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ORIGINAL PAPERS: Risk factors

Incidence and risk factors for progression from prehypertension to hypertension: a 12-year Korean Cohort Study

Yu, Eun Suna,b; Hong, Kwanb,c; Chun, Byung Chulb,c

Author Information

aNational Health Insurance Service

bKorea University Graduate School of Public Health

cDepartment of Preventive Medicine, Korea University College of Medicine, Seoul, Korea

Correspondence to Byung Chul Chun, Department of Preventive Medicine, Korea University College of Medicine, Seoul 02841, Korea. Tel: +82 2 2286 1169; fax: +82 2 927 7220; e-mail: [email protected]

Abbreviations: ALT, alanine transaminase; BP, blood pressure; CIs, confidence intervals; DASH, dietary approaches to stop hypertension; FBS, fasting blood glucose; Hb, hemoglobin; ICD-10, The 10th edition of the International Classification of Diseases ; JNC 7, The seventh report of the Joint National Committee on Hypertension; NHIS-HEALS, National Health Insurance Service-National Health Screening Cohort; SD, standard deviation; TC, total cholesterol

Received 19 March, 2020

Revised 6 April, 2020

Accepted 7 April, 2020

This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0

doi: 10.1097/HJH.0000000000002494
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Abstract

INTRODUCTION

Hypertension is a chronic medical condition that involves persistently elevated arterial blood pressure, although most people do not exhibit related symptoms [1]. Hypertension is an important public health challenge worldwide, as more than 26% of the world's adult population has hypertension [2]. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) proposed that individuals with SBP of 120–139 mmHg or DBP of 80–89 mmHg be classified as having ‘prehypertension’ [3]. This group of individuals has an elevated risk of developing hypertension and cardiovascular disease, relative to individuals with normal BP [4,5]. Moreover, approximately 90% of prehypertensive individuals have at least one other cardiovascular risk factor, and 68% of these individuals have at least one significant clinical risk factor for heart disease or stroke [6].

Since the JNC 7 proposal, epidemiological studies have shown that prehypertension is common worldwide, with a reported prevalence of 30–50% depending on the studied population [7–9]. However, it is important to note that early interventions are able to reduce the related risks of cardiovascular disease and death [10]. Therefore, it is important to identify the risk factors that are involved in the progression from prehypertension to hypertension, which may be targeted in future interventions. Previous studies have attempted to identify relevant risk factors in Asian populations, although those studies were limited by the use of cross-sectional data [11], short-term outcomes [12], or logistic regression models that did not consider the participants; characteristics over time [13]. Moreover, we are not aware of any studies with stratification according to sex, which may be a major risk factor, and no large-scale study has evaluated the progression from prehypertension to hypertension in the Korean population. Therefore, this study estimated the incidence of progression to hypertension among a nationally representative sample of middle-aged and elderly Korean adults with prehypertension and evaluated related risk factors including personal characteristics, lifestyle factors, environmental factors, and medical histories.

METHODS

Study population

This study used data from the National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS). The present study initially considered 514 866 participants (40–79 years old) who were randomly selected to form a 10% sample of all individuals who participated in the National Health Screening Program during 2002 or 2003. All participants were followed until 2015. The National Health Screening Program invites individuals to participate at least every 2 years in a general free-of-charge health screening program. The program collects data regarding medical diagnoses, drug prescriptions, demographic characteristics, causes of death, and information from health examinations, such as self-administered health surveys, physical examinations, and biochemical test results. Details of the cohort have been published previously [14]. In 2018, the hypertension guideline published by the Korean Society of Hypertension suggested a new definition of prehypertension as a SBP of 130–139 mmHg or a DBP of 80–89 mmHg. The expansion of the DBP from 85–90 to 80–90 mmHg in prehypertension criteria was aimed at providing a warning message for the rising blood pressure and encouraging active preventive lifestyles. For the present study, prehypertension was defined as SBP of 130–139 mmHg or a DBP of 80–89 mmHg, based on the 2018 guidelines of the Korean Society of Hypertension [15].

The study flowchart is shown in Fig. 1. We selected individuals with prehypertension in 2003–2004 from among the 514 866 individuals in the NHIS-HEALS sample. Participants were excluded if they received antihypertensive treatment or were diagnosed with hypertension during 2002–2003. On the basis of these criteria, the study ultimately included 115 456 individuals with prehypertension at the baseline assessment. The BP values were measured using a BP meter after at least 5 min of rest. If the measured value indicated that the SBP was less than 120 mmHg and the DBP was less than 80 mmHg, measured only once. However, if the measured value indicated that the SBP was more than 120 mmHg or the DBP was greater than 80 mmHg, the BP value was re-measured after a resting interval of at least 2 min. The number of re-measurements is three.

