HIPERTENSI PADA SINDROM METABOLIK
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articles
Relationship Between the Metabolic Syndrome
and the Development of Hypertension in the
Hong Kong Cardiovascular Risk Factor Prevalence
Study-2 (CRISPS2)
Bernard M.Y. Cheung1, Nelson M.S. Wat1, Y. B. Man1, Sidney Tam2, C. H. Cheng1, Gabriel M. Leung3,
Jean Woo4, Edward D. Janus5, C. P. Lau1, T. H. Lam3 and Karen S.L. Lam1
BACkgROuNd
The metabolic syndrome is a predictor of diabetes and coronary
events. We hypothesized that it also predicts hypertension.
METhOdS
a total of 1,944 subjects (901 men and 1,043 women;
age 46 ± 12 years) from the Hong Kong Cardiovascular Risk Factor
Prevalence Survey were recruited in 1995–1996 and restudied in
2000–2004. The prevalence of hypertension and factors predicting
its development were determined.
RESulTS
In 2000–2004, hypertension was found in 23.2% of the men and
17.2% of the women. Of the 1,602 subjects who were normotensive
at baseline, 258 subjects developed hypertension after a median
interval of 6.4 years. according to the National Cholesterol Education
Program (NCEP) and International Diabetes Federation (IDF)
criteria, the hazard ratios associated with the metabolic syndrome
were 1.89 (95% confidence interval (CI): 1.41–2.54) and
1.72 (95% CI: 1.24–2.39), respectively. The positive and negative
Hypertension is an important cardiovascular risk factor and a
major health problem worldwide. In the United States, 29.3% of
the population has hypertension, but only 36.8% of people with
hypertension have good blood pressure control.1 There is a need
for improvement because controlling blood pressure markedly
reduces cardiovascular risk.
Although there are many drugs that effectively lower blood
pressure, it is not a cure. Curable forms of hypertension are of
low prevalence. In the vast majority of hypertensive patients,
1Department of Medicine, University of Hong Kong, Hong Kong; 2Clinical
Biochemistry Unit, Queen Mary Hospital, Hong Kong; 3Department of
Community Medicine, University of Hong Kong, Hong Kong; 4Department
of Medicine and Therapeutics, Chinese University of Hong Kong, Shatin,
Hong Kong; 5Department of General Medicine, University of Melbourne,
Western Hospital, Footscray, australia. Correspondence: Bernard M.y. Cheung
(b.cheung@bham.ac.uk)
Received 5 June 2007; first decision 5 July 2007; accepted 26 July 2007.
doi:10.1038/ajh.2007.19
© 2008 American Journal of Hypertension, Ltd.
predictive values of the metabolic syndrome for identifying
subjects who will develop hypertension in this population were
34.7 and 85.4% (NCEP criteria), and 33.1 and 85.5% (IDF criteria),
respectively. The development of hypertension was related to
the number of components of the metabolic syndrome
(other than raised blood pressure), present in men (P = 0.003)
and in women (P = 0.001). Using multivariate analysis, age,
baseline systolic blood pressure (SBP), body mass index (BMI),
and the triglycerides/high-density lipoprotein (HDL) ratio were found
to be significant predictors of the development of hypertension.
Compared with optimal blood pressure, the hazards of developing
hypertension associated with normal or high-normal blood
pressure were 2.31 (95% CI: 1.68–3.17) and 3.48 (95% CI: 2.52–4.81),
respectively.
CONCluSiONS
Blood pressure, when not optimal, is the predominant predictor
of hypertension. The metabolic syndrome contributes to the risk,
especially when blood pressure is optimal.
Am J Hypertens 2008; 21:17-22 © 2008 American Journal of Hypertension, Ltd.
the cause of hypertension is multifactorial. Therefore, there is a
need to identify modifiable factors that lead to the development
of hypertension.
The metabolic syndrome is a cluster of cardiovascular risk factors including central obesity, high blood pressure, raised blood
glucose and triglyceride levels, and low high-density lipoprotein
(HDL) cholesterol levels.2,3 In recent years, the syndrome has
been found to be useful in identifying people predisposed to
diabetes and coronary heart disease.4–6 It is not known whether
the syndrome also predicts the development of hypertension.
As high blood pressure is a component of this syndrome, we
set out to examine the association of the metabolic syndrome
and its components with the development of hypertension in a
Chinese population.
METhOdS
The Hong Kong Cardiovascular Risk Factor Prevalence Study is
a unique and comprehensive study of cardiovascular risk factors
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among the general population in Hong Kong.6 In 1995–1996,
2,895 Chinese in Hong Kong (1,412 men and 1,483 women, aged
25–74) were selected randomly by their telephone numbers. The
study protocol was approved by the Ethics Committee of the
University of Hong Kong Faculty of Medicine. This method has
been validated locally, and it was shown that those who did not
attend were closely matched in all other respects (in terms of
demographics, health, socioeconomic status, and risk factors)
to those who were enrolled. The participation rate was 37.1%. In
2000–2004, the subjects were contacted for the follow-up study,
the Hong Kong Cardiovascular Risk Factor Prevalence Study-2
(CRISPS2). Patient recruitment was temporarily stopped in 2003
because of the Severe Acute Respiratory Syndrome.
The participants came in the morning having fasted overnight. They were asked about their age, occupation, smoking
and alcohol-drinking habits, and history of cardiovascular diseases, hypertension, and diabetes. All participants gave written
informed consent. Height was measured to the nearest 0.5 cm
and weight to the nearest 0.1 kg (DETECTO Instrument, MO).
Waist and hip circumferences were measured two times to
the nearest 0.5 cm and the arithmetic means were adopted for
subsequent analyses. Waist circumference was measured halfway between the xiphisternum and the umbilicus, whereas
hip circumference was measured at the level of the greater
trochanters.
Blood pressure was measured in the right arm manually using
a mercury sphygmomanometer. The subjects sat for at least
10 min and three measurements were taken at 5-min intervals.
The first measurement was to familiarize the subject with the
procedure; the mean of the second and third readings was used
for data analysis. The Korotkoff V sound was used to determine
diastolic pressure. A subject was classified hypertensive if the
systolic blood pressure (SBP) was =140 mm Hg, or the diastolic blood pressure (DBP) was =90 mm Hg, or if the subject had
previously been diagnosed with hypertension and was taking
antihypertensive medications. We used the European Society
of Hypertension and the European Society of Cardiology definition of optimal (SBP < 120 mm Hg and DBP < 80 mm Hg),
normal (SBP 120–129 mm Hg and/or DBP 80–84 mm Hg), and
high-normal (SBP 130–139mmHg and/or DBP 85–89mmHg)
blood pressure.7 Venous blood (20 ml) was taken for blood biochemistry and lipid profile. Lipids were measured on a Hitachi
912 analyzer as described previously.6 Low-density lipoprotein
(LDL) cholesterol was calculated using Friedewald's equation
if the total triglycerides did not exceed 4.5 mmol/l (400 mg/dl).
