Original article
Is multiple sclerosis a risk factor for atherosclerosis?

https://doi.org/10.1016/j.neurad.2019.10.002Get rights and content

Highlights

  • CIMT seemed to be affected in patients with MS when comparing with healthy controls.who had similar demographic variables (age, sex, body mass index [BMI], blood pressure, and cholesterol levels).

  • During remission Hs-CRP has been found at normal levels.

  • Different disease-modifying therapies may have altered the inflammation process.

Abstract

Background

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system. We aimed to discuss possible predisposing factors to atherosclerosis such as carotid intima-media thickness (CIMT) and high-sensitivity C-reactive protein (Hs-CRP) levels in MS.

Methods

Thirty-five ambulatory patients with relapsing-remitting MS (RRMS) (22 females and 13 males) and 34 healthy controls (21 females and 13 males) with similar demographic variables were included. Blood cell counts, cholesterol levels, vitamin D and B12, Hs-CRP levels, body mass index (BMI), history of smoking, and CIMT of both groups, Expanded Disability Status Scale (EDSS) scores, and disease duration of patients were recorded. Patients with a history of other vascular diseases such as hypertension, diabetes mellitus, peripheral artery disease, and acute relapses were excluded.

Results

Sixty-nine participants were included. The mean age of the study population was 35.8 ± 7.1 years. Right CIMT was significantly greater in the patient population (P < 0.001). Spearman's correlation coefficient between age and right CIMT was r = 0.41, P = 0.01. When we compared the Hs-CRP with a cut-off value of ≤ 3, the right, left, and mean CIMT levels were not statistically significant (P = 0.17; P = 0.22; P = 0.15). The mean serum vitamin D levels were higher in the patient group and this was statistically significant (P < 0.001). The statistically significant factors identified with univariate analysis with P < 0.2 were further entered into multivariate modelling.

Conclusion

CIMT seems to be affected in patients with MS by means of the disease itself and age. Thus, CIMT might reflect the predisposition to subclinical atherosclerosis more than Hs-CRP. Further investigation in a large MS population is still needed.

Graphical abstract

Box-plot representing right and mean CIMT in patient and control groups. CIMT: carotid intima-media thickness.

Introduction

Multiple sclerosis (MS) is a chronic disease of the central nervous system with an incidence of 1.74/100.000 in Turkey [1]. The disease itself rarely causes death, but co-morbidities such as cardiovascular disease are the main contributors to mortality in MS [2]. Co-morbidities increase disability and disability causes progression of disease [3]. Previous studies showed that co-morbidities such as diabetes, ischemic heart disease, depression, lung diseases, and stroke have been associated with increased mortality in patients with MS [4], [5]. Smoking and obesity are also the established risk factors for atherosclerosis, and cardiovascular and cerebrovascular disease [6]. The underlying mechanism for all these conditions is chronic inflammation, which plays a pivotal role in atherosclerosis and atherosclerotic cardiovascular diseases [7], [8].

Carotid intima-media thickness (CIMT) has been broadly considered as an important parameter to identify the early status of atherosclerosis. It is known that increased intima-media thickness is a non-invasive marker of arterial wall alteration, which can easily be assessed in the carotid arteries with high-resolution B-mode ultrasound. Based on previous studies, it was reasonable to explain the relationship between CIMT and increased risk of cerebrovascular or cardiovascular events [9], [10], [11], [12].

Ever since its discovery by Tillett and Francis in 1930, C-reactive protein (CRP) has been accepted as a marker of inflammation [13]. Although CRP and high-sensitivity (Hs)-CRP signify the same biochemical molecule, it is important to request a high-sensitivity test for the purpose of risk assessment [14]. CRP has been observed to be related to cerebrovascular events and cardiovascular events [15], [16]. Therefore, guidelines have recommended cytokines such as Hs-CRP to be in the algorithm of cardiovascular risk evaluation [17]. Similarly, several studies showed that Hs-CRP had been elevated in the circulation of patients after acute stroke [18], [19], [20]. There is a need for risk detection and prediction in these diseases, which have to be managed immediately. Such a marker is of immense importance as a screening tool for prediction.

Vascular diseases may be more frequent in patients with MS for several reasons:

  • the shared common pathophysiology including endothelial dysfunction, platelet activation, and hypercoagulation;

  • the increased surveillance of patients with MS;

  • MS treatments (e.g. glucocorticoids);

  • and shared risk factors such as smoking, physical inactivity, vitamin D deficiency, and diabetes may influence the risk of vascular disease [21].

Therefore, with a different perspective, in this current study, we aimed to discuss whether MS might predispose to atherosclerosis, and as screening tools – owing to their availability in our lab – we measured CIMT, an early and sensitive indicator for subclinical atherosclerosis, and Hs-CRP levels, a non-specific inflammatory cytokine that accelerates the formation of atherosclerotic plaques.

We hypothesized that patients with MS would exhibit increased CIMT and Hs-CRP compared with healthy controls. Evaluation of these parameters may provide the early identification of potential vascular co-morbidities and minimize the worsening of disability by reducing the risk of vascular disease. Increased awareness and early diagnosis of the potential risk factors in this primarily young patient group may prevent catastrophic results.

Section snippets

Subjects

Thirty-five (22 females and 13 males) ambulatory (Kurtzke Expanded Disability Status Score (EDSS) 0–5) patients with a definite clinical diagnosis of MS according to the 2010 McDonald criteria who have been followed up regularly in Antalya Training and Research Hospital's Multiple Sclerosis outpatient clinic since 2013 and 34 healthy controls (21 females and 13 males) with similar demographic variables (age, sex, body mass index [BMI], blood pressure, and cholesterol levels) were enrolled in

Discussion

According to the results of this study, CIMT seems to be affected in patients with MS by means of the disease itself and age. Thus, CIMT might reflect the predisposition to subclinical atherosclerosis more than Hs-CRP.

Several studies showed that vascular dysfunction might be involved in the pathogenesis of MS [22], [24]. Due the inflammatory nature of the disease, a predisposition to vascular diseases may be more frequent in patients with MS. Vascular diseases include coronary artery disease,

Conclusions

CIMT seems to be affected in patients with MS by means of the disease itself and age. Also, the increase in CIMT might reflect the predisposition to subclinical atherosclerosis more than Hs-CRP. Long-term follow-up evaluation is needed for a better understanding of the role of factors that contribute to inflammation.

Funding

This research did not receive any grant from funding agencies. No funding was received for this study.

Ethical statement

Informed consent was obtained from all individual participants included in the study.

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

This study was approved by ethics committee and informed consent was obtained from all individual participants included in the study.

Disclosure of interest

The authors declare that they have no competing interest.

Acknowledgements

The authors thank Prof. Dr. Erkan Goksu for his kind contribution to the data analysis.

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