Cardiovascular (CV) comorbidities are common among people with multiple sclerosis (pwMS).1 In this article, we look at data presented at ECTRIMS 2019 that add to our understanding of this subject.
Prevalence of CV comorbidities in people with MS
CV disease is the leading cause of mortality globally (accounting for 40% of deaths) and the second most common cause in high-income countries (23% of deaths) after cancer. Authors of a systematic review calculated estimated prevalence rates using available population-based studies, and, according to this measure, 10.9% of pwMS had hyperlipidaemia, 18.6% had hypertension, 2.5% had ischaemic heart disease and 3.3% had cerebrovascular disease. These prevalence rates were greater than in the general population.1,2
Data presented at this year’s ECTRIMS confirm a high burden of CV comorbidities among pwMS. For example, among 231 pwMS treated in Greece, hypertension was present in 8.2%, hyperlipidaemia in 6% and diabetes in 3.9%. In a retrospective cohort study of 6602 pwMS and 61,828 people without MS in Sweden, there was a higher frequency of stroke, transient ischaemic attack (TIA) and peripheral vascular disease among pwMS 10 years before MS diagnosis. After diagnosis of MS, pwMS had an increased incidence of major adverse cardiac events, TIA and heart failure.3,4
This high level of comorbidities translates into an increase in mortality: data recently presented at EAN 2019 showed that pwMS were at increased risk of CV-related death compared with people without MS (incidence rate per 10,000 person-years, 16.8 vs 11.6).5
Interaction of CV comorbidities with MS
CV disease interacts with MS and may contribute to disability progression: in a study of 8983 patients, the risk of early gait disability increased by 51% for each CV condition and the median time from diagnosis to the need for ambulatory assistance was decreased by 6 years in pwMS with CV comorbidities vs those without. Among pwMS, hypertension and heart disease are independently associated with decreased grey matter and cortical volume. Furthermore, low-density lipoprotein cholesterol and total cholesterol levels are associated with MRI measures of inflammatory activity.6–8
Data presented at ECTRIMS 2019 provide further evidence of this link. A network of 10 MS centres showed that patients with elevated serum neurofilament light chain (NfL) had poorer neurologic function than those with normal levels, and patients with diabetes (a well-known CV risk factor) had over two-fold higher odds than those without diabetes to have elevated NfL. Furthermore, Nikolaidis et al. showed there was a significant correlation between the number of comorbidities and expanded disability status score (EDSS).3,9
Who is at risk?
The overall risk of comorbidities increases with age in pwMS, just as in the general population. While pwMS are at increased risk of comorbidities compared with the general population, the gap between the two groups is particularly marked in younger patients compared with older patients: the risk for an additional disease diagnosis among 25,476 pwMS in Sweden was x2 that in the general population (n=25,117) up to age 35, and this decreased with age to x1.3 in patients aged > 80 years. 10,11
The risk of comorbidities also varies according to stage of MS. In data from the Argentinean RelevarEM registry (n=1588), the Charlson comorbidities index was 3.9% in patients with clinically isolated syndrome, 13.5% in RRMS, 28.7% in SPMS and 17.4% in PPMS.10
Results from a post-mortem study presented at ECTRIMS 2019 provides further information on CV risk in MS. Among pwMS who died at a young age, an MS-related arteriopathy was observed, even in those who did not have a high burden of CV disease. In patients who did have a high burden of CV disease, pwMS were more susceptible to develop cerebral small vessel disease than people without MS.12
Management of patients with CV comorbidities
CV comorbidities can influence treatment decisions regarding disease-modifying treatments (DMTs). For example, neurologists frequently delay DMT initiation in pwMS with ischaemic heart disease. This highlights that some DMTs may not be suitable in the presence of CV comorbidities, because either the DMTs are associated with side effects that are particularly deleterious in these patients (e.g. hypertension) or because these patients are susceptible to certain side effects (e.g. macular oedema).13,14
Ruth Ann Marrie recommends that pwMS and CV conditions be empowered to adopt positive health behaviours (including smoking cessation, weight loss and increasing physical exercise), and that MS care teams implement policies to identify patients at risk and provide appropriate treatment (including antihypertensive therapy, lipid-lowering and blood glucose control). These treatments may have a positive impact on MS: blood glucose treatment in pwMS and metabolic syndrome is associated with reduction in MRI lesion load vs no treatment. Also, preliminary data suggest that statin therapy reduces brain atrophy vs placebo in patients with progressive MS.14–16
Given the high prevalence of CV comorbidities among pwMS and the potential impact of these conditions on disability progression, it is important that the MS care team identify those at risk and ensure appropriate risk factor modification.
