Long-Term PPI Use Linked to Damaged Blood Vessels

Long-term use of proton pump inhibitors (PPIs) for gastroesophageal reflux is associated with accelerated aging in blood vessel cells, according to a recent study.

Previous research has drawn connections between long-term PPI use and several serious conditions, including heart disease, kidney disease, and dementia, but the mechanism behind this relationship is not yet understood.
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To explore this relationship, researchers exposed human endothelial cells to 2 PPIs, and found that prolonged exposure to the drugs led to “accelerated biological aging.”^1,2

Long-term exposure impaired acid production in the lysosomes within the cells lining blood vessel walls, preventing the cells from clearing waste and causing the premature aging.  

“With the knowledge that PPIs are being used by millions of people for indications and durations that were never tested or approved, it may be time for the pharmaceutical industry and regulatory agencies to re-visit the specificity and the safety of these agents,” they concluded.

“Unless otherwise indicated, physicians should consider PPIs only for short-term use for relief of symptoms of [gastroesophageal reflux disease], since we now have a ‘smoking gun’ that helps explain the consistent observational evidence of increased risk.”

The researchers recommended lifestyle modifications, surgical approaches, and H₂ antagonists—another antacid that did not show the same adverse effects—for the long-term treatment of reflux.

The authors listed several limitations for their study. Only one of the 2 tested PPIs is commercially available, the study did not show how PPIs impair lysomsome's acid production, and because of the laboratory setting, the study could not establish whether PPIs act the same way within the human body. They noted that to further understanding of the safety and efficacy of PPIs, long-term clinical trials are necessary.

—Michael Potts

References:

1. Yepuri G, Sukhovershin R, Nazari-Shafti TZ, Petrascheck M, Ghebre YT, Cooke JP. Proton pump inhibitors accelerate endothelial senescence [published online May 10, 2016]. Circ Res. doi: 10.1161/CIRCRESAHA.116.308807.
2. American Heart Association. Heartburn drug damages blood vessel cells in lab finding [press release. May 10, 2016. http://www.alphagalileo.org/ViewItem.aspx?ItemId=163817&CultureCode=en.