Age, Anthracycline Dose, Hypertension Contribute to Higher CVD Risk in HCT Recipients

In a study published in Blood Advances, investigators reviewed data from a large cohort of patients who had undergone a hematopoietic cell transplantation (HCT) to determine factors that increase the risk for developing cardiovascular disease (CVD) – a leading cause of late morbidity and mortality in this population.

Their risk-prediction model was able to identify distinct groups of patients who are at low, intermediate, and high risk for developing CVD one year after HCT, which could “help clinicians refine surveillance strategies for early detection and treatment of preclinical disease,” according to lead author Saro H. Armenian, DO, MPH, from the department of population sciences at City of Hope in Duarte, California, and colleagues.

“Our model’s one-year post-HCT starting time point capitalizes on the so-called ‘teachable moment’ effect, where survivors, having survived one life-threatening disease, may be more motivated to try [to] prevent additional illness,” the authors wrote. “Information from this study can be used to further refine current [screening recommendations for late effects] and to develop tailored interventions to minimize the morbidity associated with CVD after HCT.”

To create the risk-prediction model, the authors evaluated 1,828 patients who underwent a first HCT for a hematologic malignancy at City of Hope between 1995 and 2004 and had survived without clinical evidence of CVD at one year. Patients were then followed until date of CVD diagnosis or death. Most participants (n=1,031; 56.4%) underwent autologous HCT, and the most common indication for HCT was lymphoma (n=704; 38.5%).

After a median of 7.1 years after the index date (1-year post-HCT; range = 0.1-18.6 years), 135 patients (7.4%) developed CVD. Of this group, 92 patients (68.1%) had heart failure (HF) as their first CVD event, developing at a median of 5.0 years from index date (range not reported); 43 (31.9%) had coronary artery disease as their first CVD event, developing at a median of 7.6 years (range not reported).

Compared with patients who did not develop CVD, those who did were significantly more likely to have:

  • older age: 53.0 years vs. 44.2 years (p<0.001)
  • received high-dose anthracycline (>250 mg/m2): 48.1% vs. 34.3% (p=0.001)
  • undergone autologous HCT: 70.4% vs. 55.3% (p=0.001)
  • hypertension: 49.6% vs. 26.3% (p<0.001)
  • diabetes: 27.4% vs. 9.5% (p<0.001)
  • ever smoked: 43.7% vs. 29.5% (p=0.001)

Using this information, the authors next created a set of predictors that were available at one-year post-HCT survival timepoint, then converted those predictors into corresponding integer scores (TABLE).

The risk scores were collapsed to form three distinct risk groups (low, intermediate, and high) that corresponded to 10-year incidences of CVD of 3.7 percent, 9.9 percent, and 26.2 percent, respectively.

Compared with those in the low-risk group, individuals in the high- and intermediate-risk groups were at 7.8-fold (95% CI 5.0-12.2; p<0.001) and 2.9-fold (95% CI 1.9-4.6; p<0.001) risk of developing CVD.

These scores were validated in an external cohort of 580 HCT recipients from the Fred Hutchinson Cancer Research Center. In this cohort, areas under the curve ranged from 0.66 to 0.75, the authors reported, which showed “that the discriminatory power of [the] model was consistent [despite] different demographics and treatment-related exposures.”

By combining established risk factors in a rational manner, this model allows for individualized risk-prediction and counseling, the researchers concluded, offering the following example: “In survivors at high risk for CVD due to past exposure to cardiotoxic treatments … and hypertension, aggressive management of systolic blood pressure may reduce the risk of future cardiovascular events. … For others with multiple risk factors, a more holistic approach may be necessary, such as incorporating a heart-healthy lifestyle.”

The researchers noted several potential limitations of this risk-prediction model, including CVD risk factors that could not be accounted for in the model and the variation between methods for collecting information about modifiable risk factors.

“We acknowledge that our models may not take into account changes in treatment that have occurred over the past decade, such as the greater use of molecular-targeted agents, some of which have unique cardiotoxicity profiles,” the authors added. “Future studies will need to refine the current estimates, using contemporary cohorts of HCT survivors and taking into consideration the health-economic impact of early screening and prevention strategies in at-risk survivors.”

The authors report no conflicts of interest.

Reference

Armenian SH, Yang D, Teh JB, et al. Prediction of cardiovascular disease among hematopoietic cell transplantation survivors. Blood Advances. 2018;2:1756-64.

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