Serum Vitamin C Concentration Is Low in Peripheral Arterial Disease and Is Associated With Inflammation and Severity of Atherosclerosis
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Serum Vitamin C Concentration Is Low in Peripheral
Arterial Disease and Is Associated With Inflammation and
Severity of Atherosclerosis
Michel Langlois, MD, PhD; Daniel Duprez, MD, PhD; Joris Delanghe, MD, PhD;
Marc De Buyzere, PhD; Denis L. Clement, MD, PhD
Background—Peripheral arterial disease (PAD) is a severe atherosclerotic condition frequently accompanied by
inflammation and oxidative stress. We hypothesized that vitamin C antioxidant levels might be low in PAD and are
related to inflammation and disease severity.
Methods and Results—We investigated vitamin C (L-ascorbic acid) levels in 85 PAD patients, 106 hypertensives without
PAD, and 113 healthy subjects. Serum L-ascorbic acid concentrations were low among PAD patients (median, 27.8
mol/L) despite comparable smoking status and dietary intake with the other groups (P⬍0.0001). Subclinical vitamin
C deficiency (⬍11.4 mol/L), confirmed by low serum alkaline phosphatase activity, was found in 14% of the PAD
patients but not in the other groups. Serum C-reactive protein (CRP) concentrations were significantly higher in PAD
patients (P⬍0.0001) and negatively correlated with L-ascorbic acid levels (r⫽⫺0.742, P⬍0.0001). In stepwise
multivariate analysis, low L-ascorbic acid concentration in PAD patients was associated with high CRP level
(P⫽0.0001), smoking (P⫽0.0009), and shorter absolute claudication distance on a standardized graded treadmill test
(P⫽0.029).
Conclusions—Vitamin C concentrations are lower in intermittent claudicant patients in association with higher CRP levels
and severity of PAD. Future studies attempting to relate vitamin C levels to disease occurrence should include in their
analysis an inflammatory marker such as CRP. (Circulation. 2001;103:1863-1868.)
Key Words: arteries 䡲 atherosclerosis 䡲 antioxidants 䡲 inflammation 䡲 claudication
P eripheral arterial disease (PAD) is a severe atheroscle-
rotic condition causing intermittent claudication and is
associated with increased cardiovascular and cerebrovascular
In this study, we assessed whether inflammation is associ-
ated with antioxidant status in patients with intermittent
claudication. Vitamin C (L-ascorbic acid) is a water-soluble
morbidity and mortality.1,2 Moreover, it has a major impact antioxidant capable of scavenging free radicals and is the
on the quality of life because of the reduction in walking first-line defense in the control of the redox state, sparing
ability. In clinical practice, PAD is assessed noninvasively by other endogenous antioxidants from consumption.10,11 We
the determination of the ankle/brachial systolic blood pres- tested the hypothesis that vitamin C status might be low in
sure index (ABI) and absolute claudication distance (ACD) PAD and that it correlates with measures of inflammation and
on a treadmill test, a parameter of functional adaptation to the functional status in patients with intermittent claudication.
disease.3–5
Smoking, diabetes mellitus, hyperlipidemia, and hyperten- Methods
sion are the key risk factors for PAD,6 but it is now equally
recognized that low-grade inflammation contributes impor- Study Groups
We investigated 85 PAD patients (Fontaine stage II) who were
tantly to the initiation and the progression of the vascular regularly followed for at least 12 months at our department, 106
atherosclerotic lesions. Specifically, slightly elevated levels patients with essential hypertension without PAD (to account for the
of C-reactive protein (CRP), an acute phase reactant, are effect of pulse pressure), and 113 healthy volunteers of the same
associated with PAD and are found among apparently healthy region. Hypertensives were defined along the WHO/ISH criteria for
subjects at risk for developing future PAD.7,8 It has been at least 12 months and were receiving treatment with antihyperten-
sive drugs.12 Patients with either surgical revascularization or per-
suggested that inflammation within the atherosclerotic lesions
cutaneous transluminal angioplasty procedures at the lower limb
and the subsequent release of free radicals by phagocytes arteries were excluded, as well as patients with acute myocardial
result in oxidative stress that further enhances vascular infarction, angina pectoris, heart failure, coronary revascularization
damage.9 procedures, or cerebrovascular events during the last 6 months. Other
Received September 28, 2000; revision received December 21, 2000; accepted December 21, 2000.
