Alessandro Pezzini1, Mario Grassi2, Licia Iacoviello3, Marialuisa Zedde4, Simona Marcheselli5, Giorgio Silvestrelli6, Maria Luisa DeLodovici7, Maria Sessa8, Andrea Zini9, Maurizio Paciaroni10, Cristiano Azzini11, Massimo Gamba12, Massimo Del Sette13, Antonella Toriello14, Carlo Gandolfo15, Domenico Marco Bonifati16, Rossana Tassi17, Anna Cavallini18, Alberto Chiti19, Rocco Salvatore Calabrò20, Rossella Musolino21, Paolo Bovi22, Giampaolo Tomelleri22, Augusto Di Castelnuovo3, Laura Vandelli9, Marco Ritelli23, Giancarlo Agnelli10, Alessandro De Vito11, Nicola Pugliese14, Giuseppe Martini17, Alessia Lanari6, Alfonso Ciccone6, Corrado Lodigiani24, Giovanni Malferrari4, Elisabetta Del Zotto25, Andrea Morotti1, Paolo Costa1, Loris Poli1, Valeria De Giuli1, Silvia Bonaiti1, Paolo La Spina21, Norina Marcello4, Giuseppe Micieli18, Giovanni de Gaetano3, Marina Colombi23, Alessandro Padovani1. 1. Dipartimento di Scienze Cliniche e Sperimentali, Clinica Neurologica, Università degli Studi di Brescia, Brescia, Italia. 2. Dipartimento di Scienze del Sistema Nervoso e del Comportamento, Unità di Statistica Medica e Genomica, Università di Pavia, Pavia, Italia. 3. Laboratorio di Epidemiologia Molecolare e Nutrizionale, Dipartimento di Epidemiologia e Prevenzione, IRCCS Istituto Neurologico Mediterraneo, NEUROMED, Pozzilli, Italia. 4. SC Neurologia, IRCCS-Arcispedale Santa Maria Nuova, Reggio Emilia, Italia. 5. Neurologia d'Urgenza and Stroke Unit, IRCCS Istituto Clinico Humanitas, Rozzano-Milano, Italia. 6. Stroke Unit, Dipartimento di Neuroscienze, Azienda Socio Sanitaria Territoriale di Mantova, Mantova, Italia. 7. Unità di Neurologia, Ospedale di Circolo, Università dell'Insubria, Varese, Italia. 8. SC Neurologia ASST Cremona, Cremona, Italia. 9. Stroke Unit, Clinica Neurologica, Nuovo Ospedale Civile "S Agostino Estense", AUSL, Modena, Italia. 10. Stroke Unit and Divisione di Medicina Cardiovascolare, Università di Perugia, Perugia, Italia. 11. Stroke Unit, Divisione di Neurologia, Dipartimento di Neuroscienze e Riabilitazione, Azienda Ospedaliero-Universitaria di Ferrara, Italia. 12. Stroke Unit, Neurologia Vascolare, Spedali Civili di Brescia, Italia. 13. Unità di Neurologia, EO Ospedali Galliera, Genova, Italia. 14. U.O.C Neurologia ad Indirizzo Riabilitativo, AO Universitaria "San Giovanni di Dio e Ruggi d'Aragona", Salerno, Italia. 15. Dipartimento di Neuroscienze, Riabilitazione, Oftalmologia, Genetica e Scienze Materno-Infantili, Università di Genova, Italia. 16. Stroke Unit, UO Neurologia, Ospedale "S Chiara", Trento, Italia. 17. Stroke Unit, AOU Senese, Siena, Italia. 18. U.C Malattie Cerebrovascolari e Stroke Unit and U.C Neurologia d'Urgenza, IRCCS Fondazione Istituto Neurologico Nazionale "C Mondino", Pavia, Italia. 19. U.O Neurologia, Azienda Ospedaliero Universitaria Pisana, Pisa, Italia. 20. Istituto di Ricovero e Cura a Carattere Scientifico, Centro Neurolesi Bonino-Pulejo, Messina, Italia. 21. Dipartimento di Neuroscienze, Scienze Psichiatriche e Anestesiologiche Clinica Neurologica, Università di Messina, Italia. 22. USD Stroke Unit, DAI di Neuroscienze, Azienda Ospedaliera Universitaria Integrata Verona, Italia. 23. Divisione di Biologia e Genetica, Dipartimento di Medicina Molecolare e Traslazionale, Università degli Studi di Brescia, Italia. 24. Centro Trombosi, IRCCS Istituto Clinico Humanitas, Rozzano-Milano, Italia. 25. UO di Recupero e Rieducazione Funzionale, IRCCS Fondazione Don Gnocchi, Rovato, Italia.
