Chronic COX-2 suppression caused diastolic dysfunction and heart failure features specifically in aged female mice, linking long-term NSAID use to HFpEF risk.
Aged female-specific effectOnly aged female mice developed cardiac dysfunction from COX-2 suppression, while young mice and males were unaffected
What the researchers found
Long-term COX-2 suppression caused diastolic dysfunction and features of HFpEF in aged female mice, while younger mice were unaffected.
Why it matters
Millions of people take NSAIDs regularly, and heart failure is a known risk. This study suggests that the risk may be specifically for HFpEF — a type of heart failure that is poorly understood and has few effective treatments.
The numbers in context
The study used inducible COX-2 knockout mice. Aged female mice developed diastolic dysfunction; young mice and pharmacologically inhibited mice did not show acute effects.
How the study worked
Genetic knockout and pharmacological inhibition of COX-2 in mice, comparing cardiac function across age groups and sexes.
Who was studied
C57BL/6 mice with inducible COX-2 knockout, aged females primarily affected
What this study cannot tell us
This is a mouse study, and the findings may not directly translate to humans. The sex-specific effect (females only) needs further investigation.
How to read the evidence
Rated preliminary: animal study using genetic knockout and pharmacological inhibition, showing a clear sex- and age-specific effect needing human confirmation.
When this study was published
Published in 2024. Adds mechanistic understanding to the well-known association between NSAIDs and heart failure risk.
The bigger picture
Millions of people take NSAIDs regularly, and heart failure is a known risk. This study suggests the specific risk may be HFpEF — a poorly understood form of heart failure with limited treatment options that disproportionately affects older women.
Questions still open
- Is there a safe duration of NSAID use before heart risk increases?
- Why are aged females specifically vulnerable to this effect?
Common questions
Can long-term NSAID use cause heart failure?
Why are older women more affected?
Read the original research
Suppression of cyclooxygenase-2 predisposes to heart failure with preserved ejection fraction.
bioRxiv : the preprint server for biology
Citation
Ricciotti, Emanuela; Haines, Philip G; Beerens, Manu; Kartoun, Uri; Castro, Cecilia; Tang, Soon Yew; Ghosh, Soumita; Das, Ujjalkumar S; Lahens, Nicholas F; Wang, Tao; Griffin, Jules L; Shaw, Stanley Y; MacRae, Calum A; FitzGerald, Garret A. (2024). Suppression of cyclooxygenase-2 predisposes to heart failure with preserved ejection fraction.. bioRxiv : the preprint server for biology. https://doi.org/10.1101/2024.09.28.615616