Cardiovascular events following pregnancy complicated by pre-eclampsia with emphasis on comparison between early- and late-onset forms: systematic review and meta-analysis

Objective: To elucidate whether pre-eclampsia (PE) and the gestational age at onset of the disease (early- vs late-onset PE) have an impact on the risk of long-term maternal cardiovascular complications. Methods: MEDLINE, EMBASE and Scopus databases were searched until 15 April 2020 for studies evaluating the incidence of cardiovascular events in women with a history of PE, utilizing combinations of the relevant MeSH terms, keywords and word variants for ‘pre-eclampsia’, ‘cardiovascular disease’ and ‘outcome’. Inclusion criteria were cohort or case–control design, inclusion of women with a diagnosis of PE at the time of the first pregnancy, and sufficient data to compare each outcome in women with a history of PE vs women with previous normal pregnancy and/or in women with a history of early- vs late-onset PE. The primary outcome was a composite score of maternal cardiovascular morbidity and mortality, including cardiovascular death, major cardiovascular and cerebrovascular events, hypertension, need for antihypertensive therapy, Type-2 diabetes mellitus, dyslipidemia and metabolic syndrome. Secondary outcomes were the individual components of the primary outcome analyzed separately. Data were combined using a random-effects generic inverse variance approach. MOOSE guidelines and the PRISMA statement were followed. Results: Seventy-three studies were included. Women with a history of PE, compared to those with previous normotensive pregnancy, had a higher risk of composite adverse cardiovascular outcome (odds ratio (OR), 2.05 (95% CI, 1.9–2.3)), cardiovascular death (OR, 2.18 (95% CI, 1.8–2.7)), major cardiovascular events (OR, 1.80 (95% CI, 1.6–2.0)), hypertension (OR, 3.93 (95% CI, 3.1–5.0)), need for antihypertensive medication (OR, 4.44 (95% CI, 2.4–8.2)), dyslipidemia (OR, 1.32 (95% CI, 1.3–1.4)), Type-2 diabetes (OR, 2.14 (95% CI, 1.5–3.0)), abnormal renal function (OR, 3.37 (95% CI, 2.3–5.0)) and metabolic syndrome (OR, 4.30 (95% CI, 2.6–7.1)). Importantly, the strength of the associations persisted when considering the interval (< 1, 1–10 or > 10 years) from PE to the occurrence of these outcomes. When stratifying the analysis according to gestational age at onset of PE, women with previous early-onset PE, compared to those with previous late-onset PE, were at higher risk of composite adverse cardiovascular outcome (OR, 1.75 (95% CI, 1.0–3.0)), major cardiovascular events (OR, 5.63 (95% CI, 1.5–21.4)), hypertension (OR, 1.48 (95% CI, 1.3–1.7)), dyslipidemia (OR, 1.51 (95% CI, 1.3–1.8)), abnormal renal function (OR, 1.52 (95% CI, 1.1–2.2)) and metabolic syndrome (OR, 1.66 (95% CI, 1.1–2.5). Conclusions: Both early- and late-onset PE represent risk factors for maternal adverse cardiovascular events later in life. Early-onset PE is associated with a higher burden of cardiovascular morbidity and mortality compared to late-onset PE. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.