Abstract
Objective
To investigate the association between the use of common medications on hypertension, hyperlipidemia, diabetes, and the risk of amyotrophic lateral sclerosis (ALS).
Methods
PubMed, EMBASE, OVID, and Web of Science were searched systematically until December 2021 for studies quantitatively investigating the effect of medications on hypertension, hyperlipidemia, and diabetes on the risk of ALS. We conducted a fixed-effects model or random-effects meta-analysis to calculate the summary ORs (odds ratios) and 95%CIs (confidence intervals).
Results
Regular intake of angiotensin-converting enzyme inhibitors (ACEIs) (OR: 0.81, 95%CI: 0.74, 0.89), beta-blockers (OR: 0.82, 95%CI: 0.76, 0.90), calcium-channel blockers (CCBs) (OR: 0.85, 95%CI: 0.79, 0.93), or diuretics (OR: 0.87, 95%CI: 0.81, 0.93) was inversely associated with the incidence of ALS. There was no significant association between statin use and risk of ALS (OR: 0.92, 95%CI: 0.83, 1.03). Metformin (OR: 0.83, 95%CI: 0.75, 0.93) and sulfonylureas (OR: 0.79, 95%CI:0.71, 0.89) use could significantly reduce the risk of ALS.
Conclusion
Regular use of anti-hypertensive drugs and anti-diabetes including ACEIs, beta-blockers, CCBs, diuretics, metformin, and sulfonylureas could protect against the incidence of ALS. No significant association between anti-hyperlipidemia drug use and risk of ALS was revealed. Regular medications for hypertension, hyperlipidemia, and diabetes should be recommended regardless of the diagnosis of ALS.
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Data availability
All data analyzed during this study are included in published articles.
References
Kiernan MC et al (2011) Amyotrophic lateral sclerosis. Lancet 377(9769):942–955
Visser J et al (2007) Disease course and prognostic factors of progressive muscular atrophy. Arch Neurol 64(4):522–528
Knibb JA et al (2016) A clinical tool for predicting survival in ALS. J Neurol Neurosurg Psychiatry 87(12):1361–1367
Longinetti E, Fang F (2019) Epidemiology of amyotrophic lateral sclerosis: an update of recent literature. Curr Opin Neurol 32(5):771–776
Rosa Silva JP et al (2020) Quality of life and functional independence in amyotrophic lateral sclerosis: a systematic review. Neurosci Biobehav Rev 111:1–11
De Marchi F et al (2019) Depression and risk of cognitive dysfunctions in amyotrophic lateral sclerosis. Acta Neurol Scand 139(5):438–445
McElhiney MC et al (2009) Prevalence of fatigue and depression in ALS patients and change over time. J Neurol Neurosurg Psychiatry 80(10):1146–1149
Rabkin JG et al (2015) Depression and wish to die in a multicenter cohort of ALS patients. Amyotroph Lateral Scler Frontotemporal Degener 16(3–4):265–273
Thakore NJ, Lapin BR, Pioro EP (2020) Stage-specific riluzole effect in amyotrophic lateral sclerosis: a retrospective study. Amyotroph Lateral Scler Frontotemporal Degener 21(1–2):140–143
(2017) Safety and efficacy of edaravone in well defined patients with amyotrophic lateral sclerosis: a randomised, double-blind, placebo-controlled trial. Lancet Neurol 16(7): 505–512
Miller RG, Mitchell JD, Moore DH (2012) Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND). Cochrane Database Syst Rev 2012(3):Cd001447
Moglia C et al (2017) Influence of arterial hypertension, type 2 diabetes and cardiovascular risk factors on ALS outcome: a population-based study. Amyotroph Lateral Scler Frontotemporal Degener 18(7–8):590–597
Kioumourtzoglou MA et al (2015) Diabetes mellitus, obesity, and diagnosis of amyotrophic lateral sclerosis: a population-based study. JAMA Neurol 72(8):905–911
Moreau C et al (2012) Modifying effect of arterial hypertension on amyotrophic lateral sclerosis. Amyotroph Lateral Scler 13(2):194–201
