Atherogenic index of plasma identifies subjects with severe liver steatosis

Abstract

The Atherogenic Index of Plasma (AIP), calculated by log (Triglycerides/HDL-C), has been proposed as a marker of atherogenic and cardiovascular risk. Atherosclerosis and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) share some pathogenic features and may be considered clinical manifestations of Metabolic Syndrome. In this study, we aimed to investigate the role of increased AIP as a putative metabolic biomarker for MASLD. 1,496 individuals (49% males and 51% females) underwent clinical examination for Metabolic Syndrome at Internal Medicine Division "C. Frugoni" of University Hospital of Bari, Italy in the period between January 2016 and April 2024. Clinical history was recorded, and physical examination, anthropometric measures, biochemical assessment, and abdomen ultrasound were performed. In the overall population, AIP significantly correlated with fasting glycemia (FPG, r = 0.26, p < 0.0001), HbA1c (r = 0.20, p < 0.0001), LDL (r = 0.11, p < 0.0001) and total cholesterol (r = 0.09; p < 0.0001), and anthropometric measures of obesity BMI (r = 0.37, p < 0.0001) and Waist Circumference (r = 0.44; p < 0.001). We then investigated AIP values in patients with and without dysmetabolic conditions, finding that AIP significantly increased as steatosis worsened (p < 0.001). ROC curves identified an optimal cut-off of 0.31 for accurately diagnosing severe steatosis and AIP values above this cut-off discriminated patients with significantly increased (p < 0.0001) fasting glycemia, LDL, and waist circumference, and were strongly associated (p < 0.0001) with MASLD (LLR 85.3), type 2 diabetes (LLR 85.5), abdominal obesity (LLR 72.9), overweight (LLR 151.8), and systemic obesity (LLR 178.4). The risk for being diagnosed with such conditions was found to be even higher in the subpopulation of patients with severe liver steatosis. To validate our findings, we considered another cohort of patients with and without biopsy-proven liver steatosis (public dataset GSE89632), confirming that a significant increase (p < 0.001) in AIP values could be found in patients with liver steatosis compared to healthy controls. AIP can be considered a specific biomarker of fatty liver disease with high sensitivity for the diagnosis of the severe form of liver steatosis. Considering AIP in the evaluation of patients with liver steatosis may augment the accuracy for diagnosing metabolic impairment and MASLD.

Keywords: Atherosclerosis; Diabetes; MASLD; Mediterranean diet; Metabolic syndrome; Obesity.

Fig. 1

Correlations between AIP and main metabolic biomarkers. AIP Pearson’s correlations (r) and p-values (p) with FPG (a), HbA1c (b), Total Cholesterol (c), HDL Cholesterol (d), LDL Cholesterol (e), Triglycerides (f), Waist circumference (g), BMI (h), CMDS (i) are reported. AIP atherogenic index of plasma, FPG fasting plasma glucose, HbA1c glycosylated haemoglobin, BMI body mass index, CMDS chrono med diet score.

Fig. 2

Comparisons of AIP values in patients with and without dysmetabolic conditions. The scatter plots show the mean and SD with each point representing one observation. Student T-test was performed for comparisons between two groups, while One-way ANOVA was used for comparisons among more than two groups. Statistical significance was assessed for p-values (p) < 0.05; ****p < 0.0001. (a) Abdominal obesity was diagnosed for Waist Circumference values ≥ 80 cm in females and ≥ 94 cm in males. (b) BMI ≥ 25 kg/sqm depicts a condition of overweight, while BMI ≥ 30 kg/sqm a condition of obesity. (c) Metabolic Syndrome was diagnosed when subjects had increased waist circumference plus at least two other criteria among hyperglycaemia, low HDL, hypertriglyceridemia, and hypertension. (d) Type 2 Diabetes was diagnosed for FPG > 126 mg/dl or HbA1c > 6.4% or ongoing anti-diabetic treatment. (e) Liver steatosis was assessed through Abdomen Ultrasound. Mild steatosis is represented by a mild diffuse increase in fine echoes in the hepatic parenchyma with normal visualisation of the diaphragm and intrahepatic vessel borders. Moderate steatosis is represented by a moderate diffuse increase in fine echoes with slightly impaired visualisation of the intrahepatic vessels and diaphragm. Severe steatosis is represented by a marked increase in fine echoes with poor or no visualisation of the intrahepatic vessel borders, diaphragm, and posterior portion of the right lobe of the liver. (f) Hypertension was assessed for systolic arterial blood pressure (SAP) ≥ 130mmHg and/or diastolic arterial blood pressure (DAP) ≥ 85mmHg and/or treatment with antihypertensive agents. BMI Body Mass Index; ns not-significant.

Fig. 3

ROC curves of AIP in prediction of liver steatosis and Metabolic Syndrome. Empirical ROC curves of AIP for prediction of Metabolic Syndrome in the overall population (a) and in subjects with liver steatosis (b), of liver steatosis (c), and severe liver steatosis (d). Area under curve (AUC) and p-value together with calculated cut-off and respective Sensitivity and Specificity are reported for each condition. Statistical significance was assessed for p-values (p) < 0.05.

Fig. 4

Comparisons of metabolic biomarkers in patients with AIP values over and below the cut-off value of 0.31. The scatter plots show the mean and SD with each point representing one observation The scatter plots show the mean and SD with each point representing one observation. Student T-test was performed for comparisons between two groups. Statistical significance was assessed for p-values (p) < 0.05; *p < 0.05; ****p < 0.0001. AIP atherogenic index of plasma, FPG fasting plasma glucose, ns not significant.

Fig. 5

ORs of being diagnosed with dysmetabolic conditions when AIP ≥ 0.31. ORs with their 95% Confidence Interval are represented. All the conditions were significantly associated (p < 0.0001) to increased AIP. Also log-likelihood ratios (G-squared) are reported. OR odd ratio, AIP atherogenic index of plasma, MASLD metabolic-dysfunction associated steatotic liver diseases, BMI body mass index.