Among the 611 hypertensive patients with elevated ARR who underwent a SIT at Henan Provincial People’s Hospital from June 2021 to June 2023, 544 patients were screened according to the inclusion and exclusion criteria. The process of selecting the research subjects is shown in Figure 1 . There were 144 patients with a PAC of less than 50 ng/L after the SIT (control group), 312 patients with a post-SIT PAC between 50 and 100 ng/L (indeterminate post-SIT results group), and 118 patients with a post-SIT PAC greater than 100 ng/L (PA group). The inclusion criteria were as follows: age ≥ 18 years and meeting the diagnostic criteria for hypertension according to the Chinese Guidelines for the Prevention and Control of Hypertension (2024 Revision) (8): an SBP ≥ 140 mmHg and/or a DBP ≥ 90 mmHg based on three in-office blood pressure measurements, which were not taken on the same day and without the use of antihypertensive drugs. If a patient has a previous history of hypertension and is currently on antihypertensive medication, a diagnosis of hypertension should be made even if the blood pressure is less than 140/90 mmHg. An ARR of ≥30 (ng/dL)/[μg/(L·h)] above the screening test cutoff point was also used.

The following patients were excluded: those with secondary hypertension other than PA, such as Cushing’s syndrome and pheochromocytoma; those with a history of renal disease, such as nephritis, nephrotic syndrome and nephrectomy; those with severe organic heart disease, such as Hypertrophic cardiomyopathy, dilated cardiomyopathy; New York Heart Association class III or higher cardiac insufficiency; those who were pregnant or lactating; those who were using hormones or oral contraceptives; those with a positive PA screening but refused to complete confirmatory testing; those who were unable to cooperate due to mental illness; those who underwent confirmatory tests other than the SIT, such as the captopril test and the fludrocortisone test; those diagnosed with PA when post-SIT PAC was within the range of 50-100 ng/l ( Supplementary Table S1 ); and those with substantial missing data.

The patients with negative or indeterminate SIT results were treated according to essential hypertension. Of the 25 excluded patients with indeterminate SIT results but empirically diagnosed with PA, 9 patients agreed to undergo renal venous sampling (AVS) according to the patients’ wishes, and 2 of them underwent unilateral adrenal adenoma resection. The pathological results showed that both were adrenal cortical adenomas, and no medication was taken after surgery. The remaining 23 patients received mineralocorticoid receptor antagonists (MRA) treatment according to the treatment of PA.

The information collected included age, sex, body mass index (BMI), duration of hypertension, type of antihypertensive medication, history of hypokalemia, history of smoking, history of diabetes mellitus, biochemical results, hormone levels at the time of the screening test and confirmatory test, imaging data, and hypertensive target organ damage.

All patients were required to discontinue medications that had an effect on the ARR, including b-blockers, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers, for ≥2 weeks. Spironolactone and other diuretics were discontinued for ≥4 weeks. α1 receptor blockers and nondihydropyridine calcium channel blockers (verapamil or diltiazem) were permitted for blood pressure control. In patients with hypokalemia, potassium was replaced with oral potassium supplementation to normalize blood potassium levels prior to screening. Blood samples were collected according to the 2016 American Endocrine Society guidelines for the diagnosis and treatment of primary aldosteronism: blood was collected after the patient had been up (sitting, standing, or walking) for at least 2 hours and had rested for 5 to 15 minutes; blood was delivered under conditions that maintained room temperature to prevent the conversion of inactive renin to active renin; and plasma was frozen and stored immediately after centrifugation (3).

Beginning at 8:00 a.m., patients were instructed to rest in bed for more than 1 hour, during which 2000 ml of saline was infused over 4 hours. Blood was collected to detect PAC and renin activity before and after saline infusion, respectively. Throughout the entire process, the patients remained fasting and were kept in a recumbent position, and they were monitored for vital signs such as blood pressure and heart rate. The plasma aldosterone concentration and plasma renin activity were determined by radioimmunoassay (counter model MGLM20) in the laboratory of nuclear medicine, using the instrument and plasma aldosterone concentration kit from Shenzhen New Industry Biomedical Engineering Cooperation.

The diagnosis of PA was based on a positive SIT result (a post-infusion PAC >100 ng/L) or, in the case of an indeterminate SIT result (a post-infusion PAC between ≥50 and ≤100 ng/L), a diagnosis made through discussion by three professors with more than 20 years of experience in the diagnosis and treatment of PA at our center. They based their discussion on the patient’s SIT result, age, blood pressure, blood potassium level, imaging findings (i.e., the presence or absence of an adrenal adenoma), and antihypertensive medication use. These variables were repeatedly used as predictors in PA’s predictive model (9–11). We did not use other confirmation tests.

