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

Pezzini, Alessandro; Grassi, Mario; Iacoviello, Licia; Zedde, Marialuisa; Marcheselli, Simona; Silvestrelli, Giorgio; DeLodovici, Maria Luisa; Sessa, Maria; Zini, Andrea; Paciaroni, Maurizio; Azzini, Cristiano; Gamba, Massimo; Sette, Massimo Del; Toriello, Antonella; Bonifati, Domenico Marco; Tassi, Rossana; Cavallini, Anna; Chiti, Alberto; Calabrò, Rocco Salvatore; Musolino, Rossella; Bovi, Paolo; Tomelleri, Giampaolo; Castelnuovo, Augusto Di; Vandelli, Laura; Ritelli, Marco; Agnelli, Giancarlo; Vito, Alessandro De; Pugliese, Nicola; Martini, Giuseppe; Lanari, Alessia; Ciccone, Alfonso; Lodigiani, Corrado; Malferrari, Giovanni; Zotto, Elisabetta Del; Morotti, Andrea; Costa, Paolo; Poli, Loris; Giuli, Valeria De; Bonaiti, Silvia; Spina, Paolo; Marcello, Norina; Micieli, Giuseppe; Gaetano, Giovanni de; Colombi, Marina; Padovani, Alessandro

doi:10.1136/jnnp-2015-312736

Cited by 35 publications

(27 citation statements)

References 23 publications

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“…Finally, a retrospective multivariate analysis of patients with intracerebral hemorrhage found that patients who were treated with statins had almost twice as many cortical MB compared to patients not treated with statins 5 . Unfortunately, these studies are not completely comparable with our study since they include patients without stroke or with hemorrhagic stroke 4 , 5 , 8 , 9 . Because we found that lobar MB and cortical SS are not related to previous statin therapy, we propose that statins do noy play a role in the development of intracranial angiopathies.…”

Section: Discussionmentioning

confidence: 69%

“…Conversely, other studies suggest that statins might cause cerebral amyloid angiopathy (CAA) or MB, and may therefore trigger bleeding complications, but it is unknown whether statin treatment or low colesterol levels increase the amount of MB 10 . A recent study reported that the protective effect of serum cholesterol against intracerebral hemorrhage was reduced by statins but only in lobar regions 8 . The Framingham Heart Study indicated that statin increased the risk of lobar and mixed location MB 4 .…”

Section: Discussionmentioning

confidence: 99%

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Statins do not increase Markers of Cerebral Angiopathies in patients with Cardioembolic Stroke

Martí‐Fàbregas

Medrano-Martorell

Martín-Merino

et al. 2018

Sci Rep

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We investigated whether pre-treatment with statins is associated with surrogate markers of amyloid and hypertensive angiopathies in patients who need to start long-term oral anticoagulation therapy. A prospective multicenter study of patients naive for oral anticoagulants, who had an acute cardioembolic stroke. MRI was performed at admission to evaluate microbleeds, leukoaraiosis and superficial siderosis. We collected data on the specific statin compound, the dose and the statin intensity. We performed bivariate analyses and a logistic regression to investigate variables associated with microbleeds. We studied 470 patients (age 77.5 ± 6.4 years, 43.7% were men), and 193 (41.1%) of them received prior treatment with a statin. Microbleeds were detected in 140 (29.8%), leukoaraiosis in 388 (82.5%) and superficial siderosis in 20 (4.3%) patients. The presence of microbleeds, leukoaraiosis or superficial siderosis was not related to pre-treatment with statins. Microbleeds were more frequent in patients with prior intracerebral hemorrhage (OR 9.7, 95% CI 1.06–90.9) and in those pre-treated antiplatelets (OR 1.66, 95% CI 1.09–2.53). Prior treatment with statins was not associated with markers of bleeding-prone cerebral angiopathies in patients with cardioembolic stroke. Therefore, previous statin treatment should not influence the decision to initiate or withhold oral anticoagulation if these neuroimaging markers are detected.

