Editing Statin (section)

===Other effects===
As noted above, statins exhibit action beyond lipid-lowering activity in the prevention of [[atherosclerosis]] through so-called "pleiotropic effects of statins".<ref name=":1" /> The pleiotropic effects of statins remain controversial.<ref name=":2">{{cite journal | vauthors = Liao JK, Laufs U | title = Pleiotropic effects of statins | journal = Annual Review of Pharmacology and Toxicology | volume = 45 | pages = 89–118 | year = 2005 | pmid = 15822172 | pmc = 2694580 | doi = 10.1146/annurev.pharmtox.45.120403.095748 }}</ref> The ASTEROID trial showed direct [[intravascular ultrasound|ultrasound]] evidence of [[atheroma]] regression during statin therapy.<ref name="Nissen2006">{{cite journal | vauthors = Nissen SE, Nicholls SJ, Sipahi I, Libby P, Raichlen JS, Ballantyne CM, Davignon J, Erbel R, Fruchart JC, Tardif JC, Schoenhagen P, Crowe T, Cain V, Wolski K, Goormastic M, Tuzcu EM | title = Effect of very high-intensity statin therapy on regression of coronary atherosclerosis: the ASTEROID trial | journal = JAMA | volume = 295 | issue = 13 | pages = 1556–1565 | date = April 2006 | pmid = 16533939 | doi = 10.1001/jama.295.13.jpc60002 | doi-access = free | title-link = doi }}</ref> Researchers hypothesize that statins prevent [[cardiovascular disease]] via four proposed mechanisms (all subjects of a large body of biomedical research):<ref name=":2" />

# Improve [[endothelium|endothelial]] function
# Modulate [[inflammation|inflammatory]] responses
# Maintain [[atherosclerosis|plaque]] stability
# Prevent [[thrombosis|blood clot]] formation

In 2008, the [[JUPITER trial]] showed statins provided benefit in those who had no history of [[hyperlipidemia|high cholesterol]] or heart disease, but only in those with elevated high-sensitivity [[C-reactive protein]] (hsCRP) levels, an indicator for inflammation.<ref name="Ridker2008">{{cite journal | vauthors = Ridker PM, Danielson E, Fonseca FA, Genest J, Gotto AM, Kastelein JJ, Koenig W, Libby P, Lorenzatti AJ, MacFadyen JG, Nordestgaard BG, Shepherd J, Willerson JT, Glynn RJ | title = Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein | journal = The New England Journal of Medicine | volume = 359 | issue = 21 | pages = 2195–2207 | date = November 2008 | pmid = 18997196 | doi = 10.1056/NEJMoa0807646 | doi-access = free | title-link = doi }}</ref> The study has been criticized due to perceived flaws in the study design,<ref>{{cite journal | vauthors = Kones R | title = Rosuvastatin, inflammation, C-reactive protein, JUPITER, and primary prevention of cardiovascular disease—a perspective | journal = Drug Design, Development and Therapy | volume = 4 | pages = 383–413 | date = December 2010 | pmid = 21267417 | pmc = 3023269 | doi = 10.2147/DDDT.S10812 | doi-access = free | title-link = doi }}</ref><ref>{{cite journal | vauthors = Ferdinand KC | title = Are cardiovascular benefits in statin lipid effects dependent on baseline lipid levels? | journal = Current Atherosclerosis Reports | volume = 13 | issue = 1 | pages = 64–72 | date = February 2011 | pmid = 21104458 | doi = 10.1007/s11883-010-0149-9 | s2cid = 32142669 }}</ref><ref>{{cite journal | vauthors = Devaraj S, Siegel D, Jialal I | title = Statin therapy in metabolic syndrome and hypertension post-JUPITER: what is the value of CRP? | journal = Current Atherosclerosis Reports | volume = 13 | issue = 1 | pages = 31–42 | date = February 2011 | pmid = 21046291 | pmc = 3018293 | doi = 10.1007/s11883-010-0143-2 }}</ref> although [[Paul Ridker|Paul M. Ridker]], lead investigator of the JUPITER trial, has responded to these criticisms at length.<ref>{{cite journal | vauthors = Ridker PM, Glynn RJ | title = The JUPITER Trial: responding to the critics | journal = The American Journal of Cardiology | volume = 106 | issue = 9 | pages = 1351–1356 | date = November 2010 | pmid = 21029837 | doi = 10.1016/j.amjcard.2010.08.025 }}</ref>

{{StatinPathway_WP430}}

As the target of statins, the HMG-CoA reductase, is highly similar between [[eukaryota]] and [[archaea]], statins also act as antibiotics against archaea by inhibiting archaeal mevalonate biosynthesis. This has been shown in vivo and in vitro.<ref name="pmid30702149">{{cite journal | vauthors = Vögeli B, Shima S, Erb TJ, Wagner T | title = Crystal structure of archaeal HMG-CoA reductase: insights into structural changes of the C-terminal helix of the class-I enzyme | journal = FEBS Letters | volume = 593 | issue = 5 | pages = 543–553 | date = March 2019 | pmid = 30702149 | doi = 10.1002/1873-3468.13331 | s2cid = 73412833 | doi-access = free | title-link = doi }}</ref> Since patients with a constipation phenotype present with higher abundance of methanogenic archaea in the gut, the use of statins for management of [[irritable bowel syndrome]] has been proposed and may actually be one of the hidden benefits of statin use.<ref name="pmid26559904">{{cite journal | vauthors = Gottlieb K, Wacher V, Sliman J, Pimentel M | title = Review article: inhibition of methanogenic archaea by statins as a targeted management strategy for constipation and related disorders | journal = Alimentary Pharmacology & Therapeutics | volume = 43 | issue = 2 | pages = 197–212 | date = January 2016 | pmid = 26559904 | pmc = 4737270 | doi = 10.1111/apt.13469 }}</ref><ref name="pmid26066650">{{cite journal | vauthors = Lurie-Weinberger MN, Gophna U | title = Archaea in and on the Human Body: Health Implications and Future Directions | journal = PLOS Pathogens | volume = 11 | issue = 6 | pages = e1004833 | date = June 2015 | pmid = 26066650 | pmc = 4466265 | doi = 10.1371/journal.ppat.1004833 | doi-access = free | title-link = doi }}</ref>