title: A gender gap in primary and secondary heart dysfunctions in systemic sclerosis: a EUSTAR prospective study.
abstract: OBJECTIVE
  In agreement with other autoimmune diseases, systemic sclerosis (SSc) is associated with a strong sex bias. However, unlike lupus, the effects of sex on disease phenotype and prognosis are poorly known. Therefore, we aimed to determine sex effects on outcomes.
  
  
  METHODS
  We performed a prospective observational study using the latest 2013 data extract from the EULAR scleroderma trials and research (EUSTAR) cohort. We looked at (i) sex influence on disease characteristics at baseline and (ii) then focused on patients with at least 2 years of follow-up to estimate the effects of sex on disease progression and survival.
  
  
  RESULTS
  9182 patients with SSc were available (1321 men) for the baseline analyses. In multivariate analysis, male sex was independently associated with a higher risk of diffuse cutaneous subtype (OR: 1.68, (1.45 to 1.94); p<0.001), a higher frequency of digital ulcers (OR: 1.28 (1.11 to 1.47); p<0.001) and pulmonary hypertension (OR: 3.01 (1.47 to 6.20); p<0.003). In the longitudinal analysis (n=4499), after a mean follow-up of 4.9 (±2.7) years, male sex was predictive of new onset of pulmonary hypertension (HR: 2.66 (1.32 to 5.36); p=0.006) and heart failure (HR: 2.22 (1.06 to 4.63); p=0.035). 908 deaths were recorded, male sex predicted deaths of all origins (HR: 1.48 (1.19 to 1.84); p<0.001), but did not significantly account for SSc-related deaths.
  
  
  CONCLUSIONS
  Although more common in women, SSc appears as strikingly more severe in men. Our results obtained through the largest worldwide database demonstrate a higher risk of severe cardiovascular involvement in men. These results raise the point of including sex in the management and the decision-making process.
authors.affiliation: Department of Rheumatology A, Paris Descartes University, Cochin Hospital, Paris, France.
authors.forename: Muriel
authors.initials: M
authors.lastname: Elhai
authors.affiliation: Department of Rheumatology A, Paris Descartes University, Cochin Hospital, Paris, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Avouac
authors.affiliation: Department of Rheumatology, Basel University, Unispital Basel, Basel, Switzerland.
authors.forename: Ulrich A
authors.initials: UA
authors.lastname: Walker
authors.affiliation: Department of Experimental and Clinical Medicine, Section of Internal Medicine and Division of Rheumatology, Azienda Ospedaliero-Universitaria Careggi (AOUC), University of Florence, Florence, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Matucci-Cerinic
authors.affiliation: Department of Rheumatology, Charitè University Hospital, Berlin, German Rheumatism Research Centre Berlin (DRFZ), a Leibniz institute, Berlin, Germany.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Riemekasten
authors.affiliation: UO Reumatologia ed Immunologia Clinica Spedali Civili Brescia, Brescia, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Airò
authors.affiliation: Department of Internal Medicine, Hôpital Claude Huriez, University Lille Nord-de-France, Lille cedex, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Hachulla
authors.affiliation: Department of Clinical and Experimental Medicine "F-Magrassi" II, Naples, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Valentini
authors.affiliation: Servicio de Reumatologia, Hospital Universitario 12 de Octubre, Madrid, Spain.
authors.forename: Patricia E
authors.initials: PE
authors.lastname: Carreira
authors.affiliation: Rheumatology Unit, Department of Medicine-DIMED, University of Padova, Padova, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Cozzi
authors.affiliation: B. Shine Department of Rheumatology, Rambam Health Care Campus, Rappaport Faculty of Medicine, Technion-Institute of Technology, Haifa, Israel.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Balbir Gurman
authors.affiliation: B. Shine Department of Rheumatology, Rambam Health Care Campus, Rappaport Faculty of Medicine, Technion-Institute of Technology, Haifa, Israel.
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Braun-Moscovici
authors.affiliation: Institute of Rheumatology, University of Belgrade Medical School, Belgrade, Serbia.
authors.forename: Nemanja
authors.initials: N
authors.lastname: Damjanov
authors.affiliation: Institute of Rheumatology, Russian Academy of Medical Science, Moscow, Russia.
authors.forename: Lidia P
authors.initials: LP
authors.lastname: Ananieva
authors.affiliation: U.O. Immunologia Clinica-Centro di Riferimento per le Malattie Autoimmuni Sistemiche, Milano, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Scorza
authors.affiliation: Scleroderma Center of Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
authors.forename: Sergio
authors.initials: S
authors.lastname: Jimenez
authors.affiliation: Scleroderma Center of Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
authors.forename: Joanna
authors.initials: J
authors.lastname: Busquets
authors.affiliation: Department of Rheumatology, Peking Union Medical College Hospital (West Campus), Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Mengtao
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Rheumatology and Clinical Immunology, Justus-Liebig University Giessen, Kerckhoff Clinic, Bad Nauheim, Germany.
authors.forename: Ulf
authors.initials: U
authors.lastname: Müller-Ladner
authors.affiliation: Department of Rheumatology A, Paris Descartes University, Cochin Hospital, Paris, France.
authors.forename: André
authors.initials: A
authors.lastname: Kahan
authors.affiliation: Department of Rheumatology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Oliver
authors.initials: O
authors.lastname: Distler
authors.affiliation: Department of Rheumatology A, Paris Descartes University, Cochin Hospital, Paris, France.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Allanore
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000209:etiology*; D016208:Databases, Factual; D018450:Disease Progression; D005060:Europe / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D012595:Scleroderma, Systemic / Q000150:complications* / Q000453:epidemiology; D017678:Sex Distribution; D012737:Sex Factors
keywords: Autoimmune Diseases; Epidemiology; Systemic Sclerosis