Phenotypic age and cardiometabolic factors in patients with metabolic dysfunction-associated steatotic liver disease

Objective — to explore the association between cardiometabolic risk factors (CMRFs) for metabolic dysfunction‑associated steatotic liver disease (MASLD), phenotypic age (PA), age delta (AD), and cardiometabolic indicators in MASLD patients. Materials and methods. The study group comprised 96 MASLD patients with low‑moderate fibrosis risk (mean age 50.2 (42.1; 57.2) years; 44.8% female) and 17 gender‑matched healthy adults as controls (mean age of 25.0 (23.7;27.1) years), assessed during 2022—2024. PA and ΔA were calculated using the formula developed by M. Levine et al (2018). The calculated indices included non‑high‑density lipoprotein cholesterol (non‑HDL‑C), triglyceride‑glucose (TyG) index, atherogenic index of plasma (AIP), metabolic score for insulin resistance (METS‑IR), lipid accumulation product (LAP), and cardiometabolic index (CMI). Results. Patients with MASLD had significantly higher calendar age and PA compared to the controls (p<0.05), but there was no significant difference in AD. In MASLD patients, PA showed a significant association with waist circumference (WC) (p=0.027), level of visceral fat (VF) (p=0.0001), systolic blood pressure (sBP) (p=0.010), glycosylated hemoglobin (HbA1c) (p=0.025), HOMA‑IR (p=0.001) and FIB‑4 (p=0.0001). AD was associated with the percent of skeletal muscle (SM) (p=0.034), VF (p=0.009), sBP (p=0.019), diastolic BP (dBP) (p=0.003), High‑Density Lipoprotein Cholesterol (HDL‑C) (p=0.025), uric acid (p=0.005), TyG index (p=0.014) and AIP (p=0.022). The prevalence of hypertension among MASLD patients was 95.8% and the elevation of waist‑to‑hip ratio and/or body mass index was 91.7%. Subgroup analysis based on low HDL‑C levels revealed differences in WC (p=0.040), HbA1c (p=0.023), creatinine (p=0.028), non‑HDL‑C values (p=0.028). Patients with elevated triglycerides (TG) levels showed significant differences (p<0.05) in dBP, aspartate transaminase, alanine transaminase, HOMA‑IR, non‑HDL‑C, TyG index, AIP, METS‑IR, LAP, and CMI. Patients with 4—5 CMRFs (n=40) had a significantly higher PA compared to those with 1—3 CMRFs (p=0.045) and showed significant differences (p<0.05) in HOMA‑IR, total cholesterol, triglycerides, very low density lipoprotein cholesterol, total protein, non‑HDL‑C, TyG index, AIP, METS‑IR, LAP, and CMI. Conclusions. Higher PA in patients with MASLD is linked to a heightened risk of fibrosis. In MASLD patients with increased AD, special attention should be given to monitoring anthropometric status, BP, HDL‑C, uric acid, TyG index, and AIP. Arterial hypertension, the most prevalent CMRF in MASLD, underscores the need for blood pressure based indices. Having 4—5 CMRFs is associated with higher PA.