AJP - Heart Journal of Applied Physiology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Heart Circ Physiol 286: H1389-H1393, 2004; doi:10.1152/ajpheart.00298.2003
0363-6135/04 $5.00
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (22)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Agatisa, P. K.
Right arrow Articles by McLaughlin, M. K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Agatisa, P. K.
Right arrow Articles by McLaughlin, M. K.

Impairment of endothelial function in women with a history of preeclampsia: an indicator of cardiovascular risk

Patricia K. Agatisa,1,2,3 Roberta B. Ness,1,2,3 James M. Roberts,1,2,3 Joseph P. Costantino,4 Lewis H. Kuller,3 and Margaret K. McLaughlin1,2

1Magee-Womens Research Institute, 2Department of Obstetrics and Gynecology and Reproductive Sciences, School of Medicine; and 3Department of Epidemiology and 4Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15213

Submitted 1 April 2003 ; accepted in final form 24 November 2003


   ABSTRACT
TOP
 ABSTRACT
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Preeclampsia is a disorder of pregnancy diagnosed by gestational hypertension and proteinuria. Epidemiological evidence suggests that women who experience preeclampsia are at a greater risk of hypertension and heart disease later in life compared with women who had normal pregnancies. Our objective was to determine whether endothelial function is impaired in postpartum women with a history of preeclampsia in their first pregnancy. We measured forearm blood flow (FBF) by venous occlusion plethysmography in 50 healthy women: 16 with prior preeclampsia, 14 with a prior normotensive pregnancy, and 20 never pregnant controls. The postpartum women participated 6–12 mo after delivery. Heart rate (HR) and blood pressure (BP) were concurrently monitored on the contralateral arm. Hemodynamic variables were assessed at baseline and during a mental stress test known to elicit endothelium-dependent vasodilatation. We found that baseline FBF, HR, systolic BP, and diastolic BP did not significantly differ among the groups, whereas mean arterial pressure in the preeclamptic group was greater than that of the normal pregnancy group (P = 0.03). Stress-induced FBF (percent change over baseline) was reduced in the preeclamptic group compared with both the normal pregnancy and never pregnant groups (P = 0.06) and was significantly attenuated compared with women with prior normal pregnancies (91% vs. 147%, P = 0.006). These data demonstrate that women with a history of preeclampsia exhibit impaired endothelial function up to 1 yr postpartum. This observation may explain their increased risk for hypertension and cardiovascular disease.

endothelium; cardiovascular disease; risk factors; plethysmography

PREECLAMPSIA IS A MAJOR CAUSE of maternal and neonatal mortality worldwide (20, 21) and a major contributor to premature births and intrauterine growth restriction (12). It occurs in ~5–7% of first pregnancies and recurs at an alarming rate of 20–25% (33). This pregnancy-specific disorder is diagnosed by elevated blood pressure (BP) and proteinuria and characterized by clinical features including edema and coagulation abnormalities (28). Although many of the clinical and physiological manifestations associated with preeclampsia resolve soon after delivery, its impact persists in the postpartum period.

Epidemiological studies provide evidence that women with a history of preeclampsia are more likely to develop hypertension compared with women who had normal pregnancies (2, 11, 14, 22, 24), and women who experience recurrent preeclamptic pregnancies are at even greater risk (7, 30, 31). Prior preeclampsia is also associated with increased risk of cardiovascular disease (CVD), including myocardial infarction (14, 23), ischemic heart disease (19), and stroke (18).

