3 METABOLISME DE L'HOMOCYSTEINE
ROLE DES FOLATES ET DE LA VITAMINE B12 ET DE LA TMG
4 HOMOCYSTEINE, MORBIDITE ET VIEILLISSEMENT
Un mécanisme ubiquitaire : DNA, enzymes, etc
Dégradation avec l’age
La méhylation est nécessairepour la transformation homocystéine > méthionine
Acide aminé toxique ; toujours présent
Découverte chez les enfants (Mc Cully 1960 - 1968) : l’impossibilité d’abaisser l’homocysteine > mortalité cardiaque précoce
Nombreux travaux depuis 1960 : homocystéine élevée = risque cardiovasculaire +++
3
METABOLISME DE L’HOMOCYSTEINE
ROLE DES FOLATES ET DE LA VITAMINE B12 ET DE LA TMG
Acide folique = donneur de méthyl
l’acide folique requiert la B12
TMG (trimethyl glycine) = donneur de méthyl
Supplémentation en folate + B12
> baisse de l’homocystéine
HOMOCYSTEINE ET TRANSULFURATION
Le phosphate de pyridoxal (vit B6) est nécessaire pour :
Homocystéine > Cystathionine > Cystéine
NB : pauvreté en B6 dans aliments conditionnés
destruction B6 chez le fumeur
diminution des taux avec pilule contraceptive
HOMOCYSTÉINE / COMPLEX VIT B / MITOCHONDRIES
Surproduction de radicaux libres> Dysfonction Mitochondriale
> Mutagénèse somatique
4
HOMOCYSTEINE, MORBIDITE ET VIEILLISSEMENT
Nombreuses publications depuis moins de 5 ans
Une certitude pour les pathologies cardio-vasculaires
> Voir les pages suivantes résumant un certain nombre d’articles princeps
Pour d’autres situations pathologiques ?
Le plus argumenté actuellement : amplification de la neurodégénerescence et MALADIE D’ALZHEIMER
Des travaux de confirmation sont encore necessaires pour conclure
Ce qui n’est plus contestable :HOMOCYSTEINE = MARQUEUR DE RISQUE CV CHEZ LA PA
Ce qui demande encore confirmation :
HOMOCYSTEINE = TEMOIN BIOLOGIQUE DE VULNERABILITE,
en particulier au plan cérébral,
mais peut être pour d’autres tissus
(accroissement de l’attaque radicalaire)
Ce qui représente une retombée immédiate pratiqueHOMOCYSTEINE = BON REFLET DE LA CARENCE
EN VITAMINES DU GROUPE B et en FOLATES ;
plus exactement reflet du défaut de biodisponibilité
Dosage plasmatique peu onéreux
Folate and vitamin B•12 and risk of fatal cardiovascular
disease: cohort study from Busselton, Western Australia
Joseph Hung, John P Beilby, Matthew W Knuiman, Mark Divitini
BMJ VOLUME 326 18 JANUARY 2003
Circulation.
2006 Mar 14;113(10):1335-43.
Improvement in stroke mortality in Canada
and the United States, 1990 to 2002.
Yang
Q,
Botto
LD,
Erickson
JD,
Berry
RJ,
Sambell
C,
Johansen
H,
Friedman
JM.
National Center on Birth Defects and Developmental Disabilities,
Centers for Disease Control and Prevention, Atlanta,
BACKGROUND: In the United States and Canada, folic acid fortification
of enriched grain products was fully implemented by 1998. The
resulting population-wide reduction in blood homocysteine
concentrations might be expected to reduce stroke mortality if high
homocysteine levels are an independent risk factor for stroke.
METHODS AND RESULTS: In this population-based cohort study with
quasi-experimental intervention, we used segmented log-linear
regression to evaluate trends in stroke-related mortality before and
after folic acid fortification in the United States and Canada and,
as a comparison, during the same period in England and Wales, where
fortification is not required. Average blood folate concentrations
increased and homocysteine concentrations decreased in the United
States after fortification. The ongoing decline in stroke mortality
observed in the United States between 1990 and 1997 accelerated in
1998 to 2002 in nearly all population strata, with an overall change
from -0.3% (95% CI, -0.7 to 0.08) to -2.9 (95% CI, -3.5 to -2.3) per
year (P=0.0005). Sensitivity analyses indicate that changes in other
major recognized risk factors are unlikely to account for the reduced
number of stroke-related deaths in the United States. The fall in
stroke mortality in Canada averaged -1.0% (95% CI, -1.4 to -0.6) per
year from 1990 to 1997 and accelerated to -5.4% (95% CI, -6.0 to
-4.7) per year in 1998 to 2002 (P< or =0.0001). In contrast, the
decline in stroke mortality in England and Wales did not change
significantly between 1990 and 2002.
CONCLUSIONS: The improvement in stroke
mortality observed after folic acid fortification in the United
States and Canada but not in England and Wales is consistent with the
hypothesis that folic acid fortification helps to reduce deaths from
stroke.
J Neurol Neurosurg
Psychiatry. 2006 Apr 19;
Interaction of homocysteine and
conventional predisposing factors on risk of ischemic stroke in young
adults. Consistency of phenotype-disease analysis and
genotype-disease analysis.
Pezzini
A,
Grassi
M,
Del Zotto
E,
Assanelli
D,
Archetti
S,
Negrini
R,
Caimi
L,
Padovani
A.
Clinica Neurologica, Universita degli Studi di Brescia, Brescia,
Italia, Italy.
