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Interaction between proatherosclerotic factors and right-to-left shunt on the risk of cryptogenic stroke: the Italian Project on Stroke in Young Adults
  1. Alessandro Pezzini1,
  2. Mario Grassi2,
  3. Corrado Lodigiani3,
  4. Rosalba Patella4,
  5. Carlo Gandolfo5,
  6. Andrea Zini6,
  7. Rossella Musolino7,
  8. Rocco Salvatore Calabrò8,
  9. Paolo Bovi9,
  10. Alessandro Adami10,
  11. Maria Luisa DeLodovici11,
  12. Elisabetta Del Zotto1,
  13. Lidia Luciana Rota3,
  14. Maurizia Rasura4,
  15. Massimo Del Sette12,
  16. Alessandra Spalloni4,
  17. Alessia Giossi1,
  18. Irene Volonghi1,
  19. Federica Casoni6,
  20. Paolo Cerrato13,
  21. Paolo Costa1,
  22. Mauro Magoni14,
  23. Antonella Toriello15,
  24. Maurizio Paciaroni16,
  25. Giorgio Dalla Volta17,
  26. Licia Iacoviello18,
  27. Alessandro Padovani1 on behalf of the Italian Project on Stroke in Young Adults (IPSYS) Investigators
  1. 1Dipartimento di Scienze Mediche e Chirurgiche, Clinica Neurologica, Università degli Studi di Brescia, Brescia, Italia
  2. 2Dipartimento di Scienze Sanitarie Applicate, Sezione di Statistica Medica e Epidemiologia, Università di Pavia, Pavia, Italia
  3. 3Centro Trombosi, IRCCS Istituto Clinico Humanitas, Rozzano-Milano, Italia
  4. 4Stroke Unit, Azienda Ospedaliera Sant'Andrea, Roma, Italia
  5. 5Dipartimento di Neuroscienze, Oftalmologia e Genetica, Università di Genova, Genova, Italia
  6. 6Stroke Unit, Clinica Neurologica, Nuovo Ospedale Civile ‘S. Agostino Estense’, AUSL Modena, Italia
  7. 7Dipartimento di Neuroscienze, Scienze Psichiatriche e Anestesiologiche, UOC Neurologia, Università di Messina, Messina, Italia
  8. 8Istituto di Ricovero e Cura a Carattere Scientifico, Centro Neurolesi Bonino-Pulejo, Messina, Italia
  9. 9UO Neurologia, Azienda Ospedaliera-Universitaria Borgo Trento, Verona, Italia
  10. 10Stroke Center, Dipartimento di Neurologia, Ospedale Sacro Cuore Negrar, Verona, Italia
  11. 11Unità di Neurologia, Ospedale di Circolo, Università dell'Insubria, Varese, Italia
  12. 12Unità di Neurologia, Ospedale S. Andrea, La Spezia, Italia
  13. 13Dipartimento di Neuroscienze, Stroke Unit, Università di Torino, Torino, Italia
  14. 14Stroke Unit, Neurologia Vascolare, Spedali Civili di Brescia, Brescia, Italia
  15. 15U.O.C. Neurologia, A.O Salerno, Salerno, Italia
  16. 16Stroke Unit, Divisione di Medicina Cardiovascolare, Università di Perugia, Perugia, Italia
  17. 17U.O. Neurologia, Istituto Clinico Città di Brescia, Brescia, Italia
  18. 18Laboratori di Ricerca, Centro di Ricerca e Formazione ad Alta Tecnologia nelle Scienze Biomediche, ‘Giovanni Paolo II’, Università Cattolica del Sacro Cuore, Campobasso, Italia
  1. Correspondence to Dr Alessandro Pezzini, Dipartimento di Scienze Mediche e Chirurgiche, Clinica Neurologica, Università degli Studi di Brescia, P.le Spedali Civili, 1, 25100 Brescia, Italia; ale_pezzini{at}


Objective To explore the interaction effects between cardiac interatrial right-to-left shunt (RLS) and proatherosclerotic factors on the risk of brain ischaemia.

Design Multicentre Italian case–control study.

Setting University hospitals.

Participants 588 patients with cryptogenic stroke (CS) aged ≤45 years and 585 control subjects consecutively enrolled as part of the Italian Project on Stroke in Young Adults.

Methods Interaction effects between RLS and an individual proatherosclerotic score computed from the number of conventional vascular risk factors for the risk of CS were investigated. Data were examined by logistic regression models and expressed as interaction OR or interaction risk difference (RD).

Results CS risk increased with increasing number of proatherosclerotic factors in subjects without RLS (OR 2.73; 95% CI 1.98 to 3.76; RD +0.246; 95% CI +0.17 to +0.32; for subjects with one or more factors), but was higher in subjects with RLS and no additional proatherosclerotic factors (OR 5.14; 95% CI 3.49 to 7.58; RD +0.388; 95% CI +0.31 to +0.47) compared with subjects without RLS and no risk factors. Negative interaction and antagonistic effects between RLS and proatherosclerotic factors were observed (interaction OR 0.52; 95% CI 0.31 to 0.91; interaction RD −0.17; 95% CI −0.29 to −0.05).

Conclusions The influence of RLS on the risk of CS decreases with increasing number of atherosclerotic factors, and is highest when such factors are absent. Individual proatherosclerotic profiles may help to identify patients with CS whose patent foramen ovale is probably pathogenic.

  • stroke in young adults
  • cardiac
  • risk factors in epidemiology
  • stroke
  • transient ischaemic attack (TIA)
  • gene association
  • homocysteine
  • thrombolysis
  • coagulation factors
  • atrial fibrillation
  • stroke
  • platelet abnormalities
  • deep vein thrombosis

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  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval The study was conducted with the approval of the local ethics committee.

  • Provenance and peer review Not commissioned; externally peer reviewed.