Marrie RA, Reider N, Cohen J, et al. A systematic review of the incidence and prevalence of cardiac, cerebrovascular, and peripheral vascular disease in multiple sclerosis. Mult Scler J 2015; 21: 318–31
Dagenais GR, Leong DP, Rangarajan S, et al. Variations in common diseases, hospital admissions, and deaths in middle-aged adults in 21 countries from five continents (PURE): a prospective cohort study. Lancet 2019; 0. DOI:10.1016/S0140-6736(19)32007-0
Nikolaidis I, Bakirtzis C, Boziki M, et al. Comorbidities in multiple sclerosis patients in a Greek tertiary MS Center. In: ECTRIMS. 2019: P1197.
Piehl F, Castelo-Branco A, Chiesa F, et al. Cardiovascular disease in patients with multiple sclerosis: a nationwide cohort study in Sweden. In: ECTRIMS. 2019: 148
Persson R, Lee S, Minton N, et al. Cause and Age of Mortality in Patients Diagnosed with Multiple Sclerosis. In: EAN. 2019: O1206
Kappus N, Weinstock-Guttman B, Hagemeier J, et al. Cardiovascular risk factors are associated with increased lesion burden and brain atrophy in multiple sclerosis. J Neurol Neurosurg Psychiatry 2016; 87: 181–7
Marrie RA, Rudick R, Horwitz R, et al. Vascular comorbidity is associated with more rapid disability progression in multiple sclerosis. Neurology 2010; 74: 1041–7
Weinstock-Guttman B, Zivadinov R, Horakova D, et al. Lipid profiles are associated with lesion formation over 24 months in interferon-β treated patients following the first demyelinating event. J Neurol Neurosurg Psychiatry 2013; 84: 1186–91
Fitzgerald K, Sotirchos E, Smith M, et al. Serum neurofilament light chain is associated with MS outcomes and comorbidity in a large population of people with multiple sclerosis. In: ECTRIMS. 2019: A23
Alonso-Serena M, Rojas J., Silveira F, et al.. Comorbidities in multiple sclerosis in Argentina: baseline data from the Argentinean MS Registry (RelevarEM). In: ECTRIMS. 2019: P1195
Smith K., Burkill S, Hiyoshi A, et al.. Burden of comorbid diseases among MS patients in Sweden. In: ECTRIMS. 2019: P1194
Geraldes R, Esiri M, Palace J, et al. Vascular disease in Multiple Sclerosis: a whole body approach. In: ECTRIMS. 2019: 146
Zhang T, Tremlett H, Leung S, et al. Examining the effects of comorbidities on disease-modifying therapy use in multiple sclerosis. Neurology 2016; 86: 1287–95
Marrie RA. Comorbidity in multiple sclerosis: Implications for patient care. Nat. Rev. Neurol. 2017. DOI:10.1038/nrneurol.2017.33
Chataway J, Schuerer N, Alsanousi A, et al. Effect of high-dose simvastatin on brain atrophy and disability in secondary progressive multiple sclerosis (MS-STAT): a randomised, placebo-controlled, phase 2 trial. Lancet 2014; 383: 2213–21
Negrotto L, Farez MF, Correale J. Immunologic Effects of Metformin and Pioglitazone Treatment on Metabolic Syndrome and Multiple Sclerosis. JAMA Neurol 2016; 73: 520–8