Postpartum Hypertension and Vascular Biomarkers Among HIV-Infected Women with Preeclampsia in Zambia

Abstract

Background Hypertension is a significant global public health problem, that affects nearly one in five women of reproductive age. Women with hypertensive disorders of pregnancy have a higher risk of persistent hypertension after giving birth and beyond. It remains unclear how preeclampsia leads to persistent hypertension and other cardiovascular diseases after pregnancy. Therefore, this PhD examined whether the combined exposure to HIV and antiretroviral therapy (ART) is associated with persistent hypertension and cardiovascular risk biomarkers six months after giving birth. Methods A systematic review of studies from low and middle income countries (LMICs) was conducted to assess the prevalence of persistent hypertension after hypertensive disorders of pregnancy. We searched four databases from inception through 2nd January 2024 and included cohort and cross-sectional studies. A narrative synthesis of data was conducted, and prevalence was reported at different time points. The systematic review was followed by a six-month prospective cohort study of women after preeclampsia. These women were followed up from delivery to six months postpartum at Women and Newborn and Kanyama General hospitals in Lusaka, Zambia, from January 01, 2022, to June 30, 2023. At study visits (at delivery, six weeks, three months, and six months), we collected sociodemographics and clinical characteristics. Additionally, at delivery and six weeks, we measured high sensitivity C-reactive protein (hs-CRP), interleukin-2 (IL2), interleukin-6 (IL6), tumor necrosis factor-alpha (TNFa) and cystatin C. Results In the systematic review, 1584 abstracts were screened, of which 22 studies reported persistent hypertension after preeclampsia. The overall prevalence of persistent hypertension within 12 months following delivery ranged between 6.9% and 62.2% from 14 countries. From the prospective study, we noted that 16.9% of postpartum women experienced persistent hypertension six months after giving birth. Six-week postpartum prevalence was higher in the HIV group than HIV-negative group (54.6% vs 28.8%, p<0.001), with no measurable difference at three months (24.3% vs 13.2%, p = 0.145) or six months (18.2% vs 16.3%, p = 0.787). Additionally, women living with HIV on treatment were more likely to have persistent hypertension than HIV-negative women over the follow-up period (adjusted odds ratio [aOR] = 1.68, 95% CI: 1.09–2.60) after accounting for age, body mass index and time since vi delivery. Furthermore, women living with HIV on ART had higher hs-CRP, a marker of inflammation and future cardiovascular risk. However, we did not observe IL-2, IL-6, TNFa, and cystatin C differences by HIV status. Living with HIV while on ART was associated with an increased risk of presenting as hypertensive with elevated hs-CRP (aRR=2.88, 95% CI: 1.09-7.60). Conclusion The thesis findings are critical in contributing to hypertension prevention and early identification strategies. Paper 1 reports a high prevalence of persistent hypertension in LMICs following a pregnancy complicated by hypertensive disorders. Paper 2 showed that Women living with HIV on ART had elevated hs-CRP, a marker of inflammation and future cardiovascular diseases. The findings in paper 2 where corroborated in a longitudinal follow-up (paper 3) where we noted an elevated risk of persistent hypertension among postpartum women with comorbid preeclampsia and treated HIV. Taken together these findings suggest that peripartum women in HIV-endemic settings may benefit from timely detection of hypertension and treatment interventions to improve maternal and infant health.