Cardiovascular Risk Assessment with Vascular Function, Carotid Atherosclerosis and the UKPDS Risk Engine in Korean Patients with Newly Diagnosed Type 2 Diabetes.
ABSTRACT Patients with type 2 diabetes have an increased risk of cardiovascular disease. Few studies have evaluated the cardiovascular disease (CVD) risk simultaneously using the United Kingdom Prospective Diabetes Study (UKPDS) risk engine and non-invasive vascular tests in patients with newly diagnosed type 2 diabetes.
Participants (n=380; aged 20 to 81 years) with newly diagnosed type 2 diabetes were free of clinical evidence of CVD. The 10-year coronary heart disease (CHD) and stroke risks were calculated for each patient using the UKPDS risk engine. Carotid intima media thickness (CIMT), flow mediated dilation (FMD), pulse wave velocity (PWV) and augmentation index (AI) were measured. The correlations between the UKPDS risk engine and the non-invasive vascular tests were assessed using partial correlation analysis, after adjusting for age, and multiple regression analysis.
The mean 10-year CHD and 10-year stroke risks were 14.92±11.53% and 4.03±3.95%, respectively. The 10-year CHD risk correlated with CIMT (P<0.001), FMD (P=0.017), and PWV (P=0.35) after adjusting for age. The 10-year stroke risk correlated only with the mean CIMT (P<0.001) after adjusting for age. FMD correlated with age (P<0.01) and systolic blood pressure (P=0.09). CIMT correlated with age (P<0.01), HbA1c (P=0.05), and gender (P<0.01).
The CVD risk is increased at the onset of type 2 diabetes. CIMT, FMD, and PWV along with the UKPDS risk engine should be considered to evaluate cardiovascular disease risk in patients with newly diagnosed type 2 diabetes.
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ABSTRACT: Arterial distensibility measures, generally from pulse-wave velocity (PWV), are widely used with little knowledge of relationships to patient outcome. We tested whether aortic PWV predicts cardiovascular and all-cause mortality in type 2 diabetes and glucose-tolerance-tested (GTT) multiethnic population samples. Participants were randomly sampled from (1) a type 2 diabetes outpatient clinic and (2) primary care population registers, from which nondiabetic control subjects were given a GTT. Brachial blood pressures and Doppler-derived aortic PWV were measured. Mortality data over 10 years' follow-up were obtained. At any level of systolic blood pressure (SBP), aortic PWV was greater in subjects with diabetes than in controls. Mortality risk doubled in subjects with diabetes (hazard ratio 2.34, 95% CI 1.5 to 3.74) and in those with glucose intolerance (2.12, 95% CI 1.11 to 4.0) compared with controls. For all groups combined, age, sex, and SBP predicted mortality; the addition of PWV independently predicted all-cause and cardiovascular mortality (hazard ratio 1.08, 95% CI 1.03 to 1.14 for each 1 m/s increase) but displaced SBP. Glucose tolerance status and smoking were other independent contributors, with African-Caribbeans experiencing reduced mortality risk (hazard ratio 0.41, 95% CI 0.25 to 0.69). Aortic PWV is a powerful independent predictor of mortality in both diabetes and GTT population samples. In displacing SBP as a prognostic factor, aortic PWV is probably further along the causal pathway for arterial disease and may represent a useful integrated index of vascular status and hence cardiovascular risk.Circulation 11/2002; 106(16):2085-90. · 15.20 Impact Factor
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ABSTRACT: Studies in selected samples have linked impaired endothelial function with cardiovascular disease and its risk factors. The clinical correlates and heritability of endothelial function in the community have not been described. We examined a measure of endothelial function, brachial artery flow-mediated dilation (FMD), expressed as both percent (FMD%) and actual dilation by ultrasound with the occlusion cuff below the elbow in 2883 Framingham Study participants (52.9% women; mean age, 61 years). A subset of 1096 participants performed a 6-minute walk test before FMD determination. Mean FMD% was 3.3+/-3.0% in women and 2.4+/-2.4% in men. In stepwise multivariable linear regression models, FMD% was inversely related to age, systolic blood pressure, body mass index (BMI), lipid-lowering medication, and smoking, whereas it was positively related to female gender, heart rate, and prior walk test. The estimated heritability of FMD% was 0.14. FMD actual dilation findings were similar, except that female sex and BMI were not significantly associated. Increasing age, systolic blood pressure, BMI, and smoking were associated with lower FMD% in our community-based sample, whereas prior exercise and increasing heart rate were associated with higher FMD%. The estimated heritability of FMD was modest. Future research will permit more complete characterization of the genetic and environmental determinants of endothelial function and its prognostic value in the community.Circulation 03/2004; 109(5):613-9. · 15.20 Impact Factor
