Future risk of cardiovascular disease risk factors and events in women after a hypertensive disorder of pregnancy
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* Laura Benschop
* Johannes J Duvekot
* Jeanine E Roeters van Lennep

## Abstract

Hypertensive disorders of pregnancy (HDP), such as gestational hypertension and pre-eclampsia, affect up to 10% of all pregnancies. These women have on average a twofold higher risk to develop cardiovascular disease (CVD) later in life as compared with women with normotensive pregnancies. This increased risk might result from an underlying predisposition to CVD, HDP itself or a combination of both. After pregnancy women with HDP show an increased risk of classical cardiovascular risk factors including chronic hypertension, renal dysfunction, dyslipidemia, diabetes and subclinical atherosclerosis. The prevalence and onset of cardiovascular risk factors depends on the severity of the HDP and the coexistence of other pregnancy complications. At present, guidelines addressing postpartum cardiovascular risk assessment for women with HDP show a wide variation in their recommendations. This makes cardiovascular follow-up of women with a previous HDP confusing and non-coherent. Some guidelines advise to initiate cardiovascular follow-up (blood pressure, weight and lifestyle assessment) 6–8 weeks after pregnancy, whereas others recommend to start 6–12 months after pregnancy. Concurrent blood pressure monitoring, lipid and glucose assessment is recommended to be repeated annually to every 5 years until the age of 50 years when women will qualify for cardiovascular risk assessment according to all international cardiovascular prevention guidelines.

*   cardiac risk factors and prevention
*   pregnancy
*   hypertension
*   lipoproteins and hyperlipidemia
*   diabetes

## Introduction

Cardiovascular disease (CVD) is currently the main cause of death among men and women worldwide.1 Although certain cardiovascular risk factors are already apparent at a younger age, women develop CVD on average 10–15 years later than men.1 This provides a window of opportunity to treat cardiovascular risk factors at a younger age and reduce the risk of developing CVD. One of these early cardiovascular risk factors is a hypertensive disorder of pregnancy (HDP), such as gestational hypertension and pre-eclampsia. In this review, we will summarise available data on the development of and follow-up for CVD risk factors and events among women with a history of HDP. We will also provide a practical approach to cardiovascular follow-up after pregnancy for these women.

### Hypertensive disorder of pregnancy: definition and epidemiology

Table 1 gives an overview of the different types of hypertension that may occur during pregnancy. Chronic hypertension, gestational hypertension and (superimposed) pre-eclampsia or eclampsia are referred to as HDP.2 This review will focus on HDP conditions involving new-onset high blood pressure in pregnancy: gestational hypertension and pre-eclampsia. The prevalence increased by 25% in the last decade and is expected to continue to grow with the rise of risk factors associated with developing HDP, such as diabetes, obesity and advanced maternal age. This is expected to also increase the rates of adverse obstetric outcomes associated with HDP, including fetal growth restriction, preterm birth and perinatal death.3 In the USA, HDP account for 7.4% of maternal deaths due to the increased risk of renal failure, pulmonary oedema, respiratory distress syndrome and stroke.4–6 These women are also more at risk to develop CVD later in life.7 Although the exact underlying pathophysiology for this excessive CVD risk remains unknown, the current literature suggests three pathways: 1) pregnancy-induced CVD risk, 2) a prepregnancy predisposition towards an increased risk of CVD or 3) a combination of both pathways.8 

View this table:
[Table 1](http://heart.bmj.com/content/105/16/1273/T1)

Table 1 
Types of hypertension that can occur in pregnancy2 

## Cardiovascular risk factors after pregnancy

### Chronic hypertension

Compared with women with normotensive pregnancies, women with HDP have a twofold to eightfold increased risk of future chronic hypertension.9–18 This was confirmed by a recent Danish register-based cohort study which included 1.5 million primiparous women with information on HDP and chronic hypertension diagnosis during a follow-up time of 1–20 years.9 Women with gestational hypertension had the highest risk of developing chronic hypertension after pregnancy, followed by women with severe pre-eclampsia and moderate pre-eclampsia. Taking into account confounding factors the risk of chronic hypertension was 4–10 times higher in women with an HDP compared with women with a normotensive pregnancy 1–5 years after pregnancy. By the age of 50 years, this risk became similar between the different HDP; a 2-fold to 2.5-fold higher risk compared with women with a previous normotensive pregnancy. Up to 32% of women with HDP developed chronic hypertension in the first 10 years after pregnancy versus up to 11% of women with normotensive pregnancies, depending on their age during the first pregnancy. Eight years post partum, 10% of women aged 20–29 years with a previous HDP had chronic hypertension, which is comparable to the prevalence of chronic hypertension of women with previous normotensive pregnancies aged 40–49 years 10 years post partum. A meta-analysis by Heida *et al* demonstrated that women with pre-eclampsia have a relative risk (RR) 2.76 (95% CI 1.63 to 4.69) increased risk of having chronic hypertension after pregnancy compared with women with a normotensive pregnancy.10 This risk was comparable for women with gestational hypertension (RR 2.87, 95% CI 0.84 to 9.77). These results are in line with other large studies which show that the relative risk of having chronic hypertension is especially high shortly after pregnancy and eventually plateaus.11 

Several studies also examined the severity of the HDP in relation to the risk of developing chronic hypertension after pregnancy.9 13–15 study by Behrens *et al* demonstrated that women with severe pre-eclampsia had a higher risk to develop chronic hypertension 1 year after pregnancy (HR 6.45, 95% CI 5.35 to 7.78) than women with moderate pre-eclampsia (HR 5.25, 95% CI 4.64 to 5.94).9 We recently showed that 1 year post partum, 42.5% of women with severe pre-eclampsia, assessed by ambulatory blood pressure monitoring, had night-time hypertension and 44.5% had an insufficient decrease in systolic blood pressure at night-time compared with daytime. Both conditions are associated with an increased risk of CVD.16 17 

The risk of chronic hypertension also depends on the number of pregnancies affected by HDP as was recently demonstrated in a meta-analysis by Brouwers *et al*.18 Women with recurrent pre-eclampsia had a higher risk of chronic hypertension after pregnancy than women with a subsequent uncomplicated pregnancy after a pre-eclamptic pregnancy (RR 2.3, 95% CI 1.9 to 2.9).

