Linkbucks

Friday, March 05, 2010

PENYAKIT KARDIOVASKULAR DAN DIABETES MELITUS PADA SINDROM METABOLIK

International Journal of Obesity (2008) 32, S21–S24
& 2008 Nature Publishing Group All rights reserved 0307-0565/08 $30.00

www.nature.com/ijo

ORIGINAL ARTICLE

Metabolic syndrome risk for cardiovascular disease
and diabetes in the ARIC study

CM Ballantyne1,2, RC Hoogeveen1,2, AM McNeill3,4, G Heiss4, MI Schmidt4,5, BB Duncan4,5
and JS Pankow6

1

Section of Atherosclerosis and Vascular Medicine, Department of Medicine, Baylor College of Medicine, Houston, TX, USA;

2

Center for Cardiovascular Disease Prevention, Methodist DeBakey Heart Center, Houston, TX, USA; 3Department of
Epidemiology, Merck Research Labs, North Wales, PA, USA; 4Department of Epidemiology, School of Public Health,
University of North Carolina, Chapel Hill, NC, USA; 5Graduate Studies Program in Epidemiology, School of Medicine,
Federal University of Rio Grande do Sul, Porto Alegre, Brazil and 6Division of Epidemiology and Community Health, School
of Public Health, University of Minnesota, Minneapolis, MN, USA

Objective: The metabolic syndrome is associated with increased risk for cardiovascular disease and diabetes. Several analyses
from the Atherosclerosis Risk in Communities (ARIC) study have been performed to examine the role of the metabolic syndrome
and its components in predicting risk for cardiovascular disease and diabetes.
Design and subjects: The large, biracial, population-based ARIC study enrolled 15 792 middle-aged Americans in four
communities in the United States and has followed them for the development of cardiovascular disease and diabetes.
Measurements: Outcome parameters included prevalence of the metabolic syndrome and its individual components, carotid
intima-media thickness, incident coronary heart disease, incident ischemic stroke and incident diabetes.
Results and conclusion: Several analyses from the ARIC study have shown that the metabolic syndrome, as well as individual
metabolic syndrome components, is predictive of the prevalence and incidence of coronary heart disease, ischemic stroke,
carotid artery disease and diabetes.
International Journal of Obesity (2008) 32, S21–S24; doi:10.1038/ijo.2008.31

Keywords: metabolic syndrome; coronary heart disease; cardiovascular disease; diabetes; risk factors

Introduction

The metabolic syndrome has been shown to increase risk for
cardiovascular disease (CVD) and diabetes and was established
as a secondary target of therapy in the Adult
Treatment Panel III (ATP III) guidelines of the US National
Cholesterol Education Program.1 According to the ATP III
definition, the metabolic syndrome is diagnosed by the
presence of three or more of the following characteristics:
waist circumference 440 inches (102 cm) in men, 435
inches (88 cm) in women; triglycerides X107 mmol l1;highdensity
lipoprotein cholesterol (HDL-C) o100 mmoll1 in
men, o103 mmol l1 in women; blood pressure X130/
X85mmHg; and fasting glucose 601–609mmoll1.2 Data
from the US National Health and Nutrition Examination
Survey indicate that age-adjusted prevalence of the metabolic

Correspondence: Dr CM Ballantyne, Department of Medicine, Baylor College
of Medicine, 6565 Fannin, MS A-601, Houston, TX 77030, USA.
E-mail: cmb@bcm.tmc.edu

syndrome, as defined by the ATP III guidelines, is 27% in
adults and has been increasing.3

The role of the metabolic syndrome and its individual
components in predicting risk for CVD and diabetes has
been examined in the Atherosclerosis Risk in Communities
(ARIC) study, a large, prospective, biracial cohort study of
cardiovascular risk factors in 15 792 middle-aged (aged 45–64
years) Americans.4 Analyses have evaluated the influence of
the metabolic syndrome on both prevalence and incidence
of CVD as well as on the prediction of diabetes.

