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ORIGINAL ARTICLE
Left ventricular hypertrophy in controlled hypertension: Is blood pressure variability blamed?
Alaa El-Din R. Abdel-Rheim, Amr S. Amin *, Hazem M. Ali, Hassan M. Hassan
Cardiology Department, Al Minia University, Egypt
Received 29 December 2014; accepted 14 February 2015
KEYWORDS
Ambulatory blood pressure monitoring; Echocardiography; Hypertension;
Left ventricular hypertrophy; Blood pressure variability
Abstract Background: Blood pressure (BP) has been shown to exhibit important variations not only in the short term but also over more prolonged periods of time.
Aim: To evaluate the impact of different ambulatory BP variability indices on left ventricular hypertrophy (LVH) in controlled hypertensive patients (Pts).
Patients and methods: Ninety controlled hypertensive Pts (office and ambulatory BP control criteria) with mean age 55.9 ± 8.5 years were enrolled. Pts were classified into two groups: Non-LVH group including 75 Pts with normal LV mass index and LVH group including 15 patients with LV mass index >134 g/m2 in men and >110 g/m2 in women. Mean BP and BP load values were obtained for the full 24 h and day-time and night-time periods. Similarly Standard Deviation (SD) and Average Reading Variability (ARV) were calculated in all pts. Results: Regarding office BP, Dipping status and average ambulatory BP, there was no statistically significant difference between both groups. Meanwhile, SD of BP readings and ARV showed a significant difference. After step-wise regression, ARV of systolic BP 24 h was the most powerful variability index that was associated with LVH (R2 = 0.944). The ROC curve analysis showed that the discriminative power was best at more than 14.23 mmHg with sensitivity and specificity 100% and 96% respectively for prediction of LVH.
Conclusion: The adverse cardiovascular consequences of hypertension not only depend on mean BP values but may also depend on BPV, which independently adds to CV risk over elevated mean BP levels.
© 2015 Production and hosting by Elsevier B.V. on behalf of Egyptian Society of Cardiology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
1. Introduction
Hypertension has a serious harmful effect on the physiological and biochemical functions of heart that end with the appearance of cardio-vascular diseases.1 Blood pressure is characterized by large spontaneous variations from time to time in a
* Corresponding author. Peer review under responsibility of Egyptian Society of Cardiology.
hypertensive patient during the day and between days, months and seasons so called blood pressure variability (BPV).2 It is an independent predictor of progression of subclinical organ damage (i.e., increased left ventricular mass index or carotid intima-media thickness)3 and cardiovascular (CV) mortality.4 Accordingly, the purpose of the present work was to evaluate the impact of different ambulatory BP variability indices on left ventricular hypertrophy (LVH) in controlled hypertensive patients (Pts).
http://dx.doi.org/10.1016/j.ehj.2015.02.003
1110-2608 © 2015 Production and hosting by Elsevier B.V. on behalf of Egyptian Society of Cardiology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Alaa El-Din R. Abdel-Rheim et al.
2. Patients and methods
This prospective study included 90 hypertensive pts who presented to Minia University hospital outpatient cardiology clinic, during the period from May 2013 to May 2014 for regular follow up of blood pressure.
All included pts had a history of hypertension for at least 3 years, and were compliant on antihypertensive treatment for at least the last year and their office blood pressure (BP) and ambulatory blood pressure monitoring (ABPM) represented controlled hypertension (i.e. <140/90 mmHg office BP readings and < 135/85 mmHg average 24 h ABPM readings respectively). Smoking, Diabetes Mellitus, renal impairment, Impaired LV systolic function (LVEF 45%), valvular heart disease, coronary artery disease, atrial fibrillation and obesity were the exclusion criteria. The studied pts were subjected to the following:
1. Full detailed clinical evaluation including blood pressure measurements at morning hours in sitting position after at least 5 min of rest. An average value of 3 measurements was obtained. BMI (kg/m2) and BSA (m2) were calculated and Local cardiac examination was performed.
2. Laboratory investigations: including fasting blood sugar and Serum creatinine.
3. 24-h ambulatory BP monitoring: Pts were fitted with an ABPM device (Contec model ABPM 50, China).
The device was programmed to obtain BP readings at 15-min interval during the day (07:00-23:00 h) and at 30-min intervals during the night (23:00-07:00 h). Mean systolic BP (SBP), Diastolic BP (DBP), Mean arterial pressure (MAP) and BP load values were obtained for the full 24 h, day-time and night-time periods.
I Calculation of blood pressure variability indices:
• Dipping status: Normal dippers are defined as those with average night BP decreasing 10-20% of the average daytime BP. Non-dippers are those with average night BP decreasing 0-10% of the average daytime BP. Extreme-dippers are those with average night BP decreasing >20% of the average daytime BP. Meanwhile, reversed dippers are those with average night BP higher than the average daytime BP.
• Standard Deviation (SD) and Average Reading Variability (ARV) of 24 h BP, daytime BP and nighttime BP (systolic & diastolic) were calculated
i. Standard Deviation (SD)3:
(N) Number of valid BP measurements - (X) denotes each single ABPM reading (X') average of ABPM readings -(£]) denotes that we sum across the values. ii. Average Reading Variability (ARV)3:
ARV = ——I BP k + 1 - BP k\
(N) Number of valid blood pressure (BP) measurements -(K) ranges from 1 to N — 1 - (£]) denotes that we sum across the values. I Trans-thoracic echocardiography.
• Echocardiography examination was performed by using General Electric Vivid 3 ultrasound with simultaneous ECG tracing. The measurements represent a mean of 3 consecutive cardiac cycles.
• Left ventricular mass (LV Mass) was calculated by Devereux's formula.5 as follows:
• LV mass = 0.8 [1.04{(IVSd + LVEDd + PWTd)3 — LVEDd3}] + 0.6 g.
• BSA is calculated by Mosteller square root method6
• BSA = Height (m) x Weight (kg)/36 (m2).
• LV mass Index (LVMI) = LVmass
■ (g/m2).
Standard Deviation (SD) =
E(X - X ) n-1
According to this formula, LVMI is increased if >134 g/m2 in men and >110 g/m2 in women.5
3. Statistical methodology
The Statistical Package of SPSS version 16 for windows was used for data entry and analysis. Standard descriptive statistics were done and all values were given as mean ± SD.
Correlations were done by Pearson correlation coefficient test. Correlation was considered significant if its P value was <0.05.
Multivariate stepwise regression analyses were done for all ABPM indices that showed significant correlation with LVMI. Roc curve analysis was done for the most powerful ABPM index detected by multivariate stepwise regression analysis.
4. Results
Based on echocardiographic measurement of LV mass index (g/m2), patients were classified into two groups:
A - Non-LVH group. This group included 75 patients. B - LVH group (where LV mass index is >134 g/m2 in men and >110 g/m2 in women). This group included 15 patients.
There was no statistically significant difference between Non-LVH group and LVH group as regard age, sex and duration of hypertension. (Table 1).
Table 1 Comparing Non-LVH group and LVH group regarding age, sex and hypertension duration.
Non-LVH (n = 75) LVH (n = 15) P value
Age (y) mean ± SD 55.75 ± 8.76 57.07 ± 7.02 0.585
Sex prevalence (male/female) 32/43 3/12 0.100
Duration of hypertension diagnosis (y) mean ± SD 4.75 ± 2.99 5. 24 ± 3.61 <0.07
LVH = left ventricular hypertrophy.
Left ventricular hypertrophy in controlled hypertension 3
Table 2 Comparison between Non-LVH group and LVH group regarding office BP, Dipping status, (24 h, daytime and nighttime)
average BP and blood pressure load.
Non-LVH (n = 75) Mean ± SD LVH (n = 15) Mean ± SD P value
Office systolic BP (mmHg) 134.33 ± 8.75 132.67 ± 8.61 0.511
Office diastolic BP (mmHg) 77.07 ± 8.1 80.67 ± 7.99 0.119
Dipping status: n (%)
Dipper 17 (22.7%) 3 (20%) 0.898
Non dipper 42 (56%) 8 (53.3%)
Reversed dipper 16 (21.3%) 4 (26.7%)
Average systolic BP 24 h (mmHg) 122.27 ± 9.06 124.73 ± 9.22 0.346
Average diastolic BP 24 h (mmHg) 67.51 ± 9.35 71.53 ± 8.43 0.126
Average systolic BP daytime (mmHg) 121.01 ± 9.62 126.47 ± 10.47 0.051
Average diastolic BP daytime (mmHg) 69.27 ± 9.65 72.87 ± 9.09 0.186
Average systolic BP nighttime (mmHg) 114.97 ± 10.34 119.67 ± 11.47 0.119
Average diastolic BP nighttime (mmHg) 63.93 ± 8.98 67 ± 8.75 0.229
Systolic BP load 24 h (%) 19.53 ± 16.47 30.63 ± 17.73 0.023
Diastolic BP load 24 h (%) 8.73 ± 10.23 17.91 ± 12.65 0.004
Systolic BP load daytime (%) 12.18 ± 14.1 26.23 ± 17.52 0.003
Diastolic BP load daytime (%) 7.09 ± 10.28 17.03 ± 14.12 0.001
Systolic BP load nighttime (%) 34.95 ± 28.27 44.07 ± 26.72 0.179
Diastolic BP load nighttime (%) 11.74 ± 14.71 25.29 ± 21.97 0.013
LVH = left ventricular hypertrophy and BP = blood pressure.
Table 3 Comparison between Non-LVH group and LVH group regarding standard deviation of BP readings and Average Reading Variability in 24 h, daytime and nighttime recordings.
Non-LVH (n = 75) Mean ± SD LVH (n = 15) Mean ± SD P value
SD of systolic BP 24 h (mmHg) 13.79 ± 2.53 19.05 ± 3.2 <0.001
SD of diastolic BP 24 h (mmHg) 11.54 ± 2.81 16.57 ± 4.25 <0.001
SD of systolic BP daytime (mmHg) 13.37 ± 2.91 18.83 ± 3.49 <0.001
SD of diastolic BP daytime (mmHg) 11.31 ± 3.1 16.76 ± 4.68 <0.001
SD of systolic BP nighttime (mmHg) 11.41 ± 3.07 15.29 ± 2.77 <0.001
SD of diastolic BP nighttime (mmHg) 9.12 ± 2.36 12.11 ± 3 <0.001
ARV of systolic BP 24 h (mmHg) 10.88 ± 2.17 16.76 ± 2.17 <0.001
ARV of diastolic BP 24 h (mmHg) 9.03 ± 2.07 14.6 ± 3.89 <0.001
ARV of systolic BP daytime (mmHg) 11.04 ± 2.45 17.38 ± 2.77 <0.001
ARV of diastolic BP daytime (mmHg) 9.29 ± 2.39 15.35 ± 4.56 <0.001
ARV of systolic BP nighttime (mmHg) 10.29 ± 3.19 14.53 ± 2.45 <0.001
ARV of diastolic BP nighttime (mmHg) 8.08 ± 2.53 11.9 ± 3.22 <0.001
LVH = left ventricular hypertrophy, BP = blood pressure, AVR = Average Reading Variability and SD = Standard deviation.
No statistically significant difference was present between both groups as regard office BP, Dipping status and (24 h, daytime and nighttime) average ambulatory BP readings. Meanwhile, standard deviation and Average Reading Variability of (24 h, daytime and nighttime) BP showed statistically significant difference between both groups. Also 24 h, daytime, diastolic nighttime BP load showed the same behavior (Tables 2 and 3).
There was a weak correlation between LVMI and Blood Pressure Load, fair to moderate correlation between LVMI and SD of BP readings and moderate to strong correlation between LVMI and ARV (Table 4). After step-wise regression, ARV of systolic BP 24 h was the most powerful ABPM parameter that could predict LVH (R2 = 0.944). The discriminative power of ARV of systolic BP 24 h was best at more than 14.23 mmHg with sensitivity and specificity 100% and 96% respectively (Fig. 1).
5. Discussion
BP variations in the very short term (i.e., beat to beat) and in the short term (i.e., within 24 h) mainly reflect the influences of central neural factors either in response to behavioral challenges or as a result of rhythmic influences originating in the central nervous system or the influences of reflex autonomic modulation.7-10 An increased central sympathetic drive and reduced sensitivity of arterial and cardiopulmonary reflexes may both lead to an increased BPV.7-10 In this context, changes in elastic properties of large arteries (i.e., an increased arterial stiffness)11 and the effects of humoral (insulin, angiotensin II, bradykinin, endothelin-1, and nitric oxide) and rheological (i.e., blood viscosity) factors12 may play a role. In addition, BP fluctuations also occur in response to the mechanical forces generated by ventilation.
Table 4 Correlations between ABPM parameters (With significant statistical difference) and LV mass index.
LV Mass index with R P
Systolic BP load 24 h 0.136 0.023
Diastolic BP load 24 h 0.126 0.004
Systolic BP load daytime 0.306 0.003
Diastolic BP load daytime 0.190 0.001
Diastolic BP load nighttime 0.114 0.013
SD of systolic BP 24 h 0.795 <0.001
SD of diastolic BP 24 h 0.635 <0.001
SD of systolic BP daytime 0.782 <0.001
SD of diastolic BP daytime 0.631 <0.001
SD of systolic BP nighttime 0.498 <0.001
SD of diastolic BP nighttime 0.372 <0.001
ARV of systolic BP 24 h 0.972 <0.001
ARV of diastolic BP 24 h 0.729 <0.001
ARV of systolic BP daytime 0.936 <0.001
ARV of diastolic BP daytime 0.705 <0.001
ARV of systolic BP nighttime 0.636 <0.001
ARV of diastolic BP nighttime 0.514 <0.001
SD = Standard deviation, BP = blood pressure and AVR = Average Reading Variability.
Figure 1 Roc curve analysis of ARV of systolic BP 24 h versus LVH.
In the present study, we demonstrated the relationship between ABPM variability indices [Standard Deviation (SD) and Average Reading Variability (ARV)] and LVMI. Average Reading Variability (ARV) of systolic blood pressure 24 h was the most powerful ABPM variability index in prediction of abnormally increased LVMI.
The evidence that ABPM gives information over and above conventional BP measurement has been growing steadily over the past 25 years, and the rationale for its use in clinical practice is soundly based. The principal advantages of ABPM are the number of readings obtained in the outpatient setting. Frequent readings lead a closer estimate of 'true BP' and allow for the analysis of BP variability and circadian rhythm of BP.13 Recently, Angeli et al. concluded that end organ damage
Alaa El-Din R. Abdel-Rheim et al.
associated with hypertension is more closely related to ambulatory BP than clinic or casual BP measurements, and it is now well established that ambulatory BP measurements give better prediction of clinical outcomes compared with conventional office BP measurements.13
Our study actually confirms Frattola et al., observation that hypertensive patients with the same 24-h BP mean values and greater BP variability have shown overall target organ damage and left ventricular mass index more than patients with a lesser BP variability.14 However, their patients were hypertensive with different levels of control (four groups according to whether their 24 h average mean arterial pressure was less than 95 mmHg, 95-108 mmHg, 109-120 mmHg or more than 120 mmHg). Twenty-four hour blood pressure was measured intra-arterially by the oxford method15 and the two indices for blood pressure variability evaluation were the average of the standard deviations obtained for each half hour (within half hour standard deviation) and the standard deviation of the average of the half hour mean values (among half hour standard deviation).
Sasaki et al., showed that inducing increase in blood pressure variability without blood pressure elevation by sinoaortic denervation (SAD) in rats, would be followed by cardiovascular damage. They hypothesized that the organ damage accompanying hypertension was in part due to the extent of the BP variability and thus not only average BP values but also upward and downward BP excursions around them should be reduced by the treatment.16
The PAMELA study (Pressioni Arteriose Monitorate E Loro Associazioni) investigated the relationship between BP variability and target organ damage in general population (not only hypertensive patients). This study actually provided the first demonstration in the general population that there is also a positive independent association between LVMI and BPV.17
In their study, Hansen et al. used the International Database on Ambulatory Blood Pressure in Relation to Cardiovascular Outcome that included prospective studies from 11 centers (8938 Subjects). These data were used to assess short-term reading-to-reading blood pressure variability by two different parameters, the first one is the usual Standard Deviation (SD) and the second one is the Average Reading Variability (ARV). This group of population underwent a follow-up of 11.3 years in average for mortality (Cardiovascular and Non-cardiovascular), cardiovascular complications (Fatal and Non-fatal). Finally this study concluded that1: Blood pressure variability was a significant and independent predictor of mortality and of cardiovascular and stroke events.2 ARV was a better predictor than SD24, probably because subjects with different blood pressure profiles might have similar SD but different ARV. Thus, ARV might be a more specific measure of blood pressure variability than SD.3
Short-term BPV has been associated with left ventricular hypertrophy in normotensive Africans in the SABPA Study.18 The study included 409 african and caucasian teachers aged 25-60 years showing a positive correlation between 24 h systolic BPV and markers of left ventricular hypertrophy in African but not Caucasian normotensive subjects. Considering this association, the authors stress out that the assessment of short-term BPV could potentially add to the early detection of normotensive Africans at increased risk for the development of cardiovascular complications.18
Left ventricular hypertrophy in controlled hypertension
Wei et al., 2014 and Ryu et al., 2014 showed that although included patients had a similar 24-h mean BP values, patients with higher BP variability had a greater comprehensive score for organ damage.19'20
Although, both Mancia et al., 2002 and Sega et al., 2005 showed no significant correlation between LVMI and BP variability assessed by 24-h SD, and demonstrated a significant correlation between LVMI and mean BP values,17,21 yet this has been challenged by many studies specially those that test the newer variability parameter ARV.
The demonstration that the patients with LVH are still showing increased blood pressure variability despite the perfectly controlled BP, sheds a strong light on the role of BPV on the pathogenesis of target organ damage in arterial hypertension.
6. Conclusion
Based on the results of this study, we can conclude that blood pressure variability is an important issue to be studied in hypertensive patients that might contribute to the pathogenesis of target organ damage even after control of BP. The ARV as an index of BP variability is superior to the traditional index (SD) in prediction of increased LV mass. At a cutoff value of 14.23 mmHg, the ARV of 24 h systolic BP could predict the presence of increased LVMI above normal values with a sensitivity of 100% and specificity of 96%.
Conflict of Interest
We have no conflict of interest. References
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