### Renal dysfunction

Microalbuminuria is a persistent, increased urinary excretion of albumin and is recognised as a marker for renal dysfunction and a risk factor for CVD.19 20 A meta-analysis of 606 women showed that 7.1 (95% CI 4.5 to 9.7) years post  partum those with a history of pre-eclampsia, taking into account chronic hypertension and diabetes, have a fourfold increased risk of microalbuminuria compared with women with uncomplicated pregnancies (31% vs 7%, respectively).21 Both in and outside pregnancy, a negative association between blood pressure levels and renal function was observed. This might explain why especially women with pre-eclampsia are at risk for impaired renal function.22 23 A recent Canadian population-based follow-up study examined the risk of end-stage renal disease (ESRD) among 1.5 million women over a median follow-up time of 16.2(IQR 13.3–18.3) years.22 This study showed that the absolute risk of ESRD is very low; 0.15% for women with a previous HDP vs 0.03% for women with a previous normotensive pregnancy.22 After partial adjustment for age and region, women with a history of pre-eclampsia were most at risk of ESRD after pregnancy (HR 4.7, 95% CI 3.6 to 6.0), followed by women with a history of gestational hypertension (HR 3.3, 95% CI 2.1 to 5.1) compared with women with previous normotensive pregnancies. The risk of ESRD increases when multiple pregnancies are affected by pre-eclampsia, as was previously demonstrated in a large register-based Norwegian study which adjusted for results for main confounders including age and year of delivery.24 Women with pre-eclampsia in their first pregnancy had a RR for ESRD of 4.7 (95% CI 3.6 to 6.1), whereas women with pre-eclampsia in more than one pregnancy had a RR of 15.5 (95% CI 7.8 to 30.8).24 

### Dyslipidemia

Women with HDP are at increased risk for having an adverse lipid profile after pregnancy than women with a normotensive pregnancy.13 25 26 A meta-analysis of 15 studies, including 736 women with a previous HDP and 701 women with previous normotensive pregnancies showed that the former have more often dyslipidemia than women with normotensive pregnancies (pooled unadjusted mean differences varied between 0.13 and 0.22 mmol/L).25 We recently showed that dyslipidemia was more frequent in women with a history of HDP than in women with normotensive pregnancies 6 years after delivery in a group of 4933 women.26 After adjustment for all relevant confounders, total-cholesterol, triglycerides, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, lipoprotein(a) and apolipoprotein B levels were all higher in women with previous gestational hypertension compared with women with a previous normotensive pregnancy. Women with previous pre-eclampsia had higher triglyceride levels compared with women with a previous normotensive pregnancy. Nevertheless, this risk was predominantly driven by prepregnancy body mass index (BMI).

### Diabetes

In addition to an increased risk of insulin resistance during pregnancy, women with HDP are also more at risk of developing diabetes later in life. A large Canadian study retrospectively examined the risk of diabetes after pregnancy partially adjusted for relevant confoundersand comorbidity, in 1 million women with a median follow-up of 8.5 years.27 Women without gestational diabetes, were more likely to develop diabetes after gestational hypertension (3.9%) or pre-eclampsia (6.6%)than after a normotensive pregnancy (2.5%). A register-based cohort study from Denmark also demonstrated that the fully adjusted risk of type 2 diabetes 14.6 years after pregnancy (range 0.25–30.2) was 3.12-fold (range 2.63–3.70) for women with gestational hypertension and 3.68 (range 3.04–4.46) after pre-eclampsia.15 

### Subclinical atherosclerosis

Both during and after pregnancy, women with pre-eclampsia have a larger carotid intima media thickness (CIMT) than women without pre-eclampsia.28 29 Several studies have shown that the coronary artery calcium score (CACS) is higher in women who had previous pre-eclampsia compared with women without a hypertensive pregnancy.30 31 Most of these studies were small and performed in women of approximately 60 years, >30 years after pregnancy. In the Cardiovascular Risk Profile: Imaging and Gender-Specific Disorders (CREW-IMAGO)study, we showed that 31% of women with previous pre-eclampsia aged 45–55 years had a CACS of >0 in comparison with 18% of women with a previous normotensive pregnancy who were matched for gender, age and ethnicity.26 Moreover, 47% of women with previous pre-eclampsia had coronary atherosclerotic plaques on coronary computed tomography angiography (CCTA) and 4.3% significant stenosis.26 