From the Departments of Clinical Chemistry (M.L., J.D.) and Cardiology (D.D., M.D.B., D.L.C.), Ghent University Hospital, Ghent, Belgium.
Correspondence to Dr Michel Langlois, Laboratory of Clinical Chemistry, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent, Belgium.
E-mail michel.langlois@rug.ac.be
© 2001 American Heart Association, Inc.
Circulation is available at http://www.circulationaha.org
1863
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TABLE 1. Clinical Characteristics of Study Groups
Healthy Subjects Hypertension Without PAD
(n⫽113) (n⫽106) PAD (n⫽85)
Age, y 61⫾12 62⫾14 68⫾10
Male sex, % 45 42 78†
Postmenopausal, % of women 89 87 89
Body mass index, kg/m2 25⫾4 28⫾5 26⫾5
Hypertension, % 0 100 50
Diabetes mellitus, % 0 19 17
Smoking, % 31 34 33
No. of cigarettes/d 22⫾9 19⫾8 18⫾8
Vitamin C intake, mg/d 121⫾39 117⫾36 118⫾40
Physical activity, MET h/wk* 27⫾16 24⫾15 20⫾13‡
Blood pressures, mm Hg
Systolic 126⫾10 147⫾15 142⫾20‡
Diastolic 75⫾8 91⫾12 82⫾9‡
Pulse pressure 51⫾9 56⫾13 60⫾19‡
ABI ⬎1 ⬎1 0.61⫾0.15
Medication, % of patients
-Blockers 0 64 31
Calcium antagonists 0 44 21
ACE inhibitors 0 35 19
Diuretics 0 29 11
Aspirin 0 0 68
Lipid-lowering agents 0 20 19
Values are mean⫾SD or percentages.
*Intensity (MET, metabolic units) multiplied by the duration (h/wk) of specified activities.16
†P⬍0.001 (2 test).
‡P⬍0.05 (Kruskal-Wallis test).
exclusion criteria were intake of antioxidant vitamin supplements, tration was calculated by the Friedewald formula. Diabetes control
alcohol intake ⬎20 g/d, and hormone replacement therapy. PAD status was assessed by hemoglobin A1c (HbA1c) with a Variant II
patients had been motivated to participate in an exercise rehabilita- chromatographic system (Bio-Rad). Intra-assay coefficients of vari-
tion program that included 3 walking sessions per week with a ation were ⬍5.0% for L-ascorbic acid, ⬍1.3% for alkaline phospha-
duration ⬎30 minutes per session, with near maximal pain during tase, ⬍3.8% for CRP, ⬍4.4% for fibrinogen, ⬍1.8% for lipids, and
training as the end point and program length ⬎6 months.13,14 ⬍1.5% for HbA1c.
Table 1 summarizes clinical characteristics of the study groups. A
dietary history was taken to estimate the amount of vitamin C Vascular Investigations
ingested by means of a food frequency questionnaire according to
After blood sampling, all subjects underwent clinical examinations
Donnan et al.15 Intensity and duration of physical activity were also
including blood pressure measurements at the left and right brachial
assessed with a questionnaire.16 Smoking status was classified as
current smokers and nonsmokers; individuals who stopped smoking artery by sphygmomanometry (3 times in sitting position with
within 4 weeks before enrollment in the study were excluded to 2-minute intervals) and 12-lead ECG. In PAD patients, arterial
account for the effect of smoking cessation on vitamin C status.17 systolic blood pressures at the left and the right brachial and posterior
Informed consent was obtained from all subjects, and the study was tibial arteries were measured by a Doppler 8-MHz ultrasound device
approved by the ethics committee of Ghent University Hospital. (Scimed Digitop 840S). ABI was calculated for both legs, and the
lowest ABI was taken as the study parameter.
