Evaluation of Unattended Automated Office, Conventional Office and Ambulatory Blood Pressure Measurements and Their Correlation with Target Organ Damage in an Outpatient Population of Hypertensives: Study Design and Methodological Aspects.

Accurate measurement of blood pressure (BP) has a pivotal role in the management of patients with arterial hypertension. Recently, introduction of unattended office BP measurement has been proposed as a method allowing more accurate management of hypertensive patients and prediction of hypertension-mediated target organ damage (HMOD). This approach to BP measurement has been in particular proposed to avoid the white coat effect (WCE), which can be easily assessed once both attended and unattended BP measurements are obtained. In spite of its interest, the role of WCE in predicting HMOD remains largely unexplored. To fill this gap the Young Investigator Group of the Italian Hypertension Society (SIIA) conceived the study "Evaluation of unattended automated office, conventional office and ambulatory blood pressure measurements and their correlation with target organ damage in an outpatient population of hypertensives". This is a no-profit multicenter observational study aiming to correlate attended and unattended BP measurements for quantification of WCE and to correlate WCE with markers of HMOD, such us left ventricular hypertrophy, left atrial dilatation, and peripheral atherosclerosis. The Ethical committee of the Federico II University hospital has approved the study.

The relationship between soluble CD40 ligand level and atherosclerosis in white-coat hypertension.

This study was designed to examine the distribution of plasma soluble CD40 ligand (sCD40L), and its relationship with carotid intima-media thickness (CIMT) in healthy controls and subjects with white-coat hypertension (WCH) or hypertension (HT). Thirty-five patients with HT, 35 patients with WCH, and 35 healthy controls were enrolled. The normal group (CIMT < 0.9 mm), subclinical atherosclerosis group (0.9 mm ≤ CIMT < 1.2 mm) and atherosclerosis group (CIMT ≥ 1.2 mm) were grouped based on the value of CIMT. The highest level of sCD40L was observed in HT group, followed by WCH group and healthy controls. The level of sCD40L was significantly increased in atherosclerosis group compared with subclinical atherosclerosis group and healthy controls. In the WCH group, sCD40L level was significantly and positively correlated with CIMT and systolic blood pressure. Multiple logistic regression indicated that sCD40L was a risk factor for increased CIMT (odds ratio, 1.504; 95% confidence interval, 1.054-1.956, P < 0.001). The data provided evidence that sCD40L levels in subjects with WCH and HT were significantly and consistently higher than those in healthy controls. SCD40L may represent a potential non-invasive atherosclerosis marker in WCH patients.

The influence of white-coat hypertension on left atrial phasic function.

We aimed to investigate the association between white-coat hypertension (WCH) and left atrial (LA) phasic function assessed by the volumetric and speckle tracking method. This cross-sectional study included 52 normotensive individuals, 49 subjects with WCH and 56 untreated hypertensive patients who underwent a 24-h ambulatory BP monitoring and complete two-dimensional echocardiographic examination (2DE). WCH was diagnosed if clinic blood pressure (BP) was elevated and 24-h BP was normal. We obtained that maximum, minimum LA and pre-A LAV volumes and volume indexes gradually and significantly increased from the normotensive subjects, throughout the white-coat hypertensive individuals to the hypertensive patients. Passive LA emptying fraction (EF), representing the LA conduit function, gradually reduced from normotensive to hypertensive subjects. Active LA EF and the parameter of the LA booster pump function increased in the same direction. Similar results were obtained by 2DE strain analysis. The LA stiffness index gradually increased from normotensive controls, throughout white-coat hypertensive subjects to hypertensive patients. Clinic systolic BP was associated with LA passive EF (ß= -0.283, p = 0.001), LA active EF (ß = 0.342, p < 0.001), LA total longitudinal strain (ß= -0.356, p < 0.001), LA positive longitudinal strain (ß= -0.264, p = 0.009) and LA stiffness index (ß = 0.398, p < 0.001) without regard to age, BMI, left ventricular structure and diastolic function in the whole study population. In the conclusion, WCH significantly impacts LA phasic function and stiffness. Clinic systolic BP was associated with functional and mechanical LA remodeling in the whole study population.

