Background
The purpose of this investigation was to evaluate the association between blood pressure (BP) variability and right ventricular (RV) mechanical function in normal-weight, overweight, and obese untreated patients with hypertension.
Methods
This retrospective cross-sectional study included 127 untreated subjects with hypertension who underwent 24-hour ambulatory BP monitoring and complete two-dimensional and three-dimensional echocardiographic examination. All participants were divided into three groups according to body mass index (BMI): normal-weight patients (BMI < 25 kg/m 2 ), overweight patients (25 ≤ BMI < 30 kg/m 2 ), and obese patients (BMI ≥ 30 kg/m 2 ).
Results
Daytime, nighttime, and 24-hour BP variability parameters were higher in overweight and obese subjects with hypertension than in lean subjects. Two-dimensional RV longitudinal strain and systolic strain rate were significantly lower in obese patients with hypertension than in normal-weight patients (−24.1 ± 3% vs −23.3 ± 3.2% vs −21.7 ± 3.3%, P = .004). Three-dimensional echocardiographic RV volumes indexed to body surface area were lower in lean and overweight subjects than in obese participants with hypertension (mean RV end-diastolic volume index, 65 ± 6 vs 67 ± 7 vs 71 ± 8 mL/m 2 , P = .001), while three-dimensional RV ejection fraction decreased in the same direction (60 ± 4% vs 58 ± 3% vs 57 ± 3%, P < .001). Nighttime BP variability indices, more than daytime BP variability parameters, correlated with two-dimensional RV global longitudinal strain and three-dimensional echocardiographic RV volumes.
Conclusions
BP variability and RV structure, function, and mechanics are significantly affected by obesity in patients with untreated hypertension. BP variability is significantly associated with RV remodeling in patients with hypertension.
Blood pressure (BP) variability has appeared as a complex phenomenon that includes both short-term and long-term BP changes. A recently published large study that included 25,814 patients from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial showed that higher visit-to-visit BP variability of systolic BP was associated with increased risk for cardiovascular morbidity (nonfatal cardiac infarction, heart failure, stroke) and all-cause mortality. The Pressioni Arteriose Monitorate e Loro Associazioni study demonstrated that short-time BP variability (over 24 hours) could predict mortality in general population. Investigations of BP variability in overweight and obese subjects with or without arterial hypertension are scarce. A recent large study demonstrated that high nocturnal BP variability greatly increased the risk for mortality related to obesity.
The Multi-Ethnic Study of Atherosclerosis included 4,127 participants and revealed that overweight and obesity were independently associated with right ventricular (RV) remodeling even after adjustment for the respective left ventricular (LV) measures. However, to our knowledge no study has investigated the mutual relationship among BP variability, RV remodeling, and overweight or obesity in patients with arterial hypertension.
Considering that BP variability, RV remodeling, and obesity are related to worse cardiovascular outcomes, we aimed to investigate the relationship between BP variability and RV function and mechanics in normal-weight, overweight, and obese patients with hypertension because this association could partially explain unfavorable outcomes in obese patients with hypertension. We hypothesized that BP variability indices are related with parameters of RV function and deformation in patients with hypertension with different body sizes, from normal weight to obese.
Methods
The present retrospective cross-sectional study included 127 recently diagnosed subjects with untreated hypertension referred to the outpatient clinic of University Hospital “Dr. Dragisa Misovic – Dedinje” (Belgrade, Serbia) for echocardiographic examination or ambulatory BP monitoring. Patients with heart failure ( n = 7), sleep apnea syndrome ( n = 3), coronary artery disease ( n = 2), previous cerebrovascular insult ( n = 4), atrial fibrillation ( n = 7), congenital heart disease ( n = 1), valve heart disease ( n = 8), neoplastic disease ( n = 4), cirrhosis of the liver ( n = 2), kidney failure ( n = 7), or endocrine diseases including type 2 diabetes mellitus ( n = 11) were also excluded from the study. Stress testing was performed in 14 patients because of suspected coronary artery disease; the results of two tests were positive for decreased coronary reserve, and these patients were excluded from further study. Polysomnography was performed in eight patients (two overweight and six obese) because they reported symptoms that could be related to obstructive sleep apnea syndrome, and in three patients obstructive sleep apnea was confirmed (one overweight and two obese). Subjects with poor quality three-dimensional (3D) acquisition ( n = 6) or poor two-dimensional (2D) RV visualization ( n = 4) were also excluded from any further analyses. Dropout of one segment during RV strain analysis was detected in 12 subjects. Patients in whom two or more segments dropped out were excluded from the study ( n = 14); three patients were excluded from the normal-weight group, five patients from the overweight group, and six patients from the obese group. Ultimately, 127 patients with hypertension were analyzed in our study.