Abstract
OBJECTIVE: Although a concern exists that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) might increase the risk of intracerebral haemorrhage (ICH), the contribution of these agents to the relationship between serum cholesterol and disease occurrence has been poorly investigated. METHODS: We compared consecutive patients having ICH with age and sex-matched stroke-free control subjects in a case-control analysis, as part of the Multicenter Study on Cerebral Haemorrhage in Italy (MUCH-Italy), and tested the presence of interaction effects between total serum cholesterol levels and statins on the risk of ICH. RESULTS: A total of 3492 cases (mean age, 73.0±12.7 years; males, 56.6%) and 3492 control subjects were enrolled. Increasing total serum cholesterol levels were confirmed to be inversely associated with ICH. We observed a statistical interaction between total serum cholesterol levels and statin use for the risk of haemorrhage (Interaction OR (IOR), 1.09; 95% CI 1.05 to 1.12). Increasing levels of total serum cholesterol were associated with a decreased risk of ICH within statin strata (average OR, 0.87; 95% CI 0.86 to 0.88 for every increase of 0.26 mmol/l of total serum cholesterol concentrations), while statin use was associated with an increased risk (OR, 1.54; 95% CI 1.31 to 1.81 of the average level of total serum cholesterol). The protective effect of serum cholesterol against ICH was reduced by statins in strictly lobar brain regions more than in non-lobar ones. CONCLUSIONS: Statin therapy and total serum cholesterol levels exhibit interaction effects towards the risk of ICH. The magnitude of such effects appears higher in lobar brain regions. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
OBJECTIVE: Although a concern exists that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) might increase the risk of intracerebral haemorrhage (ICH), the contribution of these agents to the relationship between serum cholesterol and disease occurrence has been poorly investigated. METHODS: We compared consecutive patients having ICH with age and sex-matched stroke-free control subjects in a case-control analysis, as part of the Multicenter Study on Cerebral Haemorrhage in Italy (MUCH-Italy), and tested the presence of interaction effects between total serum cholesterol levels and statins on the risk of ICH. RESULTS: A total of 3492 cases (mean age, 73.0±12.7 years; males, 56.6%) and 3492 control subjects were enrolled. Increasing total serum cholesterol levels were confirmed to be inversely associated with ICH. We observed a statistical interaction between total serum cholesterol levels and statin use for the risk of haemorrhage (Interaction OR (IOR), 1.09; 95% CI 1.05 to 1.12). Increasing levels of total serum cholesterol were associated with a decreased risk of ICH within statin strata (average OR, 0.87; 95% CI 0.86 to 0.88 for every increase of 0.26 mmol/l of total serum cholesterol concentrations), while statin use was associated with an increased risk (OR, 1.54; 95% CI 1.31 to 1.81 of the average level of total serum cholesterol). The protective effect of serum cholesterol against ICH was reduced by statins in strictly lobar brain regions more than in non-lobar ones. CONCLUSIONS: Statin therapy and total serum cholesterol levels exhibit interaction effects towards the risk of ICH. The magnitude of such effects appears higher in lobar brain regions. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
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