Circulating fatty acid profiles and risk of pulmonary arterial hypertension: Evidence from a large prospective cohort study

Fatty acids (FAs) have cardioprotective properties. However, their role in the development of pulmonary arterial hypertension (PAH) has not been thoroughly examined. This study aimed to investigate the relationship between circulating FA profiles and the risk of PAH. Data from the UK Biobank were used to assess the association between 8 circulating FAs and PAH risk. Cox proportional hazards regression models estimated hazard ratios and 95% confidence intervals, with stratified analyses conducted across demographic and clinical subgroups. Restricted cubic spline models were employed to explore potential nonlinear dose-response relationships, while accelerated failure time models assessed the effect of FA levels on the timing of PAH onset. Higher levels of all 8 FAs were linked to a reduced risk of PAH, with the strongest inverse associations observed for docosahexaenoic acid, omega-3, and polyunsaturated fatty acids (hazard ratio range: 0.76 to 0.85, all P < .001). Restricted cubic spline analysis revealed nonlinear relationships between docosahexaenoic acid, omega-3 FAs, and PAH risk. Additionally, accelerated failure time models showed that participants in the highest quartile of FA concentrations experienced a delay in PAH onset by approximately 60 to 120 months compared to those in the lowest quartile. Elevated circulating FA levels were associated with a lower risk of incident PAH, with consistent patterns across most demographic and clinical subgroups. These findings provide novel population-based evidence supporting the potential of FAs as biomarkers for PAH prevention and therapeutic targets.