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ABSTRACT: Increased arterial stiffness, determined invasively, has been shown to predict a higher risk of coronary atherosclerosis. However, invasive techniques are of limited value for screening and risk stratification in larger patient groups. We prospectively enrolled 465 consecutive, symptomatic men undergoing coronary angiography for the assessment of suspected coronary artery disease. Arterial stiffness and wave reflections were quantified noninvasively using applanation tonometry of the radial artery with a validated transfer function to generate the corresponding ascending aortic pressure waveform. Augmented pressure (AP) was defined as the difference between the second and the first systolic peak, and augmentation index (AIx) was AP expressed as a percentage of the pulse pressure. In univariate analysis, a higher AIx was associated with an increased risk for coronary artery disease (OR, 4.06 for the difference between the first and the fourth quartile [1.72 to 9.57; P<0.01]). In multivariate analysis, after controlling for age, height, presence of hypertension, HDL cholesterol, and medications, the association with coronary artery disease risk remained significant (OR, 6.91; P<0.05). The results were exclusively driven by an increase in risk with premature vessel stiffening in the younger patient group (up to 60 years of age), with an unadjusted OR between AIx quartiles I and IV of 8.25 (P<0.01) and a multiple-adjusted OR between these quartiles of 16.81 (P<0.05). AIx and AP, noninvasively determined manifestations of arterial stiffening and increased wave reflections, are strong, independent risk markers for premature coronary artery disease.Circulation 02/2004; 109(2):184-9. · 15.20 Impact Factor
D I A B E T E S & M E T A B O L I S M J O U R N A L
This is an Open Access article distributed under the terms of the Creative Commons At-
tribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/)
which permits unrestricted non-commercial use, distribution, and reproduction in any
medium, provided the original work is properly cited.
Copyright © 2011 Korean Diabetes Association http://e-dmj.org
Diabetes Metab J 2011;35:619-627
pISSN 2233-6079 · eISSN 2233-6087
Cardiovascular Risk Assessment with Vascular
Function, Carotid Atherosclerosis and the UKPDS Risk
Engine in Korean Patients with Newly Diagnosed Type
Choon Sik Seon1, Kyung Wan Min1,2, Seung Yup Lee1, Kyoung Woo Nho1, Se Hwan Park1, Bo Kyung Koo3, Kyung Ah Han1,2
1Department of Internal Medicine, Eulji University School of Medicine, Seoul,
2Diabetes Clinic, Eulji Medical Center, Seoul,
3Department of Internal Medicine, Boramae Hospital, Seoul, Korea
Background: Patients with type 2 diabetes have an increased risk of cardiovascular disease. Few studies have evaluated the car-
diovascular disease (CVD) risk simultaneously using the United Kingdom Prospective Diabetes Study (UKPDS) risk engine and
non-invasive vascular tests in patients with newly diagnosed type 2 diabetes.
Methods: Participants (n=380; aged 20 to 81 years) with newly diagnosed type 2 diabetes were free of clinical evidence of CVD.
The 10-year coronary heart disease (CHD) and stroke risks were calculated for each patient using the UKPDS risk engine. Carotid
intima media thickness (CIMT), flow mediated dilation (FMD), pulse wave velocity (PWV) and augmentation index (AI) were
measured. The correlations between the UKPDS risk engine and the non-invasive vascular tests were assessed using partial cor-
relation analysis, after adjusting for age, and multiple regression analysis.
Results: The mean 10-year CHD and 10-year stroke risks were 14.92±11.53% and 4.03±3.95%, respectively. The 10-year CHD
risk correlated with CIMT (P<0.001), FMD (P=0.017), and PWV (P=0.35) after adjusting for age. The 10-year stroke risk cor-
related only with the mean CIMT (P<0.001) after adjusting for age. FMD correlated with age (P<0.01) and systolic blood pres-
sure (P=0.09). CIMT correlated with age (P<0.01), HbA1c (P=0.05), and gender (P<0.01).
