistance; risk difference 12.8 percentage points (95% CI 2.5-22.6). Insulin resistance was associated with the composite (adjusted OR 3.08, 95% CI 1.55-6.14; adjusted RR 2.29, 95% CI 1.39-3.75); each doubling of HOMA2-IR was associated with higher odds (adjusted OR 1.47, 95% CI 1.09-1.99). The association persisted after GRACE adjustment (adjusted OR 2.83, 95% CI 1.32-6.06) and was attenuated after adding left ventricular ejection fraction, a possible mediator (adjusted OR 2.25, 95% CI 0.97-5.22). Acute heart failure, cardiogenic shock, or pulmonary edema accounted for 53 of the 57 events. Conclusions: Acute-phase HOMA2-IR-defined insulin resistance was associated with cardiovascular complications during the index hospitalization, mainly heart-failure-related events. These findings are associational and require confirmation in multicenter cohorts.