Elevated lipoprotein(a), trimethylamine n-oxide, and gut dysbiosis are associated with subclinical coronary atherosclerosis independent of metabolic dysfunction-associated steatotic liver disease

Subclinical coronary atherosclerosis (SCA), detectable by coronary artery calcification (CAC), is an early marker of cardiovascular disease (CVD) that enables timely preventive interventions. Lipoprotein(a) [Lp(a)], trimethylamine N-oxide (TMAO), and gut dysbiosis have emerged as potential contributors to cardiovascular events, but their roles in SCA, particularly among older Asians with or without metabolic dysfunction-associated steatotic liver disease (MASLD), are unclear. We conducted a cross-sectional study in 232 adults aged ≥ 50 years without established CVD. CAC scores were measured using non-contrast computed tomography, MASLD severity was assessed by transient elastography, and fecal gut microbiota were analyzed via 16 S rRNA sequencing. Detectable CAC was present in 78.9% of participants, with no significant difference regarding MASLD. Higher CAC severity was significantly associated with elevated Lp(a) (cut-off ≥ 75 nmol/L) and TMAO (cut-off ≥ 4.0 µM) when analyzed by category. Multivariate analysis identified older age, diabetes, hypertension, obesity, and elevated Lp(a) and TMAO as independent predictors of detectable CAC. Gut microbiota analysis revealed enrichment of beneficial genera, including Faecalibacterium , in participants without CAC, whereas potentially atherogenic bacteria, including Agathobacter and Streptococcus , were abundant in those with CAC. These findings suggest that elevated Lp(a) and TMAO, and distinct microbial signatures, are linked to SCA. Integrating these biomarkers with traditional risk factors may improve early CVD detection and prevention.