Serum Lipid Profiles, Disability and MRI Outcomes in MS

In This Article

Abstract and Introduction
Methods
Results
Discussion
References

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.

Table 1. Demographic and clinical characteristics of the cohort.
Demographic Variables	Value
Females: Males (% Female)	370: 122 (75.2%)
MS course:
Relapsing-remitting	395 (80.3%)
Secondary progressive	82 (16.6%)
Primary progressive	15 (3.0%)
Age*, years	47.1 ± 10.8
Disease duration*, years	12.8 ± 10.1
Median EDSS* (IQR)	2.50 (2.50)
MSSS	3.79 ± 2.46
Time to follow-up, years	2.2 ± 1.0
Statin usage^§	109/491 (22.2%)
Lipid Profile Variables
Body mass index, kg/m²	27.8 ± 6.5
HDL, mg/dL	55.2 ± 16.6
LDL, mg/dL	116 ± 32.8
Total cholesterol, mg/dL	197 ± 38.1
Triglycerides, mg/dL	133 ± 82.0
Cholesterol to HDL ratio	3.85 ± 1.30
MRI Characteristics
CEL present	29/197 (14.7%)
CEL number	0.52 ± 0.15
CE-LV, cm³	0.032 ± 0.13
T2-LV, cm³	14.0 ± 14.7
T1-LV, cm³	3.1 ± 5.4
BPF	0.856 ± 0.0285

The continuous variables expressed as mean ± SD and categorical variables as frequency (%).
* At baseline lipid profile assessment. ^§Statin usage status unavailable for one patient.

Table 2. Demographic, clinical and MRI characteristics, and lipid profiles of patient subsets with and without statins.
Variable	No Statins	Statins	p-value
Females: Males (% Female)	301: 81 (78.8%)	69: 40 (63.3%)	< 0.002^§
MS course:			0.075^‡
Relapsing-remitting	314	81 (74.3%)
Secondary progressive	(82.2%)
Primary progressive	55 (12.8%) 13 (3.4%)	27 (24.8%) 1 (0.9%)
Age*, years	45.3 ± 10.7	53.4 ± 8.4	< 0.001
Disease duration*, years	11.9 ± 9.7	16.2 ± 11.0	< 0.001
Median EDSS* (IQR)	2.5 (2.0)	3.50 (3.50)	< 0.001^#
MSSS	3.67 ± 2.51	4.15 ± 2.18	0.061
Time to follow-up, years	2.13 ± 1.0	2.22 ± 1.0	0.43
Body mass index, kg/m²	27.4 ± 6.5	29.1 ± 6.5	0.013^¶
HDL, mg/dL	55.6 ± 16.6	53.7 ± 16.5	0.72^¶
LDL, mg/dL	115 ± 30.8	118 ± 39.0	0.62^¶
Total cholesterol, mg/dL	196 ± 36.0	201 ± 44.7	0.38^¶
Triglycerides, mg/dL	128 ± 84.0	149 ± 75.5	0.15^¶
Cholesterol to HDL ratio	3.81 ± 1.28	4.00 ± 1.40	0.60^¶
Presence of CEL CEL number CE-LV, cm³	25/156 (16%) 0.60 ± 2.3 0.035 ± 0.15	4/40 (10%) 0.23 ± 0.86 0.019 ± 0.080	0.47^¶ 0.026^¶ 0.035^¶
T2-LV, cm³	13.6 ± 14.7	16.0 ± 14.7	0.30^¶
T1-LV, cm³	2.7 ± 5.1	4.5 ± 6.3	0.019^¶
BPF	0.858 ± 0.027	0.848 ± 0.035	0.056^¶

Statin usage data were available for 491 patients.
* At time of baseline lipid profile assessment.
^§ Fisher exact test
^‡ Fisher exact test for presence of secondary progressive or progressive forms of MS.
# Mann-Whitney test
^¶ p-values for statin variable from regression analyses with sex, disease duration and statin use as predictor variables.

Table 3. Lipid profile associations with disability changes.
Lipid Profile	Group	EDSS Change			MSSS Change
Lipid Profile	Group	Slope ± SE	r_p	p-value	Slope ± SE	r_p	p-value
HDL	All	0.001 ± 0.003	0.012	0.79	0.000 ± 0.005	-0.010	0.83
	No statin	0.000 ± 0.004	-0.008	0.87	-0.003 ± 0.005	-0.030	0.56
LDL	All	0.004 ± 0.002	0.13	0.006	0.005 ± 0.002	0.12	0.012
	No statin	0.003 ± 0.002	0.093	0.078	0.006 ± 0.003	0.11	0.038
Total cholesterol	All	0.004 ± 0.001	0.15	0.001	0.005 ± 0.002	0.12	0.008
	No statin	0.004 ± 0.002	0.12	0.020	0.005 ± 0.002	0.11	0.030
Triglycerides	All	0.001 ± 0.0006	0.10	0.025	0.002 ± 0.0009	0.096	0.037
	No statin	0.002 ± 0.007	0.12	0.025	0.002 ± 0.001	0.10	0.055
Cholesterol to HDL ratio	All	0.083 ± 0.042	0.091	0.047	0.079 ± 0.062	0.059	0.20
	No statin	0.093 ± 0.050	0.098	0.062	0.12 ± 0.074	0.082	0.12

Significant p-values are underlined.
SE is standard error of the slope and r_p is the partial correlation.

Commenting is limited to medical professionals. To comment please Log-in.

Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.

My Alerts