Children with Kawasaki Disease at higher risk for heart problems 10 years later

November 06, 2020

ATLANTA -- New research shows that children with Kawasaki Disease remain at an increased risk for cardiovascular events more than 10 years after hospitalization for their condition, highlighting the need for long-term heart disease surveillance and risk reduction strategies for these young patients. Details of the study was presented at ACR Convergence, the American College of Rheumatology's annual meeting (ABSTRACT #0937).

Kawasaki disease (KD) is a childhood illness that causes blood vessels to become inflamed (vasculitis) and swell. KD is most common in children younger than five years old; however, older children can be affected too. Its exact cause is unknown. Without prompt medical evaluation and treatment, serious damage to the blood vessels of the heart may develop. KD is associated with coronary artery aneurysms.

Researchers in Ontario, Canada noticed that the incidence of KD has significantly increased in their province over the past two decades. However, the risk of long-term cardiovascular events after childhood KD diagnosis remains unknown. They launched this study to determine the risk and timing of long-term cardiovascular events and death among KD survivors.

"The motivation to perform this study came from a conversation I had with a patient's family as a first-year pediatric resident. Their child had been diagnosed with KD and was almost ready to be discharged from the hospital. They asked me whether their child would be at risk of heart disease later in life," says study co-author Cal Robinson, MD, BSc, Pediatric Nephrology Resident at The Hospital for Sick Children and the University of Toronto. "Not knowing the answer, I dug deeper into the published literature about cardiovascular outcomes after KD and found that a significant knowledge gap existed, particularly in children who did not develop coronary artery aneurysms during their acute illness. It's very important that we better understand the cardiovascular risk after childhood KD. Earlier diagnosis provides opportunities for intervention, which may mitigate the risk of heart disease later in life."

The researchers identified all children up to 18 years of age who survived hospitalization for KD in Ontario between 1995-2018 using health administrative databases. They included only the first eligible hospitalization, excluding children who were previously diagnosed with KD, as well as non-residents of Ontario. They matched each KD case to 100 non-exposed control cases by age, sex and year. They then followed these patients until death or March 2019, or up to 24 years old. They determined the rates of cardiovascular events, major adverse cardiac events (such as heart attack or stroke) and death, comparing children who had KD with those who were not exposed to the disease. They looked specifically at four time periods after hospital discharge: 0-1 year, 1-5 years, 5-10 years and more than 10 years.

They found that, among 4,597 KD survivors, 746 or 16.2% experienced cardiovascular events compared with 5.2% of children without the disease. They also found that 79 or 1.7% experienced major adverse cardiac events compared to 0.7% of children without the disease, and nine died during the median 11-year follow-up period. The most frequent cardiovascular events experienced by KD survivors were ischemic heart disease, arrhythmias, high blood pressure and peripheral vascular disease. KD survivors were at higher risk of heart problems compared to patients who did not have the disease and they experienced cardiovascular events sooner. Their risk was highest in the first year after they were discharged from the hospital. They were also at higher risk of heart surgery like coronary artery bypass grafting. However, their risk of death during follow-up was lower than non-exposed patients.

"Our study results provide a signal that KD survivors have a higher risk of developing heart disease more than ten years after their initial diagnosis. This suggests that KD survivors should be screened at regular intervals for cardiovascular diseases and associated risk factors," says Dr. Robinson. "Cardiovascular risk reduction strategies should be implemented for all KD survivors, including healthy active lifestyle counselling and early intervention when cardiovascular risk factors are identified."
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About ACR Convergence

ACR Convergence, the ACR's annual meeting, is where rheumatology meets to collaborate, celebrate, congregate, and learn. Join ACR for an all-encompassing experience designed for the entire rheumatology community. ACR Convergence is not just another meeting - it's where inspiration and opportunity unite to create an unmatched educational experience. For more information about the meeting, visit https://www.rheumatology.org/Annual-Meeting, or join the conversation on Twitter by following the official hashtag (#ACR20).

About the American College of Rheumatology

The American College of Rheumatology (ACR) is an international medical society representing over 7,700 rheumatologists and rheumatology health professionals with a mission to empower rheumatology professionals to excel in their specialty. In doing so, the ACR offers education, research, advocacy and practice management support to help its members continue their innovative work and provide quality patient care. Rheumatologists are experts in the diagnosis, management and treatment of more than 100 different types of arthritis and rheumatic diseases.

ABSTRACT:

Late Cardiovascular Outcomes in Children with Kawasaki Disease: A Population-based Cohort Study

Background/Purpose:

Kawasaki disease (KD) is a common childhood vasculitis associated with coronary artery aneurysms (CAA). Based on our recent work, the incidence of KD has significantly increased in Ontario over the past two decades. However, the risk of long-term cardiovascular events in children without large CAA remains unknown. Our objectives were to: 1) determine the risk and timing of long-term cardiovascular events (diagnoses and procedures) among KD survivors; and 2) determine the risk of all-cause mortality.

Methods:

We identified all children (0-18yr) surviving hospitalization with a KD diagnosis in Ontario between 1995-2018, through validated algorithms using population health administrative databases. We included only the first eligible hospitalization and excluded children previously diagnosed with KD and non-residents. KD cases were matched to 100 non-exposed controls by age, sex and index year. Follow-up continued until death or March 2019 (maximum 24 years). We determined incidence rates (per 1000 person-years (py)) and unadjusted hazard ratios (HR) for cardiovascular events, major adverse cardiac events (MACE; cardiovascular death, myocardial infarction (MI) or stroke composite) and all-cause mortality, comparing KD and non-exposed cohorts during the following time periods: 0-1yr, 1-5yr, 5-10yr and >10yr.

Results:

Among 4,597 KD survivors, 746 (16.2%) experienced cardiovascular events, 79 (1.7%) MACE and 9 (0.2%) died during median 11.1-year follow-up (Table 1). The most frequent cardiovascular events among KD survivors were ischemic heart disease (231 children, 4.6 events/1000py), arrhythmias (229, 4.5/1000py), hypertension (159, 3.1/1000py) and peripheral vascular disease (107, 2.1/1000py). KD survivors were at increased risk of cardiovascular events and MACE vs. non-exposed children between 0-1yr, 1-5yr and 5-10yr, and cardiovascular events at >10yr follow-up (Table 1). KD survivors experienced cardiovascular events sooner than non-exposed children (Figure 1; Kaplan-Meier curve, log-rank p< 0.0001). Their risk of cardiovascular events was highest in the first year post-discharge (HR 14.13 [12.57-15.89]). KD survivors were at increased risk of undergoing percutaneous coronary intervention or coronary artery bypass grafting throughout follow-up (KD: 12 (0.3%) vs. non-exposed: 63 (0.01%), HR 14.68 [7.73-27.88]). KD survivors were at lower risk of mortality throughout follow-up (KD: 9 (0.2%) vs. non-exposed: 2,012 (0.4%), HR 0.42 [0.22-0.81]).

Conclusions:

Children diagnosed with KD remain at increased risk of cardiovascular events for >10 years after index hospitalization. Despite the prevalence of cardiovascular disease, they have a lower risk of long-term mortality. Our findings highlight the need for cardiovascular disease surveillance and risk reduction strategies among KD survivors.

American College of Rheumatology

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