Anthropometric measures (height and weight) and laboratory analyses (fasting glucose, total cholesterol, triglycerides, and serum creatinine) were performed in all subjects included in the study. Body mass index (BMI) was calculated for each patient. Patients were divided into three groups according the definition of the World Health Organization using BMI : normal-weight patients (BMI < 25 kg/m 2 ), overweight patients (25 ≤ BMI < 30 kg/m 2 ), and obese patients (BMI ≥ 30 kg/m 2 ).
The study was approved by the ethics committee of the University Clinic “Dr. Dragisa Misovic – Dedinje,” and informed consent was obtained from all participants.
Clinic BP Measurement and 24-Hour Ambulatory BP Monitoring
All participants underwent 24-hour BP monitoring. Clinic arterial BP values were obtained by aneroid manometer in the morning hours by measuring the average value of three consecutive measurements in the sitting position, taken within an interval of 5 to 10 min, after the subject had rested for ≥5 min in that position.
Noninvasive 24-hour ambulatory BP monitoring was performed on the nondominant arm, using the Schiller BR-102 plus system (Schiller AG, Baar, Switzerland). The device was programmed to obtain BP readings at 20-min intervals during the day (7 am to 11 pm ) and at 30-min intervals during the night (11 pm to 7 am ). Patients were asked to attend to their usual daily activities but to keep still at times of measurement and to keep a diary of daily activities, including the times of awakening and going to bed. Nighttime BP was defined as the average of BPs from the time when patients went to bed until the time they got out of the bed and daytime BP as the average of BPs recorded during the rest of the day. The recording was then analyzed to obtain 24-hour daytime and nighttime average systolic BP, diastolic BP, mean arterial pressure, and heart rate. When the readings exceeded ≥70% of the total readings programmed for the testing period, the recording was considered valid and satisfactory. Arterial hypertension was defined according to current guidelines.
BP variability was evaluated using two different groups of indices: (1) the SD of average daytime, nighttime, and 24-hour BPs and (2) the coefficient of variation (CV) of daytime, nighttime, and 24-hour BPs, which represents the average SD of BP divided by the corresponding mean BP and multiplied by 100 (CV = [SD/BP average values] × 100).
Echocardiography
Echocardiographic examination was performed using a 2.5-MHz transducer with harmonic capability and real-time 3D data set acquisition of the left ventricle obtained using a 3D volumetric transducer and a Vivid 7 ultrasound machine (GE Vingmed Ultrasound AS, Horten, Norway).
Conventional Echocardiographic Examination
The values of all 2D parameters were obtained as the average value of three consecutive cardiac cycles. LV end-systolic and end-diastolic diameters and interventricular septal thickness were determined by using 2D-guided linear measurements. Relative wall thickness was calculated as (2 × posterior wall thickness)/LV end-diastolic diameter. LV ejection fraction was assessed using the biplane method. Two-dimensional echocardigoraphic LV mass was calculated by using the formula of the American Society of Echocardiography for indexing by body surface area, and Penn’s formula was used for indexing by height.
Left atrial volume was measured just before mitral valve opening, according to the biplane method in four- and two-chamber views, and all values were indexed to body surface area.
Transmitral Doppler inflow and tissue pulsed Doppler velocities were obtained in the apical four-chamber view. Pulsed Doppler measurements included the ratio between transmitral early and late diastolic peak flow velocity (E/A). The spectral tissue Doppler method was used to obtain LV myocardial velocities in the apical four-chamber view, with a sample volume placed just above the septal and lateral segment of the mitral annulus during early diastole (e′). The average of the peak early diastolic velocity (e′) of the septal and lateral mitral annulus obtained by the tissue Doppler was calculated, and the E/e′ ratio was computed.
Right Ventricle and Right Atrium
RV internal diameter was measured in the parasternal long-axis view. RV thickness was measured in the subcostal view. Right atrial (RA) maximal volume was obtained in the four-chamber view during ventricular end-systole and indexed to body surface area.
Tricuspid flow velocities were assessed using pulsed-wave Doppler in the apical four-chamber view at end-expiration during quiet breathing to determine early diastolic peak flow velocity (E t ). Doppler tissue imaging was used to obtain RV myocardial velocities in the apical four-chamber view, with a sample volume placed just above the lateral segment of the tricuspid annulus during early diastole (e′ t ) and systole (s t ). Tricuspid (E/e′) t ratio was determined by using previously estimated Doppler values.
