建議

Our results revealed that chronic vascular inflammation, endothelium dysfunction and arterial stiffness were still noted even in patients late after the onset of KD with a history of CAA. However, further long-term follow-up study is required to reveal whether these systemic endothelial dysfunction and arterial stiffness could lead to an early onset of atherosclerosis and even future cardiovascular events in the chronic stage of KD, because impaired endothelial function and arterial stiffness might be the initial stage of atherosclerosis.

In our present cohort, no toxicity, serious adverse or side effects were reported by the children during the course of this study. However, the duration of the present study is too short to draw conclusions with regard to the safety of long-term use of simvastatin in KD children. The long-term safety and efficacy of statins in KD children are needed to be continuously evaluated in our ongoing trial.

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附 錄

Table 1. Baseline characteristics of study population

Data are presented as the mean ± SD

Table 2. Serum lipid profile and marker of chronic vascular inflammation

TC = total cholesterol; LDL-C = low-density lipoprotein cholesterol; HDL-C = high-density lipoprotein cholesterol; TG = triglycerides; hs-CRP = high-sensitivity C-reactive protein. Data are presented as the mean ± SD. *P < 0.001.

Table 3. Surrogates for endothelial function and arterial stiffness before treatment

Normal control KD with CAA P value

IMT (mm) 0.49 ± 0.07 0.53 ± 0.08 0.213

ASI 2.96 ± 0.89 4.82 ± 0.86 <0.001*

ba PWV (cm/s) 1070 ± 173 1261 ± 117 0.006*

ABI 1.07 ± 0.08 1.01 ± 0.11 0.149

FMD (%) 13.11 ± 1.00 6.12 ± 1.61 <0.001*

IMT, intima-media thickness; ASI, arterial stiffness index; baPWV, brachial-ankle pulse wave velocity; FMD, flow-mediated dilatation; ABI, ankle brachial pressure index. Data are presented as the mean ± SD. * Statistically significant.

Table 4. Changes in Serum Lipid profile and hs CRP after 3 months treatment

Baseline 3 month P value Normal control P value TC 170 ± 31 154 ± 20 0.015* 162 ± 21 0.355 TG 118 ± 46 117 ± 34 0.755 122 ± 41 0.744 LDL-C 97 ± 17 85 ± 14 <0.001* 91 ± 11 0.304

HDL-C 51 ± 11 55 ± 13 0.05* 53 ± 9 0.769

Hs-CRP 0. 430 ± 0.225 0. 209 ± 0.098 0.001* 0.045 ± 0.028 < 0.001*

Data are presented as the mean ± SD. * Statistically significant.

Table 5. Changes in IMT, endothelial function surrogate and arterial stiffness after 3 months treatment

Baseline 3 month P value Normal control P value IMT 0.53 ± 0.08 0.49 ± 0.07 < 0.001* 0.49 ± 0.07 0.908 ASI 4.82 ± 0.86 3.75 ± 0.77 < 0.001* 2.96 ± 0.89 0.037*

baPWV 1261 ± 117 1132 ± 132 < 0.001* 1070 ± 173 0.357 ABI 1.01 ± 0.11 1.05 ± 0.11 0.043* 1.07 ± 0.08 0.568 FMD 6.12 ± 1.61 10.32 ± 1.58 < 0.001* 13.11 ± 1.00 <0.001*

Data are presented as the mean ± SD. * Statistically significant.

Figure 1. Box plot of changes and histogram analysis of percent changes in serum lipid profiles after 3 months of simvastatin treatment.

(a)

% Change in serum TC concentration

10.0

(b)

% Change in serum LDL concentration

-8.0

(c)

% Change in serum HDL concentrations

25.0

(d)

Figure 2. Box plot of change and histogram analysis of percent change in serum high-sensitivity C-reactive protein (hs-CRP) levels after 3 months of simvastatin treatment.

% Change in serum hs CRP concentration

-30.0

Figure 3. Box plot of changes and histogram analysis of percent changes in IMT, endothelial function surrogate and arterial stiffness after 3 months of simvastatin treatment.

(b)

(c)

(d)

(e)

Figure 4. The change in ALT, AST, and CK within 3 months statin therapy

(a)

(b)

0 5 10 15 20 25 30 35 40

baseline 1 month 2 month 3 month

GPT

0 5 10 15 20 25 30 35

baseline 1 month 2 month 3 month

GOT

(c)

0 20 40 60 80 100 120 140 160

baseline 1 month 2 month 3 month

CK