Otherwise, LDL was determined by a direct assay using selective micellary solubilization of LDL by a nonionic detergent in
an enzyme-coupled colorimetric assay automated on a Hitachi
912 analyzer. As plasma triglycerides and HDL cholesterol are
closely correlated, we calculated the triglyceride to HDL ratio for
multivariate analysis. The ratio is a surrogate marker for small
dense LDL, the more atherogenic form of LDL, and is therefore
a strong predictor of myocardial infarction.8,9 An oral glucose
tolerance test was performed with blood taken before and 2 h
after ingestion of 75 g anhydrous glucose dissolved in 200 ml
distilled water. Glucose was measured by the hexokinase method
Metabolic Syndrome Predicts Hypertension
on the Hitachi 912 analyzer. Insulin was measured by microparticle enzyme immunoassay (Abbott Laboratories, Tokyo, Japan).
The homeostasis model assessment estimate of insulin resistance
(HOMA-IR) was calculated using the formula: fasting plasma
glucose (mmol/l) × fasting insulin (mIU/l)/22.5.10 A subject was
considered to be diabetic if the fasting plasma glucose concentration was =7.0 mmol/l (126 mg/dl), or if the 2-h oral glucose
tolerance test plasma glucose concentration was =11.1 mmol/l
(200 mg/dl), or if the subject had been diagnosed to have diabetes previously and was receiving medications for diabetes.
The National Cholesterol Education Program (NCEP) criteria
for the metabolic syndrome were met if at least three of the following were satisfied (i) waist circumference =90 cm (35 inches)
in Asian men or =80 cm (31 inches) in Asian women; (ii) triglyceride concentration =150 mg/dl (1.7 mmol/l); (iii) HDL
<40 mg/dl (1.03 mmol/l) in men or <50 mg/dl (1.29 mmol/l)
in women; (iv) blood pressure =130/85 mm Hg; (v) fasting glucose =100 mg/dl (5.6 mmol/l).2 Receiving specific treatment was
counted as fulfilling the criterion. The International Diabetes
Federation (IDF) criteria for the metabolic syndrome resemble
the NCEP criteria except that central obesity, defined using sex
and ethnic specific cut points, must be present.3
Data analysis. Baseline characteristics among different groups
were compared using Student's unpaired t-test or Chi-square
test as appropriate. The prevalence of hypertension was
directly standardized for age based on the Hong Kong Census
in 2001.11 In the 1,602 subjects who were normotensive initially, predictors of the development of hypertension were
determined using Cox proportional hazards regression. Age
and sex were adjusted for in univariate models. The other variables examined included smoking, body mass index (BMI),
waist circumference, waist-to-hip ratio, SBP and DBP, fasting
and 2-h plasma glucose, triglycerides, HDL, triglycerides/HDL
ratio, HOMA-IR, fasting insulin, metabolic syndrome (NCEP
or IDF criteria), and the number of metabolic syndrome components (other than raised blood pressure) present in an individual. Variables were entered stepwise in multivariate analysis. P < 0.1 was required for entering a variable into the model
and P < 0.05 to remain in the model. Analyses were performed
using SPSS 11.0 for Windows (SPSS, Chicago, IL); a P value <
0.05 (two-tailed) was considered statistically significant.
RESulTS
Attempts were made to contact all the 2,895 subjects who participated in CRISPS1. A total of 1,944 subjects (901 men, 1,043
women; age 52 ± 12 years; response rate = 67.2%) participated
in this study (CRISPS2). The 951 nonparticipants included 120
who withdrew consent, 121 who chose not to reply or show up,
6 pregnant women who were excluded, 78 who had emigrated,
89 who were confirmed dead according to the Hong Kong Death
Registry, and 537 who could not be traced.
Participants and nonparticipants did not differ significantly in
age, BMI, LDL, drinking habit and the frequencies of hypertension, stroke, and ischemic heart disease. However, those subjects who reenrolled were more likely to be female (54 vs. 47%
jaNUaRy 2008 | VOLUME 21 NUMBER 1 | AMERICAN JOURNAL OF HYPERTENSION
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in nonparticipants), married (85 vs. 77%) and nonsmokers (77
vs. 70%) (P < 0.001 for all). They were also slightly less likely
to be diabetic (9 vs. 12%, P = 0.04), which might explain the
lower plasma triglyceride (P = 0.002), and higher plasma HDL
(P = 0.004) levels.
The age-adjusted overall prevalence of hypertension in 1995–
1996 and 2000–2004 was 18.1% and 23.2% in men, and 16.9 and
17.2% in women, respectively. Out of 1,602 subjects who were
not hypertensive at baseline, 258 subjects were found to be hypertensive at follow-up. Their characteristics are shown in Table 1.
Compared with those who remained normotensive, these hypertensive subjects were older, more likely to be male and smokers, had higher BMI, waist circumference, waist-to-hip ratio,
fasting plasma glucose, plasma glucose at 2 h in an oral glucose
tolerance test, plasma triglycerides, HOMA-IR, fasting plasma
insulin, and lower levels of HDL. Table 2 shows the results of
Cox regression analysis of the predictors of the development of
Table 1 | Baseline characteristics of participants who were
normotensive at baseline in relation to blood pressure status
at follow-up
Normotensive Hypertensive
at follow-up at follow-up Pvalue
Number (%) 1,344 (84) 258 (16) —
age (y) 42.3 ± 10.8 50.2 ± 10.8 <0.001
Males (%) 44 55 0.001
Systolic blood 111 ± 12 123 ± 11 <0.001
pressure (mm Hg)
Diastolic blood 70 ± 8 77 ± 8 <0.001
pressure (mm Hg)
Body mass index 23.5 ± 3.3 25.0 ± 3.3 <0.001
(kg/m2)
Waist 76.7 ± 9.3 81.5 ± 9.2 <0.001
circumference (cm)
hypertension. Five subjects could not be included in this analysis
because of missing data. When single factors were considered,
age, BMI, waist circumference, waist-to-hip ratio, baseline SBP
or DBP, fasting plasma glucose, plasma glucose at 2 h in an oral
glucose tolerance test, plasma triglycerides, HDL, triglycerides/
HDL ratio, HOMA-IR, and fasting plasma insulin were all significantly related to the development of hypertension. The hazard
ratio associated with the metabolic syndrome by the NCEP and
IDF criteria, excluding those who were already hypertensive at
baseline, were 1.89 (95% confidence interval (CI): 1.41–2.54) and
1.72 (95% CI: 1.24–2.39), respectively. The development of hypertension was related to the number of components of the metabolic syndrome other than raised blood pressure, in men (P =
0.003) and in women (P = 0.001) (Figure 1). Using multivariate
analysis, age, baseline SBP, BMI, and the triglycerides/HDL ratio
were found to be significant predictors. If the triglycerides/HDL
ratio is not entered into the model, plasma triglycerides become
a significant predictor (hazard ratio 1.20 (95% CI: 1.06–1.36)).
A BMI of =25 was associated with a hazard ratio of 1.41 (95%
CI: 1.09–1.83), after adjusting for age, sex, presence of diabetes,
smoking status and baseline SBP.