### Cardiovascular disease

Multiple meta-analyses based on cohort studies showed that women with HDP have an increased risk of CVD that was not explained by adjustment for confounding variables.7 10 21 32 33 In women with previous pre-eclampsia, the RR of coronary heart disease ranged between 2.06 and 2.507 10 21 32 33 and the RR of cerebrovascular disease between 1.53 and 3.13.7 10 21 33 Peripheral artery disease was only assessed in one meta-analysis, finding a 1.87-fold increased risk (95% CI 0.94 to 3.37) among women with a history of pre-eclampsia or eclampsia based on three studies.21 The CVD risk also depends on specific pregnancy characteristics. For instance, women with early onset pre-eclampsia before 37 weeks of gestation have a markedly increased risk of CVD compared with women with late-onset pre-eclampsia (RR 7.71, 95% CI 4.40 to 13.52 vs RR 2.16, 95% CI 1.86 to 2.52).32 Moreover, women who had pre-eclampsia in combination with a child born small for gestational age or a preterm delivery have an increased risk of CVD compared with women with only pre-eclampsia after adjustment for confounders (HR 3.3, 95% CI 2.37 to 4.57 vs HR 5.38, 95% CI 3.74 to 7.74 and HR 2.14, 95% CI 1.73 to 2.65, respectively).34 After a pregnancy complicated by pre-eclampsia the risk of recurrent pre-eclampsia in a subsequent pregnancy is approximately 15%.35 Women with recurrent pre-eclampsia have an increased risk of ischaemic heart disease (RR 2.40, 95% CI 2.15 to 2.68), cerebrovascular disease (RR 1.69, 95% CI 1.21 to 2.35) and cardiovascular events and hospitalisation (RR 1.57, 95% CI 1.31 to 1.90) compared with women with a subsequent uncomplicated pregnancy.18 Less data are available regarding the risk of CVD in women with gestational hypertension as compared with women with pre-eclampsia. A recent review showed that the risk of fatal and non-fatal CVD as well as ischaemic heart disease and stroke was higher in women who experienced gestational hypertension than in women with an uncomplicated pregnancy (RR 1.89, 95% CI 1.31 to 2.72, RR 1.44, 95% CI 1.30 to 1.60 and RR 1.41, 95% CI 1.20 to 1.65, respectively).10 A large population-based study demonstrated that women with gestational hypertension had a 1.8-fold (95% CI 1.7 to 2.0) higher risk of developing subsequent CVD, a 1.7-fold (95% CI 1.3 to 2.1) higher risk of subsequent coronary heart disease and a 1.3-fold (95% CI 0.9 to 1.7) higher risk of developing cerebrovascular disease compared with women without an HDP.36 Furthermore, women with a gestational hypertension in combination with a child born small for gestational age and a preterm delivery had the highest CVD risk after adjustment for most confounders but not smoking, BMI and pre-existing hypertension (HR 2.3, 95% CI 2.3 to 3.0).36 

### Approach to follow-up

In summary, already 1 year after delivery women with HDP have relatively more cardiovascular risk factors than women after normotensive pregnancies. In general, women with pre-eclampsia, especially severe, early onset pre-eclampsia, have the most adverse cardiovascular risk phenotype. Also, studies show that women who had gestational hypertension have an increased cardiovascular risk profile. Women with a history of pre-eclampsia develop chronic hypertension and thereafter dyslipidemia earlier then women with previous normotensive pregnancies. By the age of 35 years, the number needed to screen (NNT) to diagnose one woman with chronic hypertension is 9 and the NNT to diagnose dyslipidemia by the age of 39 years is 18. For diabetes mellitus, the NNT is 22 between the age of 50 and 55 years.37 Subclinical atherosclerosis visible by cardiovascular imaging is already apparent by the age of 45 years, when women are on average 16.3±5.9 years post partum.26 This underlines that, to optimise cardiovascular prevention, it is important to initiate cardiovascular screening soon after delivery. Nevertheless, uniform recommendations regarding cardiovascular follow-up after HDP are lacking. This follow-up could be provided by various healthcare professionals, including general practitioners, internists, cardiologists or gynaecologists, all using different guidelines (table 2). Advise on how and when cardiovascular risk assessment should be carried out and by which healthcare provider is currently confusing as it differs between guidelines. At present, only half of the most commonly used guidelines advise cardiovascular risk assessment after pregnancy. Figure 1 provides an overview of these recommendations for cardiovascular follow-up after HDP.9 14 26 27 38–43 Initially, all women should be informed about their increased risk of future CVD after HDP.44 Healthcare providers should encourage a healthy diet and lifestyle, especially for overweight women.45 The American  Heart   Association and National Institute for Health and Care Excellence guidelines advise to perform a first cardiovascular follow-up 6–8 weeks post partum (table 2).39 40 As lipid levels increase during pregnancy and will gradually normalise, measuring lipids within 1 year post partum is not recommended. The American College of Obstetricians and Gynecologists, European Society of Cardiology/European Society of Hypertension and American Stroke Association guidelines advise cardiovascular follow-up 6–12 months post partum.41–43 Thereafter, some guidelines advise annual follow-up of blood pressure and metabolic factors by primary care physician,42 46 whereas others recommend to repeat follow-up every 5 years.9 14 26 27 38 47 At 50 years, all women including those with HDP will qualify for regular cardiovascular risk assessment according to all major international cardiovascular prevention guidelines.26 Besides obtaining a uniform approach to the cardiovascular follow-up of women with an HDP, it also remains a challenge to motivate women to attend a cardiovascular prevention programme. Evaluation of a cardiovascular screening programme in the UK observed that those adhering to the programme are mostly highly educated and often non-smokers.48 Although some cardiovascular risk factors have been identified, it remains difficult to predict who will develop CVD and who will not. Therefore, the development of clinical prediction models and biomarkers will help to personalise cardiovascular risk management in women after HDP.

![Figure 1](http://heart.bmj.com/https://heart.bmj.com/content/heartjnl/105/16/1273/F1.medium.gif)

[Figure 1](http://heart.bmj.com/content/105/16/1273/F1)

Figure 1 
Schedule for suggested cardiovascular follow-up after a hypertensive disorder of pregnancy. ASCVD, atherosclerotic cardiovascular disease; BMI, body mass index; JBS3, Joint British Societies recommendations on the prevention of Cardiovascular Disease; SCORE, Systematic COronary Risk Evaluation. *National Institute for Health and Care Excellence. Hypertension in pregnancy, 2013 (updated 2017).

View this table:
[Table 2](http://heart.bmj.com/content/105/16/1273/T2)

Table 2 
Cardiovascular follow-up after a hypertensive disorder of pregnancy

In conclusion, although women with HDP have more cardiovascular risk factors soon after pregnancy, the lag-time between pregnancy and the occurrence of CVD provides a unique window of opportunity for timely cardiovascular prevention. The current challenge is how to use this period most optimal. Therefore, it is time to focus research on optimising the implementation of cardiovascular follow-up programmes targeted to these women.

