Screening Biomarkers Kept Their Signal Long After the Initial Primary Aldosteronism Workup
Screening aldosterone-to-renin ratio and plasma renin activity appear to carry prognostic weight well beyond the first diagnostic visit in patients evaluated for primary aldosteronism. In a seven-hospital Taiwanese cohort linked to nationwide insurance and mortality data, higher screening ARR and lower screening PRA tracked with later major adverse cardiovascular events in patients ultimately classified as confirmatory-test-defined essential hypertension and in those with primary aldosteronism who did not undergo adrenalectomy. The pattern weakened after adrenalectomy, where the same screening biomarkers no longer showed a clear relationship with long-term risk.
Across 3,178 participants followed for a median 7.9 years, 441 individuals experienced a major adverse cardiovascular event, defined as myocardial infarction, stroke, heart failure hospitalization, or cardiovascular death. The cohort included 1,433 patients with essential hypertension, 834 with primary aldosteronism without adrenalectomy, and 911 with primary aldosteronism who later underwent adrenalectomy. Those are not small strata, and the separation between groups gives the biomarker analysis enough clinical texture to matter: the renin-aldosterone profile at screening did not behave as a simple diagnostic marker, but as a physiologic readout with long-range cardiovascular implications.
ARR and PRA Point in Opposite Directions Across Risk Trajectories
Per 1-unit increase in logARR, adjusted hazard ratios for major adverse cardiovascular events were 1.09 in confirmatory-test-defined essential hypertension, 1.14 in primary aldosteronism without adrenalectomy, and 0.95 in primary aldosteronism with adrenalectomy. In plain clinical terms, a higher ARR aligned with greater long-term cardiovascular risk in the first two phenotypes, while the association disappeared after surgical treatment. The renin signal moved in the opposite direction: per 1-unit increase in logPRA, adjusted hazard ratios were 0.91, 0.87, and 1.04 across the same three groups. Lower renin therefore marked higher risk in the untreated or medically managed phenotypes, which fits the biology of persistent mineralocorticoid excess and chronic volume-expanded hypertension.
Aldosterone excess suppresses renin through sodium retention, plasma volume expansion, and downstream vascular injury. When that hormonal pattern persists, the heart and vessels are exposed to a pro-hypertensive, pro-fibrotic milieu that can outlast the initial diagnostic evaluation by years. The event pattern here is consistent with that mechanism. The signal was present even among patients who ultimately did not meet confirmatory criteria for primary aldosteronism but still carried an adverse screening profile, suggesting that the ARR may be acting as a marker of clinically meaningful renin suppression rather than as a narrow binary test result.
Adrenalectomy Appeared to Blur the Prognostic Meaning of the Screening Profile
In patients who underwent adrenalectomy, neither screening ARR nor screening PRA showed a clear association with future major adverse cardiovascular events. The adjusted hazard ratio for logARR in that group was 0.95 with a 95% confidence interval crossing 1.0, while logPRA was 1.04 with a similarly non-informative interval. Primary biomarker-by-phenotype interactions did not reach conventional statistical significance, although the interaction P values for logARR and logPRA were 0.057 and 0.069, respectively. Those values sit close to the boundary, but they do not convert the analysis into a definitive interaction claim.
The most plausible explanation is physiologic rather than statistical. Adrenalectomy removes the dominant source of autonomous aldosterone secretion, and once that endocrine driver is eliminated, the original screening profile may lose some of its long-term prognostic relevance. Surgical correction can normalize the hormonal forcing that keeps renin suppressed and aldosterone excessive, so the preoperative biomarker signature no longer separates patients as sharply by future event risk. In other words, the screening test seems to preserve prognostic meaning when the underlying aldosterone excess remains present, but its predictive value becomes less distinct after definitive source control.
LogPAC Added Less to Long-Term Risk Stratification
Screening plasma aldosterone concentration did not show consistent associations with major adverse cardiovascular events across the phenotypes. That finding matters because aldosterone concentration alone is often tempting to interpret as the central endocrine exposure, yet this analysis places greater weight on the ratio between aldosterone and renin, and on the suppression of renin itself. A high aldosterone value without context can miss the hemodynamic reality of the renin-angiotensin-aldosterone axis. The ratio captures the imbalance, and the renin component may be the more sensitive marker of whether the cardiovascular system has been living under sustained mineralocorticoid pressure.
The cohort design also adds credibility to the clinical interpretation. Patients came from the Taiwan Primary Aldosteronism Investigation network, then were linked to nationwide health insurance and mortality records through June 2025. That linkage allows later cardiovascular events to be captured outside a single center, reducing the chance that follow-up stopped at the hospital door. The result is a longer view of risk than a diagnostic clinic snapshot can provide.
What This Means for Patients Undergoing Primary Aldosteronism Evaluation
For clinicians, the practical message is not that screening ARR should replace confirmatory testing or treatment decisions. It should not. The study instead suggests that the initial renin-aldosterone profile may help identify patients whose cardiovascular risk remains elevated even after diagnostic sorting has been completed, especially when adrenalectomy is not performed. In a patient with suppressed renin and a high ARR, long-term vascular risk may be baked into the endocrine phenotype itself, not merely into the label assigned during workup.
The findings also raise a useful bedside question: should a markedly abnormal screening profile prompt closer long-term cardiovascular follow-up even when confirmatory testing does not establish classic primary aldosteronism? This dataset leans toward yes, at least as a risk signal worthy of attention. The evidence remains observational and preprint-level, so it cannot define treatment thresholds or surveillance schedules. It can, however, remind clinicians that the biology of aldosterone excess does not disappear when the diagnostic algorithm reaches a branch point.
A separate caution is equally important. Time-varying adrenalectomy analyses were described as supportive but exploratory, which keeps the surgical interpretation from overreaching the data. The post-adrenalectomy pattern is encouraging, but it is not a substitute for randomized evidence or a definitive causal claim. This study instead offers a durable clinical clue: the screening hormone profile appears to track long-term cardiovascular liability most strongly when aldosterone excess remains untreated or incompletely corrected.