Inflammation, Blood Fats Linked to Cardiovascular Disease in MS

Scientists have identified a link between systemic inflammation and fat (lipid) metabolism that may underlie the increased risk of cardiovascular disease in people with multiple sclerosis (MS).

The study with that finding, “Lipoprotein profiling in early multiple sclerosis patients: effect of chronic inflammation?,” was published in the journal Lipids in Health and Disease.

People with MS have an increased risk of cardiovascular disease even without traditional risk factors such as obesity, high blood pressure, type 2 diabetes, or elevated cholesterol levels in the blood. 

Cardiovascular disease is caused by the buildup of fatty deposits (plaques) in arteries (atherosclerosis), which is linked to elevated total blood cholesterol and altered levels of two blood proteins that combine with lipids and cholesterol to form particles called either low density lipoprotein cholesterol (LDL-C) or high density lipoprotein cholesterol (HDL-C).

Overall, high levels of LDL-C (“bad” cholesterol) and low HDL-C levels (“good” cholesterol) are risk factors for cardiovascular disease.

However, the size of each particle can vary. Small, dense LDL-C particles are associated with increased cardiovascular risk, while larger LDL-C particles are not. In contrast, it is thought that larger HDL-C particles are more protective than smaller ones. 

Studies have found that reduction of HDL-C levels can be caused by pro-inflammatory signaling proteins secreted by immune cells, leading to a loss of anti-inflammatory functions and cholesterol transport. 

This suggests that chronic inflammation may be an important factor in the development of cardiovascular disease in people with MS.

To explore this further, researchers at the Comenius University in Slovakia, along with collaborators at the Slovak Academy of Sciences, designed a study (NCT03052595) to measure the overall lipids levels in the blood, and the relationship between lipoprotein particle size and inflammation in a group of people in the early stages of MS. 

The team recruited 10 women and nine men newly diagnosed with MS, ages ranging from 20 to 45, not long after their first episode of symptoms. All participants were non-smokers without a history of cardiovascular disease or other serious conditions. 

Examinations were performed at least two months after an initial glucocorticoid treatment following the first MS episode, and all patients were in remission and without any medication when tested. A group of 19 age- and gender-matched healthy people were included as the control group.

The physical activity of participants was assessed using the Lagerros Energy Expenditure Questionnaire (EEQ), which measures the total energy output of all physical activity during an average weekday.

Blood was drawn from each participant, and levels of total cholesterol, LDL-C, HDL-C, blood fat called triglyceride, as well as 15 cytokine signaling proteins, were measured. The levels of different sized LDL-C and HDL-C particles (subfractions) also were determined.

Overall, compared to control subjects, MS patients engaged in the same level of physical activity, and showed no significant differences in the levels of LDL-C, HDL-C, triglycerides, or the 15 cytokines analyzed. 

While there were no differences found in lipid levels between women with MS and controls, men with MS had significantly higher total HDL-C levels and more small-sized HDL-C particles than controls. 

Cytokine levels in all MS patients were not connected to any of the different LDL-C subfractions, even when controlled for age and body mass index (BMI). 

However, higher levels of almost all the inflammatory cytokines were linked to lower levels of total HDL-C, large-sized HDL-C, and higher levels of intermediate-sized HDL-C. This trend was found to be statistically significant in women, but not in men.

“In conclusion, our results show higher HDL-C and the small HDL-C subfraction in males with early MS suggesting that male MS patients might be at higher risk of atherosclerosis development,” the researchers wrote. 

“The observed pattern of correlations between HDL-C subfractions and several cytokines reflect mutual links between systemic inflammation and lipid metabolism in early MS with low inflammatory activity,” they concluded.