The Impact of White-Coat Hypertension on Cardiac Mechanics.

The authors aimed to investigate right ventricular (RV) and left ventricular (LV) remodeling in patients with white-coat hypertension (WCH) and sustained arterial hypertension. This cross-sectional study included 153 untreated patients who underwent 24-hour ambulatory blood pressure (BP) monitoring and complete two-dimensional echocardiographic (2DE) examination. Results showed that LV and RV longitudinal mechanics gradually deteriorated from controls to patients with sustained hypertension. Endocardial RV longitudinal strain was lower in WCH and hypertensive patients than in controls. Midmyocardial RV longitudinal strain was decreased in hypertensive patients compared with the other two groups, whereas subepicardial RV longitudinal strain was similar between the observed groups. Twenty-four-hour systolic BP was associated with 2DE global longitudinal LV and subendocardial RV strain. This study demonstrates that myocardial deformation of both ventricles is significantly impaired in patients with WCH and sustained arterial hypertension, and 24-hour systolic BP is associated with LV and RV deformation independent of cardiac structure.

Subclinical arterial and cardiac damage in white-coat and masked hypertension.

The study aimed to compare arterial and echocardiographic parameters in subjects with newly diagnosed masked (MH) or white-coat hypertension (WCH) to subjects with sustained normotension or sustained hypertension, defined according to the 2014 European Society of Hypertension practice guidelines for ambulatory blood pressure (BP) monitoring. We recruited 303 participants (mean age 46.9 years) in a family-based population study. SpaceLabs monitors and oscillometric sphygmomanometers were used to evaluate ambulatory and office BP, respectively. Central pulse pressure (PP) and aortic pulse-wave velocity (PWV) were measured with pulse-wave analysis (SphygmoCor software). Carotid intima-media thickness (IMT) and cardiac evaluation were assessed by ultrasonography. Analysing participants without antihypertensive treatment (115 sustained normotensives, 41 sustained hypertensives, 20 with WCH, 25 with MH), we detected significantly higher peripheral and central PP, PWV, IMT and left ventricular mass index in hypertensive subgroups than in those with sustained normotension. The differences between categories remained significant for peripheral PP and PWV after adjustment for confounding factors, including 24 h systolic and diastolic BP. Participants with WCH and MH, defined according to strict criteria, had more pronounced arterial and heart involvement than normotensive participants. The study demonstrates a high prevalence of these conditions in the general population that deserves special attention from physicians.

Left atrial volume and function in patients with white-coat hypertension assessed by real-time three-dimensional echocardiography.

BACKGROUND: White-coat hypertension (WCH) is a disease based on the disparity of a patient's blood pressure measurements between the physician's office and the patient's home environment. The aim of the present study is to evaluate the left atrial (LA) volume and functions in WCH. METHODS: In total, this study included 37 WCH (17 women, 20 men, mean age 48.4±5.7 years) and 30 healthy individuals (18 women, 20 men, mean age 47.9±7.5 years). All patients underwent real-time three-dimensional and comprehensive two-dimensional echocardiography (2DE) with tissue Doppler evaluation to estimate left atrial volumes and mechanical functions. RESULTS: LA diameters were significantly higher in the patients compared with the controls (37±2.8 vs. 35±3.1 mm, P=0.017). LA total systolic volume and LA maximal volume were significantly higher in the patients. (41.1±6.9 vs. 35.5±3.7 ml, P<0.001; 25.8±5.4 vs. 21.3±3.3 ml, P<0.001, respectively). LA volume before LA contraction and LA active stroke volume were significantly higher in the patients with WCH than in the normotensives (24.4±6.3 vs. 20.9±2 ml, P=0.002; 9.1±4.8 vs. 6.7±2.5 ml, P=0.007, respectively). Moreover, the LA expansion index was significantly higher in the patients with WCH than in the normotensives (178.7±53.6 vs. 155.3±36.3, P=0.037). However, the total emptying volume fraction of the LA was similar between the two groups. CONCLUSION: We showed that LA structural functions and volumes were increased in the WCH group. Although increased LA volume has been observed in many diseases, structural changes in LA may be accepted as an early sign for clinical cardiac remodeling in patients with WCH, suggesting the necessity of early intervention for preventing clinical cardiovascular disease.