Biochemical Investigations Thereafter, PAD patients (n⫽70) who did not have contraindica-
Fasting blood samples were taken between 8:00 and 9:00 AM. None tions to performing a walking test (chronic obstructive pulmonary
of the subjects took any medication during the last 12 hours before disease, cardiac rhythm disturbances, orthopedic or neurological
sampling. Within 30 minutes, serum vitamin C (L-ascorbic acid) conditions, ulcera) underwent a standardized graded treadmill pro-
concentrations were measured by the ascorbate oxidase method on a tocol with a speed of 3 km/h and adjustable grade. For the first 5
Hitachi 911 analyzer (Roche).18 Serum alkaline phosphatase activity, minutes, the patients had to walk at a grade of 0%, then the grade
a biochemical marker of vitamin C deficiency,19 was measured with increased every 5 minutes by 5% up to 15%.20,21 All patients were
commercial reagents on a Hitachi 747 analyzer (Roche). Serum CRP accustomed to treadmill tests and had at least 3 tests during the last
concentrations were measured by high-sensitive latex-enhanced 12 months. ACD on the present treadmill test was taken as study
immunonephelometry (BN II nephelometer, Dade Behring). Plasma parameter. Clinical characteristics of patients who participated in the
fibrinogen was assayed by prothrombin time– derived measurements treadmill protocol were age, 69⫾9 years; male sex, 77%; body mass
on an ACL-200 analyzer (Instrumentation Laboratory). Serum total index, 26⫾4 kg/m2; smokers, 36%; diabetes mellitus, 11%; hyper-
cholesterol, HDL cholesterol, and triglycerides were assayed with tension, 53%; pulse pressure, 59⫾19 mm Hg; ABI, 0.60⫾0.14; and
commercial reagents (Hitachi 747, Roche); LDL cholesterol concen- ACD, 389⫾165 m.
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TABLE 2. Vitamin C Levels, Inflammatory Markers, Lipids, and Diabetes Control
Healthy Subjects Hypertension Without Wilcoxon Test*
(n⫽113) PAD (n⫽106) PAD (n⫽85) (P )
L-Ascorbic acid, mol/L 51.7 (42.8–63.5) 49.6 (38.1–62.5) 27.8 (15.8–42.5) ⬍0.0001
CRP, mg/L 2.51 (0.78–4.16) 2.32 (1.28–3.58) 4.80 (2.00–9.55) ⬍0.0001
Fibrinogen, g/L 3.12 (2.35–3.86) 3.64 (2.99–4.84) 4.95 (3.99–5.73) 0.002
Cholesterol, mmol/L 5.21 (4.58–6.20) 5.22 (5.15–6.55) 5.78 (5.19–6.87) 0.003
HDL cholesterol, mmol/L 1.52 (1.21–1.82) 1.32 (1.15–1.62) 1.04 (0.79–1.30) 0.0004
LDL cholesterol, mmol/L 3.47 (2.51–4.04) 3.60 (2.98–4.22) 4.30 (3.60–5.05) 0.0003
Triglycerides, mmol/L 1.11 (0.88–1.71) 1.48 (1.05–1.92) 2.20 (1.27–2.86) 0.0003
HbA1c,† % 䡠䡠䡠 7.6 (6.4–9.3) 7.4 (7.0–8.8) NS
Data are median (interquartile range).
*Kruskal-Wallis test: P⬍0.05 for L-ascorbic acid, inflammatory parameters, and lipids. Subtesting PAD vs
hypertension without PAD (Wilcoxon test).
†Hemoglobin A1c in diabetic patients (20 hypertensives without PAD, 14 PAD patients).
