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Correspondence: Yonghong Zhang, Department of Epidemiology, School of Public Health, Medical College of Soochow University, 199 Ren’ai Road, Industrial Park District, Suzhou 215123, China. Tel: 086-512-6588-2625. Fax: 086-512-65884830. Email: [email protected] (Received 6 August 2012; accepted 23 October 2012) ORIGINAL ARTICLE Association of hypertension with coexistence of abnormal metabolism and inflammation and endothelial dysfunction MINGZHI ZHANG 1 , GUIYAN WANG 1,2 , AILI WANG 1 , WEIJUN TONG 1 & YONGHONG ZHANG 1 1 Department of Epidemiology, School of Public Health, Medical College of Soochow University, Suzhou, China, 2 Department of Prevention and Care, Xiamen Municipal Maternity and Child Care Hospital, Xiamen, China Abstract To explore association of hypertension with coexistence of inflammation and endothelial dysfunction and abnormal metab- olism, a community-based study was conducted among Mongolian people in China. Demographic characteristics and lifestyle risk factors were investigated, blood pressure, body weight and waist circumference were measured, fasting blood samples were obtained to measure blood lipids, fasting plasma glucose and the biomarkers of inflammation and endothe- lial dysfunction, C-reactive protein (CRP), soluble intercellular cell adhesion molecule-1 (sICAM-1), soluble E-selectin (sE-selectin) and angiotensin II. Rates of abnormal metabolism, elevated CRP, elevated sICAM-1, elevated sE-selectin and elevated angiotensin II as well as coexistence of abnormal metabolism with the elevated biomarkers were all higher in hypertensives than these in normotensives (all p 0.01). Compared with subjects with normal metabolism and without any elevated biomarker, multivariate adjusted odds ratio (95% confidence interval) of hypertension associated with abnor- mal metabolism, elevated CRP, elevated sICAM-1, elevated sE-selectin, elevated angiotensin II, coexistences of abnormal metabolism with elevated CRP, elevated sICAM-1,elevated sE-selectin and elevated angiotensin II were 2.209 (1.594– 3.062), 2.820 (1.992–3.992), 2.370 (1.665–3.374), 1.893 (1.331–2.691), 2.545 (1.793–3.612), 2.990 (2.102–4.252), 2.551 (1.775–3.667), 2.223 (1.544–3.220), 3.135 (2.185–4.519), respectively. In conclusion, this study indicated that inflamma- tion and endothelial dysfunction was associated with hypertension and abnormal metabolism, and individuals with co- existence of abnormal metabolism with inflammation and endothelial dysfunction had higher risk of prevalent hypertension among Mongolian population. This study suggests that further study on treatment for hypertension patients with coexist- ence of abnormal metabolism with inflammation and endothelial dysfunction should be conducted in the near future. Key Words: Abnormal metabolism, endothelial dysfunction, hypertension, inflammation Introduction In recent decades, some studies showed that chronic inflammation and endothelial dysfunction were asso- ciated with hypertension (1–4), and other studies demonstrated that chronic metabolic abnormality, including abdominal obesity (5–7), lipid abnormality (6,8–10) and diabetes (11), was also associated with hypertension. Some studies have further shown that inflammation and endothelial dysfunction are not only associated with atherosclerosis, cardiovascular disease and hypertension, but also with metabolic syndrome (MetS), a condition of multiple metabolic abnormality including obesity or abdominal obesity, high blood pressure (BP), hyperlipidemia, abnormal glucose metabolism (12), increasing the risk of type 2 diabetes and cardiovascular disease (13). For example, the biomarkers of inflammation and endothelial dysfunction such as C-reactive protein (CRP), interleukin-6, soluble intercellular cell adhe- sion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 and soluble E-selectin (sE- selectin) have been reported to be associated with chronic metabolic abnormality (14–16). Therefore, it is possible that there is a co-effect between chronic inflammation and endothelial dysfunction and chronic metabolic abnormality on hypertension. However, few studies focused on co-effect of inflam- mation and endothelial dysfunction with chronic Blood Pressure, 2012; Early Online: 1–7 ISSN 0803-7051 print/ISSN 1651-1999 online © 2012 Scandinavian Foundation for Cardiovascular Research DOI: 10.3109/08037051.2012.745226 Blood Press Downloaded from informahealthcare.com by University of Calgary on 03/13/13 For personal use only.

