Abstract
The authors sought to investigate the association between different hypertensive phenotypes and left atrial (LA) function assessed by the volumetric method and the strain method in patients with untreated hypertension. This cross‐sectional study involved 236 untreated patients who underwent 24‐hour ambulatory blood pressure monitoring and two‐dimensional echocardiographic examination. Our findings showed that LA function gradually deteriorated from patients with normotension, across patients with daytime hypertension, to patients with night‐ and day‐nighttime hypertension. LA reservoir and conduit functions were particularly deteriorated in patients with nighttime and day‐nighttime hypertension compared with patients with normotension and patients with daytime hypertension, whereas LA pump function was compensatorily increased only in the participants with day‐nighttime hypertension. Only nighttime hypertension and day‐nighttime hypertension were independently associated with the reduced reservoir and conduit LA function. The difference between patients with daytime and nighttime hypertension was found in reservoir and conduit LA but not LA pump function.
Keywords: function, left atrium, nighttime hypertension, strain
1. INTRODUCTION
Left atrial (LA) enlargement represents a very important and well‐known risk factor for cardiovascular and overall morbidity and mortality.1, 2 LA phasic function has long been considered as unimportant. The number of studies that demonstrate the importance of LA reservoir, conduit, and active pump function is increasing.2, 3, 4 LA reservoir and conduit flow volumes are drawn into the left ventricle during the early diastolic phase. LA reservoir function represents the atrial ability to store blood when the mitral valve is closed. Conduit function characterizes passive blood transfer directly from pulmonary veins to the left ventricle when the mitral valve is open, whereas LA booster pump function represents active LA contraction during late diastole, which is necessary to complete ventricular filling and increase left ventricular (LV) end‐diastolic volume.
Results regarding LA phasic function in hypertension are still conflicting and there is still no consensus about the influence of hypertension on LA remodeling. Most researchers agree about the negative impact of hypertension.3, 4, 5, 6, 7 However, there are studies that do not fully support this result.8 The relationship between 24‐hour blood pressure (BP) patterns and LA function has been insufficiently investigated.9, 10 The existing data show that nondipping BP pattern is associated with deterioration of LA function and mechanics, which follows LV remodeling in these patients.10, 11
A new classification of hypertensive phenotypes on daytime, nighttime, and day‐nighttime hypertension reveals that nighttime hypertension rather than nondipping pattern represents an independent factor associated with LV mass index (LVMI) and LV hypertrophy.12, 13 Considering the fact that LV mass and geometry induce LA remodeling,14 we hypothesized that nighttime hypertension could influence LA mechanics and function. This association would be particularly interesting because nighttime hypertension, as well as LA volumes and function, is related to worse cardiovascular and overall outcome.1, 2, 15
LA remodeling has been reported in patients with hypertension who have asymptomatic diastolic dysfunction.16, 17 Although LA enlargement could be a potential mechanism for compensating the impairment of LV compliance and progression of LV diastolic dysfunction in the hypertrophic left ventricle, it has been known that LA dilatation and dysfunction occur significantly before hypertensive LV hypertrophy develops. A large meta‐analysis that included 10 141 patients with hypertension showed that LV hypertrophy was significantly more common in patients with LA enlargement (68.2%) than in their counterparts without LA dilatation (41.8%).18 LA remodeling in arterial hypertension is primarily induced by impaired LV filling and relaxation, and secondarily attributable to increased LV mass.
The aim of the present study was to investigate LA phasic function in patients with untreated hypertension with different hypertension phenotypes (daytime, nighttime, and day‐nighttime hypertension), as well to determine the association between various hypertensive phenotypes and different LA functions in this population.
2. METHODOLOGY
This cross‐sectional investigation involved 236 consecutive patients with untreated hypertension referred to our outpatient clinic at the Cardiology Department, University Hospital “Dr Dragisa Misovic” in Belgrade, Serbia, for screening of hypertension or echocardiographic examination. All included patients recently received a diagnosis of untreated hypertension. Individuals with symptoms or signs of coronary artery disease, heart failure, previous cerebrovascular insult, valvular heart disease, atrial fibrillation, neoplastic disease, liver cirrhosis, renal failure, sleeping disorders, or diabetes mellitus were also excluded from the study.
