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December 1, 1999

Antibiotic Use and Risk of Myocardial Infarction

Author Affiliations

Phil B.FontanarosaMD, Interim CoeditorIndividualAuthorMargaret A.WinkerMD, Deputy EditorIndividualAuthorStephenLurieMD PhD, Fishbein FellowIndividualAuthor

JAMA. 1999;282(21):1997-1999. doi:10-1001/pubs.JAMA-ISSN-0098-7484-282-21-jbk1201

To the Editor: Dr Meier and colleagues1 discuss their findings in the context of a potential association between the risk of AMI and bacterial infection with organisms susceptible to tetracyclines (and quinolones), particularly C pneumoniae. We wish to emphasize an alternative explanation for these intriguing observations.

Tetracyclines are now known to exhibit a wide range of nonantimicrobial therapeutic properties. As recently reviewed2,3 and confirmed in more than 30 laboratories around the United States and abroad, these properties include the ability to inhibit expression, activation, and extracellular activity of matrix metalloproteinases (MMPs), which represent a family of enzymes that help mediate connective tissue breakdown in various diseases, including periodontitis, osteoarthritis and rheumatoid arthritis, osteoporosis, cancer invasion and metastasis, abdominal aortic aneurysms, and atherosclerotic plaques. Tetracyclines also can suppress the production of inflammatory mediators involved in many of these disorders, such as prostaglandin E2, nitric oxide, interleukin 11β, tumor necrosis factor α, and interleukin 6, and they can scavenge reactive oxygen metabolites such as hypochlous acid, superoxide anion, and hydroxyl anion. By synthesizing a series of nonantimicrobial analogs of tetracycline (chemically modified tetracyclines), we and others have shown that the tetracyclines can inhibit connective tissue breakdown by a mechanism(s) independent of their antibiotic activity.2,3 We recently reported that both doxycycline and several nonantimicrobial chemically modified tetracyclines inhibit the development of aortic aneurysms in rats, an effect associated with suppressed MMP activity in the arterial wall.4