Serum high concentrations of homocysteine and low levels of folic acid and vitamin B12 are significantly correlated with the categories of coronary artery diseases

Abstract

Background
Homocysteine (Hcy) has been considered as an independent risk factor for coronary artery disease (CAD). Folic acid and vitamin B12 are two vital regulators in Hcy metabolic process. We evaluated the correlations between serum Hcy, folic acid and vitamin B12 with the categories of CAD.

Methods
Serum Hcy, folic acid and vitamin B12 from 292 CAD patients, including 73 acute myocardial infarction (AMI), 116 unstable angina pectoris (UAP), 103 stable angina pectoris (SAP), and 100 controls with chest pain patients were measured, and the data were analyzed by SPSS software.

Results
Compared to SAP patients, patients with AMI and UAP had higher Hcy levels with approximately average elevated (4-5) μmol/L, while SAP patients were approximately higher 8 μmol/L than controls. However, the levels of folic acid and vitamin B12 had opposite results, which in AMI group was the lowest, while in controls was the highest. CAD categories were positively correlated with Hcy (r = 0.286, p < 0.001), and negatively correlated with folic acid (r = -0.297, p < 0.001) and vitamin B12 (r = -0.208, p < 0.001). There were significant trend toward increase in the prevalence of high Hcy, low folic acid and vitamin B12 from controls, to SAP, to UAP, and to AMI.

Conclusions
The present study provide the valuable evidence that high concentrations of Hcy and low levels of folic acid and vitamin B12 are significantly correlated with CAD categories.

Full text

R E S E A R C H A R T I C L E Open Access
Serum high concentrations of homocysteine
and low levels of folic acid and vitamin B
12
are significantly correlated with the
categories of coronary artery diseases
Yan Ma
1
, Duanliang Peng
1
, Chenggui Liu
2*
, Chen Huang
2
and Jun Luo
1
Abstract
Background: Homocysteine (Hcy) has been considered as an independent risk factor for coronary artery disease
(CAD). Folic acid and vitamin B
12
are two vital regulators in Hcy metabolic process. We evaluated the correlations
between serum Hcy, folic acid and vitamin B
12
with the categories of CAD.
Methods: Serum Hcy, folic acid and vitamin B
12
from 292 CAD patients, including 73 acute myocardial infarction
(AMI), 116 unstable angina pectoris (UAP), 103 stable angina pectoris (SAP), and 100 controls with chest pain
patients were measured, and the data were analyzed by SPSS software.
Results: Compared to SAP patients, patients with AMI and UAP had higher Hcy levels with approximately average
elevated (4-5) μmol/L, while SAP patients were approximately higher 8 μmol/L than controls. However, the levels of
folic acid and vitamin B
12
had opposite results, which in AMI group was the lowest, while in controls was the
highest. CAD categories were positively correlated with Hcy (r = 0.286, p<0.001),andnegativelycorrelatedwithfolic
acid (r = -0.297, p< 0.001) and vitamin B
12
(r = -0.208, p< 0.001). There were significant trend toward increase in the
prevalence of high Hcy, low folic acid and vitamin B
12
from controls, to SAP, to UAP, and to AMI.
Conclusions: The present study provide the valuable evidence that high concentrations of Hcy and low levels of folic
acid and vitamin B
12
are significantly correlated with CAD categories.
Keywords: Homocysteine, Folic acid, Vitamin B
12
, Coronary artery disease, Atherosclerosis, Endothelial dysfunction
Background
Coronary artery disease (CAD) is seriously to harm peo-
ple’s healthy disease in borth developed and developing
countries, which was predominantly caused by athero-
sclerosis with endothelial dysfunction [1, 2]. Despite best
efforts, available therapies protect only 30–40% of indi-
viduals at risk, and no therapeutic cure is anticipated for
those who currently suffer from the disease [3]. The
endothelium is a single layer of cells lining all blood ves-
sels. It plays an important role in many physiological
functions, including the control of blood cell trafficking,
vasomotor tone, vessel permeability, and hemostatic bal-
ance. Endothelial cells produce a wide variety of sub-
stances in response to various physical and chemical
stimuli, including vasodilator substances, and vasocon-
strictor substances [4].