BACKGROUND AND OBJECTIVES: Whether the association between mild
hyperhomocysteinemia and ischemic stroke is the consequence of a
predisposing genetic background or it is due to the confounding
influence of established predisposing factors remains to be
determined. Methoda: Plasma total homocysteine concentration(tHcy)
and the distribution of the C677T genotypes of the
methylenetetrahydrofolate reductase (MTHFR) gene were compared in 174
consecutive stroke patients aged <45 years and 155 controls. The
effect of conventional risk factors on phenotype-disease and
genotype-disease relation was analysed by two- and three-way
interaction analysis and by the classification and regression trees
(CART) model. RESULTS: tHcy levels were significantly higher in cases
(11.9 micromol/l, range 2.0 to 94.0) compared with controls (9.8
micromol/l, range 4.7 to 49.6). An increased risk was also associated
with the TT677 genotype (OR, 1.98; 95% CI, 1.04 to 3.78) and with the
T allele (OR, 1.40; 95% CI, 1.03 to 1.92) of the MTHFR gene. A
differential effect of Hcy on stroke risk was observed according to
the distribution of environmental-behavioral risk factors, with
stronger influence in the subcategory of hypertensive and smokers
(OR, 24.8; 95% CI, 3.15 to 196). A comparable environmental-dependent
TT677 MTHFR genotype-stroke association was observed in the
genotype-disease analysis.
CONCLUSIONS: The analysis of specific
subcategories of patients defined by the distribution of established
risk factors indicates a consistency of phenotype-disease analysis
and genotype-disease analysis. Our data indirectly support the
assumption that the Hcy-stroke relation is unlikely due to a
reverse-causality bias.
Neurol
Sci. 2005 Dec;26(5):310-8.
Elevated plasma homocysteine in acute
stroke was not associated with severity and outcome: stronger
association with small artery disease.
Perini
F,
Galloni
E,
Bolgan
I,
Bader
G,
Ruffini
R,
Arzenton
E,
Alba
S,
Azzini
C,
Bartolomei
L,
Billo
G,
Bortolon
F,
Dudine
P,
Garofalo
PG,
L'Erario
R,
Morra
M,
Parisen
P,
Stenta
G,
Toso
V.
Headache and Stroke Center, Department of Neurology, St. Bortolo
Hospital, Ulss 6, Vicenza, Italy. f
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 department. Seven hundred and seventy-five
ischaemic stroke patients, 39 cerebral haemorrhages and 421 healthy
control subjects have been enrolled. Stroke severity and clinical
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 higher than
controls (p<0.05). Homocysteine had an adjusted odds ratios (OR)
of 4.2 (95% CI 2.77-6.54) for ischaemic stroke and of 3.69 (95% CI
1.90-7.17) for haemorrhagic stroke. Compared with the lowest
quartile, the upper quartile was associated with an adjusted OR of
ischaemic stroke due to small artery disease of 17.4 (95% CI
6.8-44.3).
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.
Semin Neurol. 2006 Feb;26(1):24-32.
Homocyst(e)ine and
stroke.
Furie
KL,
Kelly
PJ.
Stroke Service, Massachusetts General Hospital, Harvard Medical
School, Boston, 02114, USA.
Homocyst(e)ine elevation is associated with a two- to threefold fold
increased risk of ischemic stroke. Although most commonly associated
with large-artery atherosclerosis and venous thrombosis,
hyperhomocysteinemia may contribute to stroke by other mechanisms as
well. Levels of homocysteine are determined by genetic regulation of
the enzymes involved in homocyst(e)ine metabolism and by levels of
the vitamin cofactors (folate, B (6), and B (12)) associated with
those reactions. Emerging evidence suggests that genetic variation
within this pathway, such as the methyleneterahydrofolate reductase
and cystathionine beta-synthase and nicotinamide N-methyltransferase
genes, increases the risk of ischemic stroke. The introduction of
grain folate fortification in 1998 has reduced homocyst(e)ine
concentrations in the U.S. population. However, it is important to
screen for vitamin B (12) deficiency and be cognizant that vitamin B
(6) levels may be low in the elderly and in individuals with
inflammatory disorders.
The Vitamin Intervention in Stroke
Prevention study failed to prove that high-dose supplementation with
folate, B (6), and B (12) reduced the risk of recurrent stroke or
myocardial infarction at 2 years; however, there is an ongoing
clinical trial evaluating the potential benefit of vitamin
supplementation.
CMAJ. 2006 Feb 14;174(4):479-80.
Relative value of multiple plasma
biomarkers as risk factors for coronary artery disease and death in
an angiography cohort.
Lee
KW,
Hill
JS,
Walley
KR,
Frohlich
JJ.
James Hogg iCAPTURE Centre of Cardiovascular and Pulmonary Research
and the Healthy Heart Program, St. Paul's Hospital, Department of
Pathology and Laboratory Medicine, and the University of British
Columbia, Vancouver, BC.
BACKGROUND: Although elevated levels of C-reactive protein (CRP),
interleukin (IL)-6, serum amyloid A protein (SAA) and total
homocysteine (tHcy) have been associated with the increased
likelihood of cardiovascular events, the relative or combined utility
of these biomarkers in predicting atherosclerosis and death in an
angiography cohort is unknown. METHODS: A cohort of 1117 consecutive
patients (797 men and 320 women), referred to 2 Vancouver teaching
hospitals for selective coronary angiography, was recruited between
1993 and 1995. Angiography results were obtained for 1019 patients.
