Early Pregnancy Atherogenic Profile in a First Pregnancy and Hypertension Risk 2 to 7 Years After Delivery

Abstract

Background Cardiovascular risk in young adulthood is an important determinant of lifetime cardiovascular disease risk. Women with adverse pregnancy outcomes (APOs) have increased cardiovascular risk, but the relationship of other factors is unknown. Methods and Results Among 4471 primiparous women, we related first-trimester atherogenic markers to risk of APO (hypertensive disorders of pregnancy, preterm birth, small for gestational age), gestational diabetes mellitus (GDM) and hypertension (130/80 mm Hg or antihypertensive use) 2 to 7 years after delivery. Women with an APO/GDM (n=1102) had more atherogenic characteristics (obesity [34.2 versus 19.5%], higher blood pressure [systolic blood pressure 112.2 versus 108.4, diastolic blood pressure 69.2 versus 66.6 mm Hg], glucose [5.0 versus 4.8 mmol/L], insulin [77.6 versus 60.1 pmol/L], triglycerides [1.4 versus 1.3 mmol/L], and high-sensitivity C-reactive protein [5.6 versus 4.0 nmol/L], and lower high-density lipoprotein cholesterol [1.8 versus 1.9 mmol/L]; P<0.05) than women without an APO/GDM. They were also more likely to develop hypertension after delivery (32.8% versus 18.1%, P<0.05). Accounting for confounders and factors routinely assessed antepartum, higher glucose (relative risk [RR] 1.03 [95% CI, 1.00-1.06] per 0.6 mmol/L), high-sensitivity C-reactive protein (RR, 1.06 [95% CI, 1.02-1.11] per 2-fold higher), and triglycerides (RR, 1.27 [95% CI, 1.14-1.41] per 2-fold higher) were associated with later hypertension. Higher physical activity was protective (RR, 0.93 [95% CI, 0.87-0.99] per 3 h/week). When evaluated as latent profiles, the nonobese group with higher lipids, high-sensitivity C-reactive protein, and insulin values (6.9% of the cohort) had increased risk of an APO/GDM and later hypertension. Among these factors, 7% to 15% of excess RR was related to APO/GDM. Conclusions Individual and combined first-trimester atherogenic characteristics are associated with APO/GDM occurrence and hypertension 2 to 7 years later. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02231398.

Keywords: high blood pressure; hypertension; lipids; preeclampsia/pregnancy; pregnancy and postpartum.

Figure 1. Flow diagram for participation in analysis.

APO indicates adverse pregnancy outcomes; ASCVD, atherosclerotic cardiovascular disease; BMI, body mass index; CVD, cardiovascular disease; DBP, diastolic blood pressure; GDM, gestational diabetes mellitus; HDL, high‐density lipoprotein; HDP, hypertensive disorders of pregnancy; HHS, Heart Health Study; HTN, hypertension; hsCRP, high‐sensitivity C‐reactive protein; LDL, low‐density lipoprotein; PTB, preterm birth; SBP, systolic blood pressure; and SGA, small for gestational age.

Figure 2. Schematic to assess mediation by APO/GDM of the association between an early pregnancy CVD risk factor (triglycerides) and hypertension 2 to 7 years following delivery after adjustment for covariates.

Estimates are components of excess relative risk. APO indicates adverse pregnancy outcome; ASCVD, atherosclerotic cardiovascular disease; BMI, body mass index; CDE, controlled direct effect; CVD, cardiovascular disease; DBP, diastolic blood pressure; GDM, gestational diabetes mellitus; HDL, high‐density lipoprotein; HDP, hypertensive disorders of pregnancy; hsCRP, high‐sensitivity C‐reactive protein; HTN, hypertension; Int, interaction only; LDL, low‐density lipoprotein; MedInt, mediation and interaction; PIE, pure indirect effect; PTB, preterm birth; SBP, systolic blood pressure; SGA, small for gestational age; and ST, supplemental table.