Cardiac Dysfunction in Non-Hodgkin Lymphomas: The Influence of Comorbidities and Cardiovascular Risk Factors

Abstract

Introduction: Non-Hodgkin lymphomas (NHL) are common malignant tumors with variable progression, and current treatments can increase the risk of cardiovascular complications, including chemotherapy-induced cardiac dysfunction (CTRCD). NHL survivors have a cardiovascular death risk 5.35 times higher than the general population. Although cardiovascular risk stratification is recommended before treatment, the impact of risk factors and comorbidities in the absence of major cardiovascular diseases remains insufficiently studied. Aim of the study: To assess the cardiovascular risk factors and comorbidities associated with chemotherapy-induced cardiac dysfunction in patients with non-Hodgkin lymphoma, to identify predictors of cardiotoxicity. Materials and methods: We conducted a prospective analytical cohort study on 127 patients with non-Hodgkin lymphoma, randomly selected from the hematology departments of the Oncology Institute in Chișinău (2022-2024). The research was approved by the Ethics Committee of the “Nicolae Testemițanu” State University of Medicine and Pharmacy. Eligible patients were over 18 years old, diagnosed with NHL, and provided written informed consent. Exclusion criteria included patients with a history of other oncological diseases, pre-existing cardiovascular conditions, and advanced heart failure. The study was conducted in two stages: before and 6 months after the initiation of antitumor therapy, evaluating cardiovascular risk factors, comorbidities, and the Charlson score. Chemotherapy-induced cardiac dysfunction was defined according to the 2022 European Society of Cardiology cardio-oncology guidelines. Results: Among the cardiovascular risk factors and comorbidities associated with CTRCD development, we found that an BMI > 30 kg/m² was significantly more common in the CTRCD group (44.4%) compared to the non-CTRCD group (21.1%) (p=0.043). Patients with grade II and III hypertension had a higher prevalence in the CTRCD group (66.6%) compared to the non-CTRCD group (p<0.001). Dyslipidemia was significantly more frequent in patients with CTRCD: 94.4% in the CTRCD group vs. 61.5% in the non-CTRCD group (p=0.006). Patients with CTRCD had significantly higher median values of total cholesterol (5.9 mmol/l vs. 4.8 mmol/l, p=0.008) and LDL cholesterol (2.8 mmol/l vs. 2.2 mmol/l, p=0.013). The presence of metabolic syndrome was significantly higher in the CTRCD group: 38.9% vs. 10.1% in the non-CTRCD group (p=0.005). Stage III chronic kidney disease (K/DOQI) was present in 16.7% of patients with CTRCD, compared to 1.8% in the non-CTRCD group (p=0.027). Age, sex, abdominal circumference, triglycerides, and HDL cholesterol did not show significant statistical differences between the two groups. Conclusion: Cardiovascular risk factors such as obesity, hypertension, dyslipidemia, and metabolic syndrome were determinants of chemotherapy-induced cardiotoxicity. Renal insufficiency, regardless of severity, also increases the risk of developing cardiotoxicity. Antitumor therapy associated with CTRCD included the administration of doxorubicin, with higher doses (510 mg/m²) and an increased number of chemotherapy cycles.