Volume 200, Issue 5 , Pages e60-e62, May 2009
Investigating the risk of hypertension shortly after pregnancies complicated by preeclampsia
Article Outline
Objective
Women with a history of preeclampsia are at increased risk for long-term cardiovascular morbidity and mortality. This study assessed whether a pregnancy complicated by preeclampsia is associated with an increased prevalence of maternal hypertension and other cardiovascular risk factors shortly after delivery.
Study Design
Seventy-nine cases and 140 controls that had been enrolled in a prospective case-control study were evaluated in this planned follow-up analysis. The presence of hypertension, diabetes and dyslipidemia were assessed by standardized questionnaire 6-13 months after delivery.
Results
Women with preeclampsia were significantly more likely than controls to have hypertension (adjusted odds ratio, 13.92; 95% CI, 5.17-37.4; P < .001) after adjusting for confounders. Women with preterm preeclampsia also had an increased odds of hypertension (adjusted odds ratio, 18.31; 95% CI, 5.04-66.46; P < .001) compared with controls.
Conclusion
Pregnancy complications, such as preeclampsia, may provide opportunities to identify women at risk for cardiovascular morbidity years before the onset of disease, allowing a window for prevention and intervention.
Key words: cardiovascular disease, hypertension, preeclampsia, pregnancy, pregnancy complications
Cardiovascular disease is the leading cause of death in women, both in the United States and internationally.1 It remains difficult to identify at-risk women early, when lifestyle modification and/or intervention may prevent cardiovascular morbidity and mortality. Recent population-based retrospective cohort studies suggest gestational hypertension and preeclampsia are associated with significant long-term risk of early onset cardiovascular disease and death from cardiovascular causes.2, 3, 4, 5, 6, 7, 8 Given their long time span and retrospective nature, these studies are unable to identify when these women begin to incur increased risk for cardiovascular disease.
Only 1 study has examined maternal cardiovascular status in a prospectively collected cohort of women with physician-verified gestational hypertension or preeclampsia.9 No study has characterized short-term development of hypertension in women with preeclampsia. Identifying the time at which these women have an increased risk and targeting this group for lifestyle modifications/therapeutic interventions might have a significant impact on long-term cardiovascular morbidity and mortality.
The primary objective of this study was to determine whether preeclampsia was associated with an increased prevalence of hypertension or other cardiovascular risk factors 6-13 months after delivery. Our secondary aim was to determine whether severity of preeclampsia modified the association between preeclampsia and short-term prevalence of hypertension.
Materials and Methods
A prospective, institutional review board-approved case control study, Preeclampsia: Mechanisms and Consequences (PMC), was performed at the Hospital of the University of Pennsylvania (HUP) between March 2005 and August 2007. The methods of this study have been described in detail elsewhere.10 Consent for this planned follow-up standardized telephone interview was obtained at the time of enrollment. Cases were prospectively identified based on maternal criteria for preeclampsia. Preeclampsia was defined as blood pressure ≥ 140/90 mm Hg on 2 measurements ≥ 6 hours apart or ≥ 160/105 mm Hg, and proteinuria. Those women who met criteria for blood pressure but not proteinuria were also included, as up to 20% of eclamptic women do not have proteinuria. For this study's analysis, preterm preeclampsia was defined by the same blood pressure criteria, and delivery at ≤ 34 weeks secondary to the diagnosis of preeclampsia.
The presence of hypertension and other cardiovascular risk in cases and controls was assessed through telephone interviews 6-13 months after delivery. Cases and controls enrolled in the PMC study from January 2006-October 2006 were contacted by telephone between January 2007 and April 2007. All telephone interviews were conducted by the primary author (A.G.E.) with a standardized script.
If the patient was not reached or if no valid contact information for the patient was available, the patient was designated “not reached.” Contacted patients were asked a series of questions to determine the prevalence of hypertension and other cardiovascular risk factors after preeclampsia (Table 1). Postpartum body mass index (BMI) at follow-up was assessed by using height documented at initial enrollment and reported weight at follow-up interview. The prevalence of hypertension at time of follow-up was assessed as a dichotomous variable. Patients who had not received medical care after their postpartum visit to have their blood pressure measured were excluded from the hypertension analysis (13 controls and 5 cases).
