Abstract
The nocturnal blood pressure (BP) has been identified as a prognostic factor for cardiovascular events. This study aimed to investigate the association between different patterns of nocturnal masked hypertension (MH) and the echocardiographic parameters in the untreated nocturnal MH patients. A total of 721 untreated MH patients (309 females and 412 males, mean age = 56.59 ± 15.20 years) from June 2006 and June 2016 were included and divided into nocturnal systolic MH (n = 77), nocturnal diastolic MH (n = 232), and nocturnal systolic/diastolic MH (n = 412) groups according to the ambulatory blood pressure monitoring. Baseline characteristics, office BP values, ambulatory BP monitoring parameters, and echocardiographic parameters were compared among the three groups. The independent factors associated with echocardiographic parameters were analyzed by multivariate linear regression. The nocturnal systolic group had the highest ratio of males, mean age, and office systolic BP (SBP), and the lowest office, 24‐hour, daytime, nocturnal diastolic BP and heart rate among the three groups. The nocturnal diastolic group had the lowest interventricular septum (IVS) thickness, left atrium (LA) dimension, and left ventricular (LV) mass among the three groups. Multivariate linear regression analysis revealed that 24‐hour, daytime, and nocturnal SBPs were all positively associated with LA dimension, IVS thickness, and LV mass (all B were positive and P < .050). Pearson's correlation analysis showed that nocturnal SBP was positively correlated with LA dimension, IVS thickness, and LV mass. These results suggested that different patterns of nocturnal MH had different echocardiographic outcomes. Nocturnal SBP was the independent factor associated with the echocardiographic parameters.
Keywords: cardiac damage, echocardiographic parameters, masked hypertension, nocturnal systolic hypertension
1. INTRODUCTION
Hypertension is a major risk factor for cardiovascular (heart attack, stroke),1 renal,2 and metabolic (type 2 diabetes) diseases.3 It is well accepted that conventional in‐office blood pressure (BP) measurement is no longer the only gold standard for screening, diagnosis, and management of hypertension.4 Ambulatory blood pressure monitoring (ABPM) is a method for automated blood pressure (BP) measurements at fixed time intervals during a 24‐hour period away from the clinic setting (out‐of‐office). Combining in‐office and out‐of‐office BP measurements allow identifying different BP patterns, namely sustained normotension, sustained hypertension, white‐coat hypertension, and masked hypertension (MH).5, 6, 7 Masked hypertension originally referred to in‐office normotension with elevated daytime BP (ambulatory systolic BP [SBP] ≥135 mm Hg or diastolic BP [DBP] ≥85 mm Hg) by Pickering in 2002.8 After the definition of MH was extended to elevated nocturnal ambulatory BP (nocturnal ambulatory SBP ≥ 120 mm Hg or DBP ≥ 70 mm Hg), the prevalence of masked hypertension has been markedly increased from 30% to 60%.9, 10, 11 At present, the pathogenic mechanism of MH remains not fully understood. Several mechanisms have been proposed, such as overactivity of the adrenergic nervous system.12 Studies have demonstrated that similar to those with sustained hypertension, MH patients have increased risks of target organ damage and cardiovascular complications.11, 13, 14, 15 Accumulating evidence has suggested that nocturnal hypertension is associated with increased risks of hypertensive target organ damage and adverse cardiovascular outcomes.16, 17, 18 It is believed that sympathetic drive‐induced nighttime BP surges may advance age‐related organ damages and nighttime onset of cardiovascular events.19 Moreover, Fagard et al have been reported that nocturnal BP has a better prognostic value for cardiovascular events than the daytime BP in hypertensive patients.20 The Jackson Heart Study demonstrates that isolated nocturnal hypertension is associated with increased left ventricular (LV) mass as compared to normal tension in African Americans.21 De la Sierra et al report that nocturnal hypertension is associated with increased urinary albumin excretion in the 37 096 untreated patients and 62 788 patients receiving antihypertensive treatment.22 A meta‐analysis of 17 312 hypertensive patients by Salles et al23 have confirmed the prognostic significance of nocturnal hypertension in MH and sustained hypertension.
Although the prognostic value of nocturnal BP has been demonstrated, however, it is still unknown whether nocturnal systolic or diastolic BP has a prognostic value in patients with untreated MH. Therefore, the purpose of this study was to investigate the association between different patterns of nocturnal MH and the echocardiographic parameters in untreated nocturnal MH.
