Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Focus on today’s evidence while keeping an eye on the future: lessons derived from hypertension in women

Abstract

While evidence-based medicine has contributed enormously to the uniformity and rationale of patient care, it is necessary that we anticipate changes in order to implement their rapid translation to practice. The purpose of this review is to expose three issues regarding cardiovascular health in women, including milestones to reflect the pace at which these are incorporated into public policies. Two of these matters, as changes in the thresholds of normal blood pressure in gestation and in nonpregnant women, need further evidence and deserve to be retrospectively analyzed in high-quality databases. The third subject derives from the association of remote cardiovascular complications of hypertensive pregnancies, an example of the unnecessary delay of more than two decades to install a wide prevention strategy when the health system is not on the watch.

This is a preview of subscription content

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Fig. 1: Diagram depicting the main mechanisms that lead to the generalized endothelial dysfunction that constitutes the pathological and clinical expression of preeclampsia.

References

  1. Mauvais-Jarvis F, Bairey Merz N, Barnes PJ, et al. Sex and gender: modifiers of health, disease, and medicine. Lancet. 2020;396:565–82.

    PubMed  PubMed Central  Google Scholar 

  2. Fourny N, Beauloye C, Bernard M, Horman S, Desrois M, Bertrand L. Sex differences of the diabetic heart. Front Physiol. 2021;12:661297.

    PubMed  PubMed Central  Google Scholar 

  3. Brown MA, Magee LA, Kenny LC, Karumanchi SA, McCarthy FP, Saito S, et al. The hypertensive disorders of pregnancy: ISSHP classification, diagnosis & management recommendations for international practice. Pregnancy Hypertens. 2018;13:291–310.

    CAS  PubMed  Google Scholar 

  4. Whelton PK, Carey RM, Aronow WS, Casey DE, Collins KJ, Dennison Himmelfarb C, 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: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. 2018;71:e13–5.

  5. Li Q, Zheng L, Jiang D, Gu Y, Wang G, Li J, et al. Early pregnancy stage 1 hypertension and high mean arterial pressure increased risk of adverse pregnancy outcomes in Shanghai, China. J Hum Hypertens. 2021;35:1–8. https://doi.org/10.1038/s41371-021-00523-6.

  6. Darwin KC, Federspiel JJ, Schuh BL, Baschat AA, Vaught AJ. ACC-AHA diagnostic criteria for hypertension in pregnancy identifies patients at intermediate risk of adverse outcomes. Am J Perinatol. 2021;38:e249–55.

    PubMed  Google Scholar 

  7. Bello NA, Zhou H, Cheetham TC, Miller E, Getahun DT, Fassett MJ, et al. Prevalence of hypertension among pregnant women when using the 2017 American College of Cardiology/American Heart Association Blood Pressure Guidelines and association with maternal and fetal outcomes. JAMA Netw Open. 2021;4:e213808.

    PubMed  PubMed Central  Google Scholar 

  8. Sabol BA, Porcelli B, Diveley E, Meyenburg K, Woolfolk C, Rosenbloom JI, et al. Defining the risk profile of women with stage 1 hypertension: a time to event analysis. Am J Obstet Gynecol MFM. 2021;3:100376.

    PubMed  Google Scholar 

  9. Greenberg VR, Silasi M, Lundsberg LS, Culhane JF, Reddy UM, Partridge C, et al. Perinatal outcomes in women with elevated blood pressure and stage 1 hypertension. Am J Obstet Gynecol. 2021;224:521.e1–521.e11.

    CAS  Google Scholar 

  10. Bone JN, Magee LA, Singer J, Nathan H, Qureshi RN, Sacoor C, et al. Blood pressure thresholds in pregnancy for identifying maternal and infant risk: a secondary analysis of Community-Level Interventions for Pre-eclampsia (CLIP) trial data. Lancet Glob Health. 2021;9:e1119–28.

  11. Macdonald-Wallis C, Silverwood RJ, Fraser A, Nelson SM, Tilling K, Lawlor DA, et al. Gestational-age-specific reference ranges for blood pressure in pregnancy: findings from a prospective cohort. J Hypertens. 2015;33:96–105.

    CAS  PubMed  Google Scholar 

  12. Valdés G, Kaufmann P, Corthorn J, Erices R, Brosnihan KB, Joyner-Grantham J. Vasodilator factors in the systemic and local adaptations to pregnancy. Reprod Biol Endocrinol. 2009;7:79.

    PubMed  PubMed Central  Google Scholar 

  13. Macedo ML, Luminoso D, Savvidou MD, McEniery CM, Nicolaides KH. Maternal wave reflections and arterial stiffness in normal pregnancy as assessed by applanation tonometry. Hypertension. 2008;51:1047–51.