Anthropometric measures (height and weight) and laboratory analyses (levels of fasting glucose, total cholesterol, triglycerides, and serum creatinine) were measured in all participants. Body mass index (BMI) was calculated for each patient ([weight in kg]/[height in m]2). The study was approved by the local ethics committee, and informed consent was obtained from all participants.
2.1. Clinic BP measurement and 24‐hour ambulatory BP monitoring
All patients underwent 24‐hour BP. A medical doctor measured clinic arterial BP values by conventional sphygmomanometer (Medisana) in the morning hours by measuring the average value of two consecutive measurements in patients in the sitting position, taken within 5 minutes, after the patient had rested for at least 5 minutes. BP was obtained on at least two separate occasions before 24‐hour ambulatory BP was assessed.
Noninvasive 24‐hour ambulatory BP monitoring was performed on the nondominant arm, using a Schiller BR‐102 plus system (Schiller AG). The device was programmed to obtain BP readings at 20‐minute intervals during the day (7 am–11 pm) and at 30‐minute intervals during the night (11 pm–7 am). Nighttime BP was defined as the average of BPs from the time when the patients went to bed until the time they got out of bed, and daytime BP as the average of BPs recorded during the rest of the day. The recording was analyzed to acquire a 24‐hour, daytime, and nighttime average systolic BP (SBP); diastolic BP (DBP); and heart rates.
According to present guidelines, nighttime hypertension was defined as nighttime SBP ≥120 mm Hg and/or DBP ≥70 mm Hg, whereas normal daytime ambulatory BP was defined as SBP <135 mm Hg and DBP <85 mm Hg.19 The patients with elevated daytime and nighttime BP and those with normal awake and nighttime BP were categorized as having daytime‐nighttime hypertension and normotension, respectively. Individuals with normal nighttime BP and increased awake BP were categorized as having isolated daytime hypertension, whereas those with elevated BP during night and normal awake BP were classified as having isolated nighttime hypertension.
2.2. Echocardiography
Echocardiographic examination was performed with a Vivid 7 ultrasound machine (GE Healthcare). Values of all two‐dimensional echocardiographic parameters were calculated as the average value of three consecutive cardiac cycles. LV end‐systolic and end‐diastolic diameters, as well as LV septum thickness, were measured according to the latest recommendations.20 Relative wall thickness was calculated as (2× posterior wall thickness)/LV end‐diastolic diameter. LV ejection fraction was estimated by the biplane method. LV mass was calculated using the ASA formula and indexed for body surface area.20
Transmitral Doppler inflow and tissue pulsed Doppler parameters were obtained in the apical four‐chamber view. Pulsed Doppler measurements included transmitral early and late diastolic peak flow velocity (E and A, respectively).21 Tissue Doppler imaging was used to obtain LV myocardial velocities in the apical four‐chamber view, with a sample volume placed at the septal and lateral segment of the mitral annulus during early diastole (e′). The average of the peak early diastolic relaxation velocity (e′) of the septal and lateral mitral annulus obtained by the tissue Doppler was computed, and the E/e′ ratio was calculated.
2.3. Two‐dimensional echocardiographic assessment of LA volumes and function
LA volumes were measured in three different segments of the cardiac cycle: maximal LA volume was acquired before the mitral valve opening, pre‐A (pre‐atrial contraction) LA volume was measured at the onset of atrial systole (peak of P wave in ECG), while minimal LA volume was evaluated at the mitral valve closure (Figure 1). All volumes were assessed by the biplane method in four‐ and two‐chamber views, and indexed for body surface area (LAVI). Total emptying fraction (EF), the parameter of LA reservoir function, was computed as (LAVImax – LAVImin)/LAVImax; passive EF, the indicator of LA conduit function, was computed as (LAVImax – LAVIpre‐A)/LAVImax; and active EF, the index of LA booster function, was calculated as (LAVIpre‐A – LAVImin)/LAVIpre‐A.
