• Ivan Arias de la Rosa, Maria Dolores López-Montilla, Cristobal Román-Rodríguez, Carlos Pérez-Sánchez, Ignacio Gómez-García, Clementina López-Medina, Maria Lourdes Ladehesa-Pineda, Maria Del Carmen Ábalos-Aguilera, Desiree Ruiz, Alejandra Maria Patiño-Trives, Maria Luque-Tévar, Isabel Añón-Oñate, Maria Jose Pérez-Galán, Rocio Guzmán-Ruiz, Maria M Malagón, Chary López-Pedrera, Alejandro Escudero-Contreras, Eduardo Collantes-Estévez, and Nuria Barbarroja.
• Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC)/Reina Sofia Hospital, University of Cordoba, Cordoba, Spain.
• J. Intern. Med. 2022 May 1; 291 (5): 676-693.

Objectives(1) To evaluate clinical and molecular cardiovascular disease (CVD) signs and their relationship with psoriatic arthritis (PsA) features and (2) to identify a clinical patient profile susceptible to benefit from methotrexate (MTX) and/or apremilast regarding CVD risk.MethodsThis cross-sectional study included 100 patients with PsA and 100 age-matched healthy donors. In addition, an exploratory cohort of 45 biologically naïve patients treated for 6 months with apremilast, MTX or combined therapy according to routine clinical practice was recruited. Extensive clinical and metabolic profiles were obtained. Ninety-nine surrogate CVD-related molecules were analysed in plasma and peripheral blood mononuclear cells (PBMCs). Hard cluster analysis was performed to identify the clinical and molecular phenotypes. Mechanistic studies were performed on adipocytes.ResultsCardiometabolic comorbidities were associated with disease activity and long-term inflammatory status. Thirty-five CVD-related proteins were altered in the plasma and PBMCs of PsA patients and were associated with the key clinical features of the disease. Plasma levels of some of the CVD-related molecules might distinguish insulin-resistant patients (MMP-3, CD163, FABP-4), high disease activity (GAL-3 and FABP-4) and poor therapy outcomes (CD-163, LTBR and CNTN-1). Hard cluster analysis identified two phenotypes of patients according to the rates of cardiometabolic comorbidities with distinctive clinical and molecular responses to each treatment.Conclusions(1) Novel CVD-related proteins associated with clinical features could be emerging therapeutic targets in the context of PsA and (2) the pleiotropic action of apremilast could make it an excellent choice for the management of PsA patients with high CVD risk, targeting metabolic alterations and CVD-related molecules.© 2022 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.

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