## Footnotes

*   Contributors LB and JERvL wrote the review. JJD gave input at all stages of the study. All authors have approved the final version of the manuscript.

*   Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

*   Competing interests None declared.

*   Provenance and peer review Commissioned; externally peer reviewed.

*   Correction notice This article has been corrected since it first published online. The open access licence type has been amended.

*   Patient consent for publication Not required.

This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: [https://creativecommons.org/licenses/by/4.0/](https://creativecommons.org/licenses/by/4.0/).

## References

1.   Benjamin EJ , Blaha MJ , Chiuve SE , et al . Heart Disease and Stroke Statistics-2017 Update: A Report From the American Heart Association. Circulation 2017;135:e146–e603.[doi:10.1161/CIR.0000000000000485](http://dx.doi.org/10.1161/CIR.0000000000000485) 
    
    [FREE Full Text](http://heart.bmj.com/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiRlVMTCI7czoxMToiam91cm5hbENvZGUiO3M6MTQ6ImNpcmN1bGF0aW9uYWhhIjtzOjU6InJlc2lkIjtzOjExOiIxMzUvMTAvZTE0NiI7czo0OiJhdG9tIjtzOjI2OiIvaGVhcnRqbmwvMTA1LzE2LzEyNzMuYXRvbSI7fXM6ODoiZnJhZ21lbnQiO3M6MDoiIjt9) 

2.   Brown MA , Magee LA , Kenny LC , et al . Ishaku S and International Society for the Study of Hypertension in P. Hypertensive Disorders of Pregnancy: ISSHP Classification, Diagnosis, and Management Recommendations for International Practice. Hypertension 2018;72:24–43.
    
    [CrossRef](http://heart.bmj.com/lookup/external-ref?access_num=10.1161/HYPERTENSIONAHA.117.10803&link_type=DOI) 
    
    [PubMed](http://heart.bmj.com/lookup/external-ref?access_num=29899139&link_type=MED&atom=%2Fheartjnl%2F105%2F16%2F1273.atom) 

3.   Wallis AB , Saftlas AF , Hsia J , et al . Secular trends in the rates of preeclampsia, eclampsia, and gestational hypertension, United States, 1987-2004. Am J Hypertens 2008;21:521–6.[doi:10.1038/ajh.2008.20](http://dx.doi.org/10.1038/ajh.2008.20) 
    
    [CrossRef](http://heart.bmj.com/lookup/external-ref?access_num=10.1038/ajh.2008.20&link_type=DOI) 
    
    [PubMed](http://heart.bmj.com/lookup/external-ref?access_num=18437143&link_type=MED&atom=%2Fheartjnl%2F105%2F16%2F1273.atom) 

4.   Kuklina EV , Ayala C , Callaghan WM . Hypertensive disorders and severe obstetric morbidity in the United States. Obstet Gynecol 2009;113:1299–306.[doi:10.1097/AOG.0b013e3181a45b25](http://dx.doi.org/10.1097/AOG.0b013e3181a45b25) 
    
    [CrossRef](http://heart.bmj.com/lookup/external-ref?access_num=10.1097/AOG.0b013e3181a45b25&link_type=DOI) 
    
    [PubMed](http://heart.bmj.com/lookup/external-ref?access_num=19461426&link_type=MED&atom=%2Fheartjnl%2F105%2F16%2F1273.atom) 
    
    [Web of Science](http://heart.bmj.com/lookup/external-ref?access_num=000266392400015&link_type=ISI) 

5.   McDermott M , Miller EC , Rundek T , et al . Preeclampsia: Association With Posterior Reversible Encephalopathy Syndrome and Stroke. Stroke 2018;49:524–30.[doi:10.1161/STROKEAHA.117.018416](http://dx.doi.org/10.1161/STROKEAHA.117.018416) 
    
    [FREE Full Text](http://heart.bmj.com/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiRlVMTCI7czoxMToiam91cm5hbENvZGUiO3M6OToic3Ryb2tlYWhhIjtzOjU6InJlc2lkIjtzOjg6IjQ5LzMvNTI0IjtzOjQ6ImF0b20iO3M6MjY6Ii9oZWFydGpubC8xMDUvMTYvMTI3My5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30=) 

6.   Creanga AA , Syverson C , Seed K , et al . Pregnancy-Related Mortality in the United States, 2011-2013. Obstet Gynecol 2017;130:366–73.[doi:10.1097/AOG.0000000000002114](http://dx.doi.org/10.1097/AOG.0000000000002114) 
    
    [CrossRef](http://heart.bmj.com/lookup/external-ref?access_num=10.1097/AOG.0000000000002114&link_type=DOI) 
    
    [PubMed](http://heart.bmj.com/lookup/external-ref?access_num=28697109&link_type=MED&atom=%2Fheartjnl%2F105%2F16%2F1273.atom) 

7.   Brown MC , Best KE , Pearce MS , et al . Cardiovascular disease risk in women with pre-eclampsia: systematic review and meta-analysis. Eur J Epidemiol 2013;28:1–19.[doi:10.1007/s10654-013-9762-6](http://dx.doi.org/10.1007/s10654-013-9762-6) 
    
    [CrossRef](http://heart.bmj.com/lookup/external-ref?access_num=10.1007/s10654-013-9762-6&link_type=DOI) 
    
    [PubMed](http://heart.bmj.com/lookup/external-ref?access_num=23397514&link_type=MED&atom=%2Fheartjnl%2F105%2F16%2F1273.atom) 

8.   Osol G , Bernstein I . Preeclampsia and maternal cardiovascular disease: consequence or predisposition? J Vasc Res 2014;51:290–304.[doi:10.1159/000367627](http://dx.doi.org/10.1159/000367627) 
    
