Study subjects
This study was designed as a retrospective cohort study. We included consecutive adult hypertensive patients without apparent end organ damage who underwent clinically indicated echocardiography between 2010 and 2015. Patients with reduced ejection fraction (< 50%), significant valvular heart disease, ischemic heart disease, idiopathic dilated cardiomyopathy, restrictive cardiomyopathy or hypertrophic cardiomyopathy, or atrial fibrillation were excluded from the study. Finally, a total of 195 patients were reviewed. Hypertension (HTN) was defined as systolic blood pressure (SBP) ≥ 140 mmHg, diastolic blood pressure (DBP) ≥ 90 mmHg, or current pharmacological treatment for HTN. Clinical data at the time of echocardiography were gathered from electronic medical records. Venous blood was collected in the morning after a 12-h fast with the patients in the sitting position to measure plasma aldosterone and renin on the same day as the echocardiography. Plasma aldosterone concentration (ng/dL) was measured by radioimmunoassay (Diagnostic Systems Laboratories Inc., TX). Plasma renin activity was measured by radioimmunoassay of angiotensin I in the presence of reagents that inhibit angiotensin I–converting enzyme and angiotensinases. The assay was performed according to the method of Sealey using gammacoat plasma renin activity radioimmunoassay kits (DiaSorin [Stillwater, MN], lower limit of determination is 0.1 ng/mL/h).
Assessments of peripheral and central BPs
Peripheral SBP and DBP measurements were performed automatically (Omron M4 Plus, Japan) at the brachial artery of the non-dominant arm in a relaxed seated position. Two BP measurements obtained at an interval of 5 min during the same visit were averaged. Central hemodynamics and parameters were assessed with pulse wave analysis of the radial artery using commercially available radial artery tonometry (SphygmoCor, AtCor Medical, Sydney, Australia) [7, 8]. The measurements were obtained in the supine position after a minimum of 5 min of rest just before the echocardiogram. Peripheral pressure wave form was recorded from the radial artery with a high-fidelity micromanometer (Millar Instruments, Houston, TX) [8, 9]. Central systolic blood pressure (BP), diastolic BP, pulse pressure (PP), augmentation pressure, and augmentation index (AIx) were analyzed from 20 sequential pulse waveforms. PP was calculated as the difference between SBP and DBP. Augmentation pressure was the maximum systolic pressure minus pressure at the inflection point. The AIx was defined as AP divided by PP and expressed as a percentage. As in previous studies, because AIx is influenced by the heart rate, it was normalized for a heart rate of 75 bpm (AIx@75) [10]. Pulse wave velocity (PWV) was measured using carotid-femoral pressure pulse transit time.
Two-dimensional and Doppler echocardiography
Each patient underwent a comprehensive transthoracic echocardiographic study using a Vivid 7 or Vivid 9 cardiovascular ultrasound system (GE Medical Systems, Horten, Norway), equipped with 2.5–3.5 MHz phased-array sector probes. Standard 2D and Doppler measurements were performed according to the recommendations of the American Society of Echocardiography guidelines [11]. LV hypertrophy was diagnosed according to the American Society of Echocardiography recommended formula for estimation of LV mass index and was indexed to body surface area (cutoff values for LV mass index were > 115 g/m2 for men and > 95 g/m2 for women). From the apical window, mitral inflow velocities were traced, and the following variables were obtained: peak velocity of early diastolic mitral inflow (E), late diastolic mitral inflow (A), and deceleration time of the E velocity. Early diastolic mitral annular velocity (e’), late diastolic mitral annular velocity, and systolic mitral annular velocity (S′) were measured from the apical four-chamber view with a 2- to 5-mm sample volume placed at the septal corner of the mitral annulus.
Two-dimensional speckle tracking strain analysis
Three consecutive cardiac cycles were recorded and averaged, and the frame rates were set to 60–80 frames/s. The analysis was performed offline using customized software (EchoPAC PC, version 113; GE Medical Systems). The endocardial border of the LV was manually traced from three apical views (apical 4-, 2-, and 3-chamber views) to obtain LV global longitudinal strain of endocardial (GLS-endo), transmural (GLS-trans), and epicardial strains (GLS-epi) by averaging all regional peak longitudinal strains. Layer-specific LV global circumferential strain (GCS) was obtained from averaging all circumferential strains from the short axis view of the mitral valve, papillary muscle, and LV apex level (LV GCS-endo, LV GCS-trans, LV GCS-epi). LV Torsion was automatically calculated as the instantaneous difference between LV apical and LV basal rotation.
The global longitudinal strain of the LA (LA-GLS) was measured by manually tracing the LA endocardial border in both four-chamber and two-chamber views. Because two segments of the LA roof demonstrated lower longitudinal strain curves than the other four, they were excluded from both 4-chamber and 2-chamber views. Therefore, global peak LALS during ventricular systole was measured by averaging the values obtained in the eight other LA segments. The time to peak LALS was also measured as the average of the eight segments and by calculating the time delay from the QRS to the positive peak LALS [12].
To examine intraobserver and interobserver variability for layer-specific LV GLS and GCS, the same observer and a second independent observer repeated the analysis of the first 10 consecutive patients. Intraobserver and interobserver intraclass coefficients were as follows: 0.97 (95% confidence interval [CI] 0.96–0.98) and 0.96 (95% CI 0.96–0.98) for LV GLS-endo; 0.96 (95% CI 0.93–0.98) and 0.95 (95% CI 0.90–0.99) for LV GLS-trans; 0.93 (95% CI 0.78–0.96) and 0.89 (95% CI 0.64–0.95) for LV GLS epi; 0.93 (95% CI 0.90–0.98) and 0.95 (95% CI 0.92–0.98) for LV GCS-endo; 0.96 (95% CI 0.93–0.98) and 0.94 (95% CI 0.89–0.98) for LV GCS-trans; 0.91 (95% CI 0.75–0.96) and 0.88 (95% CI 0.62–0.95) for LV GCS epi; 0.88 (95% CI 0.84–0.92) and 0.90 (95% CI 0.85–0.95) for LA GLS.
Statistical analysis
Continuous variables are presented as mean ± SD and categorical variables are presented as absolute and relative frequencies (%). Spearman’s simple correlation analyses were performed to determine the associations between strain parameters and parameters of arterial stiffness and log aldosterone. Multiple linear regressions were performed to determine the independent association of LV mechanical parameters with arterial stiffness and neurohormone.