Dataset Information

Effect of Simvastatin on Arterial Stiffness in Patients with Statin Myalgia.

ABSTRACT: Statins reduce arterial stiffness but are also associated with mild muscle complaints. It is unclear whether individuals with muscle symptoms experience the same vascular benefit or whether statins affect striated and smooth muscle cells differently. We examined the effect of simvastatin treatment on arterial stiffness in patients who did versus those who did not exhibit muscle symptoms. Patients with a history of statin-related muscle complaints (n = 115) completed an 8?wk randomized, double-blind, cross-over trial of daily simvastatin 20?mg and placebo. Serum lipids and pulse wave velocity (PWV) were assessed before and after each treatment. Muscle symptoms with daily simvastatin treatment were reported by 38 patients (33%). Compared to baseline, central PWV decreased (P = 0.01) following simvastatin treatment but not placebo (drug ? time interaction: P = 0.047). Changes in central PWV with simvastatin treatment were not influenced by myalgia status or time on simvastatin (P ? 0.15). Change in central PWV after simvastatin treatment was inversely correlated with age (r = -0.207, P = 0.030), suggesting that advancing age is associated with enhanced statin-mediated arterial destiffening. In patients with a history of statin-related muscle complaints, the development of myalgia with short-term simvastatin treatment did not attenuate the improvement in arterial stiffness.

SUBMITTER: Ballard KD

PROVIDER: S-EPMC4518173 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Effect of Simvastatin on Arterial Stiffness in Patients with Statin Myalgia.

Ballard Kevin D KD Lorson Lindsay L White C Michael CM Thompson Paul D PD Taylor Beth A BA

Advances in preventive medicine 20150715

Statins reduce arterial stiffness but are also associated with mild muscle complaints. It is unclear whether individuals with muscle symptoms experience the same vascular benefit or whether statins affect striated and smooth muscle cells differently. We examined the effect of simvastatin treatment on arterial stiffness in patients who did versus those who did not exhibit muscle symptoms. Patients with a history of statin-related muscle complaints (n = 115) completed an 8 wk randomized, double-bl ...[more]

PMID: 26257959

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Project description:Statins, the 3-hydroxy-3-methyl-glutaryl (HMG)-CoA reductase inhibitors, are widely prescribed for treatment of hypercholesterolemia. Although statins are generally well tolerated, up to ten percent of patients taking statins experience muscle related adverse events. Myalgia, defined as muscle pain without elevated creatinine phosphokinase (CPK) levels, is the most frequent reason for discontinuation of statin therapy. The mechanisms underlying statin-associated myalgia are not clearly understood. To elucidate changes in gene expression associated with statin-induced myalgia, we compared profiles of gene expression in the biopsied skeletal muscle from statin-intolerant patients undergoing statin re-challenge versus those of statin-tolerant controls. A robust separation of statin-intolerant and statin-tolerant cohorts was revealed by Principal Component Analysis of differentially expressed genes (DEGs). To identify putative gene expression and metabolic pathways that may be perturbed in skeletal muscles of statin intolerant patients, we subjected DEGs to Ingenuity Pathways (IPA) and DAVID (Database for Annotation, Visualization and Integrated Discovery) analyses. The most prominent pathways altered by statins included cellular stress, apoptosis, senescence and DNA repair (TP53, BARD1, Mre11 and RAD51); activation of pro-inflammatory immune response (CXCL12, CST5, POU2F1); protein catabolism, cholesterol biosynthesis, protein prenylation and RAS-GTPase activation (FDFT1, LSS, TP53, UBD, ATF2, H-ras). Based on these data we tentatively conclude that persistent myalgia in response to statins may emanate from cellular stress underpinned by mechanisms of post-inflammatory repair and regeneration. We also posit that this subset of individuals are genetically predisposed to eliciting altered statin metabolism and/or increased end-organ susceptibility that lead to a range of statin-induced myopathies. This mechanistic scenario further bolstered by the discovery that a number of single nucleotide polymorphisms (e.g., SLCO1B1, SLCO2B1 and RYR2) associated with statin myopathy were observed with increased frequency among statin-intolerant study subjects.

