Article

Cardiac Disease after Pregnancy: A Growing Problem

Register or Login to View PDF Permissions
Permissions× For commercial reprint enquiries please contact Springer Healthcare: ReprintsWarehouse@springernature.com.

For permissions and non-commercial reprint enquiries, please visit Copyright.com to start a request.

For author reprints, please email rob.barclay@radcliffe-group.com.
Average (ratings)
No ratings
Your rating

Abstract

Pregnancy complications, such as hypertensive disorders or preterm delivery, identify families predisposed to cardiovascular problems at other times in life. Whether the pregnancy complication induces cardiac disease or whether the pregnancy stress unmasks an underlying predisposition remains unclear. However, improved survival following severe pregnancy complications for both the mother and, in particular, the offspring – who is often born preterm – has resulted in a growing cohort of individuals who carry this increased cardiovascular risk. Research to understand the underlying pathological mechanisms that link these conditions might ultimately lead to novel therapeutic or prevention strategies for both cardiovascular and pregnancy disease.

Disclosure:The authors have no conflicts of interest to declare.

Received:

Accepted:

Correspondence Details:Prof Paul Leeson, Cardiovascular Clinical Research Facility, BHF Centre for Research Excellence, Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DU, UK. E: paul.leeson@cardiov.ox.ac.uk

Copyright Statement:

The copyright in this work belongs to Radcliffe Medical Media. Only articles clearly marked with the CC BY-NC logo are published with the Creative Commons by Attribution Licence. The CC BY-NC option was not available for Radcliffe journals before 1 January 2019. Articles marked ‘Open Access’ but not marked ‘CC BY-NC’ are made freely accessible at the time of publication but are subject to standard copyright law regarding reproduction and distribution. Permission is required for reuse of this content.

Historically pregnancy has been viewed as only clinically relevant to women and for the relatively brief time from conception to the puerperium. However it is now clear that events during pregnancy have much longer-term implications, particularly for cardiovascular health, both for the mother and her offspring.

Pregnancy complications such as hypertension and preterm birth appear to serve as a key early indicator of cardiovascular risk for both mother and child. For example, pregnancy complicated by de novo hypertension (preeclampsia or gestational hypertension) is frequent and affects 6–10 % of pregnancies.1–4 It is now well established that a diagnosis of hypertensive disorder of pregnancy is associated with an increased risk of maternal cardiovascular disease: almost 1.5-times increase in ischaemic heart disease, fivefold risk of hypertension, threefold risk of cardiovascular death, almost twofold risk of heart failure and twofold risk of stroke.5–8 There is also evidence of a correlation between the severity of hypertensive disorder of pregnancy and the risk of cardiac disease.9 Similarly preterm delivery (birth before 37 weeks gestation), which occurs in 11 % of births worldwide, is increasing in incidence10 and, independent of hypertension, is associated with elevated maternal cardiovascular risk.11,12

Offspring born to women who have experienced pregnancy complications also display adverse cardiovascular findings. Those born preterm have increased blood pressure in adolescence13–18 and adult life,19–26 with a 10.5 % prevalence of clinical hypertension and 45.9 % prevalence of prehypertension in 19-year-old preterm born adults.16 They are also relatively more likely to require antihypertensive medication in young adulthood.27 Preterm born women have a doubling of lifetime coronary heart disease risk28 and offspring born prior to 32 weeks have a twofold increase in cerebrovascular disease.29 Some evidence is also emerging of increased insulin resistance in those born preterm,19,20,22,23,30 which may be a precursor to later development of metabolic syndrome31 or type 2 diabetes.30

