Saloua Akoudad1, M Arfan Ikram1, Marileen L P Portegies2, Hieab H Adams3, Daniel Bos3, Albert Hofman4, Peter J Koudstaal5, Andre G Uitterlinden6, Aad van der Lugt7, Cornelia M van Duijn4, Meike W Vernooij8. 1. Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, the Netherlands; Department of Radiology, Erasmus MC, University Medical Center Rotterdam, the Netherlands; Department of Neurology, Erasmus MC, University Medical Center Rotterdam, the Netherlands. 2. Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, the Netherlands; Department of Neurology, Erasmus MC, University Medical Center Rotterdam, the Netherlands. 3. Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, the Netherlands; Department of Radiology, Erasmus MC, University Medical Center Rotterdam, the Netherlands. 4. Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, the Netherlands. 5. Department of Neurology, Erasmus MC, University Medical Center Rotterdam, the Netherlands. 6. Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, the Netherlands; Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, the Netherlands. 7. Department of Radiology, Erasmus MC, University Medical Center Rotterdam, the Netherlands. 8. Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, the Netherlands; Department of Radiology, Erasmus MC, University Medical Center Rotterdam, the Netherlands. Electronic address: m.vernooij@erasmusmc.nl.
Abstract
BACKGROUND: Serum total cholesterol and its fractions are inversely associated with intracerebral hemorrhages (ICH) and their potential subclinical precursor, cerebral microbleeds. To ascertain whether there is a genetic basis for this inverse association, we studied established genetic loci for serum total, LDL, and HDL cholesterol, and triglycerides in their association with ICH and microbleeds. METHODS: Data on 161 genetic variants for serum lipids was collected in 9011 stroke-free participants (mean age 65.8, SD 10.2; 57.9% women) of the population-based Rotterdam Study. Participants were followed from baseline (1997-2005) up to 2013 for the occurrence of ICH. A subset of 4179 participants underwent brain MRI for microbleed assessment between 2005 and 2011. We computed genetic risk scores (GRS) for the joint effect of lipid variants. Cox proportional hazards and logistic regression models were used to investigate the association of GRS of lipid fractions with ICH and microbleeds. RESULTS: After a mean follow-up of 8.7 (SD 4.1) years, 67 (0.7%) participants suffered an ICH. Microbleed prevalence was 19.6%. Higher genetic load for high serum total and LDL cholesterol was associated with an increased risk of ICH. Higher genetic load for high serum LDL cholesterol was borderline associated with a higher prevalence of multiple lobar microbleeds. CONCLUSIONS: Genetic susceptibility for high serum total and LDL cholesterol is positively associated with incident ICH and borderline associated with multiple lobar microbleeds. We did not find a genetic basis for the previously reported inverse association between serum lipid levels and ICH.
BACKGROUND: Serum total cholesterol and its fractions are inversely associated with intracerebral hemorrhages (ICH) and their potential subclinical precursor, cerebral microbleeds. To ascertain whether there is a genetic basis for this inverse association, we studied established genetic loci for serum total, LDL, and HDL cholesterol, and triglycerides in their association with ICH and microbleeds. METHODS: Data on 161 genetic variants for serum lipids was collected in 9011 stroke-free participants (mean age 65.8, SD 10.2; 57.9% women) of the population-based Rotterdam Study. Participants were followed from baseline (1997-2005) up to 2013 for the occurrence of ICH. A subset of 4179 participants underwent brain MRI for microbleed assessment between 2005 and 2011. We computed genetic risk scores (GRS) for the joint effect of lipid variants. Cox proportional hazards and logistic regression models were used to investigate the association of GRS of lipid fractions with ICH and microbleeds. RESULTS: After a mean follow-up of 8.7 (SD 4.1) years, 67 (0.7%) participants suffered an ICH. Microbleed prevalence was 19.6%. Higher genetic load for high serum total and LDL cholesterol was associated with an increased risk of ICH. Higher genetic load for high serum LDL cholesterol was borderline associated with a higher prevalence of multiple lobar microbleeds. CONCLUSIONS: Genetic susceptibility for high serum total and LDL cholesterol is positively associated with incident ICH and borderline associated with multiple lobar microbleeds. We did not find a genetic basis for the previously reported inverse association between serum lipid levels and ICH.
Authors: Pamela M Rist; Julie E Buring; Paul M Ridker; Carlos S Kase; Tobias Kurth; Kathryn M Rexrode Journal: Neurology Date: 2019-04-10 Impact factor: 9.910