Risk of heart disease and stroke among individuals with prehypertension or blood pressure progression: a national population-based cohort study

Abstract

Introduction

Cardiovascular disease (CVD) is a spectrum of disorders that affect the heart and blood vessels and caused 3.72 million deaths in 2013 [1–3]. High blood pressure is closely related to the risk of CVD, and there is a linear, and continuous association between blood pressure and cardiovascular risk [4–7]. The Prospective Studies Collaboration [4] indicated that the death risk of CVD increased steadily with increasing SBP and DBP at baseline(above a usual SBP of 115 mmHg and DBP of 75 mmHg).

The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) [8] defined prehypertension as subjects with SBP from 120 to 139 mmHg or DBP from 80 to 89 mmHg. Prehypertension has been considered to be associated with the risk of CVD [9].

In one study [10] including 5181 persons from the Framingham cohort found that prehypertension was closely related to the risk of myocardial infarction (MI) [relative risk (RR) (95% CI): 3.5 (1.6–7.5)]. A previous study [11] including 60 785 women also confirmed the positive relationship between prehypertension and cardiovascular outcomes, with adjusted hazard ratios of 1.76 (95% CI: 1.40–2.22) for MI and 1.93 (95% CI: 1.49–2.50) for stroke compared with normotensive women. However, rare studies have investigated blood pressure progression with the risk of cardiovascular events in the general Chinese population. The purpose of our study was to explore the relationship of CVD risk with prehypertension in subjects with or without progression to hypertension in a national population-based cohort study.

Method

Results

Table ​Table11 shows the baseline characteristics of the 10 122 individuals. A total of 1972 participants developed composite outcome within a mean observation period of 6.5 years, including 1505 heart disease, 631 stroke, and 164 heart disease and stroke multimorbidity. At baseline, 3557 (35.14%) of the study participants had normotension, 2857 (28.23%) had prehypertension, and 3708 (36.63%) had hypertension. At baseline, age, BMI and the prevalence rate of diabetes and dyslipidemia increased with blood pressure category.

Blood pressure category with heart disease or stroke

The association of blood pressure category with composite outcome is displayed in Table ​Table22 and Figure S1 in Supplement materials, supplemental digital content 1, http://links.lww.com/BPMJ/A216. In model 1, compared with individuals with normotension at baseline, the fully adjusted HR (95% CI) were 1.29 (1.13–1.46) and 2.15 (1.93–2.40) for composite outcome in individuals with prehypertension and hypertension at baseline, respectively. In model 2, compared with individuals with normotension at baseline, the fully adjusted HR (95% CI) were 1.26 (1.11–1.43) and 1.95 (1.74–2.18) for composite outcome in individuals with prehypertension and hypertension at baseline, respectively. In model 3, compared with individuals with normotension at baseline, the fully adjusted HR (95% CI) were 1.25 (1.10–1.42) and 1.52 (1.34–1.74) for composite outcome in individuals with prehypertension and hypertension at baseline, respectively. We also observed a significant positive trend in categorized blood pressure for incident composite outcome [HR (95% CI): 1.23 (1.16–1.32), P for trend <0.001]. However, in subgroup analysis, limited number of cases in different age groups may lead to unstable estimation for the association between blood pressure category and composite outcome(Fig. ​outcome(Fig.1).1). In model 3, prehypertension was closely related to the risk of stroke [HR (95% CI): 1.41 (1.10–1.81)] and heart disease, respectively [HR (95% CI): 1.19 (1.03–1.38)]. In subgroup analysis, prehypertension was more strongly associated with composite outcome among individuals aged 45–50 years and with history of diabetes (Fig. ​(Fig.11).

