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Update - Week 25, 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

Can we predict statin response?
Determining statin response by measuring simple biomarkers is quite relevant in clinical practice. In this analysis the authors determined the impact of Thyroid function and statin response. Correlations between TSH and lipid concentrations have been well accepted but in this cohort of 1091 of consecutive Chinese hospitalized AMI patients FT3 surfaced as a potential marker to predict the lipid lowering effects of statins. The participants were divided in 3 groups base on statin intensity; 221 patients used low intensity, 712 intermediate and 158 high intensity statins. Lipids were re-measured after 10-14 days of statin therapy and FT3 levels compared to LDL-c goals achieved. In the group using high intensity statins there was clear and significant correlations between FT3 Concentrations and plasma LDL-c (LDL-C: r = -0.113, P = 0.005; TC: r = -0.172, P = 0.029). Less distinct but still significant in the patients using intermediate intensity statins (LDL-C =-0.082, P = 0.001; TC: r = -0.105, P = 0.031). Low intensity statin use showed no correlation with FT3. Goal achievement was more likely in the patients that had high plasma concentrations of FT3 (>2,95 pg./ml) vs low FT3 (<1,79 pg./ml). Achieving an LDL-c < 3.0 mmol/l; OR 2.217 (1.001-4.839). For an LDL-c < 1.8 mmol/l; OR 2.836 (1.014-5.182). The other markers of thyroid function (TSH, FT4, TT4 and TT3) did not show any correlations with statin response. Despite the limitations of this study (e.g. short statin treatment period of 10-14 days) these finding deserve further exploration.
Wang WY, Zhang K, Zhao W et al. Free triiodothyronine level correlates with statin responsiveness in acute myocardial infarction. Journal of geriatric cardiology : JGC 2018; 15:290-297. http://www.ncbi.nlm.nih.gov/pubmed/?term=29915619
 
Atorvastatin benefits patient’s post-surgery for chronic subdural hematoma’s
Statins have proven their value in preventing ASCVD events, what remains unclear is their ant thrombotic properties and more specifically the risk associated with bleeding complications in stroke patients. In this study patient that had surgery for chronic subdural hematoma’s (CSDH) were evaluated for post procedural bleeding complications while using atorvastatin, 20 mg < 3 days postop until imaging data confirmed significant/complete CSDH resolution. This was a retrospective analysis of 245 consecutive Chinese patients from a single hospital that had a but hole craniotomy. Postop complications and mortality were not different in patients using atorvastatin vs no statin. Recurrence rates were significantly influenced in patients using atorvastatin. In patients that had surgery without atorvastatin, 15% experience a recurrence, this was 4.8% in patients that used atorvastatin. Predictors of CSDH recurrence were: atorvastatin, diabetes mellitus and preop Glasgow Coma Scale (GCS) score >15, OR’s 0.336 (p=0.039), 3.949 (P =0.01) and 0.197 (P=0.020) respectively. The authors concluded that atorvastatin use was associated with reduced recurrence rates and did not have a negative impact on postop (bleeding) complication and mortality in patients that had surgery for CSDH. Properly designed randomized trials are warranted to confirm these findings.
Tang R, Shi J, Li X et al. Effects of Atorvastatin on Surgical Treatments of Chronic Subdural Hematoma. World neurosurgery 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29920396
 
Statins after carotid artery stenting reduce postop complications and mortality
Are patients that undergo carotid stenting (CAS) equally well-off when using statins as post carotid endarterectomy patients? To discover the effects of statins after CAS the authors retrospectively explored the Primary Health Care database. During the period 2009 -2015, 17 800 patients had CAS and 12 416 (70%) were prescribed statins. Statin users were at higher CVD risk; there were more symptomatic patients (41% vs 31%; P<0.001) and more extensive co-morbidities (hypertension, diabetes, coronary artery disease, dyslipidemia, history of congestive heart failure, history of stroke, history of myocardial infarction (MI), and peripheral artery disease (all P<0.05). No Statin benefits were noted on postop stroke OR 1.09 (0.88-1.44; P=0.44) and an increased risk of MI was noted; OR 2.08 (1.26-23.45; P0.004). Postop mortality was reduced in patients using statins 1.0 % vs 1.8%; p<0.01. After multivariate adjustment, statins improved the odds ratios for mortality and stroke/death, OR 0.36 (0.27-0,47; p<0.01) and OR 0.81 (0.68-0.99; p0.03) respectively. In patients that suffered a stroke or MI, statin users had significantly fewer major complications e.g. failure to rescue and lower mortality; 11.4% vs 30.88% (P < .001). Mortality doubled in non-statin users that developed major complications of stroke and MI after CAS (21.5% vs 10.6%; P < .001). After MLR analysis, statins reduced mortality by 63% in this subgroup OR 0.37; (0.22-0.61; P<0.001). The authors concluded that statin use in CAS patients provided added protection. Properly designed studies are warranted to replicate the results as well exploring optimal duration and dosage of statin therapy.