Project description:Statins, the 3-hydroxy-3-methyl-glutaryl (HMG)-CoA reductase inhibitors, are widely prescribed for treatment of hypercholesterolemia. Although statins are generally well tolerated, up to ten percent of statin-treated patients experience myalgia symptoms, defined as muscle pain without elevated creatinine phosphokinase (CPK) levels. Myalgia is the most frequent reason for discontinuation of statin therapy. The mechanisms underlying statin myalgia are not clearly understood. To elucidate changes in gene expression associated with statin myalgia, we compared profiles of gene expression in skeletal muscle biopsies from patients with statin myalgia who were undergoing statin re-challenge (cases) versus those of statin-tolerant controls. A robust separation of case and control cohorts was revealed by Principal Component Analysis of differentially expressed genes (DEGs). To identify putative gene expression and metabolic pathways that may be perturbed in skeletal muscles of patients with statin myalgia, we subjected DEGs to Ingenuity Pathways (IPA) and DAVID (Database for Annotation, Visualization and Integrated Discovery) analyses. The most prominent pathways altered by statins included cellular stress, apoptosis, cell senescence and DNA repair (TP53, BARD1, Mre11 and RAD51); activation of pro-inflammatory immune response (CXCL12, CST5, POU2F1); protein catabolism, cholesterol biosynthesis, protein prenylation and RAS-GTPase activation (FDFT1, LSS, TP53, UBD, ATF2, H-ras). Based on these data we tentatively conclude that persistent myalgia in response to statins may emanate from cellular stress underpinned by mechanisms of post-inflammatory repair and regeneration. We also posit that this subset of individuals is genetically predisposed to eliciting altered statin metabolism and/or increased end-organ susceptibility that lead to a range of statin-induced myopathies. This mechanistic scenario is further bolstered by the discovery that a number of single nucleotide polymorphisms (e.g., SLCO1B1, SLCO2B1 and RYR2) associated with statin myalgia and myositis were observed with increased frequency among patients with statin myalgia.

Project description:ImportanceLimited studies have investigated the association between statin use and progression of arterial stiffness, a key player in the pathophysiology of cardiovascular disease.ObjectiveTo examine the association between statin use and progression of arterial stiffness in Chinese adults with high atherosclerotic risk measured by brachial-ankle pulse wave velocity (baPWV).Design, setting, and participantsThis retrospective cohort study enrolled 5105 adults with high atherosclerotic risk from the Kailuan General Hospital from 2010 to 2020. Data were analyzed from February 2021 to April 2022.ExposuresStatin use information was retrieved from electronic medical records from 2010 to 2020, and statin users were those who have been prescribed any statin medications at least 6 months before baPWV measurements. Statin users were 1:1 matched with non-statin users by propensity score method.Main outcomes and measuresProgression of baPWV was assessed using the absolute difference between baseline and follow-up baPWV, divided by the follow-up time in years. Multivariable linear regression models were used to estimate the association between statin use and arterial stiffness.ResultsAmong 5105 adults with assessment of baPWV (mean [SD] age: 60.8 [9.7] years; 3842 [75.3%] men and 1263 [24.7%] women), 1310 statin users were matched with 1310 non-statin users (mean [SD] age, 63.2 [9.3] years). Compared with non-statin users, statin users were associated with significantly lower baPWV at baseline (difference: -33.6 cm/s; 95% CI, -62.1 to -5.1 cm/s). Among 1502 adults with repeated assessment of baPWV, 410 statin users were matched with 410 non-statin users (mean [SD] age, 62.9 [9.2] years). Compared with non-statin users, statin users had significantly slower progression of baPWV (difference, -23.3 cm/s per year; 95% CI, -40.6 to -6.0 cm/s per year) during a mean (SD) follow-up of 4.8 (2.7) years. A significantly slower progression of baPWV was observed in continuous statin users (difference, -24.2 cm/s per year; 95% CI, -42.2 to -6.3 cm/s per year) and high adherent users (difference, -39.7 cm/s per year; 95% CI, -66.9 to -12.4 cm/s per year), but not in discontinued users (difference, -17.3 cm/s per year; 95% CI, -52.4 to 17.8 cm/s per year) and low adherent users (difference, -17.9 cm/s per year; 95% CI, -36.5 to 0.7 cm/s per year), compared with non-statin users.Conclusions and relevanceIn this cohort study, statin use was associated with slower progression of arterial stiffness in Chinese adults with high atherosclerotic risk.

Dataset Information

Effect of Simvastatin on Arterial Stiffness in Patients with Statin Myalgia.

Publications

Effect of Simvastatin on Arterial Stiffness in Patients with Statin Myalgia.

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