Association of hypertension with coexistence of abnormal metabolism and inflammation and endothelial dysfunction

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Correspondence: Yonghong Zhang, Department of Epidemiology, School of Public Health, Medical College of Soochow University, 199 Ren ’ ai Road, Industrial Park District, Suzhou 215123, China. Tel: 086-512-6588-2625. Fax: 086-512-65884830. Email: [email protected]

(Received 6 August 2012 ; accepted 23 October 2012 )

ORIGINAL ARTICLE

Association of hypertension with coexistence of abnormal metabolism and infl ammation and endothelial dysfunction

MINGZHI ZHANG 1 , GUIYAN WANG 1,2 , AILI WANG 1 , WEIJUN TONG 1 & YONGHONG ZHANG 1

1 Department of Epidemiology, School of Public Health, Medical College of Soochow University, Suzhou, China, 2 Department of Prevention and Care, Xiamen Municipal Maternity and Child Care Hospital, Xiamen, China

Abstract To explore association of hypertension with coexistence of infl ammation and endothelial dysfunction and abnormal metab-olism, a community-based study was conducted among Mongolian people in China. Demographic characteristics and lifestyle risk factors were investigated, blood pressure, body weight and waist circumference were measured, fasting blood samples were obtained to measure blood lipids, fasting plasma glucose and the biomarkers of infl ammation and endothe-lial dysfunction, C-reactive protein (CRP), soluble intercellular cell adhesion molecule-1 (sICAM-1), soluble E-selectin (sE-selectin) and angiotensin II. Rates of abnormal metabolism, elevated CRP, elevated sICAM-1, elevated sE-selectin and elevated angiotensin II as well as coexistence of abnormal metabolism with the elevated biomarkers were all higher in hypertensives than these in normotensives (all p � 0.01). Compared with subjects with normal metabolism and without any elevated biomarker, multivariate adjusted odds ratio (95% confi dence interval) of hypertension associated with abnor-mal metabolism, elevated CRP, elevated sICAM-1, elevated sE-selectin, elevated angiotensin II, coexistences of abnormal metabolism with elevated CRP, elevated sICAM-1,elevated sE-selectin and elevated angiotensin II were 2.209 (1.594 – 3.062), 2.820 (1.992 – 3.992), 2.370 (1.665 – 3.374), 1.893 (1.331 – 2.691), 2.545 (1.793 – 3.612), 2.990 (2.102 – 4.252), 2.551 (1.775 – 3.667), 2.223 (1.544 – 3.220), 3.135 (2.185 – 4.519), respectively. In conclusion, this study indicated that infl amma-tion and endothelial dysfunction was associated with hypertension and abnormal metabolism, and individuals with co-existence of abnormal metabolism with infl ammation and endothelial dysfunction had higher risk of prevalent hypertension among Mongolian population. This study suggests that further study on treatment for hypertension patients with coexist-ence of abnormal metabolism with infl ammation and endothelial dysfunction should be conducted in the near future.

Key Words: Abnormal metabolism , endothelial dysfunction , hypertension , infl ammation

Introduction

In recent decades, some studies showed that chronic infl ammation and endothelial dysfunction were asso-ciated with hypertension (1 – 4), and other studies demonstrated that chronic metabolic abnormality, including abdominal obesity (5 – 7), lipid abnormality (6,8 – 10) and diabetes (11), was also associated with hypertension. Some studies have further shown that infl ammation and endothelial dysfunction are not only associated with atherosclerosis, cardiovascular disease and hypertension, but also with metabolic syndrome (MetS), a condition of multiple metabolic abnormality including obesity or abdominal obesity, high blood pressure (BP), hyperlipidemia, abnormal

glucose metabolism (12), increasing the risk of type 2 diabetes and cardiovascular disease (13). For example, the biomarkers of infl ammation and endothelial dysfunction such as C-reactive protein (CRP), interleukin-6, soluble intercellular cell adhe-sion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 and soluble E-selectin (sE-selectin) have been reported to be associated with chronic metabolic abnormality (14 – 16). Therefore, it is possible that there is a co-effect between chronic infl ammation and endothelial dysfunction and chronic metabolic abnormality on hypertension. However, few studies focused on co-effect of infl am-mation and endothelial dysfunction with chronic

Blood Pressure, 2012; Early Online: 1–7

ISSN 0803-7051 print/ISSN 1651-1999 online © 2012 Scandinavian Foundation for Cardiovascular ResearchDOI: 10.3109/08037051.2012.745226

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2 M. Zhang et al.

metabolic abnormality on hypertension in an Asian population, especially in Mongolian population, a minority living in north China who maintained a tra-ditional lifestyle. In the present study, we examined the effects between coexistence of some components of abnormal metabolism with elevated infl ammation and endothelial dysfunction biomarkers including CRP, sICAM-1, sE-selectin and angiotensin II on hypertension in a Mongolian population from Inner Mongolia, China.

