Sex-Related Pathophysiological Mechanisms May Be Present Before Symptoms of HFpEF Develop
Bibliographic record
Abstract
Abstract Aims Understanding sex-related cardiovascular differences in those with pre-HFpEF (asymptomatic with normal ejection fraction, elevated natriuretic peptides and structural or functional heart disease) could help explain why females are more likely to develop symptomatic HFpEF compared with males. This study analyses sex-related cardiovascular differences in pre-HFpEF, including measures of cardiovascular stiffness and vascular resistance derived from cardiac magnetic resonance imaging (CMR) and Doppler echocardiography. Methods and results This post hoc analysis of the PARABLE trial enrolled 250 patients with pre-HFpEF. CMR and Doppler echocardiography were used to estimate baseline markers of cardiovascular stiffness and resistance, including effective arterial elastance (EAE), systemic vascular resistance (SVR), total arterial compliance (TAC), left ventricular end diastolic pressure (LVEDP) and left ventricular end diastolic chamber stiffness index (LVSId). The population median age was 72.0 [IQR 68.0; 77.0] years and 38.4% were female. Both sexes had a similar age, blood pressure, HbA1c, renal function and H2FPEF score. Fewer female participants had a diagnosis of diabetes and coronary artery disease. When adjusted for age, hypertension, diabetes, obesity and vascular disease, female participants had higher pulse pressures (62.1 (SD 15.3) vs. 60.1 (SD 12.5) mmHg, P < 0.001) as well as higher median [IQR] levels of LDL-cholesterol (2.50 [2.10; 3.25] vs. 2.00 [1.60; 2.40] mmol/L, P < 0.001), EAE (1.55 [1.26; 1.84] vs. 1.26 [1.05; 1.51] mmHg/mL/m2, P < 0.001), SVR (1609 [1288; 1887] vs. 1336 [1132; 1734] mmHg/mL/min2, P = 0.001), LVEDP (18.5 [17.2; 20.1] vs. 18.0 [16.9; 19.3] mmHg, P < 0.001) and LVSId (0.28 [0.24; 0.31] vs 0.24 [0.20; 0.29] mmHg/mL/m2, P < 0.001) than males. Females had higher median [IQR] NT-proBNP (176 [95.8; 286] vs. 127 [81.5; 242] pg/mL, P < 0.001) and lower median [IQR] TAC (1.24 [0.99; 1.58] vs. 1.55 [1.18; 1.91] mL/mmHg, P < 0.001) than male participants. Conclusions Markers of elevated cardiovascular stiffness and vascular resistance are seen in female versus male participants with pre-HFpEF, suggesting that sex-related pathophysiological mechanisms are present before symptoms of HF develop.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| 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".