Neurol Sci (2005) 26:310318

DOI 10.1007/s10072-005-0505-7

ORIGINAL

F. Perini E. Galloni I. Bolgan G. Bader R. Ruffini E. Arzenton S. Alba C. Azzini L. Bartolomei

G. Billo F. Bortolon P. Dudine P.G. Garofalo R. LErario M. Morra P. Parisen
G. Stenta V. Toso

Elevated plasma homocysteine in acute stroke was not associated with

severity and outcome: stronger association with small artery disease

Received: 25 May 2005 / Accepted in revised form: 12 September 2005

Abstract Homocysteine increases in the acute phase of
ischaemic stroke and from the acute to the convalescent
phase, suggesting that hyper-homocysteinaemia may be a
consequence rather than a causal factor. Therefore we
measured homocysteine plasma levels in stroke patients in
order to investigate possible correlations of homocysteine
with stroke severity and clinical outcome. Further we
looked for eventual differences in stroke subtypes. We
prospectively studied plasma homocysteine levels in acute
stroke patients admitted to the stroke unit of our depart-
ment. Seven hundred and seventy-five ischaemic stroke
patients, 39 cerebral haemorrhages and 421 healthy con-
trol subjects have been enrolled. Stroke severity and clini-
cal outcome were measured with the Scandinavian Stroke
Scale, the Rankin Scale and the Barthel Index. Stroke
severity by linear stepwise regression analysis was not an
independent determinant of plasma homocysteine levels.
Homocysteine was not correlated with outcome measured
by the Barthel Index. Mean plasma homocysteine of both
ischaemic and haemorrhagic stroke was significantly high-
er than controls (p<0.05). Homocysteine had an adjusted
odds ratios (OR) of 4.2 (95% CI 2.776.54) for ischaemic
stroke and of 3.69 (95% CI 1.907.17) for haemorrhagic
stroke. Compared with the lowest quartile, the upper quar-
tile was associated with an adjusted OR of ischaemic
stroke due to small artery disease of 17.4 (95% CI
6.844.3). Homocysteine in the acute phase of stroke was
not associated with stroke severity or outcome. Elevated
plasma homocysteine in the acute phase of stroke was
associated with both ischaemic and haemorrhagic stroke.
Higher levels are associated with higher risk of small
artery disease subtype of stroke.
Key words Homocysteine Stroke Severity Outcome
Risk
Introduction

Since the first report by McCully [1] in 1969 in which he

concluded that very high plasma homocysteine (Hcy) lev-
els were the cause of vascular disease in children with a
rare inborn error of B12 metabolism, a great body of evi-
dence, based mainly on case-control studies, has encour-
aged the commonly accepted idea that hyper-homocys-
F. Perini () teinaemia is an independent risk factor for atherosclerotic
Department of Neurology
vascular disease. However prospective studies give con-
Monselice Hospital ULSS 17
Via Marconi 19, I-35043 Monselice (PD), Italy trasting results [24] regarding ischaemic stroke: some
e-mail: francesco.perini@ulss17.it indicate that Hcy is a risk factor for cerebral infarction
[510], while other studies were negative [11, 12]. A
F. Perini E. Galloni I. Bolgan G. Bader R. Ruffini recent updated meta-analysis published in JAMA, which
E. Arzenton S. Alba C. Azzini L. Bartolomei G. Billo
included only prospective studies, confirmed a significant,
F. Bortolon P. Dudine P.G. Garofalo R. LErario
M. Morra P. Parisen G. Stenta V. Toso
graded and independent association between high Hcy and
Headache and Stroke Center atherothrombotic vascular risk [13].
Department of Neurology Several case-control studies have demonstrated higher
St. Bortolo Hospital Hcy levels in the ischaemic stroke patients in comparison
Ulss 6, Vicenza, Italy to control subjects, but in most of them the timing of blood
F. Perini et al.: Elevated plasma homocysteine in acute stroke 311

