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Update - Week 15, 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

Communicating risk by using peer percentiles
The authors of this article propose a new tool for risk prediction/communication. Based on data collected in the 2009–2014 National Health and Nutrition Examination Survey (NHANES) and by means of the Pooled Cohort Risk Equation tool, individual 10-year ASCVD risk of 9 160 adults was calculated. Personalized standardized risk percentiles (for age, race and sex) were estimated. In order to facilitate patients understanding, the absolute risk of an ASCVD event was reformatted to a risk percentile. This would allow for a direct comparison of an individual’s risk to peers of similar age, gender and race. A healthcare professional would than inform the patient that his or her risk at precise percentile of that group. E.g. a 55-year-old black male at the 20th percentile, of 55-year black males; or 20% would have a lower- and 80% a higher ASCVD risk compared to this individual. Standardized cardiovascular risk percentiles by age, race, and sex are available online at populationrelativerisk.dcri.org. The authors suggested that using this simplified approach would provide patients with a easy to understand information how their personal risk compares to age, gender and race matched in their community. This could enhance motivation to improve modifiable risk factors and decreased an elevated risk to an average or even low ASCVD risk level.
Navar AM, Pencina MJ, Mulder H et al. Improving patient risk communication: Translating cardiovascular risk into standardized risk percentiles. Am Heart J 2018; 198:18-24. http://www.ncbi.nlm.nih.gov/pubmed/?term=29653642
MACE risk after PCI for CTO in CKD patients
Administering a statin loading dose has become an accepted strategy before performing primary and elective PCI’s. In this article the use of statins is evaluated in CKD patients receiving a PCI for chronic total occlusions (CTOs). Between August 2004 and December 2014, 1 463 patients underwent a successful PCI for CTO. Patients with (N=555) and without (N=908) CKD were compared for MACE. Using a univariate and multivariable analysis, the risk of MACE was significantly increased in CKD patients HR 1.25 (1.04 - 1.51, p = 0.016) and 1.23 (1.02 - 1.47, p = 0.03) respectively. In patients with CKD, Statins were used by 50% and 64% of the non-CKD group were taking them. A reduced risk of MACE (log rank tests p=0.003) was observed in CKD patients but not in the participants without CKD (log rank test p=0.814), the analysis was based on non-randomized prospective follow up data. The authors concluded that CKD was an important predictor of clinical outcomes in patients receiving a PCI for CTO and that the use of statins in these patients may reduce adverse clinical outcomes.
Naganuma T, Tsujita K, Mitomo S et al. Impact of Chronic Kidney Disease on Outcomes After Percutaneous Coronary Intervention for Chronic Total Occlusions (from the Japanese Multicenter Registry). Am J Cardiol 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29627112
Is elevated hs-CRP and common finding in CAD patients?
The importance of inflammation and was recently highlighted in the CANTOS trial that evaluated an interleukin beta antagonist in CAD patients with elevated hs-CRP. In this study the authors used data collected in two Norwegian hospitals with a catchment area of roughly 7% of the total Norwegian population. Using a cross sectional design 971 post AMI (80%), and/or PCI patients without inflammatory disease were evaluated. After a follow-up period of 2-36 months, hs-CRP ≥2 mg/dl was found in 378 patients (38%). Of those 243 (64%) with and LDL-c ≥1.8 mmol/l and 147 (47%) used a low dose statin. Ideal hs-CRP (<2.0 mg/dl) and LDL-c (<1.8 mmol/l) was observed in less than ¼ of the patients (24%). In 27% of the patients both bio-makers were off target and 12% had and LDL-c, <1.8 mmol/l but hs-CRP > 2.0 mg/dl. Predictors of elevated hs-CRP were: somatic comorbidity (odds ratio (OR) 1.3/1.0 point on the Charlson score), ≥1 previous coronary event (OR 2.4), smoking (OR 2.2), higher body mass index (OR 1.2/1.0 kg/m2), high LDL-C (OR 1.4/1.0 mmol/L) and higher anxiety scores (OR 1.1/1.0-point increase on the Hospital Anxiety and Depression Scale-Anxiety subscale score). The authors concluded that elevated hs-CRP was not an uncommon finding in post AMI patients and associated with LDL-c levels not at goal, unhealthy lifestyles and psychosocial distress. Using high dose high intensity statins plus additional LDL-c lowering strategies are warranted to target these modifiable
factors and to reduce inflammation and improve LDL-C in these patients.
