{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T08:34:55Z","timestamp":1790670895225,"version":"4.1.0"},"reference-count":105,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2016,2,19]]},"abstract":"<jats:p>We can look back at &gt;100 years of cholesterol research that has brought medicine to a stage where people at risk of severe or fatal coronary heart disease have a much better prognosis than before. This progress has not come about without resistance. Perhaps one of the most debated topics in medicine, the cholesterol controversy, could only be brought to rest through the development of new clinical research methods that were capable of taking advantage of the amazing achievements in basic and pharmacological science after the second World War. It was only after understanding the biochemistry and physiology of cholesterol synthesis, transport and clearance from the blood that medicine could take advantage of drugs and diets to reduce the risk of atherosclerotic diseases. This review points to the highlights of the history of low-density lipoprotein-cholesterol lowering, with the discovery of the low-density lipoprotein receptor and its physiology and not only the development of statins as the stellar moments but also the development of clinical trial methodology as an effective tool to provide scientifically convincing evidence.<\/jats:p>","DOI":"10.1161\/circresaha.115.306297","type":"journal-article","created":{"date-parts":[[2016,2,18]],"date-time":"2016-02-18T23:42:03Z","timestamp":1455838923000},"page":"721-731","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":43,"title":["The Success Story of LDL Cholesterol Lowering"],"prefix":"10.1161","volume":"118","author":[{"given":"Terje R.","family":"Pedersen","sequence":"first","affiliation":[{"name":"From the Oslo University Hospital, Ullev\u00e5l, Center For Preventive Medicine and University of Oslo, Institute for Clinical Medicine, Oslo, Norway."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","volume-title":"The Pathological Anatomy of the Human Body 1847","author":"Vogel J.","unstructured":"Vogel J. The Pathological Anatomy of the Human Body 1847. London: H. Baillere."},{"key":"e_1_3_4_3_2","first-page":"379","article-title":"\u00dcber die ver\u00e4nderungen der kaninchenaorta bei experimenteller Cholesterinsteatose.","volume":"56","author":"Anitschkow N.","year":"1913","unstructured":"Anitschkow N. \u00dcber die ver\u00e4nderungen der kaninchenaorta bei experimenteller Cholesterinsteatose. Beitr Pathol Anat Allgem Pathol 1913;56:379\u2013404.","journal-title":"Beitr Pathol Anat Allgem Pathol"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.23.1.69"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0028-1128257"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.50.4.647"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1935.02760330001001"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1946.02870280001001"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-8703(51)90150-0"},{"key":"e_1_3_4_10_2","first-page":"1","article-title":"The effect of plasma cholesterol lowering diet in male survivors of myocardial infarction. A controlled clinical trial.","volume":"466","author":"Leren P.","year":"1966","unstructured":"Leren P. The effect of plasma cholesterol lowering diet in male survivors of myocardial infarction. A controlled clinical trial. Acta Med Scand Suppl. 1966;466:1\u201392.","journal-title":"Acta Med Scand Suppl"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.42.5.935"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(72)92208-8"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197709222971206"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(71)90911-1"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(61)92951-8"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.3181\/00379727-110-27531"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1963.03700080040013"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(61)90115-5"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(62)92422-4"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.47.3S1.I-1"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1970.03180070069012"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1972.03200070084015"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1973.03230060030009"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1975.03240160024021"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.4.5790.767"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.4.5790.775"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.4.5790.784"},{"key":"e_1_3_4_28_2","first-page":"243","article-title":"A cooperative trial on the primary prevention of ischaemic heart disease using clofibrate: design, methods, and progress.","volume":"48","author":"Heady JA.","year":"1973","unstructured":"Heady JA. A cooperative trial on the primary prevention of ischaemic heart disease using clofibrate: design, methods, and progress. Bull World Health Organ. 1973;48:243\u2013256.","journal-title":"Bull World Health Organ"},{"key":"e_1_3_4_29_2","first-page":"1069","article-title":"A co-operative trial in the primary prevention of ischemic heart disease using clofibrate.","volume":"40","author":"Committee of Principal Investigators","year":"1978","unstructured":"Committee of Principal Investigators. A co-operative trial in the primary prevention of ischemic heart disease using clofibrate. Br Med J 1978;40:1069\u20131118.","journal-title":"Br Med J"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(81)91286-1"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.73.1.1"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1136\/hrt.58.5.423"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/0735-1097(88)90327-0"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/0021-9681(79)90092-4"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)41235-0"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-79-1-51"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1984.03340270029025"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1097\/00000658-199009000-00010"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199010043231404"},{"issue":"2","key":"e_1_3_4_40_2","first-page":"6","article-title":"The hypolipidaemic effect of gemfibrozil (CI-719) in laboratory animals.","volume":"69","author":"Rodney G","year":"1976","unstructured":"Rodney G, Uhlendorf P, Maxwell RE. The hypolipidaemic effect of gemfibrozil (CI-719) in laboratory animals. Proc R Soc Med. 1976;69(suppl 2):6\u201310.","journal-title":"Proc R Soc