In a meta-analysis using data from 45,249 individuals we reported an increase in systolic and diastolic blood pressure in children and adolescents born to preeclamptic pregnancies32 that, if it tracked into adult life, would be associated with an 8 % increased risk of mortality from ischaemic heart disease and a 12 % increased risk of stroke.32 These findings are supported by our analysis of data from a 20-year prospective follow-up birth cohort study of 2,868 young adults, which reported that the clinical incidence of hypertension was increased in those born to mothers who had hypertensive disorders of pregnancy.33 These young adults were 2.5 times more likely to have global lifetime risk (QRISK®) scores above the 75th centile and 30 % of 20-year-olds with hypertensive blood pressures were born following a hypertensive pregnancy. Those whose mother had more severe hypertensive pregnancy disease, such as preeclampsia or preterm birth, had a threefold greater risk of being clinically hypertensive.33 Furthermore, one study showed that offspring of preeclamptic pregnancies were more likely to be prescribed antihypertensive medication by the age of 50 years34 and had double the risk of stroke in adult life35

Figure 1 highlights potential links between pregnancy complications in the mother and future cardiovascular health for them and their child, as well as the risk of pregnancy disease in future generations.

Potential Pathophysiological Pathways

A number of risk factors common to both pregnancy complications and cardiovascular disease might explain these links. Raised blood pressure, high maternal age, diabetes and obesity increase the risk of preeclampsia;1,36–41 whereas smoking,42 lower socioeconomic group43 and maternal age44 are risk factors for preterm delivery. Pregnancy complications might therefore unmask existing subclinical cardiovascular disease in the mother due to the physiological stress she is under. Alternatively there may be common disease mechanisms between pregnancy and cardiovascular disease. Unfortunately longitudinal studies that track from pre-pregnancy through to later life clinical events do not exist and therefore it remains difficult to unpick these associations. Cross-sectional observational studies that measure surrogate markers several months and years after affected pregnancy can be informative of potential pathophysiological associations. However, the majority of such studies recruit during or after pregnancy and so the relevance of the cardiovascular system pre-conception in these populations is not yet clear. Nevertheless, what these studies have shown is that women who delivered preterm had higher blood pressure, adverse lipid profiles and higher carotid intima media thickness 4–12 years after delivery compared to women who delivered at term.45 Women with a history of hypertensive pregnancy have an adverse cardiac structure and function, with higher left ventricular mass index and greater diastolic dysfunction.46 They also have evidence of greater blood pressure,47 arterial stiffness,48 reduced capillary density49 and adverse grey and white matter brain differences.50 These studies suggest that there is a range of adverse cardiovascular phenotypic differences in women in the months and years after complicated pregnancy prior to the development of cardiovascular events. The identification of higher risk subgroups within these populations might therefore be possible and risk reduction strategies could be targeted to reduce cardiovascular morbidity and mortality.

Similar phenotypic differences are also evident in the offspring early in life. We have demonstrated cardiovascular modifications in young adults born preterm using cardiovascular magnetic resonance.51,52 Those born preterm had an increased left ventricular mass and a distinct ventricular shape with shorter ventricles, small internal diameters and a displaced apex.52 Similar but proportionately greater differences were evident in the right ventricle51 with associated left and right systolic and diastolic dysfunction.51,52 These distinct cardiovascular phenotypes emerge in the first few months of postnatal life in preterm infants,53 probably because at birth there is a myocardial switch from a foetal hyperplastic cellular phenotype to one of hypertrophy.54 Animal models have demonstrated that this switch also happens at the time of preterm birth.55,56 This switch, in addition to significant flow changes, may result in the cardiac remodelling that has been observed in both animal and human studies.

It has been suggested that preterm birth also has an effect on vascular structure and function, with several studies reporting that large arteries are significantly smaller in children, adolescents14,57–59 and adults born preterm.60 Abnormalities in the microvascular system have also been demonstrated, with a reduction in cutaneous capillary61–63 and retinal vascular64–66 beds in individuals born preterm. Capillary rarefaction is thought to play an important role in the increased peripheral vascular resistance found in patients with hypertension.67–69 It has also been hypothesised that microvascular changes may play a causative role in the disease as it is also observed in normotensive at-risk populations70 and arteriolar narrowing in the retina has been shown to be an accurate predictor of hypertension.71 Several mechanisms for these microvascular differences have been put forward, including that preterm birth causes a shift towards a more anti-angiogenic profile, which may then have an effect on microvascular development. Young adults born preterm have been shown to exhibit an enhanced anti-angiogenic state, with elevations in soluble endoglin and soluble fms-like tyrosine kinase-1 that are associated with elevations in blood pressure mediated through capillary rarefaction.62