Munkhaugen J, Otterstad JE, Dammen T et al. The prevalence and predictors of elevated C-reactive protein after a coronary heart disease event. Eur J Prev Cardiol 2018:2047487318768940. http://www.ncbi.nlm.nih.gov/pubmed/?term=29635941
Increased risk of statin related NODM in normotensive Korean men and hyper- as well as normotensive Korean women

The impact of statin on new onset diabetes (NODM) in the context of hypertension and gender was evaluated in a relatively healthy Korean population. Using data collected in the National Health Insurance System (NHIS) of Korea, a compulsory survey for health service use. Part of the registry is a bi-annual health screening program for all adults > 40 years of age. Over a period of ± 7-8 years 40 165 participants with elevated LDL-c were evaluated. Out of 22 366 statin users, 7.63% developed new onset diabetes (NODM) vs 5.68% in the 17 798 participants without statin use. Adding hypertension as a modifying risk factor in the equation; statin use was associated with NODM only in normotensive patients (HR 1.31 (1.09-1.58, p=0.004). An intriguing difference between males and females surfaced in this analysis as well.  Women showed an increased risk of NODM with continuous statin use, regardless of hypertension status while in men increased risk for NODM was observed in normotensive males only; HR 1.61 (1.35-1.92; P<0.001). the authors concluded that statin use in normotensive Korean men and hypertensive as well as normotensive Korean women was associated with an increased risk of NODM.
Lee SE, Sung JM, Cho IJ et al. Risk of new-onset diabetes among patients treated with statins according to hypertension and gender: Results from a nationwide health-screening cohort. PLoS One 2018; 13:e0195459. http://www.ncbi.nlm.nih.gov/pubmed/?term=29630642
Large UK primary care registry shows LDL-C of very high CVD risk patients too high
Lowering LDL-c is considered one of the most effective strategies to safely reduce CVD risk Despite the solid evidence, reflected in updated lipid management guidelines, a large number of very high-risk CVD patients are not receiving adequate cholesterol lowering treatment. In this analysis of a UK primary care registry, encompassing almost 5 million patients, the ones considered to have a very high risk: those with hyperlipidemia (assessed by co-medication) and documented cardiovascular disease (CVD) or hyperlipidemia and type 2 diabetes (DM2) without CVD (DM2w/oCVD) were queried. Roughly 5% of the patients had ≥2 prescriptions for lipid lowering drugs and were considered to have a high CVD risk score; 3% with documented CVD and 2% with DM2w/oCVD. Although >95% of the very high-risk patients were taking statins only 24% used high intensity statins and 1.5% a combination of statin + ezetimibe. LDL-c levels of ≥ 1.8 mmol/L, ≥ 2.5 mmol/L, ≥ 3.5 mmol/L and ≥ 4.0 mmol/L were present in 64-66%, 27-28%, 6-7% and 3% respectively. The authors concluded that a large proportion of UK very high CVD risk patients are not receiving the appropriate statin dosage. For patients with very high LDL-C levels, multiple CV events, MI within 1 year, or CVD and DM2, add-on lipid lowering drugs are likely needed to address their extreme risk for ASCVD complications.  
Danese MD, Sidelnikov E, Kutikova L. The prevalence, low-density lipoprotein cholesterol levels and treatment of patients at very high risk of cardiovascular events in the United Kingdom: a cross-sectional study. Current medical research and opinion 2018:1-15. http://www.ncbi.nlm.nih.gov/pubmed/?term=29627994
Relevant publications
  1. Verdoodt A, Honore Pm Md PF, Jacobs R et al. Do Statins Induce or Protect from Acute Kidney Injury and Chronic Kidney Disease: An Update Review in 2018. Journal of translational internal medicine 2018; 6:21-25. http://www.ncbi.nlm.nih.gov/pubmed/?term=29607300
  2. Singh K, Crossan C, Laba TL et al. Cost-effectiveness of a fixed dose combination (polypill) in secondary prevention of cardiovascular diseases in India: Within-trial cost-effectiveness analysis of the UMPIRE trial. Int J Cardiol 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29622506
  3. Sessa M, Rafaniello C, Scavone C et al. Preventable statin adverse reactions and therapy discontinuation. What can we learn from the spontaneous reporting system? Expert opinion on drug safety 2018:1-9. http://www.ncbi.nlm.nih.gov/pubmed/?term=29619841