Researches have confirmed that endothelial dysfunc-
tion, as an impairment of endothelium-dependent re-
laxation of blood vessels, occur as the initial event in
the pathogenesis of atherosclerosis, which considered
to be the initiating factor and the key point of cardio-
vascular disease [5, 6]. Moreover, endothelial dysfunc-
tion also play the important role in all stages and
categories of CAD from stable angina pectoris (SAP)
to unstable angina pectoris (UAP), and to acute myo-
cardial infarction (AMI) [7]. Early warning and imme-
diate risk stratification of patients with different
* Correspondence: lablcg@126.com
2
Department of Clinical Laboratory, Chengdu Women’s and Children’s
Central Hospital, Chongqing Medical University, No. 1617 Ri Yue Avenue,
Qingyang District, Chengdu 610091, China
Full list of author information is available at the end of the article
© The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver
(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Ma et al. BMC Cardiovascular Disorders (2017) 17:37
DOI 10.1186/s12872-017-0475-8
Content courtesy of Springer Nature, terms of use apply. Rights reserved.

categories of CAD is frequently a challenging task in
the current.
A large number of studies have confirmed that serum
high homocysteine (Hcy) concentration (morm than
15 μmol/L), which is called hyperhomocysteinemia
(HHcy), has been associated with endothelial dysfunc-
tion of atherosclerotic CAD owing to oxidative stress
[8], endoplasmic reticulum stress [9], involved inflamma-
tion [10], increased level of asymmetric dimethylarginine
(ADMA) [11] and so on [12–14]. Elevated ADMA can
results in decreasing endothelium-derived nitric oxide
concentration and bioavailability [15]. Nitric oxide as a
most important mediator of endothelium-dependent re-
laxation, is a potent vasodilator, which plays a key role
in normal vascular physiology in preserving the vessel
wall in a quiescent state by inhibition of inflammation,
thrombosis, and cellular proliferation [16]. Decreased ni-
tric oxide bioavailability would result in the abnormal
thrombosis, vasorelaxation, and atherosclerosis, thereby
promoting the occurrence and development of CAD [17].
Folic acid and vitamin B
12
play an important role in
regulating the metabolic process of Hcy [18]. Current
studies have shown that supplement folic acid, vitamin
B
12
in patients with HHcy could reduce Hcy levels [19].
Folic acid supplementation not only may be useful in re-
ducing Hcy level in high risk patients with HHcy [20],
but also can significantly improve endothelial dysfunc-
tion in patients with CAD [21]. On the other hand, folic
acid deficiency or/and vitamin B
12
deficiency would re-
sult in HHcy [22–24]. Vitamin B
12
deficiency and HHcy
are related to cardiovascular risk factors in patients with
CAD [25]. However, the correlations of CAD categories
with Hcy, folic acid, vitamin B
12
have not been reported.
Therefore, we evaluate the correlations between CAD
categories and each of the metabolic parameters, an-
thropometric variables, life style habits and traditional
cardiovascular risk factors in CAD patients and controls
with chest pain patients.
Methods
This study included 292 CAD patients (203 male and 89
female) aged 36–85 (62.54 ± 14.52) years, and 100 controls
with chest pain symptom (69 male and 31 female) aged
38–87 (60.93 ± 15.65) years, from the Sichuan Academy of
Medical Sciences & Sichuan Provincial People’s Hospital.
There were no statistically significant difference in age
(means ± SD, t = 0.94, p= 0.348) and gender (male to
female ratio, χ
2
= 0.01, p= 0.922) between CAD group
and controlled group.
All enrolled CAD patients had been confirmed by cor-
onary angiography and were diagnosed to be103 SAP,
116 UAP, 73 AMI according to 2007 ACC/AHA guide-
lines. 100 controls with chest pain patients in the same
period were confirmed by coronary angiography too.
Patients with the following diseases were excluded from
this study: cancer, liver diseases, renal insufficiency,
blood diseases, hyperthyroidism, thyroid dysfunction,
systemic lupus erythematosus, malnutrition, pregnant
woman, and supplemented folic acid and vitamin B
12
.
