Table of Contents
ORIGINAL ARTICLE
Year : 2020  |  Volume : 5  |  Issue : 4  |  Page : 186-193

The impact of hypertension on left ventricular diastolic dysfunction and arterial stiffness in the elderly: A cross-sectional study


1 Department of Cardiology, Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University, Shanghai, China
2 Department of Cardiology, Shanghai Institute of Cardiovascular Disease, Zhongshan Hospital, Fudan University, Shanghai, China

Date of Submission17-Apr-2020
Date of Acceptance12-Aug-2020
Date of Web Publication30-Dec-2020

Correspondence Address:
Jun-Bo Ge
Department of Cardiology, Shanghai Institute of Cardiovascular Disease, Zhongshan Hospital, Fudan University, Shanghai
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2470-7511.305416

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  Abstract 


Objectives: To study the prevalence of LVDD and arterial stiffness and the association with LVDD and/or arterial stiffness among residents with HTN, as well as determine whether aging was independently correlated with LVDD and arterial stiffness. This was a cross-sectional study, using results from the Shanghai Heart Health study, a national project in China. Methods: Using data from 2086 participants, we explored the associations of HTN and LVDD with or without arterial stiffness using brachial–ankle pulse wave velocity (baPWV). Correlations of LVDD with or without arterial stiffness were analyzed in adjusted multivariable logistic models. Results: The proportion of subjects with LVDD was 37.5%, arterial stiffness was 47.5%, and HTN was 58.4%. LVDD in participants with arterial stiffness occurred in 55.2% and HTN in 65.9%. Pairwise comparisons showed that systolic blood pressure was significantly different and more strongly associated with HTN (68%) (P < 0.01). For subjects with normal diastolic function of normal baPWV or LVDD with increased value of baPWV, logistic multivariate regression showed that aging (odds ratio [OR]: 1.05, 95% confidence interval [CI]: 1.04–1.81) and HTN (OR: 1.45, 95% CI: 1.08–1.93) were independent correlates of LVDD with arterial stiffness. Conclusions: The prevalence of arterial stiffness increases in the early stages of LVDD. HTN and aging were independently related to LVDD with arterial stiffness among community-dwelling residents.

Keywords: Aged; Arterial stiffness; Diastolic function


How to cite this article:
Abudureyimu M, Zhou JM, Jin XJ, Cui XT, Hu K, Ge JB. The impact of hypertension on left ventricular diastolic dysfunction and arterial stiffness in the elderly: A cross-sectional study. Cardiol Plus 2020;5:186-93

How to cite this URL:
Abudureyimu M, Zhou JM, Jin XJ, Cui XT, Hu K, Ge JB. The impact of hypertension on left ventricular diastolic dysfunction and arterial stiffness in the elderly: A cross-sectional study. Cardiol Plus [serial online] 2020 [cited 2021 Jan 25];5:186-93. Available from: https://www.cardiologyplus.org/text.asp?2020/5/4/186/305416




  Introduction Top


Left ventricular (LV) diastolic dysfunction (LVDD) is one of the main pathophysiologic mechanisms and essential diagnostic indexes of heart failure (HF).[1] The prevalence of LVDD is high in the elderly,[2] with age being an independent risk factor for cardiovascular diseases.[3]

Recent studies also found that severity of LVDD was associated with arterial stiffness. Because of aging, large arteries show declined compliance first, mainly affecting the intima. This results in vessel expansion and arterial stiffness.[4] Arterial elasticity decline is due to several cardiovascular risk factors; however, it also results from early changes of vascular damage.[5],[6] Pulse wave velocity (PWV) is a noninvasive, convenient method to measure arterial stiffness in early stages.[7],[8] Brachial–ankle PWV (baPWV) has been widely used and was confirmed to be closely associated with cardiovascular events. Compared with femoral artery PWV, baPWV is more representative.[9],[10]

This study investigated the prevalence of LVDD and arterial stiffness in elderly residents and revealed the association with LVDD and/or arterial stiffness among residents with several cardiovascular risk factors.


  Methods Top


Population and study design

The study was part of a national project and the Shanghai Heart Health Study (SHHS). Subjects from the community of Jinshan District aged 65 years and over were recruited from May 2015 to December 2016. All subjects provided general information, serum biochemical parameters, standard 12-lead electrocardiogram, and echocardiography (ECG) examination. General information involved a questionnaire interview and physical examination. The questionnaire was administered by community doctors in face-to-face interviews and included cardiovascular disease history and lifestyle behaviors. The cardiovascular diseases included hypertension (HTN), dyslipidemia, diabetes, paroxysmal and permanent atrial fibrillation (AF), coronary heart disease (CHD), and smoking history.

