Pulmonary hypertension in anti-synthetase syndrome: prevalence, comparative risk across autoimmune diseases, and impact on survival
Sangmee Sharon Bae, Daphne Rivero Gallegos, Francisca Bozan, Gianluca Sambataro, Eduardo Dourado, Giovanni Zanframundo, Iazsmin Bauer Ventura, Akira Yoshida, Sara Faghihi-Kashani, Aravinthan Loganathan, Francesco Bonella, Miguel A Gonzalez-Gay, Masataka Kuwana, Chester V Oddis, Jorge Rojas-Serrano, Latika Gupta, Upendra Rathore, Anamika Anuja, Marco Fornaro, Florenzo Iannone, Lorenzo Bianchessi, Samuel Katsuyuki Shinjo, Fernando Henrique Carlos de Souza, Renata Miossi, Fabrizio Luppi, Siamak Moghadam-Kia, Rohit Aggarwal, Lorenzo Cavagna, , Adam Schiffenbauer, Akira Yoshida, Alain Meyer, Albert Gil-Vila, Alberto Cauli, Alessandro Biglia, Ana Villar, Anamika Anuja, André Pinto Saraiva, Andreina Manfredi, Angela Ceribelli, Anna Mandel, Antonella Notarnicola, Antony Amato, Aravinthan Loganathan, Carlo Selmi, Carlo Vancheri, Caterina Vacchi, Chiara Murru, Christina Charles-Schoeman, Christopher Fiehn, Claudia Alpini, Corrado Campochiaro, Daniela Ghetie, Daphne Rivero Gallegos, Darosa Lim, David Lacomis, Davide Rozza, Devarasetti Phani Kumar, Diana Isabel Perez Roman, Domenica Federica Briganti, Domenico Sambataro, Edoardo Conticini, Eduardo Dourado, Elena Bravi, Elena Schiopu, Elizabeth Volkmann, Erkan Alpsoy, Ernesto Trallero-Araguas, Esther Ebstein, Esther Francisca Vicente-Rabaneda, Eugenio Arrigoni, Fabian Caro, Fabrizio Luppi, Farah Tamirou, Felipe Reyes, Fernando Henrique Carlos de Souza, Florenzo Iannone, Francesca Bottazzi, Francesco Girolamo, Francisca Bozan, Franco Franceschini, Garifallia Sakellariou, George Schett, Giacomo De Luca, Giandomenco Sebastiani, Gianluca Erre, Gianluca Sambataro, Giovanni Barausse, Giovanni Cagnotto, Giovanni Franco, Giovanni Zanframundo, Giulia Dei, Harsha Gunawardena, Heather Bukiri, Hector Chinoy, Helena Andersson, Iazsmin Bauer Ventura, Ilaria Cavazzana, Iñigo Rua-Figueroa, James B Lilleker, Javier Bachiller-Corral, Jesus Loarce Martos, João Eurico Fonseca, Johannes Knitza, Jörg H W Distler, Jose Cifrian, Julia Martínez-Barrio, Julien Campagne, Jutta Bauhammer, Karen Vergara, Konstantinos Triantafyllias, Latika Gupta, Laura Nuño-Nuño, Laure Gallay, Lisa G Rider, Liza Rajasekhar, Lorenzo Bianchessi, Lorenzo Dagna, Lucian Marts, Marcello Govoni, Marco Fornaro, Marco Sebastiani, Margherita Giannini, Maria Giovanna Danieli, Maria Laura Alberti, Maria Rosa Pozzi, Marta Cheli, Martín Gerardo Greco Merino, Massimiliano Limonta, Matias Florenzano, Matteo Piga, Matthew Parker, Matthias Schneider, Mayra Mejia, Merrilee Needham, Michele Colaci, Monica Morosini, Nair Perez Gomez, Natasa Isailovic, Natsuka Umezawa, Noreen Fertig, Océane Landon-Cardinal, Osnat Klein, Paola Faverio, Paola Parronchi, Paola Tomietto, Pari Basharat, Paul Dellaripa, Paul Hansen, Pedro Abisay Rivera Matias, Pier Paolo Sainaghi, Prateek Gandiga, Ran Nakashima, Raquel Campanilho-Marques, Reinhard Edmund Voll, Renata Miossi, Ruby Taparia, Salvatore Scarpato, Samuel Katsuyuki Shinjo, Sangmee Sharon Bae, Santos Castañeda, Sara Bozzini, Sara Faghihi-Kashani, Sarah Tansley, Siamak Moghadam-Kia, Silvana Saavedra, Simone Barsotti, Stylianos Tomaras, Teresa Melo, Upendra Rathore, Vega Jovani, Veronica Codullo, Veronica Wolff, Vincent Cottin, Yair Molad, Yasuhiko Yamano, Yasuhiro Kondo, Yuko KanekoAbstract
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.