Assessment of Prevalence, Awareness, and Characteristics of Isolated Systolic Hypertension Among Younger and Middle-Aged Adults in China

Key Points Question What are the characteristics of young and middle-aged adults with isolated systolic hypertension in China, and what is the prevalence and awareness of isolated systolic hypertension among this population? Findings In this cross-sectional study of young and middle-aged adults in China, isolated systolic hypertension was identified in 27% of participants with hypertension, 87% of whom had not received treatment; less than 7% of individuals with untreated isolated systolic hypertension were aware of having hypertension. Among individuals with isolated systolic hypertension, 16% had systolic blood pressure of 160 mm Hg or higher, but awareness rates remained low even in this group. Meaning In this study, a substantial proportion of young and middle-aged adults with hypertension had isolated systolic hypertension; there is an opportunity to improve awareness of isolated systolic hypertension among this population.


Introduction
Isolated systolic hypertension (ISH), a subtype of hypertension, is experienced by more than 40% of adults with untreated hypertension. [1][2][3] Among those who do receive treatment, control of systolic blood pressure (SBP) is particularly challenging compared with control of diastolic blood pressure (DBP), making ISH the most common subtype of hypertension among patients with uncontrolled hypertension. [4][5][6][7] Isolated systolic hypertension is a well-studied condition that has received attention across various hypertension guidelines. However, ISH is disproportionately found in older adults, and many of the disease management recommendations are based on studies and data of older individuals. 1,[8][9][10][11][12][13] Young and middle-aged adults are experiencing an increasing prevalence of ISH, [14][15][16] which can increase their risk of heart disease and stroke. 17 Younger individuals with ISH may have distinct characteristics that require exploration given that the pathophysiologic characteristics of ISH may differ from those of older individuals (eg, aortic stiffness in older adults and increased cardiac output or stroke volume in younger adults), which can have implications for disease management. 18 However, most previous studies of ISH have focused on older individuals (>50 years), 1,19 and the few studies of younger individuals with ISH in China have only provided information regarding the overall prevalence of ISH in this population. 16 Thus we lack a comprehensive understanding of the prevalence, awareness, and characteristics of young and middle-aged individuals with ISH in the Chinese population and how these factors may vary across diverse subgroups of the population.

The China Patient-Centered Evaluative Assessment of Cardiac Events Million Persons Project
(China PEACE MPP), a large-scale population-based screening project, provided a suitable platform to examine ISH among young and middle-aged adults given the project's large data set (N = 3 094 655) and recruitment of participants at the community level. We performed a crosssectional study of young and middle-aged participants from the China-PEACE MPP to describe the prevalence, awareness, and individual characteristics of ISH among this population.

Study Design and Population
Details of the design of the China PEACE MPP have been described previously. 20 In brief, between December 15, 2014, and May 15, 2019, 244 sites (146 rural counties and 98 urban districts) were selected by a convenience sampling strategy from county-level geographic regions in 31 provinces of mainland China. Participants were enrolled in the China PEACE MPP if they were aged 35 to 75 years and had a Hukou (an official record that identifies area residents) for a region selected for the study.
Participants were recruited through publicity campaigns in the media and by mail. The study was approved by the central ethics committee of the China National Center for Cardiovascular Disease and the institutional review board of Yale University. All enrolled participants provided written informed consent. This study was reported in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline for cross-sectional studies. 21 Of the 3 094 655 participants enrolled in the China PEACE MPP during the study period, 899 128 young and middle-aged adults (29.1%) between ages 35 and 49 years were selected for the present cross-sectional study. We excluded 129 participants who were missing data for age and 70 participants who were missing data for blood pressure (BP) or who had BP levels that were extremely high or low (ie, SBP levels <70 mm Hg or >270 mm Hg and DBP levels <30 mm Hg or >150 mm Hg) (eFigure in the Supplement). After exclusions, the final sample comprised 898 929 young and middle-aged adults. Participants with missing data on covariates (including geographic region of residence, educational level, employment status, occupation, marital status, household income, current smoking status, and current alcohol use) were analyzed as a separate subgroup that was categorized as unknown.

