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Update - Week 22, 2018
 
Curated by Peter Lansberg,
a Dutch lipidologist and educator, and
reviewed by prof. Philip Barter, Past President of the
International Atherosclerosis Society.
The IAS Statin Newsletter will keep you up-to-date with all recent statin publications, using a curated approach to select relevant articles.

Key publications

Statins stroke and renal disease do they match?
Using data collected in the China National Stroke Registry, post stroke hospitalized patients (N=5 951) were stratified for estimated glomerular filtration rate (eGFR): normal renal function (eGFR ≥90 mL/min/1.73 m2), mild CKD (eGFR 60–90 mL/min/1.73 m2) and moderate CKD (eGFR < 60 mL/min/1.73 m2). Statins were used by 2 595 (43.6% of the admitted patients, 45.7%, 42.0% and 39.0% of the ones with normal, mild and moderate CKD respectively. The designated study endpoint was all cause mortality at three months. After correcting for confounders by employing a logistic regression statistical analysis, in all participants using statins total mortality was significantly reduced. In patient with normal renal function, OR 0.65 (0.43-0.97; p=0.04), mild CKD OR 0.59 (0.38-0.91; p=0.02) and moderate CKD OR 0.59 (0.23-0.75; p=0.004). The favorable results presented in this observational study design prompt for further in depth analyses by means of a randomized trial design to elucidate the benefits of statins in post-stroke CKD patients.
Zhang X, Jing J, Zhao X et al. Statin Use during Hospitalization and Short-Term Mortality in Acute Ischaemic Stroke with Chronic Kidney Disease. European neurology 2018; 79:296-302. http://www.ncbi.nlm.nih.gov/pubmed/?term=29852478
 
CEA patients need statins to reduce events?
Patients that undergo a carotid endarterectomy (CEA), are at high risk for developing a subsequent cerebral or cardiovascular event. The benefits of statins were evaluated in this meta-analysis of studies that included CEA patients. The authors collected data from 6 studies that included 7 053 participants, endpoints were evaluated after 30 days. Overall 157 patients (2.2%) experienced a stroke; in the statin-users 1.4% vs 3% in patients not using statins. This translated in an OR 0.40 (0.15-1.09; I2 =75.6%), hence no statistical significant difference. For myocardial infarctions within 30 days, no difference was detected between the two groups, OR 0.77 (0.26-2.24; I2 =77%). Total mortality did improve significantly in the statin users OR 0.26 (0.10-0.61; I2 = 17.7%). The authors concluded that based on this meta-analysis statin use was associated with a reduced mortality risk, despite the lack of significantly reducing MI’s and stroke’s; although numerical (1.6% absolute decrease) the latter was reduced as well. Randomized trials are needed to provide a reliable answer.
Texakalidis P, Giannopoulos S, Kokkinidis DG et al. Outcome of Carotid Artery Endarterectomy in Statin-users versus Statin-naive patients: A Systematic Review and Meta-analysis. World neurosurgery 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29859356
 
Carotid ultrasound predicts plaque vulnerabilities
Which ultrasonic carotid plaque features reflect histopathological predictors of plaque instability? The authors of this article collected data from 70 patients scheduled for a carotid endarterectomy, allowing them to compare imaging based on ultrasound examination prior to the intervention with histopathological features obtained from the surgically removed plaque.  Having a low median grey scale as well as discrete white areas were associated with increased macrophages, increased neovascularization, larger lipid core, intraplaque hemorrhages, plaque ruptures and a decrease in smooth muscle cells (SMC). The presence of a so called juxta-luminal black (JBA) area, reflected a decrease in the number of SMC’s, larger lipid core and plaque ruptures. Patients that had a thin fibrous cap, with either a large lipid cored or a plaque rupture, were found to have increased manifestation of JBA (65%). Statins were associated with a decreased number of macrophages (P=0.039), neovascularization’s (p=0.019) and increased number of SMC’s (p=0.023). the results from this study provide important clues which non-invasive ultrasonic plaque features, are prognostic of imminent vascular events. Using ultra-sound evaluations for stroke predictions seems to be an attractive approach. Statins were associated with improved histopathological plaque features. Carotid ultrasound appraisals in patient at risk for stroke plus by repeated follow up measurements after initiating medical therapy, could potentially be used to not only monitor improvements but also motivate patients to continue using their medication.
Spanos K, Tzorbatzoglou I, Lazari P et al. Carotid artery plaque echomorphology and its association with histopathologic characteristics. Journal of vascular surgery 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29803682
 
