Dose-response association and predictive value of plasma aldosterone concentration for cardiometabolic multimorbidity in patients with hypertension: a retrospective cohort study.
Zhang Z, Li N, et al. • Frontiers in endocrinology • 2026
The possibility of a CMM incident was positively correlated with PAC in a nonlinear fashion, and this correlation differed depending on serum potassium levels; adding PAC to a conventional risk model improved predictive performance and net clinical benefit in hypertensive patients.
Key Findings
Results
Higher baseline plasma aldosterone concentration (PAC) was independently associated with higher hazard of incident cardiometabolic multimorbidity (CMM) in hospitalized hypertensive patients.
Retrospective cohort of 7,677 hospitalized hypertensive patients without CMM at baseline; average follow-up 3.52 years.
1,949 incident CMM cases were documented during follow-up.
In multivariable Cox regression, each 1-ng/dL increment in PAC was associated with a 2% higher hazard (HR 1.02; 95% CI 1.02-1.03).
Results
Risk of CMM rose stepwise across PAC quartiles, with the highest quartile having the greatest cumulative incidence.
Kaplan-Meier analysis showed Q4 had considerably greater cumulative likelihood of CMM than other quartiles (log-rank P < 0.05).
Adjusted HRs versus Q1 were 1.19 (95% CI 1.04-1.36) for Q2, 1.32 (95% CI 1.16-1.52) for Q3, and 1.65 (95% CI 1.45-1.87) for Q4.
P for trend < 0.001.
Results
The PAC-CMM association was nonlinear, with an estimated inflection point near 15.34 ng/dL above which risk rose.
Restricted cubic spline analysis gave P for nonlinearity < 0.001.
The risk curve showed an upward trend above approximately 15.34 ng/dL.
Results
The PAC-CMM association may differ by serum potassium status.
Subgroup analyses indicated a significant interaction (P for interaction < 0.05).
Based on this, RCS analyses stratified by serum potassium and a bivariate penalized spline model were used to characterize the joint nonlinear association of potassium and PAC with CMM risk.
Results
Adding PAC to a conventional risk model improved 3-year risk discrimination and reclassification.
Time-dependent AUC (IPCW) increased from 0.678 to 0.735 (P < 0.001).
Survival-based net reclassification improvement was 0.372.
Integrated discrimination improvement was 0.038 (P < 0.05).
Results
Incorporating PAC may provide additional net clinical benefit across clinically relevant threshold probabilities.
Decision curve analysis suggested additional estimated net benefit with PAC in the model.
Calibration assessment was also performed as part of the evaluation.
Results
The Boruta feature-selection algorithm identified PAC as an important predictor of CMM, and findings were consistent across subgroup and sensitivity analyses.
Boruta was used for feature selection and variable importance assessment.
Overall findings remained consistent across subgroup and sensitivity analyses.
What This Means
This study followed 7,677 hospitalized people with high blood pressure who did not yet have multiple cardiometabolic conditions (such as combinations of heart disease, stroke, and diabetes). Over an average of about 3.5 years, 1,949 developed cardiometabolic multimorbidity. People with higher blood levels of aldosterone, a hormone that regulates salt and blood pressure, were more likely to develop it. Those in the highest quartile of aldosterone had about a 65% higher hazard than those in the lowest, after accounting for other factors.
The relationship was not a straight line: risk appeared to rise more clearly above roughly 15.34 ng/dL. The link also seemed to differ depending on the person's blood potassium level. When aldosterone was added to a standard risk prediction model, the model better distinguished who would and would not develop multimorbidity within three years (AUC 0.678 to 0.735) and showed more net clinical benefit.
This research suggests aldosterone could provide additional information for assessing cardiometabolic risk in people with hypertension. However, this was a retrospective, hospital-based study, so it shows association rather than cause, and the findings would need confirmation in other populations before being applied in practice.
Zhang Z, Li N, Zhu Q, Hu J, Hong J, Yang W, et al.. (2026). Dose-response association and predictive value of plasma aldosterone concentration for cardiometabolic multimorbidity in patients with hypertension: a retrospective cohort study.. Frontiers in endocrinology. https://doi.org/10.3389/fendo.2026.1965927