Figure 1: Potential Links Between Pregnancy Complications and Future Cardiovascular Health in Mother and Child

Article image

The offspring of hypertensive pregnancies also have a distinct cardiovascular phenotype characterised by impaired flow-mediated endothelial responses25 and an increased intima-media thickness25 suggesting an early atherogenic phenotype consistent with the aortic arterial thickening known to occur in preeclamptic offspring at birth.72 A recent study has also demonstrated cardiac remodelling in adolescents exposed to hypertensive disorders of pregnancy, with a greater relative wall thickness compared to controls and a reduced left ventricular end-diastolic volume.73 The natural history of these cardiovascular modifications linked with pregnancy complications and their relevance to future cardiovascular disease risk is of emerging interest.

Where does this Leave Clinicians and Researchers?

National and international guidelines include a maternal history of hypertensive pregnancy as a risk factor for cardiovascular disease and some also offer recommendations that blood pressure and other cardiovascular risk factors should be assessed postpartum.74–78 Most guidelines do not offer detailed recommendations, however, and leave the specifics on how to follow up this population to the clinician.74 The potential from using a history of pregnancy complication for the early identification of individuals at increased cardiovascular risk, both for mothers and offspring, is highly attractive as it could potentially allow a significant time window for risk attenuation. Future research into which are the most sensitive characteristics of pregnancy complications for identifying individuals at increased cardiovascular risk will be of value.

Understanding why there are links between pregnancy complications and cardiovascular disease remains of importance for two major reasons. First, it will help to identify populations who are at a higher risk of developing cardiovascular disease in later life. This could enable targeted education schemes and primary prevention strategies, in addition to rigorous monitoring pathways, for both mother and child, which might result in earlier diagnosis and treatment. Second, it raises the possibility of insights into novel mechanisms that might have relevance to our understanding and management of both pregnancy and cardiovascular disease, ultimately leading to novel therapeutic approaches.