Participating subjects were explained their participa-
tion rights and written informed consent was obtained,
and were asked about alcohol intake situation (yes or no,
it was defined as yes at least once a week and drinking
over 45° of alcohol more than 200 mL) and smoking
habits (yes or no, non-smokers including never smoking
and stop smoking more than 1 year).
The data was consecutively collected from October
2013 to September 2014. Fasting blood was sampled in
the morning within 24 h that the patients had been ad-
mitted to hospital. The blood must be collected before
the heparinization of coronary angiography. Moreover,
AMI patient’s blood was collected before percutaneous
coronary intervention and thrombolytic treatment. After
blood was separated, a fresh serum were used with
Hitachi 7600 Automatic Biochemistry Analyzer (Hitachi
High-Tech Instruments Co., Ltd., Japan) for the determi-
nations of Hcy, total cholesterol (TC), triglyceride (TG),
high density lipoprotein cholesterol (HDL-C), low dens-
ity lipoprotein cholesterol (LDL-C), glucose (GLU) and
uric acid (UA). Another fresh serum were used for the
determinations of folic acid and vitamin B
12
by ACCESS
2 Immunoassay System (Beckman Coulter, Inc., USA).
High Hcy, folic acid and vitamin B
12
were defined as
Hcy, folic acid and vitamin B
12
greater than 15 μmol/L,
26.0 nmol/L and 675 pmol/L, respectively, while low Hcy,
folic acid and vitamin B
12
were defined as Hcy, folic acid
and vitamin B
12
less than 5 μmol/L, 6.8 nmol/L and 133
pmol/L, respectively, according to their references intervals
were (5–15) μmol/L for Hcy, (6.8–26.0) nmol/L for folic
acid and (133–675) pmol/L for vitamin B
12
, respectively.
Systolic blood pressure (SBP) and diastolic blood pressure
(DBP), body weight and height were measured with stand-
ard techniques. Body mass index (BMI) was calculated as
body weight (kg) divided by the square of height (m).
Hypercholesterolemia and hypertriglyceridemia were
defined as TC ≥6.22 mmol/L and TG ≥2.26 mmol/L, re-
spectively, according to 2007 China Adult Dyslipidemia
Prevention Guide. Diabetes mellitus was diagnosed when
patients’GLU ≥7.0 mmol/L. Hypertension was diag-
nosed when patients’SBP ≥140 mmHg or DBP ≥
90 mmHg. Overweight and obesity were defined as BMI
(24.0–27.9) kg/m
2
, and ≥28 kg/m
2
, respectively, accord-
ing to 2006 Guidelines for Prevention and Control of
Overweight and Obesity in Chinese Adults.
Statistical analysis
The data were analyzed by using the statistical package
for social science SPSS software version 16.0 (SPSS, Inc.,
Ma et al. BMC Cardiovascular Disorders (2017) 17:37 Page 2 of 7
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Chicago, IL, USA). Continuous variables were expressed
as mean ± SD because the data presented in this study
showed a normal distribution. Means ± SD of two samples
were compared by the Independent-Sample t-Test, and
means ± SD of more than two samples were compared
with the One-Way ANOVA. Categorical variables were
expressed as percentage and compared by χ
2
-test. The
correlation coefficients of CAD categories with each of
the metabolic parameters, anthropometric variables and
life style habits were calculated by Spearman’sanalysisbe-
cause CAD is a grade variable, while the correlation study
between Hcy and folic acid as well as vitamin B
12
were
performed on the measured data by using Pearson’scor-
relation a coefficient because Hcy, folic acid and vitamin
B
12
are continuous variables with normal distribution. A
p-value < 0.05 was considered as significant.
Results
Comparison of principal characteristics between high Hcy,
normal Hcy and low Hcy levels in CAD patients
Compared to normal and low Hcy groups, High Hcy group
were characterized by smoking, Diabetes mellitus, hyper-
cholesterolemia, hypertriglyceridemia, low folic acid, low
vitamin B
12
, low HDL-C and high LDL-C (p<0.05). There
were no significant differences in the ratio of elder age,
male, female, alcohol drinking, hypertension, overweight
and obesity among three groups. The comparison of princi-
pal characteristics between high Hcy, normal Hcy and low
Hcy levels in 292 CAD patients are reported in Table 1.
