The association between statins exposure and peripheral neuropathy risk: A meta‐analysis

Wang, Miao; Li, Muqin; Xie, Yufeng

doi:10.1111/jcpt.13393

Cited by 6 publications

(3 citation statements)

References 35 publications

(40 reference statements)

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“…However, other studies have failed to report a protective effect of statins on neuropathy [90,[96][97][98]. A recent metanalysis of nine studies and a meta-analysis of five studies of unattended effects on statins have demonstrated a neutral effect of statins on peripheral neuropathy [99,100]. The FDA Safety Information and Adverse Event Reporting Program data analysis has demonstrated a stronger association of neuropathy with lipophilic statins and no association when statins were combined with niacin arguing for a protective effect of niacin [101].…”

Section: Lipid Therapeutics Targeting Neuropathymentioning

confidence: 99%

Lipids and peripheral neuropathy

Iqbal

Bashir

Ferdousi

et al. 2021

Current Opinion in Lipidology

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Purpose of review Hyperlipidaemia is associated with the development of neuropathy. Indeed, a mechanistic link between altered lipid metabolism and peripheral nerve dysfunction has been demonstrated in a number of experimental and clinical studies. Furthermore, post hoc analyses of clinical trials of cholesterol and triglyceride-lowering pharmacotherapy have shown reduced rates of progression of diabetic neuropathy. Given, there are currently no FDA approved disease-modifying therapies for diabetic neuropathy, modulation of lipids may represent a key therapeutic target for the treatment of diabetic nerve damage. This review summarizes the current evidence base on the role of hyperlipidaemia and lipid lowering therapy on the development and progression of peripheral neuropathy. Recent findings A body of literature supports a detrimental effect of dyslipidaemia on nerve fibres resulting in somatic and autonomic neuropathy. The case for an important modulating role of hypertriglyceridemia is stronger than for low-density lipoprotein cholesterol (LDL-C) in relation to peripheral neuropathy. This is reflected in the outcomes of clinical trials with the different therapeutic agents targeting hyperlipidaemia reporting beneficial or neutral effects with statins and fibrates. The potential concern with the association between proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor therapy and cognitive decline raised the possibility that extreme LDL-C lowering may result in neurodegeneration. However, studies in murine models and data from small observational studies indicate an association between increased circulating PCSK9 levels and small nerve fibre damage with a protective effect of PCSK9i therapy against small fibre neuropathy. Additionally, weight loss with bariatric surgery leads to an improvement in peripheral neuropathy and regeneration of small nerve fibres measured with corneal confocal microscopy in people with obesity with or without type 2 diabetes. These improvements correlate inversely with changes in triglyceride levels. Summary Hyperlipidaemia, particularly hypertriglyceridemia, is associated with the development and progression of neuropathy. Lipid modifying agents may represent a potential therapeutic option for peripheral neuropathy. Post hoc analyses indicate that lipid-lowering therapies may halt the progression of neuropathy or even lead to regeneration of nerve fibres. Well designed randomized controlled trials are needed to establish if intensive targeted lipid lowering therapy as a part of holistic metabolic control leads to nerve fibre regeneration and improvement in neuropathy symptoms.

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Section: Lipid Therapeutics Targeting Neuropathymentioning

confidence: 99%

Lipids and peripheral neuropathy

Iqbal

Bashir

Ferdousi

et al. 2021

Current Opinion in Lipidology

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“…A clinical trial revealed that simvastatin/ezetimibe and rosuvastatin could significantly reduce lipid peroxidation in patients with DN ( Villegas-Rivera et al, 2015 ). However, other studies did not find significant association between statins and DN ( Miao Wang et al, 2021 ). Fibrates are also used to lower triglyceride and increase high-density lipoprotein.…”

Section: Treatmentmentioning

confidence: 88%

Diabetic Corneal Neuropathy: Pathogenic Mechanisms and Therapeutic Strategies

Zhou

Lee

et al. 2022

Front. Pharmacol.

