Download The J-Curve Phenomenon in Stroke Recurrence

1844
The J-Curve Phenomenon in Stroke Recurrence
Katsumi Irie, MD; Takenori Yamaguchi, MD; Kazuo Minematsu, MD; Teruo Omae, MD
Downloaded from http://stroke.ahajournals.org/ by guest on June 17, 2017
Background and Purpose: The relation of poststroke blood pressure to stroke recurrence remains
undetermined, and the optimal control of blood pressure has not been established. We performed the
present study to resolve these issues.
Methods: We analyzed 368 stroke patients with a history of hypertension (mean age, 62 years) who were
admitted within 3 months after stroke onset and observed for 6 months or more. We determined stroke
recurrence rate in relation to baseline (or initial) blood pressure, mean values of poststroke blood
pressure, stroke subtypes, age, antihypertensive treatment, and other clinical features.
Results: The recurrence rate had a J-curve relation to poststroke diastolic blood pressure but not to
poststroke systolic blood pressure and baseline diastolic and systolic blood pressures. The stroke
recurrence rate was 3.8% per patient-year in 94 patients who had a poststroke diastolic blood pressure of
80 to 84 mm Hg, significantly lower than the rates of 9.2% per patient-year (P<.05) and 11.4% per
patient-year (P<.01) in those with a lower and higher poststroke diastolic blood pressure, respectively.
The range of poststroke diastolic blood pressure accompanying the lowest stroke recurrence rate was
higher in patients with atherothrombotic (85 to 89 mm Hg) than in those with lacunar infarction (80 to
84 mm Hg). Neither antihypertensive therapy nor patients' age affected this phenomenon.
Conclusions: The present study suggests that lower blood pressure does not always result in favorable
effects on stroke recurrence. The effects of poststroke blood pressure and antihypertensive therapy on
stroke recurrence may be complicated by the J-curve phenomenon. (Stroke. 1993;24:1844-1849.)
KEY WORDS * antihypertensive agents * blood pressure * cerebral infarction
ntihypertensive therapy is a general recommendation for stroke survivors with hypertension to
reduce stroke recurrence.' 2 Many, but not all,
studies have demonstrated that antihypertensive therapy effectively reduces cardiovascular morbidity, mortality, and stroke recurrence.3-8 A potential benefit of
antihypertensive therapy is to prevent further progression of pathological changes in the brain vessels.9-12 A
decrease in blood pressure (BP), however, may reduce
cerebral blood flow (CBF) in patients with impaired
cerebral autoregulation and with hemodynamically
compromised brain tissues, potentially causing recurrent ischemic events.'3-17 Recent studies in hypertensive
patients with vascular complications or in elderly patients demonstrated that lowering BP reduces cardiovascular morbidity and mortality, but an excessive drop
in BP may paradoxically increase cardiovascular complications.18-25 The relation of diastolic BP with the
incidence of cardiac events provides a J-shaped curve
with a nadir at approximately 85 mm Hg, representing a
complex effect of BP on cardiovascular events.26-29 No
studies have confirmed a similar relation for stroke
A
recurrence.
In the present study, we evaluated retrospectively the
effect of poststroke BP on stroke recurrence. We also
determined the effects of stroke subtypes, age, and
Received April 20, 1993; final revision received July 6, 1993;
accepted July 6, 1993.
From the Cerebrovascular Division (K.I., T.Y., T.O.), Department of Medicine, and Cerebrovascular Laboratory (K.M.), Research Institute, National Cardiovascular Center, Osaka, Japan.
Reprint requests to Katsumi Irie, MD, Second Department of
Internal Medicine, Faculty of Medicine, Kyushu University. 3-1-1
Maidashi, Higashiku, Fukuoka 812, Japan.
antihypertensive treatment on the BP-stroke recurrence rate curves.
Subjects and Methods
We performed the present study on 368 consecutive
hypertensive patients (266 men, 102 women; mean age,
62 years) with brain infarction, transient ischemic attack
(TIA), and brain hemorrhage who were admitted within
3 months after stroke onset and observed for at least 6
months at the Cerebrovascular Division, National Cardiovascular Center, Japan, during the period from 1982
to 1986. Their observation period was 6 to 96 months,
with an average of 38 months.
Patients were classified into the following stroke
subtypes: (1) brain hemorrhage, (2) atherothrombotic
brain infarction (ATBI), (3) lacunar brain infarction
(LBI), (4) embolic brain infarction (EBI), (5) brain
infarction of undetermined type (BIU), and (6) TIA.
