Dataset Information

Association of vitamin D and incident statin induced myalgia--a retrospective cohort study.

ABSTRACT:

Background and objectives

Evidence is conflicting with regards to the role of vitamin D in statin induced myalgia (SIM). Studies so far have assessed cross-sectional association and were limited by study sample selected predominantly from cardiology clinics. In this retrospective cohort study we assessed the association between vitamin D and SIM and attempted to establish a serum vitamin D cutoff to identify patients at risk for developing SIM.

Methods

Medical charts of 5526 consecutive patients from a primary care practice in Scranton, Pennsylvania from 2005-2012 were reviewed. Vitamin D level (25-hydroxy cholecalciferol) at statin initiation was considered "Exposure level". Vitamin D levels were categorized into quartiles (? 10, 11-20, 21-30, >30 ng/ml). SIM was identified by patient report.

Results

1160 out of 5526 patients were treated with statins. The mean age was 55.9 years. 276 (24%) developed SIM. Unadjusted 7-yr cumulative incidences of SIM for quartiles 1-4 of vitamin D were 32.3, 21.5, 18.3 and 14.6% respectively. The lowest quartile of vitamin D was independently associated with 1.21 times the hazard of the fourth quartile for developing SIM (95% CI: 1.09, 1.33; P-trend ?=?0.001). Vitamin D cut-off ?15 ng/ml, showed a positive predictive value, negative predictive value, likelihood ratio (LR) + and LR- of 81, 90, 5.1 and 0.1, respectively for predicting SIM.

Conclusions

Low vitamin D level at statin initiation is associated with SIM, levels ?15 ng/ml have a high predictive accuracy for SIM. Randomized controlled trials are needed to validate our results.

SUBMITTER: Palamaner Subash Shantha G

PROVIDER: S-EPMC3929495 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Publications

Association of vitamin D and incident statin induced myalgia--a retrospective cohort study.

Palamaner Subash Shantha Ghanshyam G Ramos Julio J Thomas-Hemak Linda L Pancholy Samir Bipin SB

PloS one 20140219 2

<h4>Background and objectives</h4>Evidence is conflicting with regards to the role of vitamin D in statin induced myalgia (SIM). Studies so far have assessed cross-sectional association and were limited by study sample selected predominantly from cardiology clinics. In this retrospective cohort study we assessed the association between vitamin D and SIM and attempted to establish a serum vitamin D cutoff to identify patients at risk for developing SIM.<h4>Methods</h4>Medical charts of 5526 conse ...[more]

PMID: 24586424

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Project description:INTRODUCTION:Musculoskeletal conditions, including osteoarthritis (OA), result in tremendous disability and cost. Statins are among the most commonly prescribed medications and their use for primary prevention in many otherwise healthy individuals, including those who are physically active, is increasing. There is conflicting evidence regarding the relationship of statin use and musculoskeletal conditions. Given the rising disability associated with musculoskeletal conditions, understanding predisposing factors, including medication-related exposures, deserves further attention. OBJECTIVES:We examined the association between statin use and the risk of being diagnosed with non-traumatic arthropathies, use-related injury, and undergoing rehabilitation in a cohort with longitudinal follow-up. METHODS:Patients enrolled in a regional military healthcare system between 2003 and 2012 were evaluated in this retrospective cohort study. A propensity score was generated to match statin-users and nonusers using 115 baseline characteristics. Outcomes included ICD-9 diagnoses codes for Agency for Healthcare Research and Quality disease categories of: non-traumatic arthropathies, use-related injury and undergoing rehabilitation. Primary analysis examined the outcomes in statin-users and nonusers after propensity score matching using conditional logistic regression analysis. RESULTS:Initially, 60,455 patients were identified. We propensity score-matched 6728 statin users with 6728 nonusers (52 years of age,?~?47% women). In the propensity score-matched cohort, non-traumatic arthropathies occurred in 59.8% of statin users and 56.0% of nonusers [odds ratio (OR) 1.17, 95% confidence interval (95% CI) 1.09-1.25] and use related injury occurred in 31.9% of statin users and 29.8% of nonusers (OR 1.11, 95% CI 1.03-1.19). There was no difference between statin users and nonusers undergoing rehabilitation (22.6% among statin users, 21.9% among nonusers, OR 1.04, 95% CI 0.96-1.13). CONCLUSION:Statin use was associated with a significant increased risk of non-traumatic arthropathies and use-related injury. Our results provide additional data that can inform patient and clinician conversations about the benefits and risks of statin use.

