Recent population studies showed that MS was associated with an almost threefold increase in the risk of death  and this may be attributed to multiple factors including cardiovascular co-morbidities . There is conflicting data about the vascular dysfunction in MS patients and its correlation with disease duration or severity. So, our work aimed at assessing vascular function and serum lipids in MS patients and correlating them with the neurological disability and imaging findings.
We found significantly impaired vascular function in patients with MS, compared to controls, shown by significantly higher peripheral PWV (P-value = 0.001) and augmentation index (P-value < 0.001) in MS patients, compared to controls, but we did not find a statistically significant difference in CCA IMT between the two groups. None of our patients had a carotid plaque. We also found a statistically significant positive correlation between PWV and both disease duration and EDSS score (P-value = 0.019, 0.029, respectively).
Similar to our findings, Talaat et al. assessed brachial–ankle PWV and carotid IMT in MS patients. They found that brachial–ankle PWV was significantly higher in MS patients compared to controls (P-value = 0.014). On the other hand, they found no statistically significant difference between patients and controls as regards carotid IMT. The investigators reported no statistically significant correlations between brachial–ankle PWV or carotid IMT, and EDSS scores in MS patients, compared to our current study which found a significant correlation between PWV and EDSS score. The authors explained the reported reduced arterial compliance in their MS patients by the status of chronic inflammation that may be a contributing factor to atherosclerosis initiation and progression .
Moreover, Ranadive et al. assessed central PWV and augmentation index using SphygmoCor device, in addition to carotid IMT, in MS patients. Physical activity was also measured by the ActiGraph single-axis accelerometer. The authors reported significantly higher central PWV in MS patients, compared to controls (P-value < 0.05), but there was no significant difference in carotid IMT between the two groups. In addition, physical activity was negatively correlated with central PWV. They concluded that physical inactivity may have accounted for some of the arterial dysfunction reported in their MS patients .
The vascular dysfunction in MS patients may be explained by the impact of chronic inflammation on the cardiovascular system. Strong evidence indicates that inflammation plays a major role in the formation and destabilization of atherosclerotic plaques, leading to acute cardiovascular events . The dysregulated pro-inflammatory cytokines in MS, including IL-1, IL-6, TNF-ƒÑ, or IFN-ƒ×, were thought to be involved in inducing atherosclerosis in those patients . Moreover, the reported increase in oxidative stress in MS is assumed to be one of the possible mechanisms of endothelial dysfunction and overt atherosclerosis .
Also, the disability status of the disease is associated with low level of physical activity which may lead to a higher susceptibility to subclinical atherosclerosis and cardiovascular disease . This may explain the reported positive correlation in our study between arterial stiffness and both disease duration and disability.
In contrast to our results, Mincu et al. assessed arterial function in MS patients by measuring carotid–femoral pulse wave velocity and augmentation index using Complior System, in addition to carotid IMT. They found that the measured parameters of arterial stiffness were similar between both the MS group and the control group. Meanwhile, similar to our findings, carotid IMT was not significantly different between the two groups . On the other hand, Garett Griffith et al. reported a significant increase in carotid IMT in older MS patients, compared to the older control group, but they did not find a significant difference between the young patients and their matched controls .
In our study, we measured the serum lipids in MS patients and control subjects. We found significantly higher serum levels of T-cholesterol (P-value < 0.001), triglycerides (P-value = 0.25) in MS patients, compared to controls. Meanwhile, serum levels of LDL-C and VLDL-C were insignificantly higher in MS patients, compared to controls, but serum levels of HDL-C were significantly lower in MS patients, compared to controls (P-value = 0.007). We did not find a significant correlation between T-cholesterol, triglycerides, or LDL-C and disease duration or disability.
Similar to our findings, Soliman et al. reported significantly higher serum levels of both LDL-C and triglycerides, and significantly lower serum levels of HDL-C in MS patients compared to controls (P-value = 0.001, 0.02 and 0.01, respectively), but they did not find a significant correlation between lipid profile in MS patients and disease duration or disability. They also reported an increased prevalence of insulin resistance (IR) among MS patients, compared to controls, suggesting that IR might have contributed to the reported impaired lipid metabolism .
Moreover, Sayonara Rangel et al. reported significantly higher serum levels of LDL-C and triglycerides, and significantly lower levels of HDL-C in MS patients, compared to controls (P-value = 0.015, 0.025 and 0.025, respectively), but there was no significant correlation between serum lipids and disease disability. The authors also assessed the serum levels of inflammatory cytokines: IL-6 and IL-17, which were found to be correlated with the levels of serum lipids, suggesting the involvement of the inflammatory status of MS in the pathogenesis of impaired lipid metabolism .
Many mechanisms were suggested to explain this relationship between multiple sclerosis and dyslipidemia. The association between inflammation and alterations in lipid metabolism is considered one of the well-established mechanisms . Inflammation-induced modifications of HDL-C are shown to affect its function with a reduced capacity of reverse cholesterol transportation . Also, many studies reported an association between the decreased insulin sensitivity in MS patients and lipoprotein abnormalities . Another hypothesis is that elevated serum lipids in MS may occur as a secondary by-product of myelin destruction in the central nervous system .
Disconcordant with our work, Selçuk Comoğlu et al. found that levels of total cholesterol were insignificantly higher in MS patients compared to controls. HDL-C and LDL-C levels were not statistically different between the MS group and the controls. However, similar to our results, the levels of triglycerides were significantly higher in the MS group, compared to healthy subjects . Likewise, Navarro et al. found that the mean levels of plasma total cholesterol, HDL-C, and triglycerides were not significantly different between MS patients and controls .
Also, in contrast to our findings, some studies demonstrated an association between dyslipidemia and disability in MS patients. Tettey et al. found that nearly all lipid-related variables were positively correlated with baseline EDSS and the subsequent change in EDSS .
Also, Bianca Weinstock-Guttman et al. found that EDSS worsening was associated with higher baseline LDL-C, T-cholesterol, and triglycerides, while higher HDL-C levels were associated with lower contrast-enhancing MRI lesion volume. They suggested that dyslipidemia may increase disease progression by activation of the inflammatory processes at the vascular endothelium . Such an association between dyslipidemia and disease progression may suggest a potential clinical benefit of lipid-lowering agents in MS.
Our study has some limitations; firstly, we only studied the vascular function in a single variant of MS, RRMS. Secondly, we did not perform clinical or neurophysiological assessment of autonomic function in MS patients, so we could not study the relationship between cardiovascular dysautonomia and arterial stiffness. Thirdly, we did not assess the levels of inflammatory mediators in MS patients and consequently, we could not establish an actual role of inflammation in vascular dysfunction in MS. The small sample size is considered also one of the limitations in our study.