Subacute decline in serum lipids precedes the occurrence of primary intracerebral hemorrhage

Chia-Ling Phuah, 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.Follow
Miriam R. Raffeld, 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.
Alison M. Ayres, 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.
Anand Viswanathan, 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.
Steven M. Greenberg, 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.
Alessandro Biffi, 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.
Jonathan Rosand, 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.
Christopher D. Anderson, 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.

Document Type

Article

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.

Medical Subject Headings

Aged; Biomarkers (blood); Case-Control Studies; Cerebral Hemorrhage (blood, drug therapy); Cholesterol (blood); Female; Humans; Longitudinal Studies; Male; Prognosis; Registries; Retrospective Studies; Time Factors; Triglycerides (blood)

Publication Date

5-31-2016

Publication Title

Neurology

E-ISSN

1526-632X

Volume

86

Issue

22

First Page

2034

Last Page

41

PubMed ID

27164693

Digital Object Identifier (DOI)

10.1212/WNL.0000000000002716

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