Aldosterone Dysregulation Linked to Notable Risk of Hypertension

Results from the retrospective, observational BREAKTHROUGH Risk study found aldosterone dysregulation an underrecognized risk factor for hypertension while confirming type 2 diabetes (T2D) as a recognized risk factor, even after adjusting for aldosterone dysregulation.1

These data, presented at the 22nd Annual World Congress Insulin Resistance Diabetes & Cardiovascular Disease (WCIRDC), revealed aldosterone levels at lower thresholds (≥5 ng/dL and 10 ng/dL) were linked to a higher prevalence of hypertension.

“This real-world evidence study utilized methods to assess the association between plasma aldosterone and hypertension in real-world clinical practice,” wrote the investigative team, led by Raymond Townsend, MD, department of internal medicine, University of Pennsylvania School of Medicine. “Hypertension after aldosterone was not new-onset hypertension since patients likely received their first aldosterone measurement after they were discovered to have hypertension.”

As a key regulator of blood pressure and electrolyte balance, aldosterone dysregulation can occur when aldosterone levels remain high, despite suppressed renin and high sodium balance, and remains a pathophysiological driver of hypertension.2 However, there is little data on the levels when aldosterone dysregulation becomes linked to the risk of hypertension.

For this analysis, the team sought to examine the connection between aldosterone dysregulation and hypertension using a real-world dataset to identify the lowest level of plasma aldosterone prognostic for hypertension.1 The TriNetX Dataworks-USA Network was evaluated for patients with plasma aldosterone from January 2013 to December 2023.

A patient’s first plasma aldosterone measurement served as the index date, meeting eligibility criteria including ≥18 years, ≥1 measure of systolic blood pressure (SBP) during the 12-month follow-up, low renin (≤1 ng/mL/hour) during the 12-month baseline, and no pregnancy within 40 weeks.

Cohorts of patients meeting aldosterone thresholds were assessed, including <5 ng/dL (low) and ≥5 ng/dL (elevated aldosterone), <10 ng/dL (low) and ≥10 ng/dL (elevated aldosterone), and <15 ng/dL (low) and ≥15 ng/dL (elevated aldosterone). Baseline measures recorded the 12 months before the patient’s index plasma aldosterone measurement were assessed including demographics, comorbidities, medications, and laboratory measurements.

Adjusted odds ratios (aOR) of hypertension, defined as the first SBP ≥130 mmHg measure during the 12-month follow-up, were measured at the thresholds of ≥5, ≥10, and ≥15 ng/dL. Adjustment was performed based on age, sex, race and ethnicity, and T2D during the 12-month baseline. The aOR of hypertension by T2D, after controlling for aldosterone, was additionally assessed using the same model.

A total of 1334 patients with qualifying aldosterone results in the final study sample had a mean age of 59 years, 55% female, and 38% Black. Among those with low and elevated aldosterone, 33% and 27% had a diagnosis of T2D during the baseline, respectively (P = .048). Of the study population, 89% and 83% were diagnosed with hypertension among the aldosterone levels≥5 ng/dL and <5 ng/dL cohorts (P = .001).

Upon analysis, the aOR of hypertension was 2.01 (95% CI, 1.38–2.92), 1.81 (95% CI, 1.20–2.72), and 1.89 (95% CI, 1.12–3.17) between those with and without excess aldosterone at the ≥5, ≥10, and ≥15 ng/dL thresholds, respectively. This association remained significant among White patients after stratification by race.

Furthermore, the aoR of hypertension between those with and without T2D was 3.04 (95% CI, 1.73–5.35), 2.98 (95% CI, 1.69–5.24), and 2.89 (95% CI, 1.64–5.07), after adjusting for excess plasma aldosterone at thresholds ≥5, ≥10, and ≥15 ng/dL, respectively.

“This study shows that aldosterone likely becomes dysregulated at a clinically significant level (5 ng/dL and 10 ng/dL) lower than previously expected (15 ng/dL),” Townsend and colleagues added. “Aldosterone was significantly associated with hypertension (SBP ≥130 mmHg) across all 3 thresholds (5 ng/dL, 10 ng/dL, and 15 ng/dL).”

References

1. Townsend R, Agiro A, Luan S, Brzozowski K, Moyneur E, et al. Aldosterone dysregulation and type 2 diabetes mellitus are associated with the risk of hypertension: BREAKTHROUGH Risk Study. Presented at World Congress Insulin Resistance Diabetes & Cardiovascular Disease (WCIRDC) 2024. Los Angeles, California. December 12-14, 2024.
2. Vaidya A, Mulatero P, Baudrand R, Adler GK. The Expanding Spectrum of Primary Aldosteronism: Implications for Diagnosis, Pathogenesis, and Treatment. Endocr Rev. 2018;39(6):1057-1088. doi:10.1210/er.2018-00139