Elevated Fib-4 levels (Fib-4 ≥ 1.3) are positively associated with CA in patients with type 2 diabetes, including increased CIMT and the presence of carotid plaques. As such, Fib-4 may serve as a potential biomarker for the detection of CA in patients with type 2 diabetes. However, its clinical utility needs further validation, particularly in larger sample sizes and multicenter studies.

Univariate analysis was conducted with CA (Supplementary Table 1), defined as the dependent variable (1 = yes, 0 = no), and included gender, age, height, weight, BMI, head circumference, neck circumference, WC, hip circumference, waist-to-hip ratio, waist-to-height ratio, systolic blood pressure, diastolic blood pressure, heart rate, fasting blood glucose, postprandial 2-hour blood glucose, insulin, HOMA-IR, HbA1c, WBC, RBC, Hb, PLT, TG, TC, HDL-C, LDL-C, ALT, AST, GGT, UA, Cr, BUN, Urinary ACR, LABI, RABI, LBAPWV, RBAPWV, hypertension, history of coronary heart disease, smoking, drinking, and Fib-4 grouping. The results indicated that gender, age, BMI, hip circumference, waist-to-hip ratio, systolic and diastolic blood pressure, FPG, RBC, PLT, LDL-C, ALT, UA, Cr, BUN, LBAPWV, RBAPWV, hypertension, history of coronary heart disease, smoking, drinking, and Fib-4 grouping are risk factors influencing carotid atherosclerosis.

The results of the multivariate logistic regression analysis are presented in Table 2 and illustrated in Fig. 2. Fib-4 exhibited a positive association with the prevalence of CA, as well as increased CIMT and carotid plaques. Specifically, concerning the prevalence of CA, the adjusted odds ratios (ORs) (95% confidence intervals, CIs) were 1.450 (1.119, 1.879) and 1.743 (1.315, 2.311) in the 1.3 ≤ Fib-4 < 2.67 group and Fib-4 ≥ 2.67 group, respectively, compared to the Fib-4 < 1.3 group, after accounting for traditional risk factors (p for trend < 0.05). Furthermore, compared to the Fib-4 < 1.3 group, the Fib-4 ≥ 2.67 group demonstrated a significant association with a higher prevalence of increased CIMT (OR: 1.440; 95% CI: 1.116–1.857, p for trend < 0.05). Regarding the prevalence of carotid plaques, the adjusted ORs (95% CIs) were 1.280 (1.005, 1.630) and 1.461 (1.124, 1.899) in the 1.3 ≤ Fib-4 < 2.67 group and Fib-4 ≥ 2.67 group, respectively, compared to the Fib-4 < 1.3 group, after controlling for traditional risk factors (p for trend < 0.05).

Logistic regression analyses of the relationship between Fib-4 and CA, increased CIMT, and carotid plaques. Summarized figure of ORs for (A) Carotid atherosclerosis, (B) Increased CIMT, (C) Carotid plaques. OR, odds ratio; CI, confidence interval. CIMT, carotid intima media thickening. Adjusted for sex, smoking, drinking, BMI, hip circumference, WHR, SBP, DBP, FPG, RBC, LDL-C, ALT, UA, Cr, BUN, LBAPWV, RBAPWV, hypertension, and coronary heart disease