More than half of the CAD patients (51.08%, 118/231)
with high Hcy had low folic acid levels, 7 times higher
than that (6.56%, 4/61) in CAD patients with normal-
low Hcy concentrations (p< 0.001), and 41.99% (97/231)
CAD patients with high Hcy had low vitamin B
12
levels,
5 times higher than that (8.20%, 5/61) in CAD patients
with normal-low Hcy concentrations (p< 0.001).
Comparison of Hcy, folic acid and vitamin B
12
between
CAD and controls
AMI patients had the highest serum concentrations of
Hcy, and UAP patients were a little lower than AMI but
were the second highest. and SAP patients had the third
higher level of Hcy, which were significantly higher than
controls (p<0.001). Compared to SAP patients, patients
with AMI and UAP had higher Hcy levels with approxi-
mately average elevated (4-5) μmol/L, while SAP patients
were approximately higher 8 μmol/L than controls. How-
ever, the levels of folic acid and vitamin B
12
had opposite
results, which in AMI group had the lowest, while in con-
trolled group had the highest. The comparison of Hcy,
folic acid and vitamin B
12
between AMI, UAP, SAP groups
and controls are shown in Table 2.
Correlation coefficients of CAD categories with each of
the variables and the correlations between Hcy with folic
acid and vitamin B
12
The correlation coefficients of CAD categories with
each of the metabolic parameters, anthropometric
variables and life style habits by Spearman’sanalysis
in 292 CAD patients are shown in Table 3. CAD cat-
egories were positively correlated with Hcy, TC, TG,
LDL-C, age, SBP, DBP, BMI, gender and smoking, and
negatively correlated with folic acid, vitamin B
12
and
HDL-C levels. On the contrary, CAD categories were
not significantly correlated with GLU, UA and alcohol
drinking. Among them, Hcy and folic acid showed
the highest positively and negatively correlated with
CAD categories, respectively.
Table 1 Comparison of principal characteristics between high Hcy, normal Hcy and low Hcy levels in 292 CAD patients
High Hcy group (n= 231) Normal Hcy group (n= 58) Low Hcy group (n=3) χ
2
pvalue
Elder age ≥61 (%) 61.47 51.72 33.33 2.67 0.264
Male (%) 71.00 63.79 66.67 1.15 0.564
Female (%) 29.00 36.21 33.33 1.15 0.564
Smoking (%) 29.87 13.79 33.33 6.19 0.045
Alcohol drinking (%) 39.39 34.48 66.67 1.47 0.479
Hypertension (%) 63.20 56.90 33.33 1.81 0.405
Diabetes mellitus (%) 30.30 13.79 33.33 6.46 0.039
Hypercholesterolemia (%) 46.32 25.86 0 10.15 0.006
Hypertriglyceridemia (%) 30.74 13.79 66.67 8.93 0.012
Overweight and Obesity (%) 40.26 44.83 33.33 0.48 0.789
Low folic acid (%) 51.08 6.90 0 39.39 <0.001
Low vitamin B
12
(%) 41.99 8.62 0 24.34 <0.001
Low HDL-C (%) 38.96 20.69 0 8.44 0.015
High LDL-C (%) 39.83 22.41 0 7.81 0.020
Ma et al. BMC Cardiovascular Disorders (2017) 17:37 Page 3 of 7
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Pearson’s correlation analysis showed that there
were strongly moderate negative correlations between
Hcyandfolicacid(r=-0.666,p<0.001) and vitamin
B
12
(r = -0.564, p< 0.001).
Prevalence of high Hcy, and low folic acid and vitamin
B
12
in CAD patients and controls with chest pain patient
Approximately four-fifths of CAD patients (79.11%, 231/
292) had a prevalence of high Hcy. However, the levels
of folic acid and vitamin B
12
in CAD patients were re-
duced, the prevalence were 41.78% (122/292) for folic
acid, and 34.93% (102/292) for vitamin B
12
, respectively.