Rizwan M, Faateh M, Aridi HD et al. Statins reduce mortality and failure to rescue after carotid artery stenting. Journal of vascular surgery 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29914834
 
The PARADIGM registry evaluated statins by coronary CTA
The Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography IMaging PARADIGM study evaluated the impact of statins on individual coronary plagues. This observational registry collected data of 2 250 patients, recruited at 13 sites in 7 countries (Brazil, Canada, Germany, Italy, Portugal, South Korea, and US). Patients scheduled for a coronary CTA and with suspected or know CAD, were consecutively enrolled between 2003 and 2015. The CTA was repeated after an interscan period of ≥2years. For the final analysis 1 355 patients were evaluated and subdivided in statin naïve (N=474) and statin users (N=781). Coronary plaques were quantitively analyzed for percent diameter stenosis (%DS), percent atheroma volume (PAV), plaque composition and the presence of high risk plaques (HRP): ≥2 characteristics of low attenuation plaque, positive arterial remodeling or spotty calcifications. Overall 1 079 coronary artery lesions were evaluated showing reduced PAV progression, 1.76 ± 2.40%/yr. vs. 2.04 ± 2.37%/yr. (p = 0.002) accelerated progression of calcified PAV 1.27 ± 1.54%/yr. vs. 0.98 ± 1.27%/yr. (p < 0.001). Progression of noncalcified PAV and annual incidence of new HRP features lesions were observed less in in statin-taking patients (0.49 ± 2.39%/yr. per year vs. 1.06 ± 2.42%/yr. and 0.9% per year vs. 1.6% per year, respectively (all p<0.001). The rates of progression to >50% DS were not significantly different, 1.0% vs. 1.4%, respectively (p > 0.05). Statins were associated with a 21% reduction in annualized total PAV progression above the median and 35% reduction in HRP development. The authors concluded that statins were unable to arrest the progression of the percentage stenosis severity but successfully reduced the risk full characteristics of the plaques, and increased calcification could reflect this as well and slowed the progression of coronary atherosclerosis volume.
Lee SE, Chang HJ, Sung JM et al. Effects of Statins on Coronary Atherosclerotic Plaques: The PARADIGM (Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography Imaging) Study. JACC. Cardiovascular imaging 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29909109
 
Accelerated CAC progression in Japanese patients with elevated Lp(a)
To study the effects of Lp(a) on atherosclerosis, changes in coronary calcium (CAC) progression were reviewed in a sub-analysis of the multi center prospective Effect of pitavastatin and EPA on coronary artery calcification detected by computed tomography (PEACH) study. In this study Japanese hypercholesterolemic patients with a CAC score of 1-999 were randomly allocated to pitavastatin 2 mg, 4 mg or 2 mg plus eicosapentaenoic acid (EPA). Patients were evaluated at baseline and after 1 year. For the final analysis 147 participants were evaluated. They were divided into 3 groups, based on CAC progression: CAC < 0 ; ≤100 and > 100. The percentage of patients with Lp(a) >30 mg/dl significantly increased in the higher CAC ranges: 5.4%, 7.7% and 23.6% respectively. Logistic regression analysis showed that elevated Lp(a) was an associated with CAC progression over a 1-year period, OR: 5.51 (1.28-23.68; p=0.02). This was after corrections for age, gender, hypertension, diabetes, smoking status, BMI and lipid lowering drug. The authors concluded that Lp(a) levels predicted CAC progression in hypercholesterolemic Japanese patients using statins.
