Gastrointestinal abnormalities as predictors of cardiovascular involvement in Kawasaki disease: a 5-year retrospective study

Abstract

Background

Kawasaki disease (KD) is an acute, self-limited vasculitis in children that can lead to significant cardiovascular complications. Gastrointestinal manifestations and related laboratory abnormalities are common in KD, but their association with cardiovascular involvement remains incompletely understood. This study aimed to evaluate the relationship between gastrointestinal-related laboratory and imaging findings and echocardiographic outcomes in pediatric KD.

Methods

We conducted a retrospective study of 258 children with KD admitted from 2019 to 2024. Demographic, clinical, laboratory, and imaging data, including echocardiography and abdominal ultrasonography, were collected. Univariate and multivariate logistic regression analyses were performed to identify cardiovascular involvement, including coronary artery aneurysm, dilatation, brightness, and valvular abnormalities.

Results

Among 258 patients (mean age 3.53 ± 2.69 years; 67.4% male), abnormal echocardiographic findings were observed in 70.7%. Coronary artery aneurysms and dilatation occurred in 9.8% and 9.4%, respectively. Abnormal abdominal sonography was detected in 21.3%. Multivariate analysis identified male sex, anemia, hypoalbuminemia, elevated alkaline phosphatase, elevated C-reactive protein, and prolonged partial thromboplastin time as independent associated factors of cardiovascular involvement in KD patients.

Conclusions

Gastrointestinal-related laboratory abnormalities are significantly associated with cardiovascular involvement in children with KD. Early recognition of high-risk patients, particularly males with anemia, hypoalbuminemia, elevated inflammatory markers, and abnormal liver enzymes, may assist in early risk stratification and intensified cardiac surveillance in the acute phase of KD.

Introduction

Kawasaki disease (KD) is a self-limited, multisystem vasculitis affecting small to medium-sized blood vessels. Although several theories have been proposed, its etiology remains unknown. KD predominantly affects children under the age of 5 years [1–4]. In addition to the classic diagnostic features, KD can involve other organ systems, including the cardiovascular, respiratory, gastrointestinal (GI), genitourinary, musculoskeletal, and neurological systems. However, these findings are not included in the formal diagnostic criteria [4, 5]. Currently, there is no single laboratory biomarker that definitively diagnoses KD. However, common laboratory abnormalities include anemia, thrombocytosis, leukocytosis with neutrophilia, elevated acute-phase reactants and inflammatory markers, as well as abnormal liver function tests and renal profiles [5, 6].

Among the various systemic involvements, cardiovascular complications are the most clinically significant, given their association with long-term morbidity and mortality. KD is the leading cause of acquired heart disease in children in many countries. Cardiovascular manifestations may include coronary artery lesions, non-coronary artery vasculitis, pericarditis, myocarditis, endocarditis, aortic root dilatation, and valvular regurgitation [7]. Echocardiography is the imaging modality of choice for detecting coronary artery abnormalities. Common echocardiographic findings include coronary artery dilatation, aneurysm formation, increased perivascular brightness of the coronary arteries, valvular abnormalities, pericardial effusion, and myocardial dysfunction. Early echocardiographic assessment is crucial, as these abnormalities are highly correlated with intravenous immunoglobulin (IVIG) resistance and the development of coronary artery lesions [7–10]. Risk of coronary artery involvement is higher in patients with unusual or severe disease presentations, very young or older age, male sex, delayed diagnosis or treatment, and those who respond poorly to standard IVIG therapy [5, 11–13].

Common GI manifestations in KD include abdominal pain, diarrhea, vomiting, and hepatitis; less frequent findings include jaundice and pancreatitis [5]. A study in Iran reported GI involvement in approximately 38% of KD patients [14]. Ultrasonographic findings in these cases include gallbladder hydrops, paralytic ileus, intestinal pseudo-obstruction, cholecystitis, splenomegaly, hepatomegaly, hemorrhagic duodenitis, and appendicular involvement [15–17]. Notably, splenomegaly has been associated with a higher incidence of coronary artery lesions [15]. Patients with abnormal gallbladder findings on ultrasound have shown greater resistance to IVIG therapy [18]. Laboratory abnormalities such as elevated liver enzymes and low albumin levels have been associated with gastrointestinal involvement in KD [19]. These markers may also indicate a higher risk of resistance to IVIG therapy and the development of coronary artery complications [19–21].