The underlying mechanism that places women with a history of preeclampsia at risk for hypertension and CVD remains speculative. Endothelial dysfunction, however, is considered a central component of the pathophysiology of preeclampsia and known to contribute to the pathogenesis of hypertension and cardiovascular sequelae. The objective of the present study was to examine whether endothelial function is impaired postpartum in the resistance vessels of women with prior preeclampsia. The presence of endothelial dysfunction could contribute to the elevated BP and increased cardiovascular risk that women with a history of preeclampsia exhibit.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Study subjects. Fifty healthy women (16 with a history of preeclampsia, 14 women with a prior normal pregnancy, and 20 never pregnant controls) between the ages of 18 and 40 yr were enrolled in this case-control study. Postpartum primiparous participants were recruited from the ongoing longitudinal study entitled Prenatal Exposures and Preeclampsia Prevention (PEPP) conducted at Magee-Womens Hospital (MWH), University of Pittsburgh. Briefly, this study enrolled women who presented for prenatal care at MWH clinics and associated obstetrics/gynecology practices at ~12–16 wk of gestation and followed them through delivery. In addition, a separate set of participants admitted to rule out preeclampsia at or near the time of labor and delivery was recruited into the parent study, PEPP. On the basis of a review of the medical history and interview information, as well as physiological data and biological specimens, PEPP participants' pregnancy outcomes were classified into diagnostic categories, including those pertinent to this study, i.e., preeclampsia with no preexisting disease and normal pregnancy. Eligible primiparous women were evaluated 6–12 mo after delivery to allow return to prepregnancy physiological baseline; none were nursing. In addition, 20 healthy never pregnant controls, recruited by age and body mass index (BMI) to match the preeclamptic history group, were enrolled into the study.

The study criteria for preeclampsia consisted of a finding of 1) gestational hypertension: elevated BP, >=30 mmHg change in systolic BP (SBP) or >=15 mmHg in diastolic BP (DBP) from before 20 wk of gestation or SBP >= 140 mmHg or DBP >= 90 mmHg in late pregnancy if prior BP was unavailable; 2) proteinuria within 24 h of labor: urine dipstick with >=1+ protein on a catheterized sample or a reading of >=2+ protein on a random collection or >=0.3 g protein in 24-h urine collection; and 3) uric acid within 24 h of labor: >1 SD above normal level for gestational age. Exclusion criteria for all participants were prior history of hypertension (defined as BP > 140/90) or use of antihypertensive medication, heart disease, diabetes mellitus, renal disease, and current pregnancy confirmed by a urine test. The study protocol was approved by the Institutional Review Board of MWH, and all subjects provided written informed consent.

Study protocol. Participants were evaluated in the General Clinical Research Center of MWH in a quiet, temperature-controlled room (21–23°C) in the morning after a light breakfast while lying supine. They abstained from caffeinated and alcoholic beverages for 12 h and physical activity for 24 h, and smokers refrained for 12 h before being tested. Forearm blood flow (FBF) was measured on the nondominant arm by venous occlusion plethysmography with the use of a mercury in-silastic strain gauge connected to a plethysmograph (EC5R Plethysmograph, DE Hokanson; Bellevue, WA). A wrist cuff was inflated to suprasystolic pressure (200 mmHg) to exclude hand circulation while an upper arm cuff cycled between 15 s of inflation (50 mmHg) and 5 s of deflation during flow measurements (E20 Rapid Cuff Inflator, DE Hokanson). The mean of six to eight consecutive FBF readings comprised baseline FBF. The subjects then rested 15 min to allow time to flush out metabolites and return hand blood flow to normal levels. Next, the Stroop Color Word Test (34), a mental stress test that induces the fight-or-flight response including endothelium-dependent vasodilatation (8), was administered. Impairment of stress response is an indicator of endothelial dysfunction. FBF was measured as above, and the peak FBF value was determined. Excess FBF was defined as the difference between peak FBF and mean baseline FBF. The percent increase in FBF was calculated as the ratio of peak FBF to baseline FBF. SBP, DBP, mean arterial pressure (MAP), and heart rate (HR) were measured continuously on the dominant arm with a Dinamap BP monitor (CrikitonVital Signs Monitor Dinamap 1846SX).

Statistical analysis. Values are presented as means ± SE, change over baseline where applicable, or number of subjects and percentages. Differences of mean group values for continuous variables were compared with one-way ANOVA, followed by Bonferroni's correction for multiple comparisons. Nonparametric tests were applied when data were not normally distributed. Univariate comparisons of variables of the postpartum groups, i.e., preeclampsia and normal pregnancy, were performed using the unpaired Student's t-test. Frequencies of categorical variables in the three groups were compared with the {chi}2-test. Repeated-measures ANOVA was used to evaluate changes in HR and BP of the three groups throughout the study. The association between diagnosis and excess FBF was assessed by linear regression analysis and limited to the postpartum groups. Small sample size necessitated the parsimonious entry of potential confounding variables into the regression model beginning with diagnostic category and baseline FBF. Continuous variables whose means significantly differed in the study groups were then entered to assess the effect of diagnostic category on excess FBF. Statistical analyses were performed using SPSS software (version 11.0, SPSS; Chicago, IL), and significance was accepted at a value of P < 0.05.