Metabolic syndrome and prevalence of CVD

In a cross-sectional analysis of 14 502 ARIC participants,
using data from 1987 to 1989, prevalence of the metabolic
syndrome as defined by ATP III was 30%, with considerable
variation across subgroups defined by sex and race.5 The
highest metabolic syndrome prevalence was in black women
(38%), and the lowest was in black men (26%); 31% of white
men and 28% of white women had the metabolic syndrome.


Metabolic syndrome and CVD risk in ARIC

CM Ballantyne et al

S22
After adjustment for age, ARIC center, low-density lipoprotein
cholesterol (LDL-C) level and smoking status, ARIC
participants who had the metabolic syndrome were two
times more likely to have prevalent coronary heart disease
(CHD; defined as prior myocardial infarction or cardiovascular
revascularization) than participants without the metabolic
syndrome.5 For each subgroup defined by sex and race,
prevalence of CHD (without this adjustment) was significantly
higher in individuals with than in individuals without
the metabolic syndrome, the highest CHD prevalence being
in white men with the metabolic syndrome (13%, compared
with 7% in white men without the metabolic syndrome).
Among participants with the metabolic syndrome in other
subgroups, CHD prevalence was 11% in black men (compared
with 4% in black men without the metabolic
syndrome), 4% in black women (compared with 2% in black
women without the metabolic syndrome) and 3% in white
women (compared with 1% in white women without the
metabolic syndrome).
The extent of carotid artery atherosclerosis, assessed by
intima-media thickness (IMT) determined by B-mode ultrasound,
was also significantly greater in ARIC participants
with the metabolic syndrome.5 Mean IMT for six segments
(carotid bifurcation, common carotid and internal carotid in
left and right carotid arteries) was 747 mm in individuals with
and 704 mm in individuals without the metabolic syndrome.
After adjustment for age, ARIC center, LDL-C level, smoking
status, lipoprotein(a) level and white blood cell count, IMT
in individuals with the metabolic syndrome was 38 mm
greater in both white men and white women, 29 mm greater
in black women and 27 mm in black men compared with the
corresponding subgroups without the metabolic syndrome.

Metabolic syndrome and incidence of CVD

The incidence of CHD and ischemic stroke over a mean 11year
follow-up was also assessed in ARIC participants with
and without the metabolic syndrome. In this analysis of data
from 12 089 individuals without diabetes, CHD or stroke at
baseline, prevalence of the metabolic syndrome as defined
by ATP III was 23%.6 Incident CHD was defined as fatal or
nonfatal CHD, silent myocardial infarction identified by
electrocardiography or coronary revascularization. The crude
incidence rate of CHD per 10 000 person-years was significantly
higher in both men and women with the metabolic
syndrome (138.4 and 57.5, respectively) compared with men
and women without (92.3 and 22.7, respectively). After
adjustment for age, race/ARIC center, LDL-C level and
smoking status, the hazard ratio (HR) for incident CHD in
ARIC participants with versus without the metabolic syndrome
was 1.46 (95% confidence interval (CI): 1.23–1.74) in
men and 2.05 (95% CI: 1.59–2.64) in women (Po0.03 for sex
interaction). The metabolic syndrome components most
strongly associated with incident CHD were elevated blood
pressure and low HDL-C level. Risk for CHD increased with

Adjusted hazard ratio for CHD

10

1

0.7

Women
Men
1 2 34+

Components of the Metabolic Syndrome

Figure 1 Association of coronary heart disease (CHD) risk with metabolic
syndrome components in ARIC. After adjustment for age, race/ARIC center,
low-density lipoprotein cholesterol (LDL-C) and smoking status, risk for CHD
over 11 years increased with the number of metabolic syndrome components
present at baseline.6 r 2005 American Diabetes Association. Reprinted with
permission from the American Diabetes Association.

the number of metabolic syndrome components present;
among individuals with four or more components present,
the HR for incident CHD was 2.23 (95% CI: 1.64–3.04) in
men and 5.25 (95% CI: 3.10–8.89) in women, compared with
the respective subgroups with no components of the
metabolic syndrome (Figure 1). Applying the lower threshold
for impaired fasting glucose (506 mmol l1)7 to the metabolic
syndrome did not change the magnitude of observed
associations between the metabolic syndrome and either
CHD or stroke estimated from the original ATP III definition.
In multivariable-adjusted models that included all individual
components of the metabolic syndrome, risk for CHD
associated with the presence of the metabolic syndrome
was not in excess of the risk explained by its individual
components. Also, a comparison of receiver operating
characteristic curves (ROC curves) estimated from logistic
regression indicated that identification of the metabolic
syndrome did not improve CHD risk prediction beyond the
Framingham risk score.