Given the shared inflammatory and vascular mechanisms underlying GI and cardiovascular involvement in KD, laboratory indicators of GI involvement may reflect systemic disease severity and help identify patients at higher risk for cardiac complications. This study aims to evaluate the relationship between GI manifestations and cardiovascular involvement in patients with KD, with particular emphasis on echocardiographic findings, including coronary artery brightness, dilatation, aneurysms, and valvular abnormalities.

Methods and materials

Study design and setting

This retrospective cohort study was conducted over five years from 2019 to 2024 at Namazi Hospital, a tertiary referral center in Shiraz, Iran. The study included all pediatric patients diagnosed with KD who were admitted during the study period, using census sampling. KD was diagnosed according to established clinical criteria consistent with American Heart Association guidelines [22]. Due to the retrospective design, complete and incomplete KD were not consistently distinguishable in all cases; therefore, both forms were included in the analysis. Patients with a prior history of cardiovascular disease, concomitant infections, inflammatory disorders, or hypersensitivity reactions were excluded. The study was conducted in accordance with the principles of the Declaration of Helsinki and was approved by the Ethics Committee of Shiraz University of Medical Sciences (Ethics Code: IR.SUMS.MED.REC.1402.503). Written informed consent was obtained from the parents or legal guardians of all participating children before inclusion in the study. All patient data were anonymized to ensure confidentiality.

Data collection

Data were retrospectively extracted from medical records using a structured checklist. Demographic and clinical information included age, sex, duration of hospitalization, and previous medical history. Laboratory parameters included white blood cell (WBC) count, hemoglobin (Hb), platelet (PLT) count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total protein, serum albumin, total bilirubin, prothrombin time (PT), and partial thromboplastin time (PTT). Abnormal laboratory parameters were defined according to age-adjusted reference ranges provided by the hospital’s central laboratory and standard pediatric reference values. Imaging studies included abdominopelvic ultrasonography and transthoracic echocardiography. Examinations were performed by experienced pediatric cardiologists using standardized institutional protocols. Coronary artery dimensions were measured in accordance with established recommendations and adjusted for body surface area. Echocardiographic interpretations were based on standardized criteria consistent with the recommendations of the American Heart Association for the diagnosis and management of KD [22]. Valvular abnormalities were recorded based on echocardiographic reports. However, due to retrospective data extraction, differentiation between physiological and pathological valvular regurgitation was not consistently available.

Statistical analysis

Continuous variables are presented as mean ± standard deviation, and categorical variables as frequencies and percentages. Comparisons between groups were performed using the Chi-square test or Fisher’s exact test for categorical variables, and the independent samples t-test or Mann–Whitney U test for continuous variables, depending on the distribution of the data. Univariate logistic regression analyses were initially conducted to identify variables associated with echocardiographic, coronary, and abdominal sonographic outcomes. Variables with a p-value of less than 0.20 in univariate analysis were subsequently included in multivariate logistic regression models. The results of regression analyses are reported as odds ratios with 95% confidence intervals. Statistical analyses were performed using SPSS 22.0 software (SPSS Inc., Chicago, IL, USA), and a p-value of less than 0.05 was considered statistically significant.

Results

Demographic and clinical characteristics

A total of 272 pediatric patients diagnosed with KD were initially included. After excluding patients with prior KD (n = 7), COVID-19 infection (n = 6), and Multisystem Inflammatory Syndrome in Children (MIS-C; n = 1), 258 patients were analyzed. Among them, 174 (67.4%) were male, and 84 (32.6%) were female, yielding a male-to-female ratio of approximately 2:1. The mean age was 3.53 ± 2.69 years (range 0.1–11 years).

The mean duration of hospitalization was 5.78 ± 3.70 days, ranging from 1 to 27 days. Most patients (226; 87.6%) had no significant past medical history. The most frequent specific condition was glucose-6-phosphate dehydrogenase (G6PD) deficiency (24; 9.3%), followed by previous KD (7; 2.7%), COVID-19 infection (6; 2.3%), and asthma (2; 1.8%). Rare conditions included B12 deficiency, Bartter syndrome, chickenpox, epilepsy, and hypothyroidism (each n = 1; 0.4%).