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Diabetes mellitus (DM) is a major global public health problem that can cause complications such as diabetic retinopathy, diabetic neuropathy, and diabetic nephropathy. Besides the reporting of reduction in corneal nerve density and decrease in corneal sensitivity in diabetic patients, there may be a subsequent result in delayed corneal wound healing and increased corneal infections. Despite being a potential cause of blindness, these corneal nerve changes have not gained enough attention. It has been proposed that corneal nerve changes may be an indicator for diabetic neuropathy, which can provide a window for early diagnosis and treatment. In this review, the authors aimed to give an overview of the relationship between corneal nerves and diabetic neuropathy as well as the underlying pathophysiological mechanisms of corneal nerve fiber changes caused by DM for improved prediction and prevention of diabetic neuropathy. In addition, the authors summarized current and novel therapeutic methods for delayed corneal wound healing, nerve protection and regeneration in the diabetic cornea.

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“…[32] Nevertheless, a recent study has reported that HMGCR inhibitors suppressed phosphorylation and activity of protein kinase B in PC cells and also arrested proliferation, migration, invasion and apoptosis of PC cells. [33] However, less literature investigated causal relationships between HMGCR inhibitors and SC except an updated meta-analysis [34] with risk-decreasing associations. The discrepancy may be due to shortcomings of both MR analysis and meta-analysis.…”

Section: Discussionmentioning

confidence: 99%

Causal association between lipid-lowering drugs and cancers: A drug target Mendelian randomization study

Ding,

Chen,

Xia

et al. 2024

Medicine

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Accumulating evidences have indicated that lipid-lowering drugs have effect for the treatment of cancers. However, causal associations between lipid-lowering drugs and the risk of cancers are still unclear. In our study, we utilized single nucleotide polymorphisms of proprotein convertase subtilis kexin 9 (PCSK9) inhibitors and 3-hydroxy-3-methylglutaryl-assisted enzyme A reductase (HMGCR) inhibitors and performed a drug target Mendelian randomization to explore the causal association between lipid-lowering drugs and the risk of cancers. Five regression methods were carried out, including inverse variance weighted (IVW) method, MR Egger, weighted median, simple mode and weighted mode methods, of which IVW method was considered as the main analysis. Our outcome dataset contained the risk of breast cancer (BC), colorectal cancer, endometrial cancer, gastric cancer (GC), hepatocellular carcinoma (HCC), lung cancer, esophageal cancer, prostate cancer (PC), and skin cancer (SC). Our results demonstrated that PCSK9 inhibitors were significant associated with a decreased effect of GC [IVW: OR = 0.482, 95% CI: 0.264–0.879, P = .017]. Besides, genetic inhibitions of HMGCR were significant correlated with an increased effect of BC [IVW: OR = 1.421, 95% CI: 1.056–1.911, P = .020], PC [IVW: OR = 1.617, 95% CI: 1.234–2.120, P = .0005] and SC [IVW: OR = 1.266, 95% CI: 1.022–1.569, P = .031]. For GC [IVW: OR = 0.559, 95% CI: 0.382–0.820, P = .0029] and HCC [IVW: OR = 0.241, 95% CI: 0.085–0.686, P = .0077], HMGCR inhibitors had a protective risk. Our method suggested that PCSK9 inhibitors were significant associated with a protective effect of GC. Genetic inhibitions of HMGCR were significant correlated with an increased effect of BC, PC and SC. Meanwhile, HMGCR inhibitors had a protective risk of GC and HCC. Subsequent studies still needed to assess potential effects between lipid-lowering drugs and the risk of cancers with clinical trials.

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The association between statins exposure and peripheral neuropathy risk: A meta‐analysis

Cited by 6 publications

References 35 publications

Lipids and peripheral neuropathy

Lipids and peripheral neuropathy

Diabetic Corneal Neuropathy: Pathogenic Mechanisms and Therapeutic Strategies

Causal association between lipid-lowering drugs and cancers: A drug target Mendelian randomization study

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