Patients without a potential cardiac source of emboli
were entered into EBI only when an occlusion of brain
vessels by an embolus or vanishing occlusion was documented by cerebral angiography. Details of our diagnostic criteria for these stroke subtypes were described
previously.303' Of 368 patients, 51 patients were classified as brain hemorrhage, 74 as ATBI, 149 as LBI, 30 as
EBI, 22 as BIU, and 42 as TIA.
Patients were diagnosed as having hypertension if
they had evidence of systolic BP (SBP) above 160
mm Hg or diastolic BP (DBP) above 95 mm Hg before
and/or 4 weeks after stroke onset or if they had received
antihypertensive medications. Baseline SBP and DBP
were determined after 4 weeks of stroke (n = 283) or just
before the initiation of antihypertensive treatment if the
treatment was needed within 4 weeks of stroke (n= 25).
Irie et al Poststroke Blood Pressure and Recurrence
1845
TABLE 1. Effect of Baseline and Poststroke Blood Pressure on Stroke Recurrence
Poststroke BP
Baseline BP
Recurrence Rate,
Recurrence Rate,
n
%/patient-year
n
%/patient-year
5.11
5.07
4.32
12.32*
8.13
109
100
81
54
24
5.30
3.98
.170
56
58
78
58
58
DBP, mm Hg
<80
80-84
85-89
90-94
>95
62
54
57
47
88
6.93
5.77
6.70
6.32
7.26
98
94
85
45
46
SBP, mm Hg
< 140
140-149
150-159
160-169
12.19t
1 1.OOt
14.75t
9.20t
3.75
6.72
Downloaded from http://stroke.ahajournals.org/ by guest on June 17, 2017
11.56§
11.31t
BP indicates blood pressure; S, systolic; and D, diastolic.
*P<.01 vs baseline SBP 150-159 mm Hg.
tP<.01 vs poststroke SBP 140-149 mm Hg.
tP<.05, §P<.01 vs poststroke DBP 80-84 mm Hg, by log-rank test.
We could not get a baseline BP for 60 patients who had
continuously received antihypertensive medications.
Mean values of poststroke SBP and DBP during the
observation period were determined by averaging all
the values recorded in the outpatient clinic at regular
intervals. Antihypertensive agents were given to 254
patients, but not to 114 during the poststroke observation period. The agents were classified into the following subgroups: calcium-channel blockers (n= 194), angiotensin converting enzyme inhibitors (n=31),
,B-blockers (n=90), thiazide derivatives (n=23), and
others (n=57). Multiple antihypertensive agents were
given in 131 patients. Antiplatelet or anticoagulant
medication was given to 133 patients with brain infarction or TIA.
We prescribed the end point of observation as the first
stroke recurrence or death from any cause. The type of
recurrent stroke was diagnosed according to the subtypes
defined above. Causes of death were divided into either
cardiovascular death or other causes of death. The
former includes death from myocardial infarction, ruptured aortic aneurysm, renal failure, and sudden death of
unknown cause. The annual stroke recurrence rate was
calculated in percentage per patient-year and then analyzed in relation to baseline SBP, baseline DBP, poststroke SBP, poststroke DBP, stroke subtypes at entry,
age, and antihypertensive and antithrombotic therapies.
Recurrence-free rate curves were obtained by using the
Kaplan-Meier method.
Statistical comparisons among the groups were performed with a one-way analysis of variance for parametric variables and with a Kruskal-Wallis test for nonparametric categories. Intergroup comparisons were
performed with Scheffe's method for parametric variables and with Duncan's method for nonparametric
categories. Recurrence-free rate was compared between the groups with the log-rank method.32 A twotailed probability value of less than 0.05 was considered
significant.
Results
Eighteen patients died during the study period: cardiovascular death in 11 and noncardiovascular cause in
7. Seven cardiovascular deaths occurred in patients with
antihypertensive treatment, which was not different in
frequency from those without such treatment. Stroke
recurrence was observed in 77 patients, among whom 51
had received antihypertensive agents. Type of recurrent
stroke was not the same as the stroke type at entry in
approximately half of the patients. Among 67 ischemic
stroke patients with recurrence, 62 (93%) recurrences
were ischemic. The recurrent stroke type in 7 brain
hemorrhage patients receiving antihypertensive agents
was characteristic: only one recurrence was hemorrhagic, but the other six were ischemic.
Annual stroke recurrence rate was 7.5% per patientyear for all patients. It was 6.9% per patient-year for
patients treated with antihypertensive agents, which was
not significantly different from the rate of 8.8% per
patient-year for patients without antihypertensive treatment. Baseline SBP and DBP had no relation to stroke
recurrence rate, except in patients with SBP of 160 to
169 mm Hg, who had a significantly higher stroke recurrence rate compared with those with SBP of 150 to 159
mm Hg (Table 1). The stroke recurrence rate was
almost the same among the five patient subgroups
classified by the baseline DBP.