Figure 1.
Determination of left atrial function by the volumetric method. LAVmax indicates maximal left atrial volume; LAVmin, minimal left atrial volume; LAVpre‐A, left atrial volume before atrial contraction. LA TotEF=(LAVmax – LAVmin)/LAVmax; LA PassEF=(LAVmax – LAVpre‐A)/LAVmax; LA ActEF=LAVpre‐A – LAVmin/LAVpre‐A
A two‐dimensional echocardiographic strain analysis was performed in the apical four‐ and two‐chamber views with a commercially available software Echo PAC 201 (GE Healthcare). LA endocardium was manually traced in both apical four‐ and two‐chamber views, and the software automatically tracked the contours on the subsequent frames. Inadequately traced segments were automatically excluded from further analysis. LA phasic function was assessed by a strain rate analysis: peak systolic, peak early diastolic, and peak late LA diastolic strain rate. Biplane LA global strain and strain rate values were calculated by averaging the values observed in apical four‐ and two‐chamber views (Figure 2).
Figure 2.
Determination of left atrial function by the strain method
2.4. Statistical analysis
Continuous variables were presented as mean±SD and compared by analysis of equal variance, as they showed normal distribution. Bonferroni post hoc analysis was used for comparison between different groups. Differences in proportions were compared using chi‐square test. Cutoff values for LA total, passive and active EF, as well as LA longitudinal strain, were used from previously published studies.22, 23 The association between daytime, nighttime, and day‐nighttime hypertension and different LA parameters was determined by univariate logistic regression analysis (odds ratio [OR] and 95% CI). The multivariate logistic regression analysis included different phenotypes of hypertension (daytime, nighttime, and day‐nighttime hypertension), age, sex, BMI, 24‐hour SBP, E/e’, and LVMI. There were four different multivariate models for each LA parameter as a dependent variable (LA total, passive, and active EF, as well as LA longitudinal strain). Intraobserver and interobserver variability for volumetric and strain parameters was analyzed in 20 randomly selected patients. The interobserver and intraobserver agreements were determined by evaluation of the intraclass correlation coefficients. A P value <.05 was considered statistically significant.
3. RESULTS
A statistically significant difference was not found in sex distribution, average age, BMI, and average creatinine level (Table 1). Glucose, triglyceride, and cholesterol levels were significantly higher in patients with day‐nighttime hypertension (Table 1).
Table 1.
Demographic characteristics and clinical parameters of the study population
| Day‐ and nighttime normotension (n=53) | Isolated daytime hypertension (n=67) | Isolated nighttime hypertension (n=35) | Day–nighttime hypertension (n=81) | P Value | |
|---|---|---|---|---|---|
| Age, y | 48±9 | 49±8 | 51±10 | 52±10 | .062 |
| Women, % | 30 (57) | 34 (51) | 17 (49) | 35 (43) | .495 |
| BMI, kg/m2 | 25.1±2.9 | 26.0±3.0 | 26.2±3.0 | 26.1±3.2 | .227 |
| Plasma glucose, mmol/L | 5.0±0.8 | 4.9±0.9 | 5.2±0.7 | 5.4±0.8a,b | .002 |
| Triglycerides, mmol/L | 1.3±0.4 | 1.5±0.6 | 1.5±0.7 | 1.7±0.7c | .004 |
| Total cholesterol, mmol/L | 5.0±0.7 | 5.4±0.9 | 5.5±0.9 | 5.6±1.0c | .002 |
| Serum creatinine, μmol/L | 72±10 | 74±9 | 75±11 | 76±12 | .194 |
Abbreviation: BMI, body mass index.
P<.05 vs daytime and nighttime normotension.