In 2004 we determined that of 1050 patients who could be traced, 231
had died, 95 of CAD-related causes. We compared the relative utility
of baseline measurements of CRP, IL-6, SAA and tHcy as well as of
lipids for predicting angiographic CAD and all-cause and CAD-related
death. RESULTS: The risk of death increased across quartiles for CRP,
IL-6, SAA and tHcy. When comparing the highest and lowest quartiles,
the greatest hazard ratios were associated with IL-6 (2.57, 95%
confidence interval [CI] 1.62-4.09) and tHcy (2.36, 95% CI
1.53-3.65). A Cox regression model containing all plasma biomarkers
and traditional risk factors indicated that age, angiographic CAD and
baseline plasma levels of IL-6 and tHcy remained independent
predictors of CAD-related death, whereas age, sex, smoking, diabetes
and apolipoprotein B levels were independent predictors of
angiographic CAD. Kaplan-Meier survival curves indicated a utility in
combining measures of CRP, SAA, IL-6 and tHcy for predicting risk of
all-cause and CAD-related death.
INTERPRETATION: A comparison of elevated
levels of CRP, IL-6, SAA and tHcy with traditional CAD risk factors
indicated that IL-6 and tHcy were the strongest independent
biomarkers for CAD-related death. Elevated levels of multiple
biomarkers were associated with an increasing rate of all-cause and
CAD-related death.
Mayo Clin
Proc. 2006 Feb;81(2):177-82.
Association of plasma homocysteine with
coronary artery calcification in different categories of coronary
heart disease risk.
Kullo
IJ,
Li
G,
Bielak
LF,
Bailey
KR,
Sheedy PF
2nd,
Peyser
PA,
Turner
ST,
Kardia
SL.
Division of Cardiovascular Diseases, Mayo Clinic College of Medicine,
200 First St SW, Rochester, MN 55905, USA.
OBJECTIVE: To Investigate the association of plasma homocystelne with
coronary artery calcification (CAC) in strata based on 10-year risk
of coronary heart disease (CHD) in a cohort enriched in persons with
hypertension. PARTICIPANTS AND METHODS: Fasting plasma homocystelne
was measured by liquid chromatography electrospray tandem mass
spectrometry. Coronary artery calcification was measured
noninvasively by electron beam computed tomography and CAC score
calculated using the method of Agatston et al. The 10-year CHD risk
was calculated based on the Framingham risk score. The association of
homocysteine with log-transformed CAC score was assessed in the
pooled sample and within each risk stratum by linear regression after
adjustment for conventional risk factors. RESULTS: In the 1071
participants studied, homocysteine was associated with CAC quantity
(P = .01) after adjustment for CHD risk factors (age, male sex, total
and high-density lipoproteln cholesterol, diabetes, history of
smoking, body mass Index, and systolic blood pressure), serum
creatinine, and statin and hypertension medication use. When the
association was assessed in strata based on 10-year CHD risk,
homocysteine was significantly (P = .003) associated with CAC
quantity in participants at Intermediate 10-year risk of CHD (6%-20%)
independent of other risk factors but not in those at lower risk or
higher risk.
CONCLUSION: Plasma homocysteine is
associated with quantity of CAC Independent of CHD risk factors. When
studied in categories of 10-year CHD risk, the association was
significant in participants at intermediate risk but not in those at
low or high risk. Plasma homocysteine levels may have clinical
utility as a marker of CHD risk in such
individuals.
Neurol
Res. 2006 Jan;28(1):25-30.
Serum level of homocysteine is correlated
to carotid artery atherosclerosis in Chinese with ischemic
stroke.
Wang
H,
Fan
D,
Zhang
H,
Fu
Y,
Zhang
J,
Shen
Y.
Department of Neurology, Peking University Third Hospital, Beijing
100083, China.
OBJECTIVES: To investigate the relationship between serum level of
homocysteine (Hcy) and carotid artery atheroscleosis (CAA). METHODS:
Both sides of the common carotid artery and internal carotid artery
in 126 Chinese patients with ischemic stroke were measured by B-mode
ultrasound. The patients were divided into groups: normal, A, B, C
and D according to the severity of CAAs. With fasting serum, Hcy as
well as folate, vitamin B(12) and lipids were detected. The mean +/-
SD age was 64 +/- 13 years (range 39-87 years). RESULTS: In a
logistic regression model, the Hcy concentrations were associated
with an elevated risk of CAAs independent of all traditional risk
factors, and when CAAs became severer, the serum Hcy was higher. The
levels of the normal group and A, B, C, D groups were 13.22 +/- 6.15
micromol/L, 16.29 +/- 9.81 micromol/l, 19.49 +/- 11.16 micromol/l,
27.21 +/- 17.47 micromol/l, and 24.14 +/- 8.64 micromol/l,
respectively. Rank test showed a significant difference between
normal and other groups (p<0.05). The levels of folate and vitamin
B(12) were negatively correlated with the Hcy concentrations.
Spearman correlation coefficient were -0.23 and -0.42
(p<0.05).
CONCLUSIONS: Hyperhomocysteinaemia is an
independent risk factor of CAAs and the degree of CAAs is highly
correlated with the level of Hcy in serum. The causes of
hyperhomocysteinemia may be the result from the decrease in folate
and vitamin B(12). Clinical trials are now required to evaluate the
effect of treatment with these vitamins on the primary and secondary
prevention of cerebral vascular diseases.
