Pre-cancer cardiovascular risk factors and anthracycline-related cardiotoxicity among non-Hodgkin lymphoma survivors.

Abstract

e19031 Background: Anthracycline-based therapy is associated with an increased risk of late-onset heart failure (HF). We investigated whether this association is potentiated by pre-existing cardiovascular (CV) risk factors. Methods: Using Danish nationwide population-based registries, we identified all adults diagnosed with primary aggressive non-Hodgkin lymphoma from 2000-2010 who were alive 9 months after diagnosis, using the lymphoma registry. Outcomes were followed through 2012. The patient registry contains ICD codes for all specialist visits; we used ICD codes to assess HF diagnosed at hospitalization or death, at least 9 months after diagnosis. Pre-cancer CV risk factors (hypertension, dyslipidemia, and diabetes) were identified algorithmically using prescription data, specialist visit ICD codes, and the diabetes registry; they were coded as 0, 1, or ≥ 2 risk factors. Anthracycline dose was coded continuously. Controlling for age, sex, and pre-existing CV disease (ischemic heart disease, cerebrovascular accident, and cardiomyopathy, identified from the patient registry), we used Cox multivariate regression to test the interaction between CV risk factors and anthracyclines on subsequent HF. Results: Among 2649 patients with NHL, the median follow-up time was 3.2 years. During this time, 115 were diagnosed with HF. Before lymphoma diagnosis, 31% of the entire cohort had at least 1 CV risk factor and 11% had ≥ 2; 93% of patients were treated with anthracyclines. Anthracycline dose was associated with increased HF risk (HR = 1.3 [95% CI = 1.1-1.5]). Those with more CV risk factors had an increased risk of HF compared to those without CV risk factors (HR for 1 risk factor = 1.7 [95% CI = 1.1-2.6], HR for ≥ 2 risk factors = 2.7 [95% CI = 1.5-4.6], overall p < 0.01). No significant interaction was found between the number of CV risk factors and anthracycline dose on HF (p = 0.4). Conclusions: In a large, well-characterized cohort of lymphoma survivors with minimal loss to follow-up, anthracyclines and CV risk factors were independently associated with later HF. Notably, underlying CV risk factors did not appear to heighten the cardiotoxic effect of anthracyclines.