Serum cholesterol levels, HMG-CoA reductase inhibitors and the risk of intracerebral haemorrhage. The Multicenter Study on Cerebral Haemorrhage in Italy (MUCH-Italy)

A. Pezzini, Mario Grassi, Licia Iacoviello, M. Zedde, Simona Marcheselli, Giorgio Silvestrelli, Maria Luisa DeLodovici, Maria Sessa, Andrea Zini, Maurizio Paciaroni, Cristiano Azzini, Massimo Gamba, Massimo Del Sette, Antonella Toriello, Carlo Gandolfo, Domenico Marco Bonifati, Rossana Tassi, Anna Maria Cavallini, Alberto Chiti, Rocco Salvatore Calabrò & 26 others R. Musolino, P. Bovi, G. Tomelleri, Augusto Filippo Di Castelnuovo, Laura Vandelli, Marco Ritelli, Giancarlo Agnelli, A. De Vito, Nicola Pugliese, Giuseppe Martini, Alessia Lanari, Alfonso Ciccone, Corrado Lodigiani, G. Malferrari, Elisabetta Del Zotto, Andrea Morotti, Paolo Costa, Loris Poli, Valeria De Giuli, Silvia Bonaiti, P. La Spina, N. Marcello, Giuseppe Micieli, Giovanni De Gaetano, Marina Colombi, A. Padovani

Research output: Contribution to journalArticle

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.

Original languageEnglish
JournalJournal of Neurology, Neurosurgery and Psychiatry
DOIs
Publication statusAccepted/In press - Mar 21 2016

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Hydroxymethylglutaryl-CoA Reductase Inhibitors
Cerebral Hemorrhage
Italy
Multicenter Studies
Cholesterol
Serum
Brain
Oxidoreductases
Stroke
Hemorrhage

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health
  • Surgery
  • Arts and Humanities (miscellaneous)

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Serum cholesterol levels, HMG-CoA reductase inhibitors and the risk of intracerebral haemorrhage. The Multicenter Study on Cerebral Haemorrhage in Italy (MUCH-Italy). / Pezzini, A.; Grassi, Mario; Iacoviello, Licia; Zedde, M.; Marcheselli, Simona; Silvestrelli, Giorgio; DeLodovici, Maria Luisa; Sessa, Maria; Zini, Andrea; Paciaroni, Maurizio; Azzini, Cristiano; Gamba, Massimo; Del Sette, Massimo; Toriello, Antonella; Gandolfo, Carlo; Bonifati, Domenico Marco; Tassi, Rossana; Cavallini, Anna Maria; Chiti, Alberto; Calabrò, Rocco Salvatore; Musolino, R.; Bovi, P.; Tomelleri, G.; Di Castelnuovo, Augusto Filippo; Vandelli, Laura; Ritelli, Marco; Agnelli, Giancarlo; De Vito, A.; Pugliese, Nicola; Martini, Giuseppe; Lanari, Alessia; Ciccone, Alfonso; Lodigiani, Corrado; Malferrari, G.; Del Zotto, Elisabetta; Morotti, Andrea; Costa, Paolo; Poli, Loris; De Giuli, Valeria; Bonaiti, Silvia; La Spina, P.; Marcello, N.; Micieli, Giuseppe; De Gaetano, Giovanni; Colombi, Marina; Padovani, A.

In: Journal of Neurology, Neurosurgery and Psychiatry, 21.03.2016.