References

  1. Ros HS, Cnattingius S, Lipworth L. Comparison of risk factors for preeclampsia and gestational hypertension in a population-based cohort study. Am J Epidemiol 1998;147: 1062–70.
    Crossref | PubMed
  2. 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.
    Crossref | PubMed
  3. Gillon TE, Pels A, von Dadelszen P, et al. Hypertensive disorders of pregnancy: A systematic review of international clinical practice guidelines. PLoS One 2014;9:e113715.
    Crossref | PubMed
  4. Abalos E, Cuesta C, Grosso AL, et al. Global and regional estimates of preeclampsia and eclampsia: A systematic review. Eur J Obstet Gynecol Reprod Biol 2013;170:1–7.
    Crossref | PubMed
  5. Männistï T, Mendola P, Vääräsmäki M, et al. Elevated blood pressure in pregnancy and subsequent chronic disease risk. Circulation 2013;127:681–90.
    Crossref | PubMed
  6. Wilson BJ, Watson MS, Prescott GJ, et al. Hypertensive diseases of pregnancy and risk of hypertension and stroke in later life: Results from cohort study. BMJ 2003;326:845.
    Crossref | PubMed
  7. Garovic VD, Bailey KR, Boerwinkle E, et al. Hypertension in pregnancy as a risk factor for cardiovascular disease later in life. J Hypertens 2010;28:826–33.
    Crossref | PubMed
  8. 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.
    Crossref | PubMed
  9. McDonald SD, Malinowski A, Zhou Q, et al. Cardiovascular sequelae of preeclampsia/eclampsia: A systematic review and meta-analyses. Am Heart J 2008;156:918–30.
    Crossref | PubMed
  10. Blencowe H, Cousens S, Oestergaard MZ, et al. National, regional, and worldwide estimates of preterm birth rates in the year 2010 with time trends since 1990 for selected countries: A systematic analysis and implications. Lancet 2012;379:2162–72.
    Crossref | PubMed
  11. Catov JM, Wu CS, Olsen J, et al. Early or recurrent preterm birth and maternal cardiovascular disease risk. Ann Epidemiol 2010;20:604–9.
    Crossref | PubMed
  12. Bonamy AK, Parikh NI, Cnattingius S, et al. Birth characteristics and subsequent risks of maternal cardiovascular disease: Effects of gestational age and fetal growth. Circulation 2011;124:2839–46.
    Crossref | PubMed
  13. Johansson S, Iliadou A, Bergvall N, et al. Risk of high blood pressure among young men increases with the degree of immaturity at birth. Circulation 2005;112:3430–6.
    Crossref | PubMed
  14. Bonamy AK, Bendito A, Martin H, et al. Preterm birth contributes to increased vascular resistance and higher blood pressure in adolescent girls. Pediatr Res 2005;58:845–9.
    Crossref | PubMed
  15. Evensen KA, Steinshamn S, Tjønna AE, et al. Effects of preterm birth and fetal growth retardation on cardiovascular risk factors in young adulthood. Early Hum Dev 2009;85:239–45.
    Crossref | PubMed
  16. Keijzer-Veen MG, Finken MJ, Nauta J, et al. Dutch POPS-19 Collaborative Study Group. Is blood pressure increased 19 years after intrauterine growth restriction and preterm birth? A prospective follow-up study in the Netherlands. Pediatrics 2005;116:725–31.
    Crossref | PubMed
  17. Pharoah PO, Stevenson CJ, West CR. Association of blood pressure in adolescence with birthweight. Arch Dis Child Fetal Neonatal Ed 1998;79:F114–8. PMCID: PMC1720839
    Crossref | PubMed
  18. Vohr BR, Allan W, Katz KH, et al. Early predictors of hypertension in prematurely born adolescents. Acta Paediatr 2010;99:1812–8.
    Crossref | PubMed
  19. Dalziel SR, Parag V, Rodgers A, et al. Cardiovascular risk factors at age 30 following pre-term birth. Int J Epidemiol 2007;36:907–15.
    Crossref | PubMed
  20. Irving RJ, Belton NR, Elton RA, et al. Adult cardiovascular risk factors in premature babies. Lancet 2000;355:2135–6.
    Crossref | PubMed
  21. Kistner A, Celsi G, Vanpee M, et al. Increased systolic daily ambulatory blood pressure in adult women born preterm. Pediatr Nephrol 2005;20:232–3.
    Crossref | PubMed
