Pulmonary hypertension in anti-synthetase syndrome: prevalence, comparative risk across autoimmune diseases, and impact on survival

Objectives: Anti-synthetase syndrome (ASyS) is a distinct entity within the myositis spectrum characterized by interstitial lung disease (ILD) which raises the concern of increased pulmonary vascular pressures. However, the prevalence of pulmonary hypertension (PH) in real-world ASyS populations remains unclear. We investigated the prevalence and impact of PH in ASyS. Methods: Data were obtained from a world-wide, physician-reported multicenter registry based on physician-diagnosed ASyS and/or a positive anti-synthetase antibody. Comparative analyses and multivariable logistic regression assessed the odds of PH in ASyS relative to other disease groups. Cox proportional hazards models evaluated associations with all-cause mortality. Results: A total of 1,868 ASyS and 2,043 controls from 103 centers were analyzed. Prevalence of PH was 8.9% of ASyS, which was higher than in non-ASyS myositis (3%, p < 0.001), rheumatoid arthritis (4%, p = 0.009), and interstitial pneumonia with autoimmune features (IPAF 3%, p = 0.003), but not significantly different from systemic sclerosis (SSc 13%, p = 0.07) or systemic lupus erythematosus (SLE 11%, p = 0.57). ASyS had higher odds of PH compared to non-ASyS myositis (OR 1.91) and IPAF (OR 3.72), but lower odds than SSc (OR 0.62) or SLE (OR 0.24), in multivariate models adjusted for age, sex, smoking and ILD. Five-year survival in ASyS was 94%, decreasing to 88.3% in those with PH (p = 0.001). PH remained associated with increased mortality in ASyS, independent of age, sex and ILD (HR 2.52, 95% CI 1.41-4.53). Conclusion: PH occurred in 8.9% of ASyS and was independently associated with increased mortality, highlighting the importance of PH evaluation in this population.