Research output: Contribution to journalArticle

Pezzini, A, Grassi, M, Iacoviello, L, Zedde, M, Marcheselli, S, Silvestrelli, G, DeLodovici, ML, Sessa, M, Zini, A, Paciaroni, M, Azzini, C, Gamba, M, Del Sette, M, Toriello, A, Gandolfo, C, Bonifati, DM, Tassi, R, Cavallini, AM, Chiti, A, Calabrò, RS, Musolino, R, Bovi, P, Tomelleri, G, Di Castelnuovo, AF, Vandelli, L, Ritelli, M, Agnelli, G, De Vito, A, Pugliese, N, Martini, G, Lanari, A, Ciccone, A, Lodigiani, C, Malferrari, G, Del Zotto, E, Morotti, A, Costa, P, Poli, L, De Giuli, V, Bonaiti, S, La Spina, P, Marcello, N, Micieli, G, De Gaetano, G, Colombi, M & Padovani, A 2016, 'Serum cholesterol levels, HMG-CoA reductase inhibitors and the risk of intracerebral haemorrhage. The Multicenter Study on Cerebral Haemorrhage in Italy (MUCH-Italy)', Journal of Neurology, Neurosurgery and Psychiatry. https://doi.org/10.1136/jnnp-2015-312736
Pezzini, A. ; Grassi, Mario ; Iacoviello, Licia ; Zedde, M. ; Marcheselli, Simona ; Silvestrelli, Giorgio ; DeLodovici, Maria Luisa ; Sessa, Maria ; Zini, Andrea ; Paciaroni, Maurizio ; Azzini, Cristiano ; Gamba, Massimo ; Del Sette, Massimo ; Toriello, Antonella ; Gandolfo, Carlo ; Bonifati, Domenico Marco ; Tassi, Rossana ; Cavallini, Anna Maria ; Chiti, Alberto ; Calabrò, Rocco Salvatore ; Musolino, R. ; Bovi, P. ; Tomelleri, G. ; Di Castelnuovo, Augusto Filippo ; Vandelli, Laura ; Ritelli, Marco ; Agnelli, Giancarlo ; De Vito, A. ; Pugliese, Nicola ; Martini, Giuseppe ; Lanari, Alessia ; Ciccone, Alfonso ; Lodigiani, Corrado ; Malferrari, G. ; Del Zotto, Elisabetta ; Morotti, Andrea ; Costa, Paolo ; Poli, Loris ; De Giuli, Valeria ; Bonaiti, Silvia ; La Spina, P. ; Marcello, N. ; Micieli, Giuseppe ; De Gaetano, Giovanni ; Colombi, Marina ; Padovani, A. / Serum cholesterol levels, HMG-CoA reductase inhibitors and the risk of intracerebral haemorrhage. The Multicenter Study on Cerebral Haemorrhage in Italy (MUCH-Italy). In: Journal of Neurology, Neurosurgery and Psychiatry. 2016.
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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.",
author = "A. Pezzini and Mario Grassi and Licia Iacoviello and M. Zedde and Simona Marcheselli and Giorgio Silvestrelli and DeLodovici, {Maria Luisa} and Maria Sessa and Andrea Zini and Maurizio Paciaroni and Cristiano Azzini and Massimo Gamba and {Del Sette}, Massimo and Antonella Toriello and Carlo Gandolfo and Bonifati, {Domenico Marco} and Rossana Tassi and Cavallini, {Anna Maria} and Alberto Chiti and Calabr{\`o}, {Rocco Salvatore} and R. Musolino and P. Bovi and G. Tomelleri and {Di Castelnuovo}, {Augusto Filippo} and Laura Vandelli and Marco Ritelli and Giancarlo Agnelli and {De Vito}, A. and Nicola Pugliese and Giuseppe Martini and Alessia Lanari and Alfonso Ciccone and Corrado Lodigiani and G. Malferrari and {Del Zotto}, Elisabetta and Andrea Morotti and Paolo Costa and Loris Poli and {De Giuli}, Valeria and Silvia Bonaiti and {La Spina}, P. and N. Marcello and Giuseppe Micieli and {De Gaetano}, Giovanni and Marina Colombi and A. Padovani",
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TY - JOUR

T1 - Serum cholesterol levels, HMG-CoA reductase inhibitors and the risk of intracerebral haemorrhage. The Multicenter Study on Cerebral Haemorrhage in Italy (MUCH-Italy)

AU - Pezzini, A.

AU - Grassi, Mario

AU - Iacoviello, Licia

AU - Zedde, M.

AU - Marcheselli, Simona

AU - Silvestrelli, Giorgio

AU - DeLodovici, Maria Luisa

AU - Sessa, Maria

AU - Zini, Andrea

AU - Paciaroni, Maurizio

AU - Azzini, Cristiano

AU - Gamba, Massimo

AU - Del Sette, Massimo

AU - Toriello, Antonella

AU - Gandolfo, Carlo

AU - Bonifati, Domenico Marco

AU - Tassi, Rossana

AU - Cavallini, Anna Maria

AU - Chiti, Alberto

AU - Calabrò, Rocco Salvatore

AU - Musolino, R.

AU - Bovi, P.

AU - Tomelleri, G.

AU - Di Castelnuovo, Augusto Filippo

AU - Vandelli, Laura

AU - Ritelli, Marco

AU - Agnelli, Giancarlo

AU - De Vito, A.

AU - Pugliese, Nicola

AU - Martini, Giuseppe

AU - Lanari, Alessia

AU - Ciccone, Alfonso

AU - Lodigiani, Corrado

AU - Malferrari, G.

AU - Del Zotto, Elisabetta

AU - Morotti, Andrea

AU - Costa, Paolo

AU - Poli, Loris

AU - De Giuli, Valeria

AU - Bonaiti, Silvia

AU - La Spina, P.

AU - Marcello, N.

AU - Micieli, Giuseppe

AU - De Gaetano, Giovanni

AU - Colombi, Marina

AU - Padovani, A.

PY - 2016/3/21

Y1 - 2016/3/21

N2 - 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.

AB - 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.

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U2 - 10.1136/jnnp-2015-312736

DO - 10.1136/jnnp-2015-312736

M3 - Article

JO - Journal of Neurology, Neurosurgery and Psychiatry

JF - Journal of Neurology, Neurosurgery and Psychiatry

SN - 0022-3050

ER -