Influence of White-Coat Hypertension on Left Ventricular Deformation 2- and 3-Dimensional Speckle Tracking Study.

We sought to compare left ventricular deformation in subjects with white-coat hypertension to normotensive and sustained hypertensive patients. This cross-sectional study included 139 untreated subjects who underwent 24-hour ambulatory blood pressure monitoring and completed 2- and 3-dimensional examination. Two-dimensional left ventricular multilayer strain analysis was also performed. White-coat hypertension was diagnosed if clinical blood pressure was elevated and 24-hour blood pressure was normal. Our results showed that left ventricular longitudinal and circumferential strains gradually decreased from normotensive controls across subjects with white-coat hypertension to sustained hypertensive group. Two- and 3-dimensional left ventricular radial strain, as well as 3-dimensional area strain, was not different between groups. Two-dimensional left ventricular longitudinal and circumferential strains of subendocardial and mid-myocardial layers gradually decreased from normotensive control to sustained hypertensive group. Longitudinal and circumferential strains of subepicardial layer did not differ between the observed groups. We concluded that white-coat hypertension significantly affects left ventricular deformation assessed by 2-dimensional traditional strain, multilayer strain, and 3-dimensional strain.

Myocardial Performance Index in Childhood Onset Essential Hypertension and White Coat Hypertension.

BACKGROUND: As a global measure of ventricular systolic and diastolic function, the myocardial performance index (MPI) can be an early indicator of hypertensive cardiomyopathy in children with essential hypertension (EH). METHODS: Children with untreated newly diagnosed EH and white coat hypertension (WCH) by a 24-hour ambulatory blood pressure monitoring (ABPM), both groups without any identifiable etiology for the hypertension, were enrolled for the study. Echocardiograms and vascular ultrasounds for carotid artery intimal medial thickness were performed on all children prior to therapy. Diastolic function (peak E and A velocities, E/A ratio, isovolumic relaxation time, and deceleration times) and MPI were evaluated by simultaneous transmitral and transaortic spectral Doppler flow velocities. Systolic function was evaluated by shortening fraction and ejection fraction. RESULTS: A cohort of 66 children (24 with EH, 42 with WCH, males 61%, median age of 13 years, range 10-17 years) were enrolled in the study. The demographic, anthropometric, laboratory tests, vascular ultrasound, and conventional echocardiographic parameters were similar between the 2 groups. There was a very small difference in MPI between the EH and WCH children (0.28 SD: 0.07 vs. 0.31 SD: 0.08, P = 0.045). However, in EH children, MPI increased by 0.14 units for every 10 unit increase in mean ABPM systolic BP (95% confidence interval: 0.03-0.25). CONCLUSIONS: We found the increasing MPI was associated with increasing 24-hour mean systolic BP in children with EH. Therefore, MPI may have utility as a single, quick, noninvasive method of detection and tracking of subclinical hypertensive heart disease.

Endothelial damage in white coat hypertension: role of lectin-like oxidized low-density lipoprotein-1.