Table 2

Risk of heart disease or stroke according to blood pressure category

Baseline blood pressure category	Model 1		Model 2		Model 3
	HR (95% CI)	P	HR (95% CI)	P-value	HR (95% CI)	P-value
Composite outcome
Normotension	1.00		1.00		1.00
Prehypertension	1.29 (1.13–1.46)	< 0.001	1.26 (1.11–1.43)	< 0.001	1.25 (1.10–1.42)	0.001
Hypertension	2.15 (1.93–2.40)	< 0.001	1.95 (1.74–2.18)	< 0.001	1.52 (1.34–1.74)	< 0.001
P for trend	1.49 (1.41–1.57)	< 0.001	1.41 (1.33–1.49)	< 0.001	1.23 (1.16–1.32)	< 0.001
stroke
Normotension	1.00		1.00		1.00
Prehypertension	1.52 (1.20–1.94)	0.001	1.44 (1.13–1.84)	0.003	1.41 (1.10–1.81)	0.006
Hypertension	3.04 (2.47–3.75)	< 0.001	2.70 (2.18–3.33)	< 0.001	2.15 (1.69–2.73)	< 0.001
P for trend	1.78 (1.61–1.97)	< 0.001	1.67 (1.51–1.86)	< 0.001	1.47 (1.31–1.66)	< 0.001
heart disease
Normotension	1.00		1.00		1.00
Prehypertension	1.21 (1.05–1.40)	0.010	1.20 (1.04–1.38)	0.015	1.19 (1.03–1.38)	0.018
Hypertension	2.00 (1.77–2.27)	< 0.001	1.83 (1.61–2.08)	< 0.001	1.41 (1.21–1.63)	< 0.001
P for trend	1.44 (1.35–1.53)	< 0.001	1.37 (1.28–1.46)	< 0.001	1.19 (1.10–1.28)	< 0.001

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Model 1 crude model. Model 2 adjusted for age and sex. Model 3 adjusted for age, sex, education level, dyslipidemia, BMI, antihypertensive drugs, smoking status, drinking status, diabetes, and site.

CI, confidence interval; HR, hazard ratio.

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Fig. 1

Subgroup analysis for the association of blood pressure category with composite outcome. All models were adjusted for age, sex, BMI, education level, dyslipidemia, antihypertensive drugs, smoking status, drinking status, diabetes, and site. Red box indicated normotension vs. prehypertension, while the blue box indicated normotension vs. hypertension. HBP, hypertension; preHBP, prehypertension.

Discussion

In this research of 10 122 participants accruing 1972 heart disease or stroke during 6.5 years of the mean observation period, blood pressure category was closely related to the risk of CVDs in fully adjusted models. Individuals with prehypertension at baseline had an increased risk of developing heart disease or stroke compared to those with normal blood pressure. Moreover, among the subjects who had normotension at baseline, those who progressed to high blood pressure during the first 48 months had a 1.58 times higher risk of heart disease or stroke than those who remained in the normal blood pressure range (Tables ​(Tables22 and ​and33).

Previous research also reported a similar relationship between prehypertension levels of blood pressure and cardiovascular risk. Findings from the Women’s Health Initiative [9] suggested that compared with normotensive women, the adjusted HR (95% CI) of any cardiovascular event for women with prehypertension was 1.66 (1.44–1.92). Yet, only female participants were included in the study and their results cannot be generalized to all populations. In one analysis from the Framingham cohort [10], men and women with baseline prehypertension appear to be associated with an increased risk of MI [RR (95% CI): 3.5 (1.6–7.5)] compared with those with normotension at baseline. In another analysis from the Framingham cohort [9], individuals with SBP 130–139 mmHg or DBP 85–89 mmHg have a 1.6 and 2.5 times risk of fatal and nonfatal cardiovascular events than those with blood pressure at or below 120/80 mmHg. Moreover, a meta-analysis [4] involving 61 prospective studies has also confirmed that blood pressure was associated with cardiovascular mortality, across the whole range of blood pressure, including blood pressure in the prehypertension range. What is more, when the HR drops due to confounding variables in different models, the association of these contributing factors and outcomes is getting closer to the underlying true HR (Table ​(Table2).2). The difference in these associations needs to be demonstrated in further experiments.