Sample size. Sample size was calculated to assess change in FBF during stress. A study of healthy individuals aged 18–42 yr that utilized the Stroop test reported a change in FBF of 6.5 ± 0.7 ml·100 ml–1·min–1 (8). With the use of these values to calculate sample size in a ratio of 1 preeclamptic case to 1 normal pregnancy control in an unmatched two-tailed analysis, 20 women in each group were needed to provide 80% power to detect a 25% reduction in excess FBF. After a subset of the study sample was enrolled, preliminary analyses were performed. Excess FBF in the preeclampsia subset (n = 16) compared with the normal pregnancy subset (n = 14), was reduced 56% more than double the predicted rate. Therefore, enrollment of postpartum subjects was considered sufficient. In addition, 20 never pregnant controls were evaluated.


   RESULTS
TOP
 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
Baseline characteristics. A total of 50 women was assessed: 16 women with history of preeclampsia, 14 women with a normal pregnancy, and 20 never pregnant controls (Table 1). The three study groups were predominantly Caucasian and comparable in age, oral contraceptive use, and current smoking practice. Compared with the normal pregnancy controls, the women with prior preeclampsia delivered earlier and had a greater body BMI (post hoc comparison, P = 0.0013) at an average of 10 mo postpartum. The stage of menstrual cycle in the noncontraceptive users was evenly distributed among the three groups. Prior reproducibility of the technique did not produce significant differences in flow response during the course of a menstrual cycle (data not shown), so subjects were randomly tested during their cycle.


View this table:
[in this window]
[in a new window]
  		Table 1. Clinical characteristics of study participants

 

Baseline HR and FBF were comparable in the three study groups (Table 1), although baseline HR and BP values were consistently lowest in the normal pregnancy group and highest in the preeclamptic group. SBP and DBP comparisons approached significance (P = 0.06 and 0.08, respectively). MAP differed among the three groups (P = 0.007) and was higher in the preeclamptic subjects compared with the normal pregnancy group (post hoc comparison, P = 0.004).

Stress-induced hemodynamic measurements. Table 2 presents a comparison of stress-induced hemodynamic variables. The mental stress test was associated with a similar change over baseline in HR, BP, and FBF in the three study groups. HR and BP values were highest in the preeclampsia group and lowest in normal pregnancy group. DBP varied significantly and was greater in the preeclamptic group compared with both the normal pregnancy (post hoc comparison, P = 0.03) and never pregnant controls (post hoc comparison, P = 0.04). MAP also differed between the preeclamptic group and normal pregnancy controls (post hoc comparison, P = 0.03).


View this table:
[in this window]
[in a new window]
  		Table 2. Stress-induced hemodynamic values of study participants

 

Stress-induced FBF is described by three measurements: peak FBF, excess FBF (the difference between stress-induced peak FBF and baseline FBF), and percent change in FBF over baseline (the ratio of peak FBF to baseline FBF). The mean values of the preeclamptic group for each of these FBF measurements were less than those of the other groups (Table 2). Overall group comparison of the percent increase in FBF with stress approached significance (P = 0.06). This measurement was highly variable in the never pregnant group ranging from <10% to nearly 500% (Fig. 1). Comparing only the preeclamptic and the normal pregnancy groups, the percent increase in FBF with stress was significantly attenuated in the preeclamptics (91 ± 12% vs. 147 ± 16%, P = 0.006).



View larger version (10K):
[in this window]
[in a new window]
  		Fig. 1. Stress-induced percent change in forearm blood flow (FBF) by diagnosis.

 

Relationship between stress flow response and covariates. To assess whether the observed difference in FBF response to stress could indicate a dissimilar perception of stress between the three study groups, stress perception was assessed after the stress flow study. Stress scores indicated that there was no difference in the groups' mean responses (Kruskal-Wallis test, P = 0.29). We also excluded the possibility that the observed difference in percent change in FBF could be due to disparate change in HR or BP in the study groups by finding no significant difference using repeat-measures ANOVA in percent change in HR (P = 0.47), MAP (P = 0.48), SBP (P = 0.52), or DBP (P = 0.68) among the three groups throughout the study protocol. In addition, activity level as assessed by the Paffenbarger Activity Questionnaire (25) was comparable in the postpartum groups (preeclamptics: 924.5 kcal/wk vs. normotensives: 1,042 kcal/wk, P = 0.313), excluding the effect of activity on the difference in stress flow response.