Among 1,602 subjects who were not hypertensive at baseline, the blood pressure was optimal in 974 subjects, normal in
251 subjects and high-normal in 119 subjects. The proportion of
a
1.0
0.8
4
3
2
1
0
No. of metabolic
syndrome components
other than high
blood pressure
Cumulative survival
0.6
0.4
0.2
Waist-to-hip ratio 0.8 ± 0.1 0.9 ± 0.1 <0.001
Fasting glucose 92.8 ± 15.9 101.3 ± 32.1 <0.001
(mg/dl) 0.0
0
OGTT 2-h glucose 113.2 ± 40.4 128.5 ± 65.6 0.001
2,000 4,000
Follow-up duration (days)
2
1
0
No. of metabolic
syndrome components
other than high
blood pressure
(mg/dl)
Triglycerides 94.7 ± 56.3 124.8 ± 85.0 <0.001 b
(mg/dl) 1.0
HDL (mg/dl) 49.8 ± 12.4 46.7 ± 12.7 <0.001
0.8
HOMa-IR 1.0 (0.7–1.6) 1.3 (0.8–1.9) <0.001
Fasting insulin 4.4 (3.0–6.7) 5.4 (3.7–8.0) <0.001
(mIU/l)
Ever smoking (%) 22 28 0.04
alcohol drinkinga 11 16 0.06
(%)
Cumulative survival
0.6
0.4
0.2
Physical activityb 34 34 1.00
3
(%)
4
0.0
Data are shown as means ± SD, medians (interquartile ranges), or percentages.
Student's unpaired t-test, Mann–Whitney test and chi-square test were used as 0 2,000 4,000
appropriate. Follow-up duration (days)
aAt least once a week. bTaking exercise at least once a week in the past month. To
convert mg/dl to mmol/l, multiply by 0.056 for glucose, 0.011 for triglycerides and
0.026 for HDL. Figure 1 | Survival without hypertension in subjects with increasing number
of components of the metabolic syndrome at baseline. (a) Men; (b) women.
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Table 2 | Baseline predictors of the development of hypertension over a median of 6.4 years of follow-up
Multivariate model Multivariate model
Multivariate modelb for menb for womenb,c
Predictor Univariate modela (Cases = 256, N= 1,593) (Cases = 140, N= 728) (Cases = 116, N= 865)
Hazard ratio Hazard ratio Hazard ratio Hazard ratio
(95% CI) Pvalue (95% CI) Pvalue (95% CI) Pvalue (95% CI) Pvalue
age, per year 1.07 (1.06–1.08) <0.001 1.05 (1.04–1.06) <0.001 1.05 (1.03–1.07) <0.001 1.05 (1.03–1.07) <0.001
Gender (0 = male, 1 = female) 0.88 (0.69–1.13) 0.31 NI – – – –
Smoking (0 = never, 1 = ever) 0.82 (0.60–1.12) 0.2 NI – NI – NI –
Body mass index, per kg/m2 1.11 (1.07–1.15) <0.001 1.06 (1.02–1.10) 0.002 1.09 (1.04–1.15) 0.001 NI –
Waist circumference, per cm 1.03 (1.02–1.05) <0.001 NI – NI – NI –
Waist-to-hip ratio 1.04 (1.02–1.05) <0.001 NI – NI – NI –
(×100, per 1 unit)
Systolic blood pressure, 1.06 (1.05–1.08) <0.001 1.06 (1.04–1.07) <0.001 1.06 (1.04–1.08) <0.001 1.06 (1.04–1.08) <0.001
per mm Hg
Diastolic blood pressure, 1.06 (1.05–1.08) <0.001 NI – NI – NI –
per mm Hg
Fasting glucose, per 10 mg/dl 1.04 (1.01–1.08) 0.02 NI – NI – NI –
OGTT 2-h glucose, per 10 mg/dl 1.03 (1.02–1.05) <0.001 NI – NI – NI –
Triglycerides, per 10 mg/dl 1.03 (1.02–1.04) <0.001 NI – 1.02 (1.00–1.04) 0.01 NI –
HDL, per 10 mg/dl 0.83 (0.74–0.91) <0.001 NI – NI – 0.83 (0.71–0.97) 0.02
Triglycerides/HDL ratio, 1.23 (1.13–1.34) <0.001 1.14 (1.04–1.25) 0.002 NI – NI –
per 1 unit
HOMa-IR, per 1 unit 1.07 (1.03–1.11) 0.001 NI – NI – NI –
Fasting insulin, per mIU/l 1.02 (1.00–1.03) 0.009 NI – NI – NI –
Metabolic syndrome 1.89 (1.41–2.54) <0.001 NI – NI – NI –
(NCEP criteria)
Metabolic syndrome 1.72 (1.24–2.39) 0.001 NI – NI – NI –
(IDF criteria)
Number of metabolic syndrome 1.24 (1.09–1.41) <0.001 NI – NI – NI –
components other than raised
blood pressure
HOMA-IR, homeostasis model assessment estimate of insulin resistance; IDF, International Diabetes Federation; NCEP, National Cholesterol Education Program; NI, Not included in
the model; OGTT, oral glucose tolerance test.
aPredictors were age-and sex-adjusted, except for age, which was sex-adjusted, and sex, which was age-adjusted. bStepwise (forward) Cox proportional hazards model was used.
P < 0.1 was necessary for a variable entering into the model and P < 0.05 for staying in the model. cAdditionally adjusted for menopausal status and use of hormone replacement
therapy. Subjects with missing data were excluded in the multivariate model.
subjects who developed hypertension at follow-up was 7.4% in the
optimal group, 25.5% in the normal group and 44.1% in the high-
normal group (P < 0.001). The rate of progression to hypertension
in these three groups was 1.1, 3.9, and 7.1% per year, respectively.
Compared with optimal blood pressure, the hazards of developing
hypertension associated with normal or high-normal blood pressure were 2.31 (95% CI: 1.68–3.17) and 3.48 (95% CI: 2.52–4.81)
fold, respectively. In subjects with optimal blood pressure at baseline, the NCEP and IDF metabolic syndrome were associated with
sex- and age-adjusted hazard ratios of 2.09 (95% CI: 1.10–3.96)
and 2.24 (95% CI: 1.15–4.36), respectively, for the development
of hypertension. In subjects with normal blood pressure, the corresponding hazard ratios were 1.34 (95% CI: 0.74–2.42) and 1.41
(95% CI: 0.74–2.67). In subjects with high-normal blood pressure,
the corresponding hazard ratios were 1.10 (95% CI: 0.72–1.69)
and 0.98 (95% CI: 0.61–1.60).
The sensitivity and specificity of the metabolic syndrome for
identifying subjects who will develop hypertension in this population were 16.3 and 94.1% (NCEP criteria), and 17.1 and 93.4%
(IDF criteria), respectively. The positive and negative predictive
values of the metabolic syndrome for identifying subjects who
will develop hypertension were 34.7 and 85.4% (NCEP criteria),
and 33.1 and 85.5% (IDF criteria), respectively.
The components of the metabolic syndrome are defined by
cutoff points. Receiver operating characteristic curves were
drawn for these components as continuous variables. The areas
under the receiver operating characteristic curves were 0.62
(waist), 0.74 (SBP), 0.67 (DBP), 0.65 (glucose), 0.60 (triglycerides), and 0.55 (HDL) in men, and 0.66 (waist), 0.81 (SBP),
0.75 (DBP), 0.57 (glucose), 0.64 (triglycerides), and 0.57 (HDL)
in women. The area under the receiver operating characteristic
curve for age was 0.69 in men and 0.73 in women.