Vitamin
B12,
homocysteine and carotid plaque in the era of folic acid
fortification of enriched cereal grain products
Julie Robertson, Francesco
Iemolo, Sally P. Stabler, Robert H. Allen, J. David Spence
CMAJ2005;172(12):1569-73
Vitamin
B12,
homocysteine and carotid plaque in the era of folic acid
fortification of enriched cereal grain products
Julie Robertson, Francesco Iemolo, Sally P. Stabler,
Robert H. Allen, J. David Spence
CMAJ2005;172(12):1569-73
Vitamin
B12,
homocysteine and carotid plaque in the era of folic acid
fortification of enriched cereal grain products
Julie Robertson, Francesco Iemolo, Sally P. Stabler,
Robert H. Allen, J. David Spence
CMAJ2005;172(12):1569-73
Relative value of multiple
plasma biomarkers as risk factors for coronary artery disease and
death in an angiography
cohort
Kenny W.J. Lee, John S. Hill, Keith R. Walley, Jiri J.
Frohlich CMAJ, fev2006, 174(4)
Background: Although elevated levels of
C-reactive protein (CRP), interleukin (IL)-6, serum amyloid A protein
(SAA) and total homocysteine (tHcy) have been associated with the
increased likelihood of cardiovascular events, the relative or
combined utility of these biomarkers in predicting atherosclerosis
and death in an angiography cohort is unknown.
Methods: A cohort of 1117 consecutive patients (797 men and
320 women), referred to 2 Vancouver teaching hospitals for selective
coronary angiography, was recruited between 1993 and 1995.
Angiography results were obtained on 1019 patients. In 2004 we
determined that of 1050 patients who could be traced, 231 had died,
95 of CAD-related causes. We compared the relative utility of
baseline measurements of CRP, IL-6, SAA and tHcy as well as of lipids
for predicting angiographic CAD and all-cause and CADrelated
death.
Results: The risk of death increased across quartiles for CRP,
IL-6, SAA and tHcy. When comparing the highest and lowest quartiles,
the greatest hazard ratios were associated with IL-6 (2.57, 95%
confidence interval [CI] 1.62&endash;4.09) and tHcy (2.36,
95% CI 1.53&endash;3.65). A Cox regression model containing all
plasma biomarkers and traditional risk factors indicated that age,
angiographic CAD and baseline plasma levels of IL-6 and tHcy remained
independent predictors of CAD-related death, whereas age, sex,
smoking, diabetes and apolipoprotein B levels were independent
predictors of angiographic CAD. Kaplan&endash;Meier survival curves
indicated a utility in combining measures of CRP, SAA, IL-6 and tHcy
for predicting risk of all-cause and CADrelated death.
Interpretation: A comparison of elevated levels of CRP, IL-6,
SAA and tHcy with traditional CAD risk factors indicated that IL-6
and tHcy were the strongest independent biomarkers for CAD-related
death. Elevated levels of multiple biomarkers were associated with an
increasing rate of all-cause and CAD-related death.
Abstract
HCy, STATUT VITAMINIQUE, ET
PRÉVENTION DU
RISQUE
Surg Today. 2006;36(4):327-31.
Hyperhomocysteinemia in patients with
arterial occlusive disease.
Aksoy
M,
Basar
Y,
Salmayenli
N,
Ayalp
K,
Genc
FA,
Dilege
S,
Kayabali
M,
Baktiroglu
S,
Kurtoglu
M.
Department of General Surgery, Istanbul University, Genel Cerrahi
ABD, 34930, Capa, Istanbul, Turkey.
PURPOSE: Hyperhomocysteinemia (HHCA) is defined as an independent
risk factor for atherothrombotic vascular disease; therefore,
screening for HHCA is recommended. However, the incidence and
characteristics of HHCA in patients with vascular disease remain
unclear. We conducted this study in an attempt to resolve these
issues. METHODS: This nonrandomized prospective study included 56
patients who were admitted with occlusive arterial disease (group I),
and 39 control patients without occlusive arterial disease (group
II). We recorded all the demographic data of both groups and
collected blood samples for fasting homocysteine, vitamin B(12), and
folic acid. All of the patients were followed up and the results were
compared. RESULTS: The mean concentration of homocysteine was 12.69
+/- 3.82 micromol/l in group I and 10.46 +/- 5.08 micromol/l in group
II (P = 0.00048). In group I, the mean homocysteine levels for
patients aged >/=70 years and those aged <70 years were 13.74
+/- 3.02 and 11.55 +/- 4.15 micromol/l, respectively (P = 0.021).
There was no significant difference in mortality between the patients
with HHCA and those with normal homocysteine levels during
follow-up.
CONCLUSION: The incidence of
hyperhomocysteinemia was higher in the patients with occlusive
vascular disease than in the control patients. More evidence of
the association with vitamins B(12) and folate and the benefits of
homocysteine-lowering therapy is needed since we found no
relationship between these vitamins and homocysteine in this
study.
HCy / MTA / autres
patho neuro
degénératives
Lancet Neurol. 2006
Mar;5(3):198-9.
Association between CSF biomarkers and
incipient Alzheimer's disease in patients with mild cognitive
impairment: a follow-up study.
Hansson
O,
Zetterberg
H,
Buchhave
P,
Londos
E,
Blennow
K,
Minthon
L.
Clinical Memory Research Unit, Department of Clinical Sciences Malmo,
Lund University, Sweden.
BACKGROUND: Disease-modifying treatment strategies for Alzheimer's
disease have led to an urgent need for biomarkers to identify the
disease at a very early stage. Here, we assess the association
between CSF biomarkers and incipient Alzheimer's in patients with
mild cognitive impairment (MCI). METHODS: From a series of 180
consecutive patients with MCI, we assessed 137 who underwent
successful lumbar puncture at baseline. Patients at risk of
developing dementia were followed clinically for 4-6 years.