2. METHODS
2.1. Patients
The current study retrospectively included untreated MH patients referred to our outpatient clinic for ABPM and echocardiography due to suspected hypertension or other diseases between June 2006 and June 2016. MH was defined as patients with normal office BP24 (office SBP < 140 and DBP < 90 mm Hg) but elevated ambulatory BP. Exclusive criteria were as follows: (a) patients with antihypertensive treatment; (b) those with history or clinical evidence of hypertension‐related complications (coronary heart disease, heart failure, cerebrovascular disease, renal insufficiency, or peripheral artery disease); and (c) those with clinical signs or laboratory evidence of secondary causes of arterial hypertension. The MH patients were divided into three subgroups according to their nocturnal ambulatory SBP and DBP levels as follows: nocturnal systolic (nocturnal SBP ≥ 120 mm Hg and DBP < 70 mm Hg), nocturnal diastolic (nocturnal SBP < 120 mm Hg and DBP ≥ 70), and systolic/diastolic (nocturnal SBP ≥ 120 mm Hg and DBP ≥ 70 mm Hg) groups. During June 2006 and June 2016, a total of 11 654 individuals received ambulatory blood pressure monitoring (ABPM). Among them, 4670 cases of sustained hypertension patients, 1542 cases of white‐coat hypertension patients, and 4311 cases of sustained normotension were excluded. Of the 1131 masked hypertension patients, only 721 patients receiving echocardiographic examinations were included in the study. Flowchart of patient selection is shown in Figure 1. This study was approved by the institutional review board of our hospital. Written informed consent was waived by the IRB due to the retrospective nature of this study.
Figure 1.
Flowchart of patient selection
2.2. Clinic BP measurement and 24‐hour ABPM
The clinic BP of the patient was measured by a physician using a mercury sphygmomanometer with an appropriate cuff in a seated position with the non‐dominant arm at the level of the heart, after at least 5‐minute quiet resting period. Three consecutive assessments of BP were taken at a 1‐minute interval, and the mean of the second and third was used for analyses.
The noninvasive 24‐hour ABPM was performed on the non‐dominant arm, using TM‐2430 device (A & D Co., Ltd., Tokyo, Japan). The ABPM was programmed to take readings at a 30‐minute interval during the daytime. During the nighttime, blood pressure was measured at a 60‐minute interval. According to the manufacturer's recommendation, systolic BP readings outside the range of 70 mm Hg (60 mm Hg during sleep) to 250 mm Hg and diastolic readings outside the range of 40 mm Hg (30 mm Hg during sleep) to 150 mm Hg were regarded as errors. Nocturnal BP was defined as the mean BPs from the time patients went to bed until the time they got out of bed, and daytime BP was defined as the mean BPs recorded during the rest of the day. The following data were not included for analysis: the data missing more than 30%, the data missing more than 2 hours, data collected under abnormal conditions, and the sleeping time <6 hours or >12 hours.
2.3. Echocardiography
Conventional two‐dimensional echocardiography was performed using a commercial ultrasound system (Vivid7, GE Health Medical, Milwaukee, WI, USA) with a multifrequency transducer (M3S1.7/3.4MHz) according to the manufacturer's protocol and the guidelines of the American and European Societies of Echocardiography25 by the same independent echocardiologist. The linear left ventricular end‐diastolic dimension (LVEDD), the thickness of interventricular septum (IVS), and the left ventricular (LV) posterior wall were acquired using a parasternal long‐axis view at the level of the tips of the mitral valve leaflets. The LV volumes were calculated according to the Teichholz formula.26 LVM was determined by the cube formula, using the Penn convention, as suggested by Devereux and Reichek.27 LA dimension was defined as the LA anteroposterior measurement in the parasternal long‐axis view using M‐mode echocardiography.
2.4. Statistical analyses
Statistical comparisons were mainly performed among the three groups, including patients’ baseline characteristics, office BP values, ambulatory BP, and heart rate monitoring parameters. Continuous variables were presented as the mean ± standard deviation (SD) and were compared among the nocturnal systolic MH, nocturnal diastolic MH, and nocturnal systolic/diastolic MH groups by one‐way ANOVA with the Tukey HSD post hoc comparison test. Categorical data were presented by number and percentage (%) among the three groups, and were compared by the chi‐square test or the Fisher exact test (if any expected value lower than 5 was observed). Multivariate analysis of covariance (MANCOVA) was used to report the estimated mean and 95% confidence interval (95% CI) of echocardiography parameters controlled for the significant correlation among dependent variables and adjusting patient's covariates, and the significance among the three groups was reported. For all patients, univariate and multivariate linear regression models were performed to identify the independent factors associated with the echocardiographic parameters (IVS thickness and LA dimension). The multivariate models were adjusted for patients’ sex and age. Only the variables that were significant in both univariate and multivariate results would be regarded as potentially associated factors. Pearson's correlation coefficient analysis was used to investigate the correlations among continuous variables under all‐patient dataset. A P‐value <.05 would be recognized as significance of each test. All analyses were performed using IBM SPSS version 20 (SPSS Statistics V20, IBM Corporation, Somers, New York, USA).