The prevalence of high Hcy, and low folic acid and vita-
min B
12
in 292 CAD patients and 100 controls with
chest pain patient are shown in Table 4 and Fig. 1,
respectively. There was a significant trend toward an in-
crease in the prevalence of high Hcy from controls, to
SAP, to UAP, and to AMI. The prevalence of high Hcy
progressively increased from 5.00% in controls, to
66.02% in SAP group, to 81.90% in UAP group, and to
93.15% in AMI group (p< 0.001). Low folic acid and
vitamin B
12
also had significant trend toward rise in the
prevalence from controls, to SAP, to UAP, and to AMI.
The prevalence of low folic acid progressively increased
from 13.00% in controls, to 32.04% in SAP group, to
39.66% in UAP group, and to 58.90% in AMI group, re-
spectively (p< 0.001). Similarly, the prevalence of low
vitamin B
12
progressively increased from 15.00% in con-
trols, to 24.27% in SAP group, to 34.48% in UAP group,
and to 50.68% in AMI group, respectively (p< 0.001).
Discussion
CAD is a multifactorial disease, and these factors are
called risk factors include a large number of traditional
cardiovascular disease risk factors such as smoking,
elder age, male, hypertension, lipid metabolism disor-
ders (hyperlipidemia), glucose metabolism disorders
(diabetes mellitus and insulin resistance), overweight
and obesity, and some newly risk factors such as HHcy
and inflammatory markers. Our previous study found
that elevated serum myeloperoxidase activities are sig-
nificantly associated with the prevalence of acute cor-
onary syndrome (AMI and UAP) and high LDL-C
levels in CAD patients, The interaction between mul-
tiple metabolic parameters, inflammatory markers and
traditional cardiovascular risk factors promoted the occur-
rence and development of CAD [26]. This study revealed
that high Hcy group in CAD patients were characterized
by smoking, diabetes mellitus, hypercholesterolemia,
hypertriglyceridemia, low HDL-C and high LDL-C. These
findings suggest that Hcy and traditional cardiovascular
risk factors may be synergistically prompt the occurrence
and development of CAD.
Vascular endothelium has important regulatory func-
tions in the cardiovascular system and a pivotal role in
regulating blood flow, mediating vasodilatation, coagula-
tion reactions, platelet activation, leukocyte adhesion,
Table 2 Comparison of Hcy, folic acid and vitamin B
12
between AMI, UAP, SAP patients and controlled group with chest pain patients
Groups Number Hcy (μmol/L) Folic acid (nmol/L) Vitamin B
12
(pmol/L)
Controls 100 10.81 ± 4.62 12.86 ± 5.85 222.34 ± 62.58
Stable angina pectoris 103 18.63 ± 6.73
a
10.33 ± 4.95
b
167.52 ± 56.25
b
Unstable angina pectoris 116 22.62 ± 6.37
ac
9.21 ± 4.38
bd
148.65 ± 62.51
bd
Acute myocardial infarction 73 23.44 ± 5.78
ac
7.08 ± 3.43
bde
144.57 ± 52.24
bd
F 90.51 22.05 35.63
pvalue <0.001 <0.001 <0.001
a
Significantly increased compared to controls,
b
Significantly decreased compared to controls,
c
Significantly increased compared to SAP group,
d
Significantly
decreased compared to SAP group,
e
Significantly decreased compared to UAP group
Table 3 Spearma’s correlation coefficients of CAD categories
with each of the metabolic parameters, anthropometric
variables and life style habits in 292 CAD patients
Variable CAD categories pvalue
Homocysteine 0.286 <0.001
Folic acid -0.297 <0.001
Vitamin B
12
-0.208 <0.001
TC 0.242 <0.001
TG 0.141 0.016
HDL-C -0.153 0.009
LDL-C 0.187 0.001
GLU 0.088 0.132
UA 0.078 0.182
Age 0.151 0.010
SBP 0.135 0.021
DBP 0.125 0.032
BMI 0.148 0.011
Gender 0.128 0.028
Smoking 0.278 <0.001
Alcohol drinking 0.072 0.218
Hcy homocysteine, TC total cholesterol, TG triglyceride, HDL-C high-density
lipoprotein cholesterol, LDL-C low-density lipoprotein cholesterol, GLU glucose,
UA uric acid, SBP systolic blood pressure, DBP diastolic blood pressure, BMI
body mass index
Ma et al. BMC Cardiovascular Disorders (2017) 17:37 Page 4 of 7
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and vascular muscle function [27]. During the last two
decades, extensive experimental evidence, both in vitro
and in vivo, indicates that Hcy is an independent risk
factor for cardiovascular disease and elevated serum Hcy
level is associated with CAD events [28–30]. Homocyst-
eine Studies Collaboration research revealed that ele-
vated approximately 3 μmol/L Hcy will increase about
10% risk of cardiovascular events [31]. Humphrey et al.