P<.01 vs isolated daytime hypertension.
P<.01 vs daytime and nighttime normotension.
3.1. Clinic BP measurement and ambulatory BP monitoring
Clinic SBP and DBP gradually increased from patients with normotension, through the patients with isolated nighttime and daytime hypertension, to the patients with day‐nighttime hypertension (Table 2). Average 24‐hour SBP and DBP were significantly elevated in all patients with hypertension compared with patients with normotension. However, BPs were higher in the patients with day‐nighttime hypertension than in patients with isolated daytime and nighttime hypertension (Table 2).
Table 2.
Clinic and ambulatory blood pressure measurements
| Daytime and nighttime normotension (n=53) | Isolated daytime hypertension (n=67) | Isolated nighttime hypertension (n=35) | Daytime and nighttime hypertension (n=81) | P Value | |
|---|---|---|---|---|---|
| Clinic | |||||
| SBP, mm Hg | 125±10 | 146±12 | 135±10 | 153±14 | <.001a |
| DBP, mm Hg | 74±6 | 88±8b | 84±7b,c | 93±8b,d | <.001 |
| Heart rate, beats per min | 71±7 | 76±7b | 74±7 | 77±8b | <.001 |
| 24‐h | |||||
| SBP, mm Hg | 118±7 | 131±8b | 127±7b | 140±10b,c, d | <.001 |
| DBP, mm Hg | 71±6 | 79±6b | 77±6b | 85±7b,c, d | <.001 |
| Heart rate, beats per min | 66±6 | 71±7b | 70±6 | 73±8b,d | <.001 |
| Daytime | |||||
| SBP, mm Hg | 122±8 | 138±8 | 127±6 | 145±11 | <.001e |
| DBP, mm Hg | 73±5 | 85±6 | 77±6 | 88±6 | <.001e |
| Heart rate, beats per min | 68±6 | 74±8b | 71±7 | 76±7b,d | <.001 |
| Nighttime | |||||
| SBP, mm Hg | 106±5 | 111±6b | 126±7b,c | 128±7b,c | <.001 |
| DBP, mm Hg | 64±5 | 63±5 | 78±6b,c | 77±6b,c | <.001 |
| Heart rate, beats per min | 60±5 | 64±6b | 68±6c,f | 69±7b,c | <.001 |
Abbreviations: DBP, diastolic blood pressure; SBP, systolic blood pressure.
P<.01 for all comparisons.
P<.01 vs daytime and nighttime normotension.
P<.01 vs isolated daytime hypertension.
P<.01 vs isolated nocturnal hypertension.
P<.05 for all comparisons.
P<.05 vs isolated daytime hypertension.
Systolic and diastolic daytime BPs gradually increased from the patients with normotension, across the patients with isolated nighttime hypertension, to the patients with isolated daytime and day‐nighttime hypertension (Table 2). Interestingly, nighttime BPs were significantly higher in the patients with day‐nighttime and isolated nighttime hypertension than in the other two groups (Table 2).
Average heart rate was significantly elevated in the day‐nighttime hypertensive individuals than in the other groups (Table 2).
3.2. Two‐dimensional echocardiographic LV structure and function
LV diameters and EF were not significantly different between the observed groups (Table 3). Interventricular septum and relative wall thickness, as well as LVMI, were higher in all patients with hypertension compared with those with normotension. Only LVMI was significantly higher in the patients with day‐nighttime hypertension than in the other observed groups (Table 3). Mitral E/e′ ratio, as the parameter of LV diastolic function, was significantly higher in the patients with day‐nighttime hypertension than in the other three groups (Table 3).
Table 3.
