Chia-Ling Phuah1, Miriam R Raffeld1, Alison M Ayres1, Anand Viswanathan1, Steven M Greenberg1, Alessandro Biffi1, Jonathan Rosand1, Christopher D Anderson2. 1. From the Division of Neurocritical Care and Emergency Neurology (C.-L.P., J.R., C.D.A.), Center for Human Genetic Research (C.-L.P., M.R.R., A.B., J.R., C.D.A.), The J. Philip Kistler Stroke Research Center (A.M.A., A.V., S.M.G., J.R., C.D.A.), and Hemorrhagic Stroke Research Group (A.M.A., A.V., S.M.G., A.B., J.R., C.D.A.), Massachusetts General Hospital, Boston; and Program in Medical and Population Genetics (C.-L.P., A.B., J.R., C.D.A.), Broad Institute, Cambridge, MA. 2. From the Division of Neurocritical Care and Emergency Neurology (C.-L.P., J.R., C.D.A.), Center for Human Genetic Research (C.-L.P., M.R.R., A.B., J.R., C.D.A.), The J. Philip Kistler Stroke Research Center (A.M.A., A.V., S.M.G., J.R., C.D.A.), and Hemorrhagic Stroke Research Group (A.M.A., A.V., S.M.G., A.B., J.R., C.D.A.), Massachusetts General Hospital, Boston; and Program in Medical and Population Genetics (C.-L.P., A.B., J.R., C.D.A.), Broad Institute, Cambridge, MA. cdanderson@mgh.harvard.edu.
Abstract
OBJECTIVE: We aimed to describe the temporal variation in circulating lipid levels among patients with intracerebral hemorrhage (ICH) and investigate their association with ICH risk. METHODS: This was a single-center, retrospective, longitudinal, case-control analysis using cases drawn from an ongoing cohort study of primary ICH and controls drawn from a hospital-based clinical data registry. Piecewise linear mixed-effect random coefficient models were used to determine the significance of changes in serum lipid trends on ICH risk. RESULTS: Two hundred twelve ICH cases and 301 control individuals were analyzed. Overall trends in serum total cholesterol (TC) and low-density lipoprotein (LDL) levels differed between ICH cases and non-ICH controls (p = 0.00001 and p = 0.0092, respectively). Patients with ICH experience accelerated decline in serum TC and LDL levels during 6 months immediately preceding ICH, compared with levels between 6 and 24 months pre-ICH (TC: -29.25 mg/dL, p = 0.001; LDL: -21.48 mg/dL, p = 0.0038), which was not observed in non-ICH controls. Subgroup analysis confirmed that this phenomenon cannot be attributed to statin or alcohol exposure. Serum triglycerides and high-density lipoprotein trends did not differ between groups. CONCLUSIONS: Longitudinal lipid levels differ between ICH cases and non-ICH controls, most notably for a decline in serum TC and LDL levels within 6 months preceding primary ICH, independent of statin or alcohol use. These changes in serum TC and LDL trends suggest a biological pathway that precipitates ICH occurrence. Further studies are needed to replicate these results and characterize rate of change in serum lipids as a potential biomarker of impending acute cerebral injury.
OBJECTIVE: We aimed to describe the temporal variation in circulating lipid levels among patients with intracerebral hemorrhage (ICH) and investigate their association with ICH risk. METHODS: This was a single-center, retrospective, longitudinal, case-control analysis using cases drawn from an ongoing cohort study of primary ICH and controls drawn from a hospital-based clinical data registry. Piecewise linear mixed-effect random coefficient models were used to determine the significance of changes in serum lipid trends on ICH risk. RESULTS: Two hundred twelve ICH cases and 301 control individuals were analyzed. Overall trends in serum total cholesterol (TC) and low-density lipoprotein (LDL) levels differed between ICH cases and non-ICH controls (p = 0.00001 and p = 0.0092, respectively). Patients with ICH experience accelerated decline in serum TC and LDL levels during 6 months immediately preceding ICH, compared with levels between 6 and 24 months pre-ICH (TC: -29.25 mg/dL, p = 0.001; LDL: -21.48 mg/dL, p = 0.0038), which was not observed in non-ICH controls. Subgroup analysis confirmed that this phenomenon cannot be attributed to statin or alcohol exposure. Serum triglycerides and high-density lipoprotein trends did not differ between groups. CONCLUSIONS: Longitudinal lipid levels differ between ICH cases and non-ICH controls, most notably for a decline in serum TC and LDL levels within 6 months preceding primary ICH, independent of statin or alcohol use. These changes in serum TC and LDL trends suggest a biological pathway that precipitates ICH occurrence. Further studies are needed to replicate these results and characterize rate of change in serum lipids as a potential biomarker of impending acute cerebral injury.
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Authors: Christopher D Anderson; Guido J Falcone; Chia-Ling Phuah; Farid Radmanesh; H Bart Brouwers; Thomas W K Battey; Alessandro Biffi; Gina M Peloso; Dajiang J Liu; Alison M Ayres; Joshua N Goldstein; Anand Viswanathan; Steven M Greenberg; Magdy Selim; James F Meschia; Devin L Brown; Bradford B Worrall; Scott L Silliman; David L Tirschwell; Matthew L Flaherty; Peter Kraft; Jeremiasz M Jagiella; Helena Schmidt; Björn M Hansen; Jordi Jimenez-Conde; Eva Giralt-Steinhauer; Roberto Elosua; Elisa Cuadrado-Godia; Carolina Soriano; Koen M van Nieuwenhuizen; Catharina J M Klijn; Kristiina Rannikmae; Neshika Samarasekera; Rustam Al-Shahi Salman; Catherine L Sudlow; Ian J Deary; Andrea Morotti; Alessandro Pezzini; Joanna Pera; Andrzej Urbanik; Alexander Pichler; Christian Enzinger; Bo Norrving; Joan Montaner; Israel Fernandez-Cadenas; Pilar Delgado; Jaume Roquer; Arne Lindgren; Agnieszka Slowik; Reinhold Schmidt; Chelsea S Kidwell; Steven J Kittner; Salina P Waddy; Carl D Langefeld; Goncalo Abecasis; Cristen J Willer; Sekar Kathiresan; Daniel Woo; Jonathan Rosand Journal: Ann Neurol Date: 2016-10-19 Impact factor: 10.422