Original Research
Obstetrics
A history of preeclampsia is associated with a risk for coronary artery calcification 3 decades later

Presented orally at the 36th annual meeting of the Society for Maternal-Fetal Medicine, Atlanta, GA, Feb. 1-6, 2016.
https://doi.org/10.1016/j.ajog.2016.02.003Get rights and content

Background

A history of preeclampsia is an independent risk factor for cardiac events and stroke. Changes in vasculature structure that contribute to these associations are not well understood.

Objective

The aim of this study was to quantify coronary artery calcification (CAC), a known risk factor for cardiac events, in a prospective cohort of women with and without histories of preeclampsia.

Study Design

Women without prior cardiovascular events (40 with and 40 without histories of preeclampsia, matched for parity and age at index birth) were recruited from a large population-based cohort of women who were residents of Olmsted County, Minnesota, and who delivered from 1976 through 1982. Computed tomography was performed to measure CAC in Agatston units. All pregnancy histories and covariates were confirmed by review of the medical records. Current clinical variables were assessed at the time of imaging. Differences between women with and without histories of preeclampsia were examined using χ2 tests and tests; CAC, in particular, was compared as a categorical and ordinal variable, with a χ2 test and with Wilcoxon 2-sample tests and ordinal logistic regression, as appropriate.

Results

Mean age (SD) at imaging was 59.5 (±4.6) years. Systolic and diastolic blood pressures, hyperlipidemia, and current diabetes status did not differ between women with and without histories of preeclampsia. However, the frequencies of having a current clinical diagnosis of hypertension (60% vs 20%, P < .001) and higher body mass index in kg/m2 (expressed as median [25th-75th percentile], 29.8 [25.9-33.7] vs 25.3 [23.1-32.0], P = .023) were both greater in the women with histories of preeclampsia compared to those without. The frequency of a CAC score >50 Agatston units was also greater in the preeclampsia group (23% vs 0%, P = .001). Compared to women without preeclampsia, the odds of having a higher CAC score was 3.54 (confidence interval [CI], 1.39–9.02) times greater in women with prior preeclampsia without adjustment, and 2.61 (CI, 0.95–7.14) times greater after adjustment for current hypertension. After adjustment for body mass index alone, the odds of having a higher CAC based on a history of preeclampsia remained significant at 3.20 (CI, 1.21–8.49).

Conclusion

In this first prospective cohort study with confirmation of preeclampsia by medical record review, a history of preeclampsia is associated with an increased risk of CAC >30 years after affected pregnancies, even after controlling individually for traditional risk factors. A history of preeclampsia should be considered in risk assessment when initiating primary prevention strategies to reduce cardiovascular disease in women. Among women with histories of preeclampsia, the presence of CAC may be able to identify those at a particularly high cardiovascular risk, and should be the subject of future studies.

Introduction

Cardiovascular disease (CVD) is the leading cause of death in women. A history of preeclampsia is a sex-specific independent risk factor for cardiac events and stroke.1, 2, 3, 4 The importance of documenting a history of adverse events in pregnancy, such as preeclampsia, is now highlighted in guidelines for the prevention of stroke and coronary artery disease.5, 6

It is important to understand the pathophysiologic processes linking preeclampsia to subsequent CVD risk, given the strong association between preeclampsia and future adverse cardiovascular outcomes. Conventional risk factors, including obesity and chronic hypertension, are shared by both conditions.7 Other nontraditional risk factors that are shared by preeclampsia and adverse CVD outcomes include increased levels of C-reactive protein and homocysteine.8, 9

Coronary artery calcification (CAC), as measured in Agatston units (AU) by computed tomography, is an important biomarker of CVD. The extent of CAC strongly correlates with a higher risk for an adverse cardiac event even in asymptomatic individuals10: for a CAC >100, the relative risk for a cardiac event in the next 4 years is >9.11 The American College of Cardiology/American Heart Association guidelines from both 2010 and 2013 stated that measurement of CAC may help to define risk in those persons at low to intermediate risk based on Framingham scoring.12 CAC measurement may be beneficial in assessing risk of CVD for women in particular as the Framingham risk score typically underestimates female CVD risk.

A systematic study of the relationship between a history of preeclampsia, as defined by accepted clinical criteria, and CAC quantification in asymptomatic women has not been undertaken. The aim of this study was to quantify and compare CAC in age- and parity-matched women with and without histories of preeclampsia, and to establish whether this association was independent of traditional CVD risk factors. We postulated that CAC would be higher in women with histories of preeclampsia and could better stratify cardiovascular risk in these women.

Section snippets

Materials and Methods

The Rochester Epidemiology Project (REP) medical records linkage system was used to identify, from a larger population-based cohort, 40 age- and parity-matched women with and without histories of preeclampsia who then were recruited to undergo imaging, examination, and laboratory assessment.

The REP medical records linkage system was established in 1966 to capture all health care information for the entire population of Olmsted County, Minnesota.13, 14, 15 The REP now encompasses the medical

Results

The mean age of the study participants at the time of delivery was 24 years. Prior to their index pregnancies, women with preeclampsia, compared to those with normotensive pregnancies, had higher BMI, expressed as median (23.9; IQR, 21.3-26.1 vs 21.0; IQR, 20.0-24.3, P = .012). The rates of gestational diabetes were similar between the groups, affecting 2 of 40 women in each group (P = 1.00). The mean age of the study participants at the time of imaging was 59.5 (±4.6) years. There were no

Comment

This is the first prospective cohort study that utilized review of the medical record to confirm the diagnosis of preeclampsia by accepted clinical criteria that demonstrated a history of preeclampsia is associated with an increased risk of CAC >3 decades after pregnancy in asymptomatic women without prior CVD events. The association between preeclampsia and CAC, in part, could be due to conventional CVD risk factors common to both processes. Indeed, women with preeclampsia had higher BMI and

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    This research was funded, in part, by grants from the National Institutes of Health (NIH) P50 AG044170; NIH R01 AG034676; UL1 TR000135 from the National Center for Advancing Translational Sciences (NCATS), a component of the NIH; the Department of Surgery; and the Mayo Foundation. The contents is solely the responsibility of the authors and do not necessarily represent the official view of NIH.

    The authors report no conflict of interest.

    Cite this article as: White WM, Mielke MM, Araoz PA, et al. A history of preeclampsia is associated with a risk for coronary artery calcification 3 decades later. Am J Obstet Gynecol 2016;214:519.e1-8.

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