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
BackgroundCardiovascular 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.MethodsHealthy 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.ResultsThirteen 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).ConclusionsThe 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 distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.000 |
| 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) | 0.000 | 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 teacher head, 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".