Med"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198711123172001"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1988.03410050061031"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199908053410604"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1985.03350380096029"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.80.4.1070"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.301.6747.309"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1991.03470090059032"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.304.6824.393"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosissup.2004.08.033"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(76)80996-9"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1039\/p19760001165"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosissup.2004.08.026"},{"key":"e_1_3_4_55_2","doi-asserted-by":"publisher","DOI":"10.1016\/0021-9150(80)90124-0"},{"key":"e_1_3_4_56_2","doi-asserted-by":"publisher","DOI":"10.7164\/antibiotics.32.852"},{"key":"e_1_3_4_57_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.77.7.3957"},{"key":"e_1_3_4_58_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI111618"},{"key":"e_1_3_4_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)42341-7"},{"key":"e_1_3_4_60_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.71.3.788"},{"key":"e_1_3_4_61_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.78.2.1194"},{"key":"e_1_3_4_63_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198801073180110"},{"key":"e_1_3_4_64_2","first-page":"46","article-title":"Rhabdomyolysis in patients receiving lovastatin after cardiac transplantation.","volume":"318","author":"East C","year":"1988","unstructured":"East C, Alivizatos PA, Grundy SM, Jones PJ, Farmer JA. Rhabdomyolysis in patients receiving lovastatin after cardiac transplantation. N Engl J Med 1988;318:46\u201347.","journal-title":"N Engl J Med"},{"key":"e_1_3_4_65_2","first-page":"48","article-title":"Response to ref, 59 \u2013 60.","volume":"318","author":"Tobert JA.","year":"1988","unstructured":"Tobert JA. Response to ref, 59 \u2013 60. N Engl J Med 1988;318:48.","journal-title":"N Engl J Med"},{"key":"e_1_3_4_66_2","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.1991.00400010067008"},{"key":"e_1_3_4_67_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200202143460720"},{"key":"e_1_3_4_68_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.109.192651"},{"key":"e_1_3_4_69_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9149(93)90438-I"},{"key":"e_1_3_4_70_2","first-page":"1383","article-title":"Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S).","volume":"344","author":"Scandinavian Simvastatin Survival Study Group","year":"1994","unstructured":"Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994;344:1383\u20131389.","journal-title":"Lancet"},{"key":"e_1_3_4_71_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199511163332001"},{"key":"e_1_3_4_72_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199610033351401"},{"key":"e_1_3_4_73_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(95)90926-5"},{"key":"e_1_3_4_74_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.97.15.1453"},{"key":"e_1_3_4_75_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.97.15.1440"},{"key":"e_1_3_4_76_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.97.15.1446"},{"key":"e_1_3_4_77_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199811053391902"},{"key":"e_1_3_4_78_2","doi-asserted-by":"publisher","DOI":"10.1161\/hc1002.105136"},{"key":"e_1_3_4_79_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa040583"},{"key":"e_1_3_4_80_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.292.11.1307"},{"key":"e_1_3_4_81_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa050461"},{"key":"e_1_3_4_82_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.294.19.2437"},{"key":"e_1_3_4_83_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)60310-8"},{"key":"e_1_3_4_84_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)61350-5"},{"key":"e_1_3_4_85_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.279.20.1615"},{"key":"e_1_3_4_86_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199701163360301"},{"key":"e_1_3_4_87_2","first-page":"810","article-title":"Results of the low dose (20 mg) pravastatin GISSI Prevenzione trial in 4271 patients with recent myocardial infarction; do stopped trials contribute to overall knowledge?","volume":"1","author":"GISSI Prevenzione Investigators (Gruppo Italiano per lo Studio della Sopravivenza nell\u2019Infarto Miocardico)","year":"2000","unstructured":"GISSI Prevenzione Investigators (Gruppo Italiano per lo Studio della Sopravivenza nell\u2019Infarto Miocardico). Results of the low dose (20 mg) pravastatin GISSI Prevenzione trial in 4271 patients with recent myocardial infarction; do stopped trials contribute to overall knowledge? Ital heart J 2000;1:810\u2013820.","journal-title":"Ital heart J"},{"key":"e_1_3_4_88_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.285.13.1711"},{"key":"e_1_3_4_89_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(02)09327-3"},{"key":"e_1_3_4_90_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.287.24.3215"},{"key":"e_1_3_4_91_2","doi-asserted-by":"publisher","DOI":"10.1185\/030079902125000787"},{"key":"e_1_3_4_92_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(02)11600-X"},{"key":"e_1_3_4_93_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.288.23.2998"},{"key":"e_1_3_4_94_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)12948-0"},{"key":"e_1_3_4_95_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)13638-0"},{"key":"e_1_3_4_96_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)16895-5"},{"key":"e_1_3_4_97_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2004.07.053"},{"key":"e_1_3_4_98_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa043545"},{"key":"e_1_3_4_99_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(06)69472-5"},{"key":"e_1_3_4_100_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa061894"},{"key":"e_1_3_4_101_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0706201"},{"key":"e_1_3_4_102_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(08)61240-4"},{"key":"e_1_3_4_103_2","first-page":"21995","article-title":"Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein.","volume":"359","author":"Ridker PM","year":"2088","unstructured":"Ridker PM, Danielson E, Fonseca FAH, Genest J, Gotto AM, Kastelein JJP, Koenig W, Libby P, Lorenzatti AJ, MacFadyen JG, Nordestgaard BG, Shepherd J, Willerson JT, Glynn RJ, for the JUPITER Study Group. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med 2088;359:21995\u20132207.","journal-title":"N Engl J Med"},{"key":"e_1_3_4_104_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0810177"},{"key":"e_1_3_4_105_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(11)60739-3"},{"key":"e_1_3_4_106_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)61368-4"},{"key":"e_1_3_4_107_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1410489"},{"key":"e_1_3_4_108_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1501031"},{"key":"e_1_3_4_109_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1500858"}],"container-title":["Circulation Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCRESAHA.115.306297","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T03:57:52Z","timestamp":1715572672000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCRESAHA.115.306297"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,2,19]]},"references-count":105,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2016,2,19]]}},"alternative-id":["10.1161\/CIRCRESAHA.115.306297"],"URL":"https:\/\/doi.org\/10.1161\/circresaha.115.306297","relation":{},"ISSN":["0009-7330","1524-4571"],"issn-type":[{"value":"0009-7330","type":"print"},{"value":"1524-4571","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,2,19]]},"assertion":[{"value":"2015-11-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-12-18","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-02-19","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}