The aims of this study included an examination of soluble lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (sLOX-1) levels in hypertensive (HT) patients. Another aim examined sLOX-1 associations with oxidized LDL (oxLDL), nitric oxide synthase (eNOS) and nitric oxide (NOx). A final aim was to compare these parameters between HT patients, white-coat hypertensive (WCH) patients and healthy controls. The three groups, HT, WCH and controls, were comprised of 35 patients each. sLOX-1 and oxLDL levels were significantly increased in WCH and HT patients compared with controls. The eNOS activation was significantly lower in HT than in the control group. sLOX-1 and oxLDL levels were significantly negatively correlated with eNOS levels in the WCH and HT groups. Carotid intima-media thickness (CIMT) measurements were significantly higher in the WCH and HT groups compared with controls. There was a significant positive correlation between CIMT and sLOX-1 and oxLDL; however, there was a negative correlation with eNOS in WCH. Regression analysis revealed that sLOX-1 was the variable that had a significant effect on blood pressure (P<0.001, odds ratio (95% confidence interval=23.273 (5.843-92.688)). A possible endothelial impairment may act as a cardiovascular risk factor in WCH. Necessary measures should be considered in terms of atherosclerosis risk with HT, especially in early identification of endothelial damage by looking at sLOX-1 levels. We believe sLOX-1 levels are strong biomarkers for determining early endothelial damage in HT, and especially in WCH patients.

Relations between white coat effects and left ventricular mass index or arterial stiffness: role of nocturnal blood pressure dipping.

BACKGROUND: Whether independent relationships between white coat effects (office minus day (office-day blood pressure (BP))) and organ damage or arterial stiffness may be explained by associations with an attenuated nocturnal BP dipping, has not been determined. METHODS: In 750 participants from a sample of African ancestry, office and 24-hour BP, carotid-femoral pulse wave velocity (PWV) (applanation tonometry and SphygmoCor software) (n = 662), and left ventricular mass indexed to height(2.7) (LVMI) (echocardiography) (n = 463) were determined. RESULTS: Office-day systolic BP (SBP) was correlated with day minus night (day-night) SBP, percentage night divided by day (night/day) SBP, and night SBP (P < 0.0005), and these relationships persisted with adjustments for confounders, including day SBP (P < 0.005). With adjustments for 24-hour SBP and additional confounders, office-day SBP was associated with LVMI (P < 0.01) and PWV (P < 0.0001). With adjustments for day SBP and additional confounders, day-night SBP, percentage night/day SBP, and night SBP were related to PWV (P < 0.05) but not to LVMI (P > 0.44). The relationships between office-day SBP and LVMI or PWV persisted with adjustments for either day-night or percentage night/day SBP (LVMI: P = 0.01; PWV: P < 0.0001) or night SBP (LVMI: P < 0.01; PWV: P = 0.0001), and in product of coefficient mediation analysis with appropriate adjustments, neither indexes of nocturnal BP dipping nor nocturnal BP per se contributed toward the impact of office-day BP on LVMI or PWV (P > 0.09). CONCLUSIONS: In a group of African ancestry, although white coat effects are independently associated with an attenuated nocturnal decrease in SBP, neither decreased BP dipping nor nocturnal BP contribute toward the independent relationships between white coat effects and LVMI or arterial stiffness.

Effect of masked, white-coat, and sustained hypertension on coronary flow reserve and peripheral endothelial functions.

In this study, we have measured coronary flow reserve (CFR) using transthoracic echocardiography and brachial artery flow-mediated dilatation using vascular ultrasound in 36 subjects with masked hypertension (MH), 62 patients with sustained hypertension (SH), 40 patients with white-coat hypertension (WCH), and 39 healthy volunteers. CFR was significantly lower in the MH and SH groups (2.30 ± 0.39 and 2.28 ± 0.52, respectively) than in the control and WCH groups (2.85 ± 0.39 and 2.77 ± 0.41, respectively; P < .05). CFR was significantly impaired in patients with MH and SH compared with WCH and normotensive subjects. MH and SH groups are comparable with regard to cardiovascular risks and target organ damage.

Nocturnal hypertension: poor correlation with office blood pressure but strong prognostic factor for target organ damage.

