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HUBUNGAN SINDROM METABOLIK, DIABETES MELITUS DAN PENYAKIT KARDIOVASKULAR

Journal of Human Hypertension (2008) 22, 358–365
& 2008 Nature Publishing Group All rights reserved 0950-9240/08 $30.00
www.nature.com/jhh

ORIGINAL ARTICLE

Effect of metabolic syndrome or type II
diabetes mellitus on the occurrence of
recurrent vascular events in hypertensive
patients

ALM Vlek1, Y van der Graaf1, W Spiering2 and FLJ Visseren2, SMART study group3

1Julius Center for Health Sciences and Primary Care, Department of Epidemiology, University Medical Center
Utrecht, Utrecht, The Netherlands and 2Department of Internal Medicine, Section of Vascular Medicine,
University Medical Center Utrecht, Utrecht, The Netherlands

Patients with hypertension and manifest vascular disease
are at high risk for recurrent cardiovascular
diseases. It is unknown if the metabolic syndrome
further increases the risk in these patients. This study
aims to quantify the effect of metabolic syndrome and
type II diabetes on cardiovascular events in hypertensive
patients with vascular disease. A total of 2196
hypertensive patients with vascular disease (cerebrovascular
disease (34%), coronary heart disease (50%),
peripheral arterial disease (28%), abdominal aortic
aneurysm (13%)) from the Second Manifestations of
Arterial Disease study were followed for up to 10 years
(mean 3.9 years) for death, stroke and myocardial
infarction. Age and sex adjusted hazard ratios (HR)
were calculated for hypertensive patients with metabolic
syndrome but without diabetes (n ¼ 775) and for
hypertensive patients with type II diabetes (n ¼ 381),
compared to merely hypertensive patients (n ¼ 1040).

Forty-nine percent had metabolic syndrome (NCEP
ATPIII definition) and 17% had type II diabetes.
Metabolic syndrome predicted vascular death (HR 1.41,
95% confidence interval (CI) 1.01–1.98), stroke
(HR 1.36, 95% CI 0.85–2.16) and myocardial infarction
(HR 1.40, 95% CI 0.97–2.01). Type II diabetes accounted
for even higher risks of vascular end points (HR 1.41–1.64).
The effect of metabolic syndrome on future events could
not be explained by the presence of type II diabetes.
Even in high-risk patients with hypertension and
vascular disease, presence of metabolic syndrome or
type II diabetes identifies patients at high risk for future
cardiovascular events. Identifying metabolic syndrome
patients may direct therapy focusing on treatment of
insulin resistance by reducing weight and increasing
physical activity.
Journal of Human Hypertension (2008) 22, 358–365;
doi:10.1038/jhh.2008.5; published online 14 February 2008

Keywords: metabolic syndrome; diabetes mellitus type II; cardiovascular diseases; epidemiology

Introduction

Patients with clinically manifest vascular disease
are at increased risk of developing recurrent vascular
events. A considerable proportion of these
patients has hypertension as well, which is also a
well-established cardiovascular risk factor.1 Patients
with both manifest vascular disease and hypertension
make up a high-risk population for recurrent
vascular disease.1,2 In about half of patients with
hypertension insulin resistance can be found and
hypertension tends to cluster with metabolic risk

Correspondence: Dr FLJ Visseren, Internal Medicine, Section of
Vascular Medicine, UMC Utrecht, F 02.126, Heidelberglaan 100,
3584 CX Utrecht, The Netherlands.
E-mail: f.l.j.visseren@umcutrecht.nl
3Members of the SMART Study Group are listed in the Appendix.
Received 3 October 2007; revised 4 December 2007; accepted 9
January 2008; published online 14 February 2008

factors.3,4 Therefore, hypertension is considered one
of the key features of the metabolic syndrome.5,6

The clustering of cardiovascular risk factors, often
referred to as metabolic syndrome, is closely
associated with central obesity and insulin resistance.
7,8 Metabolic syndrome is a highly prevalent
condition with a prevalence around 20% in the
general population8–10 and 45% in patients with
clinical manifestations of atherosclerosis,11,12 while
diabetes is present in 5% of the overall adult
population.13