Patients with poststroke SBP of 150 mm Hg or
greater had a significantly higher stroke recurrence rate
than those with poststroke SBP of 140 to 149 mm Hg.
The stroke recurrence rate in patients with poststroke
SBP of less than 140 mm Hg was not significantly
different from that in those with poststroke SBP of 140
to 149 mm Hg (Fig 1A). Patients with poststroke DBP
of 80 to 84 mm Hg had the lowest stroke recurrence rate
compared with those with poststroke DBP of less than
80 mm Hg (P<.05), 90 to 94 mm Hg (P<.01), and 95
mm Hg or greater (P<.05) (Fig 2), demonstrating a
so-called J-shaped curve with the nadir, or J point, at
Stroke Vol 24, No 12 December 1993
1846
>. 20
20
A
B
.L
20.-
15-j
15
t,1
20 -
-0- ATBI n=74
---- LBI
n=149
+ p<00s vs. 85-89
+ p<0. ns. +1' p<0.01
CL
"p1
/_--
t
Q
10 -
C 100
t
B
A
n=275
Brain Infarction
Brain Hemorrhage n=51
* p<0.01 vs. 80-84
-0-
00'
vs.
0
80-84/
p(0.00
V)
0
5-
0
*
t p<0.05 vs. 80-84
0t pa0.01 vs. 80-84
p<0.01 vs. 140-149
,
,
O-
<1490 140-149 150159 160-169 178<
85-89
80848
<80
90-94
95s
Post-stroke DBP (mmHg)
Post-stroke SBP (mmHg)
FIG 1. Line graphs show relation of blood pressure to
stroke recurrence rate. A, Poststroke systolic blood pressure (SBP). B, Poststroke diastolic blood pressure (DBP).
The log-rank test is used for statistical comparisons.
*P<.01, tP<.05, ttP<.01 different from the blood pressure range with the lowest stroke recurrence rate in each
curve.
Downloaded from http://stroke.ahajournals.org/ by guest on June 17, 2017
the range of 80 to 84 mm Hg (Fig iB). The quartile
analysis, in which patients were subdivided almost
equally into four groups according to poststroke DBP
(n=91 to 93 in each group), demonstrated that patients
in the second quartile (patients with DBP of 78.9 to 84.4
mm Hg) had the lowest recurrence rate. Patients in the
first (56.7 to 78.6 mm Hg) and the last (89.9 to 120.0
mm Hg) quartile had significantly higher recurrence
rates than those in the second quartile, again demonstrating the J-curve phenomenon.
The J-curve phenomenon in poststroke DBP was not
obvious in patients with brain hemorrhage (Fig 3A).
Brain hemorrhage patients with lower poststroke DBP
had less frequent recurrence. In subset analysis of
patients with ATBI and LBI, the J point in poststroke
DBP was higher in the former than in the latter (Fig
3B).
Comparisons of baseline clinical features among the
four patient subgroups classified by poststroke DBP
revealed that patients' age was not the same among the
four subgroups (P<.01, one-way analysis of variance;
| III
r
_
90_- i _s
80 0
\.
................
70 -
(U
05
M
cc 600
U-
50 -
0
40 -
h-
U)
30 20 -
*
Post-stroke DBP
<80
- 80-84
85-89
- - - 90-94
*
95<
**
p<0.05 vs. 80-84
p<0.01 vs. 80-84
10 (J I
0
-
12
24
36
*
48
.
60
72
Follow-up period (month )
FIG 2. Graph of Kaplan-Meier curve for probability of
recurrence-free survival by poststroke diastolic blood
pressure (DBP). The log-rank test is used for statistical
comparisons. *P<.05, **P<.01 different from the patient
group with poststroke DBP between 80 and 84 mm Hg.
0
0
<80
80-84
85-89
Post-stroke DBP (mmHg)
90<
<80
80-84
85-80
90<
Post-stroke DBP (mmHg)
FIG 3. Line graphs show subgroup comparisons of
stroke recurrence rate with poststroke diastolic blood
pressure (DBP). A, Brain hemorrhage and brain infarction. Patients with transient ischemic attack are not included in this analysis. B, Atherothrombotic brain infarction (ATBI) and lacunar infarction (LBI). *P<.01, tP<.05,
tP<.05, 14P<.01 different from the blood pressure range
with the lowest stroke recurrence rate in each curve.
