Subclinical Primary Aldosteronism and Major Adverse Cardiovascular Events: A Longitudinal Population-Based Cohort Study
Bibliographic record
Abstract
BACKGROUND: Primary aldosteronism (PA), an overt form of renin-independent aldosterone production, leads to a disproportionately high rate of major adverse cardiovascular events (MACEs). Mounting evidence suggests that milder forms of renin-independent aldosterone production (subclinical PA) are highly prevalent; however, the link between subclinical PA and MACE remains uncertain. METHODS: This prospective study included 2017 Canadian adults 40 to 69 years of age from the randomly sampled, population-based CARTaGENE cohort (Québec, Canada), in which aldosterone and renin concentrations at enrollment (2009-2010) were measured. Follow-up data were obtained via provincial health care administrative database linkage. MACE outcomes consisted of a composite of myocardial infarction, stroke, hospitalization for heart failure, and cardiovascular death. Multivariable linear and nonlinear Cox regression models measured the associations of concentrations of aldosterone, renin, and the aldosterone-to-renin ratio with MACE. Outcome-derived optimal thresholds for these markers were then determined. RESULTS: The mean (SD) age of participants was 56 (8) years, and 45% were women. Mean blood pressure was 129 (15)/76 (10) mm Hg, with hypertension being present in 27%. Over a median follow-up time of 10.8 years, 57 (3%) MACE outcomes occurred. Lower renin concentration (adjusted hazard ratio [aHR], 2.22 [95% CI, 1.02-4.76]) and higher aldosterone-to-renin ratio (aHR, 2.43 [95% CI, 1.15-5.12]) were associated with a higher risk for MACE, whereas no significant association was found with aldosterone concentration (aHR, 1.57 [95% CI, 0.42-5.90]). Renin concentration exhibited a nonlinear relationship with MACE risk. The outcome-derived optimal thresholds to discriminate a higher MACE risk were renin concentration ≤4.0 ng/L (aHR, 2.12 [95% CI, 1.21-3.72]) and aldosterone-to-renin ratio ≥70 pmol/L per ng/L (aHR, 2.03 [95% CI, 1.09-3.80]). All aforementioned associations were independent of blood pressure. CONCLUSIONS: Independent of blood pressure, the subclinical PA biochemical phenotype is associated with an increased risk of MACE. Future studies are necessary to determine whether early identification and targeted treatment of subclinical PA mitigates this risk.
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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 | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".