2.5. Estimation of sample size
The sample size was estimated by software G*Power version 3.1 (Heinrich‐Heine‐Universität Düsseldorf, Düsseldorf, German) under a 3‐group one‐way ANOVA test. The effect size was set at a medium level of 0.25, type I error (alpha) of 0.05 and power of 0.80, and the number of independent groups was 3 (nocturnal systolic, nocturnal diastolic, and systolic/diastolic groups). The estimated total sample size was 159, which indicated the minimum sample size required for each group was 53.
3. RESULTS
3.1. Patient's clinical characteristics and blood pressure parameters
A total of 721 untreated MH patients (309 females and 412 males, mean age = 56.59 ± 15.20 years) were included in this study. The mean clinic SBP was 122.80 ± 10.92 mm Hg, and the mean clinic DBP was 78.39 ± 8.38 mm Hg. The ABPM was as follows: mean daytime SBP = 128.57 ± 11.89 mm Hg, mean nocturnal DBP = 78.11 ± 7.56 mm Hg, mean nocturnal SBP = 126.36 ± 13.79 mm Hg, and mean nocturnal DBP = 76.16 ± 7.88 mm Hg. The 721 untreated MH patients were divided into the nocturnal systolic MH (n = 77, 10.68%), nocturnal diastolic MH (n = 232, 32.18%), and nocturnal systolic/diastolic MH (n = 412, 57.14%) groups. Patient's demographic and clinical characteristics are summarized in Table 1. Several variables were significantly different among the three groups (all P < .05), including sex, age, office SBP and DBP, and all the 24‐hour, daytime, nocturnal, minimum, and maximum SBP, DBP, and heart rate. The nocturnal systolic group had the highest ratio of males (77.92%), mean age (64.01 ± 17.75), and office SBP (126.21 ± 9.38), and the lowest office DBP (73.49 ± 7.92). In the 24‐hour, daytime, nocturnal, minimum and maximum record, and nocturnal systolic and nocturnal BP, the systolic‐diastolic groups had higher SBP than the nocturnal diastolic group. The nocturnal systolic group also had the lowest 24‐hour, daytime, and nocturnal DBP and heart rate among the three groups.
Table 1.
Patient's demographic blood pressure profiles
| Parameters | Nocturnal systolic (n = 77) | Nocturnal diastolic (n = 232) | Nocturnal systolic‐diastolic (n = 412) | Total | P |
|---|---|---|---|---|---|
| Sex | |||||
| Female | 17 (22.08) | 103 (44.40) | 189 (45.87) | 309 (42.86) | <.001 |
| Male | 60 (77.92) | 129 (55.60) | 223 (54.13) | 412 (57.14) | |
| Age, year | 64.01 ± 17.75 | 51.03 ± 12.02 | 58.33 ± 15.30 | 56.59 ± 15.20 | <.001 |
| Clinic SBP, mm Hg | 126.21 ± 9.38 | 121.81 ± 10.17 | 122.72 ± 11.49 | 122.80 ± 10.92 | .009 |
| Clinic DBP, mm Hg | 73.49 ± 7.92 | 81.34 ± 6.48 | 77.64 ± 8.82 | 78.39 ± 8.38 | <.001 |
| 24‐h | |||||
| SBP, mm Hg | 128.69 ± 8.28 | 118.49 ± 6.09 | 133.07 ± 11.13 | 127.91 ± 11.56 | <.001 |
| DBP, mm Hg | 68.19 ± 4.83 | 76.64 ± 4.22 | 79.80 ± 7.20 | 77.55 ± 7.09 | <.001 |
| Heart rate, beats/min | 67.21 ± 9.38 | 74.27 ± 8.49 | 73.34 ± 8.89 | 72.98 ± 9.04 | <.001 |
| Daytime | |||||
| SBP, mm Hg | 129.34 ± 9.95 | 120.69 ± 7.78 | 132.87 ± 11.91 | 128.57 ± 11.89 | <.001 |
| DBP, mm Hg | 69.38 ± 5.93 | 77.88 ± 5.46 | 79.87 ± 7.71 | 78.11 ± 7.56 | <.001 |