Multivariate analysis. In multivariate linear regression analysis, diagnosis of preeclampsia was a significant predictor of impaired blood flow response to stress (P = 0.02), after controlling for baseline blood flow alone, and, in addition, MAP (P = 0.04) (Table 3). When BMI was entered into the model, the effect of a diagnosis of preeclampsia was attenuated but approached significance (P = 0.09). The final model accounted for ~54% of the observed variability in the excess blood flow. The regression suggests that the effect of preeclampsia on stress blood flow may be masked by BMI. Stratified analyses using a BMI cutpoint of 25 illustrate that point estimates of percent change in blood flow were consistently lower in the preeclamptic group (Table 4). Of note, the percent change of the leaner preeclamptics (102.0) was lower than that observed in the overweight normotensive group (115.79).


View this table:
[in this window]
[in a new window]
  		Table 3. Multivariate linear regression analysis relating independent variables to change in FBF

 

View this table:
[in this window]
[in a new window]
  		Table 4. Mean percent change in blood flow with stress by BMI and diagnosis

 


   DISCUSSION
TOP
 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
Endothelial dysfunction is considered a central component of the pathophysiology of preeclampsia (27) and is known to contribute to the pathogenesis of CVD (9, 10, 16, 26). This systemic phenomenon plays a major role in the pathogenesis and clinical manifestations of atherosclerosis (4). A close correlation has been found between vasomotor responses of the coronary arteries and forearm vascular bed (15, 35). The forearm vascular bed can therefore serve as a useful surrogate for assessing the coronary arteries and provide a mechanism for identifying those at increased cardiovascular risk at a stage amenable to intervention.

This study demonstrated that women with a history of preeclampsia exhibit evidence of endothelial dysfunction in the forearm vasculature an average of 10 mo after delivery. Impairment occurred despite resolution of the clinical hypertension that accompanies preeclampsia. Comparable changes in hemodynamic response in the three study groups discounted the possibility that HR or BP changes during stress could explain the observed attenuation in blood flow during the mental stress test. Our results confirm those of a previous study that observed reduced brachial artery dilatation in women with prior preeclampsia a median of 3 yr postpartum (5). To our knowledge, our study provides evidence for the first time that impairment of the central conduit vessles extends to the peripheral vasculature and suggests that endothelial dysfunction in women with prior preeclampsia is systemic in nature.

Thirty-one percent of our preeclamptic participants were obese, supporting the role that obesity plays in the onset of preeclampsia. Obesity and concomitant abnormal maternal lipid metabolism (17) and insulin resistance (32) may have some bearing on the attenuated endothelial-dependent blood flow response observed in the preeclamptic study participants. The trend noted in the multivariate analysis suggests that there is an independent negative effect of preeclampsia on vasodilatory response to stress. Stratified analyses by BMI provide additional support for a negative effect of preeclampsia independent from obesity. Stress-induced flow response in the presence of obesity and prior preeclampsia was less than that found in obese women without preeclampsia. A larger study sample could provide more power to substantiate this speculation.

MAP at baseline, although within the normal range, was significantly higher in the preeclamptic cases compared with the normal pregnancy controls. As a whole, the preeclamptic group exhibited the highest DBP during mental stress. Although controversial, a heightened BP response to mental challenges has been shown to predict subsequent BP levels and risk for atherosclerosis even after adjustment for initial BP levels, age, and BMI (24a).

The problem of identifying an appropriate control group for preeclamptic cases has resulted in disparate findings in the literature regarding future cardiovascular risk. It has been argued, particularly by Chesley (6), that women with normal pregnancies have a lower rate of CVD later in life than the general population and as such are not appropriate controls for preeclamptic cases. Women with prior normal pregnancies, though, are similar to preeclamptic cases as they have similar exposure to the "stress test" of pregnancy. The normal pregnancy group demonstrated the most favorable cardiovascular profile, i.e., lowest BP, HR, and stress-induced FBF. This observation may reflect preexisting healthy endothelium that accommodated a normal pregnancy. An alternative speculation is that normal pregnancy elicits a positive, long-term effect on endothelial function. The never pregnant group exhibited wide variability in blood flow response and HR and BP measurements. These findings may reflect their lack of exposure to the beneficial effects of cardiovascular remodeling inherent to pregnancy.