sampling was in the sub-acute phase or not specified
[1423]. Lindgren et al. and Meiklejohn et al. demonstrat-
ed that Hcy levels increase from the acute (within 4 days)
to the convalescent period (>3 months) [24, 25] and in a
recent work Howard et al. demonstrated Hcy elevation
from the very acute phase (within 24 h) until the 14th day
of risk [26]. Accordingly with this evidence it has been
hypothesised that Hcy in ischaemic stroke patients may be
an acute-phase reactant and a consequence rather than a
risk factor of the disease [2, 26], and Dudman suggested
that Hcy increases as a result of tissue damage [27].
There is very little data in the literature correlating Hcy
levels with stroke severity at admission [26] and no data
regarding a correlation with clinical outcome. Data regard-
ing the correlation of Hcy in the acute phase of stroke with
stroke severity and clinical outcome may help to explain
the role of this molecule in cerebrovascular disease. On the
other hand, studies performed in the acute phase of stroke
gave controversial results: three studies in the acute phase
found no differences [24, 25, 28] while others showed an
elevation in comparison to controls [2931].
Clues in understanding the role of Hcy in stroke may
derive from studies of different stroke populations; a few
studies investigated the relationship among subtypes of
cerebral infarction, giving conflicting results [14, 17, 20,
30, 3234] and an increase of Hcy levels has been
described in previous studies in cerebral haemorrhage, but
blood was sampled at least one month after the acute event
[14, 20, 22].
We therefore carried out a case-control study including
patients consecutively admitted to the Stroke Unit of our
department, with both ischaemic and haemorrhagic stroke,
recording Hcy plasma levels, B12, folate, vascular risk fac-
tors, stroke severity and clinical outcome.
Our priorities were to address a possible relationship
between Hcy and stroke severity, and investigate if Hcy
could be a prognostic factor of clinical outcome. As a fur-
ther aim we examined whether there could be an associa-
tion of Hcy with different ischaemic stroke subtypes,
cerebral haemorrhage and vitamin status.
Subjects and methods
All patients with a stroke, consecutively referred to the
Stroke Unit of our department, were considered eligible for the
study. History, neurological examination and brain computed
tomography (CT) or magnetic resonance imaging (MRI) estab-
lished the diagnosis. Patient diagnosis was confirmed with CT or
MRI performed within 15 days.
All patients were evaluated with a standardised neurological
evaluation on admission and on the 7th day using the
Scandinavian Stroke Scale (SSS) and the modified Rankin Score
(RS). The Barthel Index (BI) was registered at 7 days and 3
months [3537]. Patients were prospectively subdivided accord-
ing to the TOAST classification into four subgroups: (a) car-
dioembolic (CE), (b) large artery disease (LA), (c) small artery
disease (SA) and (d) unknown (UN) and (e) other (OT) [38].
Transthoracic, transoesophageal cardiac ultra sound and carotid
and transcranial Doppler were performed when required to con-
firm diagnosis. Haemorrhagic strokes were subdivided into two
groups: (1) patients with primary haemorrhage within the basal
ganglia and (2) primary haemorrhage at other sites (lobar, cere-
bellar and brain stem).
Of the eligible patients we excluded only those with tran-
sient ischaemic attacks, subarachnoid haemorrhages and cere-
bral venous thrombosis. Seven hundred and seventy-five (775)
ischaemic stroke patients and 70 cerebral haemorrhages were
included. Demographic data and risk factors are shown in

Table 1 Demographics and conventional vascular risk factors

Controls Ischaemic (n=775) Haemorrhagic (n=70)

(n=421)

n Crude OR p-value* n Crude OR p-value*

(IC 95%) (IC 95%)