The sample size consisted of 2484 participants. We excluded those missing a majority of the data, baPWV data, or echocardiographic data. Ultimately, 2086 of the participants were included in the current analysis, during the follow-up study in 2015. Those without complete biochemical, baPWV, or echocardiographic data were excluded. Exclusion criteria were poor ultrasound imaging, valvar heart disease, valve replacement, and tachycardia that prevented obtaining a mitral flow pattern. All patients gave informed consent to participate.

Demographic, clinical, and biochemical parameters

Demographic and clinical data were obtained from questionnaires. Doctors recorded data from physical examinations including age, sex, cardiovascular disease history, and current smoking status. The physical examination included body weight, height, waist circumference, and blood pressure (BP). BP was measured at the right arm with the manual mercury sphygmomanometer after 5-min rest. BP was measured twice, and the average was used for analysis.

Echocardiographic assessment of cardiac structure and function

ECG used a combination of two-dimensional and Doppler imaging to assess LV diastolic function, as recommended by the updated American Society of Echocardiography guidelines. Subjects were placed in the left lateral position, allowed to breathe calmly, and subjected to ECG. ECG was performed for all subjects by two experienced sonographers, in a blinded manner, using color transthoracic ECG with a 2–4 Hz probe (German Philip IE33, s5-1 probe) according to the standardized protocol. Measurements were made online and recorded digitally with the participant's study number as the only identification. Echo imaging included three cardiac cycles and were kept for off-line digital analysis. M-mode echocardiograms of the LV were recorded from the parasternal long-axis view. Two-dimensional and Doppler images were recorded for the long and short axes in the parasternal and apical four- and two-chamber views. The mitral valve inflow, papillary muscle, and horizontal left ventricle from the short axis were assessed. The standard apical four- and two-chamber showed the left atrium completely, insuring that the dynamic images were clear. The sample volume placed at the long axis of the left ventricle was recorded using M-mode ultrasonography. The sample volume was placed at the middle of opening mitral valve from the four-chamber axis. The velocities of peak early (MV-E, cm) and late (MV-A, cm) diastolic phase were recorded using tissue Doppler imaging (TDI) from the tip of the mitral valve in the apical 4-chamber view. LV end-diastolic diameter (LVEDD), LV end-systolic diameter, interventricular septal thickness (IVST), and posterior wall thickness (PWT) were measured using M-mode ECG from the parasternal long-axis view. LV mass (grams) was calculated as 0.8 × 1.04 ([LVEDD + IVST + PWT]3 + LVEDD3) +0.6 according to Bang et al.[11] LV mass index (LVMI) was derived as LVM divided by body surface area (BSA). LV ejection fraction (LVEF) was obtained from LV end-systolic volume and LV end-diastolic volume measured from the apical 4- and 2-chamber views (Simpson's method). Left atrial (LA) volume was measured and indexed to BSA as the LA volume index (LAVI).

Tissue Doppler E′ (cm/s) velocity was measured from the apical four-chamber view with a pulsed-wave sample volume placed at the lateral and septal regions of the LV. From both mitral inflow pattern and tissue Doppler, the mitral E/E' ratio could be calculated. The sample volume was placed on the right upper pulmonary vein, and the flow velocity of the pulmonary vein was recorded.[12],[13]

Assessment of brachial–ankle pulse wave velocity

All subjects underwent baPWV test using an automatic wave form analyzer (VP1000, Colin Medical Technology, Komaki, Japan). First, subjects were in the supine position and resting for 5 min. Next, this device documented the data of wave forms about both ankles and the arm connecting with an automatic synchronization electrocardiograph. The time interval was defined as delta T, which measured between the wave fronts of the brachial and ankle wave forms automatically. The path lengths from the suprasternal notch to the elbow (La) and also from the suprasternal notch to the ankle (Lb) were calculated based on patient height. Then, the value of baPWV (cm/s) was calculated as Lb–La divided by △T, and the averages of the left and right baPWV were obtained for the data analysis. According to the cohort study by Munakata et al., including Japanese and other correlational studies, arterial stiffness was defined in this study as baPWV ≥1750 cm/s.[9],[14]