Presence of metabolic syndrome amplifies the risk
of developing type II diabetes mellitus 3-to 30-fold,
depending on the criteria used.14–18 In populations
free of cardiovascular disease at baseline, cardiovascular
morbidity and mortality increased 1.5-to
3-fold in the presence of metabolic syndrome10,19–21
and two-to fourfold in the presence of type II
diabetes.22 In spite of the use of different and
modified definitions, the metabolic syndrome is


Metabolic syndrome and vascular disease

ALM Vlek et al


associated with more extensive vascular damage
and increased risk for subsequent events in patients
with prevalent cardiovascular disease.12,23,24 In
hypertensive patients without manifest vascular
disease, the metabolic syndrome has been shown
to be associated with increased intima-media thickness
and left ventricular hypertrophy as well as with
increased incidence of cardiovascular events.25–29

It is not yet known whether the metabolic
syndrome still is a predictor of new cardiovascular
events in hypertensive patients with already clinically
manifest cardiovascular disease. If the risk for
future cardiovascular events in patients with hypertension
and the metabolic syndrome is higher
compared to those without the metabolic syndrome,
these patients may benefit from more aggressive
treatment of blood pressure and other risk factors. In
parallel, it has been shown that patients with
coronary artery disease and metabolic syndrome
benefit from achieving lower low-density lipoprotein-
cholesterol plasma levels compared to patients
with coronary artery disease without metabolic
syndrome.30

The aim of this study is to quantify the risk of new
vascular events associated with the metabolic
syndrome and type II diabetes in patients with
hypertension and manifest vascular disease.

Materials and methods

Study design and population

The Second Manifestations of Arterial Disease
(SMART) study is an ongoing prospective follow-
up study in the University Medical Center Utrecht.
Since 1996, more than 7000 newly referred patients
aged 18–80 years with clinically manifest atherosclerotic
vascular disease (cerebrovascular disease,
coronary heart disease, peripheral arterial disease or
abdominal aortic aneurysm) or risk factors for
atherosclerosis (hyperlipidemia, type I diabetes,
type II diabetes or hypertension) are included.
Patients with terminal malignant disease, those not
independent in daily activities or insufficiently
familiar with the Dutch language are not included.
All patients are assessed for atherosclerotic risk
factors and arterial diseases by non-invasive means.
The local Ethics Committee approved the study and
all participants gave their written informed consent.
Important objectives of the SMART study are to
evaluate the presence of additional arterial disease
and risk factors in patients with manifest vascular
disease or a vascular risk factor. The rationale and
design of the SMART study have been described in
detail elsewhere.31

This analysis is based on patients included in the
screening period from January 1996 to March 2005
and contains data on 2196 patients with clinically
manifest vascular disease (at inclusion or in past
history), who also had hypertension at inclusion.
Normotensive patients with manifest vascular

n=5057
manifest vascular disease
n=3323
data complete n=2196
type 1 diabetes excluded
n=2211
manifest vascular disease
+ hypertension n=2233
no hypertension
n=1090
type 1 diabetes n=22
no manifest vascular
disease n=1734
data incomplete
n=15
hypertension
only
n=1040
hypertension
+ diabetes
n=381
hypertension +
metabolic
syndrome n=775
Figure 1 Composition of the study population.
disease (n ¼ 1090) and patients with type I diabetes
mellitus (n ¼ 22) were not included in data analyses.
Clinically manifest vascular disease was defined as
cerebrovascular disease, coronary heart disease,
abdominal aortic aneurysm or peripheral arterial
disease at inclusion or in past history. Cerebrovascular
disease included transient ischaemic attack,
cerebral infarction, amaurosis fugax or retinal
infarction; coronary heart disease included myocardial
infarction and admission for percutaneous
transluminal coronary angioplasty or coronary
artery bypass graft; abdominal aortic aneurysm
included abdominal aortic aneurysm X3.0 cm or
aneurysm surgery; peripheral arterial disease included
claudication of the legs, which was symptomatic
and confirmed by a resting ankle-brachial
pressure index o0.9 in at least one leg, percutaneous
transluminal angioplasty or leg amputation.
A description of the composition of the study
population is shown in Figure 1.

