CLINICAL NEWS
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 intermediaterisk 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 .
TABLE . Integer Risk Scores and Corresponding Prediction Models Variable Hazard ratio ( 95 % CI ) p Value Risk score Age , years < 30 1.0 0 30 to < 50 2.35 ( 1.15-4.80 ) . 019 2 ≥50 4.00 ( 1.98-8.08 ) <. 001 3
Anthracycline dose ≤250 mg / m 2 1.0 0 > 250 mg / m 2 1.88 ( 1.33-2.66 ) <. 001 1
Hypertension No 1.0 0 Yes 2.03 ( 1.42-2.90 ) <. 001 2
Diabetes No 1.0 0 Yes 2.70 ( 1.84-3.97 ) <. 001 2
Smoking Never 1.0 0 Ever 1.39 ( 0.99-1.96 ) . 060 1
Chest radiation None 1.0 0 Any 1.92 ( 1.07-3.43 ) . 028 1
Risk scores of 0 , 1 , 2 , and 3 correspond to hazard ratios of < 1.3 , 1.3 to 1.9 , 2.0 to 2.9 , and 3.0 to 4.9 , respectively .
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 .”
“ [ This model could ] help clinicians refine surveillance strategies for early detection and treatment of preclinical disease .”
— SARO H . ARMENIAN , DO , MPH
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 hearthealthy 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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