To comprehensively investigate the association between Fib-4 and CA, we conducted subgroup analyses, stratifying by sex, age, hypertension, smoking, alcohol consumption, and BMI (Table 3; Fig. 3), building upon the Model 3 adjustments presented in Table 2. Notably, in the subgroup analysis by gender, among male patients, the risk of CA exhibited an increasing trend in the 1.3 ≤ Fib-4 < 2.67 group (OR: 1.673, 95% CI: 1.180–2.371) and the Fib-4 ≥ 2.67 group (OR: 1.437, 95% CI: 1.022–2.020), with statistically significant differences (p < 0.05). This trend was also observed in increased CIMT and carotid plaques, although the differences were not statistically significant after adjusting for multiple factors. In the female patient subgroup, the risk of CA (OR: 1.949, 95% CI: 1.404–2.704), increased CIMT (OR: 1.629, 95% CI: 1.208–2.198), and carotid plaques (OR: 1.513, 95% CI: 1.115–2.052) demonstrated an increasing trend in the Fib-4 ≥ 2.67 group, with statistically significant differences (p < 0.05), while the differences in the 1.3 ≤ Fib-4 < 2.67 group became non-significant after adjusting for multiple factors. In the age-stratified subgroup analysis, among participants aged < 60, the risk of CA increased in the 1.3 ≤ Fib-4 < 2.67 group (OR: 1.437, 95% CI: 1.034–1.998) and the Fib-4 ≥ 2.67 group (OR: 1.428, 95% CI: 1.006–2.027), with statistically significant differences (p < 0.05). This trend was also observed in increased CIMT and carotid plaques, although the differences were not statistically significant after adjusting for multiple factors. Among participants aged ≥ 60, there were no statistically significant differences in the risk of CA, increased CIMT, and carotid plaques after multiple-factor regression analysis when Fib-4 ≥ 1.3 and Fib-4 ≥ 2.67. In the subgroup analysis by hypertension, participants with hypertension showed an increased risk of CA in the 1.3 ≤ Fib-4 < 2.67 group (OR: 1.511, 95% CI: 1.072–2.130) and the Fib-4 ≥ 2.67 group (OR: 1.583, 95% CI: 1.154–2.172), with statistically significant differences (p < 0.05). The risk of increased CIMT increased in the 1.3 ≤ Fib-4 < 2.67 group, but the difference was not statistically significant. In the Fib-4 ≥ 2.67 group, the risk of increased CIMT showed a significant increase (OR: 1.583, 95% CI: 1.154–2.172, p < 0.05), and the risk of carotid plaques increased in both the 1.3 ≤ Fib-4 < 2.67 group and the Fib-4 ≥ 2.67 group, but the differences became non-significant after multiple-factor regression analysis. In the subgroup without hypertension, the risk of CA (OR: 1.780, 95% CI: 1.244–2.547) and carotid plaques (OR: 1.417, 95% CI: 1.103–1.981) increased in the Fib-4 ≥ 2.67 group, with statistically significant differences (p < 0.05); other differences were not statistically significant. In the subgroup analysis by smoking, among non-smokers, the risk of CA (OR: 1.974, 95% CI: 1.447–2.636), increased CIMT (OR: 1.641, 95% CI: 1.262–2.133), and carotid plaques (OR: 1.551, 95% CI: 1.187–2.026) increased in the Fib-4 ≥ 2.67 group, with statistically significant differences (p < 0.05); other trends existed but were not statistically significant after multiple-factor regression analysis. In the never-drinking subgroup, the risk of CA (OR: 1.877, 95% CI: 1.373–2.567), increased CIMT (OR: 1.443, 95% CI: 1.090–1.911), and carotid plaques (OR: 1.360, 95% CI: 1.020–1.813) increased in the Fib-4 ≥ 2.67 group, with statistically significant differences (p < 0.05). In the current-drinking subgroup, the risk of CA increased in the 1.3 ≤ Fib-4 < 2.67 group (OR: 1.727, 95% CI: 1.105–2.697), with statistically significant differences (p < 0.05); other differences were not statistically significant. In the subgroup analysis by BMI, among participants with BMI < 24, the risk of CA increased in the Fib-4 ≥ 2.67 group (OR: 1.704, 95% CI: 1.183–2.456), with statistically significant differences (p < 0.05). Among participants with BMI ≥ 24, the risk of CA increased in the 1.3 ≤ Fib-4 < 2.67 group (OR: 1.571, 95% CI: 1.131–2.182) and the Fib-4 ≥ 2.67 group (OR: 1.705, 95% CI: 1.251–2.326), with statistically significant differences (p < 0.05). The risk of increased CIMT increased in the Fib-4 ≥ 2.67 group (OR: 1.429, 95% CI: 1.083–1.886), with statistically significant differences (p < 0.05); other trends existed but were not statistically significant after multiple-factor regression analysis.

Subgroup analyses for the association of Fib-4 with CA, increased CIMT and plaques

To assess the predictive value of Fib-4 for the presence of carotid atherosclerosis (CA), increased carotid intima-media thickness (CIMT), and carotid plaques, a receiver operating characteristic (ROC) curve analysis was conducted (Fig. 4). The results demonstrated that Fib-4 has modest predictive capability for these conditions. Specifically, the area under the curve (AUC) for Fib-4 in predicting CA was 0.602 (P < 0.001, 95% CI: 0.579–0.625), indicating limited discrimination ability. Similarly, the AUC values for predicting increased CIMT and carotid plaques were 0.561 (P < 0.001, 95% CI: 0.540–0.583) and 0.580 (P < 0.001, 95% CI: 0.558–0.601), respectively, suggesting that Fib-4’s predictive power for these markers remains relatively weak.

Receiver Operating Characteristic (ROC) Curve Analysis of Fib-4 for Predicting CA, Increased CIMT, and Carotid Plaques