Title: Statins and Cholesterol: A Perspective Revisited
Authors: Dr Varshiesh Raina, Dr Konika Razdan
DOI: https://dx.doi.org/10.18535/jmscr/v6i4.203
Abstract
Over the past 36 years, the global market has witnessed a substantial demand for Statins. As a result Statins have proved to be a highly profitable and lucrative market in pharmaceutical sector. This rise in statin consumption has been mainly recognized due to its cholesterol lowering effect, particularly, the low density lipoprotein (LDL) cholesterol in the body.[1] Increased levels of LDL are considered to be one of the major risk factor that predisposes heart patients towards heart attack. Noticeably, heart disease is the number one cause of death in U.S and, increasing, worldwide. A large number of placebo-controlled studies showed that Statins can substantially reduce mortality in high risk patients, but no history of heart disease. The American Heart Association and the American College of Cardiology have provided guidelines wherein Statin treatment should be used for primary prevention of cardiovascular disease in adults with a 10-year risk of developing heart attack or stroke of 7.5% or more; LDL cholesterol ≥ 190 mg/dL or those with diabetes, age 40–75 with LDL-C 70–190 mg/dl.[2] The safety of statins became noticeable when cerivastatin was withdrawn worldwide in August 2001 as it caused fatal rhabdomyolysis.[3] In this review article we will be emphasizing on the studies which will underpin the risks associated with statins from cholesterol point of view.
References
- Stancu C, Sima AJ. Statins: mechanism of action and effects. Cell Mol Med 2001; 5:378-87.
- Stone NJ et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. American College of Cardiology/American Heart Association Task Force on Practice Guidelines.Circulation 2014; 129:S1-45.
- Davidson MH. Controversy surrounding the safety of cerivastatin. Expert Opin Drug Saf 2002;1:207-12.
- Bloch K. Summing up. Annu. Rev. Biochem 1987); 56: 1–19.
- Daniel S, Joel A, Eugene B. Feigelson.Effects of triparanol (mer-29) on cholesterol biosynthesis and on blood sterol levels in man. J Clin Invest 1961; 40: 884–893.
- Carlson LA. Nicotinic acid: the broad-spectrum lipid drug. A 50th anniversary review. J Intern Med2005;258:94-114.
- Fanny L,Bart S. Fibrates, glitazones, and peroxisome proliferator-activated receptors. Arterioscler Thromb Vasc Biol 2010; 30: 894–899.
- Kohzo A, Yoshimasa A, Toshihiko I. Role of bile acid sequestrants in the treatment of type 2 diabetes. World J Diabetes 2010; 1: 146–152.
- Endo A. A historical perspective on the discovery of statins. Proc Jpn Acad Ser B Phys Biol Sci 2010; 86: 484–493.
- Endo A, Kuroda M, Tsujita Y. ML-236A, ML-236B, and ML-236C, new inhibitors of cholesterogenis produced by Penicillium citrinum. J Antiobitics 1976; 29:1346–1348
- Michael SB, Joseph LG. A tribute to Akira Endo, discoverer of a “Penicillin” for cholesterol. Atherosclerosis 2004; 5: 13–16.
- Endo A. A historical perspective on the discovery of statins. Proc Jpn Acad. Ser B Phys Biol Sci 2010; 86: 484–493.
- Bizukojc M, Ledakowicz S. A macrokinetic modelling of the biosynthesis of lovastatin by Aspergillus terreus. J Biotechnol 2007; 130: 422–435.
- Goswami S, Vidyarthi AS, Bhunia B, Mandal T. A review on lovastatin and its production. J Biochem Tech 2012; 4: 581-587.
- Peter HJ. Comparing HMG-CoA Reductase Inhibitors. Clin Cardiol 2003; 26:15-20.
- Ravnskov Is atherosclerosis caused by high cholesterol? QJM: An Int Journal of Med 2002; 95: 397-403.
- Nicola M,Gabriele G, Stefano PC, Javier F, Federico M, Giulio A. Anxiety, Stress-Related Factors, and Blood Pressure in Young Adults. Front Psychol 2016; 7: 1682.
- Ira T. Cholesterol in health and disease. J Clin Invest 2002; 110: 583-590.
- Kenneth RF, Carl G. Introduction to Lipids and Lipoproteins. Endotext book [Internet].
- Brian A et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel. European Heart Journal 2017; 38: 2459-2472.