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diSCuSSiON
The Hong Kong Cardiovascular Risk Factor Prevalence Study
is a large and unique cohort of urbanized Hong Kong Chinese
subjects, with more than 12,000 person-years of follow up.6
Analysis of the baseline data has shown that hypertension and
diabetes are common in Hong Kong, and there is a clustering
of cardiovascular risk factors. It has particularly highlighted
the importance of obesity and its close relationship with
insulin resistance diabetes, dyslipidemia, and hypertension.
Although cross-sectional studies are useful, there is a need
for prospective data on cardiovascular risk factors in Chinese
populations. One large follow-up study in China showed that
vascular disease was a major cause of death, and hypertension
was a leading modifiable risk factor of death among Chinese
adults aged 40 years and over.12 It suggested that the prevention and control of hypertension could reduce total mortality
by 11.7%. The Guangzhou Biobank Cohort Study has followed
>100,000 elderly people in Guangzhou, China since 2003.13
The findings at baseline showed that raised blood glucose, even
within the normal range, was associated with dyslipidemia and
hypertension.14
In this prospective study, we identified a number of factors
that are related to the development of hypertension. These
include age, history of hypertension in a parent, indices of
obesity, baseline blood pressure, blood glucose, lipids, and
indices of insulin resistance. Multivariate analysis narrows
this list to age, history of hypertension in a parent, baseline
SBP, BMI, and the triglycerides/HDL ratio. Our results echo
those of the Strong Heart Study in which abdominal obesity
and abnormal lipid profile are the major predictors of development of arterial hypertension after 8 years in a group of
American Indian subjects with initial blood pressure in the
optimal range.15 Raised blood pressure, triglycerides, and low
HDL are all related to obesity,16,17 and constitute the definition
of the metabolic syndrome.2,3 Thus, the metabolic syndrome
is not only a predictor of the development of type 2 diabetes
but is also a predictor of hypertension, even in this population
which is generally not obese by Western standards. In a large
number of people in the general population, hypertension and
diabetes share a common etiology. Our findings are consistent with other recent cross-sectional studies in Chinese that
point to the clustering of hypertension with obesity and other
cardiovascular risk factors.18,19 In our cohort, obesity precedes
the development of hypertension, underlining its causal relationship with the latter. Indeed, weight reduction in those who
are overweight and hypertensive is the most effective nonpharmacological means for reducing high blood pressure.20–22
A significant proportion of adults in Hong Kong6 and China23
has the metabolic syndrome and thus the epidemic of obesity
has become an important public health problem in China,24 as
in developed countries.
Visceral obesity is held to be a more important predictor of
cardiovascular and metabolic complications than obesity per
se. In our study, however, BMI appears to be a better predictor
of hypertension than waist circumference or waist-to-hip ratio.
This may be because plasma triglycerides and HDL correlate
articles
closely with abdominal obesity and therefore reduce the contribution of the latter in a multivariate model.
The positive predictive value of the metabolic syndrome for
the development of hypertension is modest, but the negative
predictive value is high. A person without the metabolic syndrome is unlikely to develop hypertension in the next few years.
The receiver operating characteristic analysis suggested that age
and blood pressure remain the best predictor of development of
hypertension. Nevertheless, the other components of the metabolic syndrome contribute incrementally to the development
of hypertension.
We found that high-normal blood pressure was associated
with a greatly increased risk of progression to hypertension.
This is consistent with observations from other prospective
studies.25,26 In these individuals, the presence or absence of
the metabolic syndrome no longer predicts the development of
hypertension. Baseline blood pressure, when not optimal, is the
predominant risk factor for the development of hypertension.
The metabolic syndrome becomes significant only when the
baseline blood pressure is low enough that its increase over time
is unlikely to reach the hypertensive range. The high lifetime
risk of hypertension in individuals with high-normal blood
pressure is a strong reason behind the advice to institute therapeutic lifestyle changes to prevent or retard the progression
to hypertension.27 Our findings suggest that bringing down
the blood pressure from the high-normal category to the optimal category may dramatically reduce the risk of developing
hypertension. Clinical trials are needed to confirm this. Blood
pressure lowering therapy is already indicated in people with
diabetes or renal disease who have a blood pressure above
130/80 mm Hg.27 Arguably, in individuals at high cardiovascular risk who have blood pressure in the pre-hypertension
range, lowering blood pressure may be beneficial, as the relationship between blood pressure and cardiovascular event risk
is continuous.28
In summary, the Hong Kong Cardiovascular Risk Factor
Prevalence Study has documented, over a period of 10 years,
cardiovascular risk factors in a cohort of subjects drawn from
the general population. We have shown in this prospective
study that the metabolic syndrome predicts the development
of hypertension in people with optimal blood pressure. When
the blood pressure is higher than optimal, the baseline blood
pressure is the predominant factor that predicts the development of hypertension. Cardiovascular risk factors are no longer
uncommon in China and are associated with urbanization and
a drastic decrease in physical activity.29 Obesity has been postulated as the leading modifiable cause of cardiovascular disease
in Asia.30 Therefore, appropriate weight control in the general
population is warranted. The modification of lifestyle factors at
the population level is a challenge, but is necessary to prevent
cardiovascular events and complications.
acknowledgments: The Hong Kong CRISPS2 was supported by a Hong Kong
Research Grants Council grant (no. 7229/01M) and the Sun Chieh yeh Heart
Foundation.The project titled"Impairedglucose toleranceasa precursor of
diabetes and hypertension in Hong Kong Chinese,"which followed a cohort
of 434 subjects with impaired glucose tolerance identified in the Hong Kong
AMERICAN JOURNAL OF HYPERTENSION | VOLUME 21 NUMBER 1 | jaNUaRy 2008
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Metabolic Syndrome Predicts Hypertension
Cardiovascular Risk Factor Prevalence Study 1995–1996, was supported by
a Health Care and Promotion Fund Committee Research Grant (no. 212907).
j.L.F. Lo, D.F.y. Chau, C.y. Law, E.T.M. yu were the research nurses involved in
the clinical study of the subjects. B.M.y. Cheung coordinated the project.
K.S.L. Lam, T.H. Lam, C.P. Lau, C.H. Cheng were involved in planning the
study and data interpretation. S. Tam supervised the analysis of specimens
and the biochemical data. N.M.S. Wat was a co-investigator in the follow-
up study. G.M. Leung designed the questionnaire for socioeconomic data.
E.D. janus was the principal investigator of the Hong Kong Cardiovascular
Risk Factor Prevalence Study 1995–1996 and advised on study design and
methodology. j. Woo directed the dietary sub-study in 1995–1996 and
analyzed the dietary data. y.B. Man managed the data of the project.
Disclosure: The authors declared no conflict of interest.
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jaNUaRy 2008 | VOLUME 21 NUMBER 1 | AMERICAN JOURNAL OF HYPERTENSION
--
Shigenoi Haruki
See COMMENTARY page 8
articles
Relationship Between the Metabolic Syndrome
and the Development of Hypertension in the
Hong Kong Cardiovascular Risk Factor Prevalence
Study-2 (CRISPS2)
Bernard M.Y. Cheung1, Nelson M.S. Wat1, Y. B. Man1, Sidney Tam2, C. H. Cheng1, Gabriel M. Leung3,
Jean Woo4, Edward D. Janus5, C. P. Lau1, T. H. Lam3 and Karen S.L. Lam1
BACkgROuNd
The metabolic syndrome is a predictor of diabetes and coronary
events. We hypothesized that it also predicts hypertension.