Echocardiographic left ventricular and left atrial parameters in the study population
| Daytime and nighttime normotension (n=53) | Isolated daytime hypertension (n=67) | Isolated nighttime hypertension (n=35) | Day‐nighttime hypertension (n=81) | P Value | |
|---|---|---|---|---|---|
| Left ventricular parameters | |||||
| LVEDD, mm | 48.1±3.5 | 49.0±3.4 | 48.5±3.6 | 49.1±3.7 | .386 |
| LVESD, mm | 30.4±2.9 | 31.0±3.2 | 31.3±3.4 | 31.7±3.6 | .165 |
| IVS, mm | 9.2±1.0 | 10.3±1.2a | 10.2±1.0a | 10.8±1.3a | <.001 |
| RWT | 0.37±0.03 | 0.41±0.04a | 0.41±0.03a | 0.43±0.04a,b,c | <.001 |
| LVMI, g/m2 | 75.3±5.6 | 90.8±6.0a | 88.9±6.2a | 96.6±7.9a,b,d | <.001 |
| EF, % | 63±4 | 62±3 | 63±4 | 62±3 | .192 |
| E/e′ | 8.3±1.6 | 10.5±3.1a | 10.0±3.3 | 12.4±3.5 a,b,d | <.001 |
| Left atrial function parameters | |||||
| LAVmax, mL | 51.0±8.7 | 60.0±11.0a | 61.2±12.5a | 63.9±13.6a | <.001 |
| LAVmax/BSA, mL/m2 | 26.7±4.5 | 31.0±5.7a | 31.6±6.4a | 33.2±6.6a | <.001 |
| LAVmin,mL | 19.4±3.0 | 24.0±3.8 | 27.0±4.7 | 29.4±5.3 | <.001e |
| LAVmin/BSA, mL/m2 | 10.1±1.8 | 12.4±2.0a | 13.9±2.5a,f | 15.3±3.4a,b | <.001 |
| LAVpre‐A, mL | 27.7±4.5 | 35.3±6.4 | 41.5±8.2 | 46.7±9.5 | <.001g |
| LAVpre‐A/BSA, mL/m2 | 14.4±2.4 | 18.2±3.4 | 21.4±4.2 | 24.3±4.7 | <.001g |
| LA TotEF, % | 62±6 | 60±6 | 56±5a,b | 54±5a,b | <.001 |
| LA PassEF, % | 47±7 | 41±6 | 32±6 | 27±5 | <.001g |
| LA ActEF, % | 30±5 | 32±5 | 35±6a | 37±6a,b | <.001 |
| LA mechanical parameters | |||||
| Longitudinal strain, % | 37±6 | 35±6 | 33±6a | 31±5a,b | <.001 |
| Systolic strain rate, /s | 1.4±0.3 | 1.3±0.4 | 1.2±0.3a | 1.14±0.3a,b | <.001 |
| Early diastolic strain rate, /s | −1.6±0.4 | −1.5±0.4 | −1.3±0.4a | −1.22±0.3a,b | <.001 |
| Late diastolic strain rate, /s | −1.2±0.3 | −1.4±0.3 | −1.5±0.4h | −1.6±0.4a,f | <.001 |
Abbreviations: ActEF, active emptying fraction; BSA, body surface area; E, early diastolic mitral flow (pulse Doppler); e′, early diastolic flow velocity across the septal segment of mitral (e′) annulus (tissue Doppler); EF, ejection fraction; IVS, interventricular septum; LA, left atrium; LAVmax, maximal left atrial volume; LAVmin, minimal left atrial volume; LAVpre‐A, left atrial volume before atrial contraction; LVMI, left ventricular mass index; LVEDD, left ventricular end‐diastolic dimension; LVESD, left ventricular end‐systolic dimension; PassEF, passive emptying fraction; RWT, relative wall thickness; TotEF, total emptying fraction.
P<.01 vs daytime and nighttime normotension.
P<.01 vs isolated daytime hypertension.
P <.05 vs isolated nocturnal hypertension.
P<.01 vs isolated nocturnal hypertension.
P<.05 for all comparisons.
P<.05 vs isolated daytime hypertension.
P<.01 for all comparisons.
P<.05 vs daytime and nighttime normotension.
