Dataset Information

Skeletal muscle mitochondrial capacity in patients with statin-associated muscle symptoms (SAMS).

ABSTRACT:

Objective

The objective of this article is to evaluate near-infrared spectroscopy (NIRS), a non-invasive technique to assess tissue oxygenation and mitochondrial function, as a diagnostic tool for statin-associated muscle symptoms (SAMS).

Methods

We verified SAMS in 39 statin-treated patients (23 women) using a double-blind, placebo-controlled, cross-over protocol. Subjects with suspected SAMS were randomised to simvastatin 20 mg/day or placebo for 8 weeks, followed by a 4-week no treatment period and then assigned to the alternative treatment, either simvastatin or placebo. Tissue oxygenation was measured before and after each statin or placebo treatment using NIRS during handgrip exercise at increasing intensities of maximal voluntary contraction (MVC).

Results

44% (n=17) of patients were confirmed as having SAMS (11 women) because they reported discomfort only during simvastatin treatment. There were no significant differences in percent change in tissue oxygenation in placebo versus statin at all % MVCs in all subjects. The percent change in tissue oxygenation also did not differ significantly between confirmed and unconfirmed SAMS subjects on statin (-2.4% vs -2.4%, respectively) or placebo treatment (-1.1% vs -9%, respectively). The percent change in tissue oxygenation was reduced after placebo therapy in unconfirmed SAMS subjects (-10.2%) (p≤0.01) suggesting potential measurement variability.

Conclusions

NIRS in the forearm cannot differentiate between confirmed and unconfirmed SAMS, but further research is needed to assess the usability of NIRS as a diagnostic tool for SAMS.

Trial registration number

NCT03653663.

SUBMITTER: Mangone LA

PROVIDER: S-EPMC10884190 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature

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Publications

Skeletal muscle mitochondrial capacity in patients with statin-associated muscle symptoms (SAMS).

Mangone Laura A LA Taylor Beth A BA Schmelzer Robert R Noh Sung Gi SG White Michael C MC Kwon Oh Sung OS Thompson Paul D PD

Open heart 20240222 1

<h4>Objective</h4>The objective of this article is to evaluate near-infrared spectroscopy (NIRS), a non-invasive technique to assess tissue oxygenation and mitochondrial function, as a diagnostic tool for statin-associated muscle symptoms (SAMS).<h4>Methods</h4>We verified SAMS in 39 statin-treated patients (23 women) using a double-blind, placebo-controlled, cross-over protocol. Subjects with suspected SAMS were randomised to simvastatin 20 mg/day or placebo for 8 weeks, followed by a 4-week no ...[more]

PMID: 38388189

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Project description:BackgroundBetween 5-10% of patients discontinue statin therapy due to statin-associated adverse reactions, primarily statin associated muscle symptoms (SAMS). The absence of a clear clinical phenotype or of biomarkers poses a challenge for diagnosis and management of SAMS. Similarly, our incomplete understanding of the pathogenesis of SAMS hinders the identification of treatments for SAMS. Metabolomics, the profiling of metabolites in biofluids, cells and tissues is an important tool for biomarker discovery and provides important insight into the origins of symptomatology. In order to better understand the pathophysiology of this common disorder and to identify biomarkers, we undertook comprehensive metabolomic and lipidomic profiling of plasma samples from patients with SAMS who were undergoing statin rechallenge as part of their clinical care.Methods and findingsWe report our findings in 67 patients, 28 with SAMS (cases) and 39 statin-tolerant controls. SAMS patients were studied during statin rechallenge and statin tolerant controls were studied while on statin. Plasma samples were analyzed using untargeted LC-MS metabolomics and lipidomics to detect differences between cases and controls. Differences in lipid species in plasma were observed between cases and controls. These included higher levels of linoleic acid containing phospholipids and lower ether lipids and sphingolipids. Reduced levels of acylcarnitines and altered amino acid profile (tryptophan, tyrosine, proline, arginine, and taurine) were observed in cases relative to controls. Pathway analysis identified significant increase of urea cycle metabolites and arginine and proline metabolites among cases along with downregulation of pathways mediating oxidation of branched chain fatty acids, carnitine synthesis, and transfer of acetyl groups into mitochondria.ConclusionsThe plasma metabolome of patients with SAMS exhibited reduced content of long chain fatty acids and increased levels of linoleic acid (18:2) in phospholipids, altered energy production pathways (β-oxidation, citric acid cycle and urea cycles) as well as reduced levels of carnitine, an essential mediator of mitochondrial energy production. Our findings support the hypothesis that alterations in pro-inflammatory lipids (arachidonic acid pathway) and impaired mitochondrial energy metabolism underlie the muscle symptoms of patients with statin associated muscle symptoms (SAMS).