  4. Saeed A, Ballantyne CM. Bempedoic Acid (ETC-1002): A Current Review. Cardiol Clin 2018; 36:257-264. http://www.ncbi.nlm.nih.gov/pubmed/?term=29609755
  5. Rozenbaum Z, Ravid D, Margolis G et al. Association of Pre-Admission Statin Therapy and the Inflammatory Response in ST Elevation Myocardial Infarction patients. Biomarkers 2018:1-19. http://www.ncbi.nlm.nih.gov/pubmed/?term=29620476
  6. Patel SS, Guzman L, Lin FP et al. Utilization of Aspirin and Statin in Management of Coronary Artery Disease in Patients with Cirrhosis Undergoing Liver Transplant Evaluation. Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29624871
  7. Pang J, Martin AC, Bates TR et al. Parent-child genetic testing for familial hypercholesterolaemia in an Australian context. Journal of paediatrics and child health 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29626384
  8. Cesena FHY, Laurinavicius AG, Valente VA et al. Statin Eligibility in Primary Prevention: From a Risk-Based Strategy to a Personalized Approach Based on the Predicted Benefit. Am J Cardiol 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29605080
  9. Banach M, Mikhailidis DP. Statin Intolerance: Some Practical Hints. Cardiol Clin 2018; 36:225-231. http://www.ncbi.nlm.nih.gov/pubmed/?term=29609752
  10. Ako J, Hibi K, Kozuma K et al. Effect of alirocumab on coronary atheroma volume in Japanese patients with acute coronary syndromes and hypercholesterolemia not adequately controlled with statins: ODYSSEY J-IVUS rationale and design. J Cardiol 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29606415
  11. Aday AW, Everett BM. Statins in Peripheral Artery Disease: What Are We Waiting For? Circulation 2018; 137:1447-1449. http://www.ncbi.nlm.nih.gov/pubmed/?term=29610126
  12. Smit J, Schonheyder HC, Nielsen H et al. In Reply-Statin Use Associated With a Decreased Risk of Community-Acquired Staphylococcus aureus Bacteremia. Mayo Clinic proceedings 2018; 93:542. http://www.ncbi.nlm.nih.gov/pubmed/?term=29622103
  13. Sadeeqa S, Maqsood M, Ahmad M. Prevalence of statin induced myopathy in Lahore, Pakistan. Pak J Pharm Sci 2018; 31:617-622. http://www.ncbi.nlm.nih.gov/pubmed/?term=29625933
  14. Pontes HBD, Pontes J, Azevedo Neto E et al. Evaluation of the Effects of Atorvastatin and Ischemic Postconditioning Preventing on the Ischemia and Reperfusion Injury: Experimental Study in Rats. Brazilian journal of cardiovascular surgery 2018; 33:72-81. http://www.ncbi.nlm.nih.gov/pubmed/?term=29617505
  15. Nguyen S, Chuah SY, Fontas E et al. Atorvastatin in Combination With Narrowband UV-B in Adult Patients With Active Vitiligo: A Randomized Clinical Trial. JAMA dermatology 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29617528
  16. Nelson AJ, Nicholls SJ. Treating Dyslipidemia in Type 2 Diabetes. Cardiol Clin 2018; 36:233-239. http://www.ncbi.nlm.nih.gov/pubmed/?term=29609753
  17. Masaki N, Kumagai K, Sasaki K et al. Suppressive effect of pitavastatin on aortic arch dilatation in acute stanford type B aortic dissection: analysis of STANP trial. General thoracic and cardiovascular surgery 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29626287
  18. Liu Y, Song X, Zhou H et al. Gut Microbiome Associates With Lipid-Lowering Effect of Rosuvastatin in Vivo. Frontiers in microbiology 2018; 9:530. http://www.ncbi.nlm.nih.gov/pubmed/?term=29623075
  19. Lin FJ, Lin HW, Ho YF. Effect of Statin Intensity on the Risk of Epilepsy After Ischaemic Stroke: Real-World Evidence from Population-Based Health Claims. CNS drugs 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29619760
  20. Lee TC, Kaouache M, Grover SA. Evaluation of the cost-effectiveness of evolocumab in the FOURIER study: a Canadian analysis. CMAJ open 2018; 6:E162-e167. http://www.ncbi.nlm.nih.gov/pubmed/?term=29622685
  21. Ko HHT, Lareu RR, Dix BR, Hughes JD. Statin Use Associated With a Decreased Risk of Community-Acquired Staphylococcus aureus Bacteremia. Mayo Clinic proceedings 2018; 93:541-542. http://www.ncbi.nlm.nih.gov/pubmed/?term=29622101
  22. Khokhar B, Simoni-Wastila L, Slejko JF et al. In-Hospital Mortality Following Traumatic Brain Injury Among Older Medicare Beneficiaries, Comparing Statin Users With Nonusers. The Journal of pharmacy technology : jPT : official publication of the Association of Pharmacy Technicians 2017; 33:225-236. http://www.ncbi.nlm.nih.gov/pubmed/?term=29607441