Statins and prevention of hospitalizations for infection
The benefits of statins are purportedly stretching beyond their cardiovascular protective role. As the authors of this study point out, there is accumulating evidence, from in vitro and in vivo studies that statins possess antibacterial properties. To explore this fact the administrative databases, containing medical information of the total population of the Italian province of Tuscany, were queried to compare hospitalizations for infections between statin users and non-users. The study period was from 1st January 1st, 2011 – December 31st, 2015. During this period 45 599 hospital discharges for infections were registered. Statin users (N=52 049) were matched, using an elaborate propensity score and were divided in 5 prescribed daily doses (PDD) classes; 0-20%, 20-50%, 50-80%, 80-100% and >100%. Atorvastatin 20 mg was used as the WHO reference of defined daily dosage (DDD). Unmatched, statin users reported more hospitalizations compared to controls, but after matching statin use was associated with a significant reduced rate of hospitalizations for infections, but only in patients with a PDD >20%.  Benefits amounted to a NNT to prevent 1 hospitalization for infection of 54-102 across the different treatment dosage classes.  This is similar to the NNT for primary prevention of CHD of 72-119!
Policardo L, Seghieri G, Gualdani E, Franconi F. Effect of statins in preventing hospitalizations for infections: A population study. Pharmacoepidemiol Drug Saf 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29808503
 