Table 2). Patients aged older than 65 years had a higher
stroke recurrence rate than the younger patients (11.4%
per patient-year and 4.8% per patient-year, P<.05). A
trend of the J curve was noted in both groups (Table 3).
When the patients were fractionated into four groups
according to age, ie, 45 to 54, 55 to 64, 65 to 74, and 75
to 84 years, the stroke recurrence rate was consistently
the least frequent in patients with poststroke DBP of 80
to 84 mm Hg throughout all age groups, although the
result was not statistically significant because of a small
number of patients in each patient subgroup (data not
shown).
The frequency of treatment with antihypertensive
agents was different among the patient subgroups determined by the level of poststroke DBP (P<.01,
Kruskal-Wallis test; Table 2). The stroke recurrence
rates were not significantly different between patients
with and without antihypertensive agents. Subgroup
analysis of the relation between stroke recurrence rate
and poststroke DBP levels demonstrated that the
J-curve phenomenon was noted both in patients with
and without antihypertensive treatment (Table 3).
Other baseline characteristics, including stroke subtype
at entry, male-to-female ratio, other major risk factors
of stroke (diabetes mellitus, hyperlipidemia, ischemic
heart disease, arrhythmia, prior stroke, etc), and frequency of antiplatelet and anticoagulant treatment were
almost the same among the subgroups. History of
ischemic heart disease, including myocardial infarction
and angina pectoris, did not increase stroke recurrence
rate (9.1% per patient-year in 49 patients with ischemic
heart disease versus 7.2% in 319 without ischemic heart
disease; P=NS) or affect the J-curve phenomenon.
Both groups experienced the lowest stroke recurrence
rate at the DBP range of 80 to 84 mm Hg.
To clarify the interaction between SBP and DBP, we
classified patients into three groups according to poststroke SBP, then determined the relations of poststroke
DBP to stroke recurrence rate in each group. In every
group, stroke recurrence rate was the lowest in patients
with poststroke DBP of 80 to 84 mm Hg and demonstrated a J-shaped curve (Table 3). Stroke recurrence
rate increased with elevation of poststroke SBP in the
groups with poststroke DBP of 85 mm Hg or greater.
Irie et al Poststroke Blood Pressure and Recurrence
1847
TABLE 2. Historical Features of Patients Classified According to Ranges of Poststroke Diastolic
Blood Pressure
Poststroke DBP, mm Hg
<80
80-84
85-89
>90
(n=98)
(n=94)
(n=85)
(n=91)
22
35
9
6
17
9
69/29
68.0
22
34
9
7
8
14
69/25
61.7*
15
37
6
4
7
16
60/25
61.9*
69/22
59.7*
35
24
7
19
6
15
28
4
146.8
77.8
140.6
75.9
22
24
7
10
5
11
21
2
152.5
86.3
145.4
82.2
32
22
10
8
2
6
18
4
153.8
90.2
147.2
87.3
28
19
8
12
2
6
26
3
161.2
96.5
159.6
96.6
Stroke type at entry
ATBI
LBI
EBI
BIU
TIA
HEM
Male/female
Downloaded from http://stroke.ahajournals.org/ by guest on June 17, 2017
Mean age, y
Risk factors except for hypertension
Diabetes
Hyperlipidemia
15
43
6
5
10
12
Obesity
Ischemic heart disease
Rheumatic heart disease
Arrhythmia
History of BI
History of HEM
Baseline SBP, mm Hg
Baseline DBP, mm Hg
Poststroke SBP, mm Hg
Poststroke DBP, mm Hg
Poststroke medication
56t
63t
58t
77
Antihypertensive
22
23
25
33
Antiplatelet
1
4
8
9
Anticoagulant
DBP indicates diastolic blood pressure; ATBI, atherothrombotic brain infarction; LBI, lacunar brain infarction; EBI,
embolic brain infarction; BIU, brain infarction of unknown etiology; TIA, transient ischemic attack; HEM, brain
hemorrhage; BI, brain infarction; and SBP, systolic blood pressure.
*P<.01 vs poststroke DBP <80 mm Hg by Scheffe's method.
tP<.01, tP<.05 vs poststroke DBP >90 mm Hg by Duncan's method.
The J-curve phenomenon with DBP was likely to exist
even in patients with isolated systolic hypertension, with
SBP of 160 mm Hg or greater and DBP of less than 90
mm Hg.
Discussion
The present study demonstrates that the relation of
stroke recurrence rate to poststroke DBP is consistent
with a J-shaped curve. The nadir of the curve, or J
point, existed at the DBP range of 80 to 84 mm Hg.
