Download Table 3: Brain imaging studies of patients with hypertension, without

Table 1 Brain Imaging Studies of Patients With Hypertension Without Symptomatic Cardiovascular, Cerebrovascular, and Peripheral Vascular Disease
First
No. of
Subject Age, yrs
Author
Treatment of Vascular
Study Design
Subjects
Mean (SD)
Imaging Modality
Imaging Findings
Risk Factor
(Ref. #)
Beason-
Longitudinal;
One-half with HTN
1. Both HTN and non-HTN groups
15
[ O] water PET under
Held et al.
With HTN (year
mean follow-up,
treated in year 1,
1), 70.8 (8.4)
6 yrs
remaining subjects began
14 with, 14
(25)
showed regional declines in resting rCBF
the following conditions:
without HTN
of increasing areas affected from year 1 to
1. Resting state
Without HTN
antihypertensive
year 7 and some areas of increased rCBF
2. Verbal Recognition
(year 1), 67.7
treatment at year 3 or 5
of increasing areas affected from year 1 to
Memory task
(3.5)
year 7, interpreted as age-related changes.
3. Figural Memory
2. Greater longitudinal decline in rCBF in
Recognition task
HTN compared with nonhypertensive
group in the middle and inferior prefrontal
cortex, anterior cingulate,
occipitotemporal cortex, posterior
occipital cortex.
3. HTN group showed a significantly
lower increase in resting state rCBF
compared with nonhypertensive groups in
bilateral premotor (inferior frontal) cortex,
superior temporal cortex, hippocampus,
left hemisphere primary motor cortex.
1
4. HTN group showed an inverse
correlation between BP and longitudinal
decrease in rCBF.
5. HTN group showed an inverse
correlation between duration of HTN and
longitudinal decrease in rCBF (i.e., a
greater duration of HTN was associated
with a greater decrease in rCBF in the
superior, medial, middle, and inferior
frontal lobe and prefrontal cortex).
6. Subjects with uncontrolled HTN
showed a greater decline in rCBF in the
inferior frontal, precentral, midtemporal,
parahippocampal, and fusiform gyri
compared with controlled HTN subjects.
1. No longitudinal changes in total brain
Debette et
N = 1,352;
At baseline MRI,
Longitudinal;
Treatment data not
al. (17)
346 with HTN,
61 (9)
mean follow-up,
provided
1,006 without
HTN
6.3 yrs
Structural MRI
volume or temporal horn volume.
2. HTN and increasing SBP in midlife
were associated with a more rapid
increase in white matter hyperintensity
volume over the average 6.3-year followup. These associations were maintained
after adjusting for interim stroke.
2
Longitudinal;
15% of subjects taking
N = 72 (7)
1. Increasing age was associated with
Structural MRI
den Heijer
513 (with MRI
mean follow-up,
antihypertensive
increasing cortical atrophy, more
et al. (15)
+ longitudinal
20 yrs
medication
pronounced in men than in women.
data)
2. Antihypertensive medication use in late
life, but not in midlife, was associated
with more pronounced cortical atrophy.
3. U-shaped association between
concurrent DBP and degree of cortical
atrophy on MRI.
4. The U-shaped association was similar
for users and nonusers of antihypertensive
medications.
5. Concurrent SBP level was unrelated to
the degree of cortical atrophy.
6. Higher DBP levels 20 years before
MRI (midlife) predicted more cortical
atrophy in later life in subjects without
antihypertensive medication, but not in
subjects with antihypertensive medication.
7. Higher SBP levels 20 years before MRI
(midlife) was not associated with more
cortical atrophy in later life.
8. A steeper decline in DBP over the 20
3
year follow-up was associated with
significantly more cortical atrophy
compared to a stable BP level over time.
9. SBP change over 20 yrs was not
associated with the degree of cortical
atrophy.
Efimova
15 with
With untreated or Longitudinal;
All HTN subjects treated
1. Before treatment with an
SPECT with 99Tc-
et al. (26)
untreated or
ineffectively
mean follow-up, 6
with antihypertensive
antihypertensive agent, rCBF was
ineffectively
treated HTN, 53
months
medication; ACEI (5
significantly lower in hypertensive
treated HTN
(5.7)
subjects) or diuretic agent
subjects versus control subjects bilaterally
11 without HTN
Without HTN,
(10 subjects)
in the anterior parietal, posterior parietal,
HMPAO
52.5 (3.8)
superior frontal, inferior frontal, temporal,
and occipital cortices.