METhOdS
a total of 1,944 subjects (901 men and 1,043 women;
age 46 ± 12 years) from the Hong Kong Cardiovascular Risk Factor
Prevalence Survey were recruited in 1995–1996 and restudied in
2000–2004. The prevalence of hypertension and factors predicting
its development were determined.
RESulTS
In 2000–2004, hypertension was found in 23.2% of the men and
17.2% of the women. Of the 1,602 subjects who were normotensive
at baseline, 258 subjects developed hypertension after a median
interval of 6.4 years. according to the National Cholesterol Education
Program (NCEP) and International Diabetes Federation (IDF)
criteria, the hazard ratios associated with the metabolic syndrome
were 1.89 (95% confidence interval (CI): 1.41–2.54) and
1.72 (95% CI: 1.24–2.39), respectively. The positive and negative
Hypertension is an important cardiovascular risk factor and a
major health problem worldwide. In the United States, 29.3% of
the population has hypertension, but only 36.8% of people with
hypertension have good blood pressure control.1 There is a need
for improvement because controlling blood pressure markedly
reduces cardiovascular risk.
Although there are many drugs that effectively lower blood
pressure, it is not a cure. Curable forms of hypertension are of
low prevalence. In the vast majority of hypertensive patients,
1Department of Medicine, University of Hong Kong, Hong Kong; 2Clinical
Biochemistry Unit, Queen Mary Hospital, Hong Kong; 3Department of
Community Medicine, University of Hong Kong, Hong Kong; 4Department
of Medicine and Therapeutics, Chinese University of Hong Kong, Shatin,
Hong Kong; 5Department of General Medicine, University of Melbourne,
Western Hospital, Footscray, australia. Correspondence: Bernard M.y. Cheung
(b.cheung@bham.ac.uk)
Received 5 June 2007; first decision 5 July 2007; accepted 26 July 2007.
doi:10.1038/ajh.2007.19
© 2008 American Journal of Hypertension, Ltd.
predictive values of the metabolic syndrome for identifying
subjects who will develop hypertension in this population were
34.7 and 85.4% (NCEP criteria), and 33.1 and 85.5% (IDF criteria),
respectively. The development of hypertension was related to
the number of components of the metabolic syndrome
(other than raised blood pressure), present in men (P = 0.003)
and in women (P = 0.001). Using multivariate analysis, age,
baseline systolic blood pressure (SBP), body mass index (BMI),
and the triglycerides/high-density lipoprotein (HDL) ratio were found
to be significant predictors of the development of hypertension.
Compared with optimal blood pressure, the hazards of developing
hypertension associated with normal or high-normal blood
pressure were 2.31 (95% CI: 1.68–3.17) and 3.48 (95% CI: 2.52–4.81),
respectively.
CONCluSiONS
Blood pressure, when not optimal, is the predominant predictor
of hypertension. The metabolic syndrome contributes to the risk,
especially when blood pressure is optimal.
Am J Hypertens 2008; 21:17-22 © 2008 American Journal of Hypertension, Ltd.
the cause of hypertension is multifactorial. Therefore, there is a
need to identify modifiable factors that lead to the development
of hypertension.
The metabolic syndrome is a cluster of cardiovascular risk factors including central obesity, high blood pressure, raised blood
glucose and triglyceride levels, and low high-density lipoprotein
(HDL) cholesterol levels.2,3 In recent years, the syndrome has
been found to be useful in identifying people predisposed to
diabetes and coronary heart disease.4–6 It is not known whether
the syndrome also predicts the development of hypertension.
As high blood pressure is a component of this syndrome, we
set out to examine the association of the metabolic syndrome
and its components with the development of hypertension in a
Chinese population.
METhOdS
The Hong Kong Cardiovascular Risk Factor Prevalence Study is
a unique and comprehensive study of cardiovascular risk factors
AMERICAN JOURNAL OF HYPERTENSION | VOLUME 21 NUMBER 1 | 17-22 | jaNUaRy 2008
articles
among the general population in Hong Kong.6 In 1995–1996,
2,895 Chinese in Hong Kong (1,412 men and 1,483 women, aged
25–74) were selected randomly by their telephone numbers. The
study protocol was approved by the Ethics Committee of the
University of Hong Kong Faculty of Medicine. This method has
been validated locally, and it was shown that those who did not
attend were closely matched in all other respects (in terms of
demographics, health, socioeconomic status, and risk factors)
to those who were enrolled. The participation rate was 37.1%. In
2000–2004, the subjects were contacted for the follow-up study,
the Hong Kong Cardiovascular Risk Factor Prevalence Study-2
(CRISPS2). Patient recruitment was temporarily stopped in 2003
because of the Severe Acute Respiratory Syndrome.
The participants came in the morning having fasted overnight. They were asked about their age, occupation, smoking
and alcohol-drinking habits, and history of cardiovascular diseases, hypertension, and diabetes. All participants gave written
informed consent. Height was measured to the nearest 0.5 cm
and weight to the nearest 0.1 kg (DETECTO Instrument, MO).
Waist and hip circumferences were measured two times to
the nearest 0.5 cm and the arithmetic means were adopted for
subsequent analyses. Waist circumference was measured halfway between the xiphisternum and the umbilicus, whereas
hip circumference was measured at the level of the greater
trochanters.
Blood pressure was measured in the right arm manually using
a mercury sphygmomanometer. The subjects sat for at least
10 min and three measurements were taken at 5-min intervals.
The first measurement was to familiarize the subject with the
procedure; the mean of the second and third readings was used
for data analysis. The Korotkoff V sound was used to determine
diastolic pressure. A subject was classified hypertensive if the
systolic blood pressure (SBP) was =140 mm Hg, or the diastolic blood pressure (DBP) was =90 mm Hg, or if the subject had
previously been diagnosed with hypertension and was taking
antihypertensive medications. We used the European Society
of Hypertension and the European Society of Cardiology definition of optimal (SBP < 120 mm Hg and DBP < 80 mm Hg),
normal (SBP 120–129 mm Hg and/or DBP 80–84 mm Hg), and
high-normal (SBP 130–139mmHg and/or DBP 85–89mmHg)
blood pressure.7 Venous blood (20 ml) was taken for blood biochemistry and lipid profile. Lipids were measured on a Hitachi
912 analyzer as described previously.6 Low-density lipoprotein
(LDL) cholesterol was calculated using Friedewald's equation
if the total triglycerides did not exceed 4.5 mmol/l (400 mg/dl).