- Wadhera RK, Steen DL, Khan I, Giugliano RP, Foody JM. A review of low-density lipoproteincholesterol, treatment strategies, and its impact on cardiovascular disease morbidity and mortality. J Clin Lipidol 2016; 10: 472-89.
- Fernandez-Ruiz I. Atherosclerosis: Should we redefine the normal LDL cholesterol range? Nat Rev Cardiol 2018; 15: 68-69.
- Low levels of good cholesterol linked to memory loss, dementia risk. American Heart Association. ScienceDaily, 1 July 2008.
- Low LDL cholesterol is related to cancer risk. American College of Cardiology. ScienceDaily, 26 March 2012.
- Esin E,Necat Y, Ozgur A. High Density Lipoprotein and it’s Dysfunction. Open Biochem J 2012; 6: 78-93.
- Aviram M, Rosenblat M, Bisgaier CL, Newton RS, Primo-Parmo SL, La-Du Paraoxonase inhibits high-density lipoprotein oxidation and preserves its functions. A possible peroxidative role for paraoxonase. J Clin Invest 1998; 101: 1581-1590.
- Philip JB,Gunnar B, Mike KP, Stephen JN. Effect of statins on HDL-C: a complex process unrelated to changes in LDL-C: analysis of the VOYAGER Database. J Lipid Res 2010; 51: 1546-1553.
- Fergus MT,Peter J. Effects of Statins on High-Density Lipoproteins: A Potential Contribution to Cardiovascular Benefit. Cardiovasc Drugs Ther 2008; 22: 321-338.
- Sacks FM, Tonkin AM, Shepherd J, Braunwald E, Cobbe S, Hawkins CM, Keech A, Packard C, Simes J, Byington R, Furberg CD. Effect of pravastatin on coronary disease events in subgroups defined by coronary riskfactors: the Prospective Pravastatin Pooling Project. Circulation 2000; 102: 1893-900.
- van Capelleveen JC et al.Association of High‐Density Lipoprotein‐Cholesterol Versus Apolipoprotein A‐I With Risk of Coronary Heart Disease: The European Prospective Investigation Into Cancer‐Norfolk Prospective Population Study, the Atherosclerosis Risk in Communities Study, and the Women's Health Study. J Am Heart Assoc 2017; 6: e006636.
- Boekholdt SM. Levels and changes of HDL cholesterol and apolipoprotein A-I in relation to risk of cardiovascular events among statin-treated patients; a meta-analysis. Circulation2013; 128: 1504-12.
- Khera AV, Cuchel M, De LL-M, Rodrigues A, Burke MF, Jafri K, French BC, Phillips JA, Mucksavage ML, Wilensky RL, Mohler ER, Rothblat GH, Rader DJ. Cholesterol efflux capacity, high-density lipoprotein function, and atherosclerosis. N Engl J Med 2011; 364: 127-135.
- Ernst JS, Bela FA. Statins, cholesteryl ester transfer protein inhibition, high density lipoprotein particle metabolism and heart disease risk reduction. http://www.athero.org/commentaries/comm519.pdf.
- Dallinga-Thie GM, van Tol A, Dullaart RP. Plasma pre beta-HDLformation is decreased by atorvastatin treatment in type 2 diabetes mellitus: Role of phospholipid transfer protein. Biochim Biophys Acta 2009; 1791: 714-8.
- Juan Z,Qiang L. Cholesterol metabolism and homeostasis in the brain. Protein Cell 2015; 6: 254–264.
- Lange Y, Ye J, Strebel F. Movement of 25-hydroxycholesterol from the plasma membrane to the rough endoplasmic reticulum in cultured hepatoma cells. J Lipid Res 1995; 36: 1092-7.
- Anchisi L, Dessì S, Pani A, Mandas A. Cholesterol homeostasis: a key to prevent or slow down neurodegeneration. Front Physiol 2013; 3: 486.
- Maioli S, Båvner A, Ali Z, Heverin M, Ismail MA, Puerta E, Olin M, Saeed A, Shafaati M, Parini P, Cedazo-Minguez A, Bjorkhem I. Is It Possible to Improve Memory Function by Upregulation of the Cholesterol 24S-Hydroxylase (CYP46A1) in the Brain. PLoS One2013;8 :e68534.
- Hering H, Lin CC, Sheng M. Lipid Rafts in the Maintenance of Synapses, Dendritic Spines, and Surface AMPA Receptor Stability. J Neurosci2003; 23: 3262-71.
- Martin MG, Pfrieger F, Dotti CG. Cholesterol in brain disease: sometimes determinant and frequently implicated. EMBO Rep 2014; 15: 1036-52.