F1
FIGURE 1:
Study flowchart.

Definition of hypertension

Hypertension was identified based on codes from the 10th edition of the International Classification of Diseases (ICD-10: I10–I13), a SBP of greater than 140 mmHg, or a DBP of greater than 90 mmHg from the screening program. The follow-up to identify new-onset hypertension and/or death ended on 31 December 2015.

The following known risk factors for hypertension were included in the analysis. Data regarding personal or family histories of diabetes mellitus, hypertension, drinking, smoking, and exercise were obtained using self-administered questionnaires. For the same period, data regarding BP, fasting blood glucose (FBS), total cholesterol (TC), hemoglobin (Hb), alanine transaminase (ALT), and BMI were obtained using laboratory test results and physical examinations. A personal history of diabetes mellitus during 2002–2003 was identified based on ICD-10 codes (E10–E14) or responses to the self-administered questionnaire.

Statistical analysis

Continuous variables were reported as mean ± standard deviation and categorical variables were reported as number (%). Factors that were potentially related to progression to hypertension were evaluated using the chi-squared test or the t-test, as appropriate. The incidence rate of progression to hypertension was calculated by counting the number of incident events and dividing that value by the total follow-up for the study population (expressed in 1000 person-years). For the multivariate analysis, we used a Cox proportional hazards model to calculate the hazard ratios and 95% confidence intervals (95% CIs) for potential risk factors, which were identified from the univariate analyses (P value of <0.05). The final models for each sex were created after the multivariate analysis and stepwise selection of major variables. We used SAS Enterprise software (version 7.1, NHIS remote connection) for the analyses.

Ethical approval

This project was approved by the institutional review board at Korea University (KUIRB- 2018-0064-01). The requirement for written informed consent was waived as the data were de-identified before the analysis.

RESULTS

This study included 115 456 individuals (69 094 men and 46 362 women, age range: 40–79 years). The mean ages were 51.1 ± 8.6 years for men and 53.0 ± 9.0 years for women (P < 0.001). Table 1 presents the general characteristics of the participants with prehypertension. Both groups had a large proportion of low household income (63.3 and 45.6%). Men were significantly more likely than women to be current smokers, consume alcohol frequently, exercise frequently, and to have elevated values for pulse pressure, ALT, FBS, and Hb (P < 0.001). Women were significantly more likely than men to have elevated values for TC and BMI (P < 0.001). A family history of hypertension was more common among women (women: 7.9%, men: 6.3%), whereas both groups had similar rates for family and personal histories of diabetes mellitus. The family history of hypertension and diabetes were significantly more likely in 40s groups.

T1
TABLE 1:
General characteristics of the participants with prehypertension according to sex

Table 2 shows the incidence densities for progression to hypertension according to sex. The mean follow-up periods were 8.5 years for men and 8.8 years for women. During the follow-up period, progression to hypertension was observed for 48 919 participants (27 005 men and 21 914 women). Women had a higher incidence of hypertension, based on the incidence densities of 45.82/1000 person-years among men and 53.57/1000 person-years among women.

T2
TABLE 2:
The incidence density of hypertension according to sex

Table 3 shows the incidence rates for hypertension according to various clinical factors. In both groups, elevated values for BMI, pulse pressure, and FBS were significantly associated with the development of hypertension (P < 0.001). Furthermore, a family history of hypertension and a personal history of diabetes mellitus were associated with the development of hypertension (P < 0.001). However, there was no significant difference according to a family history of diabetes mellitus. Higher household income was associated with a higher incidence of hypertension among men, whereas a lower household income was associated with a higher incidence of hypertension among women. Among men, a higher incidence of hypertension was associated with current nonsmoking, more frequent alcohol consumption, and more frequent exercise (P < 0.001). Among women, a higher incidence of hypertension was associated with current smoking and less frequent alcohol consumption (P < 0.001), although there was no difference according to exercise frequency (P = 0.84).

