Elevated Angiotensin 1–7/Angiotensin II Ratio Predicts Favorable Outcomes in Patients With Heart Failure
Bibliographic record
Abstract
Background: ACE2 (angiotensin-converting enzyme 2) and Ang 1–7 (angiotensin 1–7) are endogenous negative regulators of the renin-angiotensin system exerting cardioprotective effects in models of heart failure. Recombinant human ACE2 markedly increased plasma Ang 1–7 and lowered Ang II levels in phase II clinical trials. We hypothesize that the dynamic state of this renin-angiotensin system protective arm could influence long-term outcomes in patients with heart failure. Methods: One hundred ten patients with heart failure were prospectively enrolled from our outpatient clinic and the emergency department. Comprehensive circulating and equilibrium levels of plasma angiotensin peptide profiles were assessed using novel liquid chromatography-mass spectrometry/mass spectroscopy techniques. Plasma aldosterone, B-type natriuretic peptide, active renin concentration, and clinical profiles were captured at baseline. During a median follow-up of 5.1 years (interquartile range, 4.7–5.7 years), composite clinical outcomes were assessed using all-cause in-patient hospitalizations and mortality. Results: Circulating and equilibrium angiotensin peptide levels strongly correlated in our patient cohort. Adjusting for covariates, elevated equilibrium (hazard ratio, 0.38 [95% CI, 0.18–0.81] P =0.012), and circulating (hazard ratio, 0.38 [95% CI, 0.18–0.80] P =0.011) Ang 1–7/Ang II ratios were associated with improved survival. Lower hospitalization duration was also associated with elevated equilibrium ( P <0.001) and circulating ( P =0.023) Ang 1–7/Ang II ratios. Importantly, individual Ang 1–7 and Ang II peptide levels failed to predict all-cause mortality or hospitalization duration in our patient cohort. Conclusions: We extensively profiled plasma angiotensin peptides in patients with heart failure and identified elevated Ang 1–7/Ang II ratio, as an independent and incremental predictor of beneficial outcomes, higher survival rate, and decreased hospitalization duration. These findings provide important clinical evidence supporting strategies aiming to promote the beneficial Ang 1–7/Mas axis concurrent with renin-angiotensin system blockade therapies inhibiting the detrimental Ang II/AT 1 receptor axis.
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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) | 0.001 | 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".