Additionally, 39 healthy individuals, cognitively stable over 3
years, served as controls. We analysed CSF concentrations of beta
amyloid(1-42) (Abeta42), total tau (T-tau), and phosphorylated tau
(P-tau181) using Luminex xMAP technology. FINDINGS: During follow-up,
57 (42%) patients with MCI developed Alzheimer's disease, 21 (15%)
developed other forms of dementia, and 56 (41%) remained cognitively
stable for 5.2 years (range 4.0-6.8). A combination of CSF T-tau and
Abeta42 at baseline yielded a sensitivity of 95% and a specificity of
83% for detection of incipient AD in patients with MCI. The relative
risk of progression to Alzheimer's disease was substantially
increased in patients with MCI who had pathological concentrations of
T-tau and Abeta42 at baseline (hazard ratio 17.7, p<0.0001). The
association between pathological CSF and progression to Alzheimer's
disease was much stronger than, and independent of, established risk
factors including age, sex, education, APOE genotype, and plasma
homocysteine. The combination of T-tau and Abeta42/P-tau181 ratio
yielded closely similar results (sensitivity 95%, specificity 87%,
hazard ratio 19.8).
INTERPRETATION: Concentrations of T-tau, P-tau181, and Abeta42 in CSF
are strongly associated with future development of Alzheimer's
disease in patients wit
Dement Geriatr Cogn
Disord. 2006;21(3):148-54. Epub 2006 Jan
2.
Plasma homocysteine and vascular disease in
psychogeriatric patients.
Nilsson
K,
Gustafson
L,
Hultberg
B.
Department of Psychogeriatrics, Clinical Science, Lund University
Hospital, Lund, Sweden.
BACKGROUND: There is a high frequency (40-50%) of elevated plasma
total homocysteine (tHcy) concentrations in elderly patients with
mental disorders, and patients with a history of vascular disease
exhibit significantly higher plasma tHcy concentration than patients
without vascular disease. METHOD: The main objective of the present
study was to further investigate the association between plasma tHcy
concentration and vascular disease in psychogeriatric patients. We
have therefore investigated 304 psychogeriatric patients and
determined plasma tHcy and its most important determinants (folate
and cobalamin status and renal function), and the natriuretic peptide
N-terminal-pro brain natriuretic peptide (NT-proBNP). The patients
were classified into several groups of vascular disease according to
the findings of brain imaging and presence of a history/symptoms
indicating manifest occlusive arteriosclerotic vascular disease.
RESULTS: Plasma tHcy concentration is associated with the presence of
vascular disease in psychogeriatric patients. The presence of
vascular disease is also associated with higher age, higher serum
NT-proBNP, renal impairment and lower serum folate concentration than
in patients without vascular disease. The significant association
between plasma tHcy concentration and vascular disease remained after
correction for age and for cystatin C differences between the groups
of patients without and with vascular disease. In the present
population with only 16% of the patients showing elevated plasma
tHcy, renal function was a more important determinant for plasma tHcy
concentration than folate status.
CONCLUSION: Plasma tHcy concentration is
associated with vascular disease. In the present population of
psychogeriatric patients renal function is associated with vascular
disease and elevated plasma tHcy concentration. Thus, the association
between plasma tHcy concentration and vascular disease might
partially be explained by impairment of renal function.
J Neurol Neurosurg
Psychiatry. 2006 Feb;77(2):189-92.
Plasma homocysteine levels in multiple
sclerosis.
Ramsaransing
GS,
Fokkema
MR,
Teelken
A,
Arutjunyan
AV,
Koch
M,
De Keyser
J.
Department of Neurology, University Medical Center Groningen,
Hanzeplein 1, 9713 GZ Groningen, Netherlands.
BACKGROUND: There is evidence that homocysteine contributes to
various neurodegenerative disorders, and elevated plasma homocysteine
levels have been observed in patients with multiple sclerosis (MS).
OBJECTIVE: To investigate if and why plasma homocysteine levels are
increased in MS, and whether they play a role in the disease course.
METHODS: We compared plasma levels of homocysteine in 88 patients
with MS and 57 healthy controls. In the MS group, 28 had a benign
course, 37 were secondary progressive, and 23 primary progressive. To
explore the underlying mechanisms, we measured serum levels of
vitamins B6 and B12, folate, interleukin (IL)-12, tumour necrosis
factor (TNF)-alpha, leukocyte nitric oxide production, and plasma
diene conjugate levels (measure of oxidative stress). RESULTS: Mean
(SD) plasma homocysteine concentration was higher in patients (13.8
(4.9) micromol/l) than in controls (10.1 (2.5) micromol/l;
p<0.0001). However, there were no significant differences in
homocysteine levels between the three clinical subgroups of MS. Serum
concentrations of vitamin B6, vitamin B12, and folate were not
different between patients with MS and controls. In the MS group,
there were no correlations between plasma homocysteine levels and the
serum concentrations of IL-12 or TNF-alpha, leukocyte nitric oxide
production, or plasma diene conjugate levels.
CONCLUSIONS: Elevated plasma homocysteine
occurs in both benign and progressive disease courses of MS, and
seems unrelated to immune activation, oxidative stress, or a
deficiency in vitamin B6, vitamin B12, or
folate.
INFLAMMATION et Hcy
PATHO OCULAIRE et Hcy
Glaucome et Hcy :
DMLA et Hcy
Thrombose veine centrale rétine
DENSITÉ OSSEUSE et
Hcy
ANTIOXYDANTS et DOMMAGES RELIÉS À
Hcy
Scand J Clin Lab Invest.
