VOLUME 11 NUMBER 2 • JUNE 2014
55
SA JOURNAL OF DIABETES & VASCULAR DISEASE
RESEARCH ARTICLE
lipid-lowering medication or dietary modification. Hypertension
was defined as a seated systolic blood pressure > 140 mmHg or
diastolic pressure > 90 mmHg on at least three occasions, or if such
a diagnosis had been made in the past and the patient was being
treated with medications or lifestyle modification.
Cardiac medications were withdrawn for > 48 hours and
at least five half-lives before the study. Angiotensin converting
enzyme inhibitors and aspirin or other cyclooxygenase inhibitors
were discontinued ≥ seven days before the study. The protocol
was approved by the institutional review board of the National
Heart, Lung and Blood Institute, and informed written consent was
obtained from each subject.
Anthropometric variables and atherosclerosis risk factors
Subjects had their height (m) and weight (kg) measured and
body mass index (BMI) calculated (weight/height
2
). Subjects were
categorised as normal weight if BMI was < 25 kg/m
2
, overweight
if BMI was between 25 and < 30 kg/m
2
, and obese if BMI was ≥
30 kg/m
2
. Blood pressure, fasting lipid profile, fasting glucose and
high sensitivity C-reactive protein (CRP) levels were also measured.
All subjects with a history of current or prior tobacco smoking were
classified as smokers.
Subjects were also categorised according to a modified definition
of the NCEP/ATPIII criteria for MetS. Waist circumference data were
not available for most subjects; therefore BMI values were used
to define adiposity. Five MetS components were identified: 1 =
overweight or obesity (BMI ≥ 25 kg/m
2
); 2 = elevated blood pressure
(≥ 130/≥ 85 mmHg or treatment with antihypertensive medication);
3 = elevated triglycerides (≥ 150 mg/dl); 4 = low HDL [< 40 mg/dl
(male) or < 50 mg/dl (female)]; 5= elevated fasting glucose (≥ 110
mg/dl or treatment with glucose-lowering medication). Subjects
were deemed to have MetS if they fulfilled three or more of these
criteria.
Vascular function studies
A 6-French guide catheter was introduced into an unobstructed (<
30% stenosis) coronary artery, and coronary blood flow (CBF)
velocity was measured using a 0.014- or 0.018-inch Doppler flow
wire (Flowire, Volcano Corp, Rancho Cordova, CA) as described
previously.
23
Endothelium-dependent vasodilation was estimated
by measuring CBF responses to an infusion of intracoronary
acetylcholine (ACH) at a rate of 15 µg/min for two minutes to obtain
an estimated 10-6 mol/l intracoronary concentration. Endothelium-
independent vasomotion was estimated with intracoronary sodium
nitroprusside (SNP) (20 µg/min) infusion for three minutes. When
drugs were infused into the left main coronary artery, the infusion
rate was doubled. Coronary flow reserve was determined with
adenosine infused at 2.2 mg/min for two minutes.
For calculating CBF, diameter was measured in a 0.25- to 0.5-cm
segment of vessel beginning 0.25 cm beyond the tip of the flow
wire. CBF was determined from the Doppler-derived flow velocity
and diameter measurements using the formula: π × average peak
velocity × 0.125 × diameter
2
as previously described.
23
Coronary
vascular resistance (CVR) was calculated as mean arterial pressure
divided by CBF. Additionally, mid and distal segments of the study
vessel that were straight and free of overlap or major branch points
were also measured after each intervention. Epicardial coronary
responses in these segments were determined by assessment of
the percent change in diameter (∆Diam) with each drug compared
to baseline. Quantitative angiography was performed with the
ARTREK software (Quantim 2001, Statview, Image Comm Systems,
Inc) or PIE medical CAAS system.
24
Statistical analysis
Continuous variables are expressed as mean value ± standard
deviation (SD). Normality was tested using the Kolmogorov-Smirnov
criterion. Logarithmic transformation was performed for skewed
All patients Normal weight Overweight/obese
p
-value
No MetS
MetS
p
-value
n
(%)
418
90 (22)
328 (78)
179 (43)
239 (57)
Age, years
55.2 ± 11.3
55.8 ± 13.0
55.1 ± 10.8
0.59
53.7 ± 10.3
56.3 ± 10.3
0.021
Gender, males/females
239/179
49/41
190/138
0.55
91/88
148/91
0.023
Weight, kg
85 ± 19
66 ± 9
90 ± 18
< 0.001
77 ± 17
91 ± 19
< 0.001
Height, cm
169 ± 10
168 ± 10
169 ± 11
0.64
168 ± 10
169 ± 11
0.2
BMI, kg/m
2
29.7 ± 6.2
22.7 ± 2.1
31.6 ± 5.5
< 0.001
27.1 ± 5.8
31.7 ± 5.8
< 0.001
Mean blood pressure, mmHg
109 ± 15
105 ± 15
110 ± 15
0.018
105 ± 15
111 ± 15
< 0.001
Total cholesterol, mg/dl
214 ± 46
209 ± 48
216 ± 46
0.21
212 ± 48
216 ± 45
0.34
LDL-cholesterol, mg/dl
138 ± 42
132 ± 45
140 ± 41
0.13
139 ± 42
138 ± 42
0.77
HDL-cholesterol, mg/dl
43 ± 14
49 ± 17
42 ± 12
< 0.001
51 ± 15
38 ± 9
< 0.001
Triglycerides, mg/dl
145 (97−218)
112 (70−165)
151 (106−229)
0.02
108 (76−136)
184 (135−261)
< 0.001
Glucose, mg/dl
101 (92−120)
96 (89107)
103 (93−126)
0.002
95 (88−102)
112 (98−140)
< 0.001
hsCRP, mg/l
0.82 (0.46−1.15) 0.59 (0.40−0.89)
0.91 (0.48−1.20)
0.043 0.59 (0.25−0.93)
0.99 (0.65−1.34)
0.005
Risk factors
Hypertension, n (%)
213 (51)
35 (39)
178 (55)
0.13
47 (26)
166 (70)
< 0.001
Diabetes,
n
(%)
89 (22)
15 (4)
74 (18)
0.004
7 (4)
74 (31)
< 0.001
Hypercholesterolaemia,
n
(%)
261 (62)
52 (58)
209 (64)
0.16
103 (62)
158 (75)
0.007
Smoking,
n
(%)
245 (59)
54 (60)
191 (59)
0.83
96 (54)
149 (63)
0.051
CAD,
n
(%)
215 (51)
40 (44)
175 (53)
0.13
69 (39)
146 (61)
< 0.001
Diseased coronary arteries
1.7 ± 0.9
1.8 ± 1.0
1.8 ± 0.9
0.98*
1.6 ± 0.9
1.8 ± 0.9
0.10*
BMI: body mass index; CAD: coronary artery disease; hsCRP: high-sensitivity C-reactive protein, LDL: low-density lipoprotein, HDL: high-density lipoprotein.
Categorical variables are presented as absolute (relative) frequencies; continuous variables, as mean ± SD or median (interquartile range).
p
-values for between groups comparisons are derived from student’s t-test for unpaired measures (for continuous variables) or from chi-square tests (for categorical
variables). *p-value for comparison within the CAD patients.
Table 1.
Baseline characteristics of the whole study population and according to presence of overweight/obesity and metabolic syndrome (MetS).