3.3. LA function
Maximum LAVI was significantly lower in the patients with normotension than in any group with hypertension (Table 3). Minimum LAVI was higher in all hypertensive groups than in the normotensive group, but it was also higher in the nighttime and day‐nighttime hypertensive group than in the daytime group (Table 3). Finally, pre‐A LAVI gradually and significantly increased from the normotensive group, throughout the daytime hypertensive group, to the nighttime and day‐nighttime hypertensive group (Table 3).
Consequently, total LA EF, the parameter of reservoir function is significantly lower in the patients with nighttime and day‐nighttime hypertension than in the patients with normotension and daytime hypertension (Table 3, Figure 3). Passive LA EF, the indicator of LA conduit function gradually decreased from the normotensive group, across the daytime and nighttime hypertensive groups, to the day‐nighttime hypertensive group (Table 3, Figure 3). Active LA EF that corresponds with LA pump function was significantly higher in the patients with day‐nighttime hypertension than in the patients with normotension and daytime hypertension (Table 3, Figure 3).
Figure 3.
Left atrial volumetric function in the study group
All measured LA strain parameters were significantly deteriorated in the patients with day‐nighttime hypertension than in the patients with normotension and daytime hypertension (Table 3). Furthermore, all LA strain parameters were worse in the patients with nighttime hypertension than in the patients with normotension.
3.4. Univariate logistic regression analyses
Daytime hypertension was significantly associated only with decreased passive LA EF (OR, 1.9; 95% CI, 1.1–7.2 [P=.026]). The results are presented in Table 4.
Table 4.
The association between daytime, nighttime, and day‐nighttime hypertension and impaired 2DE strain (univariate and multivariate logistic regression analysis)a
| Univariate | Multivariatea | |||||
|---|---|---|---|---|---|---|
| OR | 95% CI | P Value | OR | 95% CI | P Value | |
| Reduced LA total EF | ||||||
| Daytime and nighttime normotension | 1.00 | Referent | – | 1.00 | Referent | – |
| Isolated daytime hypertension | 1.3 | 0.8–9.1 | .141 | 1.1 | 0.6–11.3 | .211 |
| Isolated nighttime hypertension | 2.4 | 1.2–7.4 | .012 | 1.7 | 1.1–8.3 | .033 |
| Daytime and nighttime hypertension | 4.6 | 1.5–12.1 | <.001 | 2.2 | 1.2–8.5 | .010 |
| Reduced LA passive EF | ||||||
| Daytime and nighttime normotension | 1.00 | Referent | – | 1.00 | Referent | – |
| Isolated daytime hypertension | 1.9 | 1.1–7.2 | .026 | 1.2 | 0.7–10.3 | .254 |
| Isolated nighttime hypertension | 3.7 | 1.1–9.6 | .003 | 2.6 | 1.3–9.7 | .011 |
| Daytime and nighttime hypertension | 5.9 | 1.7–13.3 | <.001 | 3.1 | 1.4–10.7 | <.001 |
| Elevated LA active EF | ||||||
| Daytime and nighttime normotension | 1.00 | Referent | – | 1.00 | Referent | – |
| Isolated daytime hypertension | 1.5 | 0.9–10.5 | .203 | 1.3 | 0.8–13.6 | .331 |
| Isolated nighttime hypertension | 1.8 | 0.6–11.9 | .195 | 1.4 | 0.7–10.8 | .227 |
| Daytime and nighttime hypertension | 2.1 | 1.04–8.7 | .022 | 1.8 | 0.5–15.1 | .206 |
| Reduced longitudinal LA strain, % | ||||||
| Daytime and nighttime normotension | 1.00 | Referent | – | 1.00 | Referent | – |
| Isolated daytime hypertension | 0.9 | 0.6–8.8 | .155 | 0.7 | 0.6–14.4 | .181 |
| Isolated nighttime hypertension | 1.7 | 1.1–6.9 | .034 | 1.4 | 0.8–12.1 | .288 |
| Daytime and nighttime hypertension | 1.9 | 1.2–6.3 | .037 | 1.6 | 0.9–16.5 | .103 |
Abbreviations: EF, ejection fraction; LA, left atrial; OR, odds ratio; TDE, two‐dimensional echocardiography.