TABLE 1. Questions asked in interview to assess cardiovascular riska
| 1) Since delivery, have you had your blood pressure measured? |
 1a) If “yes” to above: since delivery, has anyone told you that your blood pressure is high? |
| 2) Do you currently take medication for your blood pressure? |
| 3) Since delivery, have you been told that you have diabetes or blood sugar problems? |
| 4) Do you currently take insulin or medicine by mouth to control your blood sugar? |
| 5) Since delivery, have you been told that you have high cholesterol or lipid problems? |
| 6) Do you take any medication for your cholesterol or triglycerides? |
aIf “yes” to any of the questions 1a-6, patient was considered to have “any cardiovascular risk.” |
Demographic characteristics were compared by using χ2analyses. Student t test was used to compare continuous variables. Associations between case control status and hypertension, diabetes, and dyslipidemia at follow-up were evaluated by using Pearson χ2 test of association. A stratified analysis by parity (dichotomous) was performed and there was no evidence of effect modification. Multivariable logistic regression was used to control for significant confounders, including race (African American vs other), BMI (dichotomous ≥ 30), parity (dichotomous), and chronic hypertension (dichotomous). These same analyses were performed comparing women with preterm preeclampsia (≤ 34 weeks) with controls. All analyses were performed by using STATA statistical software, version 9.0 Special Edition (College Station, TX).
Results
One hundred twenty-four cases and 279 controls were enrolled in the PMC study between January 2006 and October 2006. At the time of initial enrollment, 9% (11) of cases and 14% (40) of controls declined participation in this follow-up study. The total number of patients eligible for the follow-up assessment of cardiovascular risk included 113 cases and 239 controls. Of the patients eligible, 79 cases (70%) and 140 controls (59%) completed the follow-up study. Of the 79 cases, 17 (21.5%) had preterm preeclampsia.
The primary reasons that patients were not reached included: (1) disconnected or changed phone number (59% [20/34] of cases and 53% [52/99] of controls); (2) no answer or unreturned messages (41% [14/34] of cases and 43% [43/99] of controls); and (3) patients who declined participation at time of the follow-up phone interview (3% [3/99] of controls). The demographic characteristics of cases and controls are presented in Table 2.
TABLE 2. Demographics
| Characteristics | Cases % (n = 79) | Controls % (n = 140) | P value |
|---|---|---|---|
| Race: African American | 77(61) | 60.7(85) | .01 |
| Mean age (y) | 26.6 ± 6.4 | 28.3 ± 6.8 | .07 |
| Chronic hypertension | 15.2(12) | 5.7(8) | .02 |
| BMI ≥ 30 (at follow-up)a | 48.7(37) | 40.1(55) | .23 |
| Mean BMIa | 29.3 ± 6.9 | 29.3 ± 8.3 | .98 |
| Nulliparous | 54(43) | 42(59) | .08 |
| History of preeclampsia > 1 pregnancy | 20.3(16) | 5.7(8) | .002 |
| Tobacco use | 8.8(7) | 14.3(20) | .24 |
| Mean time to follow-up (d) | 225.4 ± 44.8 | 230.4 ± 41.9 | .41 |
aTotal n = 76 for cases and 137 for controls. |
Table 3 depicts prevalence of cardiovascular risk factors in cases and controls at time of follow-up. Table 4 depicts the unadjusted and adjusted odds ratios for cardiovascular risk factors at time of follow-up in all cases vs controls. Women with preeclampsia had nearly 14-fold higher odds of hypertension compared with controls after adjusting for confounders. Women with preterm preeclampsia had 18-fold higher odds of hypertension compared with controls after controlling for confounders (Table 5).