Project description:UnlabelledPatients with familial hypercholesterolemia (FH) may be at increased risk for statin-associated muscle symptoms because they require long-term treatment with high-intensity statin therapy. We sought to determine (1) whether other predisposing factors, including the well-known genetic variant associated with statin-associated muscle symptoms-solute carrier organic anion transporter family, member 1B1 (SLCO1B1) rs4149056-also increase the risk of statin-associated muscle symptoms in FH patients, and (2) the natural history and management for FH patients with statin-associated muscle symptoms.MethodsWe queried electronic records (2004-2014) of 278 genetically screened FH patients (113 men, 165 women; mean [SD] pretreatment low-density lipoprotein cholesterol [LDL-C] 259 [72] mg/dL) recruited from lipid clinics in the Dallas, TX, area from 2004 to 2014. Statin-associated muscle symptoms were defined as muscle symptoms arising while taking a statin and interrupting therapy.ResultsThe risk of muscle symptoms was associated with age (odds ratio 1.6 [95% CI 1.2-2.2]), body mass index in non-African Americans (0.90 [0.83-0.97]), and hypertension (0.4 [0.2-0.9]). Simvastatin was the most commonly used statin, and it was the statin most associated with muscle symptoms. Among FH patients with muscle symptoms, 41% (n = 40) reestablished statin therapy ("eventually tolerant") and 29% (n = 28) never reestablished statin therapy ("never tolerant"). Rosuvastatin (43%) and pravastatin (30%) were the most common eventually tolerated statins, and eventually tolerant patients achieved lower treated LDL-C levels (eventually tolerant 127 vs never tolerant 192 mg/dL, P < .001). Never tolerant patients also developed muscle symptoms on nonstatins (16% vs 50%, P = .003). SLCO1B1 rs4149056 genotyping revealed 224 wild-type patients (TT) and 49 heterozygotes (TC). SLCO1B1 genotype was not associated with the risk of statin-associated muscle symptoms (odds ratio 1.40 [95% CI 0.74-2.64]).ConclusionAge, not SLCO1B1 rs4149056 genotype, was the strongest risk factor for statin-associated muscle symptoms in FH patients. After developing muscle symptoms, many patients reestablished statin therapy and achieved significant LDL-C reductions. Overall, 10% of all FH patients had statin-associated muscle symptoms and never reestablished statin therapy. Such patients developed muscle symptoms even on nonstatin lipid-lowering drugs and continued to have elevations in LDL-C. Further insight is needed into the relationship between FH and statin-associated muscle symptoms so all FH patients can be adequately treated.

Project description:IntroductionAlthough statins are commonly used for prevention of cardiovascular disease, there is limited evidence about statin-related adverse effects in older people. Statin-related adverse events (AEs), especially the statin-associated muscle symptoms (SAMS), are the most common reasons for their discontinuation. Therefore, it is important to determine the risk of SAMS in the older population. We will undertake a systematic review and meta-analysis primarily focusing on the risk of SAMS and secondarily targeting myopathy, rhabdomyolysis, AEs and serious AEs, dropouts due to SAMS in run-in period, related permanent discontinuation rate of statins and creatine kinase level, among older people who received statins for primary prevention.Methods and analysisThis study has been developed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols statement. We will include randomised controlled trials in which statin was compared with placebo with at least 1 year follow-up among older adults aged ≥65. This review is an update of a Cochrane systematic review that included the articles published before 2012. Cochrane Central Register of Controlled Trials, Medline OvidSP and Embase electronic database searches will be performed to identify relevant articles, limiting the publication date from 1 January 2012 to 13 February 2017. There will be no language limitation. Two independent reviewers will screen titles and abstracts and full text in duplicate. Risk of bias and evidence quality will be assessed using the Cochrane Collaboration's tool and the Grading of Recommendations Assessment, Development and Evaluation approach, respectively. A meta-analysis using pooled data will be undertaken, if appropriate. We will also perform metaregression and subgroup analyses to identify sources of heterogeneity.Ethics and disseminationThis study is exempt from ethics approval due to the anonymous and aggregated data used. The outcomes will be disseminated by conference presentations and published in a peer-reviewed journal.Trial registration numberCRD42017058436.

Dataset Information

Skeletal muscle mitochondrial capacity in patients with statin-associated muscle symptoms (SAMS).

Objective

Methods

Results

Conclusions

Trial registration number

Publications

Skeletal muscle mitochondrial capacity in patients with statin-associated muscle symptoms (SAMS).

Similar Datasets

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