Ida J, Kotani K, Miyoshi T et al. High Baseline Lipoprotein(a) Level as a Risk Factor for Coronary Artery Calcification Progression: Sub-analysis of a Prospective Multicenter Trial. Acta medica Okayama 2018; 72:223-230. http://www.ncbi.nlm.nih.gov/pubmed/?term=29925999
Relevant publications
  1. Vilahur G, Ben-Aicha S, Diaz E et al. Phytosterols and inflammation. Curr Med Chem 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29932029
  2. Toure PS, Leye YM, Diop MM et al. [Thrombocytopenia purpura, myositis and cytolitic hepatitis: a rare association linked with atorvastatin]. Le Mali medical 2013; 28:49-51. http://www.ncbi.nlm.nih.gov/pubmed/?term=29925222
  3. Skeldon SC, Carleton B, Brophy J et al. Statin Medications and the Risk of Gynecomastia. Clinical endocrinology 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29923212
  4. Rezende LFM, Rey-Lopez JP, Sa TH et al. Reporting bias in the literature on the associations of health-related behaviors and statins with cardiovascular disease and all-cause mortality. PLoS biology 2018; 16:e2005761. http://www.ncbi.nlm.nih.gov/pubmed/?term=29912869
  5. Lemaster KA, Frisbee SJ, DuBois L et al. CHRONIC ATORVASTATIN AND EXERCISE CAN PARTIALLY REVERSE ESTABLISHED SKELETAL MUSCLE MICROVASCULOPATHY IN METABOLIC SYNDROME. American journal of physiology. Heart and circulatory physiology 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29932769
  6. Kozlov SG, Khamchieva LS, Pogorelova OA et al. [Dynamics of asymptomatic atherosclerosis of carotid arteries depending on the achieved level of cholesterol in moderate-risk patients]. Angiologiia i sosudistaia khirurgiia = Angiology and vascular surgery 2018; 24:11-18. http://www.ncbi.nlm.nih.gov/pubmed/?term=29924771
  7. Hartgers ML, Besseling J, Stroes ES et al. Achieved LDL cholesterol levels in patients with heterozygous familial hypercholesterolemia: A model that explores the efficacy of conventional and novel lipid-lowering therapy. J Clin Lipidol 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29934068
  8. Fujisue K, Nagamatsu S, Shimomura H et al. Impact of statin-ezetimibe combination on coronary atheroma plaque in patients with and without chronic kidney disease - Sub-analysis of PRECISE-IVUS trial. Int J Cardiol 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29925472
  9. Dyg Sperling C, Verdoodt F, Kjaer Hansen M et al. Statin use and mortality among endometrial cancer patients: a Danish nationwide cohort study. International journal of cancer. Journal international du cancer 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29923185
  10. De Ferrari GM, Perna GP, Nicosia A et al. Available oral lipid-lowering agents could bring most high-risk patients to target: an estimate based on the Dyslipidemia International Study II-Italy. Journal of cardiovascular medicine (Hagerstown, Md.) 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29917002
  11. Burton JK, Papworth R, Haig C et al. Statin Use is Not Associated with Future Long-Term Care Admission: Extended Follow-Up of Two Randomised Controlled Trials. Drugs Aging 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29916140
  12. Borgquist S, Bjarnadottir O, Kimbung S, Ahern TP. Statins - a role in breast cancer therapy? Journal of internal medicine 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29923256
  13. Ballantyne CM, Banach M, Mancini GBJ et al. Efficacy and safety of bempedoic acid added to ezetimibe in statin-intolerant patients with hypercholesterolemia: A randomized, placebo-controlled study. Atherosclerosis 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29910030
  14. Akouchekian S, Omranifard V, Moshfegh P et al. The Effect of Atorvastatin on Obsessive-compulsive Symptoms of Refractory Obsessive-compulsive Disorder (Add-on Therapy). Advanced biomedical research 2018; 7:90. http://www.ncbi.nlm.nih.gov/pubmed/?term=29930930
  15. Abd Elgwad ER, Behiry EG, Swailem FM et al. Association between Q192R polymorphism in the PON1 gene and statin responses in cardiac patients. Annals of medicine and surgery (2012) 2018; 31:1-5. http://www.ncbi.nlm.nih.gov/pubmed/?term=29922459
  16. Zhao J, Xu C, Yao J et al. Statins and Thyroid Carcinoma: a Meta-Analysis. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 2018; 47:1422-1431. http://www.ncbi.nlm.nih.gov/pubmed/?term=29929194
  17. Yoshida K, Guo C, Sane R. Quantitative prediction of OATP-mediated drug-drug interactions with model-based analysis of endogenous biomarker kinetics. CPT Pharmacometrics Syst Pharmacol 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29924471
  18. Sequeira Gross T, Naito S, Neumann N et al. Does statin therapy impact the proximal aortopathy in aortic valve disease? QJM : monthly journal of the Association of Physicians 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29917097