Measurements

All patients who entered the SMART study underwent
a diagnostic screening-protocol for detection of
manifestations of atherosclerotic disease and vascular
risk factors. Physical examination included
assessments of height, weight, waist and hip
circumferences and blood pressure. Blood pressure
was measured by sphygmomanometry at the right
and left upper arm and repeated on the side with the
highest values. The mean of all obtained measurements
was used in the analysis.31 This assessment
seems to be reliable as in a sample of 211 patients
who underwent a second blood pressure measurement
after 5.5±1.3 years, 94% of newly diagnosed
hypertensive subjects at inclusion were still

Journal of Human Hypertension


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ALM Vlek et al

hypertensive or receiving blood pressure lowering
agents at the second measurement.

Fasting blood samples were taken to ascertain
levels of lipid, glucose, creatinine and homocysteine.
Urinary albumin and creatinine concentrations
were determined and duplex scanning of the
carotid arteries, ultrasonography of the abdomen,
electrocardiography and ankle-brachial pressure
index were performed. The techniques of the baseline
examinations have been published formerly.31
All subjects completed a health questionnaire on
cardiovascular history, risk factors, familial vascular
history and medication use.

Definitions

Hypertension was defined as a systolic blood
pressure X140 mm Hg and/or a diastolic blood
pressure X90 mm Hg and/or use of antihypertensive
drug therapy. According to 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),7 metabolic syndrome is defined as the
presence of three or more of the following: (1) waist
circumference 488 cm in women and 4102 cm
in men; (2) fasting triglycerides X1.70 mmol l1
(150 mg per 100 ml); (3) high-density lipoprotein
cholesterol o1.29 mmol l1 (50 mg per 100 ml) in
women and o1.04 mmol l1 in men (40 mg per
100 ml); (4) blood pressure X130/85 mm Hg or use
of antihypertensive drug therapy and (5) fasting
glucose X6.1 mmol l1 (110 mg per 100 ml) or use of
hypoglycaemic agents. As all patients in this study
satisfy the blood pressure criterion, the metabolic
syndrome was diagnosed when two or more of the
other criteria were present in addition to the blood
pressure criterion. Type II diabetes was diagnosed as
self-reported type II diabetes or use of glucose-
lowering therapy. On the basis of these definitions,
study subjects were divided into three separate
groups. Those diagnosed with type II diabetes made
up the diabetic group, irrespective of additional
presence of the metabolic syndrome. The second
group consisted of non-diabetic patients fulfilling
the metabolic syndrome criteria, and remaining
patients constituted the reference group of nondiabetic
hypertensive patients without the metabolic
syndrome.

Follow-up procedure and end point evaluation

On a half-yearly basis, information on hospitalization
and outpatient clinic visits was obtained
by questionnaires and telephone interviews with
patients. For the subjects who reported a cardiovascular
event, original source documents were
retrieved and reviewed to determine the occurrence
of cardiovascular disease. Additional information
was collected on vascular interventions and death
from other causes.

Outcome events used in our study include

(1) vascular death; (2) non-fatal and fatal stroke;
(3) non-fatal and fatal myocardial infarction and
sudden death and (4) combined vascular events
(non-fatal and fatal stroke, non-fatal and fatal
myocardial infarction and sudden death). Vascular
death was defined as sudden death (unexpected
cardiac death occurring within 1 h after onset of
symptoms or within 24 h given convincing circumstantial
evidence) or death from stroke, myocardial
infarction, congestive heart failure or rupture of
abdominal aortic aneurysm. Patients with stroke
had relevant clinical features causing an increase in
impairment of at least one grade on the modified
Rankin scale, accompanied by an infarction or
haemorrhage on a repeat CT scan. Myocardial
infarction was defined by at least two of the
following criteria: (1) chest pain for at least 20 min,
not disappearing after administration of nitrates;
(2) ST-elevation 41 mm in two following leads or a
left bundle branch block on the electrocardiogram;
(3) creatine kinase elevation of at least two times the
normal value of creatine kinase and a myocardial
band-fraction 45% of the total creatine kinase.
All possible events were audited independently
by three members of the Endpoint Committee.

