Objective
The purpose of this study was to investigate the recurrence risk of hypertensive disorders in subsequent pregnancies and to explore the associations among hypertensive disorders of pregnancy and maternal cardiovascular risk factor profile and the development of cardiovascular diseases later in life.
Study Design
We used population-based, cross-sectional data from the fourth survey of the Tromsø Study.
Results
Preeclampsia in the first pregnancy increased the risk of recurrence in later pregnancies (relative risk, 6.6; 95% confidence interval, 5.5–7.9) compared with a normotensive first pregnancy. Women with a history of preeclampsia or nonproteinuric hypertension had an unfavorable cardiovascular risk profile. Hypertension was prevalent in 25% and 28% of the women, respectively. The carotid artery intima-media thickness and total carotid plaque area were significantly larger in women with previous preeclampsia.
Conclusion
A strong association between hypertensive disorders of pregnancy and an increased risk of atherosclerosis and cardiovascular diseases was demonstrated by the assessment of risk factors that can be potentially modified.
Hypertensive disorders of pregnancy affect approximately 10% of gestations. Defective placentation and maternal endothelial cell dysfunction have been hypothesized as the antecedents of clinical presentation. However, it is unclear whether the underlying mechanism is a constitutional predisposition or defective placentation. The changes in uteroplacental circulation that is associated with incomplete remodeling of the spiral arteries and the extent of placental vascular lesions vary between different clinical conditions, such as gestational hypertension and preeclampsia. Preeclampsia has been associated with an increased risk of cardiovascular disease (CVD) in later life. However, the relative risk that is associated with different types of hypertensive disorders of pregnancy has not been clarified. Despite the epidemiologic evidence of increased risk for hypertension, stroke, coronary artery disease, and end-stage renal disease, a clear pathophysiologic explanation remains elusive and mostly hypothetic. Although preeclampsia and CVD share many of the same constitutional risk factors and endothelial dysfunction may persist after the pregnancy, no study so far has demonstrated unequivocally that the risk profile is altered in association with preeclampsia. Furthermore, whether and for how long the impaired vascular function persists after preeclampsia remains controversial. A recent study showed that the vascular dysfunction persists 6-24 months after delivery only in women with early-onset preeclampsia, but not in women who had late-onset disease, whereas the risk of CVD is increased in both.
Ultrasound-assessed carotid plaques and intima-media thickness (IMT) are useful markers of early atherosclerosis and are predictive of future CVD. Information on associations between hypertensive disorders of pregnancy and carotid atherosclerosis is limited, however, to smaller case-control studies and has shown partly conflicting results.
In this population-based study, we aimed to evaluate the recurrence risk of hypertensive disorders in subsequent pregnancies in women who report this in their first pregnancy. Additionally, we wanted to investigate the associations among hypertensive disorders of pregnancy and a maternal cardiovascular risk factor profile, atherosclerosis of the carotid arteries, and the risk of maternal CVD later in life.
Materials and Methods
The Tromsø Study is a population-based multipurpose, single-center study with a main focus on cardiovascular risk factors and disease. The University of Tromsø, in cooperation with the National Health Screening Service, conducted the surveys. The Tromsø Study consists of different surveys that were conducted at 6- to 7-year intervals from 1974. The data in the present study are from the fourth survey (1994-95), which was the first survey that included questions on parity and hypertensive disorders of pregnancy. The survey had 2 different parts: a first visit to which everybody ≥25 years old (born before 1970) were invited and a second visit with more extensive examinations to which all men who were 55-74 years old (born 1920-1939), all women who were 50-74 years old (born 1920-1944) and smaller random samples (5-8%) were invited.
Study population
A total of 12,862 men and 14,293 women participated (77% of those who were eligible). The female participants were asked to answer questionnaires on parity and hypertensive complications in pregnancies. Women who did not answer a question on parity (n = 1749), nulliparous women (n = 1964), parous women who did not answer the questions on hypertensive complications in their pregnancies (n = 434), and women who did not consent to participate in the research (n = 172) were excluded, which left 9974 women who were included in the study ( Figure ).
