title: Serum cholesterol levels, HMG-CoA reductase inhibitors and the risk of intracerebral haemorrhage. The Multicenter Study on Cerebral Haemorrhage in Italy (MUCH-Italy).
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Dipartimento di Scienze Cliniche e Sperimentali, Clinica Neurologica, Università degli Studi di Brescia, Brescia, Italia.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Pezzini
authors.affiliation: Dipartimento di Scienze del Sistema Nervoso e del Comportamento, Unità di Statistica Medica e Genomica, Università di Pavia, Pavia, Italia.
authors.forename: Mario
authors.initials: M
authors.lastname: Grassi
authors.affiliation: Laboratorio di Epidemiologia Molecolare e Nutrizionale, Dipartimento di Epidemiologia e Prevenzione, IRCCS Istituto Neurologico Mediterraneo, NEUROMED, Pozzilli, Italia.
authors.forename: Licia
authors.initials: L
authors.lastname: Iacoviello
authors.affiliation: SC Neurologia, IRCCS-Arcispedale Santa Maria Nuova, Reggio Emilia, Italia.
authors.forename: Marialuisa
authors.initials: M
authors.lastname: Zedde
authors.affiliation: Neurologia d'Urgenza and Stroke Unit, IRCCS Istituto Clinico Humanitas, Rozzano-Milano, Italia.
authors.forename: Simona
authors.initials: S
authors.lastname: Marcheselli
authors.affiliation: Stroke Unit, Dipartimento di Neuroscienze, Azienda Socio Sanitaria Territoriale di Mantova, Mantova, Italia.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Silvestrelli
authors.affiliation: Unità di Neurologia, Ospedale di Circolo, Università dell'Insubria, Varese, Italia.
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: DeLodovici
authors.affiliation: SC Neurologia ASST Cremona, Cremona, Italia.
authors.forename: Maria
authors.initials: M
authors.lastname: Sessa
authors.affiliation: Stroke Unit, Clinica Neurologica, Nuovo Ospedale Civile "S Agostino Estense", AUSL, Modena, Italia.
authors.forename: Andrea
authors.initials: A
authors.lastname: Zini
authors.affiliation: Stroke Unit and Divisione di Medicina Cardiovascolare, Università di Perugia, Perugia, Italia.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Paciaroni
authors.affiliation: Stroke Unit, Divisione di Neurologia, Dipartimento di Neuroscienze e Riabilitazione, Azienda Ospedaliero-Universitaria di Ferrara, Italia.
authors.forename: Cristiano
authors.initials: C
authors.lastname: Azzini
authors.affiliation: Stroke Unit, Neurologia Vascolare, Spedali Civili di Brescia, Italia.
authors.forename: Massimo
authors.initials: M
authors.lastname: Gamba
authors.affiliation: Unità di Neurologia, EO Ospedali Galliera, Genova, Italia.
authors.forename: Massimo
authors.initials: M
authors.lastname: Del Sette
authors.affiliation: U.O.C Neurologia ad Indirizzo Riabilitativo, AO Universitaria "San Giovanni di Dio e Ruggi d'Aragona", Salerno, Italia.
authors.forename: Antonella
authors.initials: A
authors.lastname: Toriello
authors.affiliation: Dipartimento di Neuroscienze, Riabilitazione, Oftalmologia, Genetica e Scienze Materno-Infantili, Università di Genova, Italia.
authors.forename: Carlo
authors.initials: C
authors.lastname: Gandolfo
authors.affiliation: Stroke Unit, UO Neurologia, Ospedale "S Chiara", Trento, Italia.
authors.forename: Domenico Marco
authors.initials: DM
authors.lastname: Bonifati
authors.affiliation: Stroke Unit, AOU Senese, Siena, Italia.
authors.forename: Rossana
authors.initials: R
authors.lastname: Tassi
authors.affiliation: U.C Malattie Cerebrovascolari e Stroke Unit and U.C Neurologia d'Urgenza, IRCCS Fondazione Istituto Neurologico Nazionale "C Mondino", Pavia, Italia.
authors.forename: Anna
authors.initials: A
authors.lastname: Cavallini
authors.affiliation: U.O Neurologia, Azienda Ospedaliero Universitaria Pisana, Pisa, Italia.
authors.forename: Alberto
authors.initials: A
authors.lastname: Chiti
authors.affiliation: Istituto di Ricovero e Cura a Carattere Scientifico, Centro Neurolesi Bonino-Pulejo, Messina, Italia.
authors.forename: Rocco Salvatore
authors.initials: RS
authors.lastname: Calabrò
authors.affiliation: Dipartimento di Neuroscienze, Scienze Psichiatriche e Anestesiologiche Clinica Neurologica, Università di Messina, Italia.
authors.forename: Rossella
authors.initials: R
authors.lastname: Musolino
authors.affiliation: USD Stroke Unit, DAI di Neuroscienze, Azienda Ospedaliera Universitaria Integrata Verona, Italia.
authors.forename: Paolo
authors.initials: P
authors.lastname: Bovi
authors.affiliation: USD Stroke Unit, DAI di Neuroscienze, Azienda Ospedaliera Universitaria Integrata Verona, Italia.