Age, meanSD 56.614.8 71.612.1 <0.001 69.513.8 <0.001

Male sex 201 (47.7%) 399 (51.5%) NS 39 (54.9%) NS
Hypertension 134 (31.8%) 546 (70.4%) 5.1 (3.96.6) <0.001 50 (70.4%) 5.1 (2.98.8) <0.001
Diabetes 58 (13.8%) 229 (29.5%) 2.6 (1.93.6) <0.001 15 (21.1%) 1.7 (0.93.2) NS
Previous myocardial 10 (2.4%) 106 (13.7%) 6.5 (3312.6) <0.001 3 (4.2%) 1.8 (0.56.8) NS
infarction
Hypercholesterolaemia 93 (22.1%) 213 (27.5%) 1.3 (1.01.8) 0.041 18 (25.7%) 1.2 (0.72.2) NS
Smoke 52 (12.4%) 152 (19.6%) 1.7 (1.22.4) 0.001 10 (14.3%) 1.2 (0.62.4) NS
Atrial fibrillation NA 209 (27.0%) 6 (8.57%)
Oral contraceptives 20 (4.8%) 9 (1.2%) 0.2 (0.10.5) <0.001 1 (1.4%) 0.3 (0.02.2) NS
Obesity 64 (15.2%) 154 (19.9%) 1.4 (1.01.9) 0.046 6 (8.5%) 0.5 (0.21.2) NS

*c2 for categorical data, unpaired t test for continuous data

NA, data not available for controls
312 F. Perini et al.: Elevated plasma homocysteine in acute stroke

Table 1 along with data of the control group. Patients gave
informed consent to the study. The proportion of patients with
follow-up at three months was 84.52%. The medians at admis-
sion for SSS, RS and BI were 35.6, 3.8 and 56.7 respectively.
There were 98 (15.5%) deceased patients at six months in the
ischaemic stroke group and 11 (23.4%) in the primary haemor-
rhages group.
Four hundred and twenty-one control subjects, with or with-
out risk factors for vascular diseases, made up our control group.
During the study period, 421 control subjects were consecutive-
ly recruited from the list of the national health system by gener-
al practitioners in our area and their demographic data and vas-
cular risk factors were recorded. Criteria for selection were ran-
dom among those between 40 and 70 years old. Peripheral blood
samples were drawn at admission within 24 h in a fasting state.
The mean time from symptom onset was 13 h. Blood was drawn
in supine position from an antecubital vein, EDTA-anticoagulat-
ed and separated by centrifugation at 3500xg for 15 min at 4C.
Plasma was then stored at 80C until, analysis. The total plas-
ma Hcy concentration was assayed by reverse-phase high-per-
formance liquid chromatography (Waters HPLC) with a fluores-
cence detector (Perkin Elmer) according to the method of Bio-
Rad laboratories GmbH (Munchen). The same conditions were
used for control subjects. Analyses were performed in the labo-
ratory of the Headache and Stroke Center affiliated to our depart-
ment, while B12 and folate were measured by the central hospi-
tal laboratories.
analysis was performed using Pearson product moment correla-
tion coefficient.
Baselines differences between cases and controls were
examined by means of the c2-test for categorical data while dif-
ferences in the means of continuous data were analysed with
Students t-test for independent samples. When continuous data
had no normal distribution, the Mann-Whitney test (between two
groups) or Kruskal-Wallis (among three or more groups) were
used. Data are reported as meanSD. A p-value less than 0.05
was considered statistically significant (Tables 1 and 3). ANOVA
was used to compare mean Hcy levels between aetiologic sub-
types of ischaemic and haemorrhagic stroke (Table 3).
The associations between Hcy and both ischaemic and haem-
orrhagic stroke were examined by means of two separated logis-
tic regression model, with adjustment for age, sex and conven-
tional vascular risk factor listed in Table 1. Results were expressed
as odds ratios (OR) together with their 95% CI (Figs. 13).
The analysis of Hcy levels as discrete quartile categories bet-
ter reflects the non-linear relationship between Hcy and stroke.
Logarithmic transformations were used in ANOVA and logistic
and linear regression for variables that showed a marked positive
skew (Hcy, folate and B12). Statistical analysis was performed
using the SPSS 11.5 software package.
Results

Demographic data and risk factors of patients and controls

Statistical method
Determinants of Hcy in patients with ischaemic stroke were
assessed by stepwise linear regression (Table 2). Correlation
are shown in Table 1. Cases had higher prevalence of vas-
cular risk factors compared to controls: the absence of any
control with atrial fibrillation does not preclude the analy-
sis of this variable and the excess of oral contraceptives
probably depends on the younger age of controls.