Because our object was to determine the optimal range
of BP control, we did not select the DBP range by
quartile or quintile method but used an arbitrary ranging of DBP, which may be more appropriate from a
clinical point of view. Baseline SBP and DBP had no
relation to stroke recurrence, except for a high stroke
recurrence rate in patients with baseline SBP of 160 to
169 mm Hg. Poststroke SBP had a positive and linear
correlation with stroke recurrence. Isolated systolic
hypertension had no specific effect on the J-curve
phenomenon with poststroke DBP.
Several epidemiologic and clinical studies have found
that hypertension or elevated baseline SBP and DBP
entails a risk of stroke recurrence.633-35 Hier et a135
reported that diastolic hypertension (greater than 100
mm Hg) at the time of the initial examination was a
significant risk factor for stroke recurrence. The relative
risk ratio, however, was quite modest (95% confidence
interval, 1.003 to 1.021). In a community study in
Rochester, Minn, neither level of BP before the first
stroke nor management of hypertension had any effect
on mortality and stroke recurrence rates throughout the
follow-up period.6 Acute lowering of BP may cause
ischemic stroke in elderly hypertensive patients and
some stroke survivors.13'15-17 However, there is no definite evidence that sustained reduction in BP enhances
stroke recurrence. Most recent studies in hypertensive
patients without stroke demonstrated that overall car-
1848
Stroke Vol 24, No 12 December 1993
TABLE 3. Stroke Recurrence Rate by Poststroke Diastolic Blood Pressure Range in Relation to Stroke Type, Age,
Antihypertensive Treatment, and Poststroke Systolic Blood Pressure
Stroke Type
Age, y
Antihypertensive
Treatment
Poststroke SBP, mm Hg
DBP,
BI
ATBI
LBI
<65
mm Hg
HEM
>65
Treated
Nontreated
<140
140-159
>160
3.74
9.47
4.50 11.63
9.62**
8.1 1*
7.33
12.35*
<80
6.55
9.84*t
18.30
4.12
2.67
0.89
2.09
80-84
5.68
6.90
4.30
2.39
2.67
4.51
4.19
7.44
5.60
8.11
6.03
1.98
3.36 13.41
1.30
85-89
6.62
6.92
16.36
>90
13.04 12.03**
9.87
22.09**
5.43
10.78
18.00t 1 1.01** 9.93 15.41
13.47
Stroke recurrence rate values are percentage per patient-year. DBP indicates diastolic blood pressure; SBP, systolic blood pressure;
HEM, brain hemorrhage; BI, brain infarction (except for transient ischemic attack); ATBI, atherothrombotic B1; and LBI, lacunar B.
*P<.05, **P<.01 vs poststroke DBP 80-84 mm Hg.
tP<.05 vs poststroke DBP 85-89 mm Hg, by log-rank test.
Poststroke
Downloaded from http://stroke.ahajournals.org/ by guest on June 17, 2017
diovascular events occurred in a J-shaped manner with
DBP,20-25,28 although this is not fully confirmed.36 The
main cardiovascular event in these studies was myocardial infarction, and the J point was usually present at
DBP of 84 to 90 mm Hg. Reduced coronary perfusion
due to excessive diastolic hypotension may not only
cancel benefits of antihypertensive therapy but also
cause a paradoxical increase in ischemic events. We can
also apply a similar scenario to the relation of poststroke BP to stroke recurrence.
In the present study, the J-curve phenomenon was
observed in patients with brain infarction but not in
those with brain hemorrhage. The J point was higher in
patients with ATBI than in patients with LBI. These
results suggest that hypertensive patients with ATBI
were particularly vulnerable to low poststroke DBP.
The lower limit of autoregulation of CBF shifts to a
higher level of BP in hypertensive than in normotensive
subjects, so that only mild hypotension or normalization
of BP may induce a decrease in CBF.'3 Hemodynamically compromised brain tissues in some patients with
ATBI are theoretically vulnerable to a decrease in
systemic BP, although effects of chronic hemodynamic
failure on stroke recurrence remain unknown.'4,37 38
These pathophysiological mechanisms may be responsible for a paradoxical increase in stroke recurrence rate
at the lower poststroke DBP.