2. 6 months of antihypertensive treatment
produced significant increases in rCBF in
all regions in the HTN subjects. ACEIs
and diuretic agents showed no differences.
3. Decreased attention correlated with a
decrease in rCBF in the upper frontal,
anterior parietal, and temporal regions in
4
HTN subjects. Decreased psychomotor
speed correlated with a decrease in rCBF
in frontal, anterior parietal, and temporal
regions in HTN subjects.
4. 6 months of antihypertensive treatment
improved performance of HTN subjects
on tests of attention, psychomotor speed,
and abstraction, which correlated with
increased rCBF in inferior frontal and
anterior parietal regions.
1. Gray matter atrophy correlated with
Firbank et
92 with HTN
With HTN, 77
Longitudinal;
All subjects with HTN
Structural MRI
baseline SBP but not DBP.
al. (19)
41 without HTN
(4)
mean follow-up,
treated with
2. Baseline total WMH fraction correlated
Without HTN, 76 711 days
antihypertensive
with age.
(4)
medication.
3. Baseline total and deep WMH fractions
were greater in HTN subjects compared
with subjects without HTN.
4. No associations between total WMH
fraction and SBP or between deep WMH
fraction and BP.
5. Over 2-yr follow-up, total WMH
fraction increased in both subjects with
and without HTN.
5
6. Over 2-yr follow-up, change in total
WMH fraction was greater in subjects
with HTN compared with subjects without
HTN.
7. Over 2-yr follow-up, the deep WMH
fraction increased in subjects with HTN
but not in subjects without HTN.
Guo et al.
N = 539 (100%
N = 78.03
Longitudinal;
3.4% taking
CT scan
1. The presence of white matter lesions
(23)
women)
mean follow-up:
antihypertensive
was associated with an increase in DBP,
1. First CT scan =
medication at baseline (24
24 yrs
yrs before first scan).
2. Second CT scan
22.8% receiving
= 32 yrs
antihypertensive
SBP, PP, and MAP over 24 yrs.
2. Higher middle- and late-life DBP and
MAP, but not SBP and PP over 32 yrs,
were associated with increased frequency
medication at first CT
and severity of white matter lesions.
scan.
Hannesdot
40 with treated
With treated
ir et al.
HTN
HTN, 69.3 (11.3)
1. Total brain volume significantly higher
Cross-sectional
Treated = 40
1. Structural MRI
in untreated HTN vs. treated HTN.
Untreated = 10
(24)
10 with
With untreated
2. DTI MRI
2. No significant differences in gray
untreated HTN
HTN, 57.6 (6.1)
3. 1H-MRS
matter N-acetylaspartate/creatine.
30 without HTN
Without HTN,
3. White matter lesion volume load
68.2 (8.5)
significantly higher in treated HTN vs.
untreated HTN.
4. Fractional anisotropy significantly
6
lower in treated HTN vs. untreated HTN.
5. Positive correlations between executive
functioning and mean diffusivity and
between psychomotor speed and mean Nacetylaspartate/creatine in untreated HTN
subjects.
6. No correlations between
neuropsychological performance and
MRS in treated HTN subjects.
7. Subjects with treated HTN performed
more poorly only on memory tests
compared to subjects without HTN.
8. Subjects with untreated HTN
performed more poorly on a broader array
of neuropsychological testing compared to
subjects without HTN.
(Subjects with treated HTN were
significantly older than patients with
treated HTN.)
[15O] water PET during
1. Subjects with HTN showed
range, 60–76
2 cognitive activation
significantly greater left hemispheric
Without HTN:
tasks:
increases in rCBF during CPT and trend
range, 59–68
1. CPT
level greater left hemispheric increases in
With HTN:
9 with untreated
Jennings
Cross-sectional
None treated
HTN
et al. (27)
5 without HTN
7
2. Auditory free recall
rCBF during verbal free recall.
task.
2. Subjects without HTN showed
significantly greater right hemispheric
increases in rCBF during both CPT and
verbal free recall tasks.