Methods

Study subjects

A community-based, cross-sectional study on hyper-tension was conducted between 2002 and 2003 in Inner Mongolia, China. The methods for the study participant selection and data collection are pre-sented in detail elsewhere (17). Briefl y, all local resi-dents aged 20 years and older were recruited from 32 villages in two adjacent townships located in Kezuohou Banner (county) and Naiman Banner. Most participants were Mongolian who maintained a traditional diet that was high in fat and salt. Among the eligible 3475 residents, 2589 individuals signed informed consent forms and participated in the study. This study was approved by the Soochow University ethics committee.

Data collection and examination

A standard questionnaire was administered by trained staff to obtain data on demographic characteristics, lifestyle risk factors and family history of hyperten-sion. Three BP measurements were taken for every participant using a standard mercury sphygmoma-nometer according to a standard study protocol after the subject had been resting for 30 min. The mean of the three BP measurements was used for the analysis.

Body weight, height and waist circumference were measured with a balance beam scale after sub-jects removed their shoes and were wearing light clothing. Waist circumference was measured at the level of 1 cm above the umbilicus. Body mass index (BMI) was calculated as weight in kilogram divided by the square of the height in meters.

Overnight fasting blood samples were drawn by venipuncture from all subjects in the morning after at least 8 h of fasting, and fasting plasma glucose (FPG) was examined using a glucose meter (Roche, Basel, Switzerland) in the fi eld. Serum was subse-quently isolated from whole blood, and all serum samples were frozen at � 80 ° C.

Concentration of triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C) were assessed enzymatically on a Beckman Synchrony

CX5 Delta Clinical System (Beckman Coulter, Inc., Fullerton, CA, USA) using commercial reagents. Concentration of CRP was determined by an immunoturbidimetric assay on a Beckman Syn-chron CX5 Delta Clinical System using commercial reagents. sICAM-1 and sE-selectin were measured by an ELISA assay (R & D SysteMetS, Minneapolis, MN, USA) employing the quantitative sandwich enzyme immunoassay technique. Concentration of angiotensin II was measured by radioimmunoassay following separation by high-performance liquid chromatography.

Cigarette smoking was defi ned as having smoked at least 1 cigarette per day for 1 year or more. Heavy alcohol drinking was defi ned as consuming at least 50 g of alcohol per day for 1 year or more. Hyperten-sion was defi ned as SBP � 140 mmHg and/or DBP � 90 mmHg and/or use of antihypertensive medication in the 2 weeks prior to being examined. MetS was defi ned according to the modifi ed Adult Treatment Panel III (ATP III) recommendations for Asian Americans (18). Individuals were considered to have MetS if they had three or more of the follow-ing risk factors: WC � 90 cm for men and WC � 80 cm for women; TG � 1.70 mmol/l, or specifi c treat-ment for this lipid abnormality; HDL-C � 1.04 mmol/l in men and � 1.30 mmol/l in women, or spe-cifi c treatment for this lipid abnormality; BP � 130/85 mmHg, or treatment of previously diagnosed hyper-tension; or FPG � 5.6 mmol/l, or previously diag-nosed type 2 diabetes in the present study. Abnormal metabolism was defi ned as having components of MetS except for high BP, namely abdominal obesity, TG abnormality, HDL-C abnormality and FPG abnormality. Elevated biomarkers of infl ammation and endothelial dysfunction were defi ned as the fol-lowing according to the upper quartile of the bio-markers: elevated CRP, elevated sICAM-1, elevated sE-selectin and elevated angiotensin II were defi ned as CRP � 11.40 mg/l, sICAM-1 � 395.2 ng/ml, sE-selectin � 24.80 ng/ml and angiotensin II � 71.30 pg/ml, respectively.

Statistical analysis

Demographic characteristics, levels of metabolic indices and biomarkers of infl ammation and endothe-lial dysfunction were presented with median or rate (percentage), and were compared between hyperten-sives and normotensive, and between abnormal metabolism and normal metabolism groups with Mann – Whitney U test or χ 2 test. Rates of elevated biomarkers of infl ammation and endothelial dys-function and abnormal metabolism were calculated by BP status and compared between hypertensives and normotensives with χ 2 test. Levels of biomarkers were described with median by BP status and num-ber of abnormal metabolic indices; and association

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Hypertension, abnormal metabolism and chronic low-grade infl ammation 3

between levels of biomarkers and number of abnor-mal metabolic indices was analyzed with the Spear-man correlation. Associations of hypertension with abnormal metabolism, elevated biomarkers and coexistence of abnormal metabolism with elevated biomarkers were analyzed using a logistic regres-sion model. Odds ratio (OR) and 95% confi dent interval (CI) were calculated, respectively. All p -values were two-tailed and statistical signifi cance was defi ned as p � 0.05. Statistical analyses were conducted using SAS 9.2 (SAS Institute Inc, Cary, North Carolina).