| Heart rate, beats/min | 68.98 ± 9.91 | 76.58 ± 8.83 | 75.14 ± 9.12 | 74.95 ± 9.36 | <.001 |
| Nocturnal | |||||
| SBP, mm Hg | 127.18 ± 7.52 | 112.81 ± 4.50 | 133.83 ± 12.32 | 126.36 ± 13.79 | <.001 |
| DBP, mm Hg | 64.99 ± 3.65 | 73.42 ± 2.89 | 79.78 ± 7.80 | 76.16 ± 7.88 | <.001 |
| Heart rate, beats/min | 59.46 ± 8.63 | 64.11 ± 8.79 | 65.24 ± 9.88 | 64.25 ± 9.56 | <.001 |
| Minimum record | |||||
| SBP, mm Hg | 107.58 ± 12.52 | 96.48 ± 9.40 | 115.22 ± 16.45 | 108.34 ± 16.48 | <.001 |
| DBP, mm Hg | 52.38 ± 6.22 | 60.09 ± 6.76 | 66.71 ± 10.50 | 63.04 ± 10.21 | <.001 |
| Heart rate, beats/min | 53.44 ± 8.27 | 57.88 ± 8.52 | 59.19 ± 9.51 | 58.15 ± 9.23 | <.001 |
| Maximum record | |||||
| SBP, mm Hg | 147.78 ± 16.26 | 127.19 ± 13.42 | 152.40 ± 20.81 | 143.76 ± 21.58 | <.001 |
| DBP, mm Hg | 77.38 ± 10.88 | 85.04 ± 13.45 | 93.10 ± 14.44 | 88.81 ± 14.79 | <.001 |
| Heart rate, beats/min | 68.60 ± 14.90 | 73.20 ± 12.60 | 73.80 ± 14.11 | 73.05 ± 13.80 | .010 |
Abbreviations: DBP, diastolic blood pressure; SBP, systolic blood pressure.
3.2. Echocardiographic measurements
The echocardiographic measurements are shown in Table 2. In one‐way ANOVA, the LA dimension, IVS thickness, and LV mass were significantly different among the three groups (all P < .05). In the post hoc comparisons, the nocturnal systolic‐diastolic group had significantly higher values of LA dimension and IVS thickness than the nocturnal diastolic group (both P < .05, Tukey HSD test), while in the post hoc comparisons, the nocturnal systolic group had significantly higher values of IVS thickness than nocturnal diastolic group (P < .05, Tukey HSD test).
Table 2.
Echocardiographic parameters of left ventricular structure among groups
| Parameters | Nocturnal systolic (n = 77) | Nocturnal diastolic (n = 232) | Nocturnal systolic‐diastolic (n = 412) | Total | P |
|---|---|---|---|---|---|
| Mean ± SD | |||||
| LA dimension, mm | 34.58 ± 6.37 | 33.55 ± 4.19 | 34.88 ± 4.67* | 34.42 ± 4.77 | .003 |
| IVS thickness, mm | 10.75 ± 1.64* | 10.16 ± 1.61 | 10.76 ± 1.90* | 10.56 ± 1.80 | <.001 |
| PW thickness, mm | 9.48 ± 1.63 | 9.12 ± 1.38 | 9.39 ± 1.55 | 9.31 ± 1.51 | .053 |
| LVEDD, mm | 46.60 ± 5.31 | 47.28 ± 4.40 | 47.52 ± 5.12 | 47.35 ± 4.92 | .308 |
| LV mass, g | 196.88 ± 66.24 | 185.95 ± 50.55 | 201.01 ± 66.15 | 195.72 ± 61.87 | .012 |
| Estimated mean (95% CI) after adjusting patient's age and sex | |||||
| LA dimension, mm | 34.67 (33.43‐35.91) | 34.04 (33.44‐34.65) | 34.82 (34.37‐35.26) | – | .134 |
| IVS thickness, mm | 10.72 (10.24‐11.19) | 10.32 (10.09‐10.55) | 10.74 (10.57‐10.91) | – | .016 |
| PW thickness, mm | 9.52 (9.12‐9.93) | 9.18 (8.98‐9.38) | 9.40 (9.26‐9.54) | – | .148 |
| LVEDD, mm | 47.62 (46.31‐48.93) | 47.19 (46.55‐47.83) | 47.67 (47.20‐48.14) | – | .491 |
| LV mass, g | 204.04 (187.74‐220.34) | 187.92 (179.96‐195.88) | 202.24 (196.41‐208.07) | – | .015 |
Abbreviations: IVS, interventricular septum; LA, left atrium; LV, left ventricular; LVEDD, linear left ventricular end‐diastolic dimension.
