Childhood cancer increases mortality risk after later CV events

Lower thresholds for hypertension treatment and greater statin use are suggested for long-term survivors of childhood cancer.

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Childhood cancer survivors have a higher risk of death after a cardiovascular event than noncancer peers of a similar age and akin to that in people aged decades older, according to a US study. The findings have prompted a call for increased cardiovascular risk management in childhood cancer survivors.

Researchers from the Virginia Commonwealth University compared mortality rates following a major cardiovascular event, including heart failure, heart attack or stroke, in adult survivors of childhood cancer, their siblings and a sample from a population-based cardiovascular disease research cohort.

“We found that the risk of death after a major cardiovascular event in a 50-year-old in the general population is equivalent to that of a 30-year-old who was previously treated for cancer as a child,” said the study’s lead author, cardio-oncologist Dr Wendy Bottinor, in a statement.

“This study supports the concept that survivors of childhood cancer experience what appears like accelerated aging, where their overall medical profiles are similar to people who are 10 or more years older,” said Dr Bottinor of the VCU Massey Comprehensive Cancer Center and the Pauley Heart Center.

“Given the increased burden of mortality among survivors who develop cardiovascular disease, more aggressive risk factor modification may be appropriate for this population.”

The study utilised data from the Childhood Cancer Survivors Study, which includes 25,000 survivors of childhood cancer and their siblings, and the CARDIA study, a population-based cardiology database of young adults created to gain insights on how people develop heart disease.

At the time of the study the CARDIA cohort was on average 20 years older than the cancer survivor cohort (58 vs 38 years old respectively), and the median age of first CV event among cancer survivors was 31, compared with 57 for the CARDIA cohort.

The median age of cancer onset in the survivors’ group was seven years and the most common cancer diagnoses were leukemia (40%), lymphoma (18%), and other solid tumours (20%). About half of survivors (53%) were treated with anthracyclines, or radiation of a field involving the heart (50%), and 28% received brain radiation.

There was a higher prevalence of major cardiovascular events in cancer survivors compared with siblings overall (6% vs 2%), and a similar prevalence to the much older CARDIA cohort (7%).

After a major cardiovascular event, mortality was higher among cancer survivors than their siblings across all events. Compared with the CARDIA group, mortality was lower in survivors after heart failure, higher after coronary artery disease resulting in myocardial infarction or coronary intervention, and similar after stroke.

Researchers looked at the influence of risk factors including hypertension requiring treatment, dyslipidaemia requiring treatment, current smoking and type 2 diabetes on outcomes following a major cardiovascular event.

They found that current smoking and preexisting hypertension were associated with an increased risk of death, whereas dyslipidaemia was linked to a lower risk. Previous evidence suggests statins, the usual treatment for dyslipidaemia, may be heart-protective in patients undergoing cancer treatment, the authors noted.

The study authors called for clinical heart health guidelines to address cardiovascular risk factors at an earlier age in childhood cancer survivors.

“Untreated risk factors have a larger impact on risk for death following a serious heart event among survivors of childhood cancer relative to the general population, and therefore we shouldn’t just assume that because someone is young, they don’t need risk factors like high blood pressure or high cholesterol treated,” said Dr Bottinor.

Suggested measures included lowering the threshold for treating hypertension in childhood cancer survivors, and using statins more universally in childhood cancer survivors, instead of only in the population that presents with heart problems.

“Optimised clinical care in the setting of a cardiovascular event, greater inclusion of survivors in clinical trials, enhanced risk factor modification, and improved access to care that directly considers late effects of cancer therapy, are potential pathways to address disparities in mortality among survivors compared with noncancer cohorts who experience a major cardiovascular event,” the authors concluded.

Associate Professor Rachel Conyers of the Murdoch Children’s Research Institute in Victoria authored the Australian and New Zealand cardio-oncology guidelines for paediatric oncology patients aimed at preventing and treating cardiac complications in children being treated for cancer.

She told The Medical Republic that the current study was an interesting one, focusing on a different timepoint in the childhood cancer survivors’ journey.

“Hypertension itself is linked to a number of cancer therapeutics, including molecular inhibitors and steroids, and is reversible at the cessation of therapy,” said Professor Conyers.

“However, we advocate for blood pressure monitoring during therapy with judicious control for patients with ongoing hypertension.

“We did not see high incidence of metabolic syndrome or need for statins in our clinic, but metabolic syndrome is usually a late finding after therapy finished.”

Journal of the American College of Cardiology 2024, online 27 February