  22. Rotteveel J, van Weissenbruch MM, Twisk JW, et al. Infant and childhood growth patterns, insulin sensitivity, and blood pressure in prematurely born young adults. Pediatrics 2008;122:313–21.
    Crossref | PubMed
  23. Hovi P, Andersson S, Eriksson JG, et al. Glucose regulation in young adults with very low birth weight. N Engl J Med 2007;356:2053–63.
    Crossref | PubMed
  24. Hack M, Schluchter M, Cartar L, et al. Blood pressure among very low birth weight (<1.5 kg) young adults. Pediatr Res 2005;58:677–84.
    Crossref | PubMed
  25. Lazdam M, de la Horra A, Pitcher A, et al. Elevated blood pressure in offspring born premature to hypertensive pregnancy: Is endothelial dysfunction the underlying vascular mechanism? Hypertension 2010;56:159–65.
    Crossref | PubMed
  26. Hovi P, Andersson S, Raikkonen K, et al. Ambulatory blood pressure in young adults with very low birth weight. J Pediatr 2010;156:54–9 e51.
    Crossref | PubMed
  27. Crump C, Winkleby MA, Sundquist K, et al. Risk of hypertension among young adults who were born preterm: A Swedish national study of 636,000 births. Am J Epidemiol 2011;173:797–803.
    Crossref | PubMed
  28. Kajantie E, Osmond C, Eriksson JG. Coronary heart disease and stroke in adults born preterm – the Helsinki birth cohort study. Paediatr Perinat Epidemiol 2015;29:515–9.
    Crossref | PubMed
  29. Ueda P, Cnattingius S, Stephansson O, et al. Cerebrovascular and ischemic heart disease in young adults born preterm: A population-based swedish cohort study. Eur J Epidemiol 2014;29:253–60.
    Crossref | PubMed
  30. Hofman PL, Regan F, Jackson WE, et al. Premature birth and later insulin resistance. N Engl J Med 2004;351:2179–86.
    Crossref | PubMed
  31. Alberti KG, Eckel RH, Grundy SM, et al. International Diabetes Federation Task Force on Epidemiology and Prevention; Hational Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; International Association for the Study of Obesity. Harmonizing the metabolic syndrome: A joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 2009;120:1640–5.
    Crossref | PubMed
  32. Davis EF, Lazdam M, Lewandowski AJ, et al. Cardiovascular risk factors in children and young adults born to preeclamptic pregnancies: A systematic review. Pediatrics 2012;129:e1552– 61.
    Crossref | PubMed
  33. Davis EF, Lewandowski AJ, Aye C, et al. Clinical cardiovascular risk during young adulthood in offspring of hypertensive pregnancies: Insights from a 20-year prospective followup birth cohort. BMJ Open 2015;5:e008136.
    Crossref | PubMed
  34. Ferreira I, Peeters LL, Stehouwer CD. Preeclampsia and increased blood pressure in the offspring: Meta-analysis and critical review of the evidence. J Hypertens 2009;27:1955–9.
    Crossref | PubMed
  35. Kajantie E, Eriksson JG, Osmond C, et al. Pre-eclampsia is associated with increased risk of stroke in the adult offspring: The Helsinki birth cohort study. Stroke 2009;40:1176–80.
    Crossref | PubMed
  36. Toshimitsu M, Nagamatsu T, Nagasaka T, et al. Increased risk of pregnancy-induced hypertension and operative delivery after conception induced by in vitro fertilization/ intracytoplasmic sperm injection in women aged 40 years and older. Fertil Steril 2014;102:1065–70 e1061.
    Crossref | PubMed
  37. Duckitt K, Harrington D. Risk factors for pre-eclampsia at antenatal booking: Systematic review of controlled studies. BMJ 2005;330:565.
    Crossref | PubMed
  38. van Oostwaard MF, Langenveld J, Schuit E, et al. Recurrence of hypertensive disorders of pregnancy: An individual patient data metaanalysis. Am J Obstet Gynecol 2015;212:624 e621–617.
    Crossref | PubMed
  39. Ursavas A, Karadag M, Nalci N, et al. Self-reported snoring, maternal obesity and neck circumference as risk factors for pregnancy-induced hypertension and preeclampsia. Respiration 2008;76:33–9.
    Crossref | PubMed