Data analysis

Results are expressed as mean±s.d. for continuous
variables and as percentages with the number of
patients in brackets for categorical variables. Survival
free from vascular mortality, myocardial infarction
and sudden death, stroke and combined
vascular events was evaluated with the use of the
Cox proportional hazards model separately for
hypertensive patients with metabolic syndrome but
not type II diabetes and for hypertensive patients
with type II diabetes. Merely hypertensive patients
served as the reference category in the analyses. Any
first occurrence of an event during the follow-up
period was used in the model. As all patients
already had manifest vascular disease, these were
all recurrent vascular events. The extent of confounding
was assessed by comparing the crude
hazard ratio (HR) derived from the initial model
with the adjusted HR derived from the model that
contained the potential confounding variable. HRs
were adjusted for age and sex. All statistical
analyses were performed with SPSS 14.0 for
Windows (SPSS, Chicago, IL, USA).

Results

Baseline characteristics

From the total study population of 2196 patients,
1040 patients (48%) had hypertension and did not
have metabolic syndrome or type II diabetes, 775
patients (35%) had hypertension in combination
with metabolic syndrome but not type II diabetes

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and 381 patients (17%) had hypertension and type II
diabetes (Table 1). In type II diabetic patients, 78.5%
did also meet the metabolic syndrome criteria.

In the total study population of hypertensive
patients with manifest vascular disease, the prevalence
of metabolic syndrome was 49%. After
hypertension (100%), the criterion for triglycerides
was most frequently present (76%) in patients with
metabolic syndrome, followed by high-density lipoprotein
cholesterol (69%), waist circumference
(54%) and fasting glucose (53%).

Mean blood pressure in treated hypertensives
was 150/84 mm Hg compared to 155/85 mm Hg in
untreated subjects.

Incidence of vascular events

During a mean follow-up period of 3.9 years (range
0.5–8.5 years), 176 vascular deaths, 94 non-fatal and

Table 1 Baseline characteristics of the study population

fatal strokes and 147 non-fatal and fatal myocardial
infarctions and sudden deaths were recorded. In
total, there were 283 recurrent vascular events.

Survival analysis

Event-free survival curves, derived from an age-and
sex-adjusted Cox proportional hazards model, are
shown for the end points vascular death, stroke,
non-fatal and fatal myocardial infarction and sudden
death and combined vascular events (Figures
2a–d). Metabolic syndrome was associated with a
higher risk for vascular death (HR 1.41; 95%
confidence interval (CI) 1.01–1.98) and for myocardial
infarction and sudden death (HR 1.40; 95% CI
0.97–2.01), adjusted for age and sex in this hypertensive
cohort (Table 2). Although less explicit and
not statistically significant, there was a distinct
relation between metabolic syndrome and stroke

