Dari Asosiasi Menuju Plausibilitas Kausal: Sintesis Bukti Hipertensi dalam Kehamilan dan Risiko Kardiovaskular Jangka Panjang

Lailatul Evinanta Pertiwi; Diki Tri Bagus Dermawan

doi:10.71456/jik.v5i1.2973

Authors

Lailatul Evinanta Pertiwi RSU Aulia, Indonesia
Diki Tri Bagus Dermawan IIK Bhakti Wiyata Kediri, Indonesia

DOI:

https://doi.org/10.71456/jik.v5i1.2973

Keywords:

Epidemiologi Maternal, Hipertensi dalam Kehamilan, Mendelian Randomization, Penyakit Kardiovaskular, Preeklampsia

Abstract

Hipertensi dalam kehamilan (hypertensive disorders of pregnancy/HDP) berkaitan dengan morbiditas maternal dan risiko kardiovaskular jangka panjang. Penelitian ini mengintegrasikan bukti faktor risiko, genetik, dan luaran HDP serta menilai plausibilitas kausal hubungannya dengan penyakit kardiovaskular. Metode menggunakan integrative evidence synthesis with limited quantitative meta-analysis and causal plausibility assessment terhadap 33 studi periode 2013–2026 dengan pelaporan seleksi PRISMA-informed. Meta-analisis empat kohort menunjukkan peningkatan risiko kardiovaskular jangka panjang setelah HDP (HR 1,95; IK95% 1,73–2,20; I²=0%). Riwayat keluarga hipertensi berkaitan dengan peningkatan risiko preeklampsia sekitar dua kali lipat, sedangkan Mendelian randomization menunjukkan arah asosiasi konsisten untuk penyakit jantung iskemik dan stroke. Triangulasi bukti mendukung plausibilitas kontribusi kausal, tetapi tidak membuktikan kausalitas definitif. HDP perlu diposisikan sebagai penanda dini risiko kardiovaskular dan diikuti pemantauan postpartum.

References

Alhuneafat, L., Obeidat, O., Mohammed, D., Sumzin, N., Ikbariah, K., Al-Abdouh, A., Jabri, A., Ramu, B., Schultz, J., Gottula, J., Sabol, B. A., & Carlson, S. (2026). Five-year cardiovascular outcomes across hypertensive disorders of pregnancy subtypes: A propensity-matched analysis. Frontiers in Cardiovascular Medicine, 13, 1875409. https://doi.org/10.3389/fcvm.2026.1875409

Brouwers, L., Van Der Meiden-Van Roest, A. J., Savelkoul, C., Vogelvang, T. E., Lely, A., Franx, A., & Van Rijn, B. V. (2018). Recurrence of pre-eclampsia and the risk of future hypertension and cardiovascular disease: A systematic review and meta-analysis. BJOG, 125, 1642–1654. https://doi.org/10.1111/1471-0528.15394

Chakulya, M., Mulambo, P., Chama, G. C., et al. (2025). Preeclampsia, prevalence and associated factors. PLOS ONE, 20. https://doi.org/10.1371/journal.pone.0337190

Countouris, M., Villanueva, F., Berlacher, K. L., et al. (2021). Association of hypertensive disorders of pregnancy with left ventricular remodeling later in life. Journal of the American College of Cardiology, 77, 1057–1068. https://doi.org/10.1016/j.jacc.2020.12.051

Fikadu, K., G/Meskel, F., Getahun, F., Chufamo, N., & Misiker, D. (2020). Family history of chronic illness, preterm gestational age and smoking exposure before pregnancy increases the probability of preeclampsia in Omo district in southern Ethiopia. Clinical Hypertension, 26. https://doi.org/10.1186/s40885-020-00149-9

Garovic, V. D., Dechend, R., Easterling, T., et al. (2022). Hypertension in pregnancy: Diagnosis, blood pressure goals, and pharmacotherapy: A scientific statement from the American Heart Association. Hypertension, 79(2), e21–e41. https://doi.org/10.1161/HYP.0000000000000208

Garovic, V., White, W., Vaughan, L. E., et al. (2020). Incidence and long-term outcomes of hypertensive disorders of pregnancy. Journal of the American College of Cardiology, 75, 2323–2334. https://doi.org/10.1016/j.jacc.2020.03.028