Definitions of cardiovascular disease

HTN was defined as systolic BP (SBP) ≥140 mmHg or diastolic BP (DBP) ≥90 mmHg at rest or self-reported use of antihypertensive medication with normal BP. Body mass index (BMI) was calculated as weight (kg)/height (m)2. BSA was derived as 0.0061 × height (cm) + 0.0128 × weight (kg) – 0.1529. Obesity was defined as BMI ≥28 kg/m2. Dyslipidemia was defined as a history or any of the following: total cholesterol (TC) ≥6.22 mmol/L, triglyceride (TG) levels ≥2.26 mmol/L, low-density lipoprotein cholesterol (LDL-C) ≥4.14 mmol/L, and high-density lipoprotein cholesterol (HDL-C) <1.04 mmol/L. CHD was defined as a history of confirmed angiography coronary stenosis >70%, angina pectoris, or myocardial infarction. Diabetes mellitus was defined by fasting blood glucose (FBG) ≥7 mmol/L or a disease history. AF was defined by a past history or a 12-lead electrocardiogram (including paroxysmal or persistent AF).

Lifestyle behavioral definitions

Smoking was defined as at least the use of three cigarettes a day for at least 1 year. Quitting smoking was defined as no smoking for more than 2 years. Due to the low proportion of quitters in the current study, quitters and smokers were combined into the smoking group for analysis.

Laboratory examination

Venous blood samples were obtained after a 12-h overnight fast. To ensure the quality of these samples, they were transferred to the central laboratory of Zhongshan Hospital daily. The sera were preserved at −28°C until measurement of N-terminal pro-B type natriuretic peptide (NT-pro BNP) using automated electrochemiluminescence sandwich immunoassay (onanElecsys 1010, Roche Diagnostics, Basel, Switzerland) after centrifugation and routine blood testing.

Criteria for diagnosis of left ventricular diastolic dysfunction

The HF and ECG Association of the European Society of Cardiology (ESC) recommended adopting both conventional and TDI ECG techniques to diagnose LVDD. In the present study, the LVDD diagnosis was made according to the criteria proposed by ESC.[15] We also referred to the study by Zhou et al. with minor modifications.[16] LVDD was considered to be present if any of the following criteria were met:(1) E/E' ≥8; (2) E/A <0.5 and DT >280 ms; (3) LVMI >149 g/m2 (male) or LVMI >122 g/m2 (female); or (4) LAVI >34 ml/m2.[17]

Classification of four groups

According to the LVDD status (presence or absence) and baPWV levels (higher or normal), the subjects were divided into four groups: (1) no LVDD and normal baPWV; (2) presence of LVDD and normal baPWV; (3) no LVDD and increased baPWV; and (4) presence of LVDD and increased baPWV.

Statistical analysis

All analyses were performed using Stata version 12.0 (College Station, TX, USA). Continuous data were presented as mean ± standard deviation, and differences between groups were compared using the t-test. Categorical data were presented as frequency. The prevalence among various groups was compared using the corrected Chi-square test. Participants were divided into four groups according to LV diastolic function and level of baPWV. Group comparisons were performed using one–way ANOVA or the Kruskal–Wallis test for continuous variables and Pearson's Chi-square test for categorical variables. Pairwise comparisons used the Wilcoxon rank-sum test for continuous variables. The Bonferroni test was used for the interactions between two groups. Variables with P <0.1 in baseline characteristic comparisons were entered into a logistic univariate regression analysis model, and variables with P ≤ 0.1 were continuously entered into stepwise logistic multivariate regression analysis to determine independent factors associated with LVDD and arterial stiffness. P < 0.05 was considered to indicate statistical significance.


  Results Top


Baseline characteristics of the study population

A total of 2484 residents participated in the SHHS and provided signed informed consent. All underwent ECG and sequential PWV assessments. Of these, subjects who had poor ultrasound imaging, severe valvar disease, and tachycardia were excluded. In addition, subjects with both LVEF <50% and AF were excluded. Finally, 2086 subjects were included in the analysis [Figure 1]. The average age of the cohort was 75 ± 5 years. The proportions of subjects with LVDD, arterial stiffness, and HTN were 37.5%, 47.5%, and 58.49%, respectively. Subjects with LVDD were more commonly female, older, and more likely to have HTN. Subjects with arterial stiffness were also more commonly female, older, and more likely to have HTN [all P < 0.01, [Table 1].
Figure 1: Flowchart of cohort study. Brachial–ankle pulse wave velocity, brachial–ankle pulse wave velocity; left ventricular ejection fraction, left ventricular ejection fraction. AF: Atrial fibrillation