Some of the limitations of this research may have affected our findings. First, other unidentified risk factors may contribute to the impaired vasodilatory stress response. Behavioral factors, such as chronic stress, lack of social support, and family demands (13, 29), as well as biological processes, including genetics, hyperlipidemia, and insulin resistance (1), have been shown to contribute to the development of CVD but were not assessed in this study. Moreover, whereas the normal pregnancy participants were predominantly clinic patients followed longitudinally, the preeclamptic subjects were predominantly private patients recruited at labor and delivery. This leads us to suspect that the observed association between preeclampsia and endothelial dysfunction is, in fact, a conservative estimate because the preeclamptic women were of higher socioeconomic status, a positive predictor of health status (3).

Despite its limitations, this research study benefited from a number of strengths. Application of stringent diagnostic criteria by a jury of clinicians reduced the possibility of misclassification of essential or gestational hypertension as preeclampsia. We recognize that the cross-sectional nature of the study did not permit assessment of endothelial function before pregnancy but studied the never pregnant control group to provide some insight into endothelial health before pregnancy. The study size was limited but powered to detect a 25% difference in the flow response between the preeclamptic cases and normal pregnancy controls. The observation of a 56% difference in flow in this small cohort strengthens the association between preeclampsia and impaired endothelial function.

In summary, we found that women with a history of preeclampsia exhibit impaired endothelium-dependent vasodilatation to mental stress 1 yr postpartum, which may precurse clinical disease. Although the data are limited, they are provocative because demonstration of a link between preeclampsia and CVD risk, especially if that risk is present in the reproductive years, could identify a subset of women who might benefit from heightened surveillance and early preventative interventions such as weight loss, BP control, and lipid and glycemic control.


   ACKNOWLEDGMENTS
 
GRANTS

This study was supported by the Irene McLenahan Young Investigator Research Fund of the Magee-Womens Health Foundation and National Institute of Child Health and Human Development Grant P01-HD-30367.


   FOOTNOTES
 

Address for reprint requests and other correspondence: P. K. Agatisa, Cardiovascular Behavioral Medicine Program, Univ. of Pittsburgh, 3811 O'Hara St., Pittsburgh, PA 15213 (E-mail: agatisapk{at}upmc.edu).

The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.


