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Original research
Biological and sociocultural determinants of increased blood pressure among women with a history of gestational diabetes mellitus in rural China: a retrospective cohort study
  1. Jia Guo1,
  2. Wencong Lv1,
  3. Shan Jiang1,
  4. Yujia Tang2,
  5. Qing Long1,
  6. Jundi Yang3,
  7. James Allen Wiley4,
  8. Monica Parry5
  1. 1Xiangya School of Nursing, Central South University, Changsha, Hunan, China
  2. 2Ingram School of Nursing, McGill University, Montreal, Quebec, Canada
  3. 3School of Nursing, The University of Hong Kong, Hong Kong, Hong Kong
  4. 4Department of Family and Community Medicine, University of California, San Francisco, California, USA
  5. 5Lawrence S Bloomberg Faculty of Nursing, University of Toronto, Toronto, Ontario, Canada
  1. Correspondence to Professor Jia Guo; guojia621{at}163.com

Abstract

Objectives Gestational diabetes mellitus (GDM) increases the risk of hypertension and cardiovascular events among mothers later in life. This risk has not been well recognised by healthcare professionals in rural China. Our objectives were to (1) describe the proportion of rural women with increased blood pressure and a history of GDM; and (2) explore the biological and sociocultural factors associated with increased blood pressure.

Design A retrospective cohort study using data from a cross-sectional survey.

Setting Data were collected in two county-level hospitals in the central south of China between November 2017 and June 2018.

Participants Postpartum women aged >18 years with a history of GDM (N=397).

Methods Biological and sociocultural variables were examined. We used bivariate analyses to examine the associations between time since delivery and 2-hour postload glucose, and logistic regression to determine the biological and sociocultural factors associated with increased postpartum blood pressure.

Results Approximately 20% (n=78) of women had increased blood pressure, defined as a systolic blood pressure ≥130 mm Hg and/or a diastolic blood pressure ≥85 mm Hg. The biological factors of advanced age, family history of hypertension and abnormal 2-hour postload plasma glucose levels were positively associated with increased blood pressure (p<0.05). General self-efficacy was the only sociocultural factor negatively associated with increased blood pressure (p<0.05).

Conclusions One in five rural Chinese postpartum women with a history of GDM were found to have increased blood pressure. Biological and sociocultural factors were associated with increased postpartum blood pressure; women with lower general self-efficacy were more likely to have increased blood pressure. Disseminating knowledge about the high risk of developing increased blood pressure among women with prior GDM in rural China is indicated. Diabetes prevention programmes could consider adding general self-efficacy promotion strategies in this population.

  • diabetes & endocrinology
  • hypertension
  • risk management

Data availability statement

Data are available upon reasonable request. The data sets used and/or analysed in the current study are available from the corresponding author on reasonable request.

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Strengths and limitations of this study

  • This study explored the determinants of increased blood pressure in rural Chinese women with a history of gestational diabetes mellitus using a biological and sociocultural framework.

  • Biological (eg, age, family history of hypertension and 2-hour postload plasma glucose levels) and sociocultural (eg, general self-efficacy) factors and their association with increased postpartum blood pressure were examined.

  • International guidelines were used as references for variable cut-offs (eg, blood pressure, body mass index, waist circumference), which will allow for future knowledge syntheses and meta-analyses.

  • The use of a one-time blood pressure measure is likely to have increased random error and reduced the power of our regression analyses.

  • This retrospective cohort study used data from an established database and this means that additional risk factor variables not captured in the database (eg, high blood pressure before pregnancy) were not fully explored.

Introduction

Gestational diabetes mellitus (GDM) is a glucose intolerance causing hyperglycaemia with onset or first recognition during pregnancy.1 The prevalence of GDM varies across countries, with a reported prevalence of 20% in Vietnam and Singapore,2 11.1% in China,3 and 7.6% in the USA.4 Overall, the prevalence of GDM has been increasing worldwide,5 which significantly increases the risk of adverse pregnancy and birth outcomes.6

GDM also increases the long-term risk of type 2 diabetes mellitus (T2DM) and cardiovascular disease of mothers later in life.7 The risk of developing T2DM is over seven times higher in women with a history of GDM compared with women without a history of GDM.8 The risk of developing hypertension has been reported to be two times higher in the UK9 and Canada10 and 2.54%–14.9% higher among women with a history of GDM in Western countries.9–12 Two studies from large urban cities in China reported hypertension rates after delivery in women with a history of GDM of 19.7% and 16.7%, which are five to eight times higher than of women without GDM (4.4% and 1.7%).13 14 Hypertension rates in Chinese women living in urban centres are higher than that of Western countries. Moreover, large rural–urban gaps in income, education, health resources, and minority and majority groups in China15 suggest more evidence focusing on equity, diversity and inclusion is needed.