3. Subjects with HTN showed a decreased
responsivity (lower rCBF increases) in
response to increased task difficulty
compared with subjects without HTN.
1. Subjects with HTN showed muted
Jennings
37 with
Cross-sectional
None treated
1. Structural MRI
increases in posterior parietal and
et al. (28)
untreated HTN
With HTN, 61.3
15
2. [ O] PET with 2
thalamic rCBF during both verbal and
59 without HTN
Without HTN, 60
cognitive activation
spatial working memory tasks compared
tasks:
with subjects without HTN.
a. Perceptual motor task
2. Parietal rCBF was positively related to
b. Verbal working
verbal working memory performance in
memory task
subjects with HTN and negatively related
3. Carotid artery
to verbal working memory performance in
ultrasound
subjects without HTN.
3. Subjects with HTN showed working
memory–induced rCBF correlations
between the amygdala/hippocampus and
prefrontal cortex, not observed in subjects
8
without HTN.
Longitudinal;
All subjects with HTN
1. [15O] water PET:
1. Treatment of hypertension with either
mean follow-up, 1
untreated at study entry
a. rCBF response to
lisinopril or atenolol maintained pre-
yr
randomized to
acetazolamide
treatment values for estimated CBF,
prospective treatment
b. rCBF response to
rCBF, and changes in these measures
treatment and
with:
working memory task
elicited by the working memory task.
scanned:
1. Lisinopril
2. Brachial artery
2. After 1 yr of either antihypertensive
20, lisinopril;
2. Atenolol
dilation:
treatment, the working memory tasks did
a. brachial artery flow in
not elicit a greater rCBF response.
response to
3. Cerebral dilation in response to
acetazolamide
acetazolamide was unaffected by either
Measurement of
antihypertensive medication.
peripheral and cerebral
4. Correlations between rCBF responses
vasodilatory reserve
in regions known to be involved in
43 with
Jennings
Lisinopril, 53.9
untreated HTN
et al. (32)
(5.6)
at study entry
Atenolol, 51.3
randomized to
(7.4)
23, atenolol
working memory processing (prefrontal
vs. parietal, prefrontal vs.
amygdala/hippocampus, parietal vs.
amygdala/hippocampus) increased
significantly after 1 yr of antihypertensive
treatment with no significant differences
between medication groups.
9
Jennings
41 subjects with
With HTN =
Longitudinal;
Subjects with HTN
Structural MRI
1. Reduction of BP to normotensive levels
et al. (16)
HTN from the
52.4 (7.1)
mean follow-up, 1
randomized to treatment
failed to prevent gray matter loss in
lisinopril vs
Without HTN =
yr
with lisinopril or atenolol
multiple regions over 1 yr of treatment.
atenolol study
65.9 (9.3)
per Jennings et al. (32)
2. No significant correlations with
(Jennings et al.
study.
cognitive performance scores and the gray
[32])
Subjects without HTN: no
matter regions showing change over the
16 subjects
treatment
treatment period.
without HTN
10
a. Nondippers =
Cross-sectional
No patients received any
Structural MRI
1. The number of lacunae and the
Kario et al. 131 total
72
antihypertensive
PVH graded I–IV on
prevalence of patients with lacunae and/or
(20)
subjects with
b. Dippers = 69
medication for at least 1
extent and confluence.
advanced PVH (grades III and IV) were
HTN: 31 with
c. Extreme
month before study entry.
white coat
dippers = 70
significantly higher in the extreme dippers
and nondippers compared with dippers.
HTN, 100 with
2. The number of lacunae per patient and
sustained HTN
the prevalence of patients with lacunae
(focus of study)
were, respectively, 2.3 and 52% in the
a. 46
group with the greatest nocturnal SBP dip
nondippers
(first quartile), 1.3 and 40% in the group
b. 38 dippers
with the second greatest nocturnal SBP
c. 16 extreme
dip (second quartile), 2.0 and 52% in the
dippers
group with the next greatest nocturnal
SBP dip (third quartile), and 2.3 and 64%
in the group with the lowest nocturnal
SBP dip (fourth quartile), indicating a Jshaped relationship between nocturnal BP
dip and brain MRI findings.