  19. Nunez-Manchon J, Ballester-Lopez A, Koehorst E et al. Manifesting heterozygotes in McArdle disease: a myth or a reality-role of statins. Journal of inherited metabolic disease 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29926259
  20. Lebo NL, Griffiths R, Hall S et al. Effect of statin use on oncologic outcomes in head and neck squamous cell carcinoma. Head & neck 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29934959
  21. Goyal A, Cooper HA, Aronow WS et al. Use of Statins for Primary Prevention - Selection of Risk Threshold and Implications across Race and Gender. Am J Med 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29928863
  22. Forouzanfar F, Butler AE, Banach M et al. Modulation of heat shock proteins by statins. Pharmacol Res 2018; 134:134-144. http://www.ncbi.nlm.nih.gov/pubmed/?term=29935271
  23. Dong R, Ma G, Zhang S et al. Simvastatin reverses multiple myeloma serum-induced prothrombotic phenotype in endothelial cells via ERK 1/2 signalling pathway. Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29916838
  24. de Sa A, Hart DA, Khan K, Scott A. Achilles tendon structure is negatively correlated with body mass index, but not influenced by statin use: A cross-sectional study using ultrasound tissue characterization. PLoS One 2018; 13:e0199645. http://www.ncbi.nlm.nih.gov/pubmed/?term=29928054
  25. Bird JK, Calder PC, Eggersdorfer M. The Role of n-3 Long Chain Polyunsaturated Fatty Acids in Cardiovascular Disease Prevention, and Interactions with Statins. Nutrients 2018; 10. http://www.ncbi.nlm.nih.gov/pubmed/?term=29914111
  26. Pitavastatin magnesium (Zypitamag) for hyperlipidemia. The Medical letter on drugs and therapeutics 2018; 60:106. http://www.ncbi.nlm.nih.gov/pubmed/?term=29913475
Miscellaneous publications
 
 
  1. Zhou CZ, Pan SL, Lin H et al. [Effects of rosuvastatin in homocysteine induced mouse vascular smooth muscle cell dedifferentiation and endoplasmic reticulum stress and its mechanisms]. Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology 2018; 34:43-48. http://www.ncbi.nlm.nih.gov/pubmed/?term=29926658
  2. Zhong WB, Tsai YC, Chin LH et al. A Synergistic Anti-Cancer Effect of Troglitazone and Lovastatin in a Human Anaplastic Thyroid Cancer Cell Line and in a Mouse Xenograft Model. Int J Mol Sci 2018; 19. http://www.ncbi.nlm.nih.gov/pubmed/?term=29932104
  3. Ren H, Ding M, Ma H et al. [Protective effects of combined use of atorvastatin and low molecular weight heparin on the inflammatory reaction and pulmonary functions in rats with sepsis]. Zhonghua wei zhong bing ji jiu yi xue 2016; 28:427-432. http://www.ncbi.nlm.nih.gov/pubmed/?term=29920039
  4. Nakashima Y, Miyagi-Shiohira C, Noguchi H, Omasa T. Atorvastatin Inhibits the HIF1alpha-PPAR Axis, Which Is Essential for Maintaining the Function of Human Induced Pluripotent Stem Cells. Molecular therapy : the journal of the American Society of Gene Therapy 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29929789
  5. Mohammadian M, Sadeghipour HR, Jahromi GP et al. Simvastatin and bone marrow-derived mesenchymal stem cells (BMSCs) affects serum IgE and lung cytokines levels in sensitized mice. Cytokine 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29914792
  6. Li H, Chen MH, Ibrahim JG et al. Bayesian inference for network meta-regression using multivariate random effects with applications to cholesterol lowering drugs. Biostatistics (Oxford, England) 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29912318
  7. Hao WJ, Ke SZ, Liu L et al. [The experimental study of simvastatin on improving aspirin resistance in diabetic rats]. Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology 2016; 32:395-400. http://www.ncbi.nlm.nih.gov/pubmed/?term=29931841
  8. Du RX, Ye P, Yan GT et al. [The effect of rosuvastatin therapy on CCR2 expression in mononuclear cells and its upstream pathway]. Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology 2016; 32:202-206. http://www.ncbi.nlm.nih.gov/pubmed/?term=29931877
  9. Chujan S, Suriyo T, Ungtrakul T et al. Potential candidate treatment agents for targeting of cholangiocarcinoma identified by gene expression profile analysis. Biomedical reports 2018; 9:42-52. http://www.ncbi.nlm.nih.gov/pubmed/?term=29930804
  10. Ayad MT, Taylor BD, Menon R. Regulation of p38 mitogen-activated kinase-mediated fetal membrane senescence by statins. American journal of reproductive immunology (New York, N.Y. : 1989) 2018:e12999. http://www.ncbi.nlm.nih.gov/pubmed/?term=29911323
  11. Feng D, Ge C, Tan ZY et al. Isoflavones enhance pharmacokinetic exposure of active lovastatin acid via the upregulation of carboxylesterase in high-fat diet mice after oral administration of Xuezhikang capsules. Acta pharmacologica Sinica 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29921884
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