In contrast to the previous studies, we focused our attention on the association of blood pressure progression with heart disease or stroke. We found that subjects who progressed to hypertension during the first 48 months had an increased risk of heart disease or stroke than those who did not progress to hypertension. The risk of heart disease or stroke in the subjects whose blood pressure progressed from prehypertension to hypertension was significantly higher than in those who remained free of hypertension (Table ​(Table3).3). In one cohort study with 2227 Japanese participants [14], the individuals who progressed from prehypertension to hypertension had 2.95 times higher risk of cardiovascular events than those who remained at normal blood pressure or prehypertension in a fully adjusted model. However, the number of cardiovascular events in this study was small, limiting its evaluation ability. Another prospective cohort study [15] in the USA including 39 322 women found that women who progressed to high blood pressure had a higher rate of cardiovascular events during follow-up than women who were normotensive at baseline. However, this research only included female participants, which limited its generalized ability. Generally, these results indicate that individuals free of hypertension at baseline could have an increased risk of cardiovascular events after their blood pressure progressed to hypertension during the follow-up period.

Several researchers have attempted to clarify markers of blood pressure progression. Results from the Strong Heart Study [16] suggested that higher left ventricular mass, stroke volume, prevalent diabetes and baseline SBP could predict the progression to hypertension in 38% of prehypertension subjects. Erdogan et al. [17] performed a prospective study and showed that the HDL-C level, baseline SBP, metabolic syndrome, a reflection of coronary microvascular function, and presence of microalbuminuria were significant independent markers to identify individuals with prehypertension to incident hypertension.

Generally, the results of this and other research suggest that prevention and reversal of blood pressure progression to reduce heart disease or stroke should be focused on people with prehypertension. Several interventions are beneficial in this population. Sodium reduction, previously shown to lower blood pressure, may also reduce the long-term risk of cardiovascular events in prehypertension subjects [18]. Aerobic exercise was shown to be a necessary component of lifestyle modification for the prevention and treatment of hypertension [19]. Dietary intervention was effective in preventing and treating hypertension [20].

For subgroup analysis (Fig. ​(Fig.1),1), prehypertension was more closely related to the risk of heart disease or stroke in individuals aged 45–50 years than in those aged 50 years and above. Other prospective research demonstrated that the relation between blood pressure and heart disease or stroke becomes less strong with age, although it remains strong and direct even in the oldest age groups [5,6]. In addition, participants at baseline with a history of diabetes were more associated with the risk of heart disease or stroke than those without diabetes. Recent studies have also shown that diabetic patients with mildly elevated blood pressure had higher risk of cardiovascular events compared with non-diabetic patients with similar blood pressure levels [21]. The reason for increased susceptibility to cardiovascular events among people with diabetes is not fully understood.

Our research has several methodological limitations. First, changes in blood pressure and other confounders over time were not considered. Further studies with detailed analysis would take repeated measures to better explain the potential changes. Second, the competing risk of individuals dying before they could develop heart disease and stroke was not considered in our research. Finally, some other risk factors (such as physical exercise and dietary patterns) are closely related to the risk of heart disease or stroke, we did not adjust for those potential confounders in the present models due to the lack of enough information.

Acknowledgements

We acknowledge CHARLS database for providing their platforms and contributors for uploading their meaningful datasets.

QJ and YC conceptualized and designed the study, carried out the initial analyses, drafted the initial article, and reviewed and revised the article.

Ethics approval and consent to participate: This research uses data from the China Health and Retirement Longitudinal Study (CHARLS). The CHARLS was approved by the Biomedical Ethics Review Committee of Peking University and all participants provided written informed consent.

Data from the China Health and Retirement Longitudinal Study was used in this study, which can be downloaded at https://charls.charlsdata.com/pages/data/111/zh-cn.html.

Supplementary Material

Footnotes

References