Survivors of Kawasaki disease remain at a higher long-term risk for cardiovascular events into young adulthood, including myocardial infarction, compared to people without the disease, new evidence reveals. The elevated risks emerged in survivors both with and without cardiovascular involvement at the time of initial diagnosis.
Overall risk of cardiovascular events was highest in the first year following Kawasaki disease diagnosis, and about 10 times greater than in healthy children, Cal Robinson, MD, said during a press conference at the virtual annual meeting of the American College of Rheumatology.
“The risk gradually decreased over time. However, even 10 years after diagnosis of their illness, they still had a 39% higher risk,” said study author Dr. Robinson, a PGY4 pediatric nephrology fellow at The Hospital for Sick Children in Toronto.
Dr. Robinson also put the numbers in perspective. “We fully acknowledged these are very rare events in children, especially healthy children, which is why we needed such a large cohort to study this. Interpret the numbers cautiously.”
In terms of patient and family counseling, “I would say children with Kawasaki disease have a higher risk of myocardial infarction, but the absolute risk is still low,” he added. For example, 16 Kawasaki disease survivors experienced a heart attack during follow-up, or 0.4% of the affected study population, compared to a rate of 0.1% among matched controls.
“These families are often very frightened after the initial Kawasaki disease diagnosis,” Dr. Robinson said. “We have to balance some discussion with what we know about Kawasaki disease without overly scaring or terrifying these families, who are already anxious.”
To quantify the incidence and timing of cardiovascular events and cardiac disease following diagnosis, Dr. Robinson and colleagues assessed large databases representing approximately 3 million children. They focused on children hospitalized with a Kawasaki disease diagnosis between 1995 and 2018. These children had a median length of stay of 3 days and 2.5% were admitted to critical care. The investigators matched his population 1:100 to unaffected children in Ontario.
Follow-up was up to 24 years (median, 11 years) in this retrospective, population-based cohort.
Risks raised over a decade and beyond
Compared to matched controls, Kawasaki disease survivors had a higher risk for a cardiac event in the first year following diagnosis (adjusted hazard ratio, 11.65; 95% confidence interval, 10.34-13.13). The 1- to 5-year risk was lower (aHR, 3.35), a trend that continued between 5 and 10 years (aHR, 1.87) and as well as after more than 10 years (aHR, 1.39).
The risk of major adverse cardiac events (MACE, a composite of myocardial infarction, stroke, or cardiovascular death) was likewise highest in the first year after diagnosis (aHR, 3.27), followed by a 51% greater risk at 1-5 years, a 113% increased risk at 5-10 years, and a 17% elevated risk after 10 years.
The investigators compared the 144 Kawasaki disease survivors who experienced a coronary artery aneurysm (CAA) within 90 days of hospital admission to the 4,453 others who did not have a CAA. The risk for a composite cardiovascular event was elevated at each time point among those with a history of CAA, especially in the first year. The adjusted HR was 33.12 in the CAA group versus 10.44 in the non-CAA group.
“The most interesting finding of this study was that children with Kawasaki syndrome are at higher risk for composite cardiovascular events and major adverse cardiac events even if they were not diagnosed with coronary artery aneurysm,” session comoderator, professor of medicine and director of division of rheumatology at the University of Texas Health Science Center at Houston, said when asked to comment.
Dr. Robinson and colleagues also looked at outcomes based on presence or absence of coronary involvement at the time of Kawasaki disease diagnosis. For example, among those with initial coronary involvement, 15% later experienced a cardiovascular event and 10% experienced a major cardiovascular event.
“However, we were specifically interested in looking at children without initial coronary involvement. In this group, we also found these children were at increased risk for cardiovascular events compared to children without Kawasaki disease,” Dr. Robinson said. He said the distinction is important because approximately 95% of children diagnosed with Kawasaki disease do not feature initial coronary involvement.
In terms of clinical care, “our data provides an early signal that Kawasaki disease survivors – including those without initial coronary involvement – may be at higher risk of cardiovascular events into early adulthood.”