The occurrence of hypertensive complications in pregnancy was assessed by the following questions: “If you have had high blood pressure during pregnancy, was it your first pregnancy?” and “If you have had proteinuria during pregnancy, was it your first pregnancy?” Four groups were defined based on the questionnaire responses; based on self-reporting by women; women who had preeclampsia (group I), nonproteinuric hypertension (group II), normotensive proteinuria (group III), and women without hypertension or proteinuria (group IV, control group). Comparisons are made between women with preeclampsia (group I) and the control group (group IV) and between women with nonproteinuric hypertension (group II) and the control group (group IV). The major causes of proteinuria during pregnancy are preeclampsia and urinary tract infection. Screening for proteinuria depends on the use of urine dipsticks that may give false-positive results; contamination by vaginal discharge must be excluded. Women in group III reported normotensive proteinuria, which is encountered commonly in clinical practice, but the cause of gestational proteinuria could not be ascertained in this group. It might have been a false-positive test result or contamination, infection, primary renal disease, or renal disease that resulted from systemic disorders.
The second visit with more extensive examinations included an ultrasound scan of the right carotid artery. A total of 7965 persons (76% of the eligible) attended the second visit, and carotid ultrasound examination was performed in 6727 men and women. Of the 9974 women who attended the first visit and who fulfilled the inclusion criteria for the present study, 2524 women were examined with carotid ultrasound ( Figure ).
Examination methods and measurements
The screening consisted of self-administered questionnaires, clinical physical examinations, and laboratory tests. Information about smoking habits, history of diabetes mellitus, angina pectoris, previous myocardial infarction, family history, and use of medication was collected from self-administered questionnaires. CVD was defined as previous stroke and/or myocardial infarction and/or presence of angina pectoris. Diabetes mellitus was defined as self-reported diabetes mellitus and/or regular use of insulin or oral antidiabetic drugs.
Weight and height were measured with light clothing without shoes. Body mass index was calculated as weight in kilograms divided by the square of the height in meters. Blood pressure (BP) was measured with an automatic device (Dinamap Vital Signs Monitor 1846; Critikon Inc, Tampa, FL) after a 2-minutes rest in the sitting position and 3 readings were taken at 1-minute intervals. The mean of the second and third measurements is used in our analyses. Current hypertension was defined as systolic BP >140 mm Hg and/or diastolic BP >90 mm Hg and/or current use of antihypertensive medication.
A nonfasting blood sample was taken at the first visit and analyzed for serum total cholesterol, high-density lipoprotein cholesterol, and triglycerides. Glycosylated hemoglobin was measured at the second visit in 3088 women.
Carotid ultrasound examination
Methodologic details regarding carotid artery ultrasound scanning and its reproducibility have been published previously. Briefly, high-resolution B-mode ultrasonography was performed with a duplex scanner (Acuson Xp10 128, ART-upgraded; Acuson, Mountain View, CA) that was equipped with a 7.5-MHz linear array transducer. Automated measurements of IMT were performed in 10-mm segments in the near and far walls of the distal common carotid artery and the far wall of the bifurcation. The mean IMT from 3 preselected images was calculated for each location, and the mean of these averages was used in the analyses. The far and near walls of the right common carotid artery, bifurcation, and internal carotid artery (6 locations) were scanned for the presence of plaques. Plaque was defined as a localized protrusion of the vessel wall into the lumen (>50% compared with the adjacent intima-media layer). Still images were recorded for each plaque and were digitized with the Matrox Meteor II frame grabber card and Matrox Intellicam software (version 2.07; Matrox Imaging, Quebec, Canada) at a resolution of 768 × 576 pixels. With the software Adobe Photoshop (version 7.0; Adobe Systems Incorporated, San Jose, CA), the following steps were performed: each plaque was outlined with the Lasso tool (Adobe Photoshop), and the plaque area was calculated as pixel values. For the resolution that was used in the present study, a plaque area of 167 pixels corresponded to 1 mm 2 . Total plaque area was calculated as the sum of all plaque areas from each location.
Statistical analyses
Analyses were performed with STATA software (Stata Corporation, College Station, TX) and SPSS software (version 15.0 for Windows; SPSS Inc, Chicago, IL). Comparisons between groups were performed with 1-way analysis of variance for continuous variables and with the χ 2 test for categoric variables. The statistical analyses included all 4 groups. Contrast tests were performed to evaluate differences between groups I and group (control group) and groups II and IV (control group), respectively.
Ethics
The Norwegian Data Inspectorate licensed all data. The Regional Committee for Medical Research Ethics approved the study. All participants gave informed written consent.
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