Laboratory, echocardiography, and abdominal Imaging findings

The mean WBC count was 15.0 ± 6.11 × 10³/µL (range 1.1–48.8 × 10³/µL). Leukocytosis was present in 121/254 (47.6%). Hb averaged 9.93 ± 1.62 g/dL (range 5.3–16.4 g/dL). Anemia was present in 220/256 (85.9%). PLT counts were elevated (mean 531.8 ± 281.6 × 10³/µL, range 14–1469 × 10³/µL). Inflammatory markers included ESR 78.7 ± 38.5 mm/h (range 2–140 mm/h) and CRP 78.04 ± 53.71 mg/L (range 1–180 mg/L). Liver function tests showed AST 40.59 ± 42.11 U/L (range 9–280) and ALT 49.81 ± 67.34 U/L (range 3–513). ALP levels averaged 469.79 ± 233.42 U/L (range 106–1950). Mean total protein was 6.51 ± 1.18 g/dL, albumin 3.55 ± 0.59 g/dL, and total bilirubin 0.61 ± 1.06 mg/dL. Coagulation studies showed PT 14.94 ± 3.82 s (range 10.1–57.0) and PTT 34.24 ± 6.99 s (range 20–84).

Echocardiography was performed in 256 patients. Abnormal findings were observed in 181 patients (70.7%), while 75 (29.3%) had normal results. Coronary artery aneurysms were present in 25 of 256 patients (9.8%), dilatation in 24 (9.4%), and coronary brightness in 43 of 256 (16.8%). Valvular abnormalities were noted in 155 patients (60.5%). Abdominal sonography was performed in 141 patients, with abnormal findings in 30 patients (21.3%). The most common abnormalities were free fluid (12.8%) and mesenteric lymphadenopathy (6.4%). Splenomegaly, gallbladder wall abnormalities, and intestinal wall thickening were each observed in 1.4% of patients. Echocardiography was suggestive of pulmonary hypertension in 2 (0.8%) of the patients. Full echocardiography and abdominal ultrasound details are presented in Fig. 1.

Fig. 1.

Echocardiography and abdominal sonography findings in patients with Kawasaki disease

Univariate logistic regression analyses

The univariate logistic regression analyses identified several clinical and laboratory variables associated with echocardiographic and coronary outcomes, valvular abnormalities, and abdominal sonographic findings. For echocardiographic abnormalities, age-adjusted WBC count did not reach statistical significance. Anemia was significantly associated with echocardiographic abnormalities, with an odds ratio of 2.825 (95% CI: 1.375–5.802; P = 0.005). Similarly, abnormal total protein levels were associated with increased odds of abnormal echocardiography (OR = 2.182; 95% CI: 1.200–3.968; P = 0.011). Total bilirubin exhibited a non-significant trend towards higher odds. Prolonged PTT was significantly associated with echocardiographic abnormalities (OR = 2.419; 95% CI: 1.110–5.271; P = 0.026). Female sex was associated with lower odds of abnormal echocardiography (OR = 0.542; 95% CI: 0.310–0.948; P = 0.032). Abnormal abdominal sonography was not significantly associated with echocardiographic outcomes (OR = 0.481; 95% CI: 0.190–1.218; P = 0.223) (Table 1).

Table 1.

Univariate analysis of laboratory and clinical predictors for echocardiographic abnormalities

Outcome	Variable	OR	95% CI	P-value
Echocardiographic Abnormalities	WBC	1.605	0.925–2.784	0.093*
	Hemoglobin	2.825	1.375–5.802	0.005**
	Platelets	1.467	0.851–2.528	0.167*
	ESR	0.651	0.176–2.404	0.519
	CRP	0.470	0.l32–1.674	0.244
	AST	0.964	0.555–1.677	0.897
	ALT	1.068	0.593–1.923	0.827
	ALP	1.241	0.717–2.150	0.440
	Total Protein	2.182	1.200–3.968	0.011**
	Albumin	1.287	0.749–2.211	0.361
	Total Bilirubin	4.968	0.629–39.230	0.128*
	PT	1.056	0.540–2.064	0.874
	PTT	2.419	1.110–5.271	0.026**
	Sex (Female)	0.542	0.310–0.948	0.032**
	Duration of Hospitalization	1.086	0.985–1.197	0.097*
	Abnormal abdominal sonography	0.481	0.190–1.218	0.223

Abbreviations: WBC white blood cell, ESR erythrocyte sedimentation rate, CRP C-reactive protein, AST aspartate aminotransferase, ALT alanine aminotransferase, ALP alkaline phosphatase, PT prothrombin time, PTT partial thromboplastin time, OR odds ratio, CI confidence interval