Models were adjusted for age, sex, body mass index, 24‐hour systolic blood pressure, mitral E/e’ ratio, and left ventricular mass index.
Nighttime phenotype of hypertension was significantly more associated with decreased total LA EF (OR, 2.4; 95% CI, 1.2–7.4 [P=.012]), reduced passive LA EF (OR, 3.7; 95% CI, 1.1–9.6 [P=.003]), and decreased LA global longitudinal strain (OR, 1.7; 95% CI, 1.1–6.9 [P=.034]). The day‐nighttime hypertensive phenotype was significantly more associated with decreased total LA EF (OR, 4.6; 95% CI, 1.5–12.1 [P<.001]), reduced passive LA EF (OR, 5.9; 95% CI, 1.7–13.3 [P<.001]), elevated active LA EF (OR, 2.1; 95% CI, 1.04–8.7 [P=.022]), and decreased LA global longitudinal strain (OR, 1.9; 95% CI, 1.2–6.3 [P=.037]) (Table 4).
3.5. Multivariate logistic regression analyses
Nighttime hypertension was associated with decreased total LA EF (OR, 1.7; 95% CI, 1.1–8.3 [P=.033]) and reduced passive LA EF (OR, 2.6; 95% CI, 1.3–9.7 [P=.011]) independently of other hypertensive phenotypes, age, BMI, 24‐hour SBP, E/e’, and LVMI (Table 4).
Day‐nighttime hypertension was significantly and independently of other hypertensive phenotypes, age, BMI, 24‐hour SBP, E/e’, and LVMI associated with decreased total LA EF (OR, 2.2; 95% CI, 1.2–8.5 [P=.010]) and reduced passive LA EF (OR, 3.1; 95% CI, 1.4–10.7 [P<.001]) (Table 4).
3.6. Interobserver variability
Intraclass correlation coefficients were: LA maximal volume: r=.911, P<.001; LA minimal volume: 0.890, P<.001; pre‐A LA volume: r=.850, P<.001; and LA longitudinal strain: r=.920, P<.001.
3.7. Intraobserver variability
Intraclass correlation coefficients were: LA maximal volume: r=.935, P<.001; LA minimal volume: 0.913, P<.001; pre‐A LA volume: r=.894, P<.001; and LA longitudinal strain: r=.940, P<.001.
4. DISCUSSION
The present investigation has revealed that nighttime and day‐nighttime hypertension have significantly more impact on LA function than normotension and daytime hypertension. Interestingly, the difference in LA remodeling between various hypertensive phenotypes is more pronounced with the volumetric method than with strain analysis. LA reservoir and conduit functions are particularly deteriorated in patients with nighttime and day‐nighttime hypertension compared with patients with normotension and daytime hypertension, whereas LA pump function is increased only in patients with day‐nighttime hypertension. Multivariate analysis showed that only nighttime and day‐nighttime hypertension are independently associated with reduced total and passive LA EFs reservoir and conduit LA function. At the same time, the difference between the patients with daytime and nighttime hypertension was also seen in reservoir and conduit LA function, but not in LA pump function.
Deterioration of LA function has previously been reported in patients with hypertension.4, 5, 6, 7, 8 Our results are in line with previous findings that show that total and passive LA EFs are reduced in patients with hypertension. However, our results show that active LA EF is compensatorily increased in patients with hypertension, particularly in patients with nighttime and day‐nighttime hypertension.
