Cardiovascular Risk Factors in Hematopoietic Cell Transplantation (HCT) Survivors: Role in Development of Subsequent Cardiovascular Disease

Advances in transplantation strategies and supportive care have resulted in a growing number of long-term HCT survivors. In the general U.S. population, cardiovascular disease is a leading cause of morbidity and mortality, and cardiovascular risk factors (CVRFs), including diabetes hypertension and dyslipidemia are well-established modifiers of the risk. There is increasing evidence that HCT survivors may be at risk for CVRFs that can potentially result in an increased risk of cardiovascular morbidity. However, there is a paucity of knowledge regarding the magnitude of risk and associated risk factors for CVRFs after HCT, and the role these CVRFs play in the subsequent development of cardiovascular disease such as stroke, myocardial infarction, and congestive heart failure, in long-term survivors of HCT. Methods: A retrospective cohort study design was used to describe the cumulative incidence of CVRFs and cardiovascular disease in 1+year survivors of HCT, taking into consideration the competing risk of death. Cox proportional hazards regression analysis was used to calculate relative risk (RR) estimates and 95% confidence intervals (CI), adjusted for relevant covariates. Definition of CVRFs was per the National Cholesterol Education Program Adult Treatment Panel III criteria. Survivors taking immunosuppressant medication for management of graft vs. host disease (GvHD) at the time of CVRF diagnosis were excluded from the regression analysis. Cardiovascular disease was defined per the American College of Cardiology established case definitions. Results: 2041 consecutive one-year survivors who underwent HCT for hematologic malignancies between 1995 and 2004 at City of Hope were included in the analysis. Median age at HCT was 44.1 years (0.6–78.9); 57.6% were female; 62.5% were non-Hispanic white and 24.5% were Hispanic; 41% underwent allogeneic HCT; 26.5% of allogeneic HCT survivors had a history of chronic GvHD; 49.9% received total body irradiation (TBI). Cardiovascular risk factors: After 12,551 person-years of follow-up, the 10-year cumulative incidence of diabetes, hypertension, and dyslipidemia was 16.8%, 36.1% and 43.5%, respectively; 10-year cumulative incidence for multiple (2+) CVRFs was 29.5%. The cumulative incidence of CVRFs was significantly higher for allogeneic HCT recipients (Table). Multivariate analysis adjusted for gender, race/ethnicity, diagnosis, and conditioning-related exposures, revealed older age at HCT and obesity to be risk factors for all three CVRFs. Allogeneic HCT survivors with a history of chronic GvHD were at highest risk for diabetes (RR=32.4, 95% CI: 16.6–63.2, p<0.01), hypertension (RR=12.0, 95% CI: 5.5–26.1, p<0.01), and dyslipidemia (RR=7.2, 95% CI: 4.2–12.3, p<0.01) when compared to autologous HCT recipients. Cardiovascular disease occurred in 117 individuals, at a median 3.8 years following HCT (range 0.1–13.9). The 10-year cumulative incidence of cardiovascular disease was 7.4%, and was highest among survivors with multiple CVRFs (10.9% vs. 5.9% in those with <2 CVRFs, p=0.02). Furthermore, survivors with multiple CVRFs were at 1.8-fold risk (95% CI: 1.1–3.3, p=0.04) of subsequently developing cardiovascular disease when compared to survivors with <2 CVRFs. Conclusions: Allogeneic HCT survivors are at a substantially increased risk for CVRFs following HCT, and chronic GvHD and/or its treatment are critical modifiers of this risk. Survivors with multiple CVRFs are at highest risk for development of cardiovascular disease following HCT. These findings provide rationale for close monitoring and aggressive interventions for this high-risk population in order to reduce cardiovascular morbidity and mortality.

No relevant conflicts of interest to declare.