   REFERENCES
TOP
 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

  1. 27th Bethesda Conference. Matching the Intensity of Risk Factor Management with the Hazard for Coronary Disease Events. September 14–15, 1995. J Am Coll Cardiol 27: 957–1047, 1996.[Medline]
  2. Adams E and MacGillivray I. Long-term effect of pre-eclampsia on blood pressure. Lancet 2: 1373–1375, 1961.[CrossRef][Web of Science][Medline]
  3. Adler NE and Ostrove JM. Socioeconomic status and health: what we know and what we don't. Ann NY Acad Sci 896: 3–15, 1999.[CrossRef][Web of Science][Medline]
  4. Anderson TJ, Uehata A, Gerhard MD, Meredith IT, Knab S, Delagrange D, Lieberman EH, Ganz P, Creager MA, and Yeung AC. Close relation of endothelial function in the human coronary and peripheral circulations. J Am Coll Cardiol 26: 1235–1241, 1995.[Abstract]
  5. Chambers JC, Fusi L, Malik IS, Haskard DO, DeSwiet M, and Kooner JS. Association of maternal endothelial dysfunction with preeclampsia. JAMA 2985: 1607–1612, 2001.
  6. Chesley L. Hypertension in pregnancy: definitions, familial factor, and remote prognosis. Kidney Int 18: 234–240, 1980.[Web of Science][Medline]
  7. Chesley LC. False starts in the study of preeclampsia-eclampsia. Obstet Gynecol 5: 177–187, 1976.
  8. Dietz NM, Rivera JM, Eggener SE, Fix RT, Warner DO, and Joyner MJ. Nitric oxide contributes to the rise in forearm blood flow during mental stress in humans. J Physiol 480: 361–368, 1994.[Abstract/Free Full Text]
  9. Drexler H. Endothelial dysfunction: clinical implications. Prog Cardiovasc Dis 39: 287–324, 1997.[CrossRef][Web of Science][Medline]
  10. Drexler H and Hornig B. Endothelial dysfunction in human disease. J Mol Cell Cardiol 31: 51–60, 1999.[CrossRef][Web of Science][Medline]
  11. Epstein FH. Late vascular effects of toxemia of pregnancy. N Engl J Med 271: 391–395, 1964.[Web of Science][Medline]
  12. Eskenazi B, Fenster L, Sidney S, and Elkin E. Fetal growth retardation in infants of multiparous and nulliparous women with preeclampsia. Am J Obstet Gynecol 169: 1112–1118, 1993.[Web of Science][Medline]
  13. Greenwood DC, Muir KR, Packham CJ, and Madeley RJ. Coronary heart disease: a review of the role of psychosocial stress and social support. J Public Health Med 18: 221–231, 1996.[Abstract/Free Full Text]
  14. Hannaford P, Ferry S, and Hirsch S. Cardiovascular sequelae of toxaemia of pregnancy. Heart 77: 154–158, 1997.[Abstract/Free Full Text]
  15. Hirooka Y, Egashira K, and Imaizumi T. Effect of L-arginine on acetylcholine-induced endothelium-dependent vasodilation differs between the coronary and forearm vasculatures in humans. J Am Coll Cardiol 24: 948–955, 1994.[Abstract]
  16. Hornig B and Drexler H. Reversal of endothelial dysfunction in humans. Coron Artery Dis 12: 463–473, 2001.[CrossRef][Web of Science][Medline]
  17. Hubel CA. Oxidative stress and preeclampsia. Fetal Maternal Med Rev 9: 73–101, 1997.[CrossRef]
  18. Irgens HU, Raissaeter L, Irgens LM, and Lie RT. Long term mortality of mothers and fathers after pre-eclampsia: population based cohort study. Br Med J 323: 1213–1217, 2001.[Abstract/Free Full Text]
  19. Jonsdottir L, Arngrimsson R, Geirsson R, Sigvaldason H, and Sigfusson N. Death rates from ischemic heart disease in women with a history of hypertensionin pregnancy. Acta Obstet Gynecol Scand 74: 772–776, 1995.[Web of Science][Medline]
  20. Kaunitz A, Hughes J, Grimes D, Smith J, and Rochat R. Causes of maternal mortality in the United States, 1979–1986. Am J Obstet Gynecol 163: 460–465, 1990.[Web of Science][Medline]
  21. Lenfant C. Working group report on high blood pressure in pregnancy. J Clin Hypertens (Greenwich) 3: 75–88, 2001.[Medline]
  22. Lindeberg S, Axelsson O, Jorner U, Malmberg L, and Sandstrom B. A prospective controlled five-year follow-up study of primiparas with gestational hypertension. Acta Obstet Gynecol Scand 67: 605–609, 1988.[Web of Science][Medline]
  23. Mann JI, Doll R, Thorogood M, Vessey MP, and Waters WE. Risk factors for myocardial infarction in young women. Brit J Prev Soc Med 30: 94–100, 1976.
  24. Marin R, Gorostidi M, Portal CG, Sanchez M, Sanchez E, and Alvarez J. Long-term prognosis of hypertension in pregnancy. Hyperten Preg 19: 199–209, 2000.[CrossRef][Web of Science][Medline]
  25. Matthews KA, Woodall KL, and Allen MT. Cardiovascular reactivity to stress predicts future blood pressure status. Hypertension 22: 479–485, 1993.[Abstract/Free Full Text]
  26. Paffenbarger RS Jr, Blair SN, Lee IM, and Hyde RT. Measurement of physical activity to assess health effects in free-living populations. Med Sci Sports Exerc 25: 60–70, 1993.[CrossRef][Web of Science][Medline]
  27. Panza JA. Endothelial dysfunction in essential hypertension. Clin Cardiol 20: II-26–II-33, 1997.
  28. Roberts JM. Endothelial dysfunction in preeclampsia. Semin Reprod Endocrinol 16: 5–15, 1998.[Web of Science][Medline]
  29. Roberts JM and Redman CWG. Pre-eclampsia: more than pregnancy-induced hypertension. Lancet 341: 1447–1451, 1993.[CrossRef][Web of Science][Medline]
  30. Rozanski A, Blumenthal JA, and Kaplan J. Impact of psychological factors on the pathogenesis of cardiovascular disease and implications for therapy. Circulation 99: 2192–2217, 1999.[Abstract/Free Full Text]
  31. Sibai BM, Mercer B, and Sarinoglu C. Severe preeclampsia in the second trimester: recurrence risk and long-term prognosis. Am J Obstet Gynecol 165: 1408–1412, 1991.[Web of Science][Medline]
  32. Sibai BM, Mercer B, and Sarinoglu C. Eclampsia. VII. Pregnancy outcome after eclampsia and long-term prognosis. Am J Obstet Gynecol 166: 1757–1763, 1992.[Web of Science][Medline]
  33. Steinberg H, Chaker H, Leaming R, Johnson A, Brechtel G, and Baron A. Obesity/Insulin resistance is associated with endothelial dysfunction. Implications for the syndrome of insulin resistance. J Clin Invest 97: 2601–2610, 1996.[Web of Science][Medline]
  34. Stone JL, Lockwood CJ, Berkowitz GS, Alvarez M, Lapinski R, and Berkowitz RL. Risk factors for severe preeclampsia. Obstet Gynecol 83: 357–361, 1994.[Web of Science][Medline]
  35. Stroop J. Studies of interferences in serial verbal reactions. J Exp Psychol 18: 643–662, 1935.[CrossRef][Web of Science]
  36. Tagawa T, Mohri M, and Tagawa H. Role of nitric oxide in substance P-induced vasodilatation differs between the coronary and forearm circulation in humans. J Cardiovasc Pharmacol 29: 546–553, 1997.[CrossRef][Web of Science][Medline]