[32] analyzed has also demonstrated that increased
5μmol/L Hcy concentration will increase approximately
20% risk of CAD events.
In present study, AMI patients had the highest serum
concentrations of Hcy, and UAP patients were a little
lower than AMI but were the second highest, and SAP
patients had the third higher level of Hcy, which were
significantly higher than controls. Compared to SAP pa-
tients, patients with AMI and UAP had higher Hcy
levels with approximately average elevated (4-5) μmol/L,
while SAP patients were approximately higher 8 μmol/L
than controls. CAD categories were positively correlated
with Hcy, TC, TG, LDL-C, age, SBP, DBP, BMI, gender
and smoking. Among them, Hcy showed the highest
positively correlated with CAD categories. The preva-
lence of high Hcy progressively increased from controls,
to SAP, to UAP, and to AMI. The present provide the
valuable evidence that high concentrations of Hcy are
significantly correlated with CAD categories. The more
serious patients with CAD suffer, the more higher con-
centration their Hcy have.
Folic acid and vitamin B
12
as two vital regulators
play an important role in regulating the metabolic
process of Hcy [33, 34]. In biological cells, Hcy is de-
rived from methionine after its utilization as a methyl
group donor in biological methylation reactions. However,
approximately 50% Hcy is produced to remethylate
back to methionine by the transmethylation of methio-
nine, while 50% Hcy metabolize via transsulfuration to
cystathionine [35]. In this cycle, methionine is activated
by condensation with adenosine triphosphate (ATP) to
give the methyl donor, S-adenosylmethionine (SAM).
SAM is transformed into S-adenosylhomocysteine
(SAH) by donating its methyl group to the substrates of
methylation reactions. Subsequently, SAH gives rise to
Hcy in a reversible reaction that favors SAH over Hcy
production [36]. Methyl-tetra-hydrofolic acid (MTHF)
which derivate of folic acid provide methyl to remethy-
lated of Hcy. Vitamin B
12
is agon of methionine synthe-
tase that catalyzed this reaction and participate
transfusion of methyl [13]. Folic acid deficiency will
prevent remethylation of Hcy because of raw material
deficiency. Moreover, Folic acid deficiency will also
influence the production of MTHF through to affect
activity of methylene tetrahydrofolate reductase
(MTHFR) [37, 38].
Table 4 The prevalence of high Hcy, low folic acid and vitamin B
12
in 292 CAD patients and 100 controls with chest pain patient (%)
Number High Hcy (n= 236) Low folic acid (n= 135) Low vitamin B
12
(n= 117)
Controls 100 5.00 13.00 15.00
Stable angina pectoris 103 66.02 32.04 24.27
Unstable angina pectoris 116 81.90 39.66 34.48
Acute myocardial infarction 73 93.15 58.90 50.68
χ
2
184.51 41.37 28.39
pvalue <0.001 <0.001 <0.001
Fig. 1 Prevalence of high Hcy, low folic acid and vitamin B
12
in 292 CAD patients and 100 controls with chest pain patient aged 36–87 years
Ma et al. BMC Cardiovascular Disorders (2017) 17:37 Page 5 of 7
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We found that besides HDL-C, CAD categories were
significantly negative correlated with folic acid, vitamin
B
12
. the levels of folic acid and vitamin B
12
in AMI and
in UAP patients were obviously lower compared to those
in SAP and controls. The prevalence of low folic acid
and vitamin B
12
progressively increased from controls,
to SAP, to UAP, and to AMI. Moreover, more than or
close to half of the CAD patients with high Hcy had low
folic acid or vitamin B
12
levels, 7 times or 5 times higher
than that in CAD patients with normal-low Hcy concen-
trations, respectively. Hcy was strongly moderate nega-
tive correlation with folic acid and vitamin B
12
. Our
results confirmed that serum folic acid and vitamin B
12
influence Hcy metabolism as cosubstrate and cofactor,
respectively. Low serum levels of folic acid and vitamin
B
12
are also significantly correlated with CAD categories.