P < .05 compared to the nocturnal diastolic group in the Tukey HSD test.
The estimated mean and 95% CI after adjusting the patient's age and sex are also reported in Table 2. The estimated method was MANCOVA, which controlled the significant correlations among echocardiographic measurements (coefficient r range from 0.133 to 0.702, all P < .01). After adjusting for the patient's age and sex, the values of IVS thickness and LV mass were still significantly different among the three groups (both P < .05).
3.3. Univariate and multivariate linear regression
Because of the significant differences among the groups, three echocardiographic parameters, linear regression analysis was performed to analyze the independent factors associated with LA dimension, IVS thickness, and LV mass.
As shown in Table 3, sex was significantly associated with LA dimension, IVS thickness, and LV mass. Male patients were more likely to have smaller LA dimension, IVS thickness, and LV mass than female patients (B coefficients were all negative, all P < .001). Meanwhile, older age was associated with lager LA dimension and larger IVS thickness (B coefficients were all positive, all P < .001).
Table 3.
Univariate and multivariate linear regression analyses of independent factors associated with LA and IVS
| LA dimension | IVS thickness | LV mass | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Univariate | Multivariateb | Univariate | Multivariateb | Univariate | Multivariateb | |||||||
| Ba (95% CI) | P | B (95% CI) | P | B (95% CI) | P | B (95% CI) | P | B (95% CI) | P | B (95% CI) | P | |
| Sex | ||||||||||||
| Female | Reference | – | Reference | – | Reference | – | Reference | – | Reference | – | Reference | – |
| Male | −1.29 (−1.99‐−0.59) | <.001 | −1.60 (−2.28‐−0.92) | <.001 | −0.52 (−0.78‐−0.25) | <.001 | −0.62 (−0.88‐−0.36) | <.001 | −29.73 (−38.62‐−20.85) | <.001 | −30.56 (−39.51‐−21.62) | <.001 |
| Age, year | 0.08 (0.05‐0.10) | <.001 | 0.08 (0.06‐0.10) | <.001 | 0.02 (0.02‐0.03) | <.001 | 0.03 (0.02‐0.03) | <.001 | 0.10 (−0.20‐0.40) | .520 | 0.22 (−0.07‐0.51) | .139 |
| Clinic SBP, mm Hg | 0.001 (−0.03‐0.03) | .966 | 0.01 (−0.02‐0.04) | .660 | −0.005 (−0.02‐0.01) | .420 | −0.003 (−0.01‐0.01) | .643 | −0.04 (−0.46‐0.37) | .845 | 0.04 (−0.37‐0.44) | .858 |
| Clinic DBP, mm Hg | −0.07 (−0.11‐−0.03) | .001 | −0.03 (−0.07‐0.01) | .131 | −0.03 (−0.05‐−0.02) | <.001 | −0.02 (−0.04‐−0.01) | .002 | −0.45 (−0.99‐0.09) | .105 | −0.48 (−1.03‐0.07) | .089 |
| 24‐h | ||||||||||||
| SBP, mm Hg | 0.06 (0.03‐0.09) | <.001 | 0.04 (0.01‐0.07) | .008 | 0.04 (0.03‐0.05) | <.001 | 0.03 (0.02‐0.05) | <.001 | 0.94 (0.56‐1.33) | <.001 | 0.93 (0.55‐1.31) | <.001 |
| DBP, mm Hg | −0.01 (−0.06‐0.04) | .609 | 0.02 (−0.03‐0.07) | .482 | 0.02 (0.00‐0.04) | .021 | 0.03 (0.01‐0.05) | <.001 | 0.76 (0.12‐1.40) | .020 | 0.57 (−0.08‐1.22) | .086 |
| Heart rate, beats/min | −0.09 (−0.13‐−0.06) | <.001 | −0.07 (−0.11‐−0.04) | <.001 | 0.00 (−0.02‐0.01) | .803 | 0.01 (−0.01‐0.02) | .433 | −0.59 (−1.09‐−0.09) | .022 | −0.67 (−1.17‐−0.17) | .008 |
| Daytime | ||||||||||||
| SBP, mm Hg | 0.05 (0.02‐0.08) | .001 | 0.03 (0.01‐0.06) | .019 | 0.04 (0.03‐0.05) | <.001 | 0.03 (0.02‐0.04) | <.001 | 0.85 (0.47‐1.23) | <.001 | 0.82 (0.45‐1.19) | <.001 |
