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

Chia Phuah

Miriam Raffeld

Alison Ayres

Anand Viswanathan

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.

Supplementary Material

Data Supplement:

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Accompanying Editorial:

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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.

^{Corresponding author.}

Correspondence to Dr. Anderson: ude.dravrah.hgm@nosrednadc

Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

Correspondence to Dr. Anderson: ude.dravrah.hgm@nosrednadcGo to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

Received 2015 Jul 15; Accepted 2016 Jan 5.

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:

Results:

Conclusions:

Abstract

Growing evidence supports a paradoxical role of dyslipidemia in cerebrovascular disease.¹^–⁶ Antithetical to its role in ischemic stroke, hypercholesterolemia has been associated with decreased primary intracerebral hemorrhage (ICH) risk,⁷^–¹⁰ reduced number of cerebral microhemorrhages,¹¹ reduced hemorrhagic conversion after ischemic strokes,¹² and improved ICH outcomes.¹³,¹⁴ However, the relationship between serum lipid levels drawn at the time of ICH to individual patients' long-term lipid levels is unclear and likely not representative of long-term exposures.⁸ Estimates of variation coefficients for serum lipid concentrations range from 5% to 25%,¹⁵ reflective of considerable variation due to biological and environmental factors.¹⁵^–¹⁹ Serum lipid levels also undergo considerable variation during acute illness,²⁰^–²² hypothesized to be due to catecholamine stress response.²¹,²³ For example, serum cholesterol levels decline precipitously within days after either acute ischemic or hemorrhagic stroke,⁸,²³,²⁴ then subsequently increase above those drawn at the time of stroke by 90 days after the event.⁸ Given these inter- and intraindividual variabilities, understanding of temporal serum lipid trends in ICH may improve our understanding of the biology of dyslipidemia in ICH and provide better estimates of long-term lipid exposures toward cerebrovascular disease risk.

Our objectives were as follows: (1) to describe temporal trends in serum total cholesterol (TC), low-density lipoprotein (LDL), triglycerides (TGs), and high-density lipoprotein (HDL) over 48 months, before and after ICH; (2) to determine differences in serum lipid trends between patients with ICH and non-ICH controls; and (3) to investigate whether changes in serum lipid trends are associated with increased ICH risk.

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ACKNOWLEDGMENT

The authors thank Dr. Daniel Woo for his helpful discussions regarding serum lipid confounders.

ACKNOWLEDGMENT

GLOSSARY

EMR	electronic medical record
HDL	high-density lipoprotein
ICH	intracerebral hemorrhage
LDL	low-density lipoprotein
MGH	Massachusetts General Hospital
TC	total cholesterol
TG	triglyceride

GLOSSARY

Footnotes

Supplemental data at Neurology.org

Editorial, page 2028

Footnotes

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