Hemoglobin levels and long-term mortality after acute coronary syndrome: a 26-year follow-up

Background The prognostic role of baseline hemoglobin (Hb) levels in patients with acute coronary syndrome (ACS) remains uncertain, particularly over very long-term follow-up. The interaction between anemia and age may play a key role in determining outcomes. The aim was to evaluate the association between baseline hemoglobin and long term mortality Methods We analyzed 571 patients admitted with ACS and discharged alive from three Italian hospitals (1992–1998). Only three patients were lost to follow-up before death or 26 years. Patients were followed for up to 26 years. Cox regression models stratified by year of enrollment were used. Interaction between Hb and age was formally tested. In the fully adjusted models, covariates included were age, sex, heart failure, hypertension, prior myocardial infarction, antiplatelet therapy, and estimated glomerular filtration rate. Analyses were performed using Stata version 18 (StataCorp LLC, TX, USA). Results Mean age was 66±12 years and 30% were female. Over 26 years, 483/571 patients (85%) died. At univariable analysis, baseline Hb was not significantly associated with mortality (HR 0.90, 95% CI 0.80–1.00; p=0.07). Despite this, a significant interaction between Hb and age was observed. Hb showed a positive association with mortality (HR: 1.5; 95% CI: 1.1–2.2; z=2.6; p=0.01), and a negative interaction with age (HR: 0.8; 95% CI: 0.7–0.9; z= -2.6; p=0.01). In models including the interaction term, lower Hb levels were associated with higher mortality in older patients, and lower in younger individuals. These findings remained consistent after multivariable adjustment, both with the negative interaction with age (HR: 0.8; 95% CI: 0.7–0.9; z=–2.5; p=0.01) and mortality (HR: 1.5; 95% CI: 1.1–2.1; z= –2.5; p=0.01). As illustrated in the predictive margins plot (Figure 1), lower Hb levels were associated with a higher relative hazard of global mortality in elderly patients (green line). In contrast, this risk-gradient was attenuated in the medium-age group (red line) and slightly reversed in younger participants (blue line), confirming that the clinical impact of Hb on survival is strongly modulated by age. Conclusions In this very long-term study, the prognostic impact of hemoglobin after ACS is strongly modified by age. Low Hb identifies a higher-risk subgroup among older patients, supporting the importance of considering anemia within an age-specific clinical context.