Guerrier, G., Oluyide, B., Keramarou, M., & Grais, R. F. (2013). Factors associated with severe preeclampsia and eclampsia in Jahun, Nigeria. International Journal of Women’s Health, 5, 509–513. https://doi.org/10.2147/IJWH.S47056

Hernida, I., Nuru, H., & Darmawansyah, D. (2022). Faktor-faktor yang berhubungan dengan hipertensi pada kehamilan di wilayah kerja Puskesmas Padang Tepong Kecamatan Ulu Musi Kabupaten Empat Lawang. Jurnal Kebidanan Manna, 1(2), 75–88. https://doi.org/10.58222/jkm.v1i2.175

Hill, A. B. (1965). The environment and disease: Association or causation? Proceedings of the Royal Society of Medicine, 58, 295–300.

Honigberg, M., Truong, B., Khan, R., et al. (2023). Polygenic prediction of preeclampsia and gestational hypertension. Nature Medicine, 29, 1540–1549. https://doi.org/10.1038/s41591-023-02374-9

Huang, Y., Li, Z., Zhu, J., et al. (2025). Construction of a risk prediction model for adverse pregnancy outcomes in primipara with gestational diabetes mellitus combined with pregnancy-induced hypertension syndrome. Clinical and Experimental Hypertension, 47. https://doi.org/10.1080/10641963.2025.2492621

Kay, V., Wedel, N., & Smith, G. N. (2020). Family history of hypertension, cardiovascular disease, or diabetes and risk of developing preeclampsia: A systematic review. Journal of Obstetrics and Gynaecology Canada. https://doi.org/10.1016/j.jogc.2020.08.010

Kementerian Kesehatan Republik Indonesia. (2025). Keputusan Menteri Kesehatan Republik Indonesia Nomor HK.01.07/MENKES/560/2025 tentang Pedoman Penyelenggaraan Pelayanan Obstetri Neonatal Emergensi Komprehensif di Rumah Sakit. Kementerian Kesehatan Republik Indonesia.

Khan, B., Yar, R. A., Khakwani, A., Karim, S., & Ali, H. A. (2022). Preeclampsia incidence and its maternal and neonatal outcomes with associated risk factors. Cureus, 14. https://doi.org/10.7759/cureus.31143

Lewandowska, M. (2021). The association of familial hypertension and risk of gestational hypertension and preeclampsia. International Journal of Environmental Research and Public Health, 18. https://doi.org/10.3390/ijerph18137045

Li, J., Li, D., Mo, J., Mo, L., Zhang, C., Zhang, J., Lu, Y., Wu, H., & Liang, X. (2026). Hypertensive disorders of pregnancy: Heterogeneity in risk factors and maternal and neonatal outcomes across subtypes—A 6-year retrospective cohort study. Frontiers in Cardiovascular Medicine, 13, 1781870. https://doi.org/10.3389/fcvm.2026.1781870

Mathew, V., Khan, R. R., Jowell, A. R., et al. (2025). Genetic risk and first-trimester cardiovascular health predict hypertensive disorders of pregnancy in nulliparous women. Journal of the American College of Cardiology, 85(14), 1488–1500. https://doi.org/10.1016/j.jacc.2025.02.015

Meazaw, M. W., Chojenta, C., Muluneh, M. D., & Loxton, D. (2020). Systematic review and meta-analysis of factors associated with preeclampsia and eclampsia in Sub-Saharan Africa. PLOS ONE, 15. https://doi.org/10.1371/journal.pone.0237600

Nandagopal, P., Sanaullah, A. A. R., Nandagopal, S., et al. (2025). Unveiling the risks and outcomes of preeclampsia: A case-control study in the UAE. BMC Pregnancy and Childbirth, 25. https://doi.org/10.1186/s12884-025-08448-5

Nie, X., Xu, Z., & Ren, H. (2024). Analysis of risk factors of preeclampsia in pregnant women with chronic hypertension and its impact on pregnancy outcomes. BMC Pregnancy and Childbirth, 24. https://doi.org/10.1186/s12884-024-06476-1

Nielsen, T. S., Luo, J., Tybjærg-Hansen, A., et al. (2025). Preeclampsia, gestational hypertension, and cardiovascular disease risk: A genetic epidemiological study. European Heart Journal, 46, 4316–4325. https://doi.org/10.1093/eurheartj/ehaf565