Result

General characteristics of the subjects stratifi ed by metabolic status and BP status are presented in Table I. Under stratifi cation by metabolic status, hypertensives were more likely to have older age, high rates of male, smoking and heavy drinking, greater waist circumference, high levels of TG, FPG

and CRP compared with normotensives in both normal metabolism, and abnormal metabolism stratifi cations; hypertensives were more likely to have great BMI, high sICAM-1, sE-selectin and angiotensin II levels compared with normotensives in abnormal metabolism stratifi cation (all p � 0.05) but not in normal metabolism stratifi cation ( p � 0.05). Under stratifi cation by BP status, there was no difference in age between subjects with nor-mal metabolism and those with abnormal metabo-lism in both hypertension and normotension stratifi cations ( p � 0.05); subjects with abnormal metabolism were more likely to have low rates of male, smoking and heavy drinking, greater BMI and waist circumference, high levels of TG, FPG, CRP, sICAM-1 and sE-selectin, low levels of HDL-C and angiotensin II, compared with those with normal metabolism in both hypertension and normotension stratifi cations (all p � 0.05).

Compared with normotensives, hypertensives had higher rates of abnormal metabolism, elevated CRP, elevated sICAM-1, elevated sE-selectin and

Table I. General characteristics of 2589 subjects by blood pressure status and metabolism status.

Normotensive ( n � 1621) Hypertensive ( n � 968)

Normet ( n � 479) Abmet ( n � 1142) Normet ( n � 215) Abmet ( n � 753)Age, years 41 (35 – 50) 41 (35 – 50) 52 (43 – 66) a 51 (43 – 59) a Male, % 56.3 27.4 b 74.3 a 43.9 a,b Current smoking, % 49.8 39.1 b 63.9 a 44.2 a,b Current drinking, % 39.0 22.1 b 58.5 a 40.8 a,b Body mass index, kg/m 2 20.1 (18.9 – 21.4) 22.0 (20.1 – 24.2) b 20.2 (18.9 – 21.5) 23.4 (20.9 – 26.3) a,b Waist circumference, cm 75 (71 – 78) 80 (74 – 86) b 77 (72 – 80) a 85 (79 – 92) a,b Systolic BP, mmHg 115 (110 – 120) 118 (110 – 124) 148 (136 – 170) a 147 (138 – 164) a Diastolic BP, mmHg 79 (70 – 80) 80 (71 – 80) 96 (90 – 100) a 96 (90 – 101) a Triglycerides, mmol/l 0.74 (0.55 – 1.00) 0.93 (0.65 – 1.41) b 0.86 (0.66 – 1.13) a 1.23 (0.84 – 1.96) ab HDL-C, mmol/l 1.39 (1.26 – 1.37) 1.05 (0.91 – 1.22) b 1.41 (1.24 – 1.57) 1.07 (0.91 – 1.29) b FPG, mmol/l 4.3 (3.9,4.8) 4.9 (4.3 – 5.5) b 4.6 (4.2 – 5.0) a 5.2 (4.6 – 5.8) a,b CRP, mg/l 4.5 (3.3 – 6.5) 6.0 (4.0 – 11.2) b 5.2 (4.0 – 7.4) a 8.4 (4.8 – 16.5) a,b sICAM-1, ng/ml 305.4 (239.9 – 366.3) 333.7 (261.0 – 396.6) b 315.5 (252.7 – 380.5) 347.2 (272.7 – 415.2) a,b sE-selectin, ngm/l 17.0 (13.6 – 23.0) 18.7 (14.6 – 24.8) b 17.5 (14.6 – 23.6) 19.7 (15.7 – 26.0) a,b Angiotensin II, pg/ml 51.8 (40.0 – 74.1) 46.1 (39.0 – 66.0) b 53.0 (40.0 – 79.1) 51.5 (40.7 – 85.4) a,b

Values are presented as median (quartile range) or percentage. Normet, normal metabolism; Abmet, abnormal metabolism; BP, blood pressure; HDL-C, high-density lipoprotein cholesterol; FPG, fasting plasma glucose; CRP, C-reactive protein sICAM-1, soluble intercellular cell adhesion molecule-1; sE-selectin, soluble E-selectin. a Comparisons between hypertensive and normotensive under the same metabolism status, p � 0.01. b Comparisons between normal metabolism and abnormal metabolism under the same BP status, p � 0.01.

Table II. Rates of abnormal metabolism, elevated biomarkers of infl ammation and coexistence of abnormal metabolism and elevated biomarkers of infl ammation by blood pressure status.

