Scholarly article on topic 'Values of ambulatory blood pressure monitoring for prediction of cognitive function impairment in elderly hypertensive patients'

Values of ambulatory blood pressure monitoring for prediction of cognitive function impairment in elderly hypertensive patients Academic research paper on "Clinical medicine"

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{"Ambulatory blood pressure monitoring" / "Cognitive function" / Hypertension}

Abstract of research paper on Clinical medicine, author of scientific article — Khaled S. Mahmoud, Tamer T. Ismail, Mohamad Saad, Laila A. Mohsen, Mohamed A. Ibrahiem, et al.

Abstract Background Hypertension has been shown to carry an increased risk not only for cerebrovascular stroke but also for cognitive impairment and dementia. Ambulatory blood pressure monitoring (ABPM) is a good predictor of cardiac, renal, and cerebral disease in middle-aged and older people with hypertension. Patients and methods The study included 77 elderly (mean age: 69years) subjects. Based on the history of hypertension, office blood pressure, and ABPM, patients were classified into 2 groups, Group I: 22 persons as a control group and Group II: 55 hypertensive patients. The hypertensive group was further sub classified by using data of ABPM into dippers and non-dippers. Both groups were subjected to clinical examination, laboratory analysis, ABPM, Transthoracic Echocardiographic Examination, brain magnetic resonance imaging (MRI) and mini-mental state examination (MMSE) of their cognitive function. Results There was a statistically significant positive correlation between the cerebral MRI score and each of the average 24-h systolic, diastolic and mean arterial blood pressure, average morning systolic, diastolic, mean arterial blood pressure, average night systolic, diastolic and mean arterial blood pressure. There was also a statistically significant negative correlation between the MMSE score and the previous parameters. A non significant correlation was noted between the cerebral MRI score and the office systolic and diastolic blood pressure in hypertensive group. Conclusion The study demonstrated that hypertensive patients diagnosed by ABPM have significantly more impaired cognitive function than control subjects as proved by the mini-mental state examination and brain MRI score of white matter disease.

Academic research paper on topic "Values of ambulatory blood pressure monitoring for prediction of cognitive function impairment in elderly hypertensive patients"

The Egyptian Heart Journal (2014) xxx, xxx-xxx

Egyptian Society of Cardiology The Egyptian Heart Journal

www.elsevier.com/locate/ehj www.sciencedirect.com

ORIGINAL ARTICLE

Values of ambulatory blood pressure monitoring for prediction of cognitive function impairment in elderly hypertensive patients

Khaled S. Mahmoud a *, Tamer T. Ismail a, Mohamad Saad a, Laila A. Mohsen b, Mohamed A. Ibrahiem b, Nashaat A.A. Fadeel c, Amr Sotouhy a

a Cardiology Department, Al-Minya University Hospital, Egypt b Radiology Department, Al-Minya University Hospital, Egypt c Neuro-Psychiatry Department, Al-Minya University Hospital, Egypt

Received 28 August 2013; accepted 29 March 2014

KEYWORDS

Ambulatory blood pressure monitoring; Cognitive function; Hypertension

Abstract Background: Hypertension has been shown to carry an increased risk not only for cere-brovascular stroke but also for cognitive impairment and dementia. Ambulatory blood pressure monitoring (ABPM) is a good predictor of cardiac, renal, and cerebral disease in middle-aged and older people with hypertension.

Patients and methods: The study included 77 elderly (mean age: 69 years) subjects. Based on the history of hypertension, office blood pressure, and ABPM, patients were classified into 2 groups, Group I: 22 persons as a control group and Group II: 55 hypertensive patients. The hypertensive group was further sub classified by using data of ABPM into dippers and non-dippers. Both groups were subjected to clinical examination, laboratory analysis, ABPM, Transthoracic Echocardio-graphic Examination, brain magnetic resonance imaging (MRI) and mini-mental state examination (MMSE) of their cognitive function.

Results: There was a statistically significant positive correlation between the cerebral MRI score and each of the average 24-h systolic, diastolic and mean arterial blood pressure, average morning systolic, diastolic, mean arterial blood pressure, average night systolic, diastolic and mean arterial blood pressure. There was also a statistically significant negative correlation between the MMSE

* Corresponding author. Tel.: +20 0867554403; mob.: +20 0102554137.

E-mail address: k.maghrby@hotmail.com (K.S. Mahmoud). Peer review under responsibility of Egyptian Society of Cardiology.

