Lipid profile shift in high-altitude migrants as a key promoting factor for chronic myocardial injury revealed by lipidomics.

BACKGROUND: Lipid metabolic dysregulation contributes to cardiovascular disease, yet its role in high-altitude heart disease (HAHD) remains unclear. METHODS: We enrolled 525 high-altitude immigrants and 98 plain controls. Cardiac function and serum lipids were clinically assessed. Untargeted lipidomics was performed to profile circulating lipids in a matched discovery subgroup (N = 15 per group): plain controls, high-altitude residents with normal cardiac function, and high-altitude residents with cardiac dysfunction. Correlation analyses identified lipids linked to myocardial injury biomarkers. ROC analysis evaluated diagnostic potential. RESULTS: Cardiac dysfunction prevalence was 46.4% in high-altitude subjects and correlated with hyperlipidemia. Lipidomics revealed HAHD-specific remodeling characterized by increased glycerolipids (e.g., triglycerides, diglycerides) and free fatty acids, alongside decreased sphingolipids (ceramides, hexosylceramides) and phospholipids (phosphatidylserine, phosphatidic acid). Twenty-five lipids were associated with myocardial injury biomarkers, of which eight, notably PS(20:4_20:4) and DG(16:0_20:4), showed good discriminatory performance (AUC > 0.8 in the matched group). These lipids correlated with immune traits, suggesting lipid-immune crosstalk. CONCLUSION: This study identifies a distinct lipid signature in HAHD and implicates lipid-immune interactions in disease progression. These exploratory findings provide mechanistic insights and warrant further validation as potential biomarkers for early detection and targeted intervention of high-altitude cardiac dysfunction in future independent cohorts.