Table 2 Hcy determinants: results of regression analysis

Variables Univariate analysis Multivariate analysis

Regression coefficient p-value Regression coefficient p-value

(95% CI) (95% CI)

Hypertension 0.059 (0.018 to 0.135) 0.135 0.931

Diabetes 0.044 (0.122 to 0.033) 0.261 0.508
Atrial fibrillation 0.021 (0.102 to 0.06) 0.611 0.148
Hypercholesterolaemia 0.053 (0.132 to 0.026) 0.185 0.857
Hypertriglyceridaemia 0.012 (0.077 to 0.101) 0.789 0.792
Ischaemic heart disease history 0.161 (0.057 to 0.265) 0.003 0.193
Oral contraceptives 0.329 (0.653 to 0.005) 0.047 0.985
Obesity 0.03 (0.12 to 0.06) 0.513 0.563
SSS at admission 0.003 (0.004 to 0.001) 0.011 0.240
RS at admission 0 (0.006 to 0.006) 0.924 0.823
Folate (log) 0.295 (0.375 to 0.214) 0.000 0.22 (0.30 to 0.13) 0.000
Age 0.009 (0.006 to 0.012) 0.000 0.01 (0.01 to 0.02) 0.000
Sex 0.103 (0.033 to 0.173) 0.004 0.09 (0.01 to 0.19) 0.070
Smoker 0.069 (0.02 to 0.158) 0.129 0.13 (0.00 to 0.26) 0.045
B12 (log) 0.145 (0.224 to 0.066) 0.000 0.09 (0.17 to 0.00) 0.047
Previous myocardial infarction 0.071 (0.145 to 0.004) 0.063 0.13 (0.01 to 0.27) 0.065
(Constant) 2.71 (2.05 to 3.36) 0.000
F. Perini et al.: Elevated plasma homocysteine in acute stroke 313

Table 3 Mean plasma Hcy levels in ischaemic and haemorrhagic stroke

Groups Subgroups Subjects, n Hcy, mmol/l p*

Ischaemic stroke All 775 18.9413.65 <0.001

Small artery 184 19.8014.27 <0.001
Large artery 295 19.2315.37 <0.001
Cardioembolic 207 18.339.92 <0.001
Other 21 12.885.84 NS
Unknown 68 19.0215.20 <0.001
Haemorrhagic stroke All 70 18.1814.08 <0.001
Lobar 55 16.6010.62 <0.001
Basal ganglia 15 23.9422.30 <0.001
Controls 421 11.976.61

*Test vs. controls

OR for ischemic stroke

13.5

6.4
5.4

2.5 2.8
2.1

Homocysteine quartiles
Fig. 1 Association between quartiles
of Hcy and risk of ischaemic stroke.
*p<0.05, **p<0.001

Hcy determinants and case-control differences
Stroke severity, by linear stepwise regression analysis,
was not an independent determinant of plasma Hcy levels,
indicating that the component derived from tissue damage
may not be significant; on the other hand folate, age, sex,
smoking, B12 and previous myocardial infarction deter-
mined Hcy levels accounting together for 17% of its total
variance (R2=0.17 and adjusted R2=0.15) (Table 2). We
did not find a correlation between Hcy and outcome mea-
sured with BI at 6 or 12 months (r=0.105 and r=0.003
respectively).
As ischaemic stroke patients were unmatched for age
with controls we performed a sub-analysis for decades of
age, which confirmed higher Hcy levels in patients
(p<0.05).
Mean plasma B12 levels were higher in ischaemic
stroke patients (589416 pg/ml) than controls (381141
pg/ml, p<0.001), while folate levels were lower in patients
(7.615.27 g/ml) than controls (14.2618.76 g/ml,
p<0.001). Also haemorrhagic stroke patients had higher
levels of B12 (722450 pg/ml, p<0.001) and lower levels
of folate in comparison to controls (7.713.50 g/ml,
p<0.001).
314 F. Perini et al.: Elevated plasma homocysteine in acute stroke