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1110-2608 © 2014 Production and hosting by Elsevier B.V. on behalf of Egyptian Society of Cardiology. http://dx.doi.org/10.1016/j.ehj.2014.03.006

score and the previous parameters. A non significant correlation was noted between the cerebral MRI score and the office systolic and diastolic blood pressure in hypertensive group. Conclusion: The study demonstrated that hypertensive patients diagnosed by ABPM have significantly more impaired cognitive function than control subjects as proved by the mini-mental state examination and brain MRI score of white matter disease.

© 2014 Production and hosting by Elsevier B.V. on behalf of Egyptian Society of Cardiology.

1. Introduction

High blood pressure (BP) is a risk factor for cerebrovascular disease, including stroke. Little is known about the importance of BP on the progression of microvascular disease of the brain, which has been associated with functional decline in mobility and cognition in older people.1 An important advantage of ambulatory blood pressure (ABPM) measurement over office BP assessment, is its enhanced reproducibility. Numerous studies have demonstrated that ambulatory BP is a better predictor of cardiac, renal, and cerebral disease in middle-aged and older people with hypertension.2 Small vessel disease of the brain may present as white matter hyperintensities (WMHs) and these are commonly present in the magnetic resonance images (MRI) of older persons with hypertension and other vascular disease risk factors.3 These WMHs are clinically relevant in older people because they are associated with functional deterioration of mobility, cognition4 and stroke.5 They have been proposed as an intermediate marker in the research setting.6

2. The aim of the study

The aim of this study was to test the correlation of the 24-h ABPM data to the cognitive function of elderly hypertensive patients even if their office BP is normal.

3. Patients and methods

The study included 77 elderly patients (mean age: 69 years). Hypertension is considered present if the average clinic recorded BP reading exceeded 140/90 mmHg and/or if average 24-h BP reading exceeded 130/80 mmHg.7'8 Based on history of hypertension, office blood pressure (average of 3 readings) and ABPM, patients were classified into two groups:

• Group I: 22 persons as a control group (no history of hypertension, and no office or ABPM evidence of hypertension).

• Group II: 55 hypertensive patients by history, office BP or

The hypertensive group was further sub-divided according to the data of ABPM into dipper hypertensive (n = 18) and non-dipper hypertensive (n = 37) patients. Dipper means that there is drop in nocturnal BP than day blood pressure by 1020% followed by an increase early in the morning.

Exclusion criteria: (1) Patients with underlying neurological disorders that would impair mobility or cognitive function. (2) Patients with severe or unstable cardiovascular disorders (e.g., myocardial infarction in the last 6 months, decompensated heart failure, stroke). (3) Diabetic patients. Diabetes mellitus was considered to be present if the patient was on anti diabetic medication or by abnormal HbA1C.9 (4) Renal impairment

patients. The estimated Glomerular Filtration Rate (eGFR) was calculated using Cockcroft-Gault formula.10

eGFR _ [140 - age in years]x weight (kg) ^ 0 85 72 x serum creatinine level (mg/dL)

The studied groups were subjected to:

(1) Personal history, history of previous acute coronary syndrome (ACS), interventions, diabetes mellitus and estimation of traditional risk factors as cigarette smoking and dyslipidemia.

(2) Clinical Examination, which included BP measurement. BP was measured in the supine position after 5 min of rest, using a large cuff when necessary, with a standard mercury sphygmomanometer.

(3) Laboratory analysis, which included random and fasting blood sugar, renal function tests and lipid profile after fasting for at least 12 h.

(4) Transthoracic Echocardiography: Two-dimensional, M-mode, Doppler and color-Doppler echocardiographic examinations were performed using GE Vivid III expert machine (GE Medical Systems, Waukesha, WI), equipped by Tissue-Doppler mode, with 2.5 MHz phase array transducer. M-mode, color flow mapping, pulsed and continuous wave Doppler recordings were obtained for each subject. Measurements of LV end-diastolic (EDD) and end-systolic diameters and of the interven-tricular septal (IVS) and posterior wall (PWT) thicknesses in diastole were obtained from a standard parasternal long-axis view according to the recommendations of the American Echocardiography society.11 LV mass was calculated according to the formula as corrected by Devereux and Reichek.12,13

(5) 24-h ambulatory BP monitoring (ABPM): Subjects were fitted with a BP monitor (Contec ABPM50, Germany). Patients were monitored for 24 h, with readings being obtained every 30 min during day-time (8 AM-12 PM) and at 60-min intervals during night-time (12 PM-8 AM).

