Cholesterol Management in Neurology: Time for Revised Strategies?
Abstract
:1. Introduction
2. Cholesterol and Its Functions
3. 3-Hydroxy-3-Methylglutaryl-Coenzyme A (HMG-CoA) Reductases or Statins
3.1. Myotoxic Effects of Statins
3.2. Cognitive Side-Effects of Statins
4. Statins in Clinical Practice in Specific Subgroups of Patients
4.1. Statins in Myasthenia Gravis
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- The statin’s myotoxic effects may exacerbate muscle weakness in patients with prior MG
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- via depletion of coenzyme Q10, statins could induce mitochondrial dysfunction with impairment of energy production at the presynaptic membrane [109]
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4.2. Statins in Muscular Dystrophies
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- Duchenne muscular dystrophy
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- Becker MD
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- congenital MD
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- distal MD
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- facioscapulohumeral MD
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- Emery-Dreifuss MD
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- limb-girdle MD
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- oculopharyngeal MD
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- myotonic MD
4.3. Statins and Cognitive Impairment
5. Conclusions
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- using non-statin lipid-lowering therapies in patients with muscular diseases, such as ezetimibe or PCSK9 inhibitors
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- extensive evaluation of patients with vascular events (ischemic strokes), with measurement of the LDL-cholesterol levels, neuropsychological evaluation, identification of the stroke subtype according to the TOAST criteria [158], and thorough risk stratification using, whenever possible, the coronary artery calcium (CAC) score [159]
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- when statins are necessary, the preference for a hydrophilic statin over a lipophilic one could avoid statin-induced cognitive impairment
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- the LDL-cholesterol levels should be regularly checked and the doses adjusted accordingly [148]
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- However, further clinical trials may help to develop efficient therapeutic strategies and set guidelines for particular subsets of patients.
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Statin | Dose | Solubility | Liver Metabolization | Half-Life (Hours) |
---|---|---|---|---|
Lovastatin | 10–80 mg | lipophilic | CYP450 3A4 | 2 |
Fluvastatin | 20–80 mg | lipophilic | CYP450 2C9 | 4.7 |
Simvastatin | 5–40 mg | lipophilic | CYP4503A4 | 1–2 |
Atorvastatin | 10–80 mg | lipophilic | CYP450 3A4 | 14 |
Pitavastatin | 1–4 mg | lipophilic | CYP450 2C9 | 96 |
Rosuvastatin | 5–40 mg | hydrophilic | CYP450 2C9 and 2C19 | 19 |
Pravastatin | 20–80 mg | hydrophilic | sulphation | 1–2 |
SRM Classification | Phenotype | Definition |
---|---|---|
SRM 0 | Asymptomatic | Elevations of <4× upper normal limit in serum creatine kinase (CK) |
SRM 1 | Myalgia, tolerable | Muscle aches, cramps and/or weakness with no elevation of CK |
SRM 2 | Myalgia, intolerable | Muscle aches, cramps and/or weakness with < 4× upper normal limit of CK |
SRM 3 | Myopathy | CK levels > 4× but < 10× upper normal limit of CK |
SRM 4 | Severe myopathy | CK levels >10× but < 50× upper normal limit |
SRM 5 | Rhabdomyolysis | Either CK > 10× upper normal limit, muscle symptoms and renal impairment, or CK > 50× upper normal limit |
SRM 6 | Autoimmune-mediated, necrotizing myositis | HMGCR antibodies, HMGCR expression in muscle biopsy, incomplete resolution after statin discontinuation |
Solubility | Statin | Effects of Statin Use on Cognitive Function | Number of Patients | Reference |
---|---|---|---|---|
Lipophilic | Simvastatin |
| 4724 pairs of patients 9,162,509 total number 10,888 334,861 | [154] [153] [140] [155] |
Atorvastatin |
| 4724 pairs of patients 9,162,509 total number 45,753 | [154] [153] [140] | |
Lovastatin |
| Total of 9,162,509 567 | [153] [140] | |
Fluvastatin |
| Total of 9,162,509 patients 4724 pairs of patients | [153] [154] | |
Hydrophilic | Rosuvastatin |
| 4724 pairs of patients 62,387 9,162,509 8251 | [154] [136] [153] [140] |
Pravastatin |
| 9,162,509 2524 77,795 | [153] [140] [136] |
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Andronie-Cioară, F.L.; Jurcău, A.; Jurcău, M.C.; Nistor-Cseppentö, D.C.; Simion, A. Cholesterol Management in Neurology: Time for Revised Strategies? J. Pers. Med. 2022, 12, 1981. https://doi.org/10.3390/jpm12121981
Andronie-Cioară FL, Jurcău A, Jurcău MC, Nistor-Cseppentö DC, Simion A. Cholesterol Management in Neurology: Time for Revised Strategies? Journal of Personalized Medicine. 2022; 12(12):1981. https://doi.org/10.3390/jpm12121981
Chicago/Turabian StyleAndronie-Cioară, Felicia Liana, Anamaria Jurcău, Maria Carolina Jurcău, Delia Carmen Nistor-Cseppentö, and Aurel Simion. 2022. "Cholesterol Management in Neurology: Time for Revised Strategies?" Journal of Personalized Medicine 12, no. 12: 1981. https://doi.org/10.3390/jpm12121981
APA StyleAndronie-Cioară, F. L., Jurcău, A., Jurcău, M. C., Nistor-Cseppentö, D. C., & Simion, A. (2022). Cholesterol Management in Neurology: Time for Revised Strategies? Journal of Personalized Medicine, 12(12), 1981. https://doi.org/10.3390/jpm12121981