INTRODUCTION: We investigated the correlation between systolic and diastolic nocturnal blood pressure (BP) values and office BP values, as well as parameters of 24-hour ambulatory BP monitoring, in patients with hypertension. In addition, we compared nocturnal hypertensives with nocturnal normotensives regarding their demographic, clinical, and laboratory characteristics, as well as other data from 24-hour BP monitoring. METHODS: The study included 182 consecutive patients who had newly diagnosed, never treated, uncomplicated arterial hypertension. Blood samples were obtained from all patients for the determination of glycaemic and lipidaemic profiles. All underwent a complete echocardiographic examination, including tissue Doppler imaging, measurement of carotid intima-media thickness, measurement of carotid-femoral pulse wave velocity, and determination of the augmentation index of reflected waves (Aix@75), as well as 24-hour ambulatory BP monitoring. The population was divided into nocturnal normotensives (NN, n=77) and nocturnal hypertensives (NH, n=105, nocturnal BP >120/70 mmHg). RESULTS: Although the NH did not differ from the NN as regards the classical cardiovascular risk factors, they showed an excessive inotropic response to exercise (61.9% vs. 22.7%, p=0.028), higher levels of serum uric acid (5.5 ± 1.56 mg/dl vs. 4.7 ± 1.36 mg/dl, p=0.003), as well as greater arterial stiffness, as expressed by a higher carotid-femoral pulse wave velocity (8.6 ± 1.6 m/s vs. 7.9 ± 1.4 m/s, p=0.009), and a greater carotid intima-media thickness (0.74 ± 0.17 mm vs. 0.68 ± 0.15 mm, p=0.007). In addition, although the two groups did not differ significantly as regards office BP values and did not show strong correlations between nocturnal and office BP, both nocturnal diastolic and, especially, systolic BP showed strong correlations with levels of serum uric acid and with subclinical lesions in the heart, central aorta, peripheral vessels, and renal vasculature. CONCLUSIONS: Nocturnal BP is poorly correlated with office BP values. However, the presence of nocturnal hypertension is associated with morphological and functional disturbances of the cardiovascular net. 24-hour ambulatory BP monitoring is an essential tool for revealing this subgroup of hypertensive patients who are at increased cardiovascular risk.

The impact of serum homocysteine on intima-media thickness in normotensive, white-coat and sustained hypertensive adolescents.

BACKGROUND AND PURPOSE: In recent decades, elevated levels of homocysteine (Hcy) have been found to be associated with an increased risk of vascular events. Additionally, in some case-control studies, hyperhomocysteinaemia has been found to be related to higher intima-media thickness (IMT), but the results are inconclusive. Therefore, in the present study we intended to assess the relationship between serum levels of Hcy and IMT in normotensive and hypertensive adolescents. PATIENTS AND METHODS: 59 normotensive 47 white coat hypertensive and 73 sustained hypertensive adolescents were included in our study. IMT of the common carotid arteries was measured by B-mode ultrasonography. Plasma NOx as well as homocysteine levels were measured in all cases. The relationship between IMT and Hcy and NOx were assessed by a pooled analysis. Additionally, serum levels of Hcy and NOx were compared between normotensives and hypertensive subgroups. RESULTS: IMT was elevated in hypertensive adolescents (means ± SD: 0.055 ± 0.01 cm) compared with normotensives (0.048 ± 0.008 cm, p < 0.01). Higher serum concentrations of homocysteine were measured in hypertensive teenagers (11.9 ± 7.25 µmol/l for hypertensive and 9.85 ± 3.12 µmol/l for normotensives respectively, p < 0.01). In contrast to this, serum NOx was lower in patients (28.8 ± 14.9 µmol/l) compared with controls (38.8 ± 7.6 µmol/l, p < 0.01). The pooling of homocysteine and IMT data of hypertensive and normotensive adolescents revealed a significant positive relationship between the two parameters (r = 0.43, p < 0.001). CONCLUSIONS: We conclude that elevated serum levels of homocysteine may play a role in increased IMT in adolescent hypertension.