| DBP, mm Hg | −0.03 (−0.07‐0.02) | .243 | 0.01 (−0.04‐0.06) | .703 | 0.01 (−0.01‐0.03) | .177 | 0.02 (0.01‐0.04) | .006 | 0.50 (−0.10‐1.09) | .104 | 0.36 (−0.26‐0.98) | .252 |
| Heart rate, beats/min | −0.10 (−0.14‐−0.06) | <.001 | −0.08 (−0.11‐−0.04) | <.001 | −0.01 (−0.02‐0.01) | .309 | 0.001 (−0.01‐0.02) | .846 | −0.66 (−1.14‐−0.18) | .007 | −0.75 (−1.23‐−0.26) | .003 |
| Nocturnal | ||||||||||||
| SBP, mm Hg | 0.06 (0.03‐0.08) | <.001 | 0.04 (0.01‐0.06) | .006 | 0.03 (0.02‐0.04) | <.001 | 0.02 (0.01‐0.03) | <.001 | 0.74 (0.41‐1.06) | <.001 | 0.76 (0.43‐1.09) | <.001 |
| DBP, mm Hg | 0.03 (−0.01‐0.08) | .148 | 0.03 (−0.01‐0.08) | .131 | 0.03 (0.02‐0.05) | <.001 | 0.03 (0.02‐0.05) | <.001 | 0.99 (0.42‐1.56) | <.001 | 0.74 (0.18‐1.31) | .010 |
| Heart rate, beats/min | −0.04 (−0.08‐0.00) | .027 | −0.04 (−0.08‐−0.01) | .017 | 0.02 (0.01‐0.04) | <.001 | 0.02 (0.01‐0.04) | <.001 | −0.01 (−0.48‐0.47) | .984 | −0.11 (−0.58‐0.35) | .627 |
Abbreviations: DBP, diastolic blood pressure; IVS, interventricular septum; LA, left atrium; LV, left ventricular; SBP, systolic blood pressure.
B is the estimated regression coefficient in linear regression models.
All multivariate (or multiple) regression models were adjusted with patient's sex and age.
Higher office DBP was associated with IVS thickness (both B were negative, P < .01). The 24‐hour and daytime heart rate were both negatively associated with LA dimension and LV mass (all B were negative and P < .05), while the nocturnal heart rate was negatively associated with LA dimension but positively associated with IVS thickness (all P < .05). The 24‐hour DBP was positively associated with IVS thickness, while nocturnal DBP was positively associated with IVS thickness and LV mass (all B were positive and P < .05). Notably, the 24‐hour, daytime, and nocturnal SBPs were all positively associated with LA dimension, IVS thickness, and LV mass (all B were positive and P < .050), indicating that daytime SBP and nocturnal SBP were the independent factors associated with the echocardiographic parameters.
3.4. Correlation coefficient analysis
Pearson's correlation coefficient analysis was used to further investigate the magnitudes of correlations between the BP measurements and LA dimension/IVS thickness. As shown in Table 4, 24‐hour, daytime, and nocturnal SBPs were all positively correlated with LA dimension, IVS thickness, and LV mass (all P < .01).
Table 4.
Pearson's correlation coefficients
| Parameters | LA dimension, mm | IVS thickness, mm | LV mass, mm |
|---|---|---|---|
| LA dimension, mm | – | 0.322** | 0.470** |
| IVS thickness, mm | 0.322** | – | 0.702** |
| LV mass, g | 0.470** | 0.702** | – |
| Clinic SBP, mm Hg | 0.002 | −0.030 | −0.007 |
| Clinic DBP, mm Hg | −0.120** | −0.160** | −0.060 |
| 24‐h | |||
| SBP, mm Hg | 0.146** | 0.254** | 0.176** |
| DBP, mm Hg | −0.019 | 0.086* | 0.087* |
| Heart rate, beats/min | −0.178** | −0.009 | −0.086* |
| Daytime | |||
| SBP, mm Hg | 0.121** | 0.243** | 0.163** |
| DBP, mm Hg | −0.043 | 0.050 | 0.061 |
| Heart rate, beats/min | −0.193** | −0.038 | −0.100** |
| Nocturnal | |||
| SBP, mm Hg | 0.168** | 0.222** | 0.164** |
| DBP, mm Hg | 0.054 | 0.146** | 0.126** |
| Heart rate, beats/min | −0.083* | 0.126** | −0.001 |
Abbreviations: DBP, diastolic blood pressure; IVS, interventricular septum; LA, left atrium; LV, left ventricular; SBP, systolic blood pressure.