(6) Assessment of cognitive function: The mini-mental state examination (MMSE) or Folstein test is a brief 30-point questionnaire test that is used to screen for cognitive impairment.14 It is used to estimate the severity of cognitive impairment. The questions of the MMSE include asking about Orientation (Time, date, day, month, year), Registration (Name three objects only once), Attention and calculation (Ask the patient to subtract 7 from 100 and then 7 from the result four more times), Recall (Ask the patient to repeat the names of the three objects learnt in the registration test) and Language (Score 1 point for each of two simple objects named). The scores from each step are added to give the total score. A score greater than or equal to 25 points (out

Table 1 Description of the modified Scheltens MRI score for cerebral WMH.

Cerebral hemisphere

PVCs (0-6) x3 (frontal, occipital & lateral) DWMHCs (0-24) x4 (frontal, Basal ganglia Changes x5 (0-30)

parietal, temporal, occipital (caudate, Putamen, GP, Thalamus

lobes) & IC)

0 NAD 0 NAD 0 NAD

1 65 mm 1 <3 mm in 65 1 <3 mm in 65

2 5< x <10 mm 2 <3 mm in p 6 2 <3 mm in p 6

P10 mm is not considered PVCs 3 4-10 mm in 65 3 4-10 mm in 6 5

4 4-10 mm in p6 4 4-10 mm in p 6

*if P 10 mm, Considered as 2 and the excess of the lesion is dealt 5 >11 mm in >1 5 >11 mm in >1

with as DWMHCs in its particular lobe 6 Confluent 6 Confluent

NAD: No abnormality detected.

of 30) is normal. A score of (69 points) indicates severe cognitive impairment. A score of (10-20 points) indicates moderate cognitive impairment and a score of (21-24 points) indicates mild cognitive impairment.

(7) Brain MRI and quantitative assessment of white matter hyperintensity (WMH): Patients had a customized simple brain MRI study that is composed of standard axial T1 weighted, axial T2 weighted and axial FLAIR sequences. The MRI study was done on a 0.2T GE Signa Excite machine (GE Medical Systems, Waukesha, WI). The evaluation of the MRI was to exclude other causes of cognitive impairment, e.g. Alzheimer disease and to score the white matter hyperintensities. MRI was also needed to confirm the results of the MMSE score. The deep white matter hyperintensities were evaluated and scored according to the modified Scheltens score.15 The modified Scheltens score is represented in the following table (Table 1).

4. Statistical analysis

Statistical analysis was carried out using SPSS version 16 for windows (SPSS Inc., Cary, NC). The analysis of the difference of nominal data, e.g. gender, between groups and subgroups was carried out using the Chi Square test. Statistical significance of differences in continuous variables was assessed using Student's t test. Bivariate Pearson's correlations were carried out between each of the office BP measurements and the 24-h ABPM variables and the MMSE and the MRI score. A linear regression analysis was run to find the factors with stronger impact on the cognitive function. Significance level for the used tests is P = 0.05.

5. Results

There was no statistically significant difference between the control and hypertensive groups as regards age, sex, smoking, and dyslipidemia (Table 2).

As regards the Echocardiographic data there was a statistically significant difference between hypertensive and control groups regarding LVID, IVSD, PWD and LVM (P < 0.05), however there was no statistically significant difference regarding LV systolic function (P = 0.108).

Table 2 Demographic description of the patients.

Control Hypertensive P-value

Age 68.36 ± 2.66 69.09 ± 3.58 0.393

Sex: n (%)

Male: 13 (59.1%) 28 (50.9%) 0.516

Female: 9 (40.9%) 27 (49.1%)

Smoking: n (%)

Smoker: 11 (50%) 29 (52.7%) 0.829

Non smoker: 11 (50%) 26 (47.3%)

Dyslipidemia: n (%)

Dyslipidemic: 4 (18.2%) 16 (29.1%) 0.324

Non dyslipidemic: 18 (81.8%) 39 (70.9%)

Table 3 Comparison between hypertensive and control groups regarding brain MRI & MMSE scores.

Control Hypertensive P-value

MRI score 1.54 ± 1.05 16.12 ± 9.58 <0.001

MMSE score 26.27 ± 2.18 14.50 ± 5.54 <0.001

Table 4 Comparison between dipper and non dipper hypertensive patients regarding brain MRI & MMSE scores.