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Table 1: Baseline characteristics of the study population

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The prevalence of LVDD and arterial stiffness increased with age and SBP. The prevalence rates of LVDD and LVDD with elevated baPWV were highest in the ≥85-year group. The prevalence rates of LVDD and LVDD combined with arterial stiffness were both lower in the <140 mmHg group. The prevalence of LVDD was the highest in the 160–180 mmHg group and that of LVDD combined with arterial stiffness was the highest in the ≥180 mmHg group [Figure 2]a, [Figure 2]b, [Figure 2]c, [Figure 2]d. Linear correlation analysis indicated that baPWV positively correlated with age (r = 0.34, P < 0.01) and SBP (r = 0.28, P < 0.01) [Figure 3]a and [Figure 3]b.
Figure 2: Distributions of left ventricular diastolic dysfunction with and/or arterial stiffness among age (a and b) and systolic blood pressure groups (c and d). LVDD: Left ventricular diastolic dysfunction; SBP: Systolic blood pressure

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Figure 3: Correlation analysis of brachial–ankle pulse wave velocity in various age (a) and systolic blood pressure groups (b). baPWV: Brachial–ankle pulse wave velocity; SBP: Systolic blood pressure

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Prevalence and characteristics of left ventricular diastolic dysfunction by with and/or arterial stiffness

The cohort was divided into four groups, including no LVDD and normal baPWV (35.6%), LVDD with normal baPWV (17.2%), LVDD combined with arterial stiffness (20.4%), and no LVDD with arterial stiffness (26.8%) [Table 2]. LVDD participants with arterial stiffness and HTN accounted for 55.2% and 65.9%, respectively. Pairwise comparisons among the four groups showed that age was significantly different, with the highest values in patients with LVDD and arterial stiffness (P < 0.01). In addition, SBP showed significant differences among groups, more likely associated with HTN (P < 0.01). NT-pro BNP levels were the highest in group 4 (presence of LVDD and increased baPWV) (P < 0.05). CHD and dyslipidemia showed no differences among the four groups (P > 0.05). TC, LDL-C, HDL-C, and urea levels showed no differences among the four groups (P > 0.05). Simultaneously, the echocardiogram index of LVEF also showed no differences among the four groups (P > 0.05) [Table 2].
Table 2: Prevalence and characteristics of left ventricular diastolic dysfunction with and/or arterial stiffness in the study population

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Correlates of left ventricular diastolic dysfunction with and/or arterial stiffness

After adjustment for age, sex, heart rate, TG, blood urea nitrogen, FBG, and creatine in all logistic models, subjects with normal diastolic function or asymptomatic LVDD were assessed. Logistic multivariate regression showed that age (odds ratio [OR] = 1.04, 95% confidence interval [CI]: 1.02–1.07), HTN (OR = 1.59, 95% CI: 1.25–2.03), and NT-pro BNP (OR = 1.39, 95% CI: 1.19–1.63) were independent correlates of asymptomatic LVDD [Table 3]. In subjects with normal or arterial stiffness, logistic multivariate regression showed that age (OR = 1.11, 95% CI: 1.08–1.55), HTN (OR = 1.28, 95% CI: 1.00–1.62), and NT-pro BNP (OR = 1.20, 95% CI: 1.03–1.40) were independent correlates of arterial stiffness [Table 4]. In LVDD subjects with arterial stiffness, logistic multivariate regression showed that age (OR = 1.05, 95% CI: 1.04–1.81) and HTN (OR = 1.45, 95% CI: 1.08–1.93) were independent correlates of HTN with arterial stiffness [Table 5].
Table 3: Univariate and multivariate logistic regression analyses correlates of left ventricular diastolic dysfunction

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Table 4: Univariate and multivariate logistic regression analyses for correlates of arterial stiffness

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Table 5: Univariate and multivariate logistic regression analyses correlates of left ventricular diastolic dysfunction in subjects with arterial stiffness

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  Discussion Top


In this cohort study, we found that arterial stiffness was closely associated with asymptomatic LVDD. In addition, HTN and further aging were independently associated in LVDD with arterial stiffness. The data showed that the prevalence of LVDD was high in residents and more common in females than in males. Participants with arterial stiffness accounted for 47.5% and were more likely to be older and female. Residents showing combined LVDD with arterial stiffness accounted for 20.7%, with higher rates of female, older, and hypertensive residents.

