Uncontrolled diabetes as an independent predictor of mayor adverse cardiovascular events in prostate cancer survivors

Abstract

Cardiovascular (CV) diseases are a leading cause of mortality among prostate cancer (PC) survivors. (1) Although diabetes is a well-established risk factor for CV complications, its impact on Major Adverse Cardiovascular Events (MACE) in this population is not fully characterized. We aimed to assess whether diabetes control, defined by an HbA1c of 6.5%, is associated with MACE (myocardial infarction, CABG/PCI, stroke, heart failure, unstable angina, and CV death). A retrospective cohort of 4,561 PC patients (median age: 72; IQR: 67–76) was evaluated using Fine-Gray competing risk models, comparing MACE development and non-CV death. Baseline HbA1c was defined as the measurement closest to the cancer diagnosis; the follow-up value was the final measurement recorded after diagnosis but prior to any MACE event or censoring. Patients were categorized into four groups: Optimal Control (reference: <6.5% and stable/decreasing), New Onset Diabetes (<6.5% and increasing), Controlled Diabetes (>6.5% and decreasing), and Uncontrolled Diabetes (>6.5% and stable/increasing). Models were adjusted for age (years), BMI (kg/m²) and hormone therapy. Cumulative incidence curves were plotted to visualize the temporal distribution of events across cohorts. A total of 1,179 patients experienced MACE over the study period. In multivariable-adjusted models, uncontrolled diabetes was independently associated with a significantly higher risk of MACE (HR: 1.24; 95% CI: 1.07–1.43; p = 0.004) compared to the optimal control group. Conversely, neither new-onset diabetes (HR: 1.04; 95% CI: 0.90–1.20; p = 0.611) nor controlled diabetes (HR: 1.14; 95% CI: 0.95–1.36; p = 0.150) reached statistical significance. Age (HR: 1.07 per year; 95% CI: 1.06–1.07; p < 0.001) and BMI (HR: 1.01 per kg/m²; 95% CI: 1.00–1.02; p = 0.041) remained significant predictors, while hormone therapy was not associated with the outcome (HR: 0.96; 95% CI: 0.84–1.08; p = 0.491) (Table 1). Cumulative incidence curves demonstrate a clear separation, where optimal control (red) displayed a sustained lower MACE probability compared to the other cohorts. Notably, beyond the 10-year mark, both controlled (yellow) and uncontrolled (green) diabetes groups exhibited similar event probabilities (Figure 1). In PC survivors, uncontrolled diabetes is independently associated with MACE. These findings highlight the importance of achieving and maintaining glycemic control in patients with PC.Cumulative incidence of 5point MACECharacteristics of PC patients