Hyperglycaemia and insulin resistance accelerate atherogenesis, which increases the risk of hypertension.16 Hypertension is one of the main risk factors of cardiovascular disease.17 Globally, 40% of individuals aged 25 years and older have hypertension.18 High normal blood pressure, an important predictor of hypertension,19 is defined as a systolic blood pressure (SBP) of 130–139 mm Hg and/or a diastolic blood pressure (DBP) of 85–89 mm Hg.20 In the USA, approximately 53% of individuals aged 65–94 years with high normal blood pressure developed hypertension within 4 years.21 There is an urgent need to obtain data on increased blood pressure rates among rural women with a history of GDM in China.

Hypertension prevention is a global concern.22 Identifying the factors that increase blood pressure after delivery is a preliminary step towards designing prevention programmes. The biological and sociocultural framework emphasises the collective impact and influence of biological/genetic factors as well as healthy social environmental factors on health outcomes and conditions.23 Cardiovascular health, as one of the most common health conditions, is influenced by both biological and sociocultural factors.24 Several biological risk factors (eg, ethnicity, age) contribute to risk of hypertension in women with GDM. For example, Hispanic women with a history of GDM have an increased risk of hypertension compared with white women,25 and in Taiwan women at advanced age have a higher risk of hypertension compared with younger women with a history of GDM.26 Obesity is another important biological factor that increases the risk of cardiovascular disease and related conditions.27 Women with a history of GDM are more likely to be obese compared with women with normal glycaemic status during pregnancy.28 Obesity-related variables (eg, body mass index (BMI), waist circumference) are also associated with hypertension.29 BMI is inversely associated with high-density lipoprotein cholesterol, and low high-density lipoprotein levels increase the risk of hypertension.30

Sociocultural factors (eg, health behaviours) are closely related to the development of hypertension.31 There is evidence supporting daily physical activity reduces the risk of hypertension among women.32 Women in rural China rarely have time to do enough daily physical activity due to housework responsibilities, as well as the responsibilities of taking care of children and senior family members.33 Diet is an important component of guidelines for antihypertensive therapy in America and Europe.34–36 Low fruit and vegetable consumption is associated with increased blood pressure.37 With the improvement of the economy and social life in China, the consumption of animal foods and oil/fat has increased,38 39 leading to an increased risk of developing hypertension among the general population. However, the impact of physical activity and diet on increased blood pressure in rural Chinese women with a history of GDM has rarely been reported.

Psychosocial factors (eg, perceived stress) also impact the development of hypertension in women.40 Perceived stress refers to the degree to which people perceive that they cannot meet their needs.41 Work-related issues present challenges in balancing career and family responsibilities—issues which often disproportionately increase women’s mental stress.42 General self-efficacy is a person’s confidence in achieving self-management and behavioural change.43 Health behaviours (eg, healthy dietary habits and physical activity) can be improved by increasing general self-efficacy among women with a history of GDM.44 However, the contribution of general self-efficacy and perceived stress to increased blood pressure among women with a history of GDM is not well documented.

To our knowledge, the long-term risk of hypertension and cardiovascular events later in life in women with a history of GDM has not been well recognised by healthcare professionals in China. There are very few studies exploring the factors associated with increased blood pressure in these women from both biological and sociocultural perspectives. The objectives of this study were to (1) describe the proportion of rural women with increased blood pressure and a history of history of GDM; and (2) explore the biological factors (eg, age, ethnicity, family history of hypertension, time since delivery, obesity-related factors (BMI and waist circumference) and blood glucose (fasting blood glucose (FBG) and 2-hour postload plasma glucose (2hPG)) and sociocultural factors (eg, education, occupation, income, health behaviours (physical activity, vegetable and fruit intake, and sedentary time) and psychosocial factors (stress and general self-efficacy)) associated with increased blood pressure.