1. All subjects with HTN
Mentis et
17 with HTN
With HTN =
Cross-sectional
1. Only the territory supplied by
Fluorodeoxyglucose
treated with
al. (33)
(100% men)
25 without HTN
(100% men)
68.2 (7.8)
perforator arteries from the circle of
PET: resting state
antihypertensive
Willis (base of the brain) and initial
medication at recruitment.
segments of the cerebral arteries had a
2. All subjects with HTN
significantly lower rCMglu in the group
Without HTN =
65.5 (8.9)
11
had 2-week washout of
with HTN compared with the group
antihypertensive
without HTN.
medication before CT
2. The group with HTN had reduced
scanning.
correlations (reduction of functional
neuronal connectivity, pairwise
correlations of rCMglu between regions of
interest within vascular territories) in
cortical territories of the MCA, ACA,
MCA·ACA watershed area, and the
thalamus compared with the group
without HTN.
Longitudinal;
Meyer et
12 with
69.8
Significant increases in CBF values were
All subjects with HTN
133
Xe inhalation method
mean follow-up:
al. (31)
untreated HTN
observed at 6, 12, and 24 months after
started on
1. 6 months
control of hypertension. After 36 months
antihypertensive
2. 12 months
mean CBF values failed to show
medication and low-salt
3. 24 months
significant differences from pre-treatment
diet after baseline scan.
4. 36 months
levels.
Nobili et
39 with never
Untreated HTN = Cross-sectional
61% of subjects with
1. CT
1. gCBF was significantly lower in the
al. (29)
treated HTN
42.69 (14.07)
HTN receiving
2. Carotid ultrasound
untreated HTN group compared with
62 with HTN
Treated HTN =
antihypertensive
3. 133Xe inhalation
subjects without HTN, with significant
receiving
56.46 (11.05)
medication
method
rCBF reductions all explored regions.
antihypertensive
2. Mean gCBF differed only slightly
treatment
between subjects with treated HTN
12
189 without
compared with subjects without HTN,
HTN
with fewer individual hypoperfused areas
observed relative to the untreated HTN vs.
subjects without HTN.
3. No significant correlations between
CBF and duration of HTN, MABP, total
cholesterol level, and the presence of
retinopathy or left ventricular hypertrophy
in the whole group of hypertensive
subjects.
4. Among treated HTN subjects, quality
of BP control was inversely correlated
with MABP and with cerebrovascular
resistance (cerebrovascular resistance =
CBF). Quality of BP control was
positively correlated with CBF.
Raz et al.
40 with HTN
HTN = 61.56
Cross-sectional
All subjects with HTN
Structural MRI
1. Subjects with HTN had lower PFC gray
(14)
40 without HTN
(11.58)
treated with
matter volume compared to subjects
Without HTN =
antihypertensive
without HTN.
61.63 (11.25)
medication
2. Longer duration of HTN was not
associated with any differences in regional
cortical volumes.
3. Subjects with HTN had lower
13
prefrontal cortex white matter volume
compared with subjects without HTN.
4. HTN was not associated with
differences in overall WMH volume, but
the magnitude of WMH volumetric
differences between groups varied across
regions of interest.
5. Subjects with HTN had greater frontal
WMH volume compared with subjects
without HTN.
6. Longer duration of HTN was associated
with increased WMH burden.
Cross-sectional
28% of subjects with
133
Rodriguez
26 with
With untreated
Xe inhalation method
1. Subjects with untreated HTN
et al. (30)
untreated HTN
HTN = 62.07
HTN treated with
demonstrated global reductions in CBF
10 with treated
(6.71)
antihypertensive
compared with subjects without HTN.
HTN
With treated
medication
2. Global CBF in subjects with treated
26 without
HTN = 63.1
HTN was comparable to that in subjects
HTN
(7.03)
without HTN.
14
Without HTN =
3. Subjects with untreated HTN
62.05 (9)
demonstrated reductions in right and left
hemispheric rCBF compared with subjects
without HTN; subjects with treated HTN
did not.
4. Significant negative correlation
between duration of HTN and global CBF
in subjects with untreated HTN.
5. Significant negative correlation
between MAPB and global CBF in entire
subject group (HTN and no HTN).