Conclusion: The CVD risk is increased at the onset of type 2 diabetes. CIMT, FMD, and PWV along with the UKPDS risk en-
gine should be considered to evaluate cardiovascular disease risk in patients with newly diagnosed type 2 diabetes.
Keywords: Atherosclerosis; Cardiovascular risk; Diabetes mellitus, type 2; United Kingdom Prospective Diabetes Study risk en-
gine; Vascular function
Corresponding author: Kyung Wan Min
Department of Internal Medicine, Eulji University School of Medicine,
114 Hangeulbiseok-gil, Nowon-gu, Seoul 139-711, Korea
Received: Apr. 11, 2011; Accepted: Jul. 26, 2011
The prevalence of cardiovascular disease is 2 to 5 times higher
in diabetics compared to non-diabetics [1-3]. Diabetes with
no history of myocardial infarction are equally at risk for myo-
cardial infarction as are non-diabetic subjects with a history of
myocardial infarction, and they are both classified in the same
coronary artery disease risk group .
Therefore, in order to prevent cardiovascular disease in type
2 diabetes patients, identifying and correcting risk factors are
considered important. In the past the studies have been main-
ly focused to find cardiovascular disease in type 2 diabetes.
Currently, identifying patients who are at high risk for cardio-
vascular disease prior to development of apparent cardiovas-
Seon CS, et al.
Diabetes Metab J 2011;35:619-627http://e-dmj.org
cular disease and preventing the disease have taken a higher
priority. However, identifying patients who are at high risk for
cardiovascular disease and require active prevention is not easy.
A few cardiovascular risk models and vascular tests have been
suggested to evaluate the risk of cardiovascular disease.
Among cardiovascular disease risk models, through the
United Kingdom Prospective Diabetes Study (UKPDS), the
UKPDS risk engine was developed for estimating risk of coro-
nary heart disease and stroke for 10 years in type 2 diabetes
[5,6]. UKPDS enrolled 5,100 patients who were newly diag-
nosed with type 2 diabetes and was originally aimed to know
whether glycemic control could decrease morbidity and mor-
tality that were associated with diabetic complications .
Through the UKPDS, the relationships between cardiovascu-
lar diseases and identified general risk factors in type 2 diabe-
tes was investigated and the UKPDS risk engine was devel-
In vascular examinations to predict cardiovascular disease,
flow-mediated dilation (FMD) assesses early endothelial cell
dysfunction, and pulse wave velocity (PWV) and augmenta-
tion index (AI) assess arterial stiffness. Carotid intima-media
thickness (CIMT) is used for early detection of atherosclerosis
. Vascular examinations evaluate the risk of cardiovascular
disease because vascular dysfunction and changes in the vas-
cular structure occur before the onset of cardiovascular disease.
These changes are not isolated but represent changes that oc-
cur in blood vessels throughout the entire body .
There are no studies on the correlations between the UKP-
DS risk engine and blood vessel examinations in Korean type
2 diabetes patients. In the present study, in order to assess the
risk of cardiovascular disease in patients who were just diag-
nosed with type 2 diabetes, we used the UKPDS risk engine
among cardiovascular disease risk models and easy and non-
invasive vascular examinations. The relationship between vas-
cular tests and the UKPDS risk engine as well as the relation-
ship between vascular tests and cardiovascular risk factors were
Study subjects and anthropometric measurement
This study was performed between January 2003 and August
2007 at the Eulji General Hospital Diabetes Center, and em-
ployed the use of 75 g oral glucose tolerance test to diagnose
diabetes. The diagnostic criteria set by the American Diabetes
Association were used to diagnose type 2 diabetes patients that
participated in this study . Individuals who had previously
used oral hypoglycemic agents for over 1 month, had previous-
ly received insulin treatment, or had a history of cardiovascu-
lar disease were excluded from this study.