RV systolic BP (PASP) was assessed in patients with minimal or mild tricuspid regurgitation. PASP was determined according to current guidelines and using the following formula: PASP = (tricuspid regurgitation velocity) 2 + RA pressure. The right atrium was assessed by vena cava inferior diameter and its changes during respiration. Inferior vena cava diameter < 2.1 cm that collapses >50% suggests normal RA pressure of 3 mm Hg (range, 0–5 mm Hg), whereas inferior vena cava diameter > 2.1 cm that collapses <50% suggests high RA pressure of 15 mm Hg (range, 10–20 mm Hg). In 15 patients, PASP could not be determined because of a lack of tricuspid regurgitation. In 15 patients, PASP could not be determined because of a lack of visible tricuspid regurgitation (six in the normal-weight group, five in the obese group, and four in the obese group).
Two-Dimensional RV Strain and Strain Rate
Two-dimensional strain imaging was performed by using three consecutive cardiac cycles of 2D images in the apical four-chamber view. EchoPAC 112 (GE Vingmed Ultrasound AS) was used for 2D strain analysis. The software provided values of longitudinal strain and strain rate for six segments: three segments of the interventricular septum and three segments of the RV free wall (proximal, medial, and apical segments for each wall). Global longitudinal RV strain and strain rates were calculated as the average of all six segments, and they were provided by the software. Longitudinal strain and strain rates of the interventricular septum were computed as average value of three segments that belong to the septum, whereas longitudinal strain and strain rates of the RV lateral wall were calculated as the average of three segments of the lateral wall. The values of septal and lateral RV wall strain and strain rates were calculated manually.
Three-Dimensional Echocardiographic Acquisition
A full-volume acquisition of the right ventricle required for further analyses was obtained from an apical approach. Six electrocardiographically gated consecutive beats were acquired during end-expiratory breath-hold to generate a full volume. All data sets were analyzed using commercially available software (RV TomTec) integrated in EchoPAC 112. We analyzed RV volumes, RV stroke volume, and RV ejection fraction. The frame rate was between 20 and 30 frames/sec.
Statistical Analysis
Continuous variables are presented as mean ± SD and were compared using analysis of equal variance, as they showed normal distribution. Bonferroni post hoc analysis was used for comparisons between different groups. Differences in proportions were compared using χ 2 tests. Correlation analysis was used to determine the associations between different echocardiographic and clinical parameters and BP variability indices. P values < .05 were considered to indicate statistical significance.
Results
There was no significant differences between the observed groups in age and gender distribution ( Table 1 ). Clinic systolic and diastolic BPs were higher in overweight and obese than in normal-weight patients with hypertension ( Table 1 ). There was no difference in clinic heart rate among different groups. Plasma glucose was higher in obese than in normal-weight patients, triglyceride levels were higher in obese than in normal-weight and obese patients, and total cholesterol levels were higher in overweight and obese subjects than in normal-weight subjects ( Table 1 ). Serum creatinine levels were similar between groups ( Table 1 ).
| Variable | Hypertension plus normal BMI ( n = 45) | Hypertension plus overweight ( n = 47) | Hypertension plus obesity ( n = 35) | P |
|---|---|---|---|---|
| Age (y) | 47 ± 7 | 49 ± 8 | 50 ± 7 | .178 |
| Women | 21 (47%) | 21 (45%) | 12 (34%) | .503 |
| BMI (kg/m 2 ) | 23.4 ± 1.5 | 27.7 ± 1.9 | 33 ± 2.4 | — |
| BSA (m 2 ) | 1.85 ± 0.17 | 2 ± 0.21 | 2.18 ± 0.26 | — |
| Clinic SBP (mm Hg) | 149 ± 8 | 154 ± 9 † | 159 ± 12 ‡ | <.001 |
| Clinic DBP (mm Hg) | 93 ± 7 | 97 ± 8 † | 99 ± 8 ‡ | .002 |
| Heart rate (beats/min) | 67 ± 6 | 69 ± 7 | 68 ± 8 | .390 |
| Plasma glucose (mmol/L) | 5.1 ± 0.5 | 5.4 ± 0.6 | 5.7 ± 0.7 ‡ | <.001 |
| Triglycerides (mmol/L) | 1.5 ± 0.4 | 1.8 ± 0.5 | 2.2 ± 0.5 ‡ § | <.001 ∗ |
| Total cholesterol (mmol/L) | 5.2 ± 0.6 | 5.7 ± 0.8 ‡ | 5.9 ± 0.7 ‡ | <.001 |
| Serum creatinine (μmol/L) | 73 ± 13 | 75 ± 12 | 78 ± 10 | .176 |
∗ P < .01 for all comparisons.