Dependency of coronary circulation on DBP but not
on SBP is the most likely explanation for the presence of
the J-curve phenomenon only for DBP in ischemic
heart disease. In contrast, both SBP and DBP have a
relation to tissue perfusion in the brain. In the Framingham Study, the probability of occurrence of a brain
infarction was predicted by SBP and DBP level.39
Therefore, not only DBP but also SBP may have a
J-curve relation to stroke recurrence, although our data
did not support this speculation. DBP may be more
important than SBP in determining perfusion pressure
and blood flow in the brain. This concept is supported
by recent observations with ultrasonography demonstrating that the diastolic intravascular blood flow and
velocity to the brain were kept at a higher level than
those to other organs.40-42
Because of the retrospective nature of the study, we
could not adjust patients' age and control the use of
antihypertensive agents. We found that patients with a
poststroke DBP of less than 80 mm Hg were the oldest
among the patient subgroups classified by ranges of
poststroke DBP, which is in common with a hyperten-
sive population.43.44 Stroke recurrence rate was higher
in patients older than 65 years than in the younger
patients over all ranges of poststroke DBP. Marquardsen33 suggested that advancing age is accompanied by an
increase in stroke recurrence, but this aging effect was
absent in other studies.3' Previous studies demonstrated
that the J-curve phenomenon for myocardial infarction
was consistently observed even in elderly hypertensive
patients.24,25,45 We could not determine the net effects of
poststroke DBP, independent of aging, on stroke recurrence, although similar J-curve trends in both the
younger (younger than 65 years) and older (65 years or
older) patient subgroups were observed, even in age
subgroups classified by 10-year intervals, suggesting that
the J-curve phenomenon is independent of an aging
effect.
Patients treated with antihypertensive drugs were
most frequently in the highest poststroke DBP range. In
some patients, DBP dropped spontaneously without
medication. Both patients with antihypertensive medication and those without medication exhibited the
J-curve phenomenon. A previous study reported that
the J-curve phenomenon for myocardial infarction was
dependent on DBP level but not on antihypertensive
medication.27 In ischemic heart disease, subclinical
myocardial damage may cause hypotension that precedes symptomatic events. However, we cannot apply
this possibility to stroke occurrence. Sutton-Tyrrell et
a146 reported recently that among patients with isolated
systolic hypertension, low DBP is a marker for carotid
stenosis. This observation may in part explain the
relation between the low poststroke DBP and an increase in stroke recurrence rate in the present study,
although we could not find an inverse correlation of
DBP with stroke recurrence rate among the isolated
systolic hypertension group but did confirm the J-curve
even in patients with LBI.
Prior intervention studies have consistently confirmed the beneficial effects of antihypertensive treatment on stroke occurrence in young patients with severe
arterial hypertension but not in older patients or patients with milder hypertension.3-8 Many factors, including stroke subtypes, hemodynamic state in the brain,
age, baseline BP level, and degree and speed of decrease in BP, may influence recurrence in hypertensive
stroke patients. Well-controlled prospective studies are
needed to determine the optimal control levels of
poststroke BP in each stroke subtype for preventing
recurrent stroke.-
Irie et al Poststroke Blood Pressure and Recurrence
Acknowledgments
This study was supported in part by Research Grants for
Cardiovascular Diseases 62-A2, 2-A2, and 5-A5 from the
Ministry of Health and Welfare, Japan. The authors are
grateful to Drs Takeshi Miyashita, Masahiro Yasaka, Yutaka
Kiyohara, and Yasushi Okada for their valuable comments
and suggestions, and to Dr Marc Fisher for reviewing the
manuscript.
References
Downloaded from http://stroke.ahajournals.org/ by guest on June 17, 2017
1. 1988 Joint National Committee. The 1988 report of the Joint
National Committee on detection, evaluation, and treatment of
high blood pressure. Arch Intern Med. 1988;148:1022-1038.
2. The WHO Task Force on Stroke and Other Cerebrovascular Disorders. Stroke-1989: recommendations on stroke prevention,
diagnosis, and therapy. Stroke. 1989;20:1407-1431.
3. Carter AB. Hypotensive therapy in stroke survivors. Lancet. 1970;
1:485-489.
4. Beevers DG. Antihypertensive treatment and the course of established cerebral vascular disease. Lancet. 1973;1:1407-1409.
5. Johnston JH, Beevers DG, Dunn FG, Larkin H, Titterington DM.
The importance of good blood pressure control in the prevention
of stroke recurrence in hypertensive patients. Postgrad Med J.
1981;57:690-693.
6. Meissner I, Whisnant JP, Garraway WM. Hypertension management and stroke recurrence in a community (Rochester, Minnesota, 1950-1979). Stroke. 1988;19:459-463.
7. Hypertensive Stroke Cooperative Study Group: Effect of antihypertensive treatment on stroke recurrence. JAMA. 1974;229:
409-418.