  23. Kaasenbrood L, Ray KK, Boekholdt SM et al. Estimated individual lifetime benefit from PCSK9 inhibition in statin-treated patients with coronary artery disease. Heart 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29622600
  24. Ham SY, Song SW, Nam SB et al. Effects of chronic statin use on 30-day major adverse cardiac and cerebrovascular events after thoracic endovascular aortic repair. J Cardiovasc Surg (Torino) 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29616526
  25. Desai P, Wallace R, Anderson ML et al. An analysis of the effect of statins on the risk of Non-Hodgkin's Lymphoma in the Women's Health Initiative cohort. Cancer medicine 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29608241
  26. Chen YA, Lin YJ, Lin CL et al. Simvastatin Therapy for Drug Repositioning to Reduce the Risk of Prostate Cancer Mortality in Patients With Hyperlipidemia. Frontiers in pharmacology 2018; 9:225. http://www.ncbi.nlm.nih.gov/pubmed/?term=29623039
  27. Can A, Castro VM, Dligach D et al. Lipid-Lowering Agents and High HDL (High-Density Lipoprotein) Are Inversely Associated With Intracranial Aneurysm Rupture. Stroke 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29622625
  28. Bin Abdulhak AA, Robinson JG. Optimizing Statins and Ezetimibe in Guideline-Focused Management. Cardiol Clin 2018; 36:221-223. http://www.ncbi.nlm.nih.gov/pubmed/?term=29609751
  29. Barter PJ, Rye KA. Cholesteryl Ester Transfer Protein Inhibitors as Agents to Reduce Coronary Heart Disease Risk. Cardiol Clin 2018; 36:299-310. http://www.ncbi.nlm.nih.gov/pubmed/?term=29609759
Miscellaneous publications
  1. Yoon SJ, Kim EC, Noh K, Lee DW. Supramolecular Hydrogels Based on MPEG-Grafted Hyaluronic Acid and alpha-CD Containing HP-beta-CD/Simvastatin Enhance Osteogenesis In Vivo. Journal of nanoscience and nanotechnology 2017; 17:217-223. http://www.ncbi.nlm.nih.gov/pubmed/?term=29617547
  2. Snarska A, Gonkowski S, Rytel L et al. Influence of simvastatin on red blood cell line in porcine bone marrow. Polish journal of veterinary sciences 2017; 20:811-814. http://www.ncbi.nlm.nih.gov/pubmed/?term=29611640
  3. Shahid N, Adnan S, Farooq M et al. DEVELOPMENT OF COMPRESSED COATED POLYPILL WITH MUCOADHESIVE CORE COMPRISING OF ATORVASTATIN/CLOPIDOGREL/ASPIRIN USING COMPRESSION COATING TECHNIQUE. Acta poloniae pharmaceutica 2017; 74:477-487. http://www.ncbi.nlm.nih.gov/pubmed/?term=29624252
  4. Lettiero B, Inasu M, Kimbung S, Borgquist S. Insensitivity to atorvastatin is associated with increased accumulation of intracellular lipid droplets and fatty acid metabolism in breast cancer cells. Scientific reports 2018; 8:5462. http://www.ncbi.nlm.nih.gov/pubmed/?term=29615666
  5. Huai J, Yang Z, Yi YH et al. [Regulation of pravastatin on long-chain fatty acid oxidative enzyme in pre-eclampsia-like mouse model]. Zhonghua fu chan ke za zhi 2018; 53:183-189. http://www.ncbi.nlm.nih.gov/pubmed/?term=29609233
  6. Fowke JH, Motley SS. Statin Use Linked with a Decrease in the Conversion from High-Grade Prostatic Intraepithelial Neoplasia (HGPIN) to Prostate Cancer. Carcinogenesis 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29617729
  7. Bech AP, Wetzels JFM, Nijenhuis T. Effects of sildenafil, metformin, and simvastatin on ADH-independent urine concentration in healthy volunteers. Physiological reports 2018; 6:e13665. http://www.ncbi.nlm.nih.gov/pubmed/?term=29611351
  8. Ahmadi Y, Haghjoo AG, Dastmalchi S et al. Effects of Rosuvastatin on the expression of the genes involved in cholesterol metabolism in rat: Adaptive responses by extrahepatic tissues. Gene 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29605604
  9. Wang N, Lu Y, Wang K et al. Simvastatin Attenuates Neurogenetic Damage and Improves Neurocongnitive Deficits Induced by Isoflurane in Neonatal Rats. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 2018; 46:618-632. http://www.ncbi.nlm.nih.gov/pubmed/?term=29617679
  10. Cruz P, Reyes F, Torres CG. Simvastatin modulates beta-catenin/MDR1 expression on spheres derived from CF41.Mg canine mammary carcinoma cells. Polish journal of veterinary sciences 2018; 21:95-99. http://www.ncbi.nlm.nih.gov/pubmed/?term=29624022
  11. Clementino A, Sonvico F. Development and validation of a RP-HPLC method for the simultaneous detection and quantification of simvastatin's isoforms and coenzyme Q10 in lecithin/chitosan nanoparticles. Journal of pharmaceutical and biomedical analysis 2018; 155:33-41. http://www.ncbi.nlm.nih.gov/pubmed/?term=29605683
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