Statistics Inflammatory Markers
Values are expressed as mean⫾SD or median and interquartile Biochemical markers of inflammation (CRP, fibrinogen)
ranges. Statistical differences were evaluated with the Wilcoxon were higher in PAD patients than in the other study groups
test for comparison between 2 groups, the Kruskal-Wallis test for
(P⬍0.005, Table 2). In the PAD group, serum CRP correlated
comparison between ⬎2 groups, or the 2 test. PAD patients were
stratified for L-ascorbic acid levels with the lower reference limit with plasma fibrinogen (r⫽0.600, P⬍0.0001); no significant
(28.4 mol/L) and the limit for vitamin C deficiency (11.4 associations were observed with age, sex, body mass index,
mol/L).22 The median CRP and fibrinogen levels were used to physical activity, HbA1c, blood pressures, or smoking status
categorize PAD patients above and below these levels. Correla- of the PAD patients. Serum CRP and plasma fibrinogen were
tions between data were examined by Spearman rank correlation
less elevated in PAD patients taking aspirin (Table 3).
coefficients. Stepwise multivariate analysis was performed with
L-ascorbic acid as the dependent variable. Statistical analysis was
Serum L-ascorbic acid concentration in PAD patients
carried out with MEDCALC and SPSS 9.0 software. Probability showed a negative correlation with serum CRP (r⫽⫺0.742,
values ⬍0.05 were considered statistically significant. P⬍0.0001) (Figure 2) and plasma fibrinogen (r⫽⫺0.387,
P⬍0.0001) levels. After adjustment for smoking and aspirin
Results intake, a relative risk for vitamin C deficiency of 1.68 (95%
Vitamin C Levels CI, 1.27 to 2.21) was calculated among PAD patients with
Table 2 summarizes biochemical data of the study groups. serum CRP concentration ⬎4.80 mg/L (median value). Se-
Serum L-ascorbic acid concentrations were comparable rum L-ascorbic acid levels in the PAD subgroup with CRP
among healthy subjects and hypertensives without PAD but concentration ⱕ4.80 mg/L were comparable to those in
were much lower in the PAD group (P⬍0.0001): 52% of the hypertensives without PAD and healthy subjects.
PAD patients had L-ascorbic acid levels below the lower
reference limit (28.4 mol/L), and 14% showed biochemical
evidence of vitamin C deficiency (⬍11.4 mol/L). In the
latter subgroup of patients, serum alkaline phosphatase activ-
ity was very low compared with PAD patients with L-ascorbic
acid levels ⱖ11.4 mol/L (Figure 1): 21.3 (9.1 to 45.4) U/L
versus 64.8 (50.0 to 76.7) U/L, respectively (P⬍0.0001).
Smoking was comparable between the study groups and
was associated with ⬇40% lower serum L-ascorbic acid
concentrations in PAD patients (P⫽0.0005, Table 3), hyper-
tensives (P⫽0.0013), and healthy subjects (P⫽0.0002). No
significant associations of vitamin C levels with age, sex,
body mass index, physical activity, HbA1c, or blood pres-
sures were observed in the study groups. Serum L-ascorbic
acid concentration correlated with dietary vitamin C intake
only in healthy subjects (r⫽0.297, P⫽0.004) and hyperten-
sives without PAD (r⫽0.261, P⫽0.006). PAD patients taking Figure 1. Box-and-whisker plots of serum alkaline phosphatase
aspirin showed a less pronounced reduction of serum activity in PAD patients (n⫽85) according to serum L-ascorbic
L-ascorbic acid levels (Table 3); vitamin C levels were not acid concentration, categorized by lower reference limit (28.4
mol/L) and limit for subclinical vitamin C deficiency (11.4
different in PAD patients taking antihypertensive drugs than mol/L). Boxes show median and quartiles; whiskers are 5th
in those without antihypertensive treatment. and 95th percentiles.