The crude incidence rate of ischemic stroke per 10 000
person-years was also significantly higher in ARIC participants
with the metabolic syndrome (24.6 in men and 19.0 in
women, versus 18.1 and 8.5 in men and women, respectively,
without the metabolic syndrome). After adjustment
for age, race/ARIC center, LDL-C level and smoking status,
the HR for incident ischemic stroke in ARIC participants
with versus without the metabolic syndrome was 1.42 (95%

CI: 0.96–2.11) in men and 1.96 (95% CI: 1.28–3.00) in
women.
Metabolic syndrome and prediction of diabetes

In addition to increasing risk for CVD, the metabolic
syndrome increases risk for diabetes. In an analysis of 7915
ARIC participants without diabetes at baseline, panels of risk

International Journal of Obesity


Metabolic syndrome and CVD risk in ARIC

CM Ballantyne et al


S23

60
50
40
30
20
10
0

Percent of total cases

1 2 3 4 5 6 7 8 9 10
60
50
40
30
20
10
0

Percent who developed diabetes

1 10 2 3 4 5 6 7 8 9
Decile of estimated risk

Figure 2 Predictivity of models for development of incident diabetes in ARIC. Percentage of ARIC participants with incident diabetes by decile of estimated risk (left
panel) and percentage of individuals in each decile of estimated risk who developed diabetes during 9 years of follow-up (right panel). Models: clinical information
(age, race, parental history of diabetes, systolic blood pressure, waist and height), gray bars; fasting glucose, white bars; clinical information plus fasting glucose,
black bars; and clinical information, fasting glucose, high-density lipoprotein cholesterol (HDL-C) and triglycerides, diagonally striped bars.8 r 2005 American
Diabetes Association. Reprinted with permission from the American Diabetes Association.

factors and the presence of the metabolic syndrome were
assessed for their predictivity for incident diabetes over 9
years of follow-up (Figure 2).8 For the risk factor panels,
models that included fasting glucose, triglycerides and HDLC
in addition to clinical variables (sex, ethnicity, parental
history of diabetes, systolic blood pressure, waist and height;
area under the ROC curve (AUC) ¼ 0.80, 95% CI: 0.78–0.82)
were significantly better for predicting incident diabetes
than clinical variables alone (AUC ¼ 0.71, 95% CI: 0.69–
0.73). However, in a model that assigned 1 point for each
criterion of the metabolic syndrome and additional points
for obesity and elevated fasting glucose, a score of 3 or more
labeled 46% of participants as high risk and identified 81% of
future cases of diabetes (AUC ¼ 0.78, 95% CI: 0.76–0.80). The
investigators concluded that rules based on the metabolic
syndrome, which may be easier to apply in clinical settings,
although slightly less predictive, are valid alternatives to
more complex and complete risk function equations.

In a similar investigation evaluating strategies to detect
prevalent diabetes not diagnosed by fasting glucose, ARIC
investigators evaluated the use of the metabolic syndrome to
detect individuals classified as having diabetes by a 2-h
glucose value X1101 mmol l1 during a 75-g oral glucose
tolerance test. The presence of three or more ATP III-defined
metabolic syndrome abnormalities, while labeling 28% of
the sample as positive, identified 40% of individuals with
undetected diabetes with a specificity of 72%. By comparison,
a clinical prediction rule composed of clinical findings,
fasting glucose, HDL-C and triglycerides, while labeling 30%
of the sample as positive, identified 56% of individuals with
undetected diabetes with a specificity of 71%.9

