Abstract
Cardiovascular comorbidities are associated with the risk of MS progression. Thus, we aim to measure variations of cardiovascular risk factors during Natalizumab treatment and their possible clinical associations. Seventy-one relapsing-remitting MS patients treated with Natalizumab were followed-up during a 12.9 ± 6.2 months. Cardiovascular risk factors were recorded on first and last study visits: systolic blood pressure, uric acid, total cholesterol, LDL, HDL, and triglycerides. EDSS progression and relapse occurrence were recorded. At multilevel mixed-effects linear regression models, the population presented with a significant reduction of total cholesterol (Coeff = −7.340; 95%CI = −13.152--1.527; p = 0.013), and of HDL cholesterol (Coeff = −3.473; 95%CI = −6.333--0.613; p = 0.017), and a non-significant reduction of LDL cholesterol (Coeff = −1.872; 95%CI = −8.481–0.736; p = 0.053), and of triglycerides (Coeff = −8.815; 95%CI = −34.011–5.380; p = 0.094). Uric acid levels increased during the study period (Coeff = 0.159; 95%CI = 0.212–0.340; p = 0.038). No significant associations were found with clinical outcomes. Serum lipids decreased and anti-oxidant uric acid increased during Natalizumab treatment. These biomarkers need to be further explored in relation to clinical outcomes on larger cohorts with longer follow-ups.
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References
Brescia Morra V, Coppola G, Orefice G, De Michele G, Vacca G, Filla A et al (2004) Interferon-b treatment decreases cholesterol plasma levels in multiple sclerosis patients. Neurology 62(5):829–830. https://doi.org/10.1212/01.WNL.0000113750.11090.67
Cerda A, Rodrigues AC, Alves C, Dalla F, Genvigir V, Fajardo CM et al (2015) Modulation of adhesion molecules by cholesterol-lowering therapy in mononuclear cells from Hypercholesterolemic patients. Cardiovasc Ther 33(4):168–176. https://doi.org/10.1111/1755-5922.12126
Chataway J, Schuerer N, Alsanousi A, Chan D, MacManus D, Hunter K, Anderson V, Bangham CRM, Clegg S, Nielsen C, Fox NC, Wilkie D, Nicholas JM, Calder VL, Greenwood J, Frost C, Nicholas R (2014) Eff ect of high-dose simvastatin on brain atrophy and disability in secondary progressive multiple sclerosis (MS-STAT): a randomised, placebo-controlled, phase 2 trial. Lancet 383(9936):2213–2221. https://doi.org/10.1016/S0140-6736(13)62242-4
Hon G, Hassan M, van Rensburg S, Abel S, Erasmus R, Matsha T (2009) Membrane saturated fatty acids and disease progression in multiple sclerosis patients. Metab Brain Dis 24(4):561–568. https://doi.org/10.1007/s11011-009-9159-0
Jorissen W, Wouters E, Bogie JF, Vanmierlo T, Noben J, Sviridov D et al (2017) Relapsing-remitting multiple sclerosis patients display an altered lipoprotein profile with dysfunctional HDL. Sci Rep 7:43410. https://doi.org/10.1038/srep43410
Kappus N, Weinstock-guttman B, Hagemeier J, Kennedy C, Melia R, Carl E et al (2016) Cardiovascular risk factors are associated with increased lesion burden and brain atrophy in multiple sclerosis. J Neurol Neurosurg Psychiatry 87(2):181–187. https://doi.org/10.1136/jnnp-2014-310051
Lanzillo R, Carotenuto A, Moccia M, Saccà F, Russo CV, Massarelli M, de Rosa A, Brescia Morra V (2017) A longitudinal real-life comparison study of natalizumab and fingolimod. Acta Neurol Scand 136(3):217–222. https://doi.org/10.1111/ane.12718
Lanzillo R, Orefice G, Quarantelli M, Rinaldi C, Prinster A, Ventrella G, Spitaleri D, Lus G, Vacca G, Carotenuto B, Salvatore E, Brunetti A, Tedeschi G, Brescia Morra V (2010) Atorvastatin combined to interferon to verify the efficacy (ACTIVE) in relapsing-remitting active multiple sclerosis patients: a longitudinal controlled trial of combination therapy. Mult Scler 16(4):450–454. https://doi.org/10.1177/1352458509358909
Marrie RA, Reider N, Cohen J, Stuve O, Trojano M, Cutter GA (2015) Systematic review of the incidence and prevalence of cardiac, cerebrovascular, and peripheral vascular disease in multiple sclerosis. Mult Scler 21(3):318–331. https://doi.org/10.1177/1352458514564485
Moccia M, Lanzillo R, Costabile T, Russo C, Carotenuto A, Sasso G, Postiglione E, de Luca Picione C, Vastola M, Maniscalco GT, Palladino R, Brescia Morra V (2015a) Uric acid in relapsing-remitting multiple sclerosis: a 2-year longitudinal study. J Neurol 262(4):961–967. https://doi.org/10.1007/s00415-015-7666-y