Mandrioli J et al (2018) Cardiovascular diseases may play a negative role in the prognosis of amyotrophic lateral sclerosis. Eur J Neurol 25(6):861–868
Lian L et al (2019) Environmental risk factors and amyotrophic lateral sclerosis (ALS): a case-control study of ALS in China. J Clin Neurosci 66:12–18
Freedman DM et al (2018) Relationship of statins and other cholesterol-lowering medications and risk of amyotrophic lateral sclerosis in the US elderly. Amyotroph Lateral Scler Frontotemporal Degener 19(7–8):538–546
Seelen M et al (2014) Prior medical conditions and the risk of amyotrophic lateral sclerosis. J Neurol 261(10):1949–1956
Cardoso S et al (2009) Insulin is a two-edged knife on the brain. J Alzheimers Dis 18(3):483–507
Sun H et al (2013) Therapeutic potential of N-acetyl-glucagon-like peptide-1 in primary motor neuron cultures derived from non-transgenic and SOD1-G93A ALS mice. Cell Mol Neurobiol 33(3):347–357
Pfeiffer RM et al (2020) Identifying potential targets for prevention and treatment of amyotrophic lateral sclerosis based on a screen of medicare prescription drugs. Amyotroph Lateral Scler Frontotemporal Degener 21(3–4):235–245
Stroup DF et al (2000) Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA 283(15):2008–12
Liberati A et al (2009) The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ 339:b2700
Skajaa N et al (2021) Statin initiation and risk of amyotrophic lateral sclerosis: a Danish population-based cohort study. Epidemiology
Mariosa D et al (2020) Antidiabetics, statins and the risk of amyotrophic lateral sclerosis. Eur J Neurol 27(6):1010–1016
Torrandell-Haro G et al (2020) Statin therapy and risk of Alzheimer’s and age-related neurodegenerative diseases. Alzheimers Dement (N Y) 6(1):e12108
Schumacher J et al (2020) Statins, diabetes mellitus and prognosis of amyotrophic lateral sclerosis: data from 501 patients of a population-based registry in southwest Germany. Eur J Neurol 27(8):1405–1414
Diekmann K et al (2020) Impact of comorbidities and co-medication on disease onset and progression in a large German ALS patient group. J Neurol 267(7):2130–2141
Bond L et al (2020) Associations of Patient Mood, Modulators of Quality of Life, and Pharmaceuticals with Amyotrophic Lateral Sclerosis Survival Duration. Behav Sci (Basel) 10(1)
Franchi C et al (2016) Angiotensin-converting enzyme inhibitors and motor neuron disease: an unconfirmed association. Amyotroph Lateral Scler Frontotemporal Degener 17(5–6):385–388
Lin FC et al (2015) Angiotensin-converting enzyme inhibitors and amyotrophic lateral sclerosis risk: a total population-based case-control study. JAMA Neurol 72(1):40–48
Qureshi M et al (2008) Medications and laboratory parameters as prognostic factors in amyotrophic lateral sclerosis. Amyotroph Lateral Scler 9(6):369–374
Linden D, Diehl RR, Berlit P (1998) Reduced baroreflex sensitivity and cardiorespiratory transfer in amyotrophic lateral sclerosis. Electroencephalogr Clin Neurophysiol 109(5):387–390
Scelsa SN, Khan I (2000) Blood pressure elevations in riluzole-treated patients with amyotrophic lateral sclerosis. Eur Neurol 43(4):224–227
Armon C et al (1991) Antecedent medical diseases in patients with amyotrophic lateral sclerosis. A population-based case-controlled study in Rochester, Minn, 1925 through 1987. Arch Neurol 48(3):283–6
Pereira M et al (2021) Cardiovascular comorbidities in amyotrophic lateral sclerosis. J Neurol Sci 421:117292
Kehoe PG, Wilcock GK (2007) Is inhibition of the renin-angiotensin system a new treatment option for Alzheimer’s disease? Lancet Neurol 6(4):373–378
Philips T, Robberecht W (2011) Neuroinflammation in amyotrophic lateral sclerosis: role of glial activation in motor neuron disease. Lancet Neurol 10(3):253–263