8. Kinnander G, Viitanen M, Asplund K. Beta-adrenergic blockade
after stroke: a preliminary closed cohort study. Stroke. 1987;18:
240-243.
9. Ross R. The pathogenesis of atherosclerosis: an update. N Engl J
Med. 1986;314:488-500.
10. Spence JD. Antihypertensive drugs and prevention of atherosclerotic stroke. Stroke. 1986;17:808-810.
11. Harper SL. Effect of antihypertensive treatment on the cerebral
microvasculature of spontaneously hypertensive rats. Stroke. 1987;
18:450-456.
12. Ibayashi S, Ogata J, Sadoshima S, Fujii K, Yao H, Fujishima M.
The effect of long-term antihypertensive treatment on medial
hypertrophy of cerebral arteries in spontaneously hypertensive
rats. Stroke. 1986;17:515-519.
13. Strandgaard S, Olesen J, Skinh0j E, Lassen NA. Autoregulation of
brain circulation in severe arterial hypertension. Br Med J. 1973;1:
507-510.
14. Kuriyama Y, Sawada T, Omae T. Antihypertensive drugs and
cerebral circulation. In: Omae T, Zanchetti A, eds. How Should
Elderly Hypertensive Patients Be Treated? Tokyo, Japan: SpringerVerlag; 1989:69-81.
15. Jackson G, Pierscianowski TA, Manhon W, Condon J. Inappropriate antihypertensive therapy in the elderly. Lancet. 1976;2:
1317-1318.
16. Jansen PA, Schulte BPM, Meyboom RHB, Gribnau FWJ. Antihypertensive treatment as a possible cause of stroke in the elderly.
AgeAging. 1986;15:129-138.
17. Dobkin BH. Orthostatic hypotension as a risk factor for symptomatic occlusive cerebrovascular disease. Neurology. 1989;39:
30-34.
18. Anderson TW. Re-examination of some of the Framingham bloodpressure data. Lancet. 1978;2:1139-1141.
19. Stewart IMG. Relation of reduction in pressure to first myocardial
infarction in patients receiving treatment for severe hypertension.
Lancet. 1979;1:861-865.
20. Cruickshank JM, Thorp JM, Zacharias FJ. Benefits and potential
harm of lowering high blood pressure. Lancet. 1987;1:581-583.
21. Coope J, Warrender TS. Lowering blood pressure. Lancet. 1987;
2:518.
22. Samuelsson 0, Wilhelmsen L, Anderson OK, Pennert K, Berglund
G. Cardiovascular morbidity in relation to change in blood
pressure and serum cholesterol levels in treated hypertension:
results from the primary prevention trial in Gbteborg, Sweden.
JAMA. 1987;258:1768-1776.
23. Fletcher AE, Beevers DG, Bulpitt CJ, Butler A, Coles EC, Hunt
D, Munro-Faure AD, Newson R, O'Riordan PW, Petrie JC, Raja-
24.
25.
26.
27.
28.
1849
gopalan B, Rylance PB, Twallin G, Webster J, Dollery CT. The
relationship between a low treated blood pressure and IHD mortality: a report from the DHSS Hypertension Care Computing
Project (DHCCP). J Hum Hypertens. 1988;2:11-15.
Staessen J, Bulpitt C, Clement D, De Leeuw P, Fagard R, Fletcher
A, Forette A, Leonetti G, Nissinen A, O'Malley K, Tuomilehto J,
Webster J, Williams BO. Relation between mortality and treated
blood pressure in elderly patients with hypertension: report of the
European Working Party on High Blood Pressure in the Elderly.
Br Med J. 1989;298:1552-1556.
McClskey LW, Psaty BM, Koepsell TD, Aagaard GN. Level of
blood pressure and risk of myocardial infarction among treated
hypertensive patients. Arch Intern Med. 1992;152:513 -520.
Cruickshank JM. Coronary flow reserve and the J curve relation
between diastolic blood pressure and myocardial infarction. Br
Med J. 1988;297:1227-1230.
Coope J. Hypertension: the cause of the J-curve. J Hum Hypertens.
1990;4:1-4.
Farnett L, Mulrow CD, Linn WD, Lucey CR, Tuley MR. The
J-curve phenomenon and the treatment of hypertension: is there a
point beyond which pressure reduction is dangerous? JAMA. 1991;
265:489-495.
29. Weinberger MH. Do no harm: antihypertensive therapy and the 'J'
curve. Arch Intern Med. 1992;152:473-476.
30. Yamaguchi T, Minematsu K, Choki J. Arterial embolism. In:
Wood JH, ed. Cerebral Blood Flow: Physiologic and Clinical Aspects.