MetSaDMb. n ¼ 1040
MetSa+
DMb. n ¼ 775
DMb+
n ¼ 381
Ever cerebrovascular disease 36 (375) 30 (230) 41 (157)
Ever coronary heart disease 49 (507) 51 (393) 53 (202)
Ever peripheral arterial disease 23 (238) 30 (231) 31 (119)
Ever abdominal aortic aneurysm 14 (140) 16 (120) 8 (30)
Male gender 76 (795) 72 (557) 71 (270)
Age (years) 61.9±10.0 60.3±10.1 62.9±9.1
Smoking, current or pastc 81(844) 84(649) 78(295)
Body mass index (kg m2) 25.4±3.2 28.4±4.1 28.0±4.1
Waist circumference (cm) 92±10 101±11 100±11
Triglycerides (mmol l1) 1.43±0.86 2.59±2.37 2.05±1.01
High-density lipoprotein cholesterol (mmol l1) 1.41±0.37 1.05±0.28 1.10±0.30
Glucose (mmol l1) 5.6±0.7 6.4±1.5 9.0±3.0
Systolic blood pressure (mm Hg) 153±20 150±19 154±21
Diastolic blood pressure (mm Hg) 86±11 84±11 83±11
Duration of hypertension (years) 10.2±12.7 11.0±12.0 12.5±13.5
Creatinine (mmol l1) 104.9±89.9 99.9±52.0 105.2±89.8
Creatinine clearanced (ml per min per 1.73 m2) 72.8±19.4 72.7±19.6 73.9±22.6
Albuminuriae 17 (166) 20 (141) 29 (103)
Use of lipid–lowering drugs 48 (497) 48 (371) 54 (203)
Use of glucose-lowering agents 0 (0) 0 (0) 94 (355)
Use of blood pressure-lowering agents 62 (647) 71 (552) 73 (277)
Amount of antihypertensive agents
0 agent 38 (393) 29 (223) 27 (104)
1 agent 33 (340) 31 (238) 28 (105)
2 agents 20 (205) 28 (218) 29 (110)
3 or more agents 9 (102) 12 (96) 16 (62)
Type of antihypertensive agents
b-blockers 37 (389) 47 (366) 39 (150)
Diuretics 14 (143) 20 (158) 24 (90)
Calcium channel blockers 20 (203) 25 (193) 22 (82)
ACE inhibitors 23 (239) 25 (190) 40 (153)
ATII antagonists 6 (64) 7 (53) 8 (29)
Rest groupf 4 (33) 3 (19) 5 (21)

aMetabolic syndrome according to the ATPIII criteria.
bSelf-reported type II diabetes and/or use of glucose-lowering agents.
cSmoking or previously smoking.
dModification of diet in renal disease formula.
eAlbumin-to-creatinine ratio 43 mg mmol1.
fCombination preparations, centrally active agents, a-blockers.
Continuous variables are expressed as mean±s.d. and categorical variables as percentages with the number of patients between parentheses.


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Figure 2 Fraction of hypertensive patients free from vascular death (a), stroke (b), myocardial infarction and sudden death (c) and
combined vascular events (d) according to metabolic syndrome and type II diabetes, adjusted for age and sex. Lines for metabolic

syndrome and type II diabetes overlap in (c).

(HR 1.36; 95% CI 0.85–2.16) and between metabolic
syndrome and combined vascular endpoints (HR
1.24; 95% CI 0.95–1.62). Type II diabetes was
associated with an increased risk for vascular death
(HR 1.59; 95% CI 1.07–2.35), stroke (HR 1.40; 95%
CI 0.96–2.79) and the combined vascular endpoint
(HR 1.54; 95% CI 1.13–2.09). For all analyses,
additional adjustment for the amount and type of
blood pressure lowering agents did not substantially
change the HRs.

Discussion

In a high-risk population of patients with hypertension
and clinically manifest vascular disease,
the presence of the metabolic syndrome entails a
1.41-fold greater risk for vascular death as well as a
1.40-fold greater risk for myocardial infarction and
sudden death. In hypertensive patients with type II
diabetes, the risk for vascular death (HR 1.59),
combined vascular events (HR 1.54) and stroke

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Table 2 Hazard ratios (HRs) of metabolic syndrome and type II diabetes for categories of future events