- Jones RW, Kivipelto M, Feldman H, Sparks L, Doody R, Waters DD, Hey-Hadavi J, Breazna A, Schindler RJ, Ramos H. The Atorvastatin/Donepezil in Alzheimer's DiseaseStudy (LEADe): design and baseline characteristics. Alzheimers Dement 2008; 4: 145-53.
- Ford I et al. A Prospective Study of Pravastatin in the Elderly at Risk (PROSPER): Screening Experience and Baseline Characteristics. Curr Control Trials Cardiovasc Med 2002; 3: 8.
- Bitzur R. RememberingStatins: Do Statins Have Adverse Cognitive Effects? Diabetes Care. 2016; 39: S253-9.
- Schilling JM, Cui W, Godoy JC, Risbrough VB, Niesman IR, Roth DM, Patel PM, Drummond JC, Patel HH, Zemljic-Harpf AE, Head BP. Long-term atorvastatin treatment leads to alterations in behavior, cognition, and hippocampal biochemistry. Behav Brain Res 2014; 267: 6–11.
- Scheitz JF, MacIsaac RL, Abdul-Rahim AH, Siegerink B, Bath PM, Endres M, Lees KR, Nolte CH. Statins and risk of poststroke hemorrhagic complications. Neurology2016; 86: 1590-6.
- Brenton W. The implications of statin induced peripheral neuropathy. J Foot Ankle Res 2011; 4: P57.
- Manish T,Mark WR, Herbert LB. Statins and Liver Injury. Gastroenterol Hepatol (N Y). 2013; 9: 605-606.
- Pastori D, Polimeni L, Baratta F, Pani A, Del Ben M, Angelico F. The efficacyand safety of statins for the treatment of non-alcoholic fatty liver disease. Dig Liver Dis 2015; 47: 4-11.
- Rossana MC, Luigi XC,Ronald BG, Eugene RSchiff. Statins in the Treatment of Dyslipidemia in the Presence of Elevated Liver Aminotransferase Levels: A Therapeutic Dilemma. Mayo Clin Proc 2010; 85: 349-356.
- Bohm M, Herrmann W, Wassmann S, Laufs U, Nickenig G. Does statin therapy influence steroid hormone synthesis? Z Kardiol 2004; 93: 43-8.
- Peck A, Chaikittisilpa S, Mirzaei R, Wang J, Mack WJ, Hodis HN, Stanczyk FZ. Effectof statins on estrogen and androgen levels in postmenopausal women treated with estradiol. Climacteric 2011; 14: 49-53.
- Krysiak R, Okopien B. The effect of aggressive rosuvastatin treatment on steroid hormone production in men with coronary artery disease. Basic Clin Pharmacol Toxicol 2014; 114: 330-5.
- Keyser CE, Lima FV, Jong FH, Hofman A, Rijke YB, Uitterlinden AG, Visser LE, Stricker BH. Use of statins is associated with lower serum total and non-sex hormone-binding globulin-bound testosterone levels in male participants of the Rotterdam Study. Eur J Endocrinol2015; 173: 155-65.
- Ouweneel AB, van der Sluis RJ, Nahon JE, Van Eck M, Hoekstra M. Simvastatin treatmentaggravates the glucocorticoid insufficiency associated with hypocholeste-rolemia in mice. Atherosclerosis 2017; 261: 99-104.
- Matthias W,Michael F. Holick. Sunlight and Vitamin D. A global perspective for health. Dermatoendocrinol 2013; 5: 51–108.
- Rathish N,Arun M. Vitamin D: The “sunshine” vitamin. J Pharmacol Pharmacother 2012; 3: 118–126.
- Miao H. Safety of statins: an update. Ther Adv Drug Saf 2012; 3: 133–144.
- Schwartz JB. Effects of vitamin D supplementation in atorvastatin-treated patients: a new drug interaction with an unexpected consequence. Clin Pharmacol Ther2009; 85: 198-203.
- Bischoff-Ferrari HA, Fischer K, Orav EJ, Dawson-Hughes B, Meyer U, Chocano-Bedoya PO, Meyer OW, Ernst R, Schietzel S, Eberli F, Staehelin HB, Freystätter G, Roas S, Theiler R, Egli A, Wilson NM. Statin Use and 25‐Hydroxyvitamin D Blood Level Response to Vitamin D Treatment of Older Adults. J Am Geriatr Soc 2017; 65: 1267-1273.