Otherwise, LDL was determined by a direct assay using selective micellary solubilization of LDL by a nonionic detergent in
an enzyme-coupled colorimetric assay automated on a Hitachi
912 analyzer. As plasma triglycerides and HDL cholesterol are
closely correlated, we calculated the triglyceride to HDL ratio for
multivariate analysis. The ratio is a surrogate marker for small
dense LDL, the more atherogenic form of LDL, and is therefore
a strong predictor of myocardial infarction.8,9 An oral glucose
tolerance test was performed with blood taken before and 2 h
after ingestion of 75 g anhydrous glucose dissolved in 200 ml
distilled water. Glucose was measured by the hexokinase method
Metabolic Syndrome Predicts Hypertension
on the Hitachi 912 analyzer. Insulin was measured by microparticle enzyme immunoassay (Abbott Laboratories, Tokyo, Japan).
The homeostasis model assessment estimate of insulin resistance
(HOMA-IR) was calculated using the formula: fasting plasma
glucose (mmol/l) × fasting insulin (mIU/l)/22.5.10 A subject was
considered to be diabetic if the fasting plasma glucose concentration was =7.0 mmol/l (126 mg/dl), or if the 2-h oral glucose
tolerance test plasma glucose concentration was =11.1 mmol/l
(200 mg/dl), or if the subject had been diagnosed to have diabetes previously and was receiving medications for diabetes.
The National Cholesterol Education Program (NCEP) criteria
for the metabolic syndrome were met if at least three of the following were satisfied (i) waist circumference =90 cm (35 inches)
in Asian men or =80 cm (31 inches) in Asian women; (ii) triglyceride concentration =150 mg/dl (1.7 mmol/l); (iii) HDL
<40 mg/dl (1.03 mmol/l) in men or <50 mg/dl (1.29 mmol/l)
in women; (iv) blood pressure =130/85 mm Hg; (v) fasting glucose =100 mg/dl (5.6 mmol/l).2 Receiving specific treatment was
counted as fulfilling the criterion. The International Diabetes
Federation (IDF) criteria for the metabolic syndrome resemble
the NCEP criteria except that central obesity, defined using sex
and ethnic specific cut points, must be present.3
Data analysis. Baseline characteristics among different groups
were compared using Student's unpaired t-test or Chi-square
test as appropriate. The prevalence of hypertension was
directly standardized for age based on the Hong Kong Census
in 2001.11 In the 1,602 subjects who were normotensive initially, predictors of the development of hypertension were
determined using Cox proportional hazards regression. Age
and sex were adjusted for in univariate models. The other variables examined included smoking, body mass index (BMI),
waist circumference, waist-to-hip ratio, SBP and DBP, fasting
and 2-h plasma glucose, triglycerides, HDL, triglycerides/HDL
ratio, HOMA-IR, fasting insulin, metabolic syndrome (NCEP
or IDF criteria), and the number of metabolic syndrome components (other than raised blood pressure) present in an individual. Variables were entered stepwise in multivariate analysis. P < 0.1 was required for entering a variable into the model
and P < 0.05 to remain in the model. Analyses were performed
using SPSS 11.0 for Windows (SPSS, Chicago, IL); a P value <
0.05 (two-tailed) was considered statistically significant.
RESulTS
Attempts were made to contact all the 2,895 subjects who participated in CRISPS1. A total of 1,944 subjects (901 men, 1,043
women; age 52 ± 12 years; response rate = 67.2%) participated
in this study (CRISPS2). The 951 nonparticipants included 120
who withdrew consent, 121 who chose not to reply or show up,
6 pregnant women who were excluded, 78 who had emigrated,
89 who were confirmed dead according to the Hong Kong Death
Registry, and 537 who could not be traced.
Participants and nonparticipants did not differ significantly in
age, BMI, LDL, drinking habit and the frequencies of hypertension, stroke, and ischemic heart disease. However, those subjects who reenrolled were more likely to be female (54 vs. 47%
jaNUaRy 2008 | VOLUME 21 NUMBER 1 | AMERICAN JOURNAL OF HYPERTENSION
Metabolic Syndrome Predicts Hypertension
articles
in nonparticipants), married (85 vs. 77%) and nonsmokers (77
vs. 70%) (P < 0.001 for all). They were also slightly less likely
to be diabetic (9 vs. 12%, P = 0.04), which might explain the
lower plasma triglyceride (P = 0.002), and higher plasma HDL
(P = 0.004) levels.
The age-adjusted overall prevalence of hypertension in 1995–
1996 and 2000–2004 was 18.1% and 23.2% in men, and 16.9 and
17.2% in women, respectively. Out of 1,602 subjects who were
not hypertensive at baseline, 258 subjects were found to be hypertensive at follow-up. Their characteristics are shown in Table 1.
Compared with those who remained normotensive, these hypertensive subjects were older, more likely to be male and smokers, had higher BMI, waist circumference, waist-to-hip ratio,
fasting plasma glucose, plasma glucose at 2 h in an oral glucose
tolerance test, plasma triglycerides, HOMA-IR, fasting plasma
insulin, and lower levels of HDL. Table 2 shows the results of
Cox regression analysis of the predictors of the development of
Table 1 | Baseline characteristics of participants who were
normotensive at baseline in relation to blood pressure status
at follow-up
Normotensive Hypertensive
at follow-up at follow-up Pvalue
Number (%) 1,344 (84) 258 (16) —
age (y) 42.3 ± 10.8 50.2 ± 10.8 <0.001
Males (%) 44 55 0.001
Systolic blood 111 ± 12 123 ± 11 <0.001
pressure (mm Hg)
Diastolic blood 70 ± 8 77 ± 8 <0.001
pressure (mm Hg)
Body mass index 23.5 ± 3.3 25.0 ± 3.3 <0.001
(kg/m2)
Waist 76.7 ± 9.3 81.5 ± 9.2 <0.001
circumference (cm)
hypertension. Five subjects could not be included in this analysis
because of missing data. When single factors were considered,
age, BMI, waist circumference, waist-to-hip ratio, baseline SBP
or DBP, fasting plasma glucose, plasma glucose at 2 h in an oral
glucose tolerance test, plasma triglycerides, HDL, triglycerides/
HDL ratio, HOMA-IR, and fasting plasma insulin were all significantly related to the development of hypertension. The hazard
ratio associated with the metabolic syndrome by the NCEP and
IDF criteria, excluding those who were already hypertensive at
baseline, were 1.89 (95% confidence interval (CI): 1.41–2.54) and
1.72 (95% CI: 1.24–2.39), respectively. The development of hypertension was related to the number of components of the metabolic syndrome other than raised blood pressure, in men (P =
0.003) and in women (P = 0.001) (Figure 1). Using multivariate
analysis, age, baseline SBP, BMI, and the triglycerides/HDL ratio
were found to be significant predictors. If the triglycerides/HDL
ratio is not entered into the model, plasma triglycerides become
a significant predictor (hazard ratio 1.20 (95% CI: 1.06–1.36)).
A BMI of =25 was associated with a hazard ratio of 1.41 (95%
CI: 1.09–1.83), after adjusting for age, sex, presence of diabetes,
smoking status and baseline SBP.
