Background: Metabolic-associated fatty liver disease (MAFLD) has become the predominant form of chronic liver disease worldwide, closely linked to components of metabolic syndrome such as insulin resistance, dyslipidemia, and hypertension. Although obesity is a major driver of both MAFLD and cardiovascular disease (CVD), a subset of patients—often termed "lean MAFLD"—exhibit hepatic steatosis without overt obesity, and their cardiovascular risk profile remains incompletely characterized.

Objectives: This study aims to comprehensively evaluate and compare cardiovascular risk markers in obese and non-obese MAFLD patients to determine how obesity status influences subclinical atherosclerosis, traditional CVD risk factors, and overall 10-year risk estimation.

Methods: A cross-sectional analysis was performed on 300 adult MAFLD patients (age 30–65) recruited from a tertiary hepatology center between January 2023 and December 2024. Diagnosis of MAFLD was based on imaging-confirmed hepatic steatosis and presence of metabolic dysregulation. Participants were stratified into two groups: obese (n=180; BMI ≥30 kg/m^2) and non-obese (n=120; BMI <30 kg/m^2). Comprehensive phenotyping included anthropometric measurements, laboratory assessments (lipid panel, fasting glucose, HbA1c, high-sensitivity C-reactive protein [hs-CRP], interleukin-6 [IL-6]), blood pressure readings, and carotid ultrasonography to measure carotid intima-media thickness (cIMT). The Framingham Risk Score (FRS) was calculated for 10-year CVD risk estimation. Statistical analyses utilized Student’s t-test, Mann–Whitney U test, chi-square test, and multivariate logistic regression to adjust for confounders.

Results: Obese MAFLD patients exhibited significantly elevated mean levels of LDL-C (3.8 ± 0.9 mmol/L vs. 3.2 ± 0.8 mmol/L; p<0.001), triglycerides (2.1 ± 0.6 mmol/L vs. 1.7 ± 0.5 mmol/L; p<0.001), systolic blood pressure (136 ± 12 mmHg vs. 128 ± 10 mmHg; p<0.001), hs-CRP (4.3 ± 1.5 mg/L vs. 2.2 ± 1.0 mg/L; p<0.001), and mean cIMT (0.74 ± 0.12 mm vs. 0.66 ± 0.10 mm; p<0.001) compared to non-obese MAFLD. Despite a lower inflammatory profile, non-obese patients still demonstrated an elevated mean cIMT relative to population norms (0.66 ± 0.10 mm, p=0.02) and a moderate FRS (mean 8.5% ± 3.2%). In multivariate analysis controlling for age, sex, smoking status, and presence of type 2 diabetes, MAFLD remained independently associated with increased cIMT (OR: 2.1; 95% CI: 1.4–3.2; p<0.01), irrespective of obesity. Furthermore, lean MAFLD patients with dysglycemia (impaired fasting glucose or HbA1c 5.7–6.4%) had higher cIMT than metabolically healthy non-obese counterparts (p<0.05).

Conclusions: Obesity significantly augments traditional and novel CVD risk markers in MAFLD patients; however, non-obese individuals with MAFLD also harbor subclinical atherosclerosis and moderate 10-year CVD risk. These findings underscore the imperative for comprehensive cardiovascular evaluation in all MAFLD patients, regardless of BMI. Strategies for early detection and tailored intervention should extend beyond obese populations to adequately address the full spectrum of MAFLD-related cardiovascular risk.

MAFLD, cardiovascular risk, obesity, non-obese, subclinical atherosclerosis, metabolic dysregulation, cIMT

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