Salerno et
18 with HTN
With HTN,
Cross-sectional
All 18 subjects with HTN
Structural MRI
1. The right lateral ventricle volume was
al. (12)
17 without
mean 69 (8)
were treated with
56% larger and the left lateral ventricle
HTN
Without HTN, 69
antihypertensive
volume was 86% larger in the subjects
(100% men)
(7)
medication
with HTN compared with subjects without
HTN.
2. Subjects with HTN had a significantly
smaller mean left hemisphere brain
volume compared with subjects without
HTN.
15
Longitudinal;
123
68.4 (3.6)
Söderlund
1. Higher DBP measured 10 yrs before
Not available
Structural MRI
mean follow-up,
MRI was associated with more subcortical
nondemented
1. Subcortical WMHs
et al. (22)
10 yrs
WMHs (linear relationship). SBP was not
subjects
rated by number and size
associated with subcortical WMH
(diameter), mm:
number.
a. 1–3
2. Higher DBP measured 10 yrs before
b. 4–10
MRI was associated with more
c. >10
periventricular WMHs (relationship not
2. Periventricular WMH
linear). SBP was not associated with
severity graded ranging
periventricular WMHs.
from 0, none to 3, large
3. A greater number of periventricular
confluent
WMHs was associated with lower scores
on memory test performance.
Strassburg
27 with HTN
With HTN =
Cross-sectional
All subjects with HTN
Structural MRI
1. Subjects with HTN had smaller
er et al.
20 without
67.4 (7.3)
taken off antihypertensive
thalamic nuclei and larger cerebellar CSF
(13)
HTN
Without HTN =
medication with 2-week
and temporal CSF volumes than subjects
68.7 (6.1)
washout period before
without HTN.
16
scanning.
2. There were significant interactions
between a diagnosis of HTN and age (old
age + HTN) being associated with smaller
frontal cerebral volumes, larger temporal
CSF, and occipital CSF volumes.
3. Subjects with HTN had more severe
deep WMH ratings than subjects without
HTN.
4. No differences in periventricular WMH
ratings between subjects with HTN and
subjects without HTN.
5. No significant effects of gray matter or
CSF volumes and neuropsychological
performance within HTN group.
White et
N = 72
al. (21)
82.1 (3.9)
Longitudinal;
64% of subjects treated
Structural MRI
(baseline and
mean follow-up,
with antihypertensive
was associated with change from baseline
follow-up
24 months
medication
in 24-h monitored SBP but not for
scanning)
1. The accrual of WMH over 24 months
changes in clinic SBP.
2. There were no differences in WMH
according to dipper status.
Wiseman
103 with HTN
With HTN =
et al. (11)
51 without
HTN
Cross-sectional
All subjects with HTN
Structural MRI: WMHs
1. Subjects with HTN had smaller whole-
77.2 (3.7)
were being treated with
rated using the Scheltens
brain volume than subjects without HTN.
Without HTN =
antihypertensive
scale.
2. Periventricular WMHs and basal
17
76.1 (3.9)
medication.
ganglia WMHs were positively correlated
with age.
3. WMHs were very common in both
hypertensive and normotensive subjects.
4. The severity of total periventricular
WMHs was greater in subjects with HTN
compared with subjects without HTN.
5. The severity of WMHs was greater in
subjects with HTN in frontal and temporal
areas, but not in occipital or basal ganglia,
compared with subjects without HTN.
6. The reduction in whole-brain volume
was independent of the increased burden
of WMHs.
ACA = anterior cerebral artery; ACEI = angiotensin-converting enzyme inhibitor; CSF = cerebrospinal fluid; CPT = continuous performance task; CT =
computed tomography; DBP = diastolic blood pressure; DTI = diffusion tensor imaging; MAP = mean arterial pressure; MABP = mean arterial blood
pressure; MAPH = mean arterial pulmonary hypertension; MCA = middle cerebral artery; MRI = magnetic resonance imaging; MRS = magnetic resonance
spectroscopy; PET = positron emission tomography; PP = pulmonary pressure; PVH = pulmonary venous hypertension; SBP = systolic blood pressure;
SPECT = single-photon emission computed tomography; other abbreviations as in Table 2.
18