title: How May Proton Pump Inhibitors Impair Cardiovascular Health?
abstract: Proton pump inhibitors (PPIs) are among the most widely used drugs worldwide. They are used to treat a number of gastroesophageal disorders and are usually prescribed as a long-term medication or even taken without a prescription. There are a number of clinical studies that associate PPI use with an increased cardiovascular risk. In this article, we review the clinical evidence for adverse cardiovascular effects of PPIs, and we discuss possible biological mechanisms by which PPIs can impair cardiovascular health.
authors.affiliation: Department of Cardiovascular Sciences, Houston Methodist Research Institute, 6670 Bertner Ave, Houston, TX, 77030, USA.
authors.forename: Roman A
authors.initials: RA
authors.lastname: Sukhovershin
authors.affiliation: Department of Cardiovascular Sciences, Houston Methodist Research Institute, 6670 Bertner Ave, Houston, TX, 77030, USA. jpcooke@houstonmethodist.org.
authors.forename: John P
authors.initials: JP
authors.lastname: Cooke
mesh_terms: D000818:Animals; D000897:Anti-Ulcer Agents / Q000009:adverse effects; D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000453:epidemiology / Q000378:metabolism / Q000503:physiopathology; D002319:Cardiovascular System / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D016903:Drug Monitoring; D019317:Evidence-Based Medicine; D006801:Humans; D008955:Models, Cardiovascular; D004366:Nonprescription Drugs / Q000009:adverse effects; D017410:Practice Guidelines as Topic; D054328:Proton Pump Inhibitors / Q000009:adverse effects*; D012307:Risk Factors
chemical_list: D000897:Anti-Ulcer Agents; D004366:Nonprescription Drugs; D054328:Proton Pump Inhibitors
references.citation: Circulation. 1998 Nov 3;98(18):1842-7
references.pmid: 9799202
references.citation: Nat Rev Drug Discov. 2008 Feb;7(2):156-67
references.pmid: 18167491
references.citation: South Med J. 2012 Nov;105(11):613-8
references.pmid: 23128806
references.citation: PLoS One. 2013;8(12):e84890
references.pmid: 24386430
references.citation: Pharmacogenomics J. 2015 Feb;15(1):20-5
references.pmid: 25001880
references.citation: J Gastroenterol. 2013 Dec;48(12):1343-52
references.pmid: 23478938
references.citation: Arch Intern Med. 2010 May 10;170(9):747-8
references.pmid: 20458079
references.citation: Open Heart. 2015 Jun 30;2(1):e000248
references.pmid: 26196021
references.citation: Int J Cardiol. 2014 Nov 15;177(1):292-7
references.pmid: 25499395
references.citation: Gastroenterol Nurs. 2003 Sep-Oct;26(5):182-90
references.pmid: 14603076
references.citation: Gastroenterol Rep (Oxf). 2015 Aug;3(3):243-53
references.pmid: 25138239
references.citation: J Clin Invest. 1992 Sep;90(3):1168-72
references.pmid: 1522225
references.citation: Cell Death Dis. 2010;1:e87
references.pmid: 21368860
references.citation: Pharmacotherapy. 2010 Oct;30(10):985-93
references.pmid: 20874035
references.citation: Eur J Clin Pharmacol. 2008 Oct;64(10):935-51
references.pmid: 18679668
references.citation: Surg Endosc. 2005 Dec;19(12):1610-2
references.pmid: 16211437
references.citation: Arch Intern Med. 2010 May 10;170(9):765-71
references.pmid: 20458083
references.citation: Can J Cardiol. 2004 Aug;20 Suppl B:7B-15B
references.pmid: 15309199
references.citation: Vasc Med. 2005 Jul;10 Suppl 1:S1-2
references.pmid: 16444862
references.citation: Am J Gastroenterol. 2009 Mar;104 Suppl 2:S10-6
references.pmid: 19262540
references.citation: PLoS One. 2015;10(6):e0124653
references.pmid: 26061035
references.citation: Circulation. 2003 Aug 26;108(8):933-8
references.pmid: 12912818
references.citation: Circulation. 2003 Dec 16;108(24):3042-7
references.pmid: 14638548
references.citation: Vasc Med. 2005 Jul;10 Suppl 1:S45-8
references.pmid: 16444868
references.citation: Circulation. 2013 Aug 20;128(8):845-53
references.pmid: 23825361
references.citation: Best Pract Res Clin Gastroenterol. 2001 Jun;15(3):355-70
references.pmid: 11403532
references.citation: JAMA. 2009 Mar 4;301(9):937-44
references.pmid: 19258584
references.citation: Ann Intern Med. 2008 Sep 16;149(6):391-8
references.pmid: 18794558
references.citation: CMAJ. 2009 Mar 31;180(7):713-8
references.pmid: 19176635
references.citation: Am J Clin Nutr. 1987 May;45(5 Suppl):1344-50
references.pmid: 3578122
references.citation: Aliment Pharmacol Ther. 2001 Dec;15(12):1929-37
references.pmid: 11736724
references.citation: N Engl J Med. 2010 Nov 11;363(20):1909-17
references.pmid: 20925534
references.citation: Circulation. 2014 Apr 1;129(13):e427
references.pmid: 24687653
