**5. Cardiovascular risk and management**

KD is a systemic vasculitis that can lead to atherosclerosis due to vascular dysfunction and damage. Long-term management should consider the cardiovascular risk of atherosclerosis progression in both coronary arteries and systemic vessels.

#### **5.1 Coronary arteries**

Coronary artery aneurysms that remain 30 days after the onset of KD are defined as cardiovascular complications of KD. Aneurysms impair vascular endothelial function and thrombus formation. **Figure 2** shows the giant aneurysms identified angiographically in patients with IVIG-resistant KD. This can lead to angina or myocardial infarction owing to coronary artery stenosis or occlusion. In addition, calcification of the vessel wall is frequently observed. However, it is estimated that 75% of coronary aneurysms regress within 3 years of onset [25]. Even when aneurysms remain, they often become smaller in diameter than those in the early stages.

The management strategies in the follow-up stage included (1) prevention of thrombosis in aneurysms and myocardial infarction, (2) early diagnosis of myocardial ischemia and appropriate reperfusion therapy, and (3) management of the risk of atherosclerosis and preventive education.

#### *5.1.1 Prevention of thrombosis in aneurysms and myocardial infarction*

In KD patients with CAL, it is important to prevent cardiac events. In general, these patients require aspirin or other antiplatelet agents. Anticoagulants are administered mainly in cases of giant coronary artery aneurysms. Additionally, statin therapy may improve chronic vascular inflammation and endothelial dysfunction, which has been suggested to be useful for vascular health. Statins have multifaceted pharmacological effects, including anti-inflammatory, antioxidant, anticoagulant, and thrombolytic effects, as well as a decrease in serum cholesterol levels. Additionally, statins are expected to be effective in improving vascular endothelial function. According to a statement from the American Heart Association, KD patients with CAL need to be treated prophylactically.

#### **Figure 2.**

*Giant aneurysms. (a), (b) Coronary angiography in 4-year-old patient with giant aneurysms. This patient was treated with warfarin and aspirin since diagnosis of giant aneurysm. (a) Selective right coronary arteriography. Giant aneurysm was identified. (b) Selective left coronary arteriography. Medium size aneurysm was identified at left anterior descending artery. (c), (d) Follow-up coronary angiography at age 9 (5 years later). (c) Selective right coronary arteriography. Giant aneurysm was occluded (red arrow head) and collateral arteries had developed to the periphery of the right coronary artery (yellow arrow). (b) Selective left coronary arteriography. Medium size aneurysm did not change significantly and no stenotic lesions were detected.*

#### *5.1.2 Early diagnosis of myocardial ischemia and appropriate reperfusion therapy*

Critical stenotic lesions are sometimes observed at the proximal and distal ends of coronary aneurysms. These findings are believed to be caused by vascular remodeling. Coronary artery stenosis was evaluated using coronary angiography, coronary functional flow reserve, enhanced coronary computed tomography, and stress myocardial scintigraphy. These tests should be performed periodically depending on the severity of the coronary artery aneurysm. Although coronary revascularization is required in less than 1% of patients with a history of KD, percutaneous coronary intervention or coronary artery bypass grafting is required when myocardial ischemia is detected using these modalities.

#### *5.1.3 Management of risk of atherosclerosis and the preventive education*

In cases of aneurysms larger than medium size, vascular endothelial dysfunction, chronic inflammation in the vessel wall, and subsequent vascular remodeling continue to occur even late after the onset of KD. Although the details have not yet been elucidated, vascular endothelial damage and chronic inflammation resemble the early lesions of atherosclerosis and may be predisposing factors for future atherosclerosis.

Therefore, it is necessary to actively eliminate cardiovascular risk factors at a younger age. In other words, education on the prevention of hypertension and obesity, smoking cessation, management of blood sugar and lipids, and reduction of psychological stress are important for long-term management.