Methods

Study design and participants

This study was a retrospective cohort study using data from a cross-sectional survey aimed to describe the levels and risk factors for postpartum abnormal glucose tolerance.45 The inclusion criteria included women (1) diagnosed with GDM during the last pregnancy, (2) aged >18 years, (3) >6-week postpartum period, (4) available by telephone and (5) able to speak Chinese. The exclusion criteria included women who were (1) pregnant, (2) diagnosed with abnormal glucose tolerance (eg, impaired fasting glucose, impaired glucose tolerance or diabetes) before pregnancy or after delivery, (3) previously diagnosed with hypertension or had pre-existing obstetric-related hypertension (eg, pre-eclampsia, eclampsia or gestational hypertension), (4) with physical or cognitive disabilities, (5) currently prescribed antihypertensive medication, (6) diagnosed with addictive drug abuse (eg, morphine or cocaine), and (7) showing severe psychiatric disorder.

Data collection

Participants were recruited from two county-level hospitals (Youxian and Zhangjiajie) in Hunan Province, China, between November 2017 and June 2018. Potential participants were identified through a review of the medical records of women who had given birth at the research sites. A local physician or nurse called potential participants who met the inclusion criteria to explain the purpose of the study and determine their willingness to participate. The objectives of the study and confidentiality principles were detailed according to standard operating procedures. Informed consent was obtained before the survey was administered. The research assistant checked all surveys immediately after completion in an attempt to reduce missingness of data due to skipped questions. Blood pressure, anthropometric variables (eg, height, weight, waist circumference) and blood glucose measurements were obtained by nurses.

Measurements

Blood pressures were measured on-site by registered nurses after a 12-hour fasting period using an electronic blood pressure monitor (HEM-7120; Omron, Tokyo, Japan) and the criteria recommended by the Chinese Hypertension League/National Center.46 Blood pressures were divided into two categories according to the criteria of the European Society of Cardiology and the European Society of Hypertension as follows: (1) normal blood pressure (SBP <130 mm Hg and DBP <85 mm Hg) and (2) increased blood pressure (high normal blood pressure: SBP ≥130 mm Hg and/or DBP ≥85 mm Hg; hypertension: SBP ≥140 mm Hg and/or DBP ≥90 mm Hg).20 Mean blood pressure (MBP) was calculated from SBP and DBP according to the following formula: MBP=1/3×(SBP−DBP)+DBP.

Partial biological (eg, age, ethnicity, family history of hypertension and time since delivery) and sociocultural (eg, education, occupation and monthly family income) data were collected via a self-reported survey. Ethnicity was categorised as Han or minority. Time since delivery was classified into ≤12 months and >12 months based on a meta-analysis suggesting that 12 months post partum is an important period for discerning risk of cardiovascular disease among women with a history of GDM.47 Education was categorised as junior high school and below (<12 years of schooling) and senior high school and above (≥12 years of schooling). Occupation status was categorised as employed or unemployed. Poverty was defined using the current poverty line in China, which is based on a monthly family income of less than $145.48 Monthly family income was then divided into <$145 and ≥$145.

Biological variables also included obesity-related factors (eg, BMI, waist circumference) and blood glucose. BMI was calculated as weight in kilograms divided by height in metres squared and categorised into two levels based on the guidelines for the prevention and control of overweight and obesity in Chinese adults: underweight or normal (<24 kg/m2) and overweight or obese (≥24 kg/m2).49 According to the criteria of the International Diabetes Federation50 and the National Institute for Health and Care Excellence,32 waist circumference was divided into normal (<80 cm) and central obesity (≥80 cm). Blood glucose included FBG and 2hPG. After overnight fasting, venous blood samples were collected to measure the FBG. For 2hPG, blood samples were collected after fasting for 12 hours followed by blood samples taken 2 hours after consumption of 75 g of glucose. The hexokinase enzyme method was used to measure blood glucose.

