Modifiable risk factors and major cardiac events among adult survivors of childhood cancer

Abstract

Purpose: To evaluate the relative contribution of modifiable cardiovascular risk factors on the development of major cardiac events in aging adult survivors of childhood cancer.

Patients and methods: Among 10,724 5-year survivors (median age, 33.7 years) and 3,159 siblings in the Childhood Cancer Survivor Study, the prevalence of hypertension, diabetes mellitus, dyslipidemia, and obesity was determined, along with the incidence and severity of major cardiac events such as coronary artery disease, heart failure, valvular disease, and arrhythmia. On longitudinal follow-up, rate ratios (RRs) of subsequent cardiac events associated with cardiovascular risk factors and cardiotoxic therapy were assessed in multivariable Poisson regression models.

Results: Among survivors, the cumulative incidence of coronary artery disease, heart failure, valvular disease, and arrhythmia by 45 years of age was 5.3%, 4.8%, 1.5%, and 1.3%, respectively. Two or more cardiovascular risk factors were reported by 10.3% of survivors and 7.9% of siblings. The risk for each cardiac event increased with increasing number of cardiovascular risk factors (all P(trend) < .001). Hypertension significantly increased risk for coronary artery disease (RR, 6.1), heart failure (RR, 19.4), valvular disease (RR, 13.6), and arrhythmia (RR, 6.0; all P values < .01). The combined effect of chest-directed radiotherapy plus hypertension resulted in potentiation of risk for each of the major cardiac events beyond that anticipated on the basis of an additive expectation. Hypertension was independently associated with risk of cardiac death (RR, 5.6; 95% CI, 3.2 to 9.7).

Conclusion: Modifiable cardiovascular risk factors, particularly hypertension, potentiate therapy-associated risk for major cardiac events in this population and should be the focus of future interventional studies.

Conflict of interest statement

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Figures

Fig 1.

Study population: recruitment and longitudinal participation. SMN, second malignant neoplasm. (*) 624 survivors who did not participate in follow-up #1 subsequently completed follow-up #2.

Fig 2.

Age-specific cumulative incidence of the four major cardiac events—(A) coronary artery disease, (B) valvular disease, (C) arrhythmia, and (D) heart failure—by therapeutic exposure (survivors) compared with siblings. RT, chest-directed radiotherapy.

Fig A1.

Prevalence of cardiovascular risk factors—(A) hypertension, (B), dyslipidemia, (C), diabetes, (D) obesity, and (E) multiple cardiac risk factors—with increasing age.