† P < .05 versus hypertension plus normal BMI.
‡ P < .01 versus hypertension plus normal BMI.
Ambulatory BP Monitoring
Daytime BPs were higher in obese subjects than in normal-weight patients, nighttime BPs gradually increased from lean to obese subjects, and 24-hour BPs were significantly higher in obese than in overweight and lean patients ( Table 2 ). BP nocturnal reduction rates of systolic, diastolic, and mean BP gradually decreased from normal-weight to obese patients with hypertension. Daytime, nighttime, and 24-hour heart rates were similar among the observed groups.
| Variable | Hypertension plus normal BMI ( n = 45) | Hypertension plus overweight ( n = 47) | Hypertension plus obesity ( n = 35) | P |
|---|---|---|---|---|
| 24 h | ||||
| SBP (mm Hg) | 136 ± 9 | 142 ± 11 ‡ | 146 ± 12 § | <.001 |
| DBP (mm Hg) | 81 ± 7 | 84 ± 8 | 89 ± 9 § || | <.001 |
| MAP (mm Hg) | 99 ± 7 | 103 ± 8 | 108 ± 9 § || | <.001 |
| Heart rate (beats/min) | 70 ± 8 | 72 ± 9 | 71 ± 8 | .522 |
| Daytime | ||||
| SBP (mm Hg) | 142 ± 9 | 147 ± 11 | 149 ± 12 ‡ | .010 |
| DBP (mm Hg) | 84 ± 8 | 88 ± 9 | 91 ± 8 § | .001 |
| MAP (mm Hg) | 103 ± 9 | 108 ± 11 | 110 ± 11 § | .008 |
| Heart rate (beats/min) | 73 ± 9 | 75 ± 10 | 74 ± 10 | .612 |
| Nighttime | ||||
| SBP (mm Hg) | 116 ± 8 | 125 ± 10 | 135 ± 12 | <.001 † |
| DBP (mm Hg) | 69 ± 7 | 74 ± 8 | 80 ± 9 | <.001 † |
| MAP (mm Hg) | 85 ± 8 | 91 ± 9 | 98 ± 10 | <.001 † |
| Heart rate (beats/min) | 64 ± 7 | 64 ± 8 | 62 ± 7 | .398 |
| Nocturnal reduction rate (%) | ||||
| SBP | 18 ± 3.2 | 14.8 ± 2.9 | 9.5 ± 2.2 | <.001 † |
| DBP | 17.3 ± 3.7 | 15.7 ± 3.3 | 12.2 ± 3.5 | <.001 † |
| MAP | 17.6 ± 3.6 | 15.7 ± 3.4 | 10.8 ± 3 | <.001 † |
| Heart rate | 12.7 ± 3 | 14.8 ± 3.3 | 15.7 ± 4.1 | .396 |
| SD | ||||
| 24-h SBP | 17.5 ± 5 | 18.8 ± 5.3 | 21.3 ± 6 § | .009 |
| 24-h DBP | 14.7 ± 3.7 | 16.2 ± 4.1 | 17.3 ± 4.6 ‡ | .020 |
| Daytime SBP | 15.8 ± 5.1 | 18.1 ± 5.4 | 20.6 ± 6.1 § | .001 |
| Daytime DBP | 13.2 ± 3.7 | 15.5 ± 4.2 ‡ | 17 ± 4.8 § | <.001 |
| Nighttime SBP | 12.2 ± 3 | 14.5 ± 3.6 | 17.4 ± 4.1 | <.001 † |
| Nighttime DBP | 10 ± 2.5 | 11.8 ± 3 | 14 ± 3.6 | <.001 ∗ |
| CV | ||||
| 24-h SBP | 12.9 ± 2.9 | 13.2 ± 3.1 | 14.6 ± 3.7 | .051 |
| 24-h DBP | 18.1 ± 4.1 | 19.4 ± 4.7 | 19.5 ± 5 | .290 |
| Daytime SBP | 11.1 ± 1.8 | 12.3 ± 2.1 | 13.8 ± 2.5 | <.001 ∗ |
| Daytime DBP | 15.7 ± 3 | 17.6 ± 3.3 ‡ | 18.7 ± 3.6 § | <.001 |
| Nighttime SBP | 11.1 ± 1.8 | 11.6 ± 2.2 | 12.9 ± 2.7 § || | .002 |
| Nighttime DBP | 15.6 ± 2.8 | 16 ± 3.1 | 17.5 ± 3.6 ‡ | .023 |
∗ P < .05 for all comparisons.