Sociocultural variables included health behaviours (eg, physical activity, vegetable and fruit intake, sedentary time) and psychosocial factors (stress, general self-efficacy). Physical activity was measured using the Chinese version of the Canadian Diabetes Risk Questionnaire, which was developed by Robinson et al51 and revised and translated to Chinese by Guo et al52: ‘Do you engage in regular physical activity, such as brisk walking for at least 30 minutes each day?’ Daily vegetable and fruit intake was measured by the following item: ‘Do you eat vegetables or fruits every day?’ The Chinese Diabetes Risk Questionnaire has good reliability and validity.52Sedentary time was measured using the following item of the Short-Form of the International Physical Activity Questionnaire (IPAQ-S) (Chinese version)53: ‘How much time did you usually spend sitting?’ The IPAQ-S has an intraclass correlation coefficient greater than 0.70. Stress was measured using the Perceived Stress Scale, which was designed to assess the level of stress in everyday life.54 This 14-item scale was revised and translated to Chinese,55 and total scores range from 0 to 56, with a score >26 representing higher level of stress.55 This scale has good internal consistency reliability with Cronbach’s α coefficient reported at 0.78.55

General self-efficacy was measured using the 10-item General Self-Efficacy Scale (Chinese version).56 Higher scores represent greater general self-efficacy, with scores ranging from 10 to 40, and the internal consistency is reported at 0.87.56

Data analysis

Data analyses were performed using IBM SPSS Statistics V.23. Descriptive statistics were used to describe the sample. The associations between biological and sociocultural variables and increased blood pressure were determined by one-way analysis of variance (ANOVA) and χ2 test. Multivariate logistic regression (ENTER) was used to identify factors influencing increased blood pressure . The multivariate logistic regression model included variables that obtained values of p<0.05 in the bivariate analysis (one-way ANOVA or χ2) and variables identified in existing literature (eg, ethnicity, obesity-related variables, FBG, education, income, occupation, stress and lifestyle behaviours). A two-sided p<0.05 was used to establish statistical significance, and the results were expressed as OR with 95% CI.

Patient and public involvement

Patients were not involved in developing the research questions, outcome measurements or design of the study. The findings of this retrospective cohort study will not be directly disseminated to study participants.

Results

A total of 397 women were included in this study. Since this was a retrospective cohort study, a post-hoc power analysis was used to determine an adequate sample size to detect statistical differences in the logistic regression. Assuming an α of 0.05, a base prevalence of 0.20 and R-squared with other predictors of 0.50, a two-tailed test of the null hypothesis with an OR of 1.0 for a given predictor against an alternative OR of 1.70 has a power of 0.83 in a logistic regression, with N=397 (G*Power V.3.1).

Distribution of blood pressure among rural women with a history of GDM

Approximately 20% (n=78) of women had increased blood pressure, with 30.7% (n=24) having hypertension and 69.3% (n=54) having high normal blood pressure. The MBP of women with hypertension and high normal blood pressure was 108.25 mm Hg (SD 6.78) and 96.85 mm Hg (SD 4.76), respectively. Of the 397 participants, 80.3% (n=319) had normal blood pressure. The mean SBP of high normal blood pressure was 129.11 mm Hg (SD 6.46) and the mean DBP was 80.72 mm Hg (SD 7.91) (table 1).

Table 1

Distribution of blood pressure among rural women with a history of gestational diabetes mellitus

Biological characteristics of rural women with a history of GDM

The participants’ mean age was 32.27 years (SD 5.2), ranging from 20 to 47 years. Almost half of the participants (n=182, 45.8%) were of minority ethnicity and one-third (n=137, 33.2%) had a family history of hypertension. The mean time since delivery was 15.50 months (SD 12.46). Almost half (n=182, 45.8%) of the participants were overweight or obese (≥24.0 kg/m2) and the mean BMI was 23.85 kg/m2 (SD 3.65). The mean waist circumference was 80.33 cm (SD 8.50) and over half of the participants (n=208, 52.4%) had central obesity (>80 cm). The mean FBG level was 5.35 mmol/L (SD 1.28), with 10.9% of the participants exhibiting FBG levels greater than 6.1 mmol/L. The mean 2hPG was 6.55 mmol/L (SD 2.69), with 15.1% (n=60) of the participants having glucose intolerance defined as 2hPG >7.8 mmol/L (table 2).