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TABLE 3. Effects of Smoking and Aspirin Intake in PAD Patients
Smoking Aspirin Intake†
No (n⫽57) Yes (n⫽28) P* No (n⫽27) Yes (n⫽58) P*
L-Ascorbic 37.5 (16.2–52.2) 22.2 (14.8–26.7) 0.0005 18.7 (13.9–29.0) 35.8 (17.2–47.1) 0.0004
acid, mol/L
CRP, mg/L 4.78 (2.00–9.39) 5.34 (2.05–9.85) NS 8.78 (3.98–11.5) 3.24 (1.66–6.65) 0.0014
Fibrinogen, g/L 4.86 (3.90–5.73) 5.13 (4.25–5.74) NS 5.07 (4.11–6.03) 4.70 (3.75–5.54) 0.032
Data are median (interquartile range).
*Wilcoxon test.
†160 mg/d.
Serum Lipids ence limit) were characterized by a lower ABI (P⫽0.0007)
Serum concentrations of total cholesterol, LDL cholesterol, and a shorter ACD (P⫽0.0001). These differences were
and triglycerides were higher (P⬍0.005) among PAD pa- significant in both smoking and nonsmoking patients. Ele-
tients, whereas HDL cholesterol levels were lower vated inflammatory markers were also associated with low
(P⬍0.0005) compared with the other groups (Table 2). In the ABI and ACD; no effects of serum lipids were observed. ABI
PAD group, serum HDL cholesterol positively correlated correlated with serum L-ascorbic acid (r⫽0.406, P⫽0.001),
with serum L-ascorbic acid (r⫽0.362, P⬍0.0001) and nega- serum CRP (r⫽⫺0.429, P⬍0.0001), and plasma fibrinogen
tively with serum CRP (r⫽⫺0.437, P⫽0.003). Serum (r⫽⫺0.397, P⫽0.009). Similarly, ACD correlated with se-
L-ascorbic acid concentration did not correlate with other rum L-ascorbic acid (r⫽0.552, P⬍0.0001), serum CRP
lipids (total and LDL cholesterol, triglycerides). (r⫽⫺0.476, P⬍0.0001), and plasma fibrinogen (r⫽⫺0.426,
P⫽0.006).
L-Ascorbic Acid Stability Pulse pressure of PAD patients showed a weak negative
In serum from male nonsmokers (15 PAD patients, 10 healthy correlation with serum L-ascorbic acid (r⫽⫺0.247, P⫽0.048).
control subjects), vitamin C (Fluka) was added to increase its In stepwise multivariate analysis (r⫽0.798, P⫽0.0001 for the
concentration by 114 mol/L (20 mg/L). The sera were then model), only CRP, smoking, and ACD were significantly related
incubated at 37°C for 4 hours and L-ascorbic acid concentra- to vitamin C levels in PAD (Table 5).
tions were measured (in triplicate) at baseline and at the end
of the experiment. Baseline L-ascorbic acid concentrations in Discussion
the spiked sera were 127.5⫾5.8 mol/L (PAD) and We found that circulating vitamin C (L-ascorbic acid) con-
132.4⫾6.2 mol/L (control subjects). After 4 hours, the centrations are depleted in PAD patients, whereas levels of
decrease of L-ascorbic acid concentration was significantly the antioxidant are comparable between hypertensives with-
higher in sera from PAD patients (57⫾13%) than in control out PAD and healthy subjects. Vitamin C is the most effective
sera (40⫾8%) (P⫽0.02). The L-ascorbic acid decrease was defense against free radicals in the blood and is the first
even more striking (68%) in serum from PAD patients with antioxidant to be used up during oxidative stress, thereby
high CRP concentration (range, 8.1 to 12.3 mg/L), whereas sparing other endogenous antioxidants.10,11 Therefore, our
depletion of the vitamin in patient sera with lower CRP level finding suggests a higher oxidative stress in patients with
(range, 1.5 to 4.2 mg/L) was not significantly different than in
control sera (Figure 3).