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Tomelleri
authors.affiliation: Laboratorio di Epidemiologia Molecolare e Nutrizionale, Dipartimento di Epidemiologia e Prevenzione, IRCCS Istituto Neurologico Mediterraneo, NEUROMED, Pozzilli, Italia.
authors.forename: Augusto
authors.initials: A
authors.lastname: Di Castelnuovo
authors.affiliation: Stroke Unit, Clinica Neurologica, Nuovo Ospedale Civile "S Agostino Estense", AUSL, Modena, Italia.
authors.forename: Laura
authors.initials: L
authors.lastname: Vandelli
authors.affiliation: Divisione di Biologia e Genetica, Dipartimento di Medicina Molecolare e Traslazionale, Università degli Studi di Brescia, Italia.
authors.forename: Marco
authors.initials: M
authors.lastname: Ritelli
authors.affiliation: Stroke Unit and Divisione di Medicina Cardiovascolare, Università di Perugia, Perugia, Italia.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Agnelli
authors.affiliation: Stroke Unit, Divisione di Neurologia, Dipartimento di Neuroscienze e Riabilitazione, Azienda Ospedaliero-Universitaria di Ferrara, Italia.
authors.forename: Alessandro
authors.initials: A
authors.lastname: De Vito
authors.affiliation: U.O.C Neurologia ad Indirizzo Riabilitativo, AO Universitaria "San Giovanni di Dio e Ruggi d'Aragona", Salerno, Italia.
authors.forename: Nicola
authors.initials: N
authors.lastname: Pugliese
authors.affiliation: Stroke Unit, AOU Senese, Siena, Italia.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Martini
authors.affiliation: Stroke Unit, Dipartimento di Neuroscienze, Azienda Socio Sanitaria Territoriale di Mantova, Mantova, Italia.
authors.forename: Alessia
authors.initials: A
authors.lastname: Lanari
authors.affiliation: Stroke Unit, Dipartimento di Neuroscienze, Azienda Socio Sanitaria Territoriale di Mantova, Mantova, Italia.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Ciccone
authors.affiliation: Centro Trombosi, IRCCS Istituto Clinico Humanitas, Rozzano-Milano, Italia.
authors.forename: Corrado
authors.initials: C
authors.lastname: Lodigiani
authors.affiliation: SC Neurologia, IRCCS-Arcispedale Santa Maria Nuova, Reggio Emilia, Italia.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Malferrari
authors.affiliation: UO di Recupero e Rieducazione Funzionale, IRCCS Fondazione Don Gnocchi, Rovato, Italia.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Del Zotto
authors.affiliation: Dipartimento di Scienze Cliniche e Sperimentali, Clinica Neurologica, Università degli Studi di Brescia, Brescia, Italia.
authors.forename: Andrea
authors.initials: A
authors.lastname: Morotti
authors.affiliation: Dipartimento di Scienze Cliniche e Sperimentali, Clinica Neurologica, Università degli Studi di Brescia, Brescia, Italia.
authors.forename: Paolo
authors.initials: P
authors.lastname: Costa
authors.affiliation: Dipartimento di Scienze Cliniche e Sperimentali, Clinica Neurologica, Università degli Studi di Brescia, Brescia, Italia.
authors.forename: Loris
authors.initials: L
authors.lastname: Poli
authors.affiliation: Dipartimento di Scienze Cliniche e Sperimentali, Clinica Neurologica, Università degli Studi di Brescia, Brescia, Italia.
authors.forename: Valeria
authors.initials: V
authors.lastname: De Giuli
authors.affiliation: Dipartimento di Scienze Cliniche e Sperimentali, Clinica Neurologica, Università degli Studi di Brescia, Brescia, Italia.
authors.forename: Silvia
authors.initials: S
authors.lastname: Bonaiti
authors.affiliation: Dipartimento di Neuroscienze, Scienze Psichiatriche e Anestesiologiche Clinica Neurologica, Università di Messina, Italia.
authors.forename: Paolo
authors.initials: P
authors.lastname: La Spina
authors.affiliation: SC Neurologia, IRCCS-Arcispedale Santa Maria Nuova, Reggio Emilia, Italia.
authors.forename: Norina
authors.initials: N
authors.lastname: Marcello
authors.affiliation: U.C Malattie Cerebrovascolari e Stroke Unit and U.C Neurologia d'Urgenza, IRCCS Fondazione Istituto Neurologico Nazionale "C Mondino", Pavia, Italia.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Micieli
authors.affiliation: Laboratorio di Epidemiologia Molecolare e Nutrizionale, Dipartimento di Epidemiologia e Prevenzione, IRCCS Istituto Neurologico Mediterraneo, NEUROMED, Pozzilli, Italia.
authors.forename: Giovanni
authors.initials: G
authors.lastname: de Gaetano
authors.affiliation: Divisione di Biologia e Genetica, Dipartimento di Medicina Molecolare e Traslazionale, Università degli Studi di Brescia, Italia.
authors.forename: Marina
authors.initials: M
authors.lastname: Colombi
authors.affiliation: Dipartimento di Scienze Cliniche e Sperimentali, Clinica Neurologica, Università degli Studi di Brescia, Brescia, Italia.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Padovani
mesh_terms: D000368:Aged; D001921:Brain; D016022:Case-Control Studies; D002543:Cerebral Hemorrhage / Q000139:chemically induced* / Q000517:prevention & control; D002784:Cholesterol / Q000097:blood*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D007558:Italy; D008297:Male; D012307:Risk Factors; D020521:Stroke / Q000188:drug therapy
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D002784:Cholesterol