Normotensive Hypertensive

Abmet, % 72.0 80.6 a Elevated CRP, % 19.6 33.9 a Elevated sICAM-1, % 22.2 29.7 a Elevated sE-selectin, % 24.1 27.0 a Elevated angiotensin II, % 21.6 30.6 a Abmet with elevated CRP, % 17.2 31.7 a Abmet with elevated sICAM-1, % 18.1 25.5 a Abmet with elevated sE-selectin, % 17.7 22.6 a Abmet with elevated Angiotensin II, % 14.6 24.8 a

Abmet, abnormal metabolism; CRP, C-reactive protein; sICAM-1, soluble intercellular cell adhesion molecule-1; sE-selectin, soluble E-selectin. a Compared with normontensive: p � 0.01.

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4 M. Zhang et al.

elevated angiotensin II (all p � 0.01). Furthermore, the rates of coexistence of abnormal metabolism with elevated CRP, elevated sICAM-1, elevated sE-selectin and elevated angiotensin II were also all higher in hypertensives compared with those in normotensives (all p � 0.01) (Table II).

Levels of CRP, sICAM-1, sE-selectin and angio-tensin II in subjects by BP status and number of abnormal metabolic indices are illustrated in Figure 1. Except for angiotensin II, levels of CRP, sICAM-1 and sE-selectin all increased with number of abnormal metabolic indices both in hypertensives and normo-tensives (all p � 0.001).

There were signifi cant associations between abnormal metabolism, elevated infl ammation bio-markers and the coexistence of abnormal metabo-lism, with the elevated infl ammation and endothelial dysfunction biomarkers and hypertension. Compared with subjects without both abnormal metabolism and any of elevated infl ammation and endothelial dys-function biomarkers, unadjusted ORs of hyperten-sion associated with abnormal metabolism, elevated CRP, elevated sICAM-1, elevated sE-selectin, elevated angiotensin II, and the coexistences of abnor-mal metabolism with the elevated CRP, elevated sICAM-1, elevated sE-selectin, elevated angiotensin II were 1.615, 2.861, 2.202, 1.848, 2.341, 3.027, 2.294, 2.077 and 2.785, respectively. The ORs remained signifi cant after adjusted for multivariate (Table III).

Discussion

In this cross-sectional study among a Mongolian population, we found that increased levels of infl am-mation and endothelial dysfunction biomarkers such as CRP, sICAM-1, sE-selectin and angiotensin II and their coexistences with abnormal metabolism including abdominal obesity, TG abnormality, HDL-C abnormality and FPG abnormality were positively and signifi cantly associated with hyperten-sion. Individuals with higher levels of CRP, sICAM-1, sE-selectin and angiotensin II and their coexistences with abnormal metabolism were all at an increased risk of hypertension compared with those with lower levels of the biomarkers and without abnormal metabolism. In addition, our fi ndings showed not only a trend of increasing of level of the biomarkers with number of abnormal metabolism indexes, but also a trend that coexistences of the biomarkers with abnormal metabolism increased risk of hypertension. These data provide further support that infl amma-tion and endothelial dysfunction, abnormal metabo-lism as well as coexistence of abnormal metabolism with infl ammation and endothelial dysfunction are associated with hypertension.

Our study contributes to understanding of asso-ciation among abnormal metabolism, infl ammation and endothelial dysfunction and hypertension. Firstly, abnormal metabolism was associated with biomark-ers of infl ammation and endothelial dysfunction

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Figure 1. Levels of C-reactive protein (CRP), soluble intercellular cell adhesion molecule-1 (sICAM-1), E-selectin and angiotensin II (Ang II) by number of abnormal metabolic indices and hypertension status.

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Hypertension, abnormal metabolism and chronic low-grade infl ammation 5

independently of BP status. Secondly, coexistence of abnormal metabolism with elevated biomarker of infl ammation and endothelial dysfunction probably increased risk of hypertension. Our study shows results similar to that of some studies which infl am-mation and endothelial dysfunction are not only associated with hypertension, but also with MetS (12,13).

In this study, we analyzed association of hyperten-sion with abnormal metabolism, biomarkers of infl ammation and endothelial dysfunction, and coex-istence of abnormal metabolism with biomarkers of infl ammation and endothelial dysfunction among a large Mongolian population, and angiotensin II was included as a biomarker of infl ammation and endothe-lial function. To a certain degree, the biomarkers such as CRP, sICAM-1 and sE-selectin refl ect either the status of infl ammation or the status of endothelial dysfunction (19 – 21). Aside from the role of a vaso-constrictor, angiotensin II also induces endothelial dysfunction and infl ammation resulting in acceler-ated progression of atherosclerosis (22,23).