Study participants answered a questionnaire regarding their
disease history and were measured for height and weight. Par-
ticipants then had their blood pressures measured using a mer-
cury blood pressure monitor (Yamasu, Tokyo, Japan) after sit-
ting for 10 minutes to stabilize their blood pressure. Waist cir-
cumference measurements were performed by the same ex-
aminer at the middle point between the bottom of the ribcage
and the iliac crest. Body mass index (BMI) was calculated by
dividing body weight by height squared (kg/m2).
Calculated risk of the UKPDS risk engine
Cardiovascular risk was scored for each participant using the
UKPDS risk engine (version 2.0) by inputting risk factors such
as age, gender, race, current smoking status, glycated hemoglo-
bin, systolic blood pressure, total cholesterol, high density lipo-
protein cholesterol (HDL-C), and presence or absence of atrial
fibrillation, and the 10-year risk of coronary heart disease
(CHD) and cerebrovascular disease were calculated [3,5,6].
Blood samples were taken after 8 hours of fasting, and blood
glucose, cholesterol, triglycerides, and low density lipoprotein
cholesterol (LDL-C) were measured on a Hitachi 7170 (Hita-
chi, Tokyo, Japan) using the enzymatic method. In addition,
HDL-C and VLDL were measured after their precipitation.
CIMT was measured using a high resolution B-mode ultra-
sound (LOGIC 400 CL PRO; General Electric, Milwaukee, WI,
USA) by the same well-trained examiner. Ultrasonography of
the common carotid artery, carotid bifurcation, and internal
carotid artery of the left and right carotid arteries was per-
formed. The distance between the leading edge of the first
bright line of the far wall (lumen-intima interface) and the
leading edge of the second bright line (media-adventitia inter-
face) indicates the intima-media thickness. The distance be-
tween the first and second bright lines was measured in the
separations of the low bright regions of the CIMT ultrasound.
The CIMT values used for this study were the means of 6 mea-
Cardiovascular risk assessment in type 2 diabetics
Diabetes Metab J 2011;35:619-627 http://e-dmj.org
surements from different locations [11,12].
In order to verify the functionality of vascular endothelial cells,
using a high resolution B-mode 11 MHz ultrasound, the FMD
in the brachial artery was measured using the method of Raita-
kari and Celermajer . Patients fasted and abstained from
drugs, alcohol, caffeine, and tobacco for over 8 hours prior to
Participants were stabilized in supine position, and the base-
line diameter of the brachial artery was measured using a high-
resolution B-mode ultrasonograph. A linear transducer was
located 5 to 10 cm above the antecubital fossa, and the center
of the brachial artery was set as a reference point. Under B-
mode, the diameter was defined from one side of the interface
(m-line) of the intima and media of the blood vessel to the
same part on the opposite side. In order to reduce variation
during diameter measurements, it was measured at arterial
branching points and at the end of the diastolic phase just be-
fore the origin of an R wave using electrocardiogram (ECG).
After baseline diameter measurements were completed, the
transducer was removed, and a blood pressure cuff was attached
to the middle of the upper arm and set at 250 mm Hg. After 5
minutes, we reduced the pressure on the cuff to 0 mm Hg and
then removed the cuff. We then repositioned the transducer,
and within the 50 seconds during which hyperemia sets in, we
measured the maximum diameter of the brachial artery in-
creased due to hyperemia. For baseline diameter, the measure-
ments were calculated as percentages, and a flow mediated re-
sponse was observed.
Brachial-ankle pulse wave velocity (BaPWV)
The measurements were taken in the morning after 8 hours of
fasting and 10 minutes of resting using a VP1000 waveform
analyzer (Omron, Tokyo, Japan). This instrument measured a
pulse wave from both upper extremities and ankles, and the
time difference was measured using ECG signals. The distance
was obtained using a formula based on height and was used to
calculate pulse wave velocity . The blood pressure in limbs
was measured using the vibratory method, and the left, right,
and mean BaPWV were measured simultaneously. The mean
BaPWV was used for statistical analysis.
The peripheral arterial waveform was recorded from the radial
artery using the Applanation tonometer aortic waveform anal-
ysis system (SphygmoCoR®; AtCor Medical Pty Ltd., Sydney,
Australia), and then, using a generalized transfer function, the
AI was obtained by calculating aortic waveforms . In order
to eliminate the effects of patient medication, measurements
were taken after 8 hours of fasting. In addition, in order to
eliminate the effects of heart rate during measurements, AI75
(augmentation index adjusted for 75 beats/min) was obtained
and was used for statistical analysis.