2006;66(1):45-54.
Increased levels of C-reactive protein and
interleukin-6 in hyperhomocysteinemic
subjects.
Holven
KB,
Aukrust
P,
Retterstol
K,
Hagve
TA,
Morkrid
L,
Ose
L,
Nenseter
MS.
OBJECTIVE: Elevated plasma homocysteine concentration is considered
to be an independent risk factor for cardiovascular disease. However,
the mechanisms by which hyperhomocysteinemia are related to vascular
disease are unclear. High-sensitivity C-reactive protein (CRP), a
marker of inflammation, has been reported to be an independent
predictor of future myocardial infarction among clinically healthy
individuals. Interleukin (IL)-6 is a regulator of CRP and has a key
role in initiation of inflammation. The aim of this study was to
investigate whether individuals with increased plasma homocysteine
concentrations have altered levels of serum CRP and IL-6.
MATERIAL AND METHODS: Serum concentrations of CRP and IL-6 were
measured in 39 individuals with hyperhomocysteinemia and in 39
control subjects matched for gender, age and body mass index (BMI).
In addition, the inflammatory effect of IL-6 on peripheral blood
mononuclear cells was measured. RESULTS: Compared to controls,
hyperhomocysteinemic subjects have elevated serum levels of CRP and
IL-6 (p < or =0.001 and p < 0.005, respectively). Importantly,
this raised level of IL-6 was also seen in hyperhomocysteinemic
individuals without accompanying hypercholesterolemia or
cardiovascular disease. IL-6 increased the release of monocyte
chemoattractant protein-1 from peripheral blood mononuclear cells,
with particularly enhancing effects in cells from patients with
hyperhomocysteinemia. CONCLUSIONS: These data suggest that enhanced
inflammation may be associated with homocysteine-related
cardiovascular disease, possibly involving IL-6-related
mechanisms.
Glaucome et Hcy :
BMC
Ophthalmol. 2006 Feb 23;6:6.
Serum homocysteine, vitamin B 12 and folic
acid levels in different types of
glaucoma.
Cumurcu
T,
Sahin
S,
Aydin
E.
BACKGROUND: This study was performed to compare levels of serum
homocysteine (Hcy), vitamin B12 and folic acid in patients with
primary open-angle glaucoma (POAG), pseudoexfoliative glaucoma
(PEXG), normotensive glaucoma (NTG) and healthy controls.
METHODS: Twenty-five patients with POAG, 24 with PEXG, and 18 with
NTG, along with 19 control healthy subjects were included this
prospective study. Levels of serum Hcy were measured using
immunoassay, and those of serum vitamin B12 and folic acid were
measured using competitive chemiluminescent enzyme immunoassay.
RESULTS: The mean Hcy concentration in the PEXG group was
significantly higher (P < 0.001) as compared to the other groups.
There were no significant differences with respect to the mean Hcy
concentrations among other groups (P > 0.05). There were no
statistical differences in serum vitamin B12 levels among POAG, PEXG,
NTG and control subjects (P > 0.05).The mean serum folic acid
level was significantly lower in the subjects with PEXG (P <
0.009). However, the mean folic acid concentrations among the other
groups did not differ significantly (P > 0.05).
CONCLUSION: Elevated levels of Hcy in PEXG
may explain the role of endothelial dysfunction among patients with
PEXG.
DMLA et
Hcy
Am J
Ophthalmol. 2006 Jan;141(1):201-3.
Evaluation of plasma homocysteine and risk
of age-related macular degeneration.
Seddon
JM,
Gensler
G,
Klein
ML,
Milton
RC.
PURPOSE: To assess the relationship between plasma levels of
homocysteine and age-related macular degeneration (AMD). DESIGN:
Cross-sectional, case-control study. METHODS: Fasting plasma
homocysteine levels were measured at two centers in 934 individuals
who were participating in an ancillary study of the Age-Related Eye
Disease Study. There were 547 cases and 387 control subjects, who
were determined by fundus photography. Conditional logistic
regression analyses were conducted to assess the association of
homocysteine with AMD. RESULTS: Median values of homocysteine were
higher among advanced AMD cases (9.51 mmol/l) compared with persons
with no AMD (8.81 mmol/l; P = .01). Values of >12 mmol/l vs <
or =12 mmol/l were also associated with an increased risk of AMD (P =
.023), when controlled for other covariates.
CONCLUSION: Results are consistent with a
possible association between higher homocysteine levels and AMD.
Homocysteine may be a modifiable risk factor for AMD.
Thrombose veine centrale
rétine
Retina. 2006 Jan;26(1):65-70.
Moderate hyperhomocysteinemia and
early-onset central retinal vein
occlusion.
Lattanzio
R,
Sampietro
F,
Ramoni
A,
Fattorini
A,
Brancato
R,
D'Angelo
A.
Department of Ophthalmology & Visual Sciences, University
Hospital S. Raffaele, Milan, Italy. lattanzio.rosangela@hsr.it
PURPOSE: To evaluate the prevalence of moderate fasting
hyperhomocysteinemia (HHcy) and postmethionine load (PML) HHcy among
patients with early-onset central retinal vein occlusion (CRVO).