^*: p-value < 0.2. ^**: p-value < 0.05

For coronary artery aneurysm, low albumin levels were significantly associated with aneurysm formation (OR = 0.406; 95% CI: 0.169–0.978; P = 0.045). Prolonged PTT demonstrated a borderline inverse association (OR = 0.379; 95% CI: 0.141–1.018; P = 0.054), and longer duration of hospitalization was significantly associated with decreased odds of aneurysm (OR = 0.856; 95% CI: 0.779–0.940; P = 0.001). In the analysis of coronary artery dilatation, leukocytosis was associated with decreased odds (OR = 0.411; 95% CI: 0.177–0.955; P = 0.039). Elevated AST was associated with increased odds (OR = 2.634; 95% CI: 1.013–6.851; P = 0.047), and elevated ALP significantly increased the odds of dilatation (OR = 4.100; 95% CI: 1.576–10.666; P = 0.004). CRP and ALT demonstrated non-significant trends. Duration of hospitalization was inversely associated with coronary dilatation (OR = 0.900; 95% CI: 0.821–0.986; P = 0.024). Male sex was significantly associated with coronary artery brightness (OR = 2.316; 95% CI: 1.097–4.892; P = 0.028), while lower albumin showed a non-significant trend. Valvular abnormalities were significantly associated with anemia (OR = 0.406; 95% CI: 0.198–0.832; P = 0.014), elevated ALP (OR = 0.536; 95% CI: 0.319–0.903; P = 0.019), low total protein (OR = 0.503; 95% CI: 0.294–0.863; P = 0.013), prolonged PTT (OR = 0.400; 95% CI: 0.195–0.821; P = 0.013), and male sex (OR = 1.826; 95% CI: 1.074–3.106; P = 0.026) (Table 2).

Table 2.

Univariate analysis of laboratory and clinical predictors for coronary artery and valvular abnormalities

Outcome	Variable	OR	95% CI	P-value
Coronary Artery Aneurysm	WBC	0.683	0.297–1.568	0.368
	Hemoglobin	0.231	0.030–1.763	0.158*
	Platelets	0.702	0.306–1.611	0.404
	ESR	0.716	0.090–5.723	0.753
	CRP	1.250	0.269–5.813	0.776
	AST	1.456	0.560–3.788	0.441
	ALT	1.490	0.521–4.257	0.457
	ALP	1.424	0.568–3.571	0.451
	Total protein	0.619	0.270–1.418	0.257
	Albumin	0.406	0.169–0.978	0.045**
	Total Bilirubin	1.015	0.124–8.288	0.989
	PT	0.734	0.249–2.166	0.576
	PTT	0.379	0.141–1.018	0.054*
	Sex (Male)	1.042	0.430–2.522	0.927
	Duration of Hospitalization	0.856	0.779–0.940	0.001**
	Abnormal abdominal sonography	1.010	0.263–3.879	0.988
Coronary Artery Dilatation	WBC	0.411	0.177–0.955	0.039**
	Hemoglobin	0.454	0.103–2.006	0.298
	Platelets	0.714	0.320–1.593	0.411
	ESR	0.624	0.078–4.969	0.656
	CRP	2.714	0.822–8.966	0.101*
	AST	2.634	1.013–6.851	0.047**
	ALT	2.056	0.742–5.696	0.166*
	ALP	4.100	1.576–10.666	0.004**
	Total protein	0.859	0.381–1.936	0.713
	Albumin	1.013	0.456–2.250	0.975
	Total Bilirubin	0.515	0.106–2.507	0.411
	PT	0.675	0.231–1.973	0.473
	PTT	0.698	0.258–1.884	0.478
	Sex (Male)	1.180	0.494–2.818	0.710
	Duration of Hospitalization	0.900	0.821–0.986	0.024**
	Abnormal abdominal sonography	1.010	0.263–3.879	0.988
Coronary Artery Brightness	WBC	0.720	0.387–1.340	0.300
	Hemoglobin	0.791	0.310–2.018	0.624
	Platelets	0.953	0.516–1.759	0.877
	ESR	1.617	0.486–5.383	0.434
	CRP	0.783	0.218–2.817	0.708
	AST	0.794	0.417–1.512	0.483
	ALT	0.994	0.501–1.972	0.987
	ALP	1.165	0.613–2.214	0.641
	Total protein	0.745	0.399–1.389	0.354
	Albumin	0.655	0.353–1.216	0.180*
	Total Bilirubin	0.709	0.184–2.729	0.617
	PT	0.873	0.384–1.985	0.745
	PTT	0.771	0.342–1.738	0.531
	Sex (Male)	2.316	1.097–4.892	0.028**
	Duration of Hospitalization	0.976	0.896–1.064	0.587
	Abnormal abdominal sonography	1.761	0.682–4.544	0.242
Valvular Abnormalities	WBC	1.003	0.605–1.663	0.991
	Hemoglobin	0.406	0.198–0.832	0.014**
	Platelets	1.137	0.688–1.879	0.617
	ESR	0.831	0.279–2.473	0.739
	CRP	2.317	0.739–7.258	0.149*
	AST	0.967	0.575–1.625	0.899
	ALT	0.775	0.445–1.351	0.369
	ALP	0.536	0.319–0.903	0.019**
	Total Protein	0.503	0.294–0.863	0.013**
	Albumin	0.910	0.550–1.504	0.713
	Total Bilirubin	0.491	0.129–1.862	0.296
	PT	0.675	0.359–1.272	0.224
	PTT	0.400	0.195–0.821	0.013**
	Sex (Male)	1.826	1.074–3.106	0.026**
	Duration of Hospitalization	0.954	0.881–1.034	0.255
	Abnormal abdominal sonography	0.713–3.755	1.636	0.245