P < .05.
P < .01.
4. DISCUSSION
In this study, we investigated whether different patterns of nocturnal MH had an impact on the echocardiographic parameters assessed by echocardiography in the untreated nocturnal MH. The nocturnal systolic group had the highest ratio of males, mean age, and office SBP, and the lowest office, 24‐hour, daytime, and nocturnal DBP and heart rate among the three groups. The nocturnal diastolic group had the lowest IVS thickness, LA dimension, and LV mass among the three groups. Multivariate linear regression analysis revealed that 24‐hour, daytime, and nocturnal SBPs were all positively associated with LA dimension, IVS thickness, and LV mass. Pearson's correlation analysis showed that nocturnal SBP was positively correlated with LA dimension, IVS thickness, and LV mass. Taken together, these results suggest that different patterns of nocturnal MH have different echocardiographic outcomes, and nocturnal SBP is an independent factor associated with the echocardiographic measurement outcome. To the best of our knowledge, this is the first study reporting the echocardiographic characteristics among the different MH patterns based on the nocturnal systolic and diastolic BP.
Among the 721 untreated MH patients in this study, only 77 cases (10.68%) were the nocturnal systolic MH. It has been shown that nocturnal systolic hypertension more commonly occurs in the elderly.28, 29 However, the mean age of the cohort was 56.59 ± 15.20 years, which may contribute to the relatively lower proportion of nocturnal systolic MH in the cohort. Nocturnal hypertension has been reported to be associated with subclinical cardiovascular diseases in previous studies. Hoshide et al30 have reported that patients with nocturnal MH have larger relative wall thickness and the intima‐media thickness than the normotensive individuals. Wijkman et al16 have shown that diabetic patients with nocturnal MH have a higher aortic pulse wave velocity (PWV) as compared to clinical or nocturnal normotensive individuals. Wang et al31 have reported that nocturnal systolic hypertension is an independent risk factor for target organ damage in patients with chronic kidney disease. O’Flynn et al32 demonstrate there is an association between nocturnal systolic hypertension and subclinical LV systolic dysfunction (β coefficient 0.85 for every 10 mm Hg increase, 95% CI: 0.3‐1.4). They also found nocturnal systolic BP was markedly associated with LV mass as compared to daytime systolic BP.32 Similar to their findings, our study demonstrated that IVS thickness was significantly larger in the nocturnal systolic and systolic/diastolic groups than in the nocturnal diastolic group, while LA dimension was significantly larger in the systolic/diastolic group than in the nocturnal diastolic group. Nocturnal systolic BP was the independent factor associated with LA dimension and IVS thickness in the multivariate regression analysis adjusting for sex and age. These findings indicated that nocturnal systolic BP may contribute more than nocturnal diastolic BP toward cardiac damage in MH population, and nocturnal systolic hypertension may be a potential therapeutic target for the MH patients. Further prospective studies are needed to evaluate the cardioprotective effect of treating nocturnal systolic hypertension in MH population.
In this study, there were significant differences in the LA dimension, IVS thickness, and LV mass among the three groups. The nocturnal systolic group had higher LA dimension, IVS thickness, and LV mass than the nocturnal diastolic group. It has been shown that patients with enlarged LA dimension have a significantly higher incidence of sudden death and potentially lethal arrhythmic events as compared to those with normal LA dimension.33 In addition, among patients without atrial fibrillation, enlarged LA dimension is an independent risk factor for sudden death.33 On the other hand, increased IVS thickness has been reported in amyloidosis patients with heart failure.34 It has been reported that increased IVS thickness is a risk factor for sudden cardiac arrests in patients with left ventricular ejection fraction (LVEF) >35%.35 As for LV mass, the Jackson Heart Study demonstrates that patients with nocturnal hypertension had greater LV mass than those with normal tension in African Americans.21 Accumulating evidence suggests that increased LV mass is an independent risk factor for the cardiovascular events.36, 37, 38 These findings suggest that increased LA dimension, IVS thickness, and LV mass are associated with cardiovascular risk. In this study, nocturnal SBP was identified as an influence factor associated with LA dimension, IVS thickness, and LV mass. Furthermore, nocturnal SBP was positively correlated with LA dimension, IVS thickness, and LV mass. Thus, our results indicated that nocturnal SBP was a risk factor for cardiac damage in MH population.
