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Coffee consumption in hypertensive men in older
middle-age and the risk of stroke: the Honolulu Heart
Program.
Hakim AA; Ross GW; Curb JD; Rodriguez BL; Burchfiel CM; Sharp
DS; Yano K; Abbott RD
Division of Biostatistics and Epidemiology, University of
Virginia School of Medicine, Charlottesville 22908, USA.
J Clin Epidemiol (England) Jun 1998, 51 (6)
p487-94
OBJECTIVE: To examine the association between coffee
consumption and the development of stroke in men at high risk
for cardiovascular disease.
METHODS: Coffee intake was observed from 1965 to 1968 in a
cohort of men enrolled in the Honolulu Heart Program with
follow-up for incident stroke over a 25-year period. Subjects
were 499 hypertensive men (having systolic or diastolic blood
pressures at or above 140 and 90 mm Hg, respectively) in older
middle-age (55 to 68 years) when follow-up began. Past and
current cigarette smokers were excluded from follow-up.
RESULTS: In the course of follow-up, 76 men developed a
stroke. After age-adjustment, risk of thromboembolic stroke
increased significantly with increases in coffee consumption
(P = 0.002). No relationships were observed with hemorrhagic
stroke. When adjusted for other factors, the risk of
thromboembolic stroke was more than doubled for men who
consumed three cups of coffee per day as compared to
nondrinkers of coffee (RR = 2.1; 95% CI = 1.2-3.7).
CONCLUSIONS: Although in need of further confirmation,
consumption of coffee appears to be positively associated with
an increased risk of thromboembolic stroke in hypertensive men
in older middle-age. Findings suggest that it may be prudent
to advise older middle-aged men with hypertension who consume
large amounts of coffee to consider reducing their coffee
intake.
The white blood cell and plasma fibrinogen in
thrombotic stroke. A significant correlation.
Belch J; McLaren M; Hanslip J; Hill A; Davidson D
University Department of Medicine, Ninewells Hospital &
Medical School, Dundee, Scotland.
Int Angiol (Italy) Jun 1998, 17 (2) p120-4
OBJECTIVES: Thrombotic stroke is a common disorder with
considerable mortality and morbidity. Risk factors for stroke
include cigarette smoking, hypertension and hyperlipidaemia
and these have been linked to abnormalities of haemorrheology
and coagulation such as increased fibrinogen. Other
haemorrheological abnormalities have also been documented.
These include an elevation in the white blood cell (WBC)
count. The aim of our study was to evaluate plasma fibrinogen,
WBC aggregation and the release of free radicals in thrombotic
stroke.
EXPERIMENTAL DESIGN: Thirty-four patients with thrombotic
stroke were enrolled in the study. The data were compared to
58 matched controls.
SETTING: This study was carried out in Ninewells Hospital,
Dundee on patients previously admitted to the medical wards
with acute stroke.
MEASURES: Plasma fibrinogen, WBC aggregation and plasma
malondialdehyde (MDA) were measured in this study.
RESULTS: As expected, the stroke patients have a
significantly higher fibrinogen level (4.3+/-1.2 g/dl versus
3.1+/-0.6, p<0.001). WBC aggregation is also increased in
the patient group (47.5+/-10.4% versus 42.7+/-10.6, p=0.036),
as is plasma MDA (8.6+/-2.0 micromol/l versus 7.1+/-1.07,
p<0.001). The factor VIII von Willebrand factor antigen
measured as a marker as vascular damage was also significantly
higher in the patient group (251+/-87% versus 182+/-64,
p<0.001). There was also a statistically significant
correlation between fibrinogen level and WBC aggregation, and
fibrinogen and MDA. These are both statistically significant
p=0.012 and p<0.001 respectively.
CONCLUSIONS: We believe our study suggests that enhanced
WBC aggregation/adhesion with release of free radicals may be
another mechanism whereby fibrinogen exerts its known
detrimental effect in stroke development. This may allow
planning of therapeutic strategies as yet undeveloped.
Elevated serum glycosaminoglycans with
hypomagnesemia in patients with coronary artery disease &
thrombotic stroke.
Kumari KT; Augustine J; Leelamma S; Kurup PA; Ravikumar A;
Sajeesh K; Eapen S; Nair AR; Vijayalekshmi N; Karthikeyan S;
et al
Department of Biochemistry, University of Kerala.