In this study, the prevalence of LVDD was higher than previous data from China but was similar to our earlier data (31.9%)[18],[19] The subjects enrolled in the present study were aged >65 years (i.e., the patients were much older than in other studies) and had cardiovascular comorbidities such as HTN, diabetes, dyslipidemia, and obesity more commonly than those in previous studies. Specifically, HTN was the most common comorbidity, and the BP control rate was low in this community. Notably, SBP was increased, and in accordance with the characteristics of elderly hypertensive individuals, the mean SBP and DBP were 143 ± 18 mmHg and 77 ± 9 mmHg, respectively. Lu et al. reported that in patients aged 35–79 years in four Chinese provinces (Jilin, Liaoning, Zhejiang, and Guangxi), the prevalence of HTN was 44.7%, of whom only 44.7% were aware of their diagnosis, and 7.2% achieved BP control.[20] Wu et al. reported a prevalence of HTN of 24.7% in adults in the Jilin province in northeast China.[21] All these studies expressed dramatically that the prevalence of HTN was increasing, and only few patients had BP under control during recent years in China.

Our findings demonstrated that the prevalence rates of LVDD and arterial stiffness increased with aging and were the highest in the ≥85-year group. The mean baPWV was 1779 ± 345 cm/s, which also increased in LVDD subjects. Many reports confirmed that baPWV was proportional to periphery arterial wall rigidity.[22],[23] Studies in both Asia and Western counties showed that arterial stiffness was associated with LV diastolic function[6],[24] We also found that baPWV increased significantly in both female and male participants with LVDD. baPWV is reported to change in various pathophysiological conditions such as HTN, diabetes, and metabolic syndrome[25],[26],[27] As shown above, baPWV increased most significantly in hypertensive patients with LVDD; however, LVDD patients with diabetes or obesity showed values comparable to those of patients without LVDD.

LVDD and increased baPWV affected echocardiographic findings. Arterial stiffness increases forward and backward pressure, leading to further increases in cardiac afterload. When arterial elastic properties are changed and elevated arterial stiffness is present, diastolic pump failure could result in deleterious effects on cardiac function and structure. Abhayaratna et al. showed that increased arterial stiffness is associated with severe LV diastolic dysfunction in elderly patients in Australia.[28] Xu et al. assessed 378 Chinese individuals (LVEF ≥50%) and showed that baPWV is closely associated with multiple ultrasound data, reflecting changes in cardiac structure.[29]

Age, female sex, and HTN were independently related to asymptomatic LVDD in this study. We found that NT-pro BNP was the highest in LVDD patients with arterial stiffness, constituting an independent correlate of LVDD in the present community. Age and HTN independently correlated with increased baPWV. Kawai et al. showed that baPWV of 1750 cm/sec could be a useful cutoff value for predicting cardiovascular prognosis. Aging and high BP may exert synergistic effects on the acceleration of arterial stiffening. Total TGs were related to increased baPWV in this study. Previous Japanese studies on community-dwelling individuals showed significant correlation of baPWV not with serum TC levels but with serum TG levels.[30] In this study, we found that NT-pro BNP levels correlated with arterial stiffness in elderly community-dwelling residents. LV afterload is a major determinant of serum NT-pro BNP levels. Furthermore, increased baPWV suggests elevated arterial stiffness and a higher speed of pressure wave. Consequently, increased cardiac afterload is reflected by elevated levels of NT-pro BNP.


  Conclusions Top


This study showed that HTN and aging are independently associated in LVDD with arterial stiffness. Subjects with arterial stiffness usually show cognitive dysfunction, renal dysfunction, cardiac diastolic dysfunction, and LV hypertrophy. The current results suggest that the contributions of risk factors other than aging and high BP for increasing the rate of LVDD with arterial stiffness were small or insignificant. In addition, NT-pro BNP levels were overtly elevated and associated with LVDD and arterial stiffness in the elderly.

Study limitation

We did not collect information about the socioeconomic status and education levels of study participants. Individual or family income and education may influence the risk of heart disease and risk factors for LVDD. More information about potential confounders should be collected in order to avoid any bias regarding risk factor estimation.

Financial support and sponsorship

Chinese Ministry of Technology National Technology Support Plan (2006BAI01A04) and Chinese Ministry of Technology National Technology Support Plan (2011BAI11B00).

Conflicts of interest

There are no conflicts of interest.



 
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    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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