Target organ damage was defined as the presence of lesions in at least one of the following target organs: renal impairment (RI) was defined as a UACR ≥ 30 mg/g or an eGFR < 60 mL/min/1.73 m², and the estimated glomerular filtration rate (eGFR) was calculated using the CKD-EPI equation. Left ventricular hypertrophy (LVH) was defined as LVMI ≥ 115 g/m² in men and LVMI ≥ 95 g/m² in women (12). Carotid plaque was defined as the formation of carotid atheromatous plaque observed on carotid ultrasound (with limited cIMT ≥ 1.5 mm or localized increase in cIMT > 0.5 mm or 50%) (13).

The data were analyzed using the statistical software SPSS 25.0. Measurements conforming to a normal distribution are expressed as means ± standard deviations (x ± s), and comparisons between groups were performed using one-way ANOVA with post hoc tests. Data that did not conform to a normal distribution are expressed as medians (interquartile spacing) [M (Q1, Q3)], and comparisons between groups were made using the Kruskal–Wallis test. Count data are expressed as frequencies and percentages, and comparisons between groups were made using the chi-square test or Fisher’s exact test (where necessary). Logistic regression was used to adjust for confounders, with sex, age, duration of hypertension, and history of diabetes mellitus included as confounders in the model and tested for trends, with the risk of an event expressed as a risk ratio (OR) with a confidence interval of 95% (95% CI). The relationship between continuous variables was assessed by calculating Spearman’s rank correlation coefficient. Statistically significant and/or clinically important variables from univariate analysis were included in the multivariable model, considering also the number of outcomes, to avoid overfitted models. Multiple linear regression analysis was performed using backward stepwise regression. A P value < 0.05 was considered to indicate statistical significance.

A total of 144 patients (26.47% of the total sample size) were in the control group, 282 patients (51.84% of the total sample size) were in the indeterminate post-SIT results group, and 118 patients (21.69% of the total sample size) were in the PA group. The clinical characteristics of the three groups of patients are shown in Table 1 . Compared with the control group, the indeterminate post-SIT results group had a greater proportion of male patients, a younger age, a shorter duration of hypertension, lower serum potassium levels, a greater incidence of dyslipidemia, and higher diastolic blood pressure (BP), serum creatinine levels, and homocysteine levels (P < 0.05). Compared with the PA group, the indeterminate post-SIT group had a greater proportion of female patients, a shorter duration of hypertension, lower systolic BP, urinary microalbumin/creatinine ratio (UACR), and prevalence of hypokalemia; fewer types of antihypertensive medications; and a greater level of serum potassium (P < 0.05). There were no significant differences among the three groups in BMI, estimated glomerular filtration rate (eGFR), history of diabetes mellitus, cholesterol (CHOL), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), or uric acid levels (P > 0.05).

The patients in the indeterminate post-SIT results group had higher concentrations of aldosterone before and after the SIT, as well as standing plasma renin activity (PRA) and standing PAC, than those in the control group (P < 0.05). Compared with the PA group, the indeterminate post-SIT results group had significantly lower PAC before and after the SIT, as well as standing PAC and standing ARR (P < 0.001).

Compared with the PA group, the left ventricular posterior wall thickness (LVPWT), left ventricular end-systolic diameter (LVDs), left ventricular end-diastolic diameter (LVEDD), and LVMI in the indeterminate post-SIT results group were lower (P < 0.05). However, no significant difference was observed between the indeterminate post-SIT results group and the control group in cardiac ultrasound indicators (P > 0.05) ( Table 2 ).

Among all events, carotid plaque was the most common type of target organ damage in patients with hypertension, accounting for 41.7%, 49.3%, and 52.5% of the sample sizes in the three groups ( Table 3 ). The prevalence of RI and LVH was lower in the indeterminate post-SIT results group than in the PA group (5.7% vs. 27.1%, P < 0.001; 8.9% vs. 23.7%, P < 0.001), but the prevalence of damage to each of these target organs did not differ significantly from that in the control group (P > 0.05).

Table 4 shows that, after adjusting for confounders such as sex, age, duration of hypertension, and history of diabetes mellitus, the risk of carotid plaque was greater in patients in the indeterminate post-SIT results group than in the control group (OR 1.73, 95% CI: 1.11, 2.69). In the trend test, the prevalence of RI and LVH tended to increase with increasing post-SIT PAC (P < 0.001 for trend).

We assessed the correlation between LVMI and RAAS system-related hormones using Spearman’s rank correlation coefficient and found that post-SIT PAC was significantly correlated with LVMI. No correlation was observed between PAC, PRA, or ARR and LVMI ( Table 5 ).

The association between post-SIT PAC and LVMI, a correlate of LVH, was assessed via multiple linear regression analysis. We found that post-SIT PAC was still significantly correlated with LVMI after adjusting for confounders such as sex, duration of hypertension, antihypertensive drug classes, ever smoking, systolic BP, fasting plasma glucose (FPG), Serum potassium, and hypokalemia (P < 0.05) ( Table 6 ).