Table 2

Biological and sociocultural characteristics of rural women with a history of gestational diabetes mellitus according to blood pressure (N=397)

Sociocultural characteristics of rural women with a history of GDM

Of the 397 participants, 76.3% (n=303) had completed more than 12 years of education and 97.0% (n=385) had a monthly family income above the Chinese poverty threshold (ie, ≥$145/month). Approximately 36.5% (n=145) of women were unemployed. More than two-thirds (n=267, 67.3%) of the participants engaged in physical activity for less than 30 min a day, most (n=320, 80.6%) did not consume fruit or vegetables every day, and more than two-thirds (n=279, 70.2%) of participants reported a sedentary time of less than 6 hours every day. The mean perceived stress score was 23.93 (SD 6.40), with a range of 1–39. Of the 397 participants, 37.8% reported high stress levels. The mean score for general self-efficacy was 25.81 (SD 5.89), with a range of 10–40. The details of participants’ sociocultural characteristics are displayed in table 2.

Bivariate analysis of biological and sociocultural factors and increased blood pressure among rural women with a history of GDM

Women with increased blood pressure were older than women with normal blood pressure (p=0.003). Compared with women without a family history of hypertension, women with a family history of hypertension had higher rates of increased blood pressure (p=0.001) and women with high 2hPG values had higher rates of increased blood pressure compared with women with normal 2hPG values (p<0.001). There were no statistically significant differences in blood pressure related to ethnicity, time since delivery, obesity-related variables (eg, BMI, waist circumference) and FBG between the participants (p>0.05). Bivariate analysis of sociocultural variables indicated that women reporting lower general self-efficacy had higher rates of increased blood pressure (p=0.010). There were no significant associations between blood pressure and other sociocultural variables (eg, education, income, occupation, health behaviours (physical activity, fruit and vegetable intake, sedentary time) and perceived stress) (p>0.05) (table 2).

Bivariate analysis of time since delivery and 2hPG among rural women with a history of GDM

There were no significant associations between time since delivery and 2hPG among rural women with a history of GDM (p>0.05) (table 3).

Table 3

Relationship between time since delivery and 2hPG among rural women with a history of gestational diabetes mellitus

Logistic regression of increased blood pressure among rural women with a history of GDM

Women at advanced age and those with a family history of hypertension were more likely to develop high blood pressure (OR: 1.070, 95% CI 1.015 to 1.128 and OR: 1.947, 95% CI 1.136 to 3.336, respectively; p<0.05). Similarly, women with abnormal 2hPG values had greater risk of developing increased blood pressure (OR: 2.055, 95% CI 1.061 to 3.982; p<0.05). Moreover, general self-efficacy was negatively associated with increased blood pressure (OR: 0.946, 95% CI 0.900 to 0.955; p<0.05). The results of the logistic regression analyses are displayed in table 4.

Table 4

Logistic regression of blood pressure among rural women with a history of gestational diabetes mellitus

Discussion

This retrospective cohort study obtained several key findings. First, the prevalence of increased blood pressure among rural Chinese women with a history of GDM was approximately 20% at 15.5 months after delivery. Second, both biological and sociocultural factors (eg, age, family history of hypertension, low general self-efficacy) were associated with increased blood pressure. Surprisingly, obesity indicators (eg, BMI, waist circumference) were not significantly related to increased blood pressure, although women with high 2hPG values had higher rates of increased blood pressure compared with women with normal 2hPG values.

The proportion of women with increased blood pressure was approximately 20%, which is similar to the proportion of women with hypertension and a history of GDM within 1 year following delivery in two urban cities of China (19.7% and 16.7%).13 14 The proportion of women with increased blood pressure in our retrospective cohort study is slightly higher than the proportion of hypertension reported among women with a history of GDM in Canada (15.8%).10 According to the literature, the proportion of increased blood pressure among Chinese women without GDM living in large urban cities was 1.7%–4.4%.13 14 Thus, the risk of increased blood pressure among rural Chinese women with a history of GDM is alarming.

Regarding biological factors, women at an advanced age had a higher risk of increased blood pressure after delivery, which is consistent with findings in women with a history of GDM in Taiwan.26 This might be because the metabolic and vascular environments deteriorate with age, thus increasing the risk of increased blood pressure.57 In this retrospective cohort study, women with a family history of hypertension also had higher risk of increased blood pressure after delivery, which is consistent with findings in general populations in the USA and Japan.58 59

Furthermore, women with isolated abnormal 2hPG after delivery were more likely to develop increased blood pressure, which is consistent with findings in women with a history of GDM in Finland.60 Compared with abnormal FBG, abnormal glucose tolerance (eg, 2hPG) leads to faster insulin resistance; this increases cardiac output and vascular resistance and leads to increased blood pressure.61

Surprisingly, neither BMI nor waist circumference was significantly related to increased blood pressure after delivery. This finding is inconsistent with studies in urban Chinese women with a history of GDM,3 suggesting that obesity indicators may be risk factors for increased blood pressure among women with a history of GDM in some regions but not in rural areas in the central south of China. There may be other important factors associated with increased blood pressure in this population.

