| Abstract: | Background:People whose singleton pregnancy is affected by hypertensive disorders of pregnancy (HDP) are at risk of future cardiovascular disease. It is unclear, however, whether this association can be extrapolated to twin pregnancies. We aimed to compare the association between HDP and future cardiovascular disease after twin and singleton pregnancies.Methods:We conducted a population-based retrospective cohort study that included nulliparous people in Ontario, Canada, 1992–2017. We compared the future risk of cardiovascular disease among pregnant people from the following 4 groups: those who delivered a singleton without HDP (referent) and with HDP, and those who delivered twins either with or without HDP.Results:The populations of the 4 groups were as follows: 1 431 651 pregnant people in the singleton birth without HDP group; 98 631 singleton birth with HDP; 21 046 twin birth without HDP; and 4283 twin birth with HDP. The median duration of follow-up was 13 (interquartile range 7–20) years. The incidence rate of cardiovascular disease was lowest among those with a singleton or twin birth without HDP (0.72 and 0.74 per 1000 person-years, respectively). Compared with people with a singleton birth without HDP, the risk of cardiovascular disease was highest among those with a singleton birth and HDP (1.47 per 1000 person-years; adjusted hazard ratio [HR] 1.81 [95% confidence interval (CI) 1.72–1.90]), followed by people with a twin pregnancy and HDP (1.07 per 1000 person-years; adjusted HR 1.36 [95% CI 1.04–1.77]). The risk of the primary outcome after a twin pregnancy with HDP was lower than that after a singleton pregnancy with HDP (adjusted HR 0.74 [95% CI 0.57–0.97]), when compared directly.Interpretation:In a twin pregnancy, HDP are weaker risk factors for postpartum cardiovascular disease than in a singleton pregnancy.Cardiovascular disease has been shown to be the leading cause of death among women.1–3 Classic risk factors for cardiovascular disease include obesity, diabetes mellitus, hypertension and family history of cardiovascular disease. 3 More recently, an association has been established between a history of hypertensive disorders of pregnancy (HDP) — gestational hypertension and pre-eclampsia — and future risk of cardiovascular disease.1,4–11 Consequently, some recommend using a history of HDP for cardiovascular disease risk stratification in women.3,12The leading hypothesis for the pathogenesis of HDP is that it results from abnormal placentation due to impaired trophoblast invasion,13–16 resulting in reduced placental perfusion.17–19 This, in turn, leads to abnormal secretion of the angiogenic factors soluble FMS-like tyrosine kinase 1 (sFlt1) and soluble endoglin (sEng),20 which induce endothelial dysfunction and the clinical manifestations of HDP.19,21–24 The mechanisms underlying the association between HDP and future cardiovascular disease are under debate.25 One hypothesis is that HDP are merely a marker of underlying subclinical or clinical vascular risk factors that predispose a person to both HDP and future cardiovascular disease.A person who is pregnant with twins is at about 3–4 times higher risk of HDP than a person with a singleton pregnancy,26–33 with rates of 14% and 5%, respectively.34 The higher risk of HDP in twin pregnancies may be due to higher circulating sFlt1 and sEng owing to greater placental mass in twin pregnancies, 35–37 and less related to the classic vascular risk factors for HDP in a singleton pregnancy. Therefore, a logical question is whether the established higher risk of future cardiovascular disease after singleton pregnancies with HDP also occurs in twin pregnancies with HDP. Limited data are available to answer this question.38 In the current study, we aimed to test the hypothesis that the association between HDP and future cardiovascular disease is less pronounced in twin versus singleton pregnancies. |