references.citation: J Am Coll Cardiol. 1999 Oct;34(4):1201-7
references.pmid: 10520813
references.citation: Cleve Clin J Med. 2011 Jan;78(1):39-49
references.pmid: 21199906
references.citation: Circ Cardiovasc Qual Outcomes. 2015 Jan;8(1):47-55
references.pmid: 25587094
references.citation: Arterioscler Thromb Vasc Biol. 2000 Sep;20(9):2032-7
references.pmid: 10978245
references.citation: Stroke. 2006 Aug;37(8):2024-9
references.pmid: 16809568
references.citation: J Neurogastroenterol Motil. 2013 Jan;19(1):25-35
references.pmid: 23350044
references.citation: Am J Physiol Heart Circ Physiol. 2007 Dec;293(6):H3227-45
references.pmid: 17933965
references.citation: BMJ. 2011;342:d2690
references.pmid: 21562004
references.citation: Am J Emerg Med. 2014 Jun;32(6):618-22
references.pmid: 24721025
references.citation: Eur J Clin Pharmacol. 2015 Jan;71(1):125-9
references.pmid: 25384436
references.citation: Am J Clin Pathol. 1998 Nov;110(5):615-21
references.pmid: 9802346
references.citation: Vasc Med. 2010 Aug;15(4):267-74
references.pmid: 20484311
references.citation: Arterioscler Thromb Vasc Biol. 1996 Jan;16(1):44-50
references.pmid: 8548425
references.citation: J Biomol Screen. 2012 Jun;17(5):651-61
references.pmid: 22460174
references.citation: CMAJ. 2011 Feb 22;183(3):310-9
references.pmid: 21173070
references.citation: Clin Pharmacokinet. 2000 Mar;38(3):243-70
references.pmid: 10749519
references.citation: Free Radic Biol Med. 2013 Dec;65:446-55
references.pmid: 23892053
references.citation: Drug Saf. 2014 Apr;37(4):201-11
references.pmid: 24550106
references.citation: Arterioscler Thromb Vasc Biol. 2011 Jul;31(7):1462-4
references.pmid: 21677286
references.citation: Heart Fail Rev. 2014 Mar;19(2):237-46
references.pmid: 23135208
references.citation: Int J Cardiol. 2013 Aug 10;167(3):965-74
references.pmid: 22464478
references.citation: J Am Geriatr Soc. 2011 Sep;59(9):1658-64
references.pmid: 21883102
references.citation: J Am Chem Soc. 2004 Jun 30;126(25):7800-11
references.pmid: 15212527
references.citation: Vasc Med. 2015 Aug;20(4):309-16
references.pmid: 25835348
references.citation: Am J Gastroenterol. 2009 Mar;104 Suppl 2:S5-9
references.pmid: 19262546
references.citation: Int J Clin Pharmacol Ther. 2006 Jul;44(7):297-302
references.pmid: 16961157
references.citation: Circulation. 2014 Apr 1;129(13):e426
references.pmid: 24687652
references.citation: J Med Chem. 1986 Aug;29(8):1327-9
references.pmid: 3016260
references.citation: Gut. 1994 Nov;35(11):1543-6
references.pmid: 7828969
references.citation: Pflugers Arch. 2009 Jan;457(3):609-22
references.pmid: 18536934
references.citation: Intern Med. 2010;49(23):2561-8
references.pmid: 21139293
references.citation: Circulation. 2012 Feb 28;125(8):978-86
references.pmid: 22261200
references.citation: Drug Metab Pharmacokinet. 2005 Jun;20(3):153-67
references.pmid: 15988117
references.citation: Digestion. 2001;64(4):205-13
references.pmid: 11842276
references.citation: Vasc Med. 2005 Jul;10 Suppl 1:S27-33
references.pmid: 16444866
references.citation: Scand J Gastroenterol Suppl. 1985;108:23-35
references.pmid: 3858975
references.citation: Aliment Pharmacol Ther. 2012 Jan;35(1):165-74
references.pmid: 22050009
references.citation: Ann Pharmacother. 2009 Nov;43(11):1836-47
references.pmid: 19843838
references.citation: Scand J Gastroenterol. 2010 Apr;45(4):389-94
references.pmid: 20001749
references.citation: Free Radic Biol Med. 2012 Aug 15;53(4):701-9
references.pmid: 22721923
references.citation: Free Radic Biol Med. 2015 Oct;87:252-62
references.pmid: 26159506
references.citation: Aliment Pharmacol Ther. 2011 Jan;33(1):77-88
references.pmid: 21083580
references.citation: CMAJ. 2008 Aug 12;179(4):319-26
references.pmid: 18695179
references.citation: Cardiovasc Res. 2011 Feb 15;89(3):574-85
references.pmid: 21097806
references.citation: Drugs. 2003;63(24):2739-54
references.pmid: 14664653
references.citation: Pharmacogenomics. 2004 Mar;5(2):181-202
references.pmid: 15016609
references.citation: Anesthesiology. 2010 Dec;113(6):1460-75
references.pmid: 21045638
references.citation: Methodist Debakey Cardiovasc J. 2015 Jul-Sep;11(3):166-71
references.pmid: 26634024
references.citation: Circulation. 1997 Aug 5;96(3):934-40
references.pmid: 9264504
references.citation: Kidney Int. 2013 Apr;83(4):553-6
references.pmid: 23538697
references.citation: Ann Thorac Surg. 2006 Sep;82(3):895-901
references.pmid: 16928504
references.citation: Ann Intern Med. 2010 Sep 21;153(6):378-86
references.pmid: 20855802
references.citation: Aliment Pharmacol Ther. 2012 Sep;36(5):405-13
references.pmid: 22762246