Hematopoietic cell transplantation (HCT) is an increasingly common procedure used to treat several malignant and nonmalignant diseases. Recent estimates suggest that more than 20,000 individuals in the United States undergo HCT each year. Although this procedure is highly successful in the treatment of many diseases, survivors have greater long-term morbidity and mortality as compared to the general population. With the projected increase in the number of HCT survivors in the coming years, it is increasingly important to gain a better understanding of the risk factors that are associated with the increased morbidity and mortality that these individuals face. Dr. Eric Chow and colleagues in the Public Health Sciences and Clinical Research Divisions at Fred Hutch conducted a longitudinal study to assess modifiable cardiovascular disease risk factors in survivors of HCT and recently published the results in the journal Cancer.
Cardiovascular diseases and related mortality are increased in HCT survivors and are estimated to account for up to 7% of excess deaths in this population. Poor diet, low physical activity, and smoking are known to be significant contributors to cardiovascular disease risk in the general population. In addition, potentially modifiable metabolic conditions that increase the risk for cardiovascular disease including diabetes, dyslipidemia, and hypertension are all associated with the adverse lifestyle factors. The association of these risk factors with ischemic heart disease in survivors of HCT is of interest, as early and targeted treatments and lifestyle modifications may have a significant beneficial impact on the long-term morbidity and mortality of this at-risk population.
Dr. Kasey Leger, first author of the study and assistant professor of Pediatrics at Seattle Children’s, described past work that laid the groundwork for the current study, “We and others previously demonstrated an association between adverse lifestyle factors and cardiac risk conditions with serious cardiovascular events in survivors of hematopoietic cell transplant.” The results from the new study are notable as they further elucidated the relationship, as summarized by Dr. Leger, “by showing that unhealthy lifestyle factors and cardiac risk conditions are associated with subsequent risk for ischemic heart disease and death.”
To assess the relationship of lifestyle and cardiovascular risk factors with ischemic heart disease incidence and mortality outcomes, the authors analyzed longitudinal data collected from 2,360 patients who underwent HCT at Fred Hutch between 1970 and 2010. All patients included in the study completed a baseline survey in 2010/2011 that included questions related to cardiovascular disease history and related adverse conditions (diabetes, dyslipidemia, and hypertension), tobacco use, weekly physical activity levels, and average daily fruit and vegetable consumption. After five years, the associations between lifestyle factors and cardiac risk factors with risk for ischemic heart disease and overall mortality were determined.
At the time of the baseline survey, 6.9% of the HCT survivors had a history of ischemic heart disease. This group reported a significantly greater number of cardiovascular risk conditions and adverse lifestyle factors compared to the survivors without ischemic heart disease at baseline. To determine if current risk factors affect the later development of disease and mortality, the authors then focused their analyses on the survivors without a history of ischemic heart disease at baseline. Among these individuals, more than 50% had at least one cardiac risk condition and 80% reported at least one adverse lifestyle factor. The 5-year cumulative incidence of ischemic heart disease was 4.3% in this group. When stratified by number of adverse lifestyle factors, there was a differential risk for ischemic heart disease and overall mortality by group (see Figure), with a greater number of risk factors associated with greater risk. The cumulative incidence of ischemic heart disease, but not overall mortality, was also significant when stratified by number of cardiovascular risk conditions. In addition, the risk for subsequent ischemic heart disease was increased 1.4 times for each additional cardiac risk condition and 1.9 times for each additional adverse lifestyle factor. “This temporal association emphasizes the critical importance of attention to modifiable lifestyle factors and risk conditions in a population already at markedly increased risk for serious cardiovascular disease and highlights an opportunity to improve the cardiac health of transplant survivors,” said Dr. Leger.
When asked about the next steps, Dr. Leger indicated that “Further studies are necessary to determine whether interventions targeting healthier lifestyles and minimizing/controlling cardiac risk conditions will successfully improve the health of hematopoietic cell transplant survivors.” Results from such studies would contribute to closing the knowledge gap regarding how modifiable risk factors influence cardiovascular disease risk in HCT recipients.
This research was supported by the National Institutes of Health.
Research reported in the publication is a collaboration between Cancer Consortium members at UW (Drs. Jason Mendoza and Kerryn Reding) and Fred Hutch (Drs. K. Scott Baker, Mary Flowers, Paul Martin, Karen Syrjala, Stephanie Lee, and Eric Chow).
Leger KJ, Baker KS, Cushing-Haugen KL, Flowers MED, Leisenring WM, Martin PJ, Mendoza JA, Reding KW, Syrjala KL, Lee SJ, Chow EJ. 2018. Lifestyle factors and subsequent ischemic heart disease risk after hematopoietic cell transplantation. Cancer. doi: 10.1002/cncr.31227.