Some previous studies have documented that infl ammation biomarkers might be an important pre-cursor to cardiovascular disease including hyperten-sion (24,25), MetS and type 2 diabetes (26,27). For example, Sung and colleagues reported that increased CRP was an independent risk factor of hypertension (2). Haffner et al. (28,29) provided accumulating evidences that infl ammation was an important risk factor of cardiovascular disease; their studies demon-strated that elevated CRP was associated with increased risk of cardiovascular disease and diabetes mellitus, and, accordingly, they believed that a proin-fl ammatory state should be served as one of compo-nents of MetS. Festa et al. (30) and Kraja et al. (31) also reported that elevated CRP and elevated sICAM-1 as well as elevated sE-selectin were all associated with components of MetS, infl ammation and endothelial dysfunction might induce insulin

resistance (32); insulin resistance is a key link of MetS. There were inverse results that insulin resis-tance may in turn exacerbate infl ammation by increasing cytokine and adipo-chemokine expression (including TNF- α , IL-6, leptin and others), elevating free fatty acid levels, and impairing endothelial nitric oxide synthase activity (33,34). Both infl ammation and MetS or insulin resistance are two important links in the mechanism of hypertension. Systematic infl ammation promotes the development of hyper-tension by inducing insulin resistance or abnormal metabolism, or insulin resistance promotes the devel-opment of hypertension by exacerbating the infl am-mation reaction. In our study, there was a close relation among abnormal metabolism, infl ammation and endothelial dysfunction and hypertension. Our fi ndings support that infl ammation and endothelial dysfunction are associated with hypertension and MetS, and that coexistence of abnormal metabolism with infl ammation and endothelial dysfunction increase risk of hypertension. Our study might pro-vide a clue for clinical treatment and risk evaluation for hypertension, though it was a community-based study. It is necessary to further study whether the coexistence of abnormal metabolism with infl amma-tion and endothelial dysfunction affect the effective-ness of treatment for hypertension and promote incidence of other cardiovascular diseases.

Limitations should be mentioned in the present study. First, this was a cross-sectional study, there-fore, a causal relationship between infl ammation and endothelial dysfunction and co-existence of abnor-mal metabolism with infl ammation and endothelial dysfunction and hypertension could not be estab-lished, cohort studies are warranted to further evalu-ate the causal relationship. Secondly, approximately 25% of individuals who were eligible for inclusion did not participate in the study, which would unavoid-ably cause some selection bias. However, we believe this bias is minimal because it is unlikely that par-

Table III. Odds ratios (OR) and 95% confi dence intervals (95% CI) of hypertension associated with abnormal metabolism, elevated biomarker of infl ammation and their coexistence.

Unadjusted OR (95% CI)

Mutivariate-adjusted a OR

(95% CI)

No Abmet with no elevated biomarker

1.000 (reference) 1.000 (reference)

Abmet 1.615 (1.329 – 1.962) 2.209 (1.594 – 3.062)Elevated CRP 2.861 (2.075 – 3.946) 2.820 (1.992 – 3.992)Elevated sICAM-1 2.202 (1.592 – 3.045) 2.370 (1.665 – 3.374)Elevated E-selectin 1.848 (1.336 – 2.558) 1.893 (1.331 – 2.691)Elevated angiotensin II 2.341 (1.698 – 3.229) 2.545 (1.793 – 3.612) Abmet with elevated CRP 3.027 (2.185 – 4.192) 2.990 (2.102 – 4.252)Abmet with elevated sICAM-1 2.294 (1.645 – 3.198) 2.551 (1.775 – 3.667) Abmet with elevated E-selectin 2.077 (1.484 – 2.906) 2.223 (1.544 – 3.220) Abmet with elevated Angiotensin II 2.785 (1.992 – 3.893) 3.135 (2.185 – 4.519)

a Age, gender, smoking and drinking were adjusted. Abmet, abnormal metabolism; CRP, C-reactive protein; sICAM-1, soluble intercellular cell adhesion molecule-1; sE-selectin, soluble E-selectin.

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ticipants chose not to participate due to their BP or biomarker levels, which they did not know. Further-more, several important biomarkers of infl ammation and endothelial dysfunction, such as tumor necrosis factor-alpha (TNF-a), IL-6, von Willebrand factor and VCAM-1, were not measured in our study. Data on endothelium independent fl ow-mediated vasodilation were also not collected.

In summary, our study indicated that infl amma-tion and endothelial dysfunction was associated with hypertension and abnormal metabolism, and indi-viduals with co-existence of abnormal metabolism with infl ammation and endothelial dysfunction had higher risk of prevalent hypertension among the Mongolian population. This study suggests that fur-ther study on treatment for hypertension patients with coexistence of abnormal metabolism with infl ammation and endothelial dysfunction should be conducted in future.

