Plasma aldosterone concentration is associated with white matter lesions in patients with primary aldosteronism.

PURPOSE: Primary aldosteronism (PA) is the most frequent form of secondary hypertension. Hypertension is a risk factor for cognitive decline and dementia. White matter lesions (WMLs) are linked to vascular risk factors, which increase the risk of dementia. We aimed to analyze the association of PA-related parameters and WMLs in patients with PA. METHODS: We conducted a retrospective analysis of all patients with PA in the Hypertension Center of the People's Hospital of Xinjiang Uygur Autonomous Region from January 1, 2011 to April 1, 2021. We analyzed the relationship between plasma aldosterone concentration (PAC), plasma renin activity (PRA), aldosterone-renin ratio (ARR), serum potassium, and WMLs. RESULTS: We enrolled 138 patients with WMLs and matched these to controls without WMLs at a 1:4 ratio. Among the analytic sample (N = 711) with ages ranging from 30 to 64 years, 69% were male. In the logistic regression analysis, PAC, PRA and serum potassium were treated as continuous variables. The results showed that PAC (OR 1.04, 95% CI 1.01, 1.06, P = 0.008) was positively associated with the risk of WMLs, and serum potassium (OR 0.26, 95% CI 0.16, 0.44, P < 0.001) was inversely associated with the risk of WMLs. PRA (OR 0.86, 95% CI 0.68, 1.08, P = 0.384) was not associated with the risk of WMLs after adjusting for confounders. The results of restricted cubic splines showed the dose-response association between increasing PAC, ARR, decreasing serum potassium, and the risk of WMLs. We also divided PAC, ARR and serum potassium into two groups according to the result of restricted cubic splines. After adjusting for confounders, patients who were in Q2 (≥23.12 ng/dl) of PAC (OR 2.07, 95% CI 1.36, 3.15), Q2 (≥56.81 (ng/dl per ng/ml*h) of ARR (OR 1.82, 95% CI 1.22, 2.72) and Q2 (≤3.58 mmol/l) of serum potassium (OR 2.99, 95% CI 1.95, 4.50) had a significantly higher risk of WMLs than their counterparts. In stratified analyses, there was no evidence of subgroup heterogeneity regarding the change in the risk of WMLs (P > 0.05 for interaction for all). CONCLUSION: Our results suggested that the PAC and serum potassium were related to the risk of WMLs in patients with PA. In particular, PAC ≥23.12 ng/dl significantly increased the risk of WMLs in patients with PA.

Positive Association Between Plasma Aldosterone Concentration and White Matter Lesions in Patients With Hypertension.

Background and Objective: White matter lesions (WMLs) are imaging changes in MRI of cerebral small vessel disease associated with vascular risk factors, increasing the risk of dementia, depression, and stroke. Aldosterone (ALD) or activation of mineralocorticoid receptor (MR) causes cerebrovascular injury in a mouse model. We aimed to analyze the relationship between ALD and WMLs in a population with hypertension. Methods: We conducted a retrospective review of all patients screened for causes of secondary hypertension. We enrolled 547 patients with WMLs and matched these to controls without WMLs at a 1:1 ratio. White matter lesion load was assessed by using a modified Scheltens' scale. Results: Among the analytic sample (N = 1,094) with ages ranging from 30 to 64 years, 62.2% were male. We divided plasma ALD concentration (PAC), plasma renin activity (PRA), and ALD-renin ratio (ARR) into the third tertile (Q3), second tertile (Q2), and first tertile (Q1). We also analyzed them simultaneously as continuous variables. Multivariate logistic regression analysis showed that participants in Q3 (>17.26 ng/dl) of PAC (OR 1.59, 95% CI 1.15, 2.19), Q3 (<0.80 ng/dl) of PRA (OR 2.50, 95% CI 1.81, 3.44), and Q3 (>18.59 ng/dl per ng/ml*h) of ARR (OR 2.90, 95% CI 2.10, 4.01) had a significantly higher risk of WMLs than those in Q1 (<12.48) of PAC, Q1 (>2.19) of PRA, and Q1 (<6.96) of ARR. In linear regression analysis, we separately analyzed the correlation between the modified Scheltens' scale score and log(PAC) (ß = 2.36; 95% CI 1.30, 3.41; p < 0.001), log(PRA) (ß = -1.76; 95% CI -2.09, -1.43; p < 0.001), and log(ARR) (ß = 1.86; 95% CI 1.55, 2.17; p < 0.001), which were all significantly correlated with white matter lesion load, after adjusting for confounding factors. Simple mediation analyses showed that systolic blood pressure (SBP) or diastolic blood pressure (DBP) mediated -3.83% or -2.66% of the association between PAC and white matter lesion load, respectively. In stratified analyses, there was no evidence of subgroup heterogeneity concerning the change in the risk of WMLs (p > 0.05 for interaction for all). Conclusion: Higher PAC, especially in PAC >17.26 ng/dl, increased the risk of WMLs. PAC was positively associated with white matter lesion load independent of SBP or DBP.

Basal Plasma Aldosterone Concentration Predicts Therapeutic Outcomes in Primary Aldosteronism.

PURPOSE: Normal basal plasma aldosterone concentration (PAC) reflects mild aldosterone excess compared to high basal PAC. We previously reported lower risk for cardiovascular and cerebrovascular events in patients with primary aldosteronism (PA) and normal basal PAC (nPA) than in those with high basal PAC (hPA). However, the differences in therapeutic outcomes between nPA and hPA are unclear. The aim of this multi-institutional, retrospective cohort study was to determine the clinical significance of nPA to therapeutic outcomes, including adrenalectomy (ADX) and treatment with mineralocorticoid receptor antagonists (MRAs). METHODS: A total of 1146 patients with PA who were diagnosed and underwent adrenal venous sampling (AVS) between January 2006 and October 2016 were enrolled. The clinical parameters at baseline and after ADX or treatment with MRA were compared between the nPA and hPA groups. RESULTS: Significantly higher rates of absent clinical success (36.6 vs. 21.9%, P = 0.01) and absent biochemical success (26.4 vs. 5.2%, P < 0.01) were found for the nPA group than for the hPA group, respectively. Logistic regression analysis identified baseline PAC as a significant independent predictor of absent clinical success of ADX and MRAs. CONCLUSIONS: Plasma aldosterone concentration at baseline was a significant and independent predictor of absent clinical success of ADX and MRA. Mineralocorticoid receptor antagonist treatment appeared to be a better therapeutic choice than ADX in the nPA group.