Indian J Med Res (India) Mar 1995, 101 p115-9
Elevated levels of serum glycosaminoglycans (GAG),
associated with hypomagnesemia were observed in patients of
proven CAD and thrombotic stroke in Kerala. Serum lipid
profile was normal in the majority of these patients,
indicating that elevated serum GAG may be an even more
reliable indicator of atherosclerosis than elevated serum
total cholesterol or LDL cholesterol. Autopsy samples of
carotid artery and aorta which had atheroma showed
significantly higher GAG when compared to samples which showed
no atheroma. Serum Mg levels were significantly lower in CAD
and thrombotic stroke patients as compared to controls. Mg
deficiency may be one of the factors involved in the increased
level of GAG.
Serum lipids and lipoprotein abnormalities in
patients with thrombotic stroke--with exploring the protective
role of HDL subfractions.
Shieh SM; Shen MM; Tsai WJ; Shiuan LR; Wang DJ
Proc Natl Sci Counc Repub China [B] (Taiwan) Oct 1985, 9 (4)
p298-304
The main purpose of this report is to demonstrate the
presence of subfractions in serum HDL and to explore their
role in the pathogenesis of thrombotic stroke Preparative
untracentrifugation was used to isolate the differing density
fractions of serum lipoproteins, and 2-27% polyacrylamide
gradient gel electrophoresis was used to identify the
character of the HDL subfractions. The study was performed on
59 Chinese males, in whom 31 were patients with thrombotic
stroke affecting the cerebral cortex diagnosed by neurological
examination and computed tomography; and the others grouped as
healthy control. The age and Broca index of both groups were
similar. The serum levels of total cholesterol and
LDL-cholesterol were normal. However, in the thrombotic stroke
group HDL-cholesterol was significantly lower and correlated
inversely with both significantly higher levels of
VLDL-cholesterol (r=-0.5392, p less than 0.01) and
VLDL-triglyceride (r=-0.5866, p less than 0.01). The serum
levels of total triglycerides and LDL-triglyceride were also
significantly higher in patient with thrombotic stroke. The
mean area percentage of HDL2b subfraction measured in the
diameter range as determined by gradient gel electrophoresis
was significantly lower and HDL2 also showed the same tendency
in patients with thrombotic stroke. Our finding was consistent
with the postulation that HDL2 or HDL2b in in particular,
probably played a more protective role than any other HDL
subfractions against thrombotic stroke, one of the major
atherosclerotic complications.
Effect of piracetam on recovery and rehabilitation
after stroke: a double-blind, placebo-controlled study.
Enderby P, Broeckx J, Hospers W, Schildermans F, Deberdt
W
Speech and Language Therapy Research Unit, Frenchay Hospital,
Bristol, England.
Clin Neuropharmacol 1994 Aug;17(4):320-31
The nootropic agent piracetam has been shown to improve
learning and memory, and it may, by this means, facilitate
recovery and rehabilitation after a stroke. We report the
results of a pilot study exploring its effects in patients
undergoing rehabilitation after acute cerebral infarction in
the carotid artery territory. We compared piracetam and
placebo, each given for 12 weeks, in a multicenter,
double-blind, randomized trial of parallel-group design;
testing was performed at baseline (6-9 weeks poststroke),
weeks 5 and 12, and, in fewer patients, 12 weeks after
termination of treatment. Standardized tests of activities of
daily living (Barthel Index, Kuriansky Test), aphasia (Aachen
Aphasia Test), and perception (Rivermead Perception Assessment
Battery) were the primary efficacy variables. Of 158 patients,
137 (81 males, 56 females) were studied after treatment and 88
at 24-week follow-up. Thirty patients on piracetam (45%) and
37 on placebo (53%) were aphasic on entry. Both groups,
including the subgroups with aphasia, were well matched at
baseline for demographic data, stroke sequelae, type and
severity of aphasia, and prognostic parameters. Multivariate
analysis of Aachen Aphasia subtest scores showed a significant
overall improvement relative to baseline in favor of piracetam
(p = 0.02) at 12 weeks. This was not seen at 24 weeks when,
however, fewer patients were available for evaluation so that
we could neither confirm nor deny whether improvement was
maintained after cessation of piracetam. We were unable to
demonstrate an effect on tests of activities of daily living
and could neither confirm nor exclude an effect on perceptual
deficit. We have shown an improvement in aphasia in patients
undergoing rehabilitation after a stroke after 12 weeks'
treatment with piracetam that requires confirmation in further
studies.
