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Update - Week 33, 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

Meta-analysis of statins peri-procedural carotid stenting
Employing statins is expanding beyond the traditional routes of prolonged administration after ASCVD events or in qualifying primary prevention patients. In this meta-analysis the benefits/harms of peri-procedural statin use in patients scheduled for carotid stenting were re-evaluated. There were 11 studies, targeting 4088 patients, included in this meta-analysis. All studies were either randomized clinical trials or observational studies that evaluated statin use just before and during the surgical procedures of carotid stenting, and that reported relevant outcomes such as stroke, transient ischemic attack, myocardial infarction, and death at 30 days. The risk of stroke and death were significantly reduced when statins were used.  Stroke OR 0.39 (0.27-0.58, p<0.01; I2=0%) and death OR 0.30 (0.10-0.96, p=0.042; I2=0%). No relevant improvements could be discerned for TIA’s OR 1.05 (0.06-17.15; p=0.662; I2=0%)or MI’s OR 0.48 (0.16-1.50, p=0.89; I2=0%). None of the other studied baseline variables had any significant effect on the studied endpoints; including stroke and death. The authors concluded that statin use is associate with significant improvements of important clinical endpoints such as stroke and deaths but no changes in TIA’s or MI’s were noted.
Texakalidis P, Giannopoulos S, Jonnalagadda AK et al. Preoperative Use of Statins in Carotid Artery Stenting: A Systematic Review and Meta-analysis. Journal of endovascular therapy : an official journal of the International Society of Endovascular Specialists 2018:1526602818794030. http://www.ncbi.nlm.nih.gov/pubmed/?term=30101624
The alpha and omega of measuring and evaluating lipids
Measuring lipid fractions has expanded over the last decade and we have gone from the simple “Good cholesterol” (LDL) – “Bad cholesterol” towards a far more complex spectrum of lipid lipoprotein subclasses, apo-lipoproteins, metabolomics as well as genetic profiling of proteins and enzymes involved in lipid metabolism such as the LPL and Apo A V gene. In this comprehensive overview the authors provide a concise summary of each individual marker including relevant information on intrinsic/extrinsic modifications as well as therapeutic approaches. They position their review in the context of the recently released recommendations on the quantification of atherogenic lipoproteins by the multidisciplinary consensus panel of the European Atherosclerosis Society (EAS) and the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM). The aspiration of the authors is that this review will provide a lipid diagnostic framework that can contribute to improved precision medicine approaches and help clinicians to find better and individualized treatment options for patients at high risk of CVD.
Langlois MR, Nordestgaard BG. Which Lipids Should Be Analyzed for Diagnostic Workup and Follow-up of Patients with Hyperlipidemias? Current cardiology reports 2018; 20:88. http://www.ncbi.nlm.nih.gov/pubmed/?term=30120626
Do run-in phase of RCT’s explain the difference in adherence to observational trials
The difference between reported adverse events in randomized controlled statin trials and observational adverse vents was examined in this review. The authors evaluate if a run-in period by which statin intolerant patients were excluded from the trial could be the cause of this discrepancy. They included trials with >1000 participants with, and without a run-in period from the Cholesterol Treatment Trialist Collaboration (CTTC) analysis. No discernable differences were noted in reported adverse events and non-adherence rates when comparing patients that participated in trials with a run-in phase to patients that did not. The number of trials that used a run-in design was only small, majority of included studies did not use this approach.
Vonbank A, Drexel H, Agewall S et al. Reasons for Disparity in Statin Adherence Rates between Clinical Trials and Real World Observations. A Review. European heart journal. Cardiovascular pharmacotherapy 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30099530
Korean Diabetes Risk Score
The development ethnic specific risk tools are very important to improve the prediction models predominantly based on Caucasian populations. A diabetes risk score was developed, based on data collected in the Korean National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS) that included 359,349 Koreans without diabetes at baseline. Using a cox proportional hazards regression model to calculate the of developing diabetes. The validation was of the Score was done in participants of the Korean Genome and Epidemiology Study. The median follow-up time was 10.8 years, during which 37 678 (10.4/1000) diabetics were identified. The following risk factors were tested: age, family history of diabetes, alcohol intake (only in men), smoking status, physical activity, use of antihypertensive therapy, use of statin therapy, body mass index, systolic blood pressure, total cholesterol, fasting glucose, and γ glutamyl transferase (only in women). The C-statistic (10-year risk of developing diabetes) of both the risk development model and the validation data set were 0.71 and 0.63 for men and 0.76 and 0.66 for women respectively. The 10-year Korean Diabetes Risk Score (KDRS) can be used to identify and calculate the potential risk of developing diabetes in participants of (national) screening programs as well as individual care related risk factor evaluation. Delaying or preventing diabetes, by means of early – proper management of risk factors associated with diabetes, would be the ultimate aim. The modeling used to develop the KDRS could be used for different populations or ethnic groups as well.
