Clinical Management
.jpg "Laurence Watelle, MD photo")
Laurence Watelle, MD
Clinician-researcher
Department of Pediatrics, Faculty of Medicine and Health Sciences, Centre de recherche du Centre Hospitalier Universitaire de Sherbrooke
Université de Sherbrooke
Sherbrooke, Quebec, Canada
Background: Kawasaki disease is the leading cause of acquired childhood coronary artery aneurysms (CAA). Boys are more affected than girls (male / female ratio 1.5:1). Survival from major cardiac events and normalization rate of CAA is lower in males. We sought to determine the association of biological sex on the risk of developing CAA, and to evaluate the association of baseline biochemical inflammatory markers in each biological sex group.
Methods: This is a multicenter retrospective cohort study of children diagnosed with KD in 5 Canadian centers. Adjusted CAA risk differences between sexes were computed by binomial regression. Association between inflammatory markers and CAA risk according to biological sex was done using logistic regression with an interaction term between sex and each inflammatory marker. Age at diagnosis, complete or incomplete KD diagnostic criteria, initial treatment, repeated treatment and duration of fever were used for adjustment.
RESULTS: There were 1390 subjects diagnosed between 2004 and 2015. Of them, 573 (41.2%) were females, 418 (30.8%) had incomplete diagnostic criteria, and 351 (25.3%) required repeated IVIG therapy. The age at diagnosis (3.5 ± 2.4 years), the fever duration time, and the number of days of fever at initiation of therapy were similar between sexes. The risk of medium to large (Z >5) CAA was higher in boys [70/812 (8.6%)] compared to girls [19/570 (3.3%)]; adjusted risk difference of 4.4 percentage points higher in boys (95%CI: 2.0 to 6.8). The risk of large (Z >10) CAA was 37/812 (4.6%) in boys and 6/570 (1.1%) in girls; adjusted risk difference of 3.0 percentage points higher in boys (95%CI: 1.1 to 4.8). Most biochemical markers of inflammation were positively associated with the risk of medium to large (Z >5) CAA, but biological sex did not significantly change this association.
CONCLUSION: Male biological sex is at a higher risk of developing CAA in KD patients compared to female, all classical confounding variables considered. Nearly all patients were pre-pubertal, rejecting the role of major hormonal influence. Future KD research based on biological sex categorization should be considered for best patient risk stratification acutely and for long-term prognostic valuation.