JAMA Network Open | Cardiology
Prevalence, Awareness, and Characteristics of ISH in Younger and Middle-Aged Adults in China

Data Collection and Variables
Blood pressure was measured twice (after 5 minutes of quiet rest in a seated position at an interval of 1 minute) on each participant's upper right arm using an electronic BP monitor (Omron HEM-7430; Omron Corp); measurement was performed by trained staff according to a standard operating procedure (eMethods in the Supplement). Participants were advised to stop smoking 15 minutes before the BP measurement and to turn off their mobile phones during the BP measurement. Both of the BP values and their means were recorded. If the difference between the two SBP measurements was greater than 10 mm Hg, a third BP measurement was performed; in such cases, the mean SBP and DBP were calculated using the last 2 measurements. The mean SBP and DBP values were used for all analyses.
Information on the receipt of antihypertensive, hypoglycemic, hypolipidemic, and antiplatelet medications within the past 2 weeks was collected during an in-person interview. Data regarding the participants' sociodemographic characteristics, health behaviors, medical histories, and cardiovascular risk factors were also recorded during these in-person interviews. Height and weight were measured according to standard protocols, and body mass index was calculated as weight in kilograms divided by height in meters squared.
Because this study was performed in a Chinese cohort, we used the Chinese Guidelines for the Management of Hypertension 22 to define hypertension and classify different hypertension subtypes. Hypertension was defined as a self-reported previous diagnosis of hypertension or receipt of antihypertensive medication in the past 2 weeks or as a mean SBP level of 140 mm Hg or higher or a mean DBP level of 90 mm Hg or higher at the screening visit. Isolated systolic hypertension was defined as a mean SBP level of 140 mm Hg or higher and a mean DBP level of less than 90 mm Hg.
Isolated diastolic hypertension (IDH) was defined as a mean SBP level of less than 140 mm Hg and a mean DBP level of 90 mm Hg or higher, and systolic-diastolic hypertension (SDH) was defined as a mean SBP level of 140 mm Hg or higher and a mean DBP level of 90 mm Hg or higher, regardless of the participant's treatment status. Controlled hypertension was defined as a self-reported previous diagnosis of hypertension or receipt of antihypertensive medication and an SBP level of less than 140 mm Hg and a DBP level of less than 90 mm Hg. Participants who did not have a history of receiving antihypertensive medication and who had an SBP level of less than 140 mm Hg and a DBP level of less than 90 mm Hg were defined as having normotension.
Participants were considered to be aware of having hypertension if they responded yes to the question, "Have you ever been diagnosed with hypertension?" Participants were considered to have received treatment for hypertension if they reported receiving an antihypertensive medication (including western or traditional Chinese medications) currently or within the last 2 weeks. Obesity was defined as a body mass index of 28 kg/m 2 or higher, which was in accordance with the recommendations of the Working Group on Obesity in China. 23

Statistical Analysis
We estimated the prevalence of ISH among the overall study participants and among those with hypertension, and we compared their characteristics with individuals who had other hypertension subtypes. We also described the distribution of SBP levels among men and women with ISH across different age groups. Next, we assessed the awareness of having hypertension by sex and SBP level among individuals with ISH who had not received treatment. We then developed multivariable generalized linear mixed models with a logit link function and township-specific random intercepts (to control for geographic autocorrelation) to identify individual characteristics that were independently associated with ISH prevalence and awareness. We compared participants with ISH with those with normotension, IDH, and SDH using separate models. Explanatory variables included participants' age, sex, marital status, annual household income, educational level, health insurance status, geographic region of residence, current smoking status, current alcohol use, obesity, physician-diagnosed diabetes, and previous cardiovascular events (myocardial infarction or stroke).
All analyses were conducted using R software, version 3.33 (R Foundation for Statistical Computing), and SAS software, version 9.4 (SAS Institute), with P < .05 considered statistically significant. Data were analyzed from May to November 2019.

Results
Among 898 929 young and middle-aged adults included in the final sample, the mean (SD) age was 43.8 (3.9) years; 548 657 participants (61.0%) were women, and 235 138 participants (26.2%) had hypertension ( Table 1). A total of 62 819 participants (26.7% of those with hypertension, or 7.0% of the total sample) had ISH, and 172 319 participants (73.3% of those with hypertension, or 19.2% of the total sample) had other types of hypertension ( Table 2). Among those with other types of hypertension, 35 448 individuals (20.6%, or 3.9% of the total sample) had IDH, 116 682 individuals (67.7%, or 13.0% of the total sample) had SDH, and 20 189 individuals (11.7%, or 2.2% of the total sample) had controlled hypertension. Based on age and sex standardization of our results compared with data from all of the 31 provinces included in the 2010 Chinese census, the prevalence of overall hypertension and ISH among young and middle-aged adults was 24.0% and 7.0%, respectively. In our multivariable analysis, when compared with participants with normotension, participants who were female, were older, were obese, currently used alcohol, had lower annual household income and lower educational levels, did not have health insurance, had a history of diabetes or cardiovascular events, and resided in eastern or central regions had a greater likelihood of ISH; however, marital status was not a substantial factor ( Table 3). When compared with participants with IDH and SDH, participants with ISH were more likely to be older, be female, and reside in central or eastern regions but were less likely to have higher household income, educational levels of college or higher, previous cardiovascular events, and obesity and to currently smoke and use alcohol.   . Although awareness rates increased with age, they remained low among both sexes even after stratification by SBP level (Figure 2). For example, among individuals with an SBP level of 160 mm Hg or higher, awareness rates were 7.8% for men and 7.4% for women aged 35 to 39 years, and awareness rates were 13.3% for men and 15.4% for women aged 45 to 49 years.