Vascular Investigations
Table 4 illustrates the effect of vitamin C levels and inflam-
mation on ABI and ACD. PAD patients with serum
L-ascorbic acid concentrations ⬍28.4 mol/L (lower refer-
Figure 3. L-ascorbic acid depletion in spiked sera from non-
smoking men (10 control subjects, 15 PAD patients), stratified
for serum CRP concentration above and below level of 5.0
mg/L. Shown is percentage decrease of L-ascorbic acid con-
Figure 2. Correlation between serum L-ascorbic acid and CRP centration (mean⫾SD) after incubation of sera for 4 hours
concentrations in PAD patients (r⫽⫺0.742, P⬍0.0001). at 37°C.
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TABLE 4. Effect of Vitamin C Level and Inflammation on acid levels in PAD only correlated with HDL cholesterol, a
Parameters of PAD negative acute phase reactant,27 and not with other serum
ACD, m lipids. Other confounders may be the predominance of men in
ABI (n⫽85) (n⫽70) the PAD group and the differences in physical activity and in
L-Ascorbic acid, mol/L
prevalence of antihypertensive treatment between groups, but
we found no significant associations of vitamin C status with
⬍28.4* 0.55 (0.46–0.61) ⬍28.4* 325 (175–400)
sex, physical activity, or intake of antihypertensive drugs.
ⱖ28.4 0.65 (0.59–0.73) ⱖ28.4 488 (375–600)
Potential confounding by nutrient intake15 is limited because
P⫽0.0007 P⫽0.0001 all patients had a regular dietary intake of fruits and vegeta-
CRP, mg/L bles, and none of the patients received antioxidant
ⱕ4.80† 0.64 (0.57–0.73) ⱕ4.84† 482 (375–588) supplements.
⬎4.80 0.55 (0.46–0.63) ⬎4.84 325 (150–400) In vitro, stability of L-ascorbic acid is low in serum from
P⫽0.0042 P⫽0.0001 PAD patients with high CRP levels, suggesting a higher
Fibrinogen, g/L
degree of oxidative stress associated with inflammation. It is
unclear whether vitamin C depletion in atherosclerosis is
ⱕ4.95† 0.63 (0.53–0.74) ⱕ4.89† 425 (325–518)
mainly a cause or a result of the inflammatory disease,
⬎4.95 0.57 (0.48–0.66) ⬎4.89 350 (150–475)
although both may be true. Vitamin C depletion is athero-
P⫽0.041 P⫽0.038 genic by increasing the susceptibility of LDL cholesterol to
Data are median (interquartile range). oxidation and is associated with increased cardiovascular
*Lower reference limit. risk,22 but it is now equally recognized that reactive oxygen
†Median value in the patient group. species formed by the inflammatory response in an existing
atherosclerotic lesion may in turn reduce vitamin C antioxi-
PAD. Smoking, a key risk factor in PAD and known to reduce dant levels.9
vitamin C levels,17 was comparable in the 3 study groups, and Vitamin C depletion affects the functional state of the
vitamin C depletion was also observed among nonsmoking peripheral circulation, as evidenced by low ACD. Smoking
PAD patients. Approximately 50% of the PAD patients had has been demonstrated to affect walking distance,28 but we
vitamin C levels below the lower reference limit, and ⬎10% found that the relation between vitamin C depletion and low
had vitamin C deficiency. Low serum alkaline phosphatase ACD was also consistent among nonsmoking PAD patients.