Study limitation
Since present study was just an investigation that the
correlations between CAD categories and serum Hcy,
folic acid, vitamin B
12
and traditional cardiovascular risk
factors. The larger sample number of multicenter study
and longer prospective investigation are necessary to fur-
ther observe serum Hcy changes and incidence of ad-
verse cardiovascular events by supplementation of folic
acid and vitamin B
12
in CAD patients.
Conclusions
The present study confirmed that Hcy and traditional
cardiovascular risk factors may be synergistically prompt
the formation and development of atherosclerosis in
CAD patients. High concentrations of Hcy and low
levels of folic acid and vitamin B
12
are significantly cor-
related with CAD categories.
Abbreviations
ADMA: Asymmetric dimethylarginine; AMI: Acute myocardial infarction;
ATP: Adenosine triphosphate; BMI: Body mass index; CAD: Coronary artery
disease; DBP: Diastolic blood pressure; GLU: Glucose; Hcy: Homocysteine;
HDL-C: High density lipoprotein cholesterol; HHcy: Hyperhomocysteinemia;
LDL-C: Low density lipoprotein cholesterol; MTHF: Methyl-tetra-hydrofolic
acid; MTHFR: Methylene tetrahydrofolate reductase; NO: Nitric oxide; SAH:
S-adenosylhomocysteine; SAM: S-adenosylmethionine; SAP: Stable angina
pectoris; SBP: Systolic blood pressure; TC: Total cholesterol; TG: Triglyceride;
THF: Ttrahydro-folic acid; UAP: Unstable angina pectoris
Acknowledgements
The authors would like to appreciate the staff in the Department of Clinical
Laboratory and Department of Cardiovascular at the Sichuan Academy of
Medical Sciences & Sichuan Provincial People’s Hospital and Department of
Clinical Laboratory, Chengdu Women’s and Children’s Central Hospital,
Chongqing Medical University for their support and guidance.
Funding
This research was supported by Sichuan Provincial Science and Technology
Department Research Foundation of China (No. 2013FZ0080) and Sichuan
Provincial Health and Family Planning Research Project Foundation of China
(No. 16PJ450), respectively.
Availability of data and materials
The raw date supporting the results and conclusions of the present study
will be available from the corresponding author on reasonable request. We
have shared the data which publiched on J Atheroscler Thromb: Elevated
serum myeloperoxidase activities are significantly associated with the
prevalence of ACS and high LDL-C levels in CHD patients, 2012, 19(5): 435–443.
Authors’contributions
YM, CL and JL carried out the carried out the clinical case screening,
data collection, and drafted the manuscript. DP and CH carried out the
immunoassays, and participated in the design of the study. CL and YMa
carried out the design of the study and coordination and helped to
draft the manuscript. CH and DP carried out the detection of clinical
biochemistry. JL, DP and CH carried out the sample measurements,
information classification and performed the statistical analysis. All
authors read and approved the final manuscript.
Competing interests
The authors declare that they have no competing interests.
Consent for publication
All authors have read and approve to submit this original article to BMC
Cardiovascular Disorders. Written consent for publication was obtained from
either the patients or their relatives.
Ethics approval and consent to participate
The study was approved by the Medical Ethics Committee at Chengdu
Women’s and Children’s Central Hospital, Chengdu, China [(2013)2, Medical
Ethics Committee, CWCCH], and was carried out in accordance with the
guidelines of the Declaration of Helsinki. Written informed consent was
obtained from all participants in the study.
Author details
1
East Branch, Sichuan Academy of Medical Sciences & Sichuan Provincial
People’s Hospital, No. 585 Hong He North RoadLongquan District, Chengdu
610101, China.
2
Department of Clinical Laboratory, Chengdu Women’s and
Children’s Central Hospital, Chongqing Medical University, No. 1617 Ri Yue
Avenue, Qingyang District, Chengdu 610091, China.
Received: 6 September 2016 Accepted: 16 January 2017
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