PS04.01 - Obesity and Metabolic Syndrome in MS
Metabolic syndrome constitutes a cluster of metabolic abnormalities including central obesity, hypertension, insulin resistance and atherogenic dyslipidemia, which are associated with an increased risk of cardiovascular disease. A growing body of evidence suggests that obesity, and components of the metabolic syndrome (MetS) influence the risk of multiple sclerosis (MS) or outcomes after MS onset. Specifically, obesity is associated with an increased risk of developing MS. Obesity and the components of MetS are associated with longer diagnostic delays from symptom onset to diagnosis, relapse rates, disability progression, brain atrophy and mortality. Obesity may also influence the effectiveness of disease-modifying therapy. These findings have important implications for disease management.
PS04.02 - Modifiable Lifestyle Risk Factors in MS
Background. The etiology of multiple sclerosis (MS) involves interactions between genetic loci and environmental factors. The area of MS epidemiology has expanded during the last years.
Objectives. To review established lifestyle/environmental risk factors for MS and a series of other potential candidades implicated in the pathogenesis of MS, and their interaction with genetics with regard to MS risk and progression.
Methods. A large number of studies have investigated the presence of interactions between risk factors in MS development. The current literature was summarized. Assessing interaction between causal factors using departure from additivity of effects as a criterion, often referred to as additive interaction, indicates action of the two factors in the same biological pathway.
Results. Apart from established lifestyle/environmental risk factors affecting MS risk (Epstein-Barr virus infection, sun exposure, vitamin D, smoking, high body mass index at young age), there is strong evidence for influence of exposure to organic solvents, passive smoking, shift work, alcohol, and dietary factors. There is also strong evidence that smoking affects the progression of MS. A number of established lifestyle/environmental factors seem to interact with MS risk human leukocyte antigen (HLA) genes, conferring a considerably higher risk of disease among genetically susceptible individuals.
Conclusion. Lifestyle/environmental factors influencing MS risk have important implications at the population level for the risk of developing the disease. Lifestyle/environmental factors interacting with MS risk HLA genes with regard to MS may share etiologic pathways underlying the disease, arguing for a primary role of the peripheral immune system driving MS.
PS04.03 - Environmental Exposures and MS Risk
From an epidemiologic perspective, MS is likely a rare complication of Epstein-Barr virus (EBV) infection with risk further modified by vitamin D nutrition, overweight/obesity in childhood or adolesence, and smoking. The latter two risk factros will be discussed in the talk on lifestyle factors and MS risk. This talk will present evidence supporting a causal role for EBV and vitamin D in MS development, and using the Bradford-Hill criteria for assessing causality from epidemiologic studies will argue that these environmental risk facotrs are likely causally related to MS.
PS04.04 - Evidence for an interaction between ozone pollution and HLA-DRB1*15 alleles in pediatric multiple sclerosis
We previously reported a relationship between air pollutants and increased risk of pediatric MS (ped-MS). Environmental risk factor research in ped-MS offers the advantage of shorter duration between exposure and disease onset. Ozone, an air pollutant, is a major global health hazard thought to have a role in MS pathoetiology. Identifying gene-environment interactions advances the understanding of biological processes at play in MS susceptibility.
We sought to examine the interaction between ozone pollution and DRB1*15 status as the main genetic variant associated with MS susceptibility.
Cases and controls enrolled in the Environmental and Genetic Risk Factors for Pediatric MS study of the US Network of Pediatric MS Centers were analysed. County-level modeled ozone data were acquired from the CDC’s Environmental Tracking Network air pollution database. Participants were assigned ozone values based on county of residence. Values were categorized into tertiles based on healthy controls. The association between ozone tertiles and having MS were assessed by logistic regression. Interaction between tertiles of ozone level and presence of DRB1*15 alleles on odds of ped-MS was evaluated. Models were adjusted for sex, race, ethnicity, age, second-hand smoke exposure, and mother’s education. Additive interaction was estimated using relative risk due to interaction (RERI) and attributable proportion of disease were calculated.
355 ped-MS cases and 565 controls contributed to the analyses. Ozone levels were associated with MS with an odds ratio (OR) of 2.35 (95%CI 1.57–3.51) and 2.21 (95%CI 1.48–3.32) in the upper two tertiles, respectively, compared with the lowest tertile. DRB1 status was also independently associated with MS (OR 1.99; 95%CI 1.43–2.78). There was a significant additive interaction between ozone and DRB1, with a RERI of 2.74 (95%CI 0.50–4.98) and 2.43 (95%CI 0.36–4.5) in the upper two tertiles, respectively. Approximately 60% of the ped-MS risk in those with HLA-DRB1*15 haplotype and high ozone exposure was attributable to the interaction between these risk factors.
Our data revealed additive interaction between higher exposure to ozone and DRB1 alleles on ped-MS susceptibility. Further evaluation of additional genetic variants that might play a role in ozone-induced ped-MS is underway to provide mechanistic insight.
PS04.05 - Cardiovascular risk factors affect brain volume in young MS patients
Cardiovascular (CV) risk factors have been associated with changes in clinical and MRI outcomes in patients with multiple sclerosis (MS). However, previous studies have not set an age-limit, while older patients may be affected by cerebral small vessel disease-related damage in addition to MS.
To investigate the impact of cardiovascular risk factors on brain atrophy in patients with multiple sclerosis under the age of 50.
One-hundred and twenty-four (79 relapsing-remitting, 45 progressive) MS patients (74 females, age 36 ± 8, range 18 – 50), and 95 age- and sex-matched healthy controls (HC) (47 females, age 35 ± 8, range 18 – 50) underwent brain 3T MRI with pulse sequences for assessing lesions and atrophy, and complete neurological examination. Traditional CV risk factors were assessed: having smoked ≥5 pack-years (py), and presence of hypertension, dyslipidemia, diabetes/prediabetes. More stringent cut-offs were also assessed: having smoked ≥10py, and hypertension, dyslipidemia or diabetes under treatment. Linear models adjusted for age, sex, disease duration, phenotype and treatment were used to determine the impact of CV risk factors on MRI variables.
Nineteen HC and 48 MS patients had one traditional CV risk factor, 4 HC and 15 MS patients had more than one. Ten HC and 30 MS patients had one stringent CV risk factor, 3 and 8 had more than one. Most of our subjects had a smoking history as a CV risk factor (16 HC and 42 MS patients among traditional, 8 HC and 23 MS patients among stringent). In MS patients, the presence of at least two traditional CV risk factors was associated with reduced normalized grey matter volume (NGMV) (p=0.01), white matter volume (NWMV) (p=0.03) and brain volume (NBV) (p=0.003), and not with T2-lesion volume (T2-LV) (p=0.27). Among traditional CV risk factors, only hypertension (n=8) was associated with MRI measures (NWMV and NBV). In MS patients, the presence of one stringent CV risk factor was associated with reduced NGMV (p=0.006), NWMV (p=0.003) and NBV (p<0.001), and higher T2-LV (p=0.03). In HC, no differences were observed according to either traditional or stringent risk factor presence.
The presence of CV risk factors is associated with brain atrophy in MS patients, even under age 50. CV risk factors seem to have synergistic effects, determining brain atrophy even for levels of exposure that may often be overlooked by clinicians, when present in combination.