T3
TABLE 3:
The incidence rates for hypertension according to various clinical factors

Table 4 shows the results of the Cox proportional hazard analyses for risk of hypertension among men over the 12-year follow-up. Progression to hypertension among men was associated with BMI, total cholesterol, pulse pressure, ALT, household income, personal history of diabetes mellitus, family history of hypertension or diabetes mellitus, smoking status, and drinking frequency. Relative to a normal BMI (18.5–24.9 kg/m2), a high BMI (≥30 kg/m2) was the strongest predictor of hypertension (hazard ratio: 2.01, 95% CI 1.83–2.19), whereas a low BMI (<18.5 kg/m2) appeared to have a protective effect (hazard ratio 0.83, 95% CI 0.75–0.91). Other important risk factors for hypertension were a family history of hypertension (hazard ratio 1.44, 95% CI 1.37–1.52) and a personal history of diabetes mellitus (hazard ratio 1.50, 95% CI 1.44–1.56). However, progression to hypertension was not associated with a family history of diabetes mellitus (P = 0.82) or current smoking (P = 0.78). Additional risk factors for hypertension among men included high cholesterol levels (hazard ratio 1.17, 95% CI 1.13–1.22), high ALT levels (hazard ratio 1.22, 95% CI 1.17–1.28), and more frequent drinking (hazard ratio 1.17, 95% CI 1.14–1.20). A slightly lower risk of hypertension was observed in the high household income group (hazard ratio 0.94, 95% CI 0.90–0.98).

T4
TABLE 4:
Adjusted hazard ratios and 95% confidence intervals for the risk factors associated with progression to hypertension among men

Table 5 shows the results of the Cox proportional hazard analyses for risk of hypertension among women over the 12-year follow-up, which generally revealed similar risk factors relative to those among men. Notable differences were Hb levels being a risk factor among women, whereas smoking status and drinking frequency were not significant risk factors. Relative to normal Hb levels (12–15.5 g/dl), high Hb levels (≥15.5 g/dl) were associated with an increased risk of hypertension (hazard ratio 1.16, 95% CI 1.04–1.29). Similar to men, women with a high BMI (≥30 kg/m2) had an elevated risk of progression to hypertension (hazard ratio 1.73, 95% CI 1.60–1.87), whereas low BMI (<18.5 kg/m2) also appeared to have a protective effect (hazard ratio 0.82, 95% CI 0.73–0.91). Other important risk factors among women were a family history of hypertension (hazard ratio 1.40, 95% CI 1.33–1.48) and a personal history of diabetes mellitus (hazard ratio 1.30, 95% CI 1.24–1.36); however, a family history of diabetes mellitus was not a significant factor (P = 0.96). Among women, the risk of hypertension appeared to decrease at increasing household incomes (middle income hazard ratio 0.94, 95% CI 0.91–0.97; high-income hazard ratio 0.88, 95% CI 0.85–0.92). Among both men and women, the risk of progression to hypertension increased with increasing age (hazard ratio 1.05, 95% CI 1.03–10.5) and increasing pulse pressure (hazard ratio 1.06, 95% CI 1.01–1.11).

T5
TABLE 5:
Adjusted hazard ratios and 95% confidence intervals for the risk factors associated with progression to hypertension among women

DISCUSSION

This study aimed to investigate the incidence of progression from prehypertension to hypertension among middle-aged and elderly Korean individuals and to identify related risk factors using NHIS-HEALS data. To the best of our knowledge, this is the first Korean study to measure the incidence density of hypertension among middle-aged and elderly Korean adults (40–79 years old) with prehypertension. Among the 115 456 eligible individuals, we identified 48 919 participants (27 005 men and 21 914 women) with progression to hypertension during the 12-year follow-up period. Women had a higher incidence density of hypertension, which likely reflects the elevated risk of hypertension development among middle-aged and elderly women, relative to among men [16,17]. Women's SBP is lower at young ages and gradually rises to the point that older women have a higher SBP than older men [18]. Age is a well-known risk factor for hypertension [17,19,20], and the present study confirmed this relationship for both sexes, as a 1-year increase in age was associated with a 1.05-fold increase in the risk of progression from prehypertension to hypertension.

The present study revealed that the strongest risk factor for hypertension was elevated BMI (≥25 kg/m2). This finding agrees with results from previous studies, which revealed that prehypertension and hypertension were more common among overweight and obese people [8,21]. This study also revealed that underweight status (BMI < 18.5 kg/m2) was associated with a lower risk of hypertension. An Asian study [22] also demonstrated that underweight categories (BMI of 16.0–16.9 kg/m2 and 17.0–18.4 kg/m2) protected against the development of hypertension, which led to a recommendation that the optimal BMI for the Asian population was 18.5–23.0 kg/m2.