Ravati A et al (1999) Enalapril and moexipril protect from free radical-induced neuronal damage in vitro and reduce ischemic brain injury in mice and rats. Eur J Pharmacol 373(1):21–33
Mira ML et al (1993) Angiotensin converting enzyme inhibitors as oxygen free radical scavengers. Free Radic Res Commun 19(3):173–181
Sengul G et al (2011) Neuroprotective effect of ACE inhibitors in glutamate - induced neurotoxicity: rat neuron culture study. Turk Neurosurg 21(3):367–371
Wang H et al (2011) Vitamin E intake and risk of amyotrophic lateral sclerosis: a pooled analysis of data from 5 prospective cohort studies. Am J Epidemiol 173(6):595–602
Ohrui T et al (2004) Effects of brain-penetrating ACE inhibitors on Alzheimer disease progression. Neurology 63(7):1324–1325
Reardon KA et al (2000) The angiotensin converting enzyme (ACE) inhibitor, perindopril, modifies the clinical features of Parkinson’s disease. Aust N Z J Med 30(1):48–53
Lin SY et al (2020) Effects of β-adrenergic blockade on metabolic and inflammatory responses in a rat model of ischemic stroke. Cells 9(6)
Leal SS, Gomes CM (2015) Calcium dysregulation links ALS defective proteins and motor neuron selective vulnerability. Front Cell Neurosci 9:225
Miller RG et al (1996) Controlled trial of nimodipine in amyotrophic lateral sclerosis. Neuromuscul Disord 6(2):101–104
Miller RG et al (1996) A clinical trial of verapamil in amyotrophic lateral sclerosis. Muscle Nerve 19(4):511–515
Dorst J et al (2011) Patients with elevated triglyceride and cholesterol serum levels have a prolonged survival in amyotrophic lateral sclerosis. J Neurol 258(4):613–617
Dupuis L et al (2008) Dyslipidemia is a protective factor in amyotrophic lateral sclerosis. Neurology 70(13):1004–1009
Huang R et al (2015) The serum lipid profiles of amyotrophic lateral sclerosis patients: a study from south-west China and a meta-analysis. Amyotroph Lateral Scler Frontotemporal Degener 16(5–6):359–365
Bandres-Ciga S et al (2019) Shared polygenic risk and causal inferences in amyotrophic lateral sclerosis. Ann Neurol 85(4):470–481
Beltowski J (2010) Statins and ALS: the possible role of impaired LXR signaling. Med Sci Monit 16(3):Ra73-78
Edwards IR, Star K, Kiuru A (2007) Statins, neuromuscular degenerative disease and an amyotrophic lateral sclerosis-like syndrome: an analysis of individual case safety reports from vigibase. Drug Saf 30(6):515–525
Wannarong T, Ungprasert P (2020) Diabetes mellitus is associated with a lower risk of amyotrophic lateral sclerosis: a systematic review and meta-analysis. Clin Neurol Neurosurg 199:106248
Vasta R et al (2021) The links between diabetes mellitus and amyotrophic lateral sclerosis. Neurol Sci 42(4):1377–1387
Zhang L et al (2022) Association between type 2 diabetes and amyotrophic lateral sclerosis. Sci Rep 12(1):2544
Zu T et al (2020) Metformin inhibits RAN translation through PKR pathway and mitigates disease in C9orf72 ALS/FTD mice. Proc Natl Acad Sci U S A 117(31):18591–18599
Han J et al (2018) Metformin suppresses retinal angiogenesis and inflammation in vitro and in vivo. PLoS ONE 13(3):e0193031
Mariosa D et al (2015) Association between diabetes and amyotrophic lateral sclerosis in Sweden. Eur J Neurol 22(11):1436–1442
Araki K et al (2019) TDP-43 regulates early-phase insulin secretion via CaV1.2-mediated exocytosis in islets. J Clin Invest 129(9):3578–3593
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Hu, N., Ji, H. Medications on hypertension, hyperlipidemia, diabetes, and risk of amyotrophic lateral sclerosis: a systematic review and meta-analysis. Neurol Sci 43, 5189–5199 (2022). https://doi.org/10.1007/s10072-022-06131-7
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DOI: https://doi.org/10.1007/s10072-022-06131-7
Keywords
- Medications
- Hypertension
- Hyperlipidemia
- Diabetes
- Amyotrophic lateral sclerosis