  40. Parazzini F, Bortolus R, Chatenoud L, et al. Risk factors for pregnancy-induced hypertension in women at high risk for the condition. Italian study of aspirin in pregnancy group. Epidemiology 1996;7:306–8
    Crossref | PubMed
  41. Li DK, Wi S. Changing paternity and the risk of preeclampsia/ eclampsia in the subsequent pregnancy. Am J Epidemiol 2000;151:57–62.
    Crossref | PubMed
  42. Andres RL, Day MC. Perinatal complications associated with maternal tobacco use. Semin Neonatol 2000;5:231–41.
    Crossref | PubMed
  43. Thompson JMD, Irgens LM, Rasmussen S, et al. Secular trends in socio-economic status and the implications for preterm birth. Paediatr Perinat Epidemiol 2006;20:182–7.
    Crossref | PubMed
  44. Astolfi P, Zonta LA. Risks of preterm delivery and association with maternal age, birth order, and fetal gender. Hum Reprod 1999;14:2891–4.
    Crossref | PubMed
  45. Catov JM, Dodge R, Barinas-Mitchell E, et al. Prior preterm birth and maternal subclinical cardiovascular disease 4 to 12 years after pregnancy. J Womens Health (Larchmt) 2013;22:835–43.
    Crossref | PubMed
  46. Scantlebury DC, Kane GC, Wiste HJ, et al. Left ventricular hypertrophy after hypertensive pregnancy disorders. Heart 2015;101:1584–90.
    Crossref | PubMed
  47. Fraser A, Nelson SM, Macdonald-Wallis C, et al. Associations of pregnancy complications with calculated cardiovascular disease risk and cardiovascular risk factors in middle age: The Avon Longitudinal Study of Parents and Children. Circulation 2012;125:1367–80.
    Crossref | PubMed
  48. Hausvater A, Giannone T, Sandoval YH, et al. The association between preeclampsia and arterial stiffness. J Hypertens 2012;30:17–33.
    Crossref | PubMed
  49. Nama V, Manyonda IT, Onwude J, et al. Structural capillary rarefaction and the onset of preeclampsia. Obstet Gynecol 2012;119:967–74.
    Crossref | PubMed
  50. Siepmann T, Boardman H, Bilderbeck A, et al. Longterm cerebral white and gray matter changes after preeclampsia. Neurology 2017;88:1256–64.
    Crossref | PubMed
  51. Lewandowski AJ, Bradlow WM, Augustine D, et al. Right ventricular systolic dysfunction in young adults born preterm. Circulation 2013;128:713–20.
    Crossref | PubMed
  52. Lewandowski AJ, Augustine D, Lamata P, et al. Preterm heart in adult life: Cardiovascular magnetic resonance reveals distinct differences in left ventricular mass, geometry, and function. Circulation 2013;127:197–206.
    Crossref | PubMed
  53. Aye CYL, Lewandowski AJ, Lamata P, et al. Disproportionate cardiac hypertrophy during early postnatal development in infants born preterm. Pediatr Res 2017; epub ahead of press
    Crossref | PubMed
  54. Rudolph AM. Myocardial growth before and after birth: Clinical implications. Acta Paediatr 2000;89:129–33.
    Crossref | PubMed
  55. Bensley JG, Stacy VK, De Matteo R, et al. Cardiac remodelling as a result of pre-term birth: Implications for future cardiovascular disease. Eur Heart J 2010;31:2058–66.
    Crossref | PubMed
  56. Bertagnolli M, Huyard F, Cloutier A, et al. Transient neonatal high oxygen exposure leads to early adult cardiac dysfunction, remodeling, and activation of the reninangiotensin system. Hypertension 2014;63:143–50.
    Crossref | PubMed
  57. Edstedt Bonamy AK, Bengtsson J, Nagy Z, et al. Preterm birth and maternal smoking in pregnancy are strong risk factors for aortic narrowing in adolescence. Acta Paediatr 2008;97:1080–5.
    Crossref | PubMed
  58. Singhal A, Kattenhorn M, Cole TJ, et al. Preterm birth, vascular function, and risk factors for atherosclerosis. Lancet 2001;358:1159–60.
    Crossref | PubMed
  59. Hovi P, Turanlahti M, Strang-Karlsson S, et al. Intima-media thickness and flow-mediated dilatation in the Helsinki study of very low birth weight adults. Pediatrics 2011;127:e304–11.
    Crossref | PubMed
  60. Boardman H, Birse K, Davis EF, et al. Comprehensive multimodality assessment of regional and global arterial structure and function in adults born preterm. Hypertens Res 2016;39: 39–45.