The role of piracetam in the treatment of acute and
chronic aphasia.
Huber W
Department of Neurology and School of Logopedics,
Rheinisch-Westfalische Hochschule (RWTH), Aachen,
Germany.
Pharmacopsychiatry 1999 Mar;32 Suppl 1:38-43
Piracetam has been shown to improve speech in aphasic
patients. This paper reviews the evidence for this benefit in
aphasic patients with acute stroke and, in conjunction with
language treatment, in post-acute and chronic aphasia. Early
double-blind, placebo-controlled trials in acute stroke showed
improvement in several neurologic parameters including
aphasia. Subsequently two randomized double-blind
placebo-controlled studies were performed which utilised the
Aachen Aphasia Test (AAT), a validated and standardized
procedure, to assess language function. Patients received
placebo or piracetam 4.8g daily for 12 weeks in one study and
for 6 weeks in the other. In both studies patients received
concomitant intensive speech therapy; one included patients
6-9 weeks after stroke while in the other the duration of
aphasia varied between 4 weeks and 3 years. Compared with
placebo there was improvement in both studies on piracetam in
all 5 subtests of the AAT and significant overall improvement
in aphasia. This indicated that, given in conjunction with
language therapy, piracetam improved speech in patients with
post-acute and chronic aphasia. In the Piracetam in Acute
Stroke Study (PASS), of 927 patients treated within 12 hours
of the onset of acute ischemic stroke, 373 were aphasic.
Treatment consisted of placebo or an intravenous bolus of 12g
piracetam, 12g piracetam daily for 4 weeks and 4.8 g daily for
a further 8 weeks. After 12 weeks significantly more patients
(approximately 10%, P=0.04) had recovered from aphasia on
piracetam than placebo while in 197 patients treated within 7
hours of stroke onset, the difference in favor of piracetam
was 16% (P= 0.02). These studies indicate that piracetam
improves aphasia in acute stroke and, as an adjuvant to
language therapy, in post-acute and chronic aphasia.
The clinical safety of high-dose piracetam--its use
in the treatment of acute stroke.
De Reuck J, Van Vleymen B
Department of Neurology, University Hospital, Ghent,
Belgium.
Pharmacopsychiatry 1999 Mar;32 Suppl 1:33-7
Recent post-marketing surveillance reports have confirmed
the benign safety profile and lack of organ toxicity shown by
piracetam during its 25 years of clinical usage. Tolerance has
proved equally good with the more recent use of larger doses
(up to 24 g/day) for the long-term control of cortical
myoclonus and when given intravenously to patients with acute
stroke. This paper provides a brief review of these findings
and records the safety of piracetam as found in the Piracetam
in Acute Stroke Study (PASS), a randomized multicenter
placebo-controlled study in 927 patients with acute ischemic
stroke. Patients receive one intravenous bolus injection of
placebo or 12 g piracetam, piracetam 12 g daily for 4 weeks
and maintenance treatment for 8 weeks. The major results have
been reported (De Deyn et al., Stroke 28 [1997] 2347-2352).
Safety was assessed taking into account adverse events
including abnormal laboratory test results and mortality.
Death within 12 weeks occurred more frequently in the
piracetam group but the difference from placebo was not
significant. Of many potential risk, prognostic and
treatment-related factors examined by logistic regression, 6
contributed significantly to death of which the most important
were initial severity of stroke and age. Neither treatment nor
any treatment-related factor contributed significantly to
death. Adverse events were similar in frequency, type and
severity in piracetam and placebo groups. Events of cerebral,
non-cerebral and uncertain origin likewise occurred with
similar frequency. Few patients discontinued because of
adverse events. There was no difference between treatments in
the frequency of events associated with bleeding, including
hemorrhagic transformation of infarction. An important finding
was that, of 31 patients with primary hemorrhagic stroke
enrolled, 3 piracetam-treated patients died compared with 6 on
placebo. The results suggest that piracetam in high dosage may
be given to patients with acute stroke without significant
adverse effects.
Neuroprotective therapy.
Hickenbottom SL, Grotta J
Department of Neurology, University of Texas at Houston
Medical School, 77030, USA.