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Section: Discussionmentioning

confidence: 69%

Section: Discussionmentioning

confidence: 99%

Statins do not increase Markers of Cerebral Angiopathies in patients with Cardioembolic Stroke

Martí‐Fàbregas

Medrano-Martorell

Martín-Merino

et al. 2018

Sci Rep

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“…Prospective studies in Japan also showed an elevated risk of ICH mortality in patients with LDL-C <80 mg/dL or TC <160 mg/dL [1, 3]. The interaction of use of statins and TC levels exhibit higher risk towards the ICH [35]. These findings are warning indications that aggressive lipid-lower therapy might be a concern on the ICH risk.…”

Section: Discussionmentioning

confidence: 99%

Low cholesterol level associated with severity and outcome of spontaneous intracerebral hemorrhage: Results from Taiwan Stroke Registry

Chen

Yang

et al. 2017

PLoS ONE

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The relationship between cholesterol level and hemorrhagic stroke is inconclusive. We hypothesized that low cholesterol levels may have association with intracerebral hemorrhage (ICH) severity at admission and 3-month outcomes. This study used data obtained from a multi-center stroke registry program in Taiwan. We categorized acute spontaneous ICH patients, based on their baseline levels of total cholesterol (TC) measured at admission, into 3 groups with <160, 160–200 and >200 mg/dL of TC. We evaluated risk of having initial stroke severity, with National Institutes of Health Stroke Scale (NIHSS) >15 and unfavorable outcomes (modified Rankin Scale [mRS] score >2, 3-month mortality) after ICH by the TC group. A total of 2444 ICH patients (mean age 62.5±14.2 years; 64.2% men) were included in this study and 854 (34.9%) of them had baseline TC <160 mg/dL. Patients with TC <160 mg/dL presented more often severe neurological deficit (NIHSS >15), with an adjusted odds ratio [aOR] of 1.80; 95% confidence interval [CI], 1.41–2.30), and 3-month mRS >2 (aOR, 1.41; 95% CI, 1.11–1.78) using patients with TC >200 mg/dL as reference. Those with TC >160 mg/dL and body mass index (BMI) <22 kg/m2 had higher risk of 3-month mortality (aOR 3.94, 95% CI 1.76–8.80). Prior use of lipid-lowering drugs (2.8% of the ICH population) was not associated with initial severity and 3-month outcomes. A total cholesterol level lower than 160 mg/dL was common in patients with acute ICH and was associated with greater neurological severity on presentation and poor 3-month outcomes, especially with lower BMI.

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“…While the data for statins and ICH in general remain conflicting, 150–159 observational data suggest that statins might be particularly associated with ICH in the context of CAA. A trend for association between statin use and lobar ICH for those with the ApoE ε4/ε4 or ApoE ε2/ε4 genotypes has been described, 160 and the more recent Multicenter Study on Cerebral Haemorrhage in Italy (MUCH-Italy) study 161 reported that the greatest impact of statins on future ICH risk appears to be in those with lobar haemorrhages. A decision analysis suggested that statin use in survivors of lobar ICH was associated with a reduction in quality-adjusted life years.…”

Section: Management and Treatment Dilemmasmentioning

confidence: 99%

The increasing impact of cerebral amyloid angiopathy: essential new insights for clinical practice

Banerjee

Carare

Cordonnier

et al. 2017

J Neurol Neurosurg Psychiatry

174

137

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Cerebral amyloid angiopathy (CAA) has never been more relevant. The last 5 years have seen a rapid increase in publications and research in the field, with the development of new biomarkers for the disease, thanks to advances in MRI, amyloid positron emission tomography and cerebrospinal fluid biomarker analysis. The inadvertent development of CAA-like pathology in patients treated with amyloid-beta immunotherapy for Alzheimer’s disease has highlighted the importance of establishing how and why CAA develops; without this information, the use of these treatments may be unnecessarily restricted. Our understanding of the clinical and radiological spectrum of CAA has continued to evolve, and there are new insights into the independent impact that CAA has on cognition in the context of ageing and intracerebral haemorrhage, as well as in Alzheimer’s and other dementias. While the association between CAA and lobar intracerebral haemorrhage (with its high recurrence risk) is now well recognised, a number of management dilemmas remain, particularly when considering the use of antithrombotics, anticoagulants and statins. The Boston criteria for CAA, in use in one form or another for the last 20 years, are now being reviewed to reflect these new wide-ranging clinical and radiological findings. This review aims to provide a 5-year update on these recent advances, as well as a look towards future directions for CAA research and clinical practice.

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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)

Abstract: 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.

Cited by 35 publications

References 23 publications

Statins do not increase Markers of Cerebral Angiopathies in patients with Cardioembolic Stroke

Statins do not increase Markers of Cerebral Angiopathies in patients with Cardioembolic Stroke

Low cholesterol level associated with severity and outcome of spontaneous intracerebral hemorrhage: Results from Taiwan Stroke Registry

The increasing impact of cerebral amyloid angiopathy: essential new insights for clinical practice

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