Ha KH, Lee YH, Song SO et al. Development and Validation of the Korean Diabetes Risk Score: A 10-Year National Cohort Study. Diabetes Metab J 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30113144
Rosuvastatin does not protect ARDS related sepsis patients from AKI
The protective/harmful effects of statins in patients with chronic kidney disease and/or in whom acute renal compilations develop remain confusing. The authors performed a post hoc analysis of the Statins for Acutely Injured Lungs in Sepsis (SAILS) study, a randomized controlled trial that tested the impact of rosuvastatin therapy on mortality in patients with sepsis-associated ARDS. The aim was to evaluate if rosuvastatin protected patients from acute kidney injury (AKI) in patients that developed sepsis during an episode of acute respiratory distress (ARDS). The analysis was performed in 644/745 participants. Using a multivariable regression model, outcomes were analyzed in 511 patients that did have AKI at baseline and 111 that were diagnosed with stage I AKI. The 511 patients without AKI at baseline were not better off with rosuvastatin, the adjusted OR: 0.99 (067-1.44). Those with stage I AKI did worse with rosuvastatin OR: 3.06 (1.14-8.22). However, this effect was no longer statistically significant when serum creatinine was adjusted for cumulative fluid balance; OR: 1.85 (0.70-4.84). The authors concluded that rosuvastatin was not associated with reduced risk from developing de novo or worsening of AKI in patients with ARDS related sepsis. Potential harms cannot be ruled out. If the observed effects with rosuvastatin can be extrapolated to other statins like atorvastatin is questionable, earlier studies did point towards saillant differences between atorvastatin and rosuvastatin in renal protective/harmful effects.
Hsu RK, Truwit JD, Matthay MA et al. Effect of Rosuvastatin on Acute Kidney Injury in Sepsis-Associated Acute Respiratory Distress Syndrome. Canadian journal of kidney health and disease 2018; 5:2054358118789158. http://www.ncbi.nlm.nih.gov/pubmed/?term=30116543
Relevant publications
  1. Vonbank A, Drexel H, Agewall S et al. Reasons for Disparity in Statin Adherence Rates between Clinical Trials and Real World Observations. A Review. European heart journal. Cardiovascular pharmacotherapy 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30099530
  2. Zhang X, Hong S, Yen R et al. A system to monitor statin-induced myopathy in individual engineered skeletal muscle myobundles. Lab on a chip 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30112530
  3. Williams CR, Jellison A, Martin L et al. Optimal medical management before lower extremity bypass for claudication in the veteran population. Journal of vascular surgery 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30108008
  4. Vincent J. Lipid Lowering Therapy for Atherosclerotic Cardiovascular Disease: It Is Not So Simple. Clinical pharmacology and therapeutics 2018; 104:220-224. http://www.ncbi.nlm.nih.gov/pubmed/?term=30117592
  5. Soko ND, Chimusa E, Masimirembwa C, Dandara C. An African-specific profile of pharmacogene variants for rosuvastatin plasma variability: limited role for SLCO1B1 c.521T>C and ABCG2 c.421A>C. Pharmacogenomics J 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30100615
  6. Mijailovic N, Selakovic D, Joksimovic J et al. The anxiolytic effects of atorvastatin and simvastatin on dietary-induced increase in homocysteine levels in rats. Molecular and cellular biochemistry 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30120639
  7. El-Kharashi OA, El-Din Aly El-Waseef DA, Nabih ES, Mohamed DI. Targeting NLRP3 inflammasome via acetylsalicylic acid: Role in suppressing hepatic dysfunction and insulin resistance induced by atorvastatin in naive versus alcoholic liver in rats. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 2018; 107:665-674. http://www.ncbi.nlm.nih.gov/pubmed/?term=30118883
  8. Bauer UMM, Korten MA, Diller GP et al. Cardiovascular risk factors in adults with congenital heart defects - Recognised but not treated? An analysis of the German National Register for Congenital Heart Defects. Int J Cardiol 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30100225