Sex differences in cardiac structure have been reported in hypertensive patients. It has been reported that the systolic hypertensive women had a higher LV mass and relative wall thickness.39 In a study by Vriz et al including 499 hypertensive patients with a mean age of 33 ± 9 years, LV wall thickness and LV mass were higher in female than in male patients.40 A large prospective trial with 12 329 hypertension patients showed that left ventricular hypertrophy was more prevalent in women than men (43.4% vs. 32.1%, P < .001).41 Consistent with these observations, our multivariate linear regression analysis showed that female patients were more likely to have larger LA dimension, IVS thickness, and LV mass than male patients. It has been suggested that these sex differences may be attributed to sex hormones. Postmenopausal women had evidence of early concentric left ventricular remodeling, manifested by a greater relative wall thickness than that observed in premenopausal women.42 Of the female patients of this study (N = 309, mean age = 54.43 ± 15.36), most were menopausal patients, increasing the risk of target organ damage and cardiovascular events due to the loss of estrogen protection.
The pathogenic mechanism of MH remains not fully understood. Several mechanisms have been proposed, such as overactivity of the adrenergic nervous system.12 Grassi et al12 have demonstrated that the sympathetic nerve activity in the MH patients is stable within the normal limits during in‐office BP measurement, whereas there are increased bursts of sympathetic nerve activity during the out‐of‐office BP measurement, suggesting that the mechanisms by which nocturnal hypertension contributed to MH might be secondary to the increased sympathetic nerve activity. In MH patients, overactivity of the sympathetic system is associated with structural LA remodeling that further induces LA functional and mechanical changes. Tadic et al43 have reported that MH is associated with impaired LA phasic function and stiffness, and 24‐hour systolic BP increment is closely related to LA remodeling. In this study, the nocturnal systolic group had higher LA dimension than the nocturnal diastolic group. However, after adjustment for age and sex, the difference in LA dimension among the three groups was not significant. We found that the IVS thickness but not PW thickness was smaller in the nocturnal diastolic group than the other two groups. One possible explanation for this phenomenon might be that IVS was more sensitive to the overactivity of the sympathetic system than PW. However, further study is necessary to elucidate the underlying mechanism.
There are still some limitations in the present study. First, this study is limited to the retrospective nature so that we cannot collect additional data that may influence the results. In addition, the echocardiographic measurements were evaluated at a single time point, and no follow‐up was performed. Moreover, we did not include sustained normotension, white‐coat hypertension, and sustained hypertension populations in this study. In the future, a well‐designed prospective study is necessary to validate the findings of this study. All these limitations should be addressed in the following study.
In summary, our findings suggested that different patterns of nocturnal MH have different echocardiographic outcomes, and nocturnal SBP is associated with the LA dimension, IVS thickness, and LV mass in the echocardiographic measurement, indicating that nocturnal systolic BP is a risk factor for cardiac damage in untreated MH population. Our finding helps to better understand the effect of nocturnal hypertension on the cardiac damage in the untreated MH population.
CONFLICT OF INTEREST
The authors declare that there are no conflicts of interest.
AUTHOR CONTRIBUTIONS
Jianhao Li collected data, participated in data analysis, participated in the design of the study, and drafted the manuscript; Yalin Cao carried out the statistical analyses, participated in the design of the study, and drafted the manuscript; Chen Liu collected data and critically revised the manuscript; Jiayong Li collected data; Fengjuan Yao collected data; Yugang Dong coordinated the study and helped draft the manuscript; Huiling Huang coordinated the study and helped draft the manuscript. All authors gave final approval for publication and agree to be held accountable for the work performed therein.
Li J, Cao Y, Liu C, et al. Nocturnal systolic hypertension is a risk factor for cardiac damage in the untreated masked hypertensive patients. J Clin Hypertens. 2019;21:1666–1674. 10.1111/jch.13711
Li and Cao are co‐first authors, and they contributed equally to this paper.
Funding information
This work was supported by National Key R&D Program (2017YFC0909301), Natural Science Foundation of China (No. 81500279, No. 81370338, No.81470511, No.81570354, and No.81560056), Guangdong Natural Science Foundation (No. S2013020012578, No. 2014A030313083, and No. 2015A030313111), Science and Technology Project of Guangdong Province and Guangzhou City (No. 2014A021212438 and No. 201610010125), Science and Technology Project of Guizhou Province (No. [2017]1103), Science and Technology Project of Health Planning Commission of Guizhou Province (No. gzwjkj2018‐1‐005), and Program for Training Outstanding Young Scientific and Technological Talents of Guizhou Province (No. Qian Kehe Platform Talents [2019]5662).
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