† P < .01 for all comparisons.
‡ P < .05 versus hypertension plus normal BMI.
§ P < .01 versus hypertension plus normal BMI.
Similar changes were observed in BP variability indices. Namely, daytime and 24-hour SDs were higher in obese than in normal-weight subjects, while nighttime SDs gradually increased from lean to obese patients ( Table 2 ). Daytime systolic CVs gradually increased from normal-weight to obese participants; daytime diastolic and nighttime CVs were higher in obese than in normal-weight subjects. Twenty-four-hour CVs were similar between the observed groups ( Table 2 ).
Conventional Echocardiography
LV diameters were similar among the observed groups ( Table 3 ). Interventricular septal thickness and LV mass index were significantly higher in obese than in normal-weight subjects with hypertension. Relative wall thickness of the left ventricle was higher in overweight and obese subjects than in lean subjects. Left atrial volume index progressively increased from normal-weight across overweight to obese subjects ( Table 3 ). LV ejection fraction was similar between the observed groups. Mitral E/A ratio was lowest in obese patients with hypertension, whereas E/e′ ratio was highest in this group ( Table 3 ).
| Variable | Hypertension plus normal BMI ( n = 45) | Hypertension plus overweight ( n = 47) | Hypertension plus obesity ( n = 35) | P |
|---|---|---|---|---|
| 2D LV parameters | ||||
| LVEDD (mm) | 49.3 ± 4.1 | 49.8 ± 4.2 | 51 ± 4.7 | .210 |
| LVESD (mm) | 29.6 ± 3.3 | 29.9 ± 3.4 | 31 ± 3.7 | .179 |
| LV EDV/BSA (mL/m 2 ) | 56.6 ± 6.3 | 58.3 ± 6.8 | 62.6 ± 7.2 ‡ , § | .001 |
| LV ESV/BSA (mL/m 2 ) | 35.0 ± 4.1 | 35.6 ± 4.7 | 37.6 ± 5.0 ‡ | .038 |
| IVS (mm) | 10.2 ± 1.7 | 10.9 ± 1.6 | 11.5 ± 1.7 § | .003 |
| RWT | 0.41 ± 0.02 | 0.43 ± 0.03 § | 0.44 ± 0.04 § | <.001 |
| LAV/BSA (mL/m 2 ) | 30.8 ± 4.9 | 34.3 ± 5.4 | 38.3 ± 6.4 | <.001 † |
| LVMI (g/m 2 ) | 93.7 ± 12 | 95.8 ± 13.6 | 101.7 ± 16 ‡ | .034 |
| LVMI/height 2.7 (g/m 2.7 ) | 47.8 ± 6.7 | 53.7 ± 7.7 | 58.8 ± 8.9 | <.001 ∗ |
| EF (%) | 62 ± 4 | 61 ± 4 | 60 ± 3 ‡ | .064 |
| E/A ratio | 1.06 ± 0.27 | 0.91 ± 0.3 | 0.67 ± 0.26 | <.001 ∗ |
| E/e′ m | 7.9 ± 2.3 | 9 ± 2.7 | 11 ± 3 § , ¶ | <.001 |
| 2D RV parameters | ||||
| RV diameter (mm) | 24.5 ± 2.9 | 25.3 ± 3.3 | 26 ± 3.6 | .124 |
| RV thickness (mm) | 4.3 ± 0.6 | 4.7 ± 0.8 | 5.3 ± 1.1 § , ¶ | <.001 |
| RAV/BSA (mL/m 2 ) | 27 ± 4.9 | 29.7 ± 5.8 | 33.4 ± 6.6 § || | <.001 |
| E/e′ t | 5.2 ± 1.4 | 5.8 ± 1.5 | 6.5 ± 2 § | .002 |
| s t (cm/sec) | 14 ± 2 | 14 ± 3 | 13 ± 2 | .119 |
| PASP (mm Hg) | 25 ± 5 | 27 ± 6 | 30 ± 5 § || | <.001 |
| 3D RV parameters | ||||
| RV EDV/BSA (mL/m 2 ) | 65 ± 6 | 67 ± 7 | 71 ± 8 § || | .001 |
| RV ESV/BSA (mL/m 2 ) | 26 ± 4 | 28 ± 4 | 31 ± 5 § , ¶ | <.001 |
| RV SV/BSA (mL/m 2 ) | 39 ± 5 | 39 ± 6 | 40 ± 6 | .675 |
| RV EF (%) | 60 ± 4 | 58 ± 3 ‡ | 57 ± 3 § | <.001 |
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