The Effect of Biological Sex on Arterial Stiffness and Renin-Angiotensin-Aldosterone System Activity in Response to Cyclooxygenase-2 (COX-2) Inhibition
Bibliographic record
Abstract
Background Cardiovascular disease is the leading cause of death globally. Cyclooxygenase (COX)-derived prostaglandins play an important role in cardiovascular health regulation. Animal studies suggest a greater vascular dependence on prostaglandins in females, though whether this extends to humans is unknown. We aimed to assess the effect of COX-2 inhibition on blood pressure and arterial stiffness, validated markers of cardiovascular risk, in adults. Methods Healthy premenopausal females and males were studied in high-salt balance before and after 14 days of daily oral celecoxib 200mg ingestion on two identical study days. Blood pressure and pulse-wave velocity (PWV) were measured at baseline and in response to an Angiotensin II (AngII) challenge, a validated marker of renin-angiotensin-aldosterone system activity. Results Thirteen females (38±13 years) and 11 males (34±9 years) were studied. Pre-COX-2 inhibition, resting measures of SBP ( p =0.2) and DBP ( p =0.1) were similar between sexes. Post-COX-2 inhibition, resting SBP ( p <0.001) and DBP were ( p =0.02) significantly lower in females as compared to males. COX-2 inhibition was not associated with changes in arterial parameters by sex (ΔDBP: p =0.54; ΔPWV: p =0.55; females vs. males). COX-2 inhibition was associated with increased SBP ( p =0.039 vs. pre-COX-2 inhibition), but no change in DBP ( p =0.16) or PWV ( p =0.52) response to AngII challenge in females. Measures did not differ in response to AngII pre-vs post-COX-2 inhibition in males (SBP: p =0.88; DBP: p =0.93; PWV: p =0.97). Conclusions The effects of COX-2 inhibition on arterial function may differ by sex, though further studies are needed. Given the association between NSAIDs and cardiovascular risk, increased attention into sex-specific pathophysiology is warranted.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".