Hypertensive Hypertensive P-value

dipper non dipper

MRI score 15.86 ± 9.49 16.66 ± 10.01 0.735

MMSE score 14.27 ± 5.27 14.62 ± 5.73 0.807

Regarding ambulatory blood pressure monitoring data there was no statistically significant difference between hypertensive subgroups (dipper and non-dipper) regarding data of average 24 h and morning ABPM (P > 0.1). However, there was a significant difference between hypertensive subgroups (dipper and non-dipper) regarding data of average night ABPM (P < 0.003).

There was a statistically significant difference in the MRI and MMSE scores between hypertensive and control groups (Table 3).

There was no significant difference between the hypertensive subgroups dipper and non-dipper regarding the MRI or the MMSE scores (Table 4).

Table 5 Correlation between brain MRI score and blood pressure in hypertensive patients.

Hypertensive R P

MRI score & office systolic 0.180 0.729

MRI score & office diastolic 0.093 0.502

MRI score & average 24 h SBP 0.905 <0.001

MRI score & average 24 h DBP 0.759 <0.001

MRI score & average 24 h MAP 0.772 <0.001

MRI score & average morning SBP 0.903 <0.001

MRI score & average morning DBP 0.903 <0.001

MRI score & average morning MAP 0.777 <0.001

MRI score & average night SBP 0.495 <0.001

MRI score & average night DBP 0.706 <0.001

MRI score & average night MAP 0.640 <0.001

o r = 0.827

o p < 0.001

o o O^x

o O OO

o o\ o

1-1-1-1-1-^—

00 10.00 20.00 30.00 40.00 50.00

MRI score

Figure 2 Correlation between the MMSE score and MRI score.

Table 6 Correlation between the MMSE score and blood

pressure in hypertensive patients.

Hypertensive

MMSE score & office systolic -0.185 0.177

MMSE score & office diastolic -0.115 0.402

MMSE score & average 24 h SBP -0.816 <0.001

MMSE score & average 24 h DBP -0.683 <0.001

MMSE score & average 24 h MAP -0.684 <0.001

MMSE score & average morning SBP -0.813 <0.001

MMSE score & average morning DBP -0.732 <0.001

MMSE score & average morning MAP -0.701 <0.001

MMSE score & average night SBP -0.442 <0.001

MMSE score & average night DBP -0.656 <0.001

MMSE score & average night MAP -0.564 <0.001

There was no significant correlation between the MRI score and office BP measurements. On the other hand, there was a statistically significant positive correlation between MRI score and each of the average 24-h systolic, diastolic and mean arte-

rial blood pressure, average morning systolic, diastolic, mean arterial blood pressure, average night systolic, diastolic and mean arterial blood pressure as shown in table 5.

Similarly, there was no significant correlation between the MMSE score and office BP measurements, while there was a statistically significant negative correlation between the MMSE score and each of the average 24-h systolic, diastolic and mean arterial blood pressure, average morning systolic, diastolic, mean arterial blood pressure, average night systolic, diastolic and mean arterial blood pressure as shown in table 6.

Multivariate regression analysis revealed that morning systolic ABPM was a significantly higher predictor for MRI changes (R = 0.911, R2 = 0.830, P < 0.001). Similarly, the morning systolic ABPM was also a significantly higher predictor for MMSE score (R = 0.868, R2 = 0.754, P < 0.001).

The duration of hypertension revealed a statistically significant positive correlation to the MRI score and a statistically significant negative correlation to the MMSE score (Fig. 1).

When comparing the MRI and MMSE scores, a significant negative correlation was found between them (R = —0.827, P < 0.001). (Fig. 2)

Figure 1 Correlation between the MRI & MMSE scores and duration of hypertension.