Among 1,602 subjects who were not hypertensive at baseline, the blood pressure was optimal in 974 subjects, normal in
251 subjects and high-normal in 119 subjects. The proportion of
a
1.0
0.8
4
3
2
1
0
No. of metabolic
syndrome components
other than high
blood pressure
Cumulative survival
0.6
0.4
0.2
Waist-to-hip ratio 0.8 ± 0.1 0.9 ± 0.1 <0.001
Fasting glucose 92.8 ± 15.9 101.3 ± 32.1 <0.001
(mg/dl) 0.0
0
OGTT 2-h glucose 113.2 ± 40.4 128.5 ± 65.6 0.001
2,000 4,000
Follow-up duration (days)
2
1
0
No. of metabolic
syndrome components
other than high
blood pressure
(mg/dl)
Triglycerides 94.7 ± 56.3 124.8 ± 85.0 <0.001 b
(mg/dl) 1.0
HDL (mg/dl) 49.8 ± 12.4 46.7 ± 12.7 <0.001
0.8
HOMa-IR 1.0 (0.7–1.6) 1.3 (0.8–1.9) <0.001
Fasting insulin 4.4 (3.0–6.7) 5.4 (3.7–8.0) <0.001
(mIU/l)
Ever smoking (%) 22 28 0.04
alcohol drinkinga 11 16 0.06
(%)
Cumulative survival
0.6
0.4
0.2
Physical activityb 34 34 1.00
3
(%)
4
0.0
Data are shown as means ± SD, medians (interquartile ranges), or percentages.
Student's unpaired t-test, Mann–Whitney test and chi-square test were used as 0 2,000 4,000
appropriate. Follow-up duration (days)
aAt least once a week. bTaking exercise at least once a week in the past month. To
convert mg/dl to mmol/l, multiply by 0.056 for glucose, 0.011 for triglycerides and
0.026 for HDL. Figure 1 | Survival without hypertension in subjects with increasing number
of components of the metabolic syndrome at baseline. (a) Men; (b) women.
AMERICAN JOURNAL OF HYPERTENSION | VOLUME 21 NUMBER 1 | jaNUaRy 2008
articles
Metabolic Syndrome Predicts Hypertension
Table 2 | Baseline predictors of the development of hypertension over a median of 6.4 years of follow-up
Multivariate model Multivariate model
Multivariate modelb for menb for womenb,c
Predictor Univariate modela (Cases = 256, N= 1,593) (Cases = 140, N= 728) (Cases = 116, N= 865)
Hazard ratio Hazard ratio Hazard ratio Hazard ratio
(95% CI) Pvalue (95% CI) Pvalue (95% CI) Pvalue (95% CI) Pvalue
age, per year 1.07 (1.06–1.08) <0.001 1.05 (1.04–1.06) <0.001 1.05 (1.03–1.07) <0.001 1.05 (1.03–1.07) <0.001
Gender (0 = male, 1 = female) 0.88 (0.69–1.13) 0.31 NI – – – –
Smoking (0 = never, 1 = ever) 0.82 (0.60–1.12) 0.2 NI – NI – NI –
Body mass index, per kg/m2 1.11 (1.07–1.15) <0.001 1.06 (1.02–1.10) 0.002 1.09 (1.04–1.15) 0.001 NI –
Waist circumference, per cm 1.03 (1.02–1.05) <0.001 NI – NI – NI –
Waist-to-hip ratio 1.04 (1.02–1.05) <0.001 NI – NI – NI –
(×100, per 1 unit)
Systolic blood pressure, 1.06 (1.05–1.08) <0.001 1.06 (1.04–1.07) <0.001 1.06 (1.04–1.08) <0.001 1.06 (1.04–1.08) <0.001
per mm Hg
Diastolic blood pressure, 1.06 (1.05–1.08) <0.001 NI – NI – NI –
per mm Hg
Fasting glucose, per 10 mg/dl 1.04 (1.01–1.08) 0.02 NI – NI – NI –
OGTT 2-h glucose, per 10 mg/dl 1.03 (1.02–1.05) <0.001 NI – NI – NI –
Triglycerides, per 10 mg/dl 1.03 (1.02–1.04) <0.001 NI – 1.02 (1.00–1.04) 0.01 NI –
HDL, per 10 mg/dl 0.83 (0.74–0.91) <0.001 NI – NI – 0.83 (0.71–0.97) 0.02
Triglycerides/HDL ratio, 1.23 (1.13–1.34) <0.001 1.14 (1.04–1.25) 0.002 NI – NI –
per 1 unit
HOMa-IR, per 1 unit 1.07 (1.03–1.11) 0.001 NI – NI – NI –
Fasting insulin, per mIU/l 1.02 (1.00–1.03) 0.009 NI – NI – NI –
Metabolic syndrome 1.89 (1.41–2.54) <0.001 NI – NI – NI –
(NCEP criteria)
Metabolic syndrome 1.72 (1.24–2.39) 0.001 NI – NI – NI –
(IDF criteria)
Number of metabolic syndrome 1.24 (1.09–1.41) <0.001 NI – NI – NI –
components other than raised
blood pressure
HOMA-IR, homeostasis model assessment estimate of insulin resistance; IDF, International Diabetes Federation; NCEP, National Cholesterol Education Program; NI, Not included in
the model; OGTT, oral glucose tolerance test.
aPredictors were age-and sex-adjusted, except for age, which was sex-adjusted, and sex, which was age-adjusted. bStepwise (forward) Cox proportional hazards model was used.
P < 0.1 was necessary for a variable entering into the model and P < 0.05 for staying in the model. cAdditionally adjusted for menopausal status and use of hormone replacement
therapy. Subjects with missing data were excluded in the multivariate model.
subjects who developed hypertension at follow-up was 7.4% in the
optimal group, 25.5% in the normal group and 44.1% in the high-
normal group (P < 0.001). The rate of progression to hypertension
in these three groups was 1.1, 3.9, and 7.1% per year, respectively.
Compared with optimal blood pressure, the hazards of developing
hypertension associated with normal or high-normal blood pressure were 2.31 (95% CI: 1.68–3.17) and 3.48 (95% CI: 2.52–4.81)
fold, respectively. In subjects with optimal blood pressure at baseline, the NCEP and IDF metabolic syndrome were associated with
sex- and age-adjusted hazard ratios of 2.09 (95% CI: 1.10–3.96)
and 2.24 (95% CI: 1.15–4.36), respectively, for the development
of hypertension. In subjects with normal blood pressure, the corresponding hazard ratios were 1.34 (95% CI: 0.74–2.42) and 1.41
(95% CI: 0.74–2.67). In subjects with high-normal blood pressure,
the corresponding hazard ratios were 1.10 (95% CI: 0.72–1.69)
and 0.98 (95% CI: 0.61–1.60).
The sensitivity and specificity of the metabolic syndrome for
identifying subjects who will develop hypertension in this population were 16.3 and 94.1% (NCEP criteria), and 17.1 and 93.4%
(IDF criteria), respectively. The positive and negative predictive
values of the metabolic syndrome for identifying subjects who
will develop hypertension were 34.7 and 85.4% (NCEP criteria),
and 33.1 and 85.5% (IDF criteria), respectively.
