Cardiac disease and lifestyle risk factors following hodgkin lymphoma: An eortc lymphoma group and gela follow-up study

Purpose/Objective(s): Hodgkin lymphoma (HL) survivors are known to suffer from an excess risk of cardiac disease (CD) due to radiation and anthracyclines. However, CD is also associated with other risk factors such as high blood pressure (BP), elevated levels of blood cholesterol (BChol), diabetes mellitus (DM), obesity, and smoking. For HL survivors, the effects of these factors have been difficult to quantify as it requires information from patients treated decades ago. The purpose of our study was to quantify the degree of association between traditional cardiac risk factors and incidence of CD in the EORTC (European Organisation for Research and Treatment of Cancer)-GELA (Groupe d'Étude des Lymphomes de l'Adulte, now LYSA) cohort of HL patients treated in nine randomized trials from 1964 to 2004 (n = 6,658). Purpose/Objective(s): Incidence of CD was reported during follow-up and through a patient-reported questionnaire (LSQ), mailed in 2009-2010 to patients known to be alive and for whom an address was known (56.7% of the patients enrolled in all trials). The degree of association of CD with cardiac risk factors reported at LSQ completion was measured using the Mantel-Haenszel estimate of the common odds ratio (OR) across trials with its 95% confidence interval (CI). The P-value was obtained from the Cochran-Mantel-Haenszel test. Heterogeneity of OR across trials was assessed using the Breslow-Day Test. Results: One thousand nine hundred nineteen patients responded to the LSQ, 49% were males and the median age at treatment start was 29 years (range: 10-69 years). The median duration of follow-up was 14 years (range: 5-44 years). A total of 416 patients (21.7%) reported CD events. At LSQ completion, 329 (17.1%) survivors reported high BP, 376 (19.6%) elevated BChol, 96 (5.0%) DM, 221 (11.5%) were obese (body mass index ≥ 30) and 289 (15.1%) were smokers. The OR for CD with high BP was 2.7 (95% CI = 2.1-3.5, P < 0.0001), with elevated BChol 2.6 (95% CI = 2.0-3.4, P < 0.0001), with DM 3.5 (95% CI = 2.3-5.5, P < 0.0001), with obesity 1.3 (95% CI = 0.9-1.8, P = 0.173) and with smoking 1.3 (95% CI = 0.9-1.7, P = 0.149). Heterogeneity of OR across trials was significant for high BP (P = 0.007). Conclusion: For HL patients, the continued efforts to limit treatment exposure are important for minimizing subsequent cardiac risk. In addition, traditional lifestyle risk factors such as high BP, elevated BChol, and DM are significantly associated to the risk of developing CD. Although causality cannot be concluded, patient education, lifestyle intervention, and counseling should be encouraged at all treating institutions.