Vascular death (n ¼ 176)
HR (95% CI; P-value)
Stroke (n ¼ 94)
HR (95% CI; P-value)
Myocardial infarction and
sudden death (n ¼ 147)
HR (95% CI; P-value)
Combined vascular end
points (n ¼ 283)
HR (95% CI; P-value)
Hypertension only
Hypertension+MetSa
Hypertension+DMb
1.00
(n ¼ 68)
1.41 (1.01–1.98; 0.046)
(n ¼ 68)
1.59 (1.07–2.35;0.02)
(n ¼ 40)
1.00
(n ¼ 35)
1.36 (0.85–2.16;0.2)
(n ¼ 37)
1.64 (0.96–2.79;0.07)
(n ¼ 22)
1.00
(n ¼ 57)
1.40 (0.97–2.01;0.07)
(n ¼ 60)
1.41 (0.91–2.20;0.1)
(n ¼ 30)
1.00
(n ¼ 113)
1.24 (0.95–1.62;0.1)
(n ¼ 105)
1.54 (1.13–2.09;0.006)
(n ¼ 65)

aMetabolic syndrome according to the ATPIII criteria.
bSelf-reported type II diabetes and/or use of glucose-lowering agents.
HRs are adjusted for age and sex.


(HR 1.64) is higher than for those without diabetes.
Unless similar blood pressure and age at baseline,
hypertensive patients with metabolic syndrome or
diabetes are at higher risk for new cardiovascular
events than hypertensive patients without metabolic
syndrome or diabetes.

In studies among non-diabetic hypertensive subjects
without cardiovascular disease, metabolic
syndrome was present in 25–30% of patients.25,27,29
In this study population, consisting of (treated)
hypertensive patients with clinically manifest vascular
disease, 49% of patients meet the metabolic
syndrome criteria. In patients without diabetes this
was 35%. The high prevalence of metabolic syndrome
we observed is probably due to the fact that
only hypertensive subjects with manifest vascular
disease were included.

Several studies have demonstrated an association
between metabolic syndrome and increased intima-
media thickness, higher urinary albumin excretion
and left ventricular hypertrophy in hypertensive
subjects without manifest vascular disease.25,26,29 In
this population, presence of metabolic syndrome
was also associated with an increased amount of
cardiovascular events.28 A few studies compared the
effects of metabolic syndrome and diabetes on
cardiovascular disease. The role of the metabolic
syndrome in predicting all-cause and cardiovascular
mortality in patients with established cardiovascular
disease was examined in the San Antonio
Heart Study. After adjustment for diabetes and in
subgroup analyses of non-diabetic and diabetic
patients, the metabolic syndrome was no longer
associated with both all-cause and cardiovascular
mortality, which made the authors conclude that
only diabetes accounted for the enhanced mortality
in the metabolic syndrome group.32 In NHANES III,
participants with metabolic syndrome and diabetes
showed the highest prevalence of cardiovascular
disease, followed by those with metabolic syndrome
without diabetes and patients with neither. However,
in multivariate analysis metabolic syndrome
was no longer a significant predictor of cardiovascular
disease.33 In patients with coronary heart
disease, both metabolic syndrome without diabetes

and diabetes alone were predictive of all-cause and
cardiovascular mortality.24 Similar to our population,
diabetic patients had the highest mortality risk.
A study among post-myocardial infarction patients
showed a higher probability of death and cardiovascular
events in both metabolic syndrome and
diabetic patients.34 In the Framingham Offspring
Study, stroke risks were compared between metabolic
syndrome and diabetic patients in a population
in which some but not all patients had a history
of cardiovascular disease. Patients with diabetes and
metabolic syndrome were at greatest risk of stroke,
followed by patients with diabetes alone and
metabolic syndrome alone.35 In our study, type II
diabetes was associated with an increased risk of
stroke, while metabolic syndrome and stroke risk
was evident but not statistically significant. This is
probably due to the difference in study populations
and the relatively small number of strokes (n ¼ 94)
in our study.

