Lipids, Lipid-Lowering Therapy, and Neuropathy: A Narrative Review

Pasha, Raabya; Azmi, Shazli; Ferdousi, Maryam; Kalteniece, Alise; Bashir, Bilal; Gouni‐Berthold, Ioanna; Malik, Rayaz A.; Soran, Handrean

doi:10.1016/j.clinthera.2022.03.013

Cited by 6 publications

(5 citation statements)

References 111 publications

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“…The adverse events of chronic treatment with statins have been described, such as muscle symptoms, increased liver enzymes, diabetes, and so on (Crisan & Patil, 2020). It had also been found that long term use of statins increased the risk of haemorrhagic stroke and peripheral neuropathy (Pasha et al, 2022;Ruscica et al, 2023). And the drug target MR analysis has found that statins would increase a risk of haemorrhagic stroke and lower cognitive function (Rosoff et al, 2022;Yu et al, 2022).…”

Section: Discussionmentioning

confidence: 99%

Mendelian randomization study of lipid metabolism characteristics and migraine risk

Hong,

Han,

Wan

2024

European Journal of Pain

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BackgroundThe association between serum lipids and migraine is controversial. However, randomized controlled trials have suggested that statins may be efficacious for the prevention of migraine. In this study, we aim to investigate the relationship between lipids metabolism and migraine risk.MethodsSingle‐nucleotide polymorphisms (SNPs), relating to the serum lipid traits and the effect of lipid‐lowering drugs that target APOB, CETP, HMGCR, NPC1L1, and PCSK9, were extracted from genome‐wide association studies (GWAS) summary data. The GWAS summary data were obtained from the Global Lipids Genetic Consortium (GLGC), the UK Biobank, and the FinnGen study, respectively. Mendelian randomization (MR) analysis was performed to evaluate the association between serum lipid traits and lipid‐lowering drugs with migraine risk.ResultsRegarding serum lipids, it was found that SNPs related to high‐density lipoprotein cholesterol (HDL‐C), low‐density lipoprotein cholesterol (LDL‐C), non‐high‐density lipoprotein cholesterol (non‐HDL‐C), total cholesterol (TC), or triglycerides (TG) levels were not associated with migraine, migraine with aura (MA) or migraine without aura (MO). In addition, genotypes of HMGCR related to higher LDL‐C levels were associated with increased risk of migraine (OR = 1.46, p = 0.035) and MA (OR = 2.03, p = 0.008); However, genotypes of PCSK9 related to higher LDL‐C levels were associated with decreased risk of migraine (OR = 0.75, p = 0.001) and MA (OR = 0.69, p = 0.004); And genotypes of APOB related to higher LDL‐C levels were associated with decreased risk of MO (OR = 0.62, p = 0.000).ConclusionsThere is a relationship between lipid metabolism characteristics and migraine risk.SignificanceBased on the genome‐wide association summary data, single‐nucleotide polymorphisms (SNPs) related to high‐density lipoprotein cholesterol (HDL‐C), low‐density lipoprotein cholesterol (LDL‐C), non‐high‐density lipoprotein cholesterol (non‐HDL‐C), total cholesterol (TC), or triglycerides (TG) level were not associated with risk of migraine, migraine with aura (MA) or migraine without aura (MO). However, genotypes of HMGCR related to higher LDL‐C levels have shown an increased risk on migraine and MA. And genotypes of APOB or PCSK9 related to higher LDL‐C levels have shown a decreased risk on MO, or migraine and MA, respectively. These results suggested that there may be a relationship between lipid metabolism characteristics and the risk for migraine development.

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Section: Discussionmentioning

confidence: 99%

Mendelian randomization study of lipid metabolism characteristics and migraine risk

Hong,

Han,

Wan

2024

European Journal of Pain

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“…Lowering LDLcholesterol may reduce oxidative stress and mitigate neuropathy. 3) Dyslipidemia is associated with endothelial dysfunction and microvascular damage, which can contribute to nerve damage in DPN [41,42]. Improving vascular health may help alleviate some of the symptoms associated with DPN.…”

Section: Discussionmentioning

confidence: 99%

Protective effect of alirocumab, a PCSK9 inhibitor, on the sciatic nerve of rats with diabetic peripheral neuropathy

Cui,

Feng,

Wang

et al. 2024

Endocr J

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Dyslipidemia has been considered a risk factor for diabetic peripheral neuropathy. Proprotein convertase subtilisinlike/Kexin 9 inhibitor (PCSK9) inhibitors are a new type of lipid-lowering drug currently in clinical use. The role of PCSK9 in diabetic peripheral neuropathy is still unclear. In this study, the effect of alirocumab, a PCSK9 inhibitor, on the sciatic nerve in rats with diabetic peripheral neuropathy and its underlying mechanisms were investigated. The diabetic peripheral neuropathy rat model was established by using a high-fat diet combined with streptozotocin injection, and experimental subjects were divided into normal, diabetic peripheral neuropathy, and alirocumab groups. The results showed that Alirocumab improved nerve conduction, morphological changes, and small fiber deficits in rats with DPN, possibly related to its amelioration of oxidative stress and the inflammatory response.

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“…There is no other report of an association between PCSK9 inhibitor use and demyelinating polyneuropathies. Of note, even if several cases of statin-induced peripheral neuropathy have been reported, there is no evidence for a causal relationship between statin treatment and peripheral neuropathy ( 61 ). In addition, a positive association was found between corneal nerve loss and circulating PCSK9 ( 62 ), and PCSK9 inhibitors treatment resulted in fibers regeneration in familial hypercholesterolemic patients with corneal small nerve fibers degeneration ( 63 ).…”

Section: Pcsk9 In the Peripheral Nervous Systemmentioning

confidence: 99%

PCSK9 and the nervous system: a no-brainer?

Jaafar,

Techer,

Chemello

et al. 2023

Journal of Lipid Research

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Lipids, Lipid-Lowering Therapy, and Neuropathy: A Narrative Review

Cited by 6 publications

References 111 publications

Mendelian randomization study of lipid metabolism characteristics and migraine risk

Mendelian randomization study of lipid metabolism characteristics and migraine risk

Protective effect of alirocumab, a PCSK9 inhibitor, on the sciatic nerve of rats with diabetic peripheral neuropathy

PCSK9 and the nervous system: a no-brainer?

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