Awareness
In our multivariable analysis, older age, female sex, and the presence of cardiovascular risk factors (such as current smoking and alcohol use, obesity, history of diabetes, and previous cardiovascular events) remained significant factors associated with the awareness of having hypertension (Table 3). However, marital status, educational level, health insurance status, and geographic region were not substantial factors.

Discussion
In this large population-based cross-sectional study, we found that ISH was present in approximately 1 of 4 young and middle-aged adults (26.7%) with hypertension in China, most of whom (86.7%) had not received treatment; only 6.8% of those who had not received treatment were aware of having hypertension. In addition, approximately 1 in 6 individuals (15.5%) with untreated ISH had an SBP level of 160 mm Hg or higher; however, awareness rates remained low (Յ15.4%) in this group.
Moreover, even among individuals with 1 or more cardiovascular risk factors and a history of cardiovascular events, approximately 90% and 75% of individuals with ISH, respectively, remained unaware of having hypertension.  Our study expands the existing literature on ISH in several ways. First, to our knowledge, our study is one of the largest to describe the current prevalence and characteristics of young and middle-aged adults with ISH in China, which allowed us to explore associations across a variety of diverse subgroups. We found that ISH was present in 26.7% of young and middle-aged adults with hypertension in China, which is consistent with the previously reported prevalence among cohorts from non-Chinese populations. 2,3,9,24 Young and middle-aged adults with ISH in China were more likely to be older, female, and obese and to currently use alcohol, have diabetes, and have a history of previous cardiovascular events compared with those with normotension, which is consistent with the associations previously reported in the literature for non-Chinese populations, particularly from studies in the US and Europe. 3,8,9,24,25 In addition, we found that young and middle-aged adults with ISH were more likely to have lower socioeconomic status and reside in the central or eastern regions of China than individuals with normotension, which, to our knowledge, has not been previously reported. These factors may be associated with the participants' health care access, motivation to make healthy lifestyle choices, adherence to preventive health guidelines, and management of comorbidities associated with hypertension. 26 Second, our study is the first, to our knowledge, to describe the awareness of having hypertension among young and middle-aged adults with ISH in a contemporary Chinese population. We found that only 6.8% of untreated individuals with ISH were aware of having hypertension, and awareness rates remained low even among those with high SBP levels (Յ15.4% among adults with SBPՆ160 mm Hg) or a history of previous cardiovascular events (Յ25.4%). These awareness rates are substantially lower than those for the overall population of individuals with hypertension in China (44.7%). 27 Younger adults are more difficult to reach through traditional clinic-based preventive programs because they may be less aware of the long-term benefits of early control of cardiovascular risk factors and therefore less likely to be in contact with the health system and less motivated to make lifestyle changes. [28][29][30] In addition, given that the clinical importance of the treatment of ISH in younger adults has been questioned in the past 31,32 and that most previous studies of ISH have focused on older individuals, there are currently no recommendations for the management of ISH in younger adults. 22,24,33 Thus our findings may be a reflection of the lack of clinical data in this population, and they highlight the need for clinical trials among this population.

Limitations
This study has several limitations. First, patients who received treatment for ISH and decreased their SBP level to less than 140 mm Hg were classified as having controlled hypertension, which could have underestimated the burden of ISH in China. However, very few individuals who originally had ISH would have been classified as having controlled hypertension given the low hypertension treatment rates, and the even lower control rates, in China. Second, some individuals with hypertension could have experienced a preferential improvement in their DBP levels and may have been included in the ISH group, leading to overestimation of the rates for ISH. However, overestimation is unlikely to have been a substantial factor, as most individuals (86.7%) in the ISH group had not received treatment. Third, our current study design did not permit us to examine ISH in adults younger than 35 years. Fourth, because the China PEACE MPP is a large-scale populationbased screening project, BP was only measured at a single visit. Considering the effect of regression to the mean, we may have overestimated the prevalence of hypertension and ISH. However, the effect of regression to the mean should not be substantial. Fifth, we used a convenience sample rather than a nationally representative sample for large-scale recruitment, which may have limited the generalizability of our findings to China despite their consistency with the age-and sex-standardized prevalence of ISH in the 2010 Chinese census data. Additionally, inclusion of this sample could have resulted in overestimation of the awareness and treatment rates because these participants would have been more likely to have contact with the health system.

Conclusions
In this large population-based cross-sectional study, we found that ISH was present in approximately 30% of young and middle-aged adults with hypertension in China, most of whom remained unaware of having hypertension. These results highlight the increasing need for improved awareness of ISH in this population and the need for better evidence-based guidance for the management of ISH among younger individuals.