6. Discussion

It is well known that hypertension causes damage to many of the body's organs, including the heart, kidneys, eyes, and brain, and it is a major risk factor for coronary heart disease and stroke. However, the impact of hypertension on the brain prior to stroke is presently under recognized. Even in otherwise healthy people, hypertension can lead to mild to moderate alterations in the brain's structure and function, including its ability to efficiently process information (known as cognitive function). These early hypertension related changes in the brain can be detected by sophisticated brain scans and by neuropsychological assessment of cognitive abilities.16

Silent cerebral white matter lesions (WMLs) are a common finding on brain magnetic resonance imaging (MRI) in the elderly. However, in patients with hypertension, WMLs tend to occur earlier in life and appear to be more severe. There is evidence that supports the idea that WMLs in asymptomatic hypertensive patients should be considered a silent early marker of brain damage.17

The study included 77 individuals with no significant differences regarding age, sex and risk factors (smoking and dyslipide-mia). We aimed to avoid any bias induced by these risk factors and this comes in agreement with de Groot et al.18 and Sacco RL et al.,19 who suggested that age, smoking and dyslipidemia were risk factors for the development of cognitive impairment.

In the hypertensive group, WMLs were increased, which was observed by the MRI score and the MMSE score was decreased compared to the control group. These findings were consistent with the results of William White et al., and Yusuke et al.20'21 It is well known that pressures measured in the office or clinic may not be representative of the patient's blood pressure throughout the day.22 In this study, it was demonstrated that the ABPM correlated more with cognitive impairment than office blood pressure. In disagreement with this, Shari and Christiane23,24 concluded that systolic hypertension measured in office was related to a higher risk of impaired cognitive function. However, Puisieux25 suggested that this relationship is only evident when uncontrolled hypertension is confirmed by (ABPM) which was in agreement with our results.

Our study demonstrated a significant positive correlation between the duration of hypertension and the MRI changes as well as a significant negative correlation between the duration of hypertension and the MMSE score. This is consistent with the results of Shu-jian and Willum-Hansen.26,27

The average morning systolic blood pressure and average 24-h systolic blood pressure had the strongest impact on the cerebral MRI score and the MMSE score. This finding could have several explanations. It could denote that the higher stresses of morning life cause the systolic blood pressure to exert a higher damaging effect on the CNS. Another explanation could be that the circadian rhythm of the corticosteroids assists the damaging effect of systolic blood pressure upon the CNS during day time and reduce it by night. Many studies agreed with ours regarding the effect of average 24-h and average daytime systolic blood pressure to the cognitive decline and MRI changes.28,29 Nagai M et al., however disagreed in that the sleeping systolic BP had a stronger impact upon the cognitive ability, although average overall and average awake systolic BP were also strongly correlated to cognitive function.30 To the authors' best knowledge, few researchers have found a strong correlation between

the cognitive impairment and the diastolic blood pressure at any phase of the 24-h ABPM.3132

Van Boxtel et al.,28 demonstrated that non dipping diurnal blood pressure variation is associated with target organ damage of the brain. However in our study, similar to Grandi and Cesare,33,34 we did not find any significant difference between dipper and non dipper regarding MRI changes, cognitive impairment or echocardiographic findings.

In a sample of treated dipper and non-dipper essential hypertensive patients with different clinic BP controls, the present study showed that a reduced nocturnal fall in BP, established on the basis of a single ABPM, was not associated with more pronounced cardiac involvement. In fact, we found no significant difference in left ventricular size and systolic function or prevalence of cardiac hypertrophy between patients with and without a normal fall in BP during night time.

Our study had some limitations. First, we did not include diabetic patients. We aimed to make the study sample as uniform as possible, accordingly, we excluded diabetes as an important risk factor for vasculopathy and hypertension. This implies that our results are only applicable to non-diabetic hypertensive patients.

Second, some factors could not be excluded from the study, e.g. dyslipidemia and smoking. These were however insignificant between the hypertensive and control groups. Hypertension duration is also among the strongly significant factors that were correlated with the patients' cognitive ability. This seems to be a logical relation; as the duration of hypertension increases, its target organ effect on the brain increases. However, based on the multivariate analysis, the average morning systolic blood pressure had a stronger impact on the MMSE and MRI scores than the duration of hypertension.

Finally, the effect of treatment was not evaluated in our study. This is a very important issue that needs a longitudinal study with long term follow up to record the change in cognitive function and MRI score, not to mention studying the different effects of variable drug combinations to achieve BP control.

7. Conclusion

The study demonstrated a stronger correlation between the 24-h ABPM data and the cognitive function of elderly hypertensive patients, a relation which was not evident using office BP measurement.

Conflict of interest

The work has been approved by the appropriate ethics committees related to the institution in which it was performed and that subjects gave informed consent to the work.

There are no financial and personal relationships with other people or organizations that could inappropriately influence (bias) their work, as regards all authors.

The funding source of the work was my own money.

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