Abbreviations: WBC white blood cell, ESR erythrocyte sedimentation rate, CRP C-reactive protein, AST aspartate aminotransferase, ALT alanine aminotransferase, ALP alkaline phosphatase, PT prothrombin time, PTT partial thromboplastin time, OR odds ratio, CI confidence interval

^*: p-value < 0.2. ^**: p-value < 0.05

Multivariate logistic regression analyses

In multivariate logistic regression for abnormal echocardiographic findings, independent associated factors were anemia (OR = 4.567; 95% CI: 1.492–13.983; P = 0.008), prolonged PTT (OR = 2.642; 95% CI: 1.084–6.439; P = 0.033), and male sex (OR = 0.405; 95% CI: 0.192–0.855; P = 0.018). WBC, total protein, total bilirubin, platelet count, and duration of hospitalization were not significant (p = 0.808, 0.348, 0.999, 0.141, 0.308; respectively) (Fig. 2).

Fig. 2.

Forest plot of multivariate logistic regression for predictors of abnormal echocardiographic findings

For coronary artery aneurysm, low albumin was independently associated with reduced odds of aneurysm formation (OR = 0.101; 95% CI: 0.022–0.463; P = 0.003). Longer hospitalization was also protective (OR = 0.887; 95% CI: 0.793–0.992; P = 0.036), and prolonged PTT showed a borderline inverse association (OR = 0.338; 95% CI: 0.112–1.014; P = 0.053). In coronary artery dilatation, age-adjusted WBC (OR = 0.219; 95% CI: 0.071–0.674; P = 0.008), elevated CRP (OR = 8.838; 95% CI: 1.680–46.486; P = 0.010), elevated ALP (OR = 4.966; 95% CI: 1.579–15.619; P = 0.006), and longer hospitalization (OR = 0.886; 95% CI: 0.797–0.985; P = 0.025) were independent associated factors. AST and ALT were not significant (p = 0.263, 0.690; respectively). Male sex independently predicted coronary artery brightness (OR = 2.268; 95% CI: 1.071–4.801; P = 0.032), whereas albumin was not significant (OR = 0.678; 95% CI: 0.363–1.267; P = 0.224) (Fig. 3).

Fig. 3.

Forest plots of multivariate logistic regression for predictors of coronary artery aneurysm, brightness, and dilatation

Valvular abnormalities were independently associated with anemia (OR = 0.294; 95% CI: 0.099–0.875; P = 0.028), low total protein (OR = 0.461; 95% CI: 0.217–0.977; P = 0.043), and male sex (OR = 2.601; 95% CI: 1.269–5.332; P = 0.009). CRP, ALP, and PTT demonstrated borderline associations (P = 0.076, 0.069, 0.089, respectively).