    

9.   Behrens I , Basit S , Melbye M , et al . Risk of post-pregnancy hypertension in women with a history of hypertensive disorders of pregnancy: nationwide cohort study. BMJ 2017;358:j3078.[doi:10.1136/bmj.j3078](http://dx.doi.org/10.1136/bmj.j3078) 
    
    [Abstract/FREE Full Text](http://heart.bmj.com/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6MzoiYm1qIjtzOjU6InJlc2lkIjtzOjE3OiIzNTgvanVsMTJfMy9qMzA3OCI7czo0OiJhdG9tIjtzOjI2OiIvaGVhcnRqbmwvMTA1LzE2LzEyNzMuYXRvbSI7fXM6ODoiZnJhZ21lbnQiO3M6MDoiIjt9) 

10.  Heida KY , Franx A , van Rijn BB , et al . Earlier Age of Onset of Chronic Hypertension and Type 2 Diabetes Mellitus After a Hypertensive Disorder of Pregnancy or Gestational Diabetes Mellitus. Hypertension 2015;66:1116–22.[doi:10.1161/HYPERTENSIONAHA.115.06005](http://dx.doi.org/10.1161/HYPERTENSIONAHA.115.06005) 
    
    

11.  Hannaford P , Ferry S , Hirsch S . Cardiovascular sequelae of toxaemia of pregnancy. Heart 1997;77:154–8.[doi:10.1136/hrt.77.2.154](http://dx.doi.org/10.1136/hrt.77.2.154) 
    
    [Abstract/FREE Full Text](http://heart.bmj.com/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6ODoiaGVhcnRqbmwiO3M6NToicmVzaWQiO3M6ODoiNzcvMi8xNTQiO3M6NDoiYXRvbSI7czoyNjoiL2hlYXJ0am5sLzEwNS8xNi8xMjczLmF0b20iO31zOjg6ImZyYWdtZW50IjtzOjA6IiI7fQ==) 

12.  Timpka S , Stuart JJ , Tanz LJ , et al . Lifestyle in progression from hypertensive disorders of pregnancy to chronic hypertension in Nurses' Health Study II: observational cohort study. BMJ 2017;358:j3024.[doi:10.1136/bmj.j3024](http://dx.doi.org/10.1136/bmj.j3024) 
    
    [Abstract/FREE Full Text](http://heart.bmj.com/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6MzoiYm1qIjtzOjU6InJlc2lkIjtzOjE3OiIzNTgvanVsMTJfNC9qMzAyNCI7czo0OiJhdG9tIjtzOjI2OiIvaGVhcnRqbmwvMTA1LzE2LzEyNzMuYXRvbSI7fXM6ODoiZnJhZ21lbnQiO3M6MDoiIjt9) 

13.  Bokslag A , Teunissen PW , Franssen C , et al . Effect of early-onset preeclampsia on cardiovascular risk in the fifth decade of life. Am J Obstet Gynecol 2017;216:523.e1–523.e7.[doi:10.1016/j.ajog.2017.02.015](http://dx.doi.org/10.1016/j.ajog.2017.02.015) 
    
    

14.  Benschop L , Duvekot JJ , Versmissen J , et al . Steegers EAP and Roeters van Lennep JE. Blood Pressure Profile 1 Year After Severe Preeclampsia. Hypertension 2018;71:491–8.
    
    

15.  Lykke JA , Langhoff-Roos J , Sibai BM , et al . Hypertensive pregnancy disorders and subsequent cardiovascular morbidity and type 2 diabetes mellitus in the mother. Hypertension 2009;53:944–51.[doi:10.1161/HYPERTENSIONAHA.109.130765](http://dx.doi.org/10.1161/HYPERTENSIONAHA.109.130765) 
    
    [CrossRef](http://heart.bmj.com/lookup/external-ref?access_num=10.1161/HYPERTENSIONAHA.109.130765&link_type=DOI) 
    
    [PubMed](http://heart.bmj.com/lookup/external-ref?access_num=19433776&link_type=MED&atom=%2Fheartjnl%2F105%2F16%2F1273.atom) 

16.  Hermida RC , Ayala DE , Mojón A , et al . Blunted sleep-time relative blood pressure decline increases cardiovascular risk independent of blood pressure level--the "normotensive non-dipper" paradox. Chronobiol Int 2013;30:87–98.[doi:10.3109/07420528.2012.701127](http://dx.doi.org/10.3109/07420528.2012.701127) 
    
    [CrossRef](http://heart.bmj.com/lookup/external-ref?access_num=10.3109/07420528.2012.701127&link_type=DOI) 
    
    [PubMed](http://heart.bmj.com/lookup/external-ref?access_num=23039824&link_type=MED&atom=%2Fheartjnl%2F105%2F16%2F1273.atom) 

17.  Fagard RH , Thijs L , Staessen JA , et al . Night-day blood pressure ratio and dipping pattern as predictors of death and cardiovascular events in hypertension. J Hum Hypertens 2009;23:645–53.[doi:10.1038/jhh.2009.9](http://dx.doi.org/10.1038/jhh.2009.9) 
    
    [CrossRef](http://heart.bmj.com/lookup/external-ref?access_num=10.1038/jhh.2009.9&link_type=DOI) 
    
    [PubMed](http://heart.bmj.com/lookup/external-ref?access_num=19225527&link_type=MED&atom=%2Fheartjnl%2F105%2F16%2F1273.atom) 

18.  Brouwers L , van der Meiden-van Roest AJ , Savelkoul C , et al . Recurrence of pre-eclampsia and the risk of future hypertension and cardiovascular disease: a systematic review and meta-analysis. BJOG 2018;125:1642–54.[doi:10.1111/1471-0528.15394](http://dx.doi.org/10.1111/1471-0528.15394) 
    
