Original Article

Impaired Fasting Glucose and Impaired Glucose Tolerance Do Not Predict Hypertension: A Community Cohort Study Chan Joo Lee,1 Nam-Kyoo Lim,2 Hyeon-Chang Kim,3 Sang-Hyun Ihm,4 Hae-Young Lee,5 Hyun Young Park,2 and Sungha Park6

METHODS A total of 4,039 subjects without hypertension or diabetes (1,847 men and 2,192 women; age 49.9 ± 8.2 years), from the Ansan-Ansung cohorts within the Korean Genome Epidemiology Study, were enrolled in 2001– 2002 and restudied in 2005–2006. The association between the incidence of hypertension and IFG, IGT, or other metabolic factors was studied. RESULTS During the 4-year follow-up period, 582 of the 4,039 subjects developed hypertension. At baseline, the prevalence of abdominal obesity, dyslipidemia, and IGT was higher in subjects who became hypertensive compared to those that remained normotensive. The prevalence of IFG was not significantly different between the 2 groups. In a multivariate

analysis, abdominal obesity and high serum triglyceride were significant risk factors for the development of hypertension. Neither IFG nor IGT were significantly associated with new-onset hypertension. Although the risk of hypertension was higher with the number of metabolic components present at baseline, IFG and IGT were not significant components compared to other metabolic components, especially when abdominal obesity was taken into account.

Conclusions While metabolic syndrome components related to insulin resistance present at baseline are important risk factors of hypertension, we conclude that coexisting metabolic component, mainly abdominal obesity, rather than IFG and IGT have more predictive value for determining the development of hypertension in a Korean population. Keywords: abdominal obesity; blood pressure; hypertension; impaired fasting glucose; impaired glucose tolerance; insulin resistance. doi:10.1093/ajh/hpu186

Insulin resistance, a key pathophysiological mechanism linking the various cardiovascular risk factors in metabolic syndrome, is associated with hypertension in 40%–50% of hypertensive subjects. In addition, up to one third of hypertensive subjects are diagnosed with metabolic syndrome. Insulin resistance is associated with increased renal sodium absorption, increased sympathetic neural outflow, increased peripheral vascular resistance, activation of the renin-angiotensin-aldosterone system, and impaired insulin-mediated vasodilation, which may function cooperatively to elevate blood pressure.1,2 However, among the parameters of metabolic syndrome, it is

still not clear which markers for insulin resistance are useful to predicting future development of hypertension.3,4 Fasting plasma glucose and postprandial glucose are relatively simple test for determining the degree of insulin resistance.5 It has been shown that impaired fasting glucose (IFG), defined as blood glucose between 100 and 125 mg/ dl, and impaired glucose tolerance (IGT), defined as 2-hour postprandial blood glucose of 140–199 mg/dl, are predictors for the future development of diabetes and diabetes-related complications.6,7 However, whether or not IFG or IGT are risk factors for hypertension is not clear due to confounding

Correspondence: Sungha Park ([email protected]).

1Department of Biochemistry and Molecular Biology, Institute of Genetic Science, Integrated Genomic Research Center for Metabolic Regulation, BK21 PLUS project for Medical Science, Yonsei University College of Medicine, Seoul, Korea; 2Division of Cardiovascular and Rare diseases, Center for Biomedical Science, National Institute of Health, Cheongwongun, Chungbuk, Korea; 3Department of Preventive medicine, Yonsei University College of Medicine, Seoul, Korea; 4Division of Cardiology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea; 5Department of Internal Medicine and Cardiovascular Center, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea; 6Division of Cardiology, Yonsei Cardiovascular Hospital, Yonsei Cardiovascular Research Institute, Yonsei University College of Medicine, Seoul, Korea.

Initially submitted June 4, 2014; date of first revision June 19, 2014; accepted for publication August 11, 2014; online publication September 29, 2014

© American Journal of Hypertension, Ltd 2014. All rights reserved. For Permissions, please email: [email protected]

American Journal of Hypertension  28(4)  April 2015  493

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Background Insulin resistance has an important role in the pathogenesis of hypertension. We hypothesized that impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) which represents insulin resistance would predict the development of hypertension.