Project description:BackgroundPulmonary hypertension incidence based on echocardiographic estimates of pulmonary artery systolic pressure in people living with HIV remains unstudied. We aimed to determine whether people living with HIV have higher incidence and risk of pulmonary hypertension than uninfected individuals.MethodsIn this retrospective cohort study, we evaluated data from participants in the Veterans Aging Cohort Study (VACS) referred for echocardiography with baseline pulmonary artery systolic pressure measures of 35 mm Hg or less. Incident pulmonary hypertension was defined as pulmonary artery systolic pressure higher than 35 mm Hg on subsequent echocardiogram. We used Poisson regression to estimate incidence rates (IRs) of pulmonary hypertension by HIV status. We then estimated hazard ratios (HRs) by HIV status using Cox proportional hazards regression. We further categorised veterans with HIV by CD4 count or HIV viral load to assess the association between pulmonary hypertension risk and HIV severity. Models included age, sex, race or ethnicity, prevalent heart failure, chronic obstructive pulmonary disease, hypertension, smoking status, diabetes, body-mass index, estimated glomerular filtration rate, hepatitis C virus infection, liver cirrhosis, and drug use as covariates.FindingsOf 21 314 VACS participants with at least one measured PASP on or after April 1, 2003, 13 028 VACS participants were included in the analytic sample (4174 [32%] with HIV and 8854 [68%] without HIV). Median age was 58 years and 12 657 (97%) were male. Median follow-up time was 3·1 years (IQR 0·9-6·8) spanning from April 1, 2003, to Sept 30, 2017. Unadjusted IRs per 1000 person-years were higher in veterans with HIV (IR 28·6 [95% CI 26·1-31·3]) than in veterans without HIV (IR 23·4 [21·9-24·9]; p=0·0004). The risk of incident pulmonary hypertension was higher among veterans with HIV than among veterans without HIV (unadjusted HR 1·25 [95% CI 1·12-1·40], p<0·0001). After multivariable adjustment, this association was slightly attenuated but remained significant (HR 1·18 [1·05-1·34], p=0·0062). Veterans with HIV who had a CD4 count lower than 200 cells per μL or of 200-499 cells per μL had a higher risk of pulmonary hypertension than did veterans without HIV (HR 1·94 [1·49-2·54], p<0·0001, for those with <200 cell μL and HR 1·29 [1·08-1·53], p=0·0048, for those with 200-499 cells per μL). Similarly, veterans with HIV who had HIV viral loads of 500 copies per mL or more had a higher risk of pulmonary hypertension than did veterans without HIV (HR 1·88 [1·46-2·42], p<0·0001).InterpretationHIV is associated with pulmonary hypertension incidence, adjusting for risk factors. Low CD4 cell count and high HIV viral load contribute to increased pulmonary hypertension risk among veterans with HIV. Thus, as with other cardiopulmonary diseases, suppression of HIV should be prioritised to lessen the burden of pulmonary hypertension in people living with HIV.FundingNational Heart, Lung, and Blood Institute (National Institutes of Health, USA); National Institute on Alcohol Abuse and Alcoholism (National Institutes of Health, USA).

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.

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Dataset Information

Association of vitamin D and incident statin induced myalgia--a retrospective cohort study.

Background and objectives

Methods

Results

Conclusions

Publications

Association of vitamin D and incident statin induced myalgia--a retrospective cohort study.

Similar Datasets

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