3.1 Study selection: After eliminating repeated citations, 270 articles were found. First, 209 articles unrelated to SCH and cardiovascular risk factors were excluded from the reading summary, then, the next step is by reading the full text to filter: 14 studies were excluded because there were no relevant outcomes, 14 studies were excluded because there was no control between the euthyroid group and the SCH patients group, 1 study did not meet the requirements of observational study and 19 studies were excluded because they did not meet inclusion criteria or lacked data. As for the uniform data articles, we only take the research with more complete data and a larger sample size, so there are 2 articles excluded. Finally, 11 studies were included in our analysis (Figure 1). A total of 3995 participants were included, of whom 817 children and adolescents had SCH, and 3,178 were euthyroid.
9 studies23-31 compared TC levels in 753 SCH patients and 3097 controls. 8 studies23-29,32 (540 cases and 1923 controls) evaluated TG, 6 studies23-27,29 reported LDL (453 cases and 1832 controls), 823-27,29,31,32 reported HDL (715 cases and 3107 controls), 524-27,29 reported insulin resistance (312 cases and 1160 controls), and 3 studies24,28,29 (112cases and 83 controls) assessed CIMT, isovolumic relaxation time (IVRT) was evaluated in 3 studies29,32,33 (91 cases and 110 controls).
3.2 Study characteristics: The main characteristics of the studies are shown in Table1. 7 studies are case-control studies, and the remaining four were cross-sectional studies. 4 studies included only people with mild SCH as case groups. According to the NOS, 6 studies are of high quality.
3.3 Lipid profile: Serum cholesterol was assessed in 9 studies involving a total of 3850 participants. Meta-analysis results showed that the TC level of SCH patients was significantly increased compared with the control group (Figure 2A, WMD=6.39, 95% CI: 4.02-8.76, P<0.00001). There was low heterogeneity between studies (I2 = 10%; P = 0.35). Because the number of articles is less than 10, the publication bias is not considered. Subgroup analysis was not performed because of the low heterogeneity of the literature. The results were robust by comparing and analyzing the sensitivity of the articles.
Serum triglycerides were evaluated in 8 studies involving 2465 participants. It turns out that the TG level of patients with SCH was significantly higher than that of the control group (Figure 2B, WMD=9.92, 95% CI: 5.59-14.24, P<0.00001) without heterogeneity among studies (I2 = 0%; P = 0.86). Through sensitivity analysis, the results are robust.
Seven studies, evaluating a total of 2285 participants, showed a significant increase in serum LDL in SCH patients than in control subjects (Figure 2C, WMD=4.10, 95% CI: 1.45-6.75, P=0.002), and the heterogeneity between studies was moderate (I2 = 44%; P = 0.11). Through sensitivity analysis, the results are robust. To keep the results free from confounding factors, subgroup analysis was performed. By subgroup analysis of the diagnostic thresholds for SCH, we found that when the cut-off value of TSH used in the study was less than 5mIU/L (n = 4), a larger WMD value was reported (WMD= 4.52, 95% CI: 1.59-7.45, P=0.003) and there was no heterogeneity between studies (I2 = 0%; P = 0.51).
Serum HDL was assessed in 8 studies, involving a total of 3822 individuals, indicated that there was no significant difference between the SCH group and the control group (Figure 2D, WMD=-1.81, 95% CI: -4.44-0.81, P=0.18) with significant heterogeneity among studies (I2 = 85%; P <0.00001). Subgroup analysis of study type, study country, NOS, TSH cutoff, obesity, and SCH degree did not reveal the source of heterogeneity. Through sensitivity analysis, the results are robust.
3.4 Intima-media thickness: The data of IMT came from 3 studies, involving 195 participants. The difference between the two groups was not statistically significant (Figure 2E, WMD=0.02, 95% CI: -0.01-0.06, P=0.23) with high heterogeneity among studies (I2 = 77%; P =0.01). After excluding Isik 201628 through sensitivity analysis, the results of meta-analysis showed that there was no heterogeneity in the remaining articles(WMD= 0.00, 95% CI: -0.03-0.03, P=0.85, I2 = 0%; P =0.79).
3.5 Insulin resistance: IR was calculated using the homeostasis model assessment (HOMA-IR) equation formula34. 5 studies supplied this data, including 1,472 participants. The results revealed that the differences between the SCH group and the control group were not statistically significant (Figure 2F, WMD=0.34, 95% CI: -0.07-0.75, P=0.11) and were accompanied by high heterogeneity (I2 = 75%; P =0.003). Subgroup analysis of article types revealed that case-control trials reported higher WMD value (WMD=0.46, 95% CI: 0.06-0.87, P=0.02) and less heterogeneity (I2 = 48%; P =0.17). Sensitivity analysis showed that the results were unstable.
3.6 Isovolumic relaxation time: 3 studies with a total of 201 participants indicated higher IVRT values in the SCH group compared to the control group (Figure 2G, WMD=7.85, 95% CI: 3.99-11.72, P<0.0001) with significant heterogeneity among studies (I2 = 58%; P =0.09). After excluding Yadav 201729 through sensitivity analysis, the results of meta-analysis showed that there was no heterogeneity in the remaining articles(WMD= 9.32, 95% CI: 6.86-11.79, P<0.00001, I2 = 0%; P =0.50).