    CAS  PubMed  Google Scholar 

  14. Kannel WB. Fifty years of Framingham Study contributions to understanding hypertension. J Hum Hypertens. 2000;14:83–90.

    CAS  PubMed  Google Scholar 

  15. Kotchen TA. Historical trends and milestones in hypertension research. A model of the process of translational research. Hypertension. 2011;58:522–38.

    CAS  PubMed  Google Scholar 

  16. Jousilahti P, Vartiainen E, Toumilehto J, Puska P. Sex, age and cardiovascular risk factors, and coronary heart disease: a prospective study of 14 786 middle-aged men and women in Finland. Circulation. 1999;99:1165–72.

    CAS  PubMed  Google Scholar 

  17. Nedkoff LJ, Briffa TG, Preen DB, Sanfilippo FM, Hung J, Ridout SC, et al. Age- and sex-specific trends in the incidence of hospitalized acute coronary syndromes in Western Australia. Circ Cardiovasc Qual Outcomes. 2011;4:557–64.

    PubMed  Google Scholar 

  18. Wilmot KA, O’Flaherty M, Capewell S, Ford ES, Vaccarino V. Coronary heart disease mortality declines in the United States from 1979 through 2011: evidence for stagnation in young adults, especially women. Circulation. 2015;132:997–1002.

    PubMed  PubMed Central  Google Scholar 

  19. Gabet A, Danchin N, Juillière Y, Olié V. Acute coronary syndrome in women: rising hospitalizations in middle-aged French women, 2004-14. Eur Heart J. 2017;38:1060–5.

  20. Ji H, Niirannen TJ, Rader F, Henglin M, Kim A, Ebinger JE, et al. Sex differences in blood pressure associations with cardiovascular outcomes. Circulation. 2021;143:761–3.

    PubMed  PubMed Central  Google Scholar 

  21. Kringeland E, Tell GS, Midtbø H, Igland J, Haugsgjerd TR, Gerdts E. Stage 1 hypertension, sex, and acute coronary syndromes during midlife: The Hordaland Health Study. Eur J Prev Cardiol. 2021. https://doi.org/10.1093/eurjpc/zwab068.

  22. Chesley LC, Annitto JE, Cosgrove RA. The remote prognosis of eclamptic women. Sixth periodic report. Am J Obstet Gynecol. 1976;124:446–59.

    CAS  PubMed  Google Scholar 

  23. Jónsdóttir LS, Arngrímsson R, Geirsson RT, Sigvaldason H, Sigfússon N. Death rates from ischemic heart disease in women with a history of hypertension in pregnancy. Acta Obstet Gynecol Scand. 1995;74:772–6.

    PubMed  Google Scholar 

  24. Brown MA, Roberts L, Hoffman A, Henry A, Mangos G, O’Sullivan A, et al. Recognizing cardiovascular risk after preeclampsia: The P4 Study. J Am Heart Assoc. 2020;9:e018604.

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Stuart JJ, Tanz LJ, Missmer SA, Rimm EB, Spiegelman D, James-Todd TM, et al. Hypertensive disorders of pregnancy and maternal cardiovascular disease risk factor development: an observational cohort study. Ann Intern Med. 2018;169:224–32.

    PubMed  PubMed Central  Google Scholar 

  26. Lo CCW, Lo ACQ, Leow SH, Fisher G, Corker B, Batho O, et al. Future cardiovascular disease risk for women with gestational hypertension: a systematic review and meta-analysis. J Am Heart Assoc. 2020;9:e013991.

    PubMed  PubMed Central  Google Scholar 

  27. Garovic VD, White WM, Vaughan L, Saiki M, Parashuram S, Garcia-Valencia O, et al. Incidence and long-term outcomes of hypertensive disorders of pregnancy. J Am Coll Cardiol. 2020;75:2323–34.

    PubMed  PubMed Central  Google Scholar 

  28. de Havenon A, Delic A, Stulberg E, Sheibani N, Stoddard G, Hanson H, et al. Association of preeclampsia with incident stroke in later life among women in the Framingham Heart Study. JAMA Netw Open. 2021;4:e215077.

    PubMed  PubMed Central  Google Scholar 

  29. Smith GN, Walker MC, Liu A, Wen SW, Swansburg M, Ramshaw H, et al. A history of preeclampsia identifies women who have underlying cardiovascular risk factors. Am J Obstet Gynecol. 2009;200:58.

    PubMed  Google Scholar 

  30. Veiga ECA, Rocha PRH, Caviola LL, Cardoso VC, Costa FDS, Saraiva MDCP, et al. Previous preeclampsia and its association with the future development of cardiovascular diseases: a systematic review and meta-analysis. Clinics (Sao Paulo). 2021;76:e1999.

