Serum Lipid Profiles Are Associated With Disability and MRI Outcomes in Multiple Sclerosis

Bianca Weinstock-Guttman; Robert Zivadinov; Naeem Mahfooz; Ellen Carl; Allison Drake; Jaclyn Schneider; Barbara Teter; Sara Hussein; Bijal Mehta; Marc Weiskopf; Jacqueline Durfee; Niels Bergsland; Murali Ramanathan

Disclosures

J Neuroinflammation. 2011;8(127) 

In This Article

Abstract and Introduction

Abstract

Background: The breakdown of the blood-brain-barrier vascular endothelium is critical for entry of immune cells into the MS brain. Vascular co-morbidities are associated with increased risk of progression. Dyslipidemia, elevated LDL and reduced HDL may increase progression by activating inflammatory processes at the vascular endothelium.
Objective: To assess the associations of serum lipid profile variables (triglycerides, high and low density lipoproteins (HDL, LDL) and total cholesterol) with disability and MRI measures in multiple sclerosis (MS).
Methods: This study included 492 MS patients (age: 47.1 ± 10.8 years; disease duration: 12.8 ± 10.1 years) with baseline and follow-up Expanded Disability Status Score (EDSS) assessments after a mean period of 2.2 ± 1.0 years. The associations of baseline lipid profile variables with disability changes were assessed. Quantitative MRI findings at baseline were available for 210 patients.
Results: EDSS worsening was associated with higher baseline LDL (p = 0.006) and total cholesterol (p = 0.001, 0.008) levels, with trends for higher triglyceride (p = 0.025); HDL was not associated. A similar pattern was found for MSSS worsening. Higher HDL levels (p < 0.001) were associated with lower contrast-enhancing lesion volume. Higher total cholesterol was associated with a trend for lower brain parenchymal fraction (p = 0.033).
Conclusions: Serum lipid profile has modest effects on disease progression in MS. Worsening disability is associated with higher levels of LDL, total cholesterol and triglycerides. Higher HDL is associated with lower levels of acute inflammatory activity.

Introduction and Background

Multiple sclerosis (MS) is a complex inflammatory, demyelinating and neurodegenerative disease with a heterogeneous pathology and clinical outcomes.[1] The chronic inflammatory processes that characterize MS pathology interfere with immune mechanisms that regulate and confine the inflammatory cascade to prevent irreversible tissue damage.[2]

Cholesterol is an important component of intact myelin. Lipids, especially lipoproteins, are involved in the regulation of neural functions in the central nervous system through local mechanisms that are linked to systemic lipid metabolism.[3,4] High-density lipoproteins (HDL) and low-density lipoproteins (LDL) play a key role in the transport of cholesterol and lipids in human plasma. Under normal physiological conditions, high concentrations of HDL and LDL are present in CNS as a result of transport across the blood-brain barrier.[5,6] Apolipoprotein A-I, a major component of plasma HDL, is synthesized within the vascular endothelial cells.[7] HDL has immunomodulatory and anti-oxidant effects on endothelial cells[8] and it has been shown to inhibit production of the pro-inflammatory cytokines interleukin-1beta and tumor necrosis factor.[9,10] Apolipoprotein A-1 and paraoxonase are associated with HDL and contribute to its anti-oxidant and anti-inflammatory properties.[9,11,12]

Dyslipidemia can potentiate inflammatory processes at the vascular endothelium, lead to the induction of adhesion molecules, and the recruitment of monocytes.[13–15] Associations between dyslipidemia and increased inflammation are well established in conditions such atherosclerosis, cardiovascular disease, metabolic syndrome and obesity.[16]

In the context of autoimmune diseases, a strong association between dyslipidemia and cardiovascular disease has emerged in systematic lupus erythematosus[17] and increased cardiovascular risk and lipid profile changes have been reported in rheumatoid arthritis.[18] HDL and LDL also modulate the function and survival of β-cells in Type 2 diabetes mellitus.[19] Neuromyelitis optica patients were reported to have significantly higher serum cholesterol triglycerides and lower LDL than healthy controls.[20]

However, only limited information is available on the effect of serum triglycerides and cholesterol levels and the roles of HDL and LDL levels on MS disease progression. Increased total cholesterol was associated with increases in the number of contrast-enhancing lesions on brain MRI in clinically isolated syndrome patients following a first clinical demyelinating event.[21] MS patients were found to have a higher occurrence of hypercholesterolemia and paraoxonase-1, the anti-oxidant enzyme associated with HDL, was decreased during relapses.[12] A retrospective analysis of a large dataset of 8,983 patients from the North American Research Committee on Multiple Sclerosis Registry reported that the presence of vascular comorbidities linked to dyslipidemia was associated with an increased risk for disability progression in MS.[22]

The aim of this study therefore was to assess the associations of serum lipid profile variables (serum cholesterol, HDL, LDL and triglycerides) to clinical disability and brain tissue integrity as measured with quantitative magnetic resonance imaging (MRI) metrics in a large cohort of MS patients.

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