Oliver-Williams, C., Stevens, D., Payne, R., et al. (2022). Association between hypertensive disorders of pregnancy and later risk of cardiovascular outcomes. BMC Medicine, 20. https://doi.org/10.1186/s12916-021-02218-8

Page, M. J., McKenzie, J. E., Bossuyt, P. M., et al. (2021). The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. BMJ, 372, n71. https://doi.org/10.1136/bmj.n71

Rayes, B., Ardissino, M., Slob, E., et al. (2023). Association of hypertensive disorders of pregnancy with future cardiovascular disease. JAMA Network Open, 6. https://doi.org/10.1001/jamanetworkopen.2023.0034

Schuermans, A., Truong, B., Ardissino, M., et al. (2024). Genetic associations of circulating cardiovascular proteins with gestational hypertension and preeclampsia. JAMA Cardiology, 9, 209–220. https://doi.org/10.1001/jamacardio.2023.4994

Serrano, N. C., Quintero-Lesmes, D. C., Dudbridge, F., et al. (2020). Family history of pre-eclampsia and cardiovascular disease as risk factors for pre-eclampsia: The GenPE case-control study. Hypertension in Pregnancy, 39(1), 56–63. https://doi.org/10.1080/10641955.2019.1704003

Singh, A., Wyatt, S., Kvalvik, L. G., & Skjærven, R. (2025). Hypertensive disorders of pregnancy, maternal cardiovascular disease mortality and the role of familial predisposition. American Journal of Epidemiology, 195, 991–1000. https://doi.org/10.1093/aje/kwaf257

Smith, C. J., Saftlas, A. F., Spracklen, C. N., et al. (2016). Genetic risk score for essential hypertension and risk of preeclampsia. American Journal of Hypertension, 29(1), 17–24. https://doi.org/10.1093/ajh/hpv069

Steinthorsdottir, V., McGinnis, R., Williams, N. O., et al. (2020). Genetic predisposition to hypertension is associated with preeclampsia in European and Central Asian women. Nature Communications, 11. https://doi.org/10.1038/s41467-020-19733-6

Stuart, J., Tanz, L. J., Rimm, E., et al. (2022). Cardiovascular risk factors mediate the long-term maternal risk associated with hypertensive disorders of pregnancy. Journal of the American College of Cardiology, 79, 1901–1913. https://doi.org/10.1016/j.jacc.2022.03.335

Tschiderer, L., Van Der Schouw, Y. T., Burgess, S., et al. (2023). Pregnancy associated hypertensive disorders and risk of cardiovascular disease: A Mendelian randomisation study. European Heart Journal, 44(Suppl 2). https://doi.org/10.1093/eurheartj/ehad655.2726

Tyrmi, J., Kaartokallio, T., Lokki, A., et al. (2023). Genetic risk factors associated with preeclampsia and hypertensive disorders of pregnancy. JAMA Cardiology, 8, 674–683. https://doi.org/10.1001/jamacardio.2023.1312

Wang, X., Mao, X., & Xing, C. (2026). The clinical value of nomogram combined with machine learning models in predicting the progression of hypertensive disorders in pregnancy to severe preeclampsia. Frontiers in Global Women’s Health, 7. https://doi.org/10.3389/fgwh.2026.1672534

Wu, C.-T., Kuo, C., Lin, C., et al. (2021). Association of family history with incidence and gestational hypertension outcomes of preeclampsia. International Journal of Cardiology Hypertension, 9. https://doi.org/10.1016/j.ijchy.2021.100084

Wyatt, S., Kvalvik, L. G., Singh, A., et al. (2024). Heterogeneity in the risk of cardiovascular disease mortality after the hypertensive disorders of pregnancy across mothers’ lifetime reproductive history. Paediatric and Perinatal Epidemiology, 38, 230–237. https://doi.org/10.1111/ppe.13059

Xu, J., Li, T., Wang, Y., et al. (2022). The association between hypertensive disorders in pregnancy and the risk of developing chronic hypertension. Frontiers in Cardiovascular Medicine, 9. https://doi.org/10.3389/fcvm.2022.897771

Zhao, G., Bhatia, D., Jung, F., & Lipscombe, L. (2021). Risk of type 2 diabetes mellitus in women with prior hypertensive disorders of pregnancy: A systematic review and meta-analysis. Diabetologia, 64, 491–503. https://doi.org/10.1007/s00125-020-05343-w