The components of the metabolic syndrome are defined by
cutoff points. Receiver operating characteristic curves were
drawn for these components as continuous variables. The areas
under the receiver operating characteristic curves were 0.62
(waist), 0.74 (SBP), 0.67 (DBP), 0.65 (glucose), 0.60 (triglycerides), and 0.55 (HDL) in men, and 0.66 (waist), 0.81 (SBP),
0.75 (DBP), 0.57 (glucose), 0.64 (triglycerides), and 0.57 (HDL)
in women. The area under the receiver operating characteristic
curve for age was 0.69 in men and 0.73 in women.
jaNUaRy 2008 | VOLUME 21 NUMBER 1 | AMERICAN JOURNAL OF HYPERTENSION
Metabolic Syndrome Predicts Hypertension
diSCuSSiON
The Hong Kong Cardiovascular Risk Factor Prevalence Study
is a large and unique cohort of urbanized Hong Kong Chinese
subjects, with more than 12,000 person-years of follow up.6
Analysis of the baseline data has shown that hypertension and
diabetes are common in Hong Kong, and there is a clustering
of cardiovascular risk factors. It has particularly highlighted
the importance of obesity and its close relationship with
insulin resistance diabetes, dyslipidemia, and hypertension.
Although cross-sectional studies are useful, there is a need
for prospective data on cardiovascular risk factors in Chinese
populations. One large follow-up study in China showed that
vascular disease was a major cause of death, and hypertension
was a leading modifiable risk factor of death among Chinese
adults aged 40 years and over.12 It suggested that the prevention and control of hypertension could reduce total mortality
by 11.7%. The Guangzhou Biobank Cohort Study has followed
>100,000 elderly people in Guangzhou, China since 2003.13
The findings at baseline showed that raised blood glucose, even
within the normal range, was associated with dyslipidemia and
hypertension.14
In this prospective study, we identified a number of factors
that are related to the development of hypertension. These
include age, history of hypertension in a parent, indices of
obesity, baseline blood pressure, blood glucose, lipids, and
indices of insulin resistance. Multivariate analysis narrows
this list to age, history of hypertension in a parent, baseline
SBP, BMI, and the triglycerides/HDL ratio. Our results echo
those of the Strong Heart Study in which abdominal obesity
and abnormal lipid profile are the major predictors of development of arterial hypertension after 8 years in a group of
American Indian subjects with initial blood pressure in the
optimal range.15 Raised blood pressure, triglycerides, and low
HDL are all related to obesity,16,17 and constitute the definition
of the metabolic syndrome.2,3 Thus, the metabolic syndrome
is not only a predictor of the development of type 2 diabetes
but is also a predictor of hypertension, even in this population
which is generally not obese by Western standards. In a large
number of people in the general population, hypertension and
diabetes share a common etiology. Our findings are consistent with other recent cross-sectional studies in Chinese that
point to the clustering of hypertension with obesity and other
cardiovascular risk factors.18,19 In our cohort, obesity precedes
the development of hypertension, underlining its causal relationship with the latter. Indeed, weight reduction in those who
are overweight and hypertensive is the most effective nonpharmacological means for reducing high blood pressure.20–22
A significant proportion of adults in Hong Kong6 and China23
has the metabolic syndrome and thus the epidemic of obesity
has become an important public health problem in China,24 as
in developed countries.
Visceral obesity is held to be a more important predictor of
cardiovascular and metabolic complications than obesity per
se. In our study, however, BMI appears to be a better predictor
of hypertension than waist circumference or waist-to-hip ratio.
This may be because plasma triglycerides and HDL correlate
articles
closely with abdominal obesity and therefore reduce the contribution of the latter in a multivariate model.
The positive predictive value of the metabolic syndrome for
the development of hypertension is modest, but the negative
predictive value is high. A person without the metabolic syndrome is unlikely to develop hypertension in the next few years.
The receiver operating characteristic analysis suggested that age
and blood pressure remain the best predictor of development of
hypertension. Nevertheless, the other components of the metabolic syndrome contribute incrementally to the development
of hypertension.
We found that high-normal blood pressure was associated
with a greatly increased risk of progression to hypertension.
This is consistent with observations from other prospective
studies.25,26 In these individuals, the presence or absence of
the metabolic syndrome no longer predicts the development of
hypertension. Baseline blood pressure, when not optimal, is the
predominant risk factor for the development of hypertension.
The metabolic syndrome becomes significant only when the
baseline blood pressure is low enough that its increase over time
is unlikely to reach the hypertensive range. The high lifetime
risk of hypertension in individuals with high-normal blood
pressure is a strong reason behind the advice to institute therapeutic lifestyle changes to prevent or retard the progression
to hypertension.27 Our findings suggest that bringing down
the blood pressure from the high-normal category to the optimal category may dramatically reduce the risk of developing
hypertension. Clinical trials are needed to confirm this. Blood
pressure lowering therapy is already indicated in people with
diabetes or renal disease who have a blood pressure above
130/80 mm Hg.27 Arguably, in individuals at high cardiovascular risk who have blood pressure in the pre-hypertension
range, lowering blood pressure may be beneficial, as the relationship between blood pressure and cardiovascular event risk
is continuous.28
In summary, the Hong Kong Cardiovascular Risk Factor
Prevalence Study has documented, over a period of 10 years,
cardiovascular risk factors in a cohort of subjects drawn from
the general population. We have shown in this prospective
study that the metabolic syndrome predicts the development
of hypertension in people with optimal blood pressure. When
the blood pressure is higher than optimal, the baseline blood
pressure is the predominant factor that predicts the development of hypertension. Cardiovascular risk factors are no longer
uncommon in China and are associated with urbanization and
a drastic decrease in physical activity.29 Obesity has been postulated as the leading modifiable cause of cardiovascular disease
in Asia.30 Therefore, appropriate weight control in the general
population is warranted. The modification of lifestyle factors at
the population level is a challenge, but is necessary to prevent
cardiovascular events and complications.
acknowledgments: The Hong Kong CRISPS2 was supported by a Hong Kong
Research Grants Council grant (no. 7229/01M) and the Sun Chieh yeh Heart
Foundation.The project titled"Impairedglucose toleranceasa precursor of
diabetes and hypertension in Hong Kong Chinese,"which followed a cohort
of 434 subjects with impaired glucose tolerance identified in the Hong Kong
AMERICAN JOURNAL OF HYPERTENSION | VOLUME 21 NUMBER 1 | jaNUaRy 2008
articles
Metabolic Syndrome Predicts Hypertension
Cardiovascular Risk Factor Prevalence Study 1995–1996, was supported by
a Health Care and Promotion Fund Committee Research Grant (no. 212907).
j.L.F. Lo, D.F.y. Chau, C.y. Law, E.T.M. yu were the research nurses involved in
the clinical study of the subjects. B.M.y. Cheung coordinated the project.
K.S.L. Lam, T.H. Lam, C.P. Lau, C.H. Cheng were involved in planning the
study and data interpretation. S. Tam supervised the analysis of specimens
and the biochemical data. N.M.S. Wat was a co-investigator in the follow-
up study. G.M. Leung designed the questionnaire for socioeconomic data.
E.D. janus was the principal investigator of the Hong Kong Cardiovascular
Risk Factor Prevalence Study 1995–1996 and advised on study design and
methodology. j. Woo directed the dietary sub-study in 1995–1996 and
analyzed the dietary data. y.B. Man managed the data of the project.
Disclosure: The authors declared no conflict of interest.
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jaNUaRy 2008 | VOLUME 21 NUMBER 1 | AMERICAN JOURNAL OF HYPERTENSION
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Shigenoi Haruki
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