activities, a biochemical sign of subclinical vitamin C defi- A number of studies have compared the reproducibility of the
ciency, were found in the latter subgroup of patients.19 initial and absolute claudication distance, with most demon-
Vitamin C depletion in PAD is related to low-grade strating that ACD is more reproducible and therefore presum-
inflammation. We found that serum L-ascorbic acid levels ably the more appropriate measurement to use as a primary
inversely correlated with serum CRP and plasma fibrinogen end point.20,21 ACD also has the theoretical justification that
concentrations in PAD patients, similar to what has been it probably more truly represents real life, in which the patient
observed in other clinical settings.23,24 Low vitamin C status is likely to walk even after the first appearance of claudication
has been observed in critically ill patients and could not be discomfort.
prevented by the use of parenteral nutrition containing ascor- In stepwise multivariate analysis, ACD is a determinant of
bic acid.24 Other authors have proposed that low-dose aspirin vitamin C concentration in PAD patients, whereas other
treatment might reduce CRP levels25 and oxidative stress.26 In vascular parameters (ABI, pulse pressure) failed to enter the
this study, intake of aspirin (160 mg/d) was not independently model. We found that low ABI is related to inflammation,
associated with vitamin C concentration in stepwise multi- similar to what has been observed in previous studies.29,30
variate analysis. The question arises whether antioxidant vitamin supple-
Because PAD patients show a less favorable lipid profile, ments would be useful to address reduction of oxidative stress
depressed vitamin C status may be a reflection of their in PAD. A randomized controlled trial has suggested that
hyperlipidemia. However, we found that serum L-ascorbic antioxidants may prevent cardiovascular events in PAD
patients but do not improve lower limb function.31 Recent
TABLE 5. Stepwise Multivariate Analysis With L-Ascorbic Acid trials showed no benefit of vitamin E in the treatment for
as Dependent Variable*
intermittent claudication.32–34 An ongoing multicenter Euro-
Variable -Coefficient (SE) P pean trial, the Critical Leg Ischemia Prevention Study
Log(CRP), mg/L ⫺11.862 (1.589) 0.0001* (CLIPS), investigates the effectiveness of low-dose aspirin
Smoking (yes vs no) ⫺9.828 (2.819) 0.0009*
and antioxidant vitamins (vitamin E, vitamin C, -carotene)
with a 2⫻2 factorial design. However, vitamin C adminis-
ACD, m 0.021 (0.009) 0.029
tered as a dietary supplement to humans has been shown to
This analysis was performed in PAD patients who performed a treadmill test exhibit pro-oxidant properties, which may give rise to para-
(n⫽70).
*Also significant in a model for all PAD patients (n⫽85) (ACD not included).
doxical effects in clinical intervention trials.35
Variables that failed to enter the model: alkaline phosphatase, fibrinogen, HDL
cholesterol, dietary vitamin C intake, physical activity, aspirin intake, ABI, pulse Summary
pressure. Vitamin C concentrations are low in PAD and are associated
r⫽0.798 for the model, F⫽38.4 (P⫽0.0001). with inflammation and the patient’s functional state. Low-
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oxidative stress and the resultant decrease in antioxidants peripheral arterial disease in the general population: the Edinburgh Artery
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Acknowledgments Methods of Enzymatic Analysis. Vol VI. Weinheim, Germany: Verlag
Michel Langlois is recipient of a postdoctoral fellowship of the Fund chemie; 1984:376 –385.
for Scientific Research (FWO), Flanders (Belgium). We are grateful 19. Friedman RB, Young DS, eds. Effects of Disease on Clinical Laboratory
to Dirk De Bacquer, An Maas, Annie Van Wassenhove, and Inge Tests. Washington, DC: AACC Press; 1989.
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Van Pottelbergh for their advice and skillful assistance.
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Vasc Med. 1997;2:93–97.
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Downloaded from http://circ.ahajournals.org/ by guest on September 27, 2015Serum Vitamin C Concentration Is Low in Peripheral Arterial Disease and Is Associated With
Inflammation and Severity of Atherosclerosis
Michel Langlois, Daniel Duprez, Joris Delanghe, Marc De Buyzere and Denis L. Clement
Circulation. 2001;103:1863-1868
doi: 10.1161/01.CIR.103.14.1863
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