    

19.  Melsom T , Solbu MD , Schei J , et al . Mild Albuminuria Is a Risk Factor for Faster GFR Decline in the Nondiabetic Population. Kidney Int Rep 2018;3:817–24.[doi:10.1016/j.ekir.2018.01.015](http://dx.doi.org/10.1016/j.ekir.2018.01.015) 
    
    

20.  Arnlöv J , Evans JC , Meigs JB , et al . Low-grade albuminuria and incidence of cardiovascular disease events in nonhypertensive and nondiabetic individuals: the Framingham Heart Study. Circulation 2005;112:969–75.[doi:10.1161/CIRCULATIONAHA.105.538132](http://dx.doi.org/10.1161/CIRCULATIONAHA.105.538132) 
    
    [Abstract/FREE Full Text](http://heart.bmj.com/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6MTQ6ImNpcmN1bGF0aW9uYWhhIjtzOjU6InJlc2lkIjtzOjk6IjExMi83Lzk2OSI7czo0OiJhdG9tIjtzOjI2OiIvaGVhcnRqbmwvMTA1LzE2LzEyNzMuYXRvbSI7fXM6ODoiZnJhZ21lbnQiO3M6MDoiIjt9) 

21.  McDonald SD , Han Z , Walsh MW , et al . Kidney disease after preeclampsia: a systematic review and meta-analysis. Am J Kidney Dis 2010;55:1026–39.[doi:10.1053/j.ajkd.2009.12.036](http://dx.doi.org/10.1053/j.ajkd.2009.12.036) 
    
    [CrossRef](http://heart.bmj.com/lookup/external-ref?access_num=10.1053/j.ajkd.2009.12.036&link_type=DOI) 
    
    [PubMed](http://heart.bmj.com/lookup/external-ref?access_num=20346562&link_type=MED&atom=%2Fheartjnl%2F105%2F16%2F1273.atom) 
    
    [Web of Science](http://heart.bmj.com/lookup/external-ref?access_num=000278036400011&link_type=ISI) 

22.  Dai L , Chen Y , Sun W , et al . Association Between Hypertensive Disorders During Pregnancy and the Subsequent Risk of End-Stage Renal Disease: A Population-Based Follow-Up Study. J Obstet Gynaecol Can 2018;40:1129–38.[doi:10.1016/j.jogc.2018.01.022](http://dx.doi.org/10.1016/j.jogc.2018.01.022) 
    
    

23.  Hitti J , Sienas L , Walker S , et al . Contribution of hypertension to severe maternal morbidity. Am J Obstet Gynecol 2018;219:405.e1–405.e7.[doi:10.1016/j.ajog.2018.07.002](http://dx.doi.org/10.1016/j.ajog.2018.07.002) 
    
    

24.  Vikse BE , Irgens LM , Leivestad T , et al . Preeclampsia and the risk of end-stage renal disease. N Engl J Med 2008;359:800–9.[doi:10.1056/NEJMoa0706790](http://dx.doi.org/10.1056/NEJMoa0706790) 
    
    [CrossRef](http://heart.bmj.com/lookup/external-ref?access_num=10.1056/NEJMoa0706790&link_type=DOI) 
    
    [PubMed](http://heart.bmj.com/lookup/external-ref?access_num=18716297&link_type=MED&atom=%2Fheartjnl%2F105%2F16%2F1273.atom) 
    
    [Web of Science](http://heart.bmj.com/lookup/external-ref?access_num=000258568600005&link_type=ISI) 

25.  Hermes W , Ket JC , van Pampus MG , et al . Biochemical cardiovascular risk factors after hypertensive pregnancy disorders: a systematic review and meta-analysis. Obstet Gynecol Surv 2012;67:793–809.[doi:10.1097/OGX.0b013e31827682fc](http://dx.doi.org/10.1097/OGX.0b013e31827682fc) 
    
    

26.  Zoet GA , Benschop L , Boersma E , et al . Prevalence of Subclinical Coronary Artery Disease Assessed by Coronary Computed Tomography Angiography in 45- to 55-Year-Old Women With a History of Preeclampsia. Circulation 2018;137:877–9.[doi:10.1161/CIRCULATIONAHA.117.032695](http://dx.doi.org/10.1161/CIRCULATIONAHA.117.032695) 
    
    [FREE Full Text](http://heart.bmj.com/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiRlVMTCI7czoxMToiam91cm5hbENvZGUiO3M6MTQ6ImNpcmN1bGF0aW9uYWhhIjtzOjU6InJlc2lkIjtzOjk6IjEzNy84Lzg3NyI7czo0OiJhdG9tIjtzOjI2OiIvaGVhcnRqbmwvMTA1LzE2LzEyNzMuYXRvbSI7fXM6ODoiZnJhZ21lbnQiO3M6MDoiIjt9) 

27.  Feig DS , Shah BR , Lipscombe LL , et al . Preeclampsia as a risk factor for diabetes: a population-based cohort study. PLoS Med 2013;10:e1001425.[doi:10.1371/journal.pmed.1001425](http://dx.doi.org/10.1371/journal.pmed.1001425) 
    
    [CrossRef](http://heart.bmj.com/lookup/external-ref?access_num=10.1371/journal.pmed.1001425&link_type=DOI) 
    
    [PubMed](http://heart.bmj.com/lookup/external-ref?access_num=23610560&link_type=MED&atom=%2Fheartjnl%2F105%2F16%2F1273.atom) 

28.  Milic NM , Milin-Lazovic J , Weissgerber TL , et al . Preclinical atherosclerosis at the time of pre-eclamptic pregnancy and up to 10 years postpartum: systematic review and meta-analysis. Ultrasound Obstet Gynecol 2017;49:110–5.[doi:10.1002/uog.17367](http://dx.doi.org/10.1002/uog.17367) 
    