METHODS: The prevalence of fasting HHcy and that of PML HHcy were
evaluated in a consecutive series of 58 patients with CRVO who were
younger than 56 years of age (mean age, 40.3 years) and in 103
controls (mean age, 39.6 years). Plasma folate, vitamin B12, and
pyridoxal-5'-phosphate (PLP) levels were measured in 42 patients and
67 controls. RESULTS: Mantel-Haenszel odds ratios for CRVO patients
were 3.00 (95% confidence interval [CI], 0.83-10.8) for
fasting HHcy, 3.50 (95% CI, 1.07-11.4) for PML HHcy, and 3.00
(1.18-7.6) for fasting HHcy and PML HHcy in subjects with normal
fasting total homocysteine (tHcy) levels. Moderate HHcy was
associated with reduced plasma levels of folate and PLP (P < or =
0.04). There was no significant dependence of fasting and PML tHcy
levels on any traditional risk factor evaluated.
CONCLUSIONS: Moderate HHcy is an independent risk factor for
early-onset CRVO.
Arch Intern Med. 2006 Jan
9;166(1):88-94.
Plasma total homocysteine level and bone
mineral density: the Hordaland Homocysteine
Study.
Gjesdal
CG,
Vollset
SE,
Ueland
PM,
Refsum
H,
Drevon
CA,
Gjessing
HK,
Tell
GS.
BACKGROUND: Plasma total homocysteine (tHcy) has been associated with
hip fracture but not directly with bone mineral density (BMD). We
examined the association of hip BMD with levels of plasma tHcy,
folate, and vitamin B12 and the methylenetetrahydrofolate reductase
(MTHFR) 677C-->T and 1298A-->C polymorphisms. METHODS: Bone
mineral density was measured between 1997 and 2000 in 2268 men and
3070 women, aged 47 to 50 and 71 to 75 years, from the Hordaland
Homocysteine Study cohort. Low BMD was defined as BMD in the lowest
quintile for each sex and age group. Linear, logistic, and
generalized additive regression models were used. RESULTS: Plasma
levels of tHcy were inversely related to BMD among middle-aged and
elderly women (P<.001) but not among men. The multiple adjusted
odds ratio for low BMD among subjects with high (>or=15 micromol/L
[>or=2.02 mg/L]) compared with low (<9 micromol/L
[<1.22 mg/L]) tHcy level was 1.96 (95% confidence
interval, 1.40-2.75) for women and was not significant for men.
Additional adjustments for plasma folate level or intake of calcium
and vitamin D did not substantially alter the results. Plasma folate
level was associated with BMD in women only. We observed no
association between BMD and vitamin B12 level or the MTHFR
polymorphisms.
CONCLUSIONS: Elevated tHcy and low folate
levels were associated with reduced BMD in women but not in men.
These findings suggest that tHcy may be a potential modifiable risk
factor for osteoporosis in women.
J Nutr.
2006 Mar;136(3 Suppl):810S-812S.
Garlic reduces dementia and heart-disease
risk.
Borek
C.
Department of Public Health and Family Medicine, Tufts University
School of Medicine, Boston, MA 02111, USA.
Risk factors for cardiovascular disease, including high cholesterol,
high homocysteine, hypertension and inflammation, increase the risk
of dementia, including its most common form, Alzheimer's disease
(AD). High cholesterol is also associated with elevated beta-amyloid
(Abeta), the hallmark of AD. Oxidative damage is a major factor in
cardiovascular disease and dementia, diseases whose risk increases
with age. Garlic, extracted and aged to form antioxidant-rich aged
garlic extract (AGE or Kyolic), may help reduce the risk of these
diseases. AGE scavenges oxidants, increases superoxide dismutase,
catalase, glutathione peroxidase, and glutathione levels, and
inhibits lipid peroxidation and inflammatory prostaglandins. AGE
reduces cholesterol synthesis by inhibiting
3-hydroxy-3-methylglutaryl-CoA reductase and is additive with statins
in its action. Inhibition of cholesterol, LDL oxidation, and platelet
aggregation by AGE, inhibits arterial plaque formation; AGE decreases
homocysteine, lowers blood pressure, and increases microcirculation,
which is important in diabetes, where microvascular changes increase
heart disease and dementia risks. AGE also may help prevent cognitive
decline by protecting neurons from Abeta neurotoxicity and apoptosis,
thereby preventing ischemia- or reperfusion-related neuronal death
and improving learning and memory retention. Although additional
observations are warranted in humans, compelling evidence supports
the beneficial health effects attributed to AGE in helping prevent
cardiovascular and cerebrovascular diseases and lowering the risk of
dementia and AD.
J
Nutr. 2006 Mar;136(3 Suppl):755S-758S.
Aged garlic extract inhibits
homocysteine-induced CD36 expression and foam cell formation in human
macrophages.
Ide
N,
Keller
C,
Weiss
N.
Elevated plasma homocysteine (Hcy) levels have been recognized as an
independent risk factor for atherosclerotic vascular disease. During
formation of early atherosclerotic lesions, expression of CD36, a
class B scavenger receptor on macrophages, is crucially involved in
the uptake of oxidized low-density lipoprotein (OxLDL) and foam-cell
formation. We therefore determined the effects of Hcy on CD36
expression and foam cell formation in human monocytes/macrophages
(THP-1) using flow cytometry, and the effects of aged garlic extract
(AGE) on this process. Incubation of THP-1 cells with Hcy (200
micromol/L) for 72 h in the presence of phorbol 12-myristate
13-acetate (PMA) (10 nmol/L) caused a 37.8+/-5.2% increase in CD36
expression compared with PMA-stimulated cells without Hcy
(P<0.01). Coincubation with AGE (5 g/L) significantly suppressed
CD36 expression by 61.8+/-13.9%, compared with control conditions,
and by 48.6+/-9.0% compared with Hcy-incubated cells (P<0.01).
