From April 2018 to May 2019, 84 PA patients were recruited from the inpatient department of Endocrinology and Metabolism at West China Hospital. Twenty-eight age-, sex-, body mass index-, blood pressure-, and hypertension duration-matched EH subjects were included simultaneously. All the subjects were of Han ethnicity and between 22 and 78 years old. All the patients completed the initial screening test of the plasma aldosterone/renin ratio (ARR) for PA, plasm renin activity (PRA) < 0.2 ng/ml/h was set as 0.2 for the calculation of the ARR to avoid inflation due to a very low denominator. According to the guidelines, before the initial screening, all the subjects had been on stable antihypertensive treatment with an α1-adrenergic receptor antagonist alone or verapamil sustained-release agent or hydralazine, and with normal serum potassium levels. The PA patients were further diagnosed by confirmatory tests of saline infusion and/or captopril challenge according to current guideline . The exclusion criteria included the following: ① subjects with a history of congestive heart failure, chronic steroid therapy or chronic kidney disease (estimated glomerular filtration rate < 60 ml/min); ② subjects with clinical indications of other secondary causes of hypertension except for PA, such as renal artery stenosis, pheochromocytoma, Cushing’s syndrome, and hyperthyroidism.
This study was revised and confirmed by the Ethics Committee of West China Hospital. Before the study, written informed consent was obtained from each individual. Our study was registered in the Chinese clinical trial registry (ChiCTR2000031792).
Demographic characteristics and laboratory determinations
Two trained staff members recorded the clinical characteristics of subjects with a standard questionnaire. Physical examination was performed on all the subjects, including body height, weight, waist circumference, and blood pressure. Body mass index (BMI) was computed as body weight in kilograms (kg) divided by height in meters squared (m2). The body surface areas were calculated as 0.0057×height (cm)+0.0121×weight (kg)+0.0882 for males and 0.0073×height (cm)+0.0127 ×weight (kg)-0.2106 for females. All patients underwent 24-hour ambulatory blood pressure monitoring three days before the CMR scan.
After overnight fasting (≥8 h), venous blood samples were collected to measure plasma aldosterone concentration (PAC), PRA, and other biochemical parameters. Radioimmunoassay was used to measure PAC and PRA (Beijing North Institute of Biotechnology Co., St Panjia Miao, Beijing). Serum potassium, serum sodium, total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, pro-brain natriuretic peptide (pro-BNP), creatine kinase MB, troponin T, and myoglobin concentrations were measured for all patients using automated, standardized equipment by the Clinical Laboratory at West China Hospital.
Cardiovascular magnetic resonance protocol
CMR was performed with a 3.0 T MRI imager (Trio Tim; Siemens Medical Solution, Erlangen, Germany) using an eight-channel phased-array surface coil and prospective electrocardiographic triggering. Patients assumed a supine position, and ECG gating and respiratory gating were used throughout the scan. The cine images of the short-axis covering the LV and the long-axis (two-, three- and four-chamber views) were obtained with a segmented balanced steady-state-free-precession sequence. The scanning parameters were TR/TE 3.4/1.3 msec, flip angle 50°, a field of view 320-340 mm, matrix size 256×144, and section thickness, 8 mm with no gap.
Postcontrast T1 maps were acquired using modified look-locker inversion recovery sequence (total acquisition is 17 heartbeats, TR/TE 2.9/1.12 ms, 8 mm thickness, in-plane spatial resolution 2.4 mm × 1.8 mm, matrix size 192×144, flip angle 35°, bandwidth 930 Hz/pixel, TI of first experiment 100 ms, TI increment 80 ms, parallel imaging 2), which was recommended by the Society for Cardiovascular Magnetic Resonance . Postcontrast T1 mapping was performed 15 minutes after the intravenous bolus injection administration of gadobenate dimeglumine (MultiHance; 0.5 mmol/ml; Bracco, Milan, Italy) at a dose of 0.15 mmol/kg body weight. Fig. 1 shows the contrast enhanced T1 maps of 2 PA patients and two EH patients.
CMR data analysis
All imaging data of PA patients and EH subjects were uploaded to Argus software (Siemens Healthcare, Erlangen, Germany). Two experienced radiologists blinded to clinical data defined the end-diastole, end-systole, and delineated LV endocardial and epicardial borders. LV end-diastolic volume, LV end-systolic volume, LV mass, and LV ejection fraction were then calculated, and volumes and mass were indexed to body surface area. The software also automatically calculated the global myocardial strain parameters, including radial, circumferential, and longitudinal peak strain (PS), peak systolic strain rate (PSSR), and peak diastolic strain rate (PDSR), and the intra- and inter-observer variability were calculated. To evaluate diffuse myocardial fibrosis, CVI42 software (Circle Cardiovascular Imaging, Calgary, Canada) was used to measure the value of postcontrast T1 time at the mid-layer myocardium of left ventricular basal, middle and apical segments.
Normally distributed data were expressed as the mean (±SD) for continuous variables, and categorical variables were expressed as percentages. Skewed variables were logarithmically transformed before analysis and expressed as medians (interquartile ranges). The quantitative variables were compared using a t-test, while the qualitative variables were compared using the χ2 test. Univariable analysis was performed to discover the correlation of the global circumferential PDSR and PSSR with postcontrast T1 time and other risk factors. The association of the global circumferential PDSR and PSSR with postcontrast T1 time in PA patients was analyzed with multivariate analysis. Variables included in the regression model were those parameters p ≤ 0.1 in univariable analysis. P ≤ 0.05 was considered statistically significant. Analyses were performed with SPSS 17.0 (Chicago, IL) for Windows.