    

29.  Garovic VD , Milic NM , Weissgerber TL , et al . Carotid Artery Intima-Media Thickness and Subclinical Atherosclerosis in Women With Remote Histories of Preeclampsia: Results From a Rochester Epidemiology Project-Based Study and Meta-analysis. Mayo Clin Proc 2017;92:1328–40.[doi:10.1016/j.mayocp.2017.05.030](http://dx.doi.org/10.1016/j.mayocp.2017.05.030) 
    
    

30.  White WM , Mielke MM , Araoz PA , et al . A history of preeclampsia is associated with a risk for coronary artery calcification 3 decades later. Am J Obstet Gynecol 2016;214:519.e1–519.e8.[doi:10.1016/j.ajog.2016.02.003](http://dx.doi.org/10.1016/j.ajog.2016.02.003) 
    
    [CrossRef](http://heart.bmj.com/lookup/external-ref?access_num=10.1016/j.ajog.2016.02.003&link_type=DOI) 
    
    [PubMed](http://heart.bmj.com/lookup/external-ref?access_num=26874301&link_type=MED&atom=%2Fheartjnl%2F105%2F16%2F1273.atom) 

31.  Beckman JP , Camp JJ , Lahr BD , et al . Pregnancy history, coronary artery calcification and bone mineral density in menopausal women. Climacteric 2018;21:53–9.[doi:10.1080/13697137.2017.1406910](http://dx.doi.org/10.1080/13697137.2017.1406910) 
    
    

32.  Bellamy L , Casas JP , Hingorani AD , et al . Pre-eclampsia and risk of cardiovascular disease and cancer in later life: systematic review and meta-analysis. BMJ 2007;335:974.[doi:10.1136/bmj.39335.385301.BE](http://dx.doi.org/10.1136/bmj.39335.385301.BE) 
    
    [Abstract/FREE Full Text](http://heart.bmj.com/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6MzoiYm1qIjtzOjU6InJlc2lkIjtzOjEyOiIzMzUvNzYyNy85NzQiO3M6NDoiYXRvbSI7czoyNjoiL2hlYXJ0am5sLzEwNS8xNi8xMjczLmF0b20iO31zOjg6ImZyYWdtZW50IjtzOjA6IiI7fQ==) 

33.  Wu P , Haththotuwa R , Kwok CS , et al . Preeclampsia and Future Cardiovascular Health: A Systematic Review and Meta-Analysis. Circ Cardiovasc Qual Outcomes 2017;10.[doi:10.1161/CIRCOUTCOMES.116.003497](http://dx.doi.org/10.1161/CIRCOUTCOMES.116.003497) 
    
    

34.  Riise HK , Sulo G , Tell GS , et al . Incident Coronary Heart Disease After Preeclampsia: Role of Reduced Fetal Growth, Preterm Delivery, and Parity. J Am Heart Assoc 2017;6.[doi:10.1161/JAHA.116.004158](http://dx.doi.org/10.1161/JAHA.116.004158) 
    
    

35.  Hernández-Díaz S , Toh S , Cnattingius S . Risk of pre-eclampsia in first and subsequent pregnancies: prospective cohort study. BMJ 2009;338:b2255.[doi:10.1136/bmj.b2255](http://dx.doi.org/10.1136/bmj.b2255) 
    
    [Abstract/FREE Full Text](http://heart.bmj.com/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6MzoiYm1qIjtzOjU6InJlc2lkIjtzOjE3OiIzMzgvanVuMThfMS9iMjI1NSI7czo0OiJhdG9tIjtzOjI2OiIvaGVhcnRqbmwvMTA1LzE2LzEyNzMuYXRvbSI7fXM6ODoiZnJhZ21lbnQiO3M6MDoiIjt9) 

36.  Riise HKR , Sulo G , Tell GS , et al . Association Between Gestational Hypertension and Risk of Cardiovascular Disease Among 617 589 Norwegian Women. J Am Heart Assoc 2018;7.[doi:10.1161/JAHA.117.008337](http://dx.doi.org/10.1161/JAHA.117.008337) 
    
    

37.  Groenhof TKJ , Zoet GA , Franx A , et al . Trajectory of Cardiovascular Risk Factors After Hypertensive Disorders of Pregnancy. Hypertension 2019;73:171–8.[doi:10.1161/HYPERTENSIONAHA.118.11726](http://dx.doi.org/10.1161/HYPERTENSIONAHA.118.11726) 
    
    

38.  Benschop L , Bergen NE , Schalekamp-Timmermans S , et al . Steegers EAP and Roeters van Lennep JE. Maternal lipid profile 6 years after a gestational hypertensive disorder. J Clin Lipidol 2018;12:428–36.
    
    

39.  Mosca L , Benjamin EJ , Berra K , et al . Effectiveness-based guidelines for the prevention of cardiovascular disease in women--2011 update: a guideline from the american heart association. Circulation 2011;123:1243–62.[doi:10.1161/CIR.0b013e31820faaf8](http://dx.doi.org/10.1161/CIR.0b013e31820faaf8) 
    
    [FREE Full Text](http://heart.bmj.com/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiRlVMTCI7czoxMToiam91cm5hbENvZGUiO3M6MTQ6ImNpcmN1bGF0aW9uYWhhIjtzOjU6InJlc2lkIjtzOjExOiIxMjMvMTEvMTI0MyI7czo0OiJhdG9tIjtzOjI2OiIvaGVhcnRqbmwvMTA1LzE2LzEyNzMuYXRvbSI7fXM6ODoiZnJhZ21lbnQiO3M6MDoiIjt9) 

40.  Visintin C , Mugglestone MA , Almerie MQ , et al . Walkinshaw S and Guideline Development G. Management of hypertensive disorders during pregnancy: summary of NICE guidance. Bmj 2010;341:c2207.
    