General self-efficacy was the only sociocultural factor related to increased blood pressure. Women with greater general self-efficacy were less likely to develop hypertension after delivery. It has been reported that among American adults, high self-efficacy is strongly associated with confidence and the motivation to engage in activities related to reducing hypertension.62 Women with greater self-efficacy in our study may have pursued healthy behaviours and coping strategies that reduced their risk of hypertension.44 63 However, the levels of general self-efficacy are very similar between women, so the results should be generalised cautiously.

There was no association between perceived stress and increased blood pressure after delivery. This is consistent with findings from a general adult population.64 This might be because short-term or relatively low levels of stress are unlikely to have sustained effects on behavioural and pathophysiological processes that contribute to hypertension.65 66 To confirm this hypothesis, longitudinal cohort studies exploring the association between blood pressure and perceived stress among women with a history of GDM are needed.

Limitations

Several limitations existed in our study. First, random error due to the use of a one-time blood pressure measure is likely to have reduced the power of our regression analyses. Second, because this study was a retrospective cohort study, we could not measure all the potential risk factors (eg, multiple pregnancies affected by GDM, high blood pressure before pregnancy) for increased blood pressure after delivery, which could have enhanced interpretation of study findings. Third, the results of this study should be interpreted cautiously because we lack a control cohort of women post pregnancy without GDM. Also, response bias cannot be ruled out in survey designs with self-reported questionnaires. Finally, the generalisability of our results may be limited because all samples were enrolled from Hunan Province, China.

Implications

Despite these limitations, this study has several important clinical implications for preventing increased blood pressure among rural Chinese women with GDM. First, raising awareness of the risk of increased blood pressure in rural Chinese women with a history of GDM is indicated. Healthcare providers (eg, physicians, nurses) should pay particular attention to women at an advanced age and those with a family history of hypertension. Providing education to these women will help to ensure that they are aware of their increased risk for increased blood pressure in the future. Moreover, healthcare providers must ensure that blood pressure and blood glucose levels are adequately followed up.

Furthermore, interventions aimed at preventing the development of increased blood pressure in women with a history of GDM are needed. Promoting health behaviour-related general self-efficacy by mastering tasks or skills, exchanging experiences, and setting goals related to blood pressure20 67 and maintaining normal blood glucose levels by changing dietary habits (eg, increasing intake of fruit and vegetables and reducing intake of high-fat and sugary food)68 are recommended. More longitudinal controlled studies with larger samples are needed to evaluate the level of self-efficacy and explore the association between self-efficacy and increased blood pressure after delivery in this population. Finally, studies investigating other potential influencing factors in more diverse geographical locations with different cultural contexts are needed for this specialised population of women.

Conclusion

The early development of increased blood pressure in rural Chinese women with a history of GDM is alarming. Both biological and sociocultural factors were associated with increased blood pressure. Strategies to maintain normal blood glucose tolerance and improve general self-efficacy may help reduce the risk of developing increased blood pressure, especially among those at an advanced age or those with a family history of hypertension.

Data availability statement

Data are available upon reasonable request. The data sets used and/or analysed in the current study are available from the corresponding author on reasonable request.

Ethics statements

Patient consent for publication

Ethics approval

This study involves human participants and was approved by the Nursing and Behavioral Medicine Institutional Review Board of Xiangya Nursing School of Central South University (no 2016034). Participants gave informed consent to participate in the study before taking part.

References

Footnotes

  • Twitter @parryresearch

  • Contributors JG, as a guarantor, designed the current study. WL and SJ jointly defined the analytic strategy and analysed the data. WL drafted the manuscript. JG, SJ, YT, JY and QL collected the data. JG, MP and JW reviewed and edited the manuscript. All authors have read and agreed to the final version of the manuscript.

  • Funding The study was supported by the China Medical Board (grant number: 16–256), Huxiang Youth Talent Support Program (grant number: 2019RS2006) and the Key Laboratory of Hunan Province (grant number: 2017TP1004).

  • Competing interests None declared.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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