TABLE 3. Prevalence of cardiovascular risk factors at time of follow-up
| Risk factor | Case % (n) | Controls % (n) | P value |
|---|---|---|---|
| HTN or use of antihypertensive medicine | 44.6(33) | 7.8(10) | <.0001 |
| HTN or use of antihypertensive medicine excluding chronic hypertensives | 38.7(24) | 4.4(5) | <.0001 |
| Dyslipidemia or use of lipid-lowering medicine | 8.0(6) | 3.1(4) | .18 |
| Diabetes/use of hypoglycemics | 8.0(6) | 3.9(5) | .22 |
TABLE 4. Cardiovascular risk factors at time of follow-up: all cases vs controls
| Risk factor | OR (unadjusted) | OR (adjusted) | 95% CI | P value |
|---|---|---|---|---|
| Hypertensiona | 10.5 | 13.92 | 5.2-37.4 | <.001 |
| Diabetesb | 2.2 | 1.84 | 0.5-6.5 | .35 |
| Dyslipidemiab | 2.7 | 3.12 | 0.81-12.0 | .09 |
aControlling for race, body mass index, parity, and chronic hypertension. |
bControlling for race, body mass index, and parity. |
TABLE 5. Cardiovascular risk factors at time of follow-up: preterm cases vs controls
| Risk factor | OR (unadjusted) | OR (adjusted) | 95% CI | P value |
|---|---|---|---|---|
| Hypertensiona | 19.7 | 18.31 | 5.1-66.5 | <.001 |
| Diabetesb | 1.8 | 1.86 | 0.19-18.6 | .6 |
| Dyslipidemiab | 4.8 | 5.79 | 0.8-40.7 | .08 |
aControlling for race, body mass index, parity, and chronic hypertension. |
bControlling for race, body mass index, and parity. |
Comment
Recent studies have demonstrated that a history of preeclampsia confers an increased risk for future cardiovascular disease, and a lifetime increased risk of maternal mortality from cardiovascular causes.2, 3, 4, 5, 6, 7, 8 Our study demonstrates that preeclampsia is associated with an increase in hypertension 6-13 months after delivery. Although the odds of short-term cardiovascular risk may be even higher for preterm preeclampsia, the similar confidence intervals for preterm preeclamptic women and all women limits our ability to definitively draw this conclusion from the study. Our study suggests that one of the mechanisms by which preeclampsia increases the risk for long-term cardiovascular sequelae may be through a higher prevalence of hypertension as early as 6 months after delivery.
A major strength of this study is the prospective identification of cases and controls, minimizing the risk of misclassification. Another strength is the assessment of cardiovascular risk shortly after delivery, at a point when at-risk women may be candidates for early prevention and/or intervention. The inclusion of all forms of pregnancy related-hypertension is more generalizable. It has been suggested that gestational hypertension does not confer the same magnitude of future risk as preeclampsia. This has not been fully elucidated, and if this is true, the inclusion of these patients would bias the results to the null.
This study has limitations. The use of a surrogate outcome incorporating patient report of cardiovascular risk factors is less precise than objective measurements. However, because the short-term risk after preeclampsia has not been characterized, this is the first step in identifying the need for future research. A questionnaire introduces the potential for recall bias. We attempted to control for this by having one author conduct all interviews using a standardized script.
Despite the limitations of collecting data by phone interview, studies such as this are the first step in confirming large population-based epidemiologic evaluations. The large relative risk of hypertension in cases vs controls suggests a true association. The demonstration of cardiovascular risk factors in preeclamptic women as early as 6 months postpartum suggests the postdelivery period is a critical time to identify these at-risk women, and engage them in receiving routine health care.
References
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Support was provided through a FOCUS Medical Student Fellowship in Women's Health supported by the Edna G. Kynett Memorial Foundation.
Reprints are not available from the authors.
PII: S0002-9378(08)02025-5
doi:10.1016/j.ajog.2008.10.012
© 2009 Mosby, Inc. All rights reserved.
Volume 200, Issue 5 , Pages e60-e62, May 2009