OR for hemorrhagic stroke

6.4

3.8

2.1
1.5
0.8 1.0

Homocysteine quartiles
Fig. 2 Association between quartiles
of Hcy and risk of hemorrhagic stroke
*p<0.05, **p<0.001

30

25

20
16.4 7.1
Adjusted OR

7.1
15 4.0
5.9
4.9
10
3.9
3.0
1.6 2.2 2.7 1.9
5
1.5 1.1 0.6

0
Fig. 3 Association between quartiles of
010 10.113.2 13.318.6 >18.6 Hcy and risk of large artery, small
artery, cardioembolic unknown and
Homocysteine quartiles other causes of ischaemic stroke,
adjusted for age, sex and conventional
Small artery Large artery Cardioembolic Other Unknown vascular risk factors. *p<0.05,
**p<0.001

Association between Hcy and ischaemic and haemorrhag- rhagic stroke were 7.48 (95% CI 5.3610.42) and 4.75
ic stroke (95% CI 2.718.32) respectively. The upper quartile of
Hcy was associated with a crude OR of ischaemic stroke of
Hcy had adjusted ORs of 4.26 (95% CI 2.776.54) for 13.99 (95% CI 9.1221.44) compared with the lowest
ischaemic stroke and 3.69 (95% CI 1.907.17) for haem- quartile, and, after adjustment for conventional vascular
orrhagic stroke. Crude ORs for ischaemic and haemor- risk factors, the adjusted OR was 6.74 (95% CI
F. Perini et al.: Elevated plasma homocysteine in acute stroke
3.7812.02) (Fig. 1). The upper quartile of Hcy was asso-
ciated with a crude OR of haemorrhagic stroke of 6.41
(95% CI 2.7015.21) compared with the lowest quartile;
the adjusted OR was 4.17 (95% CI 1.5711.06) (Fig. 2).
Association between Hcy and subtypes of ischaemic and
haemorrhagic stroke
Mean values of Hcy in subtypes of ischaemic and haemor-
rhagic stroke were higher in comparison to controls except
for other causes (12.95.8 mol/l) (Table 3). Compared
with the lowest quartile, after adjustment for other risk fac-
tors, the upper 3 quartiles were associated with an adjust-
ed OR of ischaemic stroke due to SA of 3.9 (95% CI
1.68.2) for the second, 5.9 (95% CI 2.614.4) for the
third and 16.4 (95% CI 6.944.3) for the fourth quartile.
Compared with the lowest quartile, the upper 3 quartiles
were associated with an adjusted OR of large artery stroke
of 1.5 (95% CI 0.82.6) for the second, 2.7 (95% CI
1.44.7) for the third and 4.9 (95% CI 2.49.8) for the
fourth quartile. The upper 3 quartiles were associated with
an adjusted OR of CE stroke of 1.6 (95% CI 0.73.4) for
the second, 3.0 (95% CI 1.36.4) for the third and 7.1 for
the fourth (95% CI 3.622.1) (Fig. 3).
Discussion
This is the first study to examine the possible correlation
between Hcy and stroke severity and outcome. We found
that Hcy plasma levels in the acute phase of ischaemic
stroke (within 24 h) did not correlate with stroke severity.
Considering that Howard et al. demonstrated a significant
elevation in non-fasting Hcy levels in 76 ischaemic stroke
patients from 2448 h to 1014 days [26] and that Lindgren
et al. and Meiklejohn et al. demonstrated that Hcy levels
increase from the acute to the convalescent period (3
months) [24, 25] it has been hypothesised that elevated Hcy
plasma levels could be a consequence rather than a causal
factor [27]. No data are available in the literature on corre-
lation between Hcy levels and clinical outcome. We failed
to demonstrate that patients with high Hcy levels in the
acute phase of ischaemic stroke have a worse outcome.
According to our data, hyper-Hcy does not have a prognos-
tic value. In 76 patients with acute ischaemic stroke
Howard et al. did not find differences between patients with
RS2 when compared with patients with RS3 [26]. No
data are available for haemorrhagic stroke. Besides RS we
also used SSS, which is a more sensitive method, to mea-
sure stroke severity. Hcy levels in the acute phase of stroke
did not correlate with stroke severity at admission, thus
confirming the data of Howard et al. Lack of correlation
315
with clinical severity may indicate that Hcy is not influ-
enced by the extent of infarction or tissue damage.
Our study confirms not only the presence of an inde-
pendent association between hyper-Hcy and ischaemic