    [FREE Full Text](http://heart.bmj.com/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiRlVMTCI7czoxMToiam91cm5hbENvZGUiO3M6MzoiYm1qIjtzOjU6InJlc2lkIjtzOjE3OiIzNDEvYXVnMjVfMy9jMjIwNyI7czo0OiJhdG9tIjtzOjI2OiIvaGVhcnRqbmwvMTA1LzE2LzEyNzMuYXRvbSI7fXM6ODoiZnJhZ21lbnQiO3M6MDoiIjt9) 

41. American College of Obstetricians and Gynecologists. Task Force on Hypertension in Pregnancy. Hypertension in pregnancy practice guideline. WQ 2013;244.
    
    

42.  Regitz-Zagrosek V , Roos-Hesselink JW , Bauersachs J , et al . ESC Guidelines for the management of cardiovascular diseases during pregnancy. Eur Heart J 2018;2018:3165–241.
    
    

43.  Bushnell C , McCullough LD , Awad IA , et al . Guidelines for the prevention of stroke in women: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2014;45:1545–88.[doi:10.1161/01.str.0000442009.06663.48](http://dx.doi.org/10.1161/01.str.0000442009.06663.48) 
    
    [Abstract/FREE Full Text](http://heart.bmj.com/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6OToic3Ryb2tlYWhhIjtzOjU6InJlc2lkIjtzOjk6IjQ1LzUvMTU0NSI7czo0OiJhdG9tIjtzOjI2OiIvaGVhcnRqbmwvMTA1LzE2LzEyNzMuYXRvbSI7fXM6ODoiZnJhZ21lbnQiO3M6MDoiIjt9) 

44. Gynaecologists RCoOa. Severe Pre-eclampsia/Eclampsia, Management (Green-top Guideline No. 10A). 2006.
    
    

45.  Magee LA , Pels A , Helewa M , et al . Diagnosis, evaluation, and management of the hypertensive disorders of pregnancy: executive summary. J Obstet Gynaecol Can 2014;36:575–6.[doi:10.1016/S1701-2163(15)30533-8](http://dx.doi.org/10.1016/S1701-2163(15)30533-8) 
    
    [CrossRef](http://heart.bmj.com/lookup/external-ref?access_num=10.1016/S1701-2163(15)30533-8&link_type=DOI) 
    
    [PubMed](http://heart.bmj.com/lookup/external-ref?access_num=25184972&link_type=MED&atom=%2Fheartjnl%2F105%2F16%2F1273.atom) 

46.  Williams B , Mancia G , Spiering W , et al . ESC/ESH Guidelines for the management of arterial hypertension. Eur Heart J 2018;2018:3021–104.
    
    

47.  Lowe SA , Bowyer L , Lust K , et al . SOMANZ guidelines for the management of hypertensive disorders of pregnancy 2014. Aust N Z J Obstet Gynaecol 2015;55:e1–e29.[doi:10.1111/ajo.12399](http://dx.doi.org/10.1111/ajo.12399) 
    
    [CrossRef](http://heart.bmj.com/lookup/external-ref?access_num=10.1111/ajo.12399&link_type=DOI) 
    
    [PubMed](http://heart.bmj.com/lookup/external-ref?access_num=26412014&link_type=MED&atom=%2Fheartjnl%2F105%2F16%2F1273.atom) 

48.  Nowik CM , Pudwell J , Smith GN . Evaluating the Postpartum Maternal Health Clinic: How Patient Characteristics Predict Follow-Up. J Obstet Gynaecol Can 2016;38:930–5.[doi:10.1016/j.jogc.2016.05.005](http://dx.doi.org/10.1016/j.jogc.2016.05.005) 
    
    

49.  Whelton PK , Carey RM , Aronow WS , et al . ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation 2017;2018:e426–e483.
    
    

50. Nederlandse Vereniging voor Obstetrie en Gynaecologie. Cardiovasculair risicomanagement na een reproductieve aandoening 2014.
    
    

51.  Piepoli MF , Hoes AW , Agewall S , et al . European Guidelines on cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts)Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). Eur Heart J 2016;2016:2315–81.
    
    

52.  Lupoli R , Vaccaro A , Ambrosino P , et al . Impact of Vitamin D deficiency on subclinical carotid atherosclerosis: a pooled analysis of cohort studies. J Clin Endocrinol Metab 2017:2146–53.[doi:10.1210/jc.2017-00342](http://dx.doi.org/10.1210/jc.2017-00342) 
    
    

53.  Meiszterics Z , Tímár O , Gaszner B , et al . Early morphologic and functional changes of atherosclerosis in systemic sclerosis-a systematic review and meta-analysis. Rheumatology 2016;55:2119–30.[doi:10.1093/rheumatology/kew236](http://dx.doi.org/10.1093/rheumatology/kew236) 
    
    [CrossRef](http://heart.bmj.com/lookup/external-ref?access_num=10.1093/rheumatology/kew236&link_type=DOI) 
    
    [PubMed](http://heart.bmj.com/lookup/external-ref?access_num=27565177&link_type=MED&atom=%2Fheartjnl%2F105%2F16%2F1273.atom) 

54.  Narverud I , Retterstøl K , Iversen PO , et al . Markers of atherosclerotic development in children with familial hypercholesterolemia: a literature review. Atherosclerosis 2014;235:299–309.[doi:10.1016/j.atherosclerosis.2014.05.917](http://dx.doi.org/10.1016/j.atherosclerosis.2014.05.917) 
    
    [CrossRef](http://heart.bmj.com/lookup/external-ref?access_num=10.1016/j.atherosclerosis.2014.05.917&link_type=DOI) 
    
    [PubMed](http://heart.bmj.com/lookup/external-ref?access_num=24908240&link_type=MED&atom=%2Fheartjnl%2F105%2F16%2F1273.atom)