Statistical analysis was performed on SPSS version 17.0 (SPSS
Inc., Chicago, IL, USA) software. Data are expressed as the
mean and standard deviation. The log values of variables that
did not follow a normal distribution were calculated. In order
to find a correlation between the vascular tests and the UKP-
DS risk engine which determined the 10-year CHD and 10-
year stroke risk , after adjusting for age, a partial correlation
analysis and multiple regression were tested. An ANCOVA
was tested for correlation between the categorical variables of
risk factors and vascular examinations, and a multiple regres-
sion analysis was used for continuous variables. P values less
than 0.05 were considered to be statistically significant.
Clinical characteristics of the subjects
Among the 380 participants, the mean age was 52 years (range,
20 to 81 years). Three patients had atrial fibrillation and 114
were smokers (Table 1). Fifty percent of the patients were obese
(BMI ≥25 kg/m2), 77% had high blood pressure (BP ≥130/80
mm Hg), and 34% were taking antihypertensive medication.
Ninety-four percent of patients had hypercholesterolemia,
which was classified as total cholesterol ≥200 mg/dL, triglyc-
eride ≥150 mg/dL, LDL-C ≥100 mg/dL, or HDL-C (HDL-C;
male, <40 mg/dL; female, <50 mg/dL).
The relevance of vascular tests and risk factors of
Among cardiovascular disease risk factors (age, gender, systol-
ic blood pressure, lipid abnormalities, glycated hemoglobin,
smoking, and atrial fibrillation), CIMT increased with age
(P<0.001) and glycated hemoglobin (P=0.048), decreased
with HDL-C (P=0.450), and was significantly different based
on gender (P<0.001). FMD decreased significantly with in-
Seon CS, et al.
Diabetes Metab J 2011;35:619-627
creasing age (P<0.001) and systolic blood pressure (P=0.017).
BaPWV increased with age (P<0.001) and total cholesterol
(P<0.001). AI75 increased with HDL-C (P=0.034), and was
different based on gender (P<0.001). No vascular tests were
related to smoking or atrial fibrillation. The intraobserver co-
efficients of variation of FMD and AI were 47% and 51%, re-
spectively. Since there was only one examiner in this study, the
interobserver coefficient of variation could not be calculated.
Correlation between the UKPDS engine and vascular tests
In the entire participants in the study, the 10-year CHD risk
and 10-year stroke risk calculated using the UKPDS risk en-
gine were 14.92% and 4.03%, respectively. The 10-year stroke
risk was lower than 10-year CHD risk because there were only
3 patients with atrial fibrillation in this study. The mean values
of study population were 50 years old, smoker, a systolic blood
pressure of 130 mm Hg, glycated hemoglobin of 8.64%, total
cholesterol of 200 mg/dL, and HDL-C of 45 mg/dL. With
these mean values, the 10-year stroke risk calculated using the
UKPDS risk engine, in a male patient with and without a his-
tory of atrial fibrillation was 16.7% and 2.1%, respectively,
which shows that atrial fibrillation has a large effect on the 10-
year stroke risk. Because of few atrial fibrillation patients, there
was a difference between 10-year CHD risk and 10-year stroke
risk in the present study. Prior to adjusting for age, the 10-year
CHD risk and 10-year stroke risk were significantly correlated
with FMD, BaPWV, and CIMT. However, there was no corre-
lation with AI75. The 10-year CHD and 10-year stroke risks
both increased with age (Fig. 1). In addition, age was signifi-
cantly correlated with the all four vascular tests. After adjust-
ing for age, there was a significant correlation between the 10-
year CHD risk and CIMT (P<0.001), FMD (P<0.017), and
BaPWV (P<0.035) and a significant correlation between the
10-year stroke risk and CIMT (P<0.001) (Table 2). CIMT,
FMD, BaPWV, age, and gender values were treated as inde-
pendent variables, and 10-year CHD risk was treated as a de-
pendent variable. Therefore, a multiple regression analysis
confirmed age, gender, CIMT and BaPWV independently af-
fect 10-year CHD. The 10-year stroke risk was treated as a de-
pendent variable, age, gender, and CIMT were treated as inde-
pendent variables. Therefore, a multiple regression analysis
confirmed age and gender affecting 10-year stroke risk (Table
Risk of cardiovascular disease calculated by the UKPDS
The Framingham risk score and SCORE  are risk models
used to assess the risk of cardiovascular disease in the general
population. The UKPDS risk engine is a risk model used only
for diabetes patients. van der Heijden et al.  found that the
UKPDS risk function was more accurate in predicting coro-
nary artery disease in a Hoorn study cohort of newly diag-
Table 1. Baseline characteristics of the study population
Sex, percentage males
SBP, mm Hg
DBP, mm Hg
Total cholesterol, mg/dL
Lipid ratio, TG/HDL-C
Atrial fibrillation, %
Current smoker, %
FMD, % increase in baseline diameter
Mean IMT, mm
UKPDS 10-yr CHD risk, %
UKPDS 10-yr fatal CHD risk, %
UKPDS 10-yr stroke risk, %
UKPDS 10-yr fatal stroke risk, %
Values are presented as mean±standard deviation.