stroke but it shows also an association with haemorrhagic
stroke, although stepwise linear regression analysis could
not be performed due to the smaller number of patients
with cerebral haemorrhage. Several studies investigated
Hcy levels in ischaemic stroke patients, but in most of them
the timing of sampling was not stated or was done in the
subacute or convalescent phase of the event. Studies that
performed Hcy measurement in the acute phase gave con-
flicting results. Lindgren et al. showed no differences in
162 patients sampled within 2 days from the onset in com-
parison to 60 controls [24]. Meiklejohn et al. investigated
106 patients and controls within 4 days, showing only a
trend for higher Hcy in male patients [24]. Eikelboom et al.
found higher Hcy in 219 patients with respect to 205 con-
trols within 7 days from the event [30]. Three Italian stud-
ies also gave conflicting results: the first showed higher
Hcy in 113 patients within 3 days compared to 135 controls
[31], the second studied 161 stroke patients and 152 con-
trols but the time of samples was not stated [29] and the
third found no differences [28]. Methodological differences
have to be taken into consideration. Our study has some
limitations: a possible reason for the high Hcy levels in our
patients could be that we did not exclude other known sec-
ondary causes of hyper-Hcy and patients were unmatched
for age in comparison to controls, but our primary aim was
to assess correlation with stroke severity, clinical outcome
and stroke subtypes. Other limitations such as the retro-
spective case-control design, the potential for misclassifi-
cation of aetiologic subtypes of stroke, the effects of known
(e.g., age, creatinine, the acute phase response) or unknown
potential confounders, and the limitations of stroke disabil-
ity score as a measure of extent of infarction or tissue dam-
age should be considered. Moreover regional differences
may account for different results in studies undertaken in
different countries. For instance we know that in Italy there
is a high prevalence of thermolabile 510 methylentetrahy-
drofolatereductase [39].
To the best of our knowledge this is the first study that
measured Hcy levels in the acute phase of cerebral haem-
orrhage. In a recent study Li et al. found increased Hcy
levels in 503 patients with cerebral haemorrhage studied 6
weeks after the acute event, while correlations with clini-
cal severity or outcome were not studied [14]. Previous
studies investigated Hcy in the convalescent phase of cere-
bral haemorrhage. Araki et al. [22] studied 20 patients
sampled between the first and the third month after the
event and found an increase from 7.3 to 9.6 nmol/ml while
Brattstrom et al. described higher Hcy levels in 14 patients
sampled between the 21st and 42nd week after the event
[20]. The Rotterdam study found the same association
with Hcy both in haemorrhagic and ischaemic stroke, but
316
there were only 12 haemorrhagic strokes [10]. We found
higher Hcy levels in the acute phase of brain haemorrhage
with respect to controls. The reason high Hcy levels
enhance the risk for cerebral haemorrhage is not known.
However it has been shown, in a recent study, that hyper-
homocysteinaemia causes elevated mRNA levels of metal-
loproteinases MMP-9 and tissue inhibitors of MMP-1
from peripheral blood mononuclear cells, which release an
increased amount of MMP-9 [40], enhancing matrix
degradation. High levels of B12 in patients have already
been described [15, 17, 32], and this may be due to a more
common use of vitamins as a diet supplement in the patient
population. Nevertheless we found an inverse correlation
between Hcy and B12 and folate levels, confirming previ-
ous studies [30]. Contrasting results on the role of vitamins
are coming from trials of prevention of vascular events
using vitamin supplementation [41, 42].
Clues in understanding the role of Hcy in ischaemic