Elevated TG’s and residual risk in statin treated patients
Residual risk in patient treated with statins remains an elusive phenomenon. The authors of this study explored the US Kayser Permanente databases including 4.5 million individuals. Patients were included if their TG measurements were performed between 2010 and December 2016, for a maximum follow up period of 6.5 years. Patients (aged ≥45 years), diagnosed with CVD, treated with statins only and LDL-c 40-100 mg/dl were divided in patients with TG <150mg/dl (N=14 481) or 200-499 mg/dl (N=2 702). Study outcomes were defined as primary outcomes, a composite of non-fatal MI, non-fatal stroke, unstable angina, coronary revascularization, and all-cause mortality, and a second composite adding peripheral revascularization and aneurysm repair. After multivariate regression the adjusted secondary endpoints were reached by more patients in the high TG group, 50.9/1,000 person-years (47.0-55.2) vs. 46.5 (44.8-48.2); RR 1.10 (1.00-1.20, p=0.041). The endpoints responsible for these differences were non-fatal MI, RR 1.20 (1.00-1.45, p=0.045), coronary revascularization RR 1.18 (1.00-1.40, p=0.045) and peripheral revascularization RR 1.56 (1.14-2.13, p=0.006). The authors concluded that elevated triglycerides could explain part of the residual risk observed in statin treated CVD patients.
Nichols GA, Philip S, Reynolds K et al. Increased Cardiovascular Risk in Hypertriglyceridemic Patients with Statin-Controlled LDL Cholesterol. J Clin Endocrinol Metab 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29850861
Relevant publications
  1. Song PS, Ryu DR, Kim MJ et al. Risk Scoring System to Assess Outcomes in Patients Treated with Contemporary Guideline-Adherent Optimal Therapies after Acute Myocardial Infarction. Korean Circ J 2018; 48:492-504. http://www.ncbi.nlm.nih.gov/pubmed/?term=29856143
  2. Bandyopadhyay D, Qureshi A, Ghosh S et al. Safety and Efficacy of Extremely Low LDL-Cholesterol Levels and Its Prospects in Hyperlipidemia Management. Journal of lipids 2018; 2018:8598054. http://www.ncbi.nlm.nih.gov/pubmed/?term=29850255
  3. Ngo-Metzger Q, Zuvekas SH, Bierman AS. Estimated Impact of US Preventive Services Task Force Recommendations on Use and Cost of Statins for Cardiovascular Disease Prevention. Journal of general internal medicine 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29855861
  4. Lee H, Choi JM, Cho JY et al. Regulation of Endogenic Metabolites by Rosuvastatin in Hyperlipidemia Patients: An Integration of Metabolomics and Lipidomics. Chemistry and physics of lipids 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29852124
  5. Lamprecht DG, Jr., Shaw PB, King JB et al. Trends in high-intensity statin use and low-density lipoprotein cholesterol control among patients enrolled in a clinical pharmacy cardiac risk service. J Clin Lipidol 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29803357
  6. Klarin D, Cambria RP, Ergul EA et al. Risk factor profile and anatomic features of previously asymptomatic patients presenting with carotid-related stroke. Journal of vascular surgery 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29804741
  7. King K, Macken A, Blake O, O'Gorman CS. Cholesterol screening and statin use in children: a literature review. Irish journal of medical science 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29858795
  8. Kim W, Yoon YE, Shin SH et al. Efficacy and Safety of Ezetimibe and Rosuvastatin Combination Therapy Versus Those of Rosuvastatin Monotherapy in Patients With Primary Hypercholesterolemia. Clinical therapeutics 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29857919
  9. Jaspers NEM, Visseren FLJ, Numans ME et al. Variation in minimum desired cardiovascular disease-free longevity benefit from statin and antihypertensive medications: a cross-sectional study of patient and primary care physician perspectives. BMJ Open 2018; 8:e021309. http://www.ncbi.nlm.nih.gov/pubmed/?term=29804065
  10. Devereaux PJ. Suboptimal Outcome of Myocardial Infarction After Noncardiac Surgery: Physicians Can and Should Do More. Circulation 2018; 137:2340-2343. http://www.ncbi.nlm.nih.gov/pubmed/?term=29844070
  11. Bartlett LE, Pratt NL, Roughead EE. Prior experience with cardiovascular medicines predicted longer persistence in people initiated to combinations of antihypertensive and lipid-lowering therapies: findings from two Australian cohorts. Patient preference and adherence 2018; 12:835-843. http://www.ncbi.nlm.nih.gov/pubmed/?term=29805251
  12. Athyros VG, Doumas M, Imprialos KP et al. Diabetes and lipid metabolism. Hormones (Athens, Greece) 2018; 17:61-67. http://www.ncbi.nlm.nih.gov/pubmed/?term=29858856
  13. Zou R, Shi W, Tao J et al. Efficacy of Statin Therapy Related to Baseline Renal Function in Patients with Rheumatic Heart Disease Undergoing Cardiac Surgery. BioMed research international 2018; 2018:5972064. http://www.ncbi.nlm.nih.gov/pubmed/?term=29850539
  14. Wang Y, Kuang ZM, Feng SJ et al. Combined antihypertensive and statin therapy for the prevention of cardiovascular events in patients with hypertension without complications: protocol for a systematic review and meta-analysis. BMJ Open 2018; 8:e019719. http://www.ncbi.nlm.nih.gov/pubmed/?term=29858408
  15. Uransilp N, Chaiyawatthanananthn P, Muengtaweepongsa S. Efficacy of High-Dose and Low-Dose Simvastatin on Vascular Oxidative Stress and Neurological Outcomes in Patient with Acute Ischemic Stroke: A Randomized, Double-Blind, Parallel, Controlled Trial. Neurology research international 2018; 2018:7268924. http://www.ncbi.nlm.nih.gov/pubmed/?term=29850244
  16. Tran PT, Meeker AK, Platz EA. Association between statin drug use and peripheral blood leukocyte telomere length in the National Health and Nutrition Examination Survey 1999-2002: a cross-sectional study. Annals of epidemiology 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29853162
  17. Rocha KCE, Pereira BMV, Rodrigues AC. An update on efflux and uptake transporters as determinants of statin response. Expert Opin Drug Metab Toxicol 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29842801
  18. Murai K, Sakata K, Mabuchi T et al. Very late bare metal stent thrombosis in the setting of discontinuation of optimal medical therapy for 2 years. Cardiovascular diagnosis and therapy 2018; 8:186-189. http://www.ncbi.nlm.nih.gov/pubmed/?term=29850411
  19. Mosepele M, Molefe-Baikai OJ, Grinspoon SK, Triant VA. Benefits and Risks of Statin Therapy in the HIV-Infected Population. Current infectious disease reports 2018; 20:20. http://www.ncbi.nlm.nih.gov/pubmed/?term=29804227
  20. Liu Y, Chen T, Xing J. Effect of rosuvastatin on the expression of candidate gene GALNT3 in atherosclerosis. Experimental and therapeutic medicine 2018; 15:4880-4884. http://www.ncbi.nlm.nih.gov/pubmed/?term=29805509
  21. Liu C, Liu Q, Xiao X. Effectiveness and safety of combinational therapy compared with intensified statin monotherapy in patients with coronary heart disease. Experimental and therapeutic medicine 2018; 15:4683-4688. http://www.ncbi.nlm.nih.gov/pubmed/?term=29805487
  22. Li Y, Zhao SP, Li Y. [Periprocedural high-dose statin strategy shown no benefits on clinical outcomes in patients with coronary artery disease undergoing percutaneous coronary interventions]. Zhonghua xin xue guan bing za zhi 2018; 46:338-340. http://www.ncbi.nlm.nih.gov/pubmed/?term=29804433
  23. Jiang LY, Jiang YH, Qi YZ et al. Integrated analysis of long noncoding RNA and mRNA profiling ox-LDL-induced endothelial dysfunction after atorvastatin administration. Medicine (Baltimore) 2018; 97:e10949. http://www.ncbi.nlm.nih.gov/pubmed/?term=29851839
  24. Hjelmesaeth J, Asberg A, Andersson S et al. Impact of body weight, low energy diet and gastric bypass on drug bioavailability, cardiovascular risk factors and metabolic biomarkers: protocol for an open, non-randomised, three-armed single centre study (COCKTAIL). BMJ Open 2018; 8:e021878. http://www.ncbi.nlm.nih.gov/pubmed/?term=29844102
  25. Degala S, Bathija NA. Evaluation of the Efficacy of Simvastatin in Bone Regeneration after Surgical Removal of Bilaterally Impacted Third Molars-A Split-Mouth Randomized Clinical Trial. Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29859160
  26. Burkholder GA, Muntner P, Zhao H et al. Low-density lipoprotein cholesterol response after statin initiation among persons living with human immunodeficiency virus. J Clin Lipidol 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29853312
  27. Anroedh SS, Hilvo M, Akkerhuis KM et al. Plasma concentrations of molecular lipid species predict long-term clinical outcome in coronary artery disease patients. Journal of lipid research 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29858423
  28. Andrade Lopes S, Fumani C, Jornayvaz FR et al. [Dyslipidemia management in patients with type 1 diabetes]. Revue medicale suisse 2018; 14:1118-1122. http://www.ncbi.nlm.nih.gov/pubmed/?term=29851318
Miscellaneous publications
 