    Crossref | PubMed
  61. Bonamy AK, Martin H, Jörneskog G, et al. Lower skin capillary density, normal endothelial function and higher blood pressure in children born preterm. J Intern Med 2007;262: 635–42.
    Crossref | PubMed
  62. Lewandowski AJ, Davis EF, Yu G, et al. Elevated blood pressure in preterm-born offspring associates with a distinct antiangiogenic state and microvascular abnormalities in adult life. Hypertension 2015;65:607–14.
    Crossref | PubMed
  63. Yu GZ, Aye CY, Lewandowski AJ, et al. Association of maternal antiangiogenic profile at birth with early postnatal loss of microvascular density in offspring of hypertensive pregnancies. Hypertension 2016;68:749–59.
    Crossref | PubMed
  64. Gishti O, Jaddoe VW, Duijts L, et al. Impact of birth parameters and early life growth patterns on retinal microvascular structure in children: The Generation R Study. J Hypertens 2015;33:1429–37.
    Crossref | PubMed
  65. Kistner A, Jacobson L, Jacobson SH, et al. Low gestational age associated with abnormal retinal vascularization and increased blood pressure in adult women. Pediatr Res 2002;51:675–80.
    Crossref | PubMed
  66. Hellstrom A, Hard AL, Niklasson A, et al. Abnormal retinal vascularisation in preterm children as a general vascular phenomenon. Lancet 1998;352:1827.
    Crossref | PubMed
  67. Montagna W, Carlisle K. Structural changes in aging human skin. J Invest Dermatol 1979;73:47–53.
    Crossref | PubMed
  68. Shore AC, Tooke JE. Microvascular function in human essential hypertension. J Hypertens 1994;12:717–28.
    Crossref | PubMed
  69. Feihl F, Liaudet L, Waeber B, et al. Hypertension: A disease of the microcirculation? Hypertension 2006;48:1012–7.
    Crossref | PubMed
  70. Antonios TF, Rattray FM, Singer DR, et al. Rarefaction of skin capillaries in normotensive offspring of individuals with essential hypertension. Heart 2003;89:175–8.
    Crossref | PubMed
  71. Mitchell P, Cheung N, de Haseth K, et al. Blood pressure and retinal arteriolar narrowing in children. Hypertension 2007;49:1156–62.
    Crossref | PubMed
  72. Akcakus M, Altunay L, Yikilmaz A, et al. The relationship between abdominal aortic intima-media thickness and lipid profile in neonates born to mothers with preeclampsia. J Pediatr Endocrinol Metab 2010;23:1143–9.
    PubMed
  73. Timpka S, Macdonald-Wallis C, Hughes AD, et al. Hypertensive disorders of pregnancy and offspring cardiac structure and function in adolescence. J Am Heart Assoc 2016;5:pii:e003906.
    Crossref | PubMed
  74. Staff AC, Redman CW, Williams D, et al. Global Pregnancy Collaboration (CoLab). Pregnancy and long-term maternal cardiovascular health: Progress through harmonization of research cohorts and biobanks. Hypertension 2016;67: 251–60.
    Crossref | PubMed
  75. National Institute for Health and Care Excellence. Clinical Guideline CG 107: Hypertension in Pregnancy: Diagnosis and Management. 2010. Available at: www.nice.org.uk/guidance/CG107/ chapter/1-Guidance#advice-and-follow-up-care-at-transfer-tocommunity- care (accessed 17.05.2017)
  76. Lowe SA, Brown MA, Dekker GA, et al. Society of Obstetric Medicine of Australia and New Zealand. Guidelines for the management of hypertensive disorders of pregnancy 2008. Aus N Z J Obstet Gynaecol 2009;49:242–6.
    Crossref | PubMed
  77. European Society of Gynaecololgy; Association for European Paediatric Cardiology (AEPC); German Society for Gender Medicine (DGesGM); Regitz-Zagrosek V, Blomstrom Lundqvist C, Borghi C, et al; ESC Committee for Practice Guidelines. ESC Guidelines on the management of cardiovascular diseases during pregnancy: The Task Force on the Management of Cardiovascular Diseases during Pregnancy of the European Society of Cardiology (ESC). Eur Heart J 2011;32:3147–97.
    Crossref | PubMed
  78. 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.
    Crossref | PubMed