Semin Neurol 1998;18(4):485-92
The concept of neuroprotection relies on the principle that
delayed neuronal injury occurs after ischemia. The phenomenon
of the "ischemic cascade" has been described, and each step
along this cascade provides a target for therapeutic
intervention. In animal models of global and focal cerebral
ischemia, numerous preclinical studies have demonstrated
various agents to be neuroprotective at different steps along
this cascade. A wide variety of drugs has also been studied in
humans. Ten classes of neuroprotective agents have reached
phase III efficacy trials but have shown mixed results. They
include calcium channel antagonists, NMDA receptor
antagonists, lubeluzole, CDP-choline, the free radical
scavenger tirilizad, anti-intercellular adhesion molecule-1
(ICAM-1) antibody, GM-1 ganglioside, clomethiazole, the sodium
channel antagonist fosphenytoin, and piracetam. In the future,
clinicians may have an armamentarium of treatments for acute
ischemic stroke at their disposal, with a combination of
agents directed at different sites in the ischemic cascade
being the ultimate goal.
Acute treatment of stroke. PASS group. Piracetam
Acute Stroke Study.
De Deyn PP, Orgogozo JM, De Reuck J
Lancet 1998 Jul 25;352(9124):326
No abstract.
[Piracetam treatment in ischemic stroke].
Tomczykiewicz K, Domzal T
Kliniki Neurologicznej Centralnego Szpitala Klinicznego
Wojskowej Akademii Medycznej, Warszawie.
Neurol Neurochir Pol 1997 Nov-Dec;31(6):1101-9
Comment on Lancet 1998 May 16;351(9114):1447-8
The increase of interest in piracetam in the treatment of
stroke has been noticed lately. The reason of that is the
unique double-action of this drug which depends on: 1. its
effect on vascular system, and 2. improving of the metabolic
process in a nerve cell. The purpose of our work was the
evaluation of the therapeutic action of piracetam in
comparison with other drugs, which are applied in treating
stroke. 171 patients were examined, and piracetam was given to
40 of them. The effects of the treatment were evaluated after
14 days of using piracetam in dose of 12.0 g i.v. The authors
estimate, that this drug is efficient in ischaemic stroke.
However, its definite superiority over other drugs has not
been firmly stated.
Treatment of acute ischemic stroke with piracetam.
Members of the Piracetam in Acute Stroke Study (PASS)
Group.
De Deyn PP, Reuck JD, Deberdt W, Vlietinck R, Orgogozo
JM
Department of Neurology, Middelheim Hospital, Antwerp,
Belgium.
Stroke 1997 Dec;28(12):2347-52
BACKGROUND AND PURPOSE: Piracetam, a nootropic agent with
neuroprotective properties, has been reported in pilot studies
to increase compromised regional cerebral blood flow in
patients with acute stroke and, given soon after onset, to
improve clinical outcome. We performed a multicenter,
randomized, double-blind trial to test whether piracetam
conferred benefit when given within 12 hours of the onset of
acute ischemic stroke to a large group of patients.
METHODS: Patients received placebo or 12 g piracetam as an
initial intravenous bolus, 12 g daily for 4 weeks and 4.8 g
daily for 8 weeks. The primary end point was neurologic
outcome after 4 weeks as assessed by the Orgogozo scale.
Functional status at 12 weeks as measured by the Barthel Index
was the major secondary outcome. CT scan was performed within
24 hours of the onset of stroke but not necessarily before
treatment. Analyses based on the intention to treat were
performed in all randomized patients (n = 927) and in an
"early treatment" population specified in the protocol as
treatment within 6 hours of the onset of stroke but
subsequently redefined as less than 7 hours after onset (n =
452).
RESULTS: In the total population, outcome was similar with
both treatments (the mean Orgogozo scale after 4 weeks:
piracetam 57.7, placebo 57.6; the mean Barthel Index after 12
weeks: piracetam 55.8, placebo 53.1). Mortality at 12 weeks
was 23.9% (111/464) in the piracetam group and 19.2% (89/463)
in the placebo group (relative risk 1.24, 95% confidence
interval, 0.97 to 1.59; P = .15). Deaths were fewer in the
piracetam group in those patients in the intention-to-treat
population admitted with primary hemorrhagic stroke. Post hoc
analyses in the early treatment subgroup showed differences
favoring piracetam relative to placebo in mean Orgogozo scale
scores after 4 weeks (piracetam 60.4, placebo 54.9; P = .07)
and Barthel Index scores at 12 weeks (piracetam 58.6, placebo
49.4; P = .02). Additional analyses within this subgroup,
confined to 360 patients with moderate and severe stroke
(initial Orgogozo scale score < 55), showed significant
improvement on piracetam in both outcomes (P < .02).