Discussion

In this retrospective cohort of pediatric patients with KD, we demonstrated significant associations between GI-related abnormalities and cardiovascular involvement. Male sex, inflammatory markers such as CRP, hypoalbuminemia, anemia, elevated ALP, and coagulation abnormalities emerged as important associated factors of echocardiographic findings. These results support the hypothesis that systemic inflammatory burden and GI-related derangements reflect disease severity and may contribute to cardiovascular complications in KD.

The overall prevalence of coronary artery abnormalities in our cohort aligns with previously reported rates. Coronary artery aneurysms were identified in approximately 10% of patients, which is comparable to the incidence reported in large observational studies and systematic reviews, where the frequency of coronary artery aneurysms ranged between 3% and 27%, depending on age, disease severity, and timing of treatment [23]. Xu et al. similarly reported coronary artery lesions in 11.72% of KD patients, with a markedly higher incidence among incomplete KD cases and infants younger than one year [24]. These findings underscore the importance of early recognition and prompt treatment, as delayed IVIG therapy has been consistently associated with increased coronary involvement [7, 24]. In our study, the high prevalence of valvular abnormalities, particularly tricuspid and pulmonary regurgitation, should be interpreted with caution, as mild regurgitation may represent physiological findings in pediatric populations

Male sex emerged as an independent predictor of coronary artery brightness and valvular abnormalities in our multivariate models. This finding is consistent with multiple studies demonstrating a male predominance in KD and an increased risk of coronary complications among boys [24, 25]. Large cohort studies and nationwide surveys have consistently shown male sex to be associated with both coronary artery dilatation and aneurysm formation [13, 26, 27]. Inflammatory markers played a central role in predicting cardiovascular involvement in our study. Elevated CRP was an independent predictor of coronary artery dilatation, consistent with prior evidence identifying CRP as a marker of disease severity and coronary risk. High CRP levels are incorporated into the American Heart Association diagnostic criteria for incomplete KD [7]. Several studies have demonstrated that elevated CRP is an independent risk factor for concurrent coronary artery lesions, with an optimal cutoff value around 105.5 mg/L [28]. Shuai et al. and Chang et al. similarly identified high CRP as a strong predictor of coronary involvement, particularly when combined with male sex and anemia [25, 28]. Although most patients with KD exhibit elevated inflammatory markers, normal or atypical laboratory findings may occur, particularly in early or incomplete presentations. In our study, anemia was independently associated with echocardiographic abnormalities and valvular involvement in our cohort. Anemia has been consistently linked to coronary artery lesions in KD across multiple studies and meta-analyses [13, 25, 29]. Changes in hepcidin, a key regulator of inflammation-associated anemia, have been shown to correlate inversely with hemoglobin levels and to be associated with coronary artery involvement in KD, providing a potential mechanistic explanation for this association [30].

Hypoalbuminemia was significantly associated with coronary artery aneurysm formation in our multivariate analysis. Low serum albumin has been repeatedly reported as a marker of severe inflammation, increased vascular permeability, and worse cardiovascular outcomes in KD [27, 31]. Large cohort studies have shown that children with low albumin levels, particularly infants, face a substantially higher risk of coronary artery lesions and aneurysm formation [13, 32]. In a large cohort study from China, Xia et al. found that hypoalbuminemia (< 30 g/L) was independently associated with progression of coronary artery lesions in children with KD [33]. The association between hypoalbuminemia and coronary involvement may reflect capillary leakage and heightened inflammatory activity during the acute stage of disease. Elevated ALP was independently associated with coronary artery dilatation in our study. Although less frequently discussed, GI and hepatobiliary manifestations in KD, including abnormal liver function tests, have been reported and are thought to reflect systemic inflammation and hepatic involvement, and have also been associated with increased IVIG resistance and a higher risk of coronary complications [25, 26, 34]. In a large retrospective study of 2,678 children with KD, Wang et al. found that a low AST/ALT ratio (< 1.13) was significantly associated with higher rates of IVIG resistance and coronary artery lesions. The low-AST/ALT ratio group also showed greater inflammatory and coagulation abnormalities and lower albumin levels [35]. In addition, in a study of 313 children with KD, Li et al. demonstrated that coagulation abnormalities in the acute phase were associated with disease severity, IVIG nonresponsiveness, and coronary artery abnormalities [36]. In a large cohort of 1,715 children with KD, Zhou et al. found that prolonged activated PTT (APTT ≥ 46 s) before IVIG treatment was independently associated with an increased risk of coronary artery lesions [37].