 
  1. Yorulmaz H, Ozkok E, Kaptan E et al. Therapeutic Effects of Simvastatin on Galectin-3, and Oxidative Stress parameters in Lung Tissue in Endotoxemia. Bioscience reports 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29853535
  2. Wang L, Lin R, Guo L, Hong M. Rosuvastatin relieves myocardial ischemia/reperfusion injury by upregulating PPARgamma and UCP2. Mol Med Rep 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29845235
  3. Kato S, Liberona MF, Cerda-Infante J et al. Simvastatin interferes with cancer 'stem-cell' plasticity reducing metastasis in ovarian cancer. Endocrine-related cancer 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29848667
  4. Hu X, Song C, Fang M, Li C. Erratum: Simvastatin inhibits the apoptosis of hippocampal cells in a mouse model of Alzheimer's disease. Experimental and therapeutic medicine 2018; 15:5153. http://www.ncbi.nlm.nih.gov/pubmed/?term=29809201
  5. Han J, Yin QH, Fang Y et al. Atorvastatin protects BV2 mouse microglia and hippocampal neurons against oxygenglucose deprivationinduced neuronal inflammatory injury by suppressing the TLR4/TRAF6/NFkappaB pathway. Mol Med Rep 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29845194
  6. Dolci GS, Ballarini A, Gameiro GH et al. Atorvastatin inhibits osteoclastogenesis and arrests tooth movement. American journal of orthodontics and dentofacial orthopedics : official publication of the American Association of Orthodontists, its constituent societies, and the American Board of Orthodontics 2018; 153:872-882. http://www.ncbi.nlm.nih.gov/pubmed/?term=29853245
  7. AlSwafeeri H, ElKenany W, Mowafy M, Karam S. Effect of local administration of simvastatin on postorthodontic relapse in a rabbit model. American journal of orthodontics and dentofacial orthopedics : official publication of the American Association of Orthodontists, its constituent societies, and the American Board of Orthodontics 2018; 153:861-871. http://www.ncbi.nlm.nih.gov/pubmed/?term=29853244
  8. Lee H, Lee H, Na CB, Park JB. Effects of Simvastatin on the Viability and Secretion of Vascular Endothelial Growth Factor of Cell Spheroids Cultured in Growth Media. Implant dentistry 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29846274
  9. Eskinazi-Budge A, Manickavasagam D, Czech T et al. Preparation of Emulsifying Wax/GMO Nanoparticles and Evaluation as a Delivery System for Repurposing Simvastatin in Bone Regeneration. Drug development and industrial pharmacy 2018:1-26. http://www.ncbi.nlm.nih.gov/pubmed/?term=29847182
  10. Araujo-Lima CF, Christoni LSA, Justo G et al. Atorvastatin Downregulates In Vitro Methyl Methanesulfonate and Cyclophosphamide Alkylation-Mediated Cellular and DNA Injuries. Oxidative medicine and cellular longevity 2018; 2018:7820890. http://www.ncbi.nlm.nih.gov/pubmed/?term=29849914
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