Moccia M, Lanzillo R, Palladino R, Maniscalco GT, De Rosa A, Russo C, Massarelli M, Carotenuto A, Postiglione E, Caporale O, Triassi M, Brescia Morra V (2015b) The Framingham cardiovascular risk score in multiple sclerosis. Eur J Neurol 22(8):1176–1183. https://doi.org/10.1111/ene.12720
Novakova L, Axelsson M, Malmeström C, Zetterberg H, Björkhem I, Karrenbauer VD, Lycke J (2015) Reduced cerebrospinal fluid concentrations of oxysterols in response to natalizumab treatment of relapsing remitting multiple sclerosis. J Neurol Sci 358(1–2):201–206. https://doi.org/10.1016/j.jns.2015.08.1537
Penesova A, Vlcek M, Imrich R, Vernerova L, Marko A, Meskova M, Grunnerova L, Turcani P, Jezova D, Kollar B (2015) Hyperinsulinemia in newly diagnosed patients with multiple sclerosis. Metab Brain Dis 30(4):895–901. https://doi.org/10.1007/s11011-015-9665-1
Polman CH, Reingold SC, Banwell B, Clanet M, Cohen JA, Filippi M, Fujihara K, Havrdova E, Hutchinson M, Kappos L, Lublin FD, Montalban X, O'Connor P, Sandberg-Wollheim M, Thompson AJ, Waubant E, Weinshenker B, Wolinsky JS (2011) Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 69(2):292–302. https://doi.org/10.1002/ana.22366
Polman CH, Reingold SC, Barkhof F, Calabresi PA, Clanet M, Cohen JA, Cutter GR, Freedman MS, Kappos L, Lublin FD, McFarland HF, Metz LM, Miller AE, Montalban X, O'Connor PW, Panitch H, Richert JR, Petkau J, Schwid SR, Sormani MP, Thompson AJ, Weinshenker BG, Wolinsky JS (2008) Ethics of placebo-controlled clinical trials in multiple sclerosis. Neurology 70(Issue 13, Part 2):1134–1140. https://doi.org/10.1212/01.wnl.0000306410.84794.4d
Solomon AJ, Bernat JLA (2016) Review of the ethics of the use of placebo in clinical trials for relapsing-remitting multiple sclerosis therapeutics. Mult Scler Relat Disord 7:109–112. https://doi.org/10.1016/j.msard.2016.03.019
Sternberg Z, Leung C, Sternberg D, Yu J, Hojnacki D (2014) Disease modifying therapies modulate cardiovascular risk factors in patients with multiple sclerosis. Cardiovasc Ther 32(2):33–39. https://doi.org/10.1111/1755-5922.12049
Tettey P, Jr SS, Taylor B, Blizzard L, Ponsonby A, Dwyer T et al (2014) An adverse lipid profile is associated with disability and progression in disability, in people with MS. Mult Scler 20(13):1737–1744. https://doi.org/10.1177/1352458514533162
Tettey P, Simpson S, Taylor B, Ponsonby A, Lucas R, Dwyer T et al (2017) An adverse lipid profile and increased levels of adiposity significantly predict clinical course after a first demyelinating event. J Neurol Neurosurg Psychiatry 88(5):395–401
Uher T, Fellows K, Horakova D, Zivadinov R, Vaneckova M, Sobisek L, Tyblova M, Seidl Z, Krasensky J, Bergsland N, Weinstock-Guttman B, Havrdova E, Ramanathan M (2017) Serum lipid profile changes predict neurodegeneration in interferon-B1a treated multiple sclerosis patients. J Lipid Res 58(2):403–411. https://doi.org/10.1194/jlr.M072751
Weinstock-Guttman B, Zivadinov R, Horakova D, Havrdova E, Qu J, Shyh G, Lakota E, O'Connor K, Badgett D, Tamaño-Blanco M, Tyblova M, Hussein S, Bergsland N, Willis L, Krasensky J, Vaneckova M, Seidl Z, Ramanathan M (2013) Lipid profiles are associated with lesion formation over 24 months in interferon-β treated patients following the first demyelinating event. J Neurol Neurosurg Psychiatry 84(11):1186–1191. https://doi.org/10.1136/jnnp-2012-304740
Zhornitsky S, Mckay KA, Metz LM, Teunissen CE (2016) Cholesterol and markers of cholesterol turnover in multiple sclerosis: relationship with disease outcomes. Mult Scler Relat Disord 5:53–65. https://doi.org/10.1016/j.msard.2015.10.005
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In compliance with current Italian applicable laws and regulations, considering that all data was publicly available and that the analyses included anonymized data, specific ethics approval was not required. The study was performed in accordance with Declaration of Helsinki.
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Moccia, M., Albero, R., Lanzillo, R. et al. Cardiovascular profile improvement during Natalizumab treatment. Metab Brain Dis 33, 981–986 (2018). https://doi.org/10.1007/s11011-017-0169-z
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DOI: https://doi.org/10.1007/s11011-017-0169-z