Whereas the cause of Kawasaki disease is still unknown, progress in treatment during its acute phase has decreased the incidence of coronary artery lesions from 25-30% to 3-5%. In addition to acute-phase coronary disturbances, sclerotic vascular changes are often observed in post-Kawasaki disease patients, including those without coronary lesions during the acute phase. Survivors of Kawasaki disease are now reaching the age of atherosclerosis and it is unknown if these individuals carry a higher risk of coronary disease. This review aims to report the current state of knowledge concerning the long-term prognosis of patients with Kawasaki disease. Histopathological studies prove the changes of Kawasaki disease to be distinctive from those of atherosclerosis. However, endothelial dysfunction and risk factors for the development of atherosclerosis, such as dyslipidemia, decreased vascular elasticity, increased C-reactive protein, oxidative stress, inflammatory cytokines, and reactive oxygen species, are known to be present in the late phase of Kawasaki disease. In addition, postarteritis coronary arteries in animal models are more prone to the development of atherosclerotic changes. Potential cardiovascular risks are present in survivors of Kawasaki disease. Epidemiological studies enrolling a large cohort of Kawasaki disease patients surviving to middle age are awaited.

Background Kawasaki disease (KD) causes coronary artery disease (CAD) in children. In addition, a history of KD is suspected to be a risk factor for the development of atherosclerotic heart disease in the future. Histological senescence changes are a common denominator in atherosclerotic lesions in adults, so the present study investigated whether histological senescence changes had already occurred in KD aneurysm. Methods and Results KD coronary aneurysms and internal mammary arteries retrieved from 5 children with KD (3, 4, 5, 6, and 11 years old, respectively) who underwent coronary artery bypass grafting, as well as giant coronary aneurysm size-reducing operations, were analyzed. Senescence-associated strong β-galactosidase activity was observed in KD aneurysms, but not in the internal mammary arteries. An immunohistochemical analysis of the KD aneurysm using anti-CD31, anti-endothelial nitric oxide synthetase (eNOS), anti-vascular adhesion molecule-1 (VCAM-1), and anti-monocyte chemoattractant protein-1 (MCP-1) showed vascular endothelium CD31 staining, decreased staining of eNOS and strong staining of MCP-1 and VCAM-1. cDNA microarray gene expression profiling revealed increased MCP-1 expression in the KD aneurysm, a finding confirmed by quantitative polymerase chain reaction. Conclusions Histological features of senescence and active remodeling gene expression show that the KD aneurysm is not a silent vasculitis terminal. The future fate of KD aneurysms, including atherosclerosis, should be monitored carefully. (Circ J 2007; 71: 709 - 715)

Kawasaki disease causes coronary artery lesions, such as dilatation, aneurysms, stenosis, and even occlusion in young children, and is one of the most common acquired heart diseases in developed countries. More than 10,000 new cases are reported in Japan every year. In its acute phase, severe coronary arteritis induces morphological changes in coronary arteries. Treatments for Kawasaki disease aim to eliminate coronary artery inflammation as quickly as possible to reduce the chance of causing coronary lesions. Immunoglobulin therapy with aspirin has become the standard therapy of first choice and helps attenuate coronary lesions. In addition to coronary artery disturbances in the acute phase, sclerotic vascular changes were observed in post-Kawasaki disease patients who did not have coronary lesions in the acute phase. Recent studies have revealed peripheral vasculature endothelial dysfunction in post-Kawasaki disease patients with and without coronary lesions. The risk factors for the development of atherosclerosis in adults, such as C-reactive protein, oxidative stress, and inflammatory cytokines, are also increased in the remote phase of Kawasaki disease. This morphological and functional endothelial dysfunction as Kawasaki disease vascular sequelae may suggest the early development of atherosclerosis in patients with Kawasaki disease. However, no direct evidence for this early development has been found so far. Kawasaki disease was first reported slightly more than 40 years ago. The first documented post-Kawasaki disease patients are now becoming old enough to have atherosclerosis. Some case reports suggest myocardial infarction with atherosclerotic changes in young adults who are believed to have a history of Kawasaki disease. This paper reviews Kawasaki disease from the perspective of long-term prognosis.

Kawasaki disease (KD) is an acute form of systemic vasculitis that may promote atherosclerosis in adulthood. This study examined the relationships between KD, atherosclerosis, and the long-term effects of HMG-CoA inhibitors (statins). Candida albicans water-soluble fraction (CAWS) was injected intraperitoneally into 5-week-old male apolipoprotein-E-deficient (Apo E-/-) mice to create KD-like vasculitis. Mice were divided into 4 groups: the control, CAWS, CAWS+statin, and late-statin groups. They were sacrificed at 6 or 10 weeks after injection. Statin was started after CAWS injection in all groups except the late-statin group, which was administered statin internally 6 weeks after injection. Lipid plaque lesions on the aorta were evaluated with Oil Red O. The aortic root and abdominal aorta were evaluated with hematoxylin and eosin staining and immunostaining. CAWS vasculitis significantly enhanced aortic atherosclerosis and inflammatory cell invasion into the aortic root and abdominal aorta. Statins significantly inhibited atherosclerosis and inflammatory cell invasion, including macrophages. CAWS vasculitis, a KD-like vasculitis, promoted atherosclerosis in Apo E-/- mice. The long-term oral administration of statin significantly suppressed not only atherosclerosis but also inflammatory cell infiltration. Therefore, statin treatment may be used for the secondary prevention of cardiovascular events during the chronic phase of KD.