stroke may derive from studies that investigated the subtypes
of cerebral infarction. Data in the literature on this topic are
controversial. The majority of previous studies failed to find
differences among subgroups [14, 20, 24, 34, 43]. The
Rotterdam study found no differences in stroke subtypes,
though there was a stronger association with lacunar strokes
[10]. Few studies found higher levels of Hcy in small artery
subtypes of stroke [17, 32, 33]. Eikelboom et al. found a
greater risk of ischaemic stroke in patients with LA [30]. The
same trend was described by Tan et al. in a population of
young people with ischaemic stroke [15]. Moreover the
methodological differences (timing of sampling [4, 14, 15,
17, 33, 34], numbers of subjects [10, 15, 17, 34, 43], failure
to include CE subtype [10, 14, 32], retrospective or use of
other classification of subtypes of stroke [10, 24], non-fast-
ing sampling [4, 10, 25, 32, 43]) may explain the different
results. In our study higher Hcy levels are associated with
higher risk of SA subtype of stroke. Regardless of the study
of Li et al., which did not find differences among subgroups,
our study included a larger number of patients and the results
were adjusted for other possible confounders.
All together our data suggest that Hcy is not linked to
stroke severity and it does not influence outcome. Lack of
correlation with stroke severity and outcome goes against
the hypothesis that Hcy could be secondary to tissue dam-
age. On the other hand, logistic regression analysis indi-
cates that it constitutes a vascular risk factor for ischaemic
stroke. These results may be in line with our finding that
higher Hcy levels determine a major risk for SA. Further
studies are needed to clarify the relationship between Hcy
and haemorrhagic stroke.
Sommario Il livello dellomocisteina (Hcy) aumenta nella
fase acuta dellictus ischemico e nellintervallo tra la fase
acuta e la convalescente, facendo supporre che liper-omo-
F. Perini et al.: Elevated plasma homocysteine in acute stroke
cisteinemia possa essere una conseguenza piuttosto che un
fattore di rischio. Abbiamo dosato lHcy nel plasma dei
pazienti con ictus per ricercare le possibili correlazioni tra
i livelli di Hcy, la gravit dellictus e loutcome clinico
di malattia. Inoltre abbiamo ricercato eventuali differenze
che possono presentarsi nei sottotipi di ictus. Sono stati
studiati in maniera prospettica i livelli di Hcy di 775
pazienti con ictus ischemico acuto e di 39 pazienti con
emorragia cerebrale primaria, ricoverati presso la stroke
unit del nostro dipartimento e 421 controlli sani. La gra-
vit dellictus e landamento clinico sono stati valutati con
la Scandinavian Stroke Scale, la Rankin Scale e il Barthel
Index. Attraverso un analisi di regressione lineare si visto
che la gravit dellictus non costituisce un predittore indi-
pendente dei livelli plasmatici dell Hcy e lHcy non cor-
rela con landamento clinico dellictus. La media dei livel-
li plasmatici dell Hcy, sia nellictus ischemico che nellic-
tus emorragico era significativamente pi alta rispetto ai
controlli (p<0.05). LHcy aveva un OR aggiustato di 4.2
(95% CI 2.776.54) per ictus ischemico e di 3.69 (95% CI
1.907.17) per ictus emorragico. Il quartile superiore
dellHcy, paragonato con il quartile pi basso, ha un OR
aggiustato di 17.4 (95% CI 6.844.3) per lictus ischemi-
co causato da malattia delle piccole arterie. In conclusio-
ne la gravit dellictus non determinava i livelli di Hcy
nella fase acuta dellictus n daltra parte questi correla-
vano con outcome clinico, indicando che i livelli di Hcy
nella fase acuta non sono una conseguenza dellictus.
Livelli elevati di Hcy nella fase acuta dellictus erano asso-
ciati sia allictus ischemico che allemorragico. Alti livelli
di Hcy erano associati ad un pi elevato rischio di ictus
causato da malattia delle piccole arterie.
References
1. McCully KS (1969) Vascular pathology of homocysteine-
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