CONCLUSIONS: Piracetam did not influence outcome when given
within 12 hours of the onset of acute ischemic stroke. Post
hoc analyses suggest that piracetam may confer benefit when
given within 7 hours of onset, particularly in patients with
stroke of moderate and severe degree. A randomized,
placebo-controlled, multicenter study, the Piracetam Acute
Stroke Study II (PASS II) will soon begin.
[Factors influencing the prescribing of nootropic
drugs. Results of a representative inquiry in Lower
Saxony].
[Article in German]
Stoppe G, Sandholzer H, Staedt J, Kiefer J, Winter S, Kochen
MM, Ruther E
Psychiatrische Klinik und Poliklinik, Universitat
Gottingen.
Dtsch Med Wochenschr 1995 Nov 24;120(47):1614-9
AIM OF INVESTIGATION: To discover (1) to what extent
patients' wishes and the extent of any abnormality of brain
performance influence the frequency with which "nootropic"
drugs (those thought to affect brain activity, e.g. piracetam,
pyritinol, or improve cerebral circulation, e.g. xanthine
derivatives, Ginkgo biloba, secale alkaloids, calcium
antagonists) are prescribed; (2) the medical practitioner's
expectations of the effectiveness of such medications.
METHOD: In a personal interview, 145 family doctors and 14
neurologists in private practice in the Gottingen area of
Germany (participation rate: 83.2% of those asked to
participate) were questioned about fictitious cases (case 1:
mild memory problem with or without expressed wish for
medication; case 2: moderate dementia, of Alzheimer or
multi-infarct type). The previously arranged interviews, which
took place in the doctors' practice rooms, consisted of
standardized open questions to the written case reports.
RESULTS: Regardless of the wish of the patient and the
extent and type of the abnormal brain function about 70% of
all participating doctors would prescribe those drugs, even
though about 56% had doubts about their effectiveness. About
28% expected a positive effect on brain performance. A nearly
equal proportion of doctors would continue an existing drug
regimen as would prescribe one.
CONCLUSION: The prescription of the named group of drugs is
influenced less by medical criteria than by factors which
concern doctor-patient relationship.
tPA in acute ischemic stroke: United States
experience and issues for the future.
Alberts MJ
Stroke Acute Care Unit, Duke University Medical Center,
Durham, NC 27710, USA.
Neurology 1998 Sep;51(3 Suppl 3):S53-5
The approval of tissue plasminogen activator (tPA) for
treatment of patients with ischemic stroke in the United
States marked the first therapy proven to reverse or limit the
effects of an acute stroke. Despite this approval and the lack
of an alternative therapy, the use of tPA in stroke has been
quite low. Several explanations for this underutilization have
been identified, including lack of patient awareness,
potential complications, infrastructure deficiencies, and
physician concerns. This article explores these issues and
suggests strategies for improving the use of tPA as an acute
therapy in stroke.
Secondary stroke prevention with low-dose aspirin,
sustained release dipyridamole alone and in combination.
ESPS Investigators.
European Stroke Prevention Study. Forbes CD University of
Dundee Medical School, Scotland, United Kingdom.
Thromb Res 1998 Sep 15;92(1 Suppl 1):S1-6
Patients who had survived a stroke or transient ischaemic
attacks (TIA) were admitted to a trial of low-dose aspirin (50
mg) alone, sustained release dipyridamole (400 mg/day) alone,
or a combination of the two agents, and results compared with
a placebo over 24 months. This low-dose aspirin regimen
produced in pairwise comparisons a significant risk reduction
of 18% for stroke, 13% for stroke and/or death but no
reduction in all cause mortality. The sustained release
dipyridamole produced a significant risk reduction of 16% for
stroke, 15% for stroke and/or death but no significant
reduction of mortality. In combination, aspirin and
dipyridamole produced a risk reduction of 37% in stroke, 24%
in stroke and/or death, and no reduction in mortality. Similar
findings were found in TIA, which was a secondary endpoint.
These results are highly significant in comparison with
placebo. As expected, there were enhanced reports of
alimentary side-effects in the aspirin groups and also
enhanced bleeding. Dipyridamole was associated with a slight
increase in headache, which resolved in most patients if
therapy was continued. The conclusions are that 50 mg/day of
aspirin alone or 400 mg/day of sustained release dipyridamole
alone are equally effective in stroke and TIA prevention. When
used in combination the effects were additive and were
significantly more effective than the single agents.
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