SBP, systolic blood pressure; DBP, diastolic blood pressure; BMI,
body mass index; HOMA-IR, homeostasis model assessment of insu-
lin resistance; HDL-C, high density lipoprotein cholesterol; LDL-C,
low density lipoprotein cholesterol; TG, triglyceride; FMD, flow-me-
diated dilation; PWV, pulse wave velocity; AI, augmentation index;
IMT, intima-media thickness; UKPDS, United Kingdom Prospective
Diabetes Study; CHD, coronary heart disease.
Cardiovascular risk assessment in type 2 diabetics
Diabetes Metab J 2011;35:619-627
Table 2. Correlation of vascular function with the UKPDS risk engine and age in newly diagnosed type 2 diabetics
(adjusted by height for AI)
10-yr CHD riska
Partial correlation, adjusted for age
(and height for AI)
10-yr CHD riska
10-yr stroke riska
10-yr stroke riska
UKPDS, United Kingdom Prospective Diabetes Study; AI, augmentation index; CHD, coronary heart disease; CIMT, carotid intima-media thick-
ness; FMD, flow-mediated dilation; PWV, pulse wave velocity.
aUsing log transformed data.
nosed type 2 diabetes patients than were the Framingham and
SCORE methods. The UKPDS studies only included newly
diagnosed type 2 diabetes patients, and the UKPDS risk en-
gine used values of patients diagnosed within 1 to 2 years .
In the present study, performed on patients who were recently
diagnosed with diabetes, the 10-year CHD risk and 10-year
stroke risk were 14.92% and 4.03%, respectively, calculated us-
ing the UKPDS risk engine. The 10-year CHD risk was rela-
tively high, and the risk of coronary heart disease tended to
increase after onset of type 2 diabetes.
CIMT increases from the onset of atherosclerosis. The Athero-
sclerosis Risk in Communities (ARIC) study examined CIMT
in 5,552 males and 7,289 females, ages 45 to 64, followed for
an average of 5.2 years between 1987 and 1993. Coronary heart
disease was 1.85 times more prevalent in males and 5.07 times
more prevalent in females who had a CIMT greater than 1 mm
compared to those with a CIMT less than 1 mm . In an-
other ARIC study that examined the relevance of CIMT and
cerebrovascular disease over an average of 7.2 years, ischemic
cerebrovascular disease was 1.78 times more prevalent in males
and 2.02 times more prevalent in females with a CIMT greater
than 1 mm compared to that of those with a CIMT less than 1
mm . One meta-analysis showed that type 2 diabetes pa-
tients had an average CIMT that was 0.13 mm greater than
normal individuals, which was associated with a 40% greater
probability of type 2 diabetics developing cardiovascular dis-
ease compared to healthy individuals .
In a Korean study, Bae et al.  showed that the mean CIMT
Fig. 1. Plot of 10-year coronary heart disease (CHD) and 10-year stroke risks according to age. (A) 10-year CHD risk. (B) 10-
year stroke risk.
10-yr CHD risk
20 40 60 80
10-yr stroke risk
20 40 60 80