  9. Bahrami A, Parsamanesh N, Atkin SL et al. Effect of statins on toll-like receptors: a new insight to pleiotropic effects. Pharmacol Res 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30120976
  10. Alkhalil M. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, reality or dream in managing patients with cardiovascular disease. Current drug metabolism 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30112987
  11. Tyerman Z, Hawkins RB, Mehaffey JH et al. Preoperative Statin Use Not Associated with Improved Outcomes After Ascending Aortic Repair (91 / 100). Seminars in thoracic and cardiovascular surgery 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30102969
  12. Rajeshuni N, Ludwig CA, Moshfeghi DM. The effect of statin exposure on choroidal neovascularization in nonexudative age-related macular degeneration patients. Eye (London, England) 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30120400
  13. Henslee AB, Steele TA. Combination statin and chemotherapy inhibits proliferation and cytotoxicity of an aggressive natural killer cell leukemia. Biomarker research 2018; 6:26. http://www.ncbi.nlm.nih.gov/pubmed/?term=30116531
  14. Eljaaly K, Alshehri S, Bhattacharjee S et al. Contraindicated drug-drug interactions associated with oral antimicrobial agents prescribed in the ambulatory care setting in the United States. Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30107284
  15. Chen YC, Xu C, Zhang JG et al. Multivariate analysis of genomics data to identify potential pleiotropic genes for type 2 diabetes, obesity and dyslipidemia using Meta-CCA and gene-based approach. PLoS One 2018; 13:e0201173. http://www.ncbi.nlm.nih.gov/pubmed/?term=30110382
Miscellaneous publications
  1. Yu B, Liu D, Zhang H et al. Anti-hypertrophy effect of atorvastatin on myocardium depends on AMPK activation-induced miR-143-3p suppression via Foxo1. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 2018; 106:1390-1395. http://www.ncbi.nlm.nih.gov/pubmed/?term=30119211
  2. Venardos N, Deng XS, Yao Q et al. Simvastatin reduces the TLR4-induced inflammatory response in human aortic valve interstitial cells. J Surg Res 2018; 230:101-109. http://www.ncbi.nlm.nih.gov/pubmed/?term=30100024
  3. Mast N, Bederman IR, Pikuleva IA. Retinal Cholesterol Content is Reduced in Simvastatin-Treated Mice Due to Inhibited Local Biosynthesis Albeit Increased Uptake of Serum Cholesterol. Drug metabolism and disposition: the biological fate of chemicals 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30115644
  4. Lu D, Liu Y, Mai H et al. Rosuvastatin Reduces Neuroinflammation in the Hemorrhagic Transformation After rt-PA Treatment in a Mouse Model of Experimental Stroke. Frontiers in cellular neuroscience 2018; 12:225. http://www.ncbi.nlm.nih.gov/pubmed/?term=30116175
  5. Li M, Liu F, Sang M et al. Effects of atorvastatin on p38 phosphorylation and cardiac remodeling after myocardial infarction in rats. Experimental and therapeutic medicine 2018; 16:751-757. http://www.ncbi.nlm.nih.gov/pubmed/?term=30116330
  6. Jia L, Wang L, Liu W et al. Fluvastatin inhibits cardiomyocyte apoptosis after myocardial infarction through Toll pathway. Experimental and therapeutic medicine 2018; 16:1350-1354. http://www.ncbi.nlm.nih.gov/pubmed/?term=30116385
  7. Iarrobino NA, Gill BS, Bernard M et al. The Impact of Serum Glucose, Anti-Diabetic Agents, and Statin Usage in Non-small Cell Lung Cancer Patients Treated With Definitive Chemoradiation. Frontiers in oncology 2018; 8:281. http://www.ncbi.nlm.nih.gov/pubmed/?term=30101126
  8. DuBrock HM, AbouEzzeddine OF, Redfield MM. High-sensitivity C-reactive protein in heart failure with preserved ejection fraction. PLoS One 2018; 13:e0201836. http://www.ncbi.nlm.nih.gov/pubmed/?term=30114262
  9. Balraj J, Jairaman K, Kalieswaran V, Jayaraman A. Bioprospecting lovastatin production from a novel producer Cunninghamella blakesleeana. 3 Biotech 2018; 8:359. http://www.ncbi.nlm.nih.gov/pubmed/?term=30105184
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