    Google Scholar 

  31. Grandi SM, Filion KB, Yoon S, Ayele HT, Doyle CM, Hutcheon JA, et al. Cardiovascular disease-related morbidity and mortality in women with a history of pregnancy complications. Circulation. 2019;139:1069–79.

    PubMed  Google Scholar 

  32. Okoth K, Singh Chandan J, Marshall T, Thangaratinam S, Thomas GN, Nirantharakumar K, et al. Association between the reproductive health of young women and cardiovascular disease in later life: umbrella review. BMJ. 2020;371:m3502.

    PubMed  PubMed Central  Google Scholar 

  33. Huppertz B. The critical role of abnormal trophoblast development in the etiology of preeclampsia. Curr Pharm Biotechnol. 2018;19:771–80.

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Burton GJ, Woods AW, Jauniaux E, Kingdom JC. Rheological and physiological consequences of conversion of the maternal spiral arteries for uteroplacental blood flow during human pregnancy. Placenta. 2009;30:473–82.

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Cooke WR, Jones GD, Redman CWG, Vatish M. Syncytiotrophoblast derived extracellular vesicles in relation to preeclampsia. Matern-Fetal Med. 2021;3:151–60.

    Google Scholar 

  36. Valdés G. Preeclampsia and cardiovascular disease: interconnected paths that enable detection of the subclinical stages of obstetric and cardiovascular diseases. Integr Blood Press Control. 2017;10:17–23.

    PubMed  PubMed Central  Google Scholar 

  37. Rana S, Burke SD, Karumanchi SA. Imbalances in circulating angiogenic factors in the pathophysiology of preeclampsia and related disorders. Am J Obstet Gynecol. 2020. https://doi.org/10.1016/j.ajog.2020.10.022.

  38. Germain AM, Romanik MC, Guerra I, Solari S, Reyes MS, Johnson R, et al. Endothelial dysfunction: a link among preeclampsia, recurrent pregnancy loss, and future cardiovascular events? Hypertension. 2007;49:90–95.

    CAS  PubMed  Google Scholar 

  39. Patten IS, Rana S, Shahul S, Rowe GC, Jang C, Liu L, et al. Cardiac angiogenic imbalance leads to peripartum cardiomyopathy. Nature. 2012;485:333–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Arnett DK, Blumenthal RS, Albert MA, Buroker AB, Goldberger ZD, Hahn EJ, et al. 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019;140:e596–e646.

    PubMed  PubMed Central  Google Scholar 

  41. Parikh NI, Gonzalez JM, Anderson CAM, Judd SE, Rexrode KM, Hlatky MA, et al. Adverse pregnancy outcomes and cardiovascular disease risk: unique opportunities for cardiovascular disease prevention in women: a scientific statement from the American Heart Association. Circulation. 2021;143:e902–16.

    CAS  PubMed  Google Scholar 

  42. Vogel B, Acevedo M, Appelman Y, Bairey, Merz CN, Chieffo A, et al. The Lancet Women and Cardiovascular Disease Commission; reducing the global burden by 2030. Lancet. 2021;397:2385–438.

    PubMed  Google Scholar 

  43. Williams D. Pregnancy: a stress test for life. Curr Opin Obstet Gynecol. 2003;15:465–71.

    PubMed  Google Scholar 

  44. Carbillon L. Pregnancy is an essential spontaneous screening stress test for the risk of early stroke in women. Stroke. 2008;39:e138.

    PubMed  Google Scholar 

  45. Smith GN, Pudwell J, Roddy M. The Maternal Health Clinic: a new window of opportunity for early heart disease risk screening and intervention for women with pregnancy complications. J Obstet Gynaecol Can. 2013;35:831–9.

    PubMed  Google Scholar 

  46. Arabin B, Baschat AA. Pregnancy: an underutilized window of opportunity to improve long-term maternal and infant health – an appeal for continuous family care and interdisciplinary communication. Front Pediatr. 2017;5:69.

    PubMed  PubMed Central  Google Scholar 

  47. Muijsers HEC, Roeleveld N, van der Heijden OWH, Maas AHEM. Consider preeclampsia as a first cardiovascular event. Curr Cardiovasc Risk Rep. 2019;13:21.

    Google Scholar 

  48. Cusimano MC, Pudwell J, Roddy M, Cho CK, Smith GN. The maternal health clinic: an initiative for cardiovascular risk identification in women with pregnancy-related complications. Am J Obstet Gynecol. 2014;210:438. e1–9.

