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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)

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Cerebrovascular disease
Research paper
Serum cholesterol levels, HMG-CoA reductase inhibitors and the risk of intracerebral haemorrhage. The Multicenter Study on Cerebral Haemorrhage in Italy (MUCH-Italy)
  1. Alessandro Pezzini1,
  2. Mario Grassi2,
  3. Licia Iacoviello3,
  4. Marialuisa Zedde4,
  5. Simona Marcheselli5,
  6. Giorgio Silvestrelli6,
  7. Maria Luisa DeLodovici7,
  8. Maria Sessa8,
  9. Andrea Zini9,
  10. Maurizio Paciaroni10,
  11. Cristiano Azzini11,
  12. Massimo Gamba12,
  13. Massimo Del Sette13,
  14. Antonella Toriello14,
  15. Carlo Gandolfo15,
  16. Domenico Marco Bonifati16,
  17. Rossana Tassi17,
  18. Anna Cavallini18,
  19. Alberto Chiti19,
  20. Rocco Salvatore Calabrò20,
  21. Rossella Musolino21,
  22. Paolo Bovi22,
  23. Giampaolo Tomelleri22,
  24. Augusto Di Castelnuovo3,
  25. Laura Vandelli9,
  26. Marco Ritelli23,
  27. Giancarlo Agnelli10,
  28. Alessandro De Vito11,
  29. Nicola Pugliese14,
  30. Giuseppe Martini17,
  31. Alessia Lanari6,
  32. Alfonso Ciccone6,
  33. Corrado Lodigiani24,
  34. Giovanni Malferrari4,
  35. Elisabetta Del Zotto25,
  36. Andrea Morotti1,
  37. Paolo Costa1,
  38. Loris Poli1,
  39. Valeria De Giuli1,
  40. Silvia Bonaiti1,
  41. Paolo La Spina21,
  42. Norina Marcello4,
  43. Giuseppe Micieli18,
  44. Giovanni de Gaetano3,
  45. Marina Colombi23,
  46. Alessandro Padovani1
  47. on behalf of the Multicenter Study on Cerebral Haemorrhage in Italy (MUCH-Italy) Investigators
  1. 1Dipartimento di Scienze Cliniche e Sperimentali, Clinica Neurologica, Università degli Studi di Brescia, Brescia, Italia
  2. 2Dipartimento di Scienze del Sistema Nervoso e del Comportamento, Unità di Statistica Medica e Genomica, Università di Pavia, Pavia, Italia
  3. 3Laboratorio di Epidemiologia Molecolare e Nutrizionale, Dipartimento di Epidemiologia e Prevenzione, IRCCS Istituto Neurologico Mediterraneo, NEUROMED, Pozzilli, Italia
  4. 4SC Neurologia, IRCCS—Arcispedale Santa Maria Nuova, Reggio Emilia, Italia
  5. 5Neurologia d'Urgenza and Stroke Unit, IRCCS Istituto Clinico Humanitas, Rozzano-Milano, Italia
  6. 6Stroke Unit, Dipartimento di Neuroscienze, Azienda Socio Sanitaria Territoriale di Mantova, Mantova, Italia
  7. 7Unità di Neurologia, Ospedale di Circolo, Università dell'Insubria, Varese, Italia
  8. 8SC Neurologia ASST Cremona, Cremona, Italia
  9. 9Stroke Unit, Clinica Neurologica, Nuovo Ospedale Civile “S Agostino Estense”, AUSL, Modena, Italia
  10. 10Stroke Unit and Divisione di Medicina Cardiovascolare, Università di Perugia, Perugia, Italia
  11. 11Stroke Unit, Divisione di Neurologia, Dipartimento di Neuroscienze e Riabilitazione, Azienda Ospedaliero-Universitaria di Ferrara, Italia
  12. 12Stroke Unit, Neurologia Vascolare, Spedali Civili di Brescia, Italia
  13. 13Unità di Neurologia, EO Ospedali Galliera, Genova, Italia
  14. 14U.O.C Neurologia ad Indirizzo Riabilitativo, AO Universitaria “San Giovanni di Dio e Ruggi d'Aragona”, Salerno, Italia
  15. 15Dipartimento di Neuroscienze, Riabilitazione, Oftalmologia, Genetica e Scienze Materno-Infantili, Università di Genova, Italia
  16. 16Stroke Unit, UO Neurologia, Ospedale “S Chiara”, Trento, Italia
  17. 17Stroke Unit, AOU Senese, Siena, Italia
  18. 18U.C Malattie Cerebrovascolari e Stroke Unit and U.C Neurologia d'Urgenza, IRCCS Fondazione Istituto Neurologico Nazionale “C Mondino”, Pavia, Italia
  19. 19U.O Neurologia, Azienda Ospedaliero Universitaria Pisana, Pisa, Italia
  20. 20Istituto di Ricovero e Cura a Carattere Scientifico, Centro Neurolesi Bonino-Pulejo, Messina, Italia
  21. 21Dipartimento di Neuroscienze, Scienze Psichiatriche e Anestesiologiche Clinica Neurologica, Università di Messina, Italia
  22. 22USD Stroke Unit, DAI di Neuroscienze, Azienda Ospedaliera Universitaria Integrata Verona, Italia
  23. 23Divisione di Biologia e Genetica, Dipartimento di Medicina Molecolare e Traslazionale, Università degli Studi di Brescia, Italia
  24. 24Centro Trombosi, IRCCS Istituto Clinico Humanitas, Rozzano-Milano, Italia
  25. 25UO di Recupero e Rieducazione Funzionale, IRCCS Fondazione Don Gnocchi, Rovato, Italia
  1. Correspondence to Dr Alessandro Pezzini, Dipartimento di Scienze Cliniche e Sperimentali, Clinica Neurologica, Università degli Studi di Brescia, P le Spedali Civili 1, Brescia 25123, Italia; ale_pezzini{at}hotmail.com

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.

https://doi.org/10.1136/jnnp-2015-312736

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