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Review Multiple Sclerosis A Review of Vascular Disease Risk Factors and Multiple Sclerosis Meena R Kannan and Vijayshree Yadav Portland Veterans Affairs Medical Center and Oregon Health Sciences University, Portland, OR, US M ultiple sclerosis (MS) is the most common demyelinating disease of the central nervous system and the most common non-traumatic cause of disability in young adults. Recent research shows that vascular disease risk factors (VDRFs) such as obesity, smoking, hyperlipidemia, hypertension, type II diabetes mellitus, and metabolic syndrome, can influence MS on its onset, disease activity, progression, and resultant disability. This review evaluates the current knowledge on the role of VDRFs on outcomes among people with MS (PwMS) and shows that while VDRF prevalence may or may not be higher among PwMS compared with the general population, its presence can influence MS in myriad ways. Management of VDRFs through early detection and treatment may be a promising approach to improving outcomes in PwMS. Keywords Multiple sclerosis, smoking, obesity, dyslipidemia, hypertension, type II diabetes, metabolic syndrome Disclosure: No funding was received in the publication of this article. Meena Kannan and Vijayshree Yadav have no relevant conflicts of interest to declare. Compliance with Ethics: This study involves a review of the literature and did not involve any studies with human or animal subjects performed by any of the authors. Authorship: All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship of this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval for the version to be published. Open Access: This article is published under the Creative Commons Attribution Noncommercial License, which permits any noncommercial use, distribution, adaptation, and reproduction provided the original author(s) and source are given appropriate credit. Received: April 13, 2017 Accepted: May 16, 2017 Citation: US Neurology, 2017;13(2):90–3 Corresponding Author: Vijayshree Yadav, Mail Code L226, 3181 S.W. Sam Jackson Park Road, Portland, OR 97239, US. E: yadavv@ohsu.edu Multiple sclerosis (MS) is the most common inflammatory demyelinating disease of the central nervous system and the most common non-traumatic cause of disability in young adults. MS affects nearly 400,000 people in the US and 2.5 million people worldwide. While the precise etiology of MS is unknown, it is suspected that the disease causation is multifactorial, in which exposure to environmental factors triggers an autoimmune response among genetically susceptible individuals. 1 Recent research suggests an important plausible role of vascular disease risk factors (VDRFs) such as smoking, obesity, hyperlipidemia, hypertension, diabetes, and metabolic syndrome on MS pathogenesis. It is estimated that nearly 50% of people with MS (PwMS) have at least one VDRF at the time of their MS diagnosis, and are more likely than healthy controls to have more than one VDRF. 2,3 The presence of VDRFs among PwMS appears to be associated not only with ongoing radiographic disease activity and progression on magnetic resonance imaging (MRI), but also with increased risk of clinical disability progression. 3–5 The purpose of this paper is to examine the current literature on the relationship between these potentially modifiable factors that affect MS onset, activity, progression, and disability, and identify potential targets for improving clinical outcome among PwMS. Smoking The association between smoking and MS susceptibility has been investigated extensively over the past several years, with studies consistently suggesting an increased risk ranging from 27–100% among current smokers compared with non-smokers, with several studies suggesting a dose–response relationship. 6–8 Passive exposure to tobacco smoke has also been associated with an increased risk of MS overall, estimated at nearly 25% compared with those not exposed to environmental tobacco smoke. 6,9,10 The prevalence of current smoking ranges from 17–29%, with one study suggesting nearly 5% of subjects started smoking after disease onset. 3,11–13 Smoking among PwMS has also been associated with poor clinical and radiographic outcomes. A longitudinal study following more than 100 people with clinically isolated syndrome over 3 years showed that 75% of current smokers and only 51% of non-smokers developed clinically definite MS (CDMS), with smokers having an 80% increased risk for progression to CDMS and significantly shorter time interval to their first relapse compared with non-smokers. 14 Current smokers with MS were not only more than twice as likely to progress from a relapsing to progressive phenotype but also underwent this transition earlier compared with non-smokers. 15,16 Current smokers had significantly worse MS disability at baseline than never-smokers, as measured by the Expanded Disability Severity Scale (EDSS) and MS Severity Scale, as well as a 64% and 34% increased risk of reaching EDSS 4 and 6 compared with non-smokers and former smokers, respectively. Smoking among PwMS has been shown to be associated with decreased whole brain volume and increased T2 lesion volume, increased contrast enhancing lesions, and T1 lesion volume on MRI. 17 90 TOUCH ME D ICA L ME D IA