Cardiovascular Morbidity and Mortality in Lean vs. Non-Lean MASLD: A Comprehensive Meta-Analysis

Lean metabolic dysfunction-associated steatotic liver disease (MASLD), characterized by a BMI < 25 kg/m² (or < 23 kg/m² in Asians), presents a challenging prognosis compared to non-lean MASLD. This study examines cardiovascular outcomes in both lean and non-lean MASLD cohorts. In this meta-analysis, pooled odds ratios (ORs) within 95% confidence intervals (CIs) were calculated for primary outcomes (cardiovascular mortality and major adverse cardiovascular events [MACE]) and secondary outcomes (cardiovascular disease [CVD], all-cause mortality, hypertension, and dyslipidemia). Studies comparing lean and non-lean MASLD within the same cohorts were analyzed, prioritizing those with larger sample sizes or recent publication dates. Twenty-one studies were identified, encompassing lean MASLD patients (n = 7153; mean age 52.9 ± 7.4; 56% male) and non-lean MASLD patients (n = 23,514; mean age 53.2 ± 6.8; 63% male). Lean MASLD exhibited a 50% increase in cardiovascular mortality odds compared to non-lean MASLD (OR: 1.5, 95% CI 1.2–1.8; p < 0.0001). MACE odds were 10% lower in lean MASLD (OR: 0.9, 95% CI 0.7–1.2; p = 0.7), while CVD odds were 40% lower (p = 0.01). All-cause mortality showed a 40% higher odds in lean MASLD versus non-lean MASLD (p = 0.06). Lean MASLD had 30% lower odds for both hypertension (p = 0.01) and dyslipidemia (p = 0.02) compared to non-lean MASLD. Despite a favorable cardiometabolic profile and comparable MACE rates, lean individuals with MASLD face elevated cardiovascular mortality risk.