Lee et al.

factors such as other metabolic components and the heterogeneity of studies investigating the relationship between insulin resistance and the development of hypertension.8–11 In this study, we sought to determine the predictive value of fasting glucose and postprandial glucose for the development of hypertension independent of other coexisting metabolic components in a cohort of subjects who had not been previously diagnosed with hypertension and diabetes at baseline. METHODS Subjects

Clinical and anthropometric measurements

All individuals underwent a baseline evaluation, comprehensive health examination, and interviews, as described

Statistical analysis

Figure 1.  Participants flowchart.

494  American Journal of Hypertension  28(4)  April 2015

Continuous variables are expressed as mean ± SD and categorical variables as numbers and percentages. Comparison of continuous variables was performed using an independent t-test. Comparison of categorical variables was performed using chi-square analysis. The association of independent clinical variables was calculated using univariate and multivariate logistic regression analysis. Multiple logistic regression analysis was chosen because the exact time of the onset of hypertension could not be accurately assessed because subjects were assessed once every 2 years. Linear-by-linear association test was used to examine the incidence of hypertension according to groups stratified by the number of metabolic syndrome components other than high blood pressure at baseline. Odds ratio (ORs) for hypertension according to the number of metabolic syndrome components other than high blood pressure was obtained after adjustment for age, sex, BMI, homeostasis model assessment insulin resistance, and systolic blood pressure. To determine whether or not

Downloaded from http://ajh.oxfordjournals.org/ at University of California, Santa Cruz on April 3, 2015

The Ansan-Ansung cohorts are 2 independent prospective cohorts embedded within the Korean Genome Epidemiology Study, which has been described previously.12 Briefly, each cohort consisted of a population sample of Korean men and women between the ages of 40–69. Detailed information on the sampling plan and the selection criteria has been previously described.13 Initial enrollment began in 2001–2002. The first follow-up was performed between 2003 and 2004, and the second follow-up was performed between 2005 and 2006. In total, 5,020 (2,523 men and 2,497 women) subjects from Ansan city (an urban community of 555,000) and 5,018 (2,239 men and 2,779 women) subjects from Ansung (a rural community of 133,000) were enrolled.12 Among the 10,038 total participants in the cohort, we analyzed 4,039 subjects who did not have hypertension and diabetes mellitus at baseline (Figure 1). We analyzed data from the initial enrollment to 2nd follow-up in 2005–2006.

previously.12,13 Briefly, participants completed standardized questionnaires to assess relevant medical and family history as well as variables related to lifestyle pattern.13 A  health check-up was performed by a health professional according to a standardized working protocol. Height, weight, body mass index (BMI), and anthropometric data (waist circumference, hip circumference) were measured. Sitting brachial blood pressure was measured twice in the dominant arm after 5 minutes of rest using a mercury sphygmomanometer according to a standardized protocol.13 The blood pressure measurements were recorded to the nearest 2 mm Hg. The average of the 2 measurements was used for analysis. Routine biochemical analyses were assessed at the Seoul Clinical Laboratories (Seoul, Korea) from blood samples obtained after a 12-hour fast. To measure fasting plasma glucose and insulin, 1-hour postprandial plasma glucose and insulin, and 2-hour postprandial plasma glucose and insulin after 75 g of oral glucose loading, an oral glucose tolerance test was performed. The homeostasis model assessment insulin resistance index was calculated as (fasting plasma glucose (mg/dl) × fasting serum insulin (μU/ml))/405. Hypertension was defined as a self-reported history of hypertension, and/or a history of antihypertensive medication use, or a blood pressure of 140/90 mm Hg or more at the time of the visit. Newly developed hypertension was assessed in the first (2003–2004) and second (2005–2006) follow-up database. Metabolic syndrome components, including abdominal obesity, high serum triglyceride, low high density lipoprotein (HDL) cholesterol, and high fasting plasma glucose, were defined based on the International Diabetes Federation criteria for metabolic syndrome (abdominal obesity: waist circumference ≥90 cm in Asian men or ≥80 cm in Asian women; high serum triglyceride: serum triglyceride ≥150 mg/dl; low serum HDL cholesterol: serum HDL cholesterol

Impaired fasting glucose and impaired glucose tolerance do not predict hypertension: a community cohort study.

Insulin resistance has an important role in the pathogenesis of hypertension. We hypothesized that impaired fasting glucose (IFG) or impaired glucose ...
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