Sources of funding

The National Natural Science Foundation of China (Grant No. 81172761) and a Project of the Priority Academic Program Development of Jiangsu Higher Education Institutions.

Acknowledgements

We are deeply appreciative of the participants who are actively engaging in the study, and thank the Kezuohouqi Banner Center for Disease Prevention and Control, and the Naiman Banner Center for Disease Prevention and Control for their support and assistance.

Declaration of interest: The authors report no confl icts of interest. The authors alone are respon-sible for the content and writing of the paper. This study was supported by National Natural Science Foundation of China (Grant No. 81172761) and a Project of the Priority Academic Program Develop-ment of Jiangsu Higher Education Institutions.

References

Bautista LE , Lopez-Jaramillo P , Vera LM , Casas JP , Otero AP , 1. Guaracao AI . Is C-reactive protein an independent risk factor for essential hypertension? J Hypertens. 2001 ; 19 : 857 – 861 . Sung KC , Suh JY , Kim BS , Kang JH , Kim H , Lee MH , et al . 2. High sensitivity C-reactive protein as an independent risk factor for essential hypertension . Am J Hypertens. 2003 ; 16 : 429 – 433 . Gupta V , Sachdeva S , Khan AS , Haque SF . Endothelial dys-3. function and infl ammation in different stages of essential hypertension . Saudi J Kidney Dis Transpl. 2011 ; 22 : 97 – 103 . Harrison DG , Guzik TJ , Lob HE , Madhur MS , Marvar PJ , 4. Thabet SR , et al . Infl ammation, immunity, and hypertension . Hypertension. 2011 ; 57 : 132 – 140 .

Chandrasekaran N , Amalraj E , Datta M , Krishnamurthy PV , 5. Sankaran JR , Rajasambandam P . Association between obesity and hypertension in south Indian patients . Indian Heart J. 1994 ; 46 : 21 – 24 . Zhang M , Batu B , Tong W , Liu YY , Liu Y , Zhang Y . Clustering 6. of hyperlipidemia, hyperglycemia, alcohol drinking, over-weight and central obesity and hypertension in Mongolian people, China . CVD Prev Control. 2009 ; 4 : 163 – 169 . Gus M , Fuchs SC , Moreira LB , Moraes RS , Wiehe M , Silva 7. AF , et al . Association between different measurements of obesity and the incidence of hypertension . Am J Hypertens. 2004 ; 17 : 50 – 53 . Guo ZR , Hu XS , Wu M , Zhou MH , Zhou ZY . [A prospective 8. study on the association between dyslipidemia and hyper-tension]. Zhonghua Liu Xing Bing Xue Za Zhi . 2009 ; 30 : 554 – 558 . Bonaa KH , Thelle DS . Association between blood pressure 9. and serum lipids in a population . The Tromso Study. Circula-tion. 1991 ; 83 : 1305 – 1314 . Sesso HD , Buring JE , Chown MJ , Ridker PM , Gaziano JM . 10. A prospective study of plasma lipid levels and hypertension in women . Arch Intern Med. 2005 ; 165 : 2420 – 2427 . Movahed MR , Sattur S , Hashemzadeh M . Independent asso-11. ciation between type 2 diabetes mellitus and hypertension over a period of 10 years in a large inpatient population . Clin Exp Hypertens. 2010 ; 32 : 198 – 201 . Miyao M , Furuta M , Kondo T , Sakakibara H , Ishihara S , 12. Yamanaka K , Yamada S . The relationship of high-density lipo-protein cholesterol to obesity, drinking and smoking habits . Nagoya J Med Sci 1993 ; 55 : 65 – 70 . Pacholczyk M , Ferenc T , Kowalski J . The metabolic syn-13. drome. Part I: Defi nitions and diagnostic criteria for its iden-tifi cation. Epidemiology and relationship with cardiovascular and type 2 diabetes risk . Postepy Hig Med Dosw (Online) 2008 ; 62 : 530 – 542 . Yudkin JS , Stehouwer CD , Emeis JJ , Coppack SW . C-reactive 14. protein in healthy subjects: Associations with obesity, insulin resistance, and endothelial dysfunction: A potential role for cytokines originating from adipose tissue? Arterioscler Thromb Vasc Biol. 1999 ; 19 : 972 – 978 . Leinonen E , Hurt-Camejo E , Wiklund O , Hulten LM , Hiukka 15. A , Taskinen MR . Insulin resistance and adiposity correlate with acute-phase reaction and soluble cell adhesion molecules in type 2 diabetes . Atherosclerosis. 2003 ; 166 : 387 – 394 . Hossain M , Faruque MO , Kabir G , Hassan N , Sikdar D , Nahar 16. Q , et al . Association of serum TNF- α and IL-6 with insulin secre-tion and insulin resistance in IFG and IGT subjects in a Bang-ladeshi population . Int J Diabetes Mellitus. 2010 ; 2 : 165 – 168 . Zhang M , Batu B , Tong W , Li H , Lin Z , Li Y , et al . Prehyper-17. tension and cardiovascular risk factor clustering among Mon-golian population in rural and animal husbandry area, Inner Mongolia, China . Circ J. 2009 ; 73 : 1437 – 1441 . Grundy SM , Cleeman JI , Daniels SR , Donato KA , Eckel RH , 18. Franklin BA , et al.; American Heart Association; National Heart, Lung, and Blood Institute. Diagnosis and manage-ment of the metabolic syndrome: An American Heart Asso-ciation/National Heart, Lung, and Blood Institute Scientifi c Statement. Circulation. 2005 ; 112 : 2735 – 2752 . Zhang C . The role of infl ammatory cytokines in endothelial 19. dysfunction . Basic Res Cardiol. 2008 ; 103 : 398 – 406 . Szmitko PE , Wang CH , Weisel RD , de Almeida JR , Anderson 20. TJ , Verma S . New markers of infl ammation and endothelial cell activation: Part I . Circulation. 2003 ; 108 : 1917 – 1923 . Ridker PM , Hennekens CH , Buring JE , Rifai N . C-reactive 21. protein and other markers of infl ammation in the prediction of cardiovascular disease in women . N Engl J Med. 2000 ; 342 : 836 – 843 . Schiffrin EL , Touyz RM . Multiple actions of angiotensin II 22. in hypertension: Benefi ts of AT1 receptor blockade . J Am Coll Cardiol. 2003 ; 42 : 911 – 913 .