A recent study has shown that both reservoir and conduit LA function are significantly decreased before any symptoms, LA enlargement, or increase of LV filling pressures.24 Russo and colleagues25 demonstrated that LA reservoir function strongly correlates with LV diastolic function, whereas Miyoshi and colleagues26 showed a significant association between LA reservoir function, LA remodeling, and LV dysfunction in patients with asymptomatic hypertension. Results from the Dallas Heart Study revealed that total LA EF reservoir function is superior and incremental to LA maximum volume index in the prediction of all‐cause mortality in a global population.2 The present findings regarding deteriorated LA function in nighttime and day‐nighttime hypertension might partly explain the unfavorable outcome in these groups. Our results do not show higher LV mass or worse LV diastolic function in patients with nighttime hypertension compared with patients with daytime hypertension. Previous investigations support our findings regarding the absence of differences in LV mass among patients with daytime and nighttime hypertension.27, 28 However, deteriorated LV mechanics could be responsible for LA changes and LA‐LV coupling, independently of LV mass or LV diastolic function.29 In addition, findings from the BEFRI (Berlin Female Risk Evaluation) trial24 show that LA dysfunction exists even in patients with all LV diastolic function parameters within normal ranges.
The present study shows that nighttime and day‐nighttime hypertension is independent of other hypertensive phenotypes (normotension and daytime hypertension) and the most important clinical and echocardiographic parameters associated with reduction of LA reservoir and conduit function. The association between these hypertensive phenotypes and LA remodeling could partly be explained by increased activation of the sympathetic autonomic nervous or renin‐angiotensin‐aldosterone system. Namely, it has been previously shown that nondippers and reverse dippers have a significantly more active sympathetic system30 and renin‐angiotensin‐aldosterone system.31
The effect of nighttime hypertension on LA function is particularly important because patients with nighttime hypertension are mostly unaware of their condition and are considered to have normotension until they undergo 24‐hour ambulatory BP monitoring. Considering the fact that LA reservoir and conduit function in these “false normotensives” is even worse than in patients with daytime hypertension, it should be noted that the target organ damage and outcome could be significantly worse in the patients with nighttime hypertension compared with those with daytime or even day‐nighttime hypertension who are aware of their condition and who are treated for hypertension.
Because novel methods of renal denervation, which are related to suppression of both biohumoral systems, significantly improve LV structure and function, as well as LA function, it could be indirectly concluded that these biohumoral changes might provoke a hemodynamic reaction, such as the elevation of nighttime cardiac output and systemic vascular resistance or a combination of both. Findings from a recent study have shown that treatment with renin‐angiotensin inhibitors could improve abnormal LA‐LV interaction and LA function in a hypertensive population,26 which confirms our hypothesis about a negative influence of this biohumoral system in patients with nighttime and day‐nighttime hypertension.
5. LIMITATIONS
The present investigation has several limitations. Patients with long‐lasting hypertension, diabetes mellitus, severe obesity, and older age were not included in the study, which limits the generalization of our results. Coronary artery disease was not excluded by angiography. However, in young patients with asymptomatic recently diagnosed hypertension, it is not indicated and unethical. The cross‐sectional nature of the study limits the ability to assume the causal relationship between nighttime hypertension and LA phasic function.
6. CONCLUSIONS
This is the first study to investigate the influence of nighttime hypertension on LA phasic function. All three LA functions: (reservoir, conduit, and pump) are affected by nighttime and day‐nighttime hypertension. The negative influence is particularly present in the relationship between these two hypertensive phenotypes and reservoir and conduit LA functions. LA phasic function in patients with nighttime hypertension is intermediate between patients with daytime and day‐nighttime hypertension and the differences are more pronounced in the LA volumetric than the strain analysis. The association between hypertensive phenotypes and LA phasic function is independent of LV systolic or diastolic function and LV structure. Further longitudinal studies are necessary to evaluate the influence of nighttime hypertension and LA phasic function in patients with hypertension and particularly the impact on the outcome in these patients.
CONFLICT OF INTEREST
None.
Tadic M, Cuspidi C, Pencic‐Popovic B, Celic V, Mancia G. The relationship between nighttime hypertension and left atrial function. J Clin Hypertens. 2017;19:1096–1104. 10.1111/jch.13066
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