In this study, metabolic syndrome is markedly
associated with an increased risk of cardiovascular
events. There are several mechanisms possibly
underlying this association. The suggestion is made
that the effect of the metabolic syndrome is
primarily driven by the inclusion of diabetes in the
definition.32 Although the vascular risk caused by
the metabolic syndrome is partly due to diabetes, as
shown by studies where the effect of the metabolic
syndrome was attenuated or disappeared after
adjustment for diabetes or after subgroup analysis
in diabetic and non-diabetic patients,32,33 it is not
likely that the vascular risk associated with the
metabolic syndrome is completely caused by the
inclusion of diabetic patients, as our study still
identifies a large association between the metabolic
syndrome and vascular events apart from diabetes.
Other possible mechanisms causing an increased
risk of vascular disorders in hypertensive patients
with metabolic syndrome are insulin-mediated renal
sodium reabsorption and vasoconstriction due to
activation of the sympathetic nerve system and the
renin-angiotensin-aldosterone system. Besides these
mechanisms, there are other not routinely measured
factors such as hypercoagulability, oxidative stress,

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ALM Vlek et al

proinflammatory state, hyperinsulinaemia and impaired
fibrinolysis associated with the metabolic
syndrome, which may contribute in increasing
cardiovascular risk. As the metabolic syndrome
may precede diabetes, the vascular risk associated
with the metabolic syndrome may also in part be
mediated by the development of type II diabetes
during follow-up. In this study, a gradual effect of
metabolic syndrome and type II diabetes was seen
on the risk of cardiovascular events. Metabolic
syndrome can be seen as a pre-diabetic state with
insulin resistance as the key feature. Owing to this
central underlying pathophysiological mechanism,
different combinations of the same number of
metabolic syndrome traits are roughly comparable
regarding vascular risk. Subjects who developed
type II diabetes during 8-year follow-up were found
to have increased triglyceride levels, decreased
high-density lipoprotein cholesterol levels, increased
systolic blood pressure, slightly increased
fasting glucose levels and much higher insulin
levels at baseline than subjects who did not develop
diabetes.36 Therefore, the cardiovascular risk accompanied
by the metabolic syndrome is lower than that
of type II diabetes patients and higher than that of
non-metabolic syndrome patients.

We acknowledge several limitations of this
study. The SMART database does not provide
information on blood pressure values during follow-
up, so we could only classify patients as hypertensive
based on their baseline blood pressure and/or
use of blood pressure lowering medication. A white-
coat effect may also be involved in the blood
pressure measurements. However, in a sample of
patients who underwent a second blood pressure
measurement, 94% of newly diagnosed hypertensives
were still hypertensive or receiving blood
pressure-lowering agents. Inclusion of patients
started in 1996, but the metabolic syndrome was
defined retrospectively according to the NCEP
criteria. In the group of patients with type II
diabetes, there are both patients with and without
the metabolic syndrome. Owing to the number of
patients in this group, we were not able to separate
these two subgroups.

In conclusion, even in a high-risk population of
hypertensive patients with manifest vascular disease,
it is still possible to differentiate between
patients with lower and higher risks of recurrent
vascular disease: metabolic syndrome increases the
risk of vascular events with 25–40%, whereas
type II diabetes shows a 40–65% increase in
vascular risk. These results support the importance
of aggressive treatment of blood pressure and other
cardiovascular risk factors in high-risk patients.
Besides aggressive treatment for individual risk
factors, hypertensive patients with the metabolic
syndrome may benefit from intensive lifestyle
therapies such as stimulating physical activity
and weight reduction aiming to decrease insulin
resistance.

What is known about the topic

K Patients with hypertension and vascular disease are at high
risk for recurrent vascular diseases

K The metabolic syndrome and diabetes increase the risk of
developing cardiovascular events in different populations

What this study adds

K Even in a hypertensive population with manifest vascular
disease the metabolic syndrome and diabetes are still
predictive of future cardiovascular disease

K Based on their higher risk for future vascular events,
hypertensive patients with the metabolic syndrome or
diabetes may benefit from aggressive risk factor treatment and
lifestyle changes

Acknowledgements

Thanks are gratefully extended to the SMART Study
Group, the members of which are listed in the
appendix.

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MD, PhD; WPThM Mali, MD, PhD; FL Moll, MD,
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PhD.

Journal of Human Hypertension




--
Shigenoi Haruki

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