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care

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Pastore L , Tessitore A , Martinotti S , Toniato E , Alesse E , Bravi 23. MC , et al . Angiotensin II stimulates intercellular adhesion molecule-1 (ICAM-1) expression by human vascular endothelial cells and increases soluble ICAM-1 release in vivo . Circulation. 1999 ; 100 : 1646 – 1652 . Anuurad E , Tracy RP , Pearson TA , Kim K , Berglund L . Syner-24. gistic role of infl ammation and insulin resistance as coronary artery disease risk factors in African Americans and Caucasians . Atherosclerosis. 2009 ; 205 : 290 – 295 . Ridker PM . C-reactive protein and the prediction of cardiovas-25. cular events among those at intermediate risk: Moving an infl ammatory hypothesis toward consensus . J Am Coll Cardiol. 2007 ; 49 : 2129 – 2138 . Han TS , Sattar N , Williams K , Gonzalez-Villalpando C , Lean 26. ME , Haffner SM , et al . Prospective study of C-reactive pro-tein in relation to the development of diabetes and metabolic syndrome in the Mexico City Diabetes Study.[see comment] . Diabetes Care . 2002 ; 25 : 2016 – 2021 . Sattar N , Gaw A , Scherbakova O , Ford I , O ’ Reilly DS , Haffner 27. SM , et al . Metabolic syndrome with and without C-reactive protein as a predictor of coronary heart disease and diabetes in the West of Scotland Coronary Prevention Study . Circulation. 2003 ; 108 : 414 – 419 .

Haffner SM . The metabolic syndrome: Infl ammation, diabetes 28. mellitus, and cardiovascular disease . Am J Cardiol. 2006 ; 97 : 3A – 11A . Executive Summary of The Third Report of The National Cho-29. lesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA . 2001 ; 285 : 2486 – 2497 . Festa A , D ’ Agostino R , Jr., Howard G , Mykkanen L , Tracy 30. RP , Haffner SM . Chronic subclinical infl ammation as part of the insulin resistance syndrome: The Insulin Resistance Atherosclerosis Study (IRAS) . Circulation. 2000 ; 102 : 42 – 47 . Kraja AT , Province MA , Arnett D , Wagenknecht L , Tang W , 31. Hopkins PN , et al . Do infl ammation and procoagulation biomarkers contribute to the metabolic syndrome cluster? Nutr Metab (Lond). 2007 ; 4 : 28 . Park K , Steffes M , Lee DH , Himes JH , Jacobs DR , Jr . Associa-32. tion of infl ammation with worsening HOMA-insulin resistance . Diabetologia. 2009 ; 52 : 2337 – 2344 . Shoelson SE , Lee J , Goldfi ne AB . Infl ammation and insulin 33. resistance . J Clin Invest. 2006 ; 116 : 1793 – 1801 . Vincent MA , Montagnani M , Quon MJ . Molecular and phys-34. iologic actions of insulin related to production of nitric oxide in vascular endothelium . Curr Diab Rep. 2003 ; 3 : 279 – 288 .

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