A higher pulse pressure was associated with an increased risk of hypertension in the present study. Higher pulse pressures are more likely to be observed in older individuals and in women, and are associated with a 57% higher risk of major cardiovascular events, relative to normal pulse pressures [23]. Furthermore, elevated cholesterol levels were associated with the risk of hypertension, and previous studies have also revealed similar findings [24,25]. This is likely because elevated cholesterol levels share a common pathophysiology with hypertension, which involves dysregulation of the release from adipose tissues function [26].

The present study revealed that development of hypertension was associated with a family history of hypertension and a personal history of diabetes mellitus. Previous studies have also indicated that a family history of hypertension was associated with hypertension [27], with an odds ratio of 1.39 (95% CI 1.22–1.59) for individuals with a family history of hypertension relative to those without [28]. A personal history of diabetes mellitus is also related to hypertension, which frequently coexist in the same patient [29–31]. Furthermore, the Epstein study revealed that, relative to individuals with optimal BP, the risk of developing diabetes was 27% higher among individuals with prehypertension and 50% higher among individuals with hypertension [32].

Current smoking status was not significantly associated with hypertension development among men in the present study. The link between smoking and hypertension remains unclear, as some studies have shown that even a low smoking rate can cause acute BP increases [33,34] and that hypertension was associated with chronic smoking [35,36]. However, other reports have indicated that BP and smoking are not related [37] or that smoking is inversely associated with hypertension [38,39]. Alcohol intake is positively correlated with BP, especially the amount of alcohol intake and the time elapsed since the last drink [40]. This study revealed differences in hypertension rates according to drinking frequency and sex, with more frequent drinking only being a risk factor among men.

Among women, elevated Hb levels were associated with an increased risk of hypertension. Similarly, a previous large cohort study revealed that Hb levels were positively associated with SBP and DBP among men and women [41]. However, it remains unclear how increased Hb levels might lead to elevated BP. Hemoglobin appears to be strongly related to arterial stiffness, based on pulse wave velocity measurements, which might explain its relationship with elevated SBP and DBP [42].

Study limitations and strengths

This study has several limitations. First, some potential risk factors were not considered because of missing data. For example, dietary patterns including a low-salt diet and the DASH diet (dietary approaches to stop hypertension) were not considered, and these diets are known to decrease the risk of hypertension development [19]. Previous studies have also indicated that high serum uric acid levels were significantly associated with an increased risk to develop hypertension [43,44]. However, it could not be included as a risk predictor for hypertension as the NHIS-HEALS data did not include the serum uric acid levels. Second, while the National Health Screening Program was performed at hospitals using standard measurement criteria, there may have been differences in the measurement times and BP meters. However, the Framework Act on the National Health Examination require health examination hospitals to complete quality assessments for BP measuring instruments every 3 years. Third, except for the United States (>130/80 mmHg), all guidelines, including International Society of Hypertension (ISH), Europe, Canada, Latin America, and Korea, define hypertension as greater than 140/90 mmHg. However, the criteria for prehypertension are slightly different. The prehypertension was defined as a SBP of 130–139 mmHg or a DBP of 80–89 mmHg in Korea, but the high normal BP was defined as a DBP of 130–139 mmHg or a DBP of 85–89 mmHg in Europe. Also, prehypertension of the International Society of Hypertension (ISH) is defined as the systolic 120–139 mmHg or a DBP of 80–89 mmHg [45,46]. Therefore, the results of hypertension incidence from the prehypertension may differ slightly.

This study also has several strengths. First, we used data from a large nationally representative cohort with a prolonged follow-up period, and identified a substantial number of validated hypertension cases. Second, we were able to perform a systematic analysis of factors influencing the progression to hypertension. Third, we were able to evaluate national medical insurance records, which was not possible in many previous studies. To the best of our knowledge, this is the first study to compare the risk factors for the development of hypertension according to sex, using a large Korean cohort of prehypertensive individuals with a 12-year follow-up.

In conclusion, among middle-aged and elderly Korean adults, the incidence densities of progression from prehypertension to hypertension were 45.82/1000 person-years among men and 53.57/1000 person-years among women. The strongest predictors of hypertension development were female sex, older age, higher BMI, family history of hypertension, and personal history of diabetes mellitus. These results indicate that individuals with prehypertension require lifestyle management and regular BP measurements to prevent progression to hypertension. In addition, public health services should focus on increasing public awareness and control of hypertension.

ACKNOWLEDGEMENTS

Conflicts of interest

There are no conflicts of interest.

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Keywords:

hypertension; incidence; Korea; prehypertension; risk factors

Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc.