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The Metabolic Syndrome and Hypertension—R Kelishadi et al The Metabolic Syndrome in Hypertensive and Normotensive Subjects:
The Isfahan Healthy Heart Programme

R Kelishadi,1MD, R Derakhshan,1MD, B Sabet,1 MD, N Sarraf-Zadegan,1MD, M Kahbazi,1MD, GH Sadri,1PhD,AA Tavasoli,1 MD, S Heidari,1MD, A Khosravi,1MD, A Amani,1MD, HR Tolouei,1MD, A Bahonar,1MD, AA RezaeiAshtiani,1MS, A Moatarian,1MS Abstract
Introduction: There are numerous correlations between hypertension and the metabolic
syndrome, although this is not always the case. The objective of this study was to compare the
prevalence of the metabolic syndrome and its different phenotypes among hypertensive and
normotensive subjects. Materials and Methods: This cross-sectional study was performed on a
representative sample of adults living in 3 cities in Iran. Among the 12,514 subjects selected by
multi-stage random sampling, 1736 (13.9%) were hypertensive. The prevalence of the metabolic
syndrome [according to the Adult Treatment Panel (ATP) III criteria] was significantly higher
in hypertensive than normotensive subjects (51.6% versus 12.9%, respectively; OR, 7.15; 95%
CI, 6.4 to 7.9). The metabolic syndrome was more prevalent in normotensive and hypertensive
subjects living in urban areas than those living in rural areas (14.2% and 53.9% versus 9.5%
and 45.6%, respectively, P
<0.05). The mean age of hypertensive subjects, with or without the
metabolic syndrome, was not significantly different (55.7 ± 12 years versus 55.4 ± 15.5 years,
P
= 0.6). Hypertension with the metabolic syndrome was more prevalent in women than men
(72% versus 28% respectively, P
<0.000), and in subjects living in urban areas than those in rural
areas (75.1% versus 24.9%, respectively, P
= 0.002). Conclusion: The findings of this study
indicate the need for metabolic screening in all hypertensive patients, and emphasise the
importance of promoting primary and secondary prevention of high blood pressure and
associated modifiable risk factors in order to counter the upcoming epidemic of non-communi-
cable disease in developing countries.

Ann Acad Med Singapore 2005;34:243-9
Key words: Gender, Hypertension, Insulin resistance, Obesity, Prevalence
Introduction
hormones.9,10As Reaven et al11 concluded in their review, The metabolic syndrome (MS) is characterised by a the accumulated findings support the possibility that clustering of metabolic risk factors and an insulin-resistant metabolic changes play a part in the regulation of blood state.1 Its prevalence is high in Western, as well as Asian, pressure, although some contradictions remain. Some populations.2-4 There are numerous correlations between epidemiologic studies have shown a direct association the MS and hypertension, although this is not always the between blood pressure and insulin resistance,12-14 but the case.5 Resistance to insulin-mediated glucose disposal and findings of other studies do not confirm this.15-17 Some compensatory hyperinsulinaemia are common in patients studies have shown that hypertension is associated with the with hypertension. However, not all hypertensive patients MS in 50% of patients.11 Different studies have shown have insulin resistance. Several mechanisms appear to be ethnic differences in the relationship between hypertension involved in the link between hypertension and insulin and insulin resistance syndrome.18-22 Some studies have resistance, involving the sympathetic nervous system,6,7 found different associations between blood pressure and renal handling of sodium,8 and vasoconstrictor insulin in the same ethnic group living in different areas.13,14,23 1 Isfahan Cardiovascular Research Centre, Iran A WHO Collaborating Centre for Research and Training in Cardiovascular Diseases Control, Prevention, and Rehabilitation for Cardiac Patients in theEastern Mediterranean Region Address for Reprints: Associate Professor Roya Kelishadi, Isfahan Cardiovascular Research Center, Isfahan University of Medical Sciences, P.O. Box 81465-1148, Isfahan, Iran.
Email: Kelishadi@med.mui.ac.ir The Metabolic Syndrome and Hypertension—R Kelishadi et al This may suggest the role of environmental factors, was recorded as systolic BP and diastolic BP (SBP and especially dietary habits, in the relationship between hypertension and insulin resistance.11,24 Participants stood without their shoes for the measurement Recent studies revealed that the age-adjusted mortality of their height, which was rounded off to the nearest 0.5 cm.
due to cardiovascular disease (CVD) has increased by 20% Measurements were taken with a secured metal ruler, while to 45% in Iran,25,26 with a high prevalence of hypertension, weight was measured using calibrated scales, with one of its major risk factors.27 Considering the effect of participants wearing light clothing. Waist circumference genetic and lifestyle factors on the MS, the aim of the (WC) was measured to the nearest half-centimetre, at a present study – performed for the first time in urban and level midway between the lower rib margin and the iliac rural areas in Iran – was to compare the prevalence of this crest. Obesity was defined as body mass index >30 kg/m2 syndrome and its different phenotypes in hypertensive and for all subjects. The cutoff point for abnormal WC was normotensive subjects in a representative sample of the >102 cm for men and >88 cm for women.29 Iranian adult population living in 3 cities in central Iran.
Blood samples were drawn by venipuncture from the left Materials and Methods
antecubital vein after 12 hours of fasting. All blood sampleswere collected in the 3 cities and kept frozen at -20°C until This cross-sectional study was performed as the baseline assayed within 72 hours in the central laboratory of Isfahan survey of a community-based interventional programme in Cardiovascular Research Centre (a WHO collaborating 3 cities in Iran, called the Isfahan Healthy Heart Programme centre), which meets the criteria of the national reference (IHHP), the details of which have been previously laboratory (a WHO collaborating centre) and is under the external quality control of St Rafael University, Leuven, Quota sampling was conducted to stratify study population Belgium. The results from the laboratories were highly by their living area (urban versus rural) according to the regional population distribution as per the national Serum total cholesterol (TC), triglyceride (TG) and fasting population census in 1999. This baseline survey of 12,514 blood sugar (FBS) were measured by standard kits (Pars randomly selected adults aged >19 years old was conducted Azmoon Co., Iran) using an auto-analyser (Ependorf, with a 2-stage cluster sampling. Initially, census blocks Germany). Serum HDL cholesterol (HDL-C) was were randomly selected from each county and divided into determined after dextran sulphate-magnesium chloride clusters, each having approximately 1000 households.
precipitation of non-HDL cholesterol. Serum low-density Approximately 5 to 10 households within these clusters lipoprotein cholesterol (LDL-C) was calculated by the were randomly selected for enumeration. After enumeration, Friedwald equation in those subjects with TG <400 mg/dL, 1 eligible individual above 19 years of age was randomly selected per household if he or she was Iranian, mentallycompetent and, in the case of females, not pregnant. The The MS and its components were defined according to sample size was calculated and distributed into different the Third Report of the Expert Panel on Detection, age groups (19 to 24; 25 to 34; 35 to 44; 45 to 54; 55 to 64 Evaluation, and Treatment of High Blood Cholesterol in and >65 years) according to the distribution in the Adults (Adult Treatment Panel III or ATP III).31 Considering community. The total number was doubled due to the that the ATP III criteria for hypertension consist of high cluster method, and after taking the missing rate into simultaneous systolic and diastolic BP, the definition of the account, the total number was calculated to be 12,600 for Seventh Report of the Joint National Committee on the 3 counties. In this study, data from 12,514 cases that Prevention, Detection, Evaluation, and Treatment of High completed the study were reported. The urban/rural ratios Blood Pressure, which includes isolated high SBP or DBP were 90/10, 60/40 and 66/34 in Isfahan, Najaf-Abad and (SBP >140 or DBP >90 mm Hg),32 was also used for dividing subjects into normotensive and hypertensive groupsfor comparison of the prevalence of the MS components The selected persons were invited to the survey centres for a clinical examination and to answer a questionnaireabout their socio-demographic and health-related The data were collected and stored in a computer database.
characteristics. Informed consent was obtained from A trained team checked the recorded information for participants at the clinic. A trained team of physicians missing values and data entry errors. After tidying up the performed physical examinations and blood sampling, data, statistical analyses were performed using the SPSS using standardised and zero-calibrated instruments. Blood statistical package version 10 for Windows (SPSS Inc., pressure (BP) was measured in duplicate in a seated position; Chicago, USA) at P <0.05. The data were presented as the average of 2 measures of first and fifth Krotkoff phase frequencies, percentages and at 95% confidence intervals.
The Metabolic Syndrome and Hypertension—R Kelishadi et al The prevalence of different phenotypes of MS was compared Iran indicate that 51.6% of hypertensive subjects had the MS. This is significantly higher than the prevalence of12.9% in the normal population. This finding is consistent with other studies revealing that hypertension tends to In this cross-sectional study performed among 12,514 cluster with metabolic risk factors, and that about half of individuals (6391 women and 6123 men), 1736 subjects hypertensive patients are insulin-resistant.11,33,34 The (13.9%), of an average age of 55.6 ± 13.9 years, were coexistence of hypertension with other components of MS hypertensive. Table 1 shows the baseline characteristics of in the present study is in line with some population-based subjects studied. The prevalence of different phenotypes of MS in hypertensive and normotensive subjects to both However, in the factor analysis by Choi et al,37 blood genders is presented in Table 2. The prevalence of the MS pressure was not closely aggregated with other CVD risk was significantly higher in hypertensive than normotensive factors. In the study by Saad and colleagues,38 which subjects (51.6% versus 12.9%, respectively; OR, 7.15; examined the relationship between blood pressure and 95% CI, 6.4 to 7.9). Among hypertensive subjects, the insulin resistance among different ethnic groups, a phenotypes of the MS consisting of high TG and low HDL- relationship was found in Caucasians but not among Pima C, as well as abdominal obesity and low HDL-C, were more prevalent. The most common phenotype of the MS In the present study, the prevalence of MS in hypertensive without the component of hypertension was the coexistence subjects living in urban areas was higher than those living of high TG, low HDL-C and abdominal obesity (Table 1).
in rural areas. It is suggested that this finding emphasises In urban areas, MS was present in 53.9% of hypertensive the impact of lifestyle on the development of the MS.
and 14.2% of normotensive subjects (OR, 7; 95% CI, 6.2 The cumulative prevalence of 5 components of the MS in to 8). In rural areas these were 45.6% and 9.5%, respectively men and women was 2.2% and 2.9%, respectively, in the (OR, 7.9; 95% CI, 6.4 to 9.4). The prevalence of the study by Ford and colleagues39 in the US, and 1% and 4%, phenotypes of the MS with at least 1 and/or all its 5 respectively, in the study by Azizi et al40 in Iran. In the components, as well as the phenotypes without high BP present study, the prevalence rates among hypertensive (based on the JNC 7 criteria), is shown in Table 3, according and normotensive men and women were 1.7%, 4.6%, 0.1% and 0%, respectively, with hypertensive women showing As shown in Table 4, the mean age of hypertensive the highest prevalence. Overall, hypertension with the MS subjects with or without the MS was not significantly was more prevalent among women than in men, which different; but hypertension with MS was more prevalent could be attributed in part to their sedentary lifestyle. In among women than men, and in subjects living in urban addition, this finding is in line with existing evidence of gender differences in the relationship between bloodpressure and insulin resistance.41-43 Discussion
In the study of a Chinese population by Chen et al,41 The findings of the present study performed among hypertension was linked to the MS in women but not in 12,514 individuals aged >19 years old living in 3 cities in men. They suggested that the role of sympathetic activity in Table 1. Baseline Characteristics in Hypertensive and Normotensive Individuals 116.3 ± 17.9 114.9 ± 20.3 115.6 ± 19.1 194.6 ± 57.7 202.5 ± 54.8 198.7 ± 56.4 216.5 ± 128.1 173.8 ± 115.7 151.4 ± 93.1 162.6 ± 105.5 DBP: diastolic blood pressure; FBS: fasting blood sugar; HDL-C: high-density lipoprotein cholesterol; LDL-C: low-density lipoprotein cholesterol;SBP: systolic blood pressure; TC: total cholesterol; TG: triglyceride; WC: waist circumference The Metabolic Syndrome and Hypertension—R Kelishadi et al Table 2. Comparison of Different Phenotypes of the Metabolic Syndrome in Hypertensive and Normotensive Men and Women AB: abdominal obesity; BP: blood pressure; CI: confidence interval; FBS: fasting blood sugar; HDL-C: high-density lipoprotein; The Metabolic Syndrome and Hypertension—R Kelishadi et al Table 3. Comparison of the Number of Metabolic Syndrome Components in Hypertensive and Normotensive Subjects* According to * Hypertension is defined according to the JNC7 criteria.32 Comparison of Characteristics Between Hypertensive in hypertensive subjects, the MS amplifies CVD risk Individuals With or Without Metabolic Syndrome associated with high blood pressure, independent of theeffect of several traditional cardiovascular risk factors.
According to the review by Christ and colleagues,47 immediate treatment of the MS is mandatory, and antihypertensive treatment is more effective than tight glucose control in reducing cardiovascular events. The lifetime process of treatment for hypertension32,48,49 and the need for aggressive lifestyle intervention for the metabolic syndrome50 highlight the need to identify and treat affected individuals with a multitargeted approach.
Conclusion
The high prevalence of the MS among hypertensive individuals indicates the need for metabolic screening in allhypertensive patients at the first diagnosis. In addition, the pathogenesis of hypertension may be different between considering that lifestyle modification is suggested as the men and women, and that hypertension in women may be first-line therapy of MS,50,51 the findings of the present more dependent on insulin resistance than in men. Contrary study emphasise the need to implement community-based to their findings, an experimental study found that insulin programmes for lifestyle changes with regard to the resistance was associated with hypertension in male rats modifiable predisposing factors of high blood pressure and the importance of controlling high blood pressure and In the study by Vazquez Vigoa et al,45 62% of hypertensive subjects were found to have MS, with a significantassociation with vascular damage. However, most available Acknowledgements
studies do not answer the question regarding the clinical The Isfahan Healthy Heart Programme (IHHP) is significance of the MS in hypertension. The recent supported by a grant (No. 31309304) from the Iranian prospective study by Schillaci et al46 provides evidence that Budget and Programming Organization, the Deputy of the MS may be useful as an integrating index on the overall Health of the Ministry of Health and Medical Education in burden imposed by metabolic factors on the cardiovascular the Islamic Republic of Iran, Isfahan Cardiovascular system in hypertensive patients. Their findings suggest that Research Centre and Isfahan Provincial Health Center, the MS represents a strong, independent risk factor for both affiliated to the Isfahan University of Medical Sciences.
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