    PubMed  Google Scholar 

  49. Park K, Minissian MB, Wei J, Saade GR, Smith GN. Contemporary clinical updates in the prevention of cardiovascular disease in women who experienced adverse pregnancy outcomes. Clin Cardiol. 2020;43:553–9.

    PubMed  PubMed Central  Google Scholar 

  50. Celi AC, Seely EW, Wang P, Thomas AM, Wilkins-Haug LE. Caring for women after hypertensive pregnancies and beyond: Implementation and integration of a postpartum transition clinic. Matern Child Health J. 2019;23:1459–66.

    PubMed  Google Scholar 

  51. Lewey J, Levine LD, Yang L, Triebwasser JE, Groeneveld PW. Patterns of postpartum ambulatory care follow-up care among women with hypertensive disorders of pregnancy. J Am Heart Assoc. 2020;9:e016357.

    PubMed  PubMed Central  Google Scholar 

  52. Blumental EA, Crosland BA, Senderoff D, Santurino K, Garg N, Bernstein M, et al. California cardiovascular screening tool: Findings from initial implementation. AJP Rep. 2020;10:e362–8.

    Google Scholar 

  53. Hauspurg A, Countouris ME, Catov JM. Hypertensive disorders of pregnancy and future maternal health: How can the evidence guide postpartum management? Curr Hypertens Rep. 2019;21:96.

    PubMed  PubMed Central  Google Scholar 

  54. Lui NA, Jeyaram G, Henry A. Postpartum interventions to reduce long-term cardiovascular disease risk in women after hypertensive disorders of pregnancy: a systematic review. Front Cardiovasc Med. 2019;6:160.

    PubMed  PubMed Central  Google Scholar 

  55. Bairey Merz CN, Pepine CJ, Walsh MN, Fleg JL. Ischemia and No Obstructive Coronary Artery Disease (INOCA): developing evidence-based therapies and research agenda for the next decade. Circulation. 2017;135:1075–92.

    PubMed  Google Scholar 

  56. Norris CM, Yip CYY, Nerenberg KA, Clavel MA, Pacheco C, Foulds HJA, et al. State of the science in women’s cardiovascular disease: a Canadian perspective on the influence of sex and gender. J Am Heart Assoc. 2020;9:e01563.

    Google Scholar 

  57. Wang MC, Freaney PM, Perak AM, Allen NB, Greenland P, William A, et al. Association of pre-pregnancy cardiovascular risk factor burden with adverse maternal and offspring outcomes. Eur J Prev Cardiol Eur. 2021. https://doi.org/10.1093/eurpc/swab121.

  58. Barker DJ, Eriksson JG, Forsén T, Osmond C. Fetal origins of adult disease: strength of effects and biological basis. Int J Epidemiol. 2002;31:1235–9.

    CAS  PubMed  Google Scholar 

  59. Aye CYL, Lewandowski AJ, Lamata P, et al. Prenatal and postnatal cardiac development in offspring of hypertensive pregnancies. J Am Heart Assoc. 2020;9:e014586.

    PubMed  PubMed Central  Google Scholar 

  60. Timpka S, Macdonald-Wallis C, Hughes AD, Chaturvedi N, Franks PW, Lawlor DA, et al. Hypertensive disorders of pregnancy and offspring cardiac structure and function in adolescence. J Am Heart Assoc. 2016;5:e003906.

    PubMed  PubMed Central  Google Scholar 

  61. Alsnes IV, Vatten LJ, Fraser A, Bjørngaard JH, Rich-Edwards J, Romundstad PR, et al. Hypertension in pregnancy and offspring cardiovascular risk in young adulthood: prospective and sibling studies in the HUNT Study (Nord-Trøndelag Health Study) in Norway. Hypertension. 2017;69:591–8.

    CAS  PubMed  Google Scholar 

  62. Brenner BM, Chertow GM. Congenital oligonephropathy and the etiology of adult hypertension and progressive renal injury. Am J Kidney Dis. 1994;23:171–5.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

I value the encouragement and advice of Professor Mónica Acevedo, MD, along with the preparation of the manuscript.

Author information

Authors and Affiliations

Authors

Contributions

GV conceived the review and its topics, performed the literature search, selected the articles and described the historical sequence of each issue, drafted all versions of the manuscript, depicted the pathophysiology of preeclamptic in Fig. 1, and selected/included and expanded topics suggested by Professor Mónica Acevedo.

Corresponding author

Correspondence to Gloria Valdés.

Ethics declarations

Competing interests

The author declares no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Valdés, G. Focus on today’s evidence while keeping an eye on the future: lessons derived from hypertension in women. J Hum Hypertens (2022). https://doi.org/10.1038/s41371-021-00652-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1038/s41371-021-00652-y

Search

Quick links