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 CalabròR. 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


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
Publication statusAccepted/In press - Mar 21 2016


ASJC Scopus subject areas

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

Cite this

Pezzini, A., Grassi, M., Iacoviello, L., Zedde, M., Marcheselli, S., Silvestrelli, G., DeLodovici, M. L., Sessa, M., Zini, A., Paciaroni, M., Azzini, C., Gamba, M., Del Sette, M., Toriello, A., Gandolfo, C., Bonifati, D. M., Tassi, R., Cavallini, A. M., Chiti, A., ... Padovani, A. (Accepted/In press). 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.