Cardiovascular profile improvement during Natalizumab treatment
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.
KeywordsMultiple sclerosis Cardiovascular Cholesterol Uric Natalizumab
Research funding played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
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.
- 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 CrossRefPubMedGoogle Scholar
- 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 CrossRefPubMedGoogle Scholar
- 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 PubMedGoogle Scholar
- 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 CrossRefPubMedGoogle Scholar
- 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 CrossRefPubMedPubMedCentralGoogle Scholar
- 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 CrossRefPubMedGoogle Scholar
- 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 CrossRefPubMedGoogle Scholar
- 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 CrossRefPubMedGoogle Scholar
- 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 CrossRefPubMedPubMedCentralGoogle Scholar
- 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 CrossRefPubMedGoogle Scholar
- 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):395–401Google Scholar
- 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 CrossRefPubMedPubMedCentralGoogle Scholar
- 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 CrossRefPubMedGoogle Scholar