Summary

The metabolic syndrome is associated with prevalence and
incidence of CHD, stroke and increased carotid IMT in
middle-aged Americans. Although the prediction of incident

CHD was not better than with the Framingham risk score,
most physicians in clinical practice do not use the Framingham
risk score.10 Furthermore, the metabolic syndrome was
also highly predictive for development of diabetes. Thus, the
simple clinical criteria of the metabolic syndrome may be
helpful in identifying middle-aged individuals with clustered
risk factors who may benefit from more intensive lifestyle
modification and pharmacotherapy accompanied by weight
loss to reduce the risk for developing CVD and diabetes.

Acknowledgements

The Atherosclerosis Risk in Communities Study is carried out
as a collaborative study supported by National Heart, Lung,
and Blood Institute contracts N01-HC-55015, N01-HC55016,
N01-HC-55018, N01-HC-55019, N01-HC-55020,
N01-HC-55021 and N01-HC-55022. Additional funding for
this study was provided by National Institute of Diabetes and
Digestive and Kidney Diseases Grant RO1-DK56918. We
thank the staff and participants of the ARIC study for their
important contributions.

Conflict of interest

A McN is an employee of Merck and owns equity in the
company. All of the other authors declared no financial
interests.

References

1 Expert Panel on Detection, Evaluation and Treatment of High
Blood Cholesterol in Adults. Executive summary of the third
report of the National Cholesterol Education Program (NCEP)
Expert Panel on Detection, Evaluation, and Treatment of High
Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA
2001; 285: 2486–2497.

International Journal of Obesity


Metabolic syndrome and CVD risk in ARIC

CM Ballantyne et al

S24

2 National Cholesterol Education Program. Third Report of the
National Cholesterol Education Program (NCEP) Expert Panel on
Detection, Evaluation, and Treatment of High Blood Cholesterol
in Adults (Adult Treatment Panel III) final report. Circulation
2002; 106: 3143–3421.

3 Ford ES, Giles WH, Mokdad AH. Increasing prevalence of the
metabolic syndrome among U.S. adults. Diabetes Care 2004; 27:
2444–2449.

4 ARIC Investigators. The Atherosclerosis Risk in Communities (ARIC)
Study: design and objectives. Am J Epidemiol 1989; 129: 687–702.

5 McNeill AM, Rosamond WD, Girman CJ, Heiss G, Golden SH,
Duncan BB et al. Prevalence of coronary heart disease and carotid
arterial thickening in patients with the metabolic syndrome (The
ARIC Study). Am J Cardiol 2004; 94: 1249–1254.

6 McNeill AM, Rosamond WD, Girman CJ, Golden SH, Schmidt MI,
East HE et al. The metabolic syndrome and 11-year risk of
incident cardiovascular disease in the Atherosclerosis Risk in
Communities Study. Diabetes Care 2005; 28: 385–390.

7 Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH,
Franklin BA et al. Diagnosis and management of the metabolic
syndrome: an American Heart Association/National Heart, Lung,
and Blood Institute Scientific Statement. Circulation 2005; 112:
2735–2752.

8 Schmidt MI, Duncan BB, Bang H, Pankow JS, Ballantyne CM,
Golden SH et al. Identifying individuals at high risk for diabetes:
the Atherosclerosis Risk in Communities study. Diabetes Care
2005; 28: 2013–2018.

9 Schmidt MI, Duncan BB, Vigo A, Pankow J, Ballantyne CM,
Couper D et al., for the ARIC Investigators. Detection of
undiagnosed diabetes and other hyperglycemia states: the
Atherosclerosis Risk in Communities Study. Diabetes Care 2003;

26: 1338–1343.
10 Mosca L, Linfante AH, Benjamin EJ, Berra K, Hayes SN, Walsh BW
et al. National study of physician awareness and adherence to
cardiovascular disease prevention guidelines. Circulation 2005;

111: 499–510.
International Journal of Obesity




--
Shigenoi Haruki

No comments:

Post a Comment