We also observed that longer hospitalization was inversely associated with coronary artery dilatation and aneurysm formation but positively associated with abnormal abdominal sonographic findings. While prolonged hospitalization may reflect closer monitoring and earlier intervention for cardiovascular complications, it may also indicate more severe systemic involvement requiring extended care. Previous studies have shown that disease severity, treatment response, and timing of IVIG administration significantly influence both acute and chronic coronary outcomes [24, 38]. The observed inverse association between duration of hospitalization and coronary artery aneurysm formation should be interpreted cautiously. This finding may reflect increased clinical monitoring and more aggressive management in patients with prolonged hospitalization, rather than a direct protective effect. Additionally, reverse causality and unmeasured confounding factors may have contributed to this association.

The strong association between systemic inflammation and coronary pathology observed in our study is consistent with the known pathophysiology of KD. Early stages of arterial wall inflammation are characterized by endothelial swelling, subendothelial edema, and infiltration of inflammatory cells, which can lead to coronary artery dilatation and aneurysm formation if inflammation persists [39, 40]. Refractory KD, representing a more severe inflammatory phenotype, has been strongly associated with coronary artery disease and worse outcomes [41, 42].

Strengths, limitations, and future directions

This study has several important strengths. First, it represents a relatively large single-center cohort of pediatric patients with KD evaluated over five years. Second, the use of multivariate logistic regression enabled adjustment for potential confounding variables and the identification of independent factors associated with echocardiographic and coronary abnormalities. Several limitations should be acknowledged when interpreting the findings of this study. First, the retrospective cohort design limits the ability to infer causality between GI-related abnormalities and cardiovascular involvement in KD. Second, this study was conducted at a single tertiary referral center, which may limit the generalizability of the findings to other populations or healthcare settings. Third, abdominal ultrasonography was not performed uniformly in all patients, and GI imaging findings were therefore available for only a subset of the cohort. Similarly, some laboratory parameters were not available for all patients. Important clinical variables such as timing of intravenous immunoglobulin administration, IVIG resistance, fever duration prior to treatment, and use of adjunctive therapies were not included in the regression models and may have influenced cardiovascular outcomes. Regarding valvular abnormalities, any finding, from trivial to mild, moderate, or severe, was classified as abnormal, which contributed to the high prevalence observed. Future studies could consider stratifying these abnormalities into specific categories. Another limitation is the inability to consistently distinguish between complete and incomplete KD due to incomplete documentation in retrospective records. Finally, echocardiographic findings were assessed during hospitalization, and long-term follow-up data regarding persistence, regression, or progression of coronary artery lesions were not available. As a result, the long-term prognostic implications of the identified risk factors could not be evaluated. Future studies should focus on prospective, multicenter designs with standardized evaluation of GI manifestations, laboratory parameters, and echocardiographic outcomes. Longitudinal follow-up is needed to determine whether GI-related abnormalities predict not only acute cardiovascular involvement but also long-term coronary artery outcomes.

Conclusion

This study demonstrates a significant association between GI abnormalities and cardiovascular involvement in children with KD. While factors such as male sex, elevated inflammatory markers, anemia, hypoalbuminemia, elevated ALP, and coagulation abnormalities were associated with echocardiographic and coronary artery findings, these should be interpreted as markers of systemic inflammation rather than as features specific to GI involvement. Our findings emphasize the systemic nature of KD, in which GI manifestations represent part of a broader inflammatory process that may parallel disease severity. Accordingly, GI abnormalities may serve as additional clinical indicators of more severe disease and increased cardiovascular risk, rather than independent predictors.

Authors' contributions

All authors collaboratively contributed to this study. SHN, NH, and SK were responsible for the study design. SK, AA, and SM were involved in data collection and analysis. The initial draft of the manuscript was prepared by SK and SM. SHN, NH, and AA critically revised and edited the manuscript. All authors reviewed and approved the final version before submission.

Funding

No funding.

Data availability

The data related to this study can be obtained from the corresponding author upon reasonable request.

Declarations

Ethics approval and consent to participate

This study was approved by the Ethics Committee of Shiraz University of Medical Sciences (Ethics Code: IR.SUMS.MED.REC.1402.503). The study was conducted in accordance with the principles of the Declaration of Helsinki. Before enrollment, written informed consent was obtained from the parents or legal guardians of all participating children. All patient information was anonymized to maintain confidentiality.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.