New York, NY: McGraw-Hill Book Co; 1987:503-517.
31. Minematsu K, Yamaguchi T, Omae T. 'Spectacular shrinking
deficit': rapid recovery from a major hemispheric syndrome by
migration of an embolus. Neurology. 1992;42:157-162.
32. Armitage P, Berry G. The logrank test. In: Statistical Methods in
Medical Research. 2nd ed. Oxford, England: Blackwell Scientific
Publications; 1987:429-433.
33. Marquardsen J. The natural history of acute cerebrovascular
disease: a retrospective study of 769 patients. Acta Neurol Scand
Suppl. 1969;45(suppl 38):11-188.
34. Sacco RL, Wolf PA, Kannel WB, McNamara PM. Survival and
recurrence following stroke: the Framingham study. Stroke. 1982;
13:290-295.
35. Hier DB, Foulkes MA, Swiontoniowski M, Sacco RL, Gorelick PB,
Mohr JP, Price TR, Wolf PA. Stroke recurrence within 2 years
after ischemic infarction. Stroke. 1991;22:155-161.
36. MacMahon S, Peto R, Cutler J, Collins R, Sorlie P, Neaton J,
Abbott R, Godwin J, Dyer A, Stamler J. Blood pressure, stroke,
and coronary heart disease, part I: prolonged difference in blood
pressure: prospective observational studies corrected for the
regression dilution bias. Lancet. 1990;1:335:765-774.
37. Powers WJ, Tempel LW, Grubb RL Jr. Influence of cerebral
hemodynamics on stroke risk: one-year follow-up of 30 medically
treated patients. Ann Neurol. 1989;25:325-330.
38. Hasegawa Y, Yamaguchi T, Tsuchiya T, Minematsu K, Nishimura
T. Sequential change of hemodynamic reserve in patients with
major cerebral artery occlusion or severe stenosis. Neuroradiology.
1992;34:15-21.
39. Kannel WB, Wolf PA, Verter J, McNamara PM. Epidemiologic
assessment of the role of blood pressure in stroke: the Framingham
study. JAMA. 1970;214:301-310.
40. Garth KE, Carroll BA, Sommer FG, Oppenheimer DA. Duplex
ultrasound scanning of the carotid arteries with velocity spectrum
analysis. Radiology. 1983;147:823-827.
TM, Nornes H. Noninvasive transcranial
Doppler ultrasound recording of flow velocity in basal cerebral
arteries. J Neurosurg. 1982;57:769-774.
42. Grolimund P, Seiler RW. Age dependence of the flow velocity in
41. Aaslid R, Markwalder
43.
44.
45.
46.
the basal cerebral arteries: a transcranial Doppler ultrasound
study. Ultrasound Med Biol 1988;14:191-198.
Kaplan NM. Primary hypertension: natural history. In: Kaplan
NM, ed. Clinical Hypertension. 5th ed. Baltimore, Md: Williams &
Wilkins Co; 1990:112-135.
Katsuki S, Hirota Y, Akazome T, Takeya S, Omae T, Takano S.
Epidemiological studies on cerebrovascular diseases in Hisayama,
Kyushu island, Japan. Jpn Heart J. 1964;5:12-36.
Cox JP, O'Brien E, O'Malley K. The J-shaped curve in elderly
hypertensives. J Hypertens. 1992;10(suppl 2):S17-S23.
Sutton-Tyrrell K, Alcorn HG, Wolfson SK, Kelsey SF, Kuller LH.
Predictors of carotid stenosis in older adults with and without
isolated systolic hypertension. Stroke. 1993;24:355-361.
The J-curve phenomenon in stroke recurrence.
K Irie, T Yamaguchi, K Minematsu and T Omae
Downloaded from http://stroke.ahajournals.org/ by guest on June 17, 2017
Stroke. 1993;24:1844-1849
doi: 10.1161/01.STR.24.12.1844
Stroke is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
Copyright © 1993 American Heart Association, Inc. All rights reserved.
Print ISSN: 0039-2499. Online ISSN: 1524-4628
The online version of this article, along with updated information and services, is located on the
World Wide Web at:
http://stroke.ahajournals.org/content/24/12/1844
Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published
in Stroke can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial Office.
Once the online version of the published article for which permission is being requested is located, click
Request Permissions in the middle column of the Web page under Services. Further information about this
process is available in the Permissions and Rights Question and Answer document.
Reprints: Information about reprints can be found online at:
http://www.lww.com/reprints
Subscriptions: Information about subscribing to Stroke is online at:
http://stroke.ahajournals.org//subscriptions/