THP-1 cells in the presence of PMA (10 nmol/L) were incubated with
Hcy or AGE for 72 h followed by incubation with
1,1'-dioctadecyl-3,3,3'3'-tetra-methylindocyanide percholorate
(DiI)-labeled OxLDL for 3 h, and fluorescence intensity was measured
by flow cytometry. AGE also inhibited DiI-labeled OxLDL uptake into
PMA-stimulated THP-1 cells by 85.6+/-2.8% (P<0.01), but Hcy had no
effects on it. Our data indicate that AGE inhibits CD36 expression
and OxLDL uptake in macrophages and suggest that the extract could
modulate the formation of early atherosclerotic lesions.
J
Nutr. 2006 Mar;136(3 Suppl):750S-754S.
Aged garlic extract improves
homocysteine-induced endothelial dysfunction in macro- and
microcirculation.
Weiss
N,
Ide
N,
Abahji
T,
Nill
L,
Keller
C,
Hoffmann
U.
Department of Metabolic Diseases, Medical Policlinic, City Campus,
University of Munich Medical Center, Munich,
Endothelial dysfunction caused by increases in vascular oxidant
stress that decrease bioavailable nitric oxide (NO) plays a critical
role in the vascular pathobiology of hyperhomocysteinemia. Boosting
cellular glutathione levels or increasing the activity of cellular
glutathione peroxidase can compensate for homocysteine's effects on
endothelial function. Aged garlic extract (AGE) contains water- and
oil-soluble sulfur compounds that modify the intracellular thiol and
redox state, minimize intracellular oxidant stress, and stimulate NO
generation in endothelial cells and animals. We performed a
placebo-controlled, blinded, crossover trial to examine whether AGE
reduces macro- and microvascular endothelial dysfunction during acute
hyperhomocysteinemia induced by an oral methionine challenge in
healthy subjects. Acute hyperhomocysteinemia leads to a significant
decrease in flow-mediated vasodilation of the brachial artery as
determined by vascular ultrasound, indicative of macrovascular
endothelial dysfunction. In addition, acute hyperhomocysteinemia
leads to a decrease in acetylcholine-stimulated skin perfusion as
measured by laser-Doppler flowmetry. This indicates microvascular
endothelial dysfunction, which is presumably a result of impairment
of the endothelium-derived hyperpolarizing factor pathway.
Pretreatment with AGE for 6 wk significantly diminished the adverse
effects of acute hyperhomocysteinemia in both vascular territories.
We conclude that AGE may at least partly prevent a decrease in
bioavailable NO and endothelium-derived hyperpolarizing factor during
acute hyperhomocysteinemia. This pilot study warrants further
investigations on the effects of AGE on endothelial dysfunction in
patients with other cardiovascular risk factors or established
vascular disease and on the clinical outcome of patients with
cardiovascular disease.
J
Nutr. 2006 Mar;136(3 Suppl):745S-749S.
Homocysteine-lowering action is another
potential cardiovascular protective factor of aged garlic
extract.
Yeh
YY,
Yeh
SM.
Department of Nutritional Sciences, The Pennsylvania State
University, University Park, PA 16803, USA.
We investigated hypohomocysteinemic action as a cardiovascular
protective property of aged garlic extract (AGE).
Hyperhomocysteinemia was induced in rats by feeding folate-depleted
diets. Plasma folate concentrations of 5, 24, and 202 nmol/L were
detected in rats fed a folate-deficient L-amino acid diet containing
succinyl sulfathiazole, an AIN-93G folate-deficient diet, and an
AIN-93G folate-sufficient diet, respectively. Plasma concentrations
of total homocysteine were elevated to the highest level (32
micromol/L) by severe folate deficiency and to a moderate level (9
micromol/L) by mild folate deficiency, compared with the lowest level
of (5 micromol/L), noted for the folate-sufficient group. The
addition of AGE to the severely folate-deficient diet decreased
plasma total homocysteine concentration by 30%. Hyperhomocysteinemia
caused by mild folate deficiency remained unaltered by AGE
supplementation. The reduction in total homocysteine of the severely
folate-deficient rats was accompanied by a proportional decrease in
protein-bound and free homocysteine, resulting in an unchanged
protein-bound:free homocysteine ratio. AGE added to the diet did not
alter plasma concentrations of other aminothiol compounds: cysteine,
glutathione, and cysteinylglycine. These data, together with
increased S-adenosylmethionine and decreased S-adenosylhomocysteine
concentrations in the liver, suggest that the hypohomocysteinemic
effect of AGE most likely stems from impaired remethylation of
homocysteine to methionine and enhanced transsulfuration of
homocysteine to cystathionine. More
importantly, in addition to its cholesterol-lowering potential, blood
pressure-lowering effect, and antioxidant property, a
hypohomocysteinemic action may be another important cardiovascular
protective factor of AGE.
COMPLÉMENTS 2009
CONCLUSIONS
Ce qui n'est plus contestable
:
HOMOCYSTEINE = MARQUEUR DE RISQUE CV CHEZ LA PA
Valeur individuelle ? index composite (Il6 + HCy + CRP+...)
?
Ce qui demande encore confirmation
:
HOMOCYSTEINE = TEMOIN BIOLOGIQUE DE VULNERABILITE,
en particulier au plan cérébral, mais peut être
pour d'autres tissus (accroissement de l'attaque radicalaire)
Ce qui représente une
retombée immédiate
pratique
HOMOCYSTEINE = BON REFLET DE LA CARENCE EN VITAMINES DU
GROUPE B et en FOLATES ;
plus exactement reflet du défaut de
biodisponibilité
Dosage plasmatique peu onéreux
mais difficile à proposer