This article has been cited by other articles:


Home page
 ICVTSHome page
A. E. Topal and M. N. Eren
Acute ventricular rupture due to myocardial infarction during postpartum period
Interactive CardioVascular and Thoracic Surgery, May 1, 2009; 8(5): 565 - 567.
[Abstract] [Full Text] [PDF]

Home page
 StrokeHome page
C.-H. Tang, C.-S. Wu, T.-H. Lee, S.-T. Hung, C.-Y. C. Yang, C.-H. Lee, and P.-H. Chu
Preeclampsia-Eclampsia and the Risk of Stroke Among Peripartum in Taiwan
Stroke, April 1, 2009; 40(4): 1162 - 1168.
[Abstract] [Full Text] [PDF]

Home page
 Mol Hum ReprodHome page
E. Fitzpatrick, M.P. Johnson, T.D. Dyer, S. Forrest, K. Elliott, J. Blangero, S.P. Brennecke, and E.K. Moses
Genetic association of the activin A receptor gene (ACVR2A) and pre-eclampsia
Mol. Hum. Reprod., March 1, 2009; 15(3): 195 - 204.
[Abstract] [Full Text] [PDF]

Home page
 HypertensionHome page
H. Valensise, B. Vasapollo, G. Gagliardi, and G. P. Novelli
Early and Late Preeclampsia: Two Different Maternal Hemodynamic States in the Latent Phase of the Disease
Hypertension, November 1, 2008; 52(5): 873 - 880.
[Abstract] [Full Text] [PDF]

Home page
 NEJMHome page
B. E. Vikse, L. M. Irgens, T. Leivestad, R. Skjaerven, and B. M. Iversen
Preeclampsia and the Risk of End-Stage Renal Disease
N. Engl. J. Med., August 21, 2008; 359(8): 800 - 809.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
L. Luksha, H. Nisell, N. Luksha, M. Kublickas, K. Hultenby, and K. Kublickiene
Endothelium-derived hyperpolarizing factor in preeclampsia: heterogeneous contribution, mechanisms, and morphological prerequisites
Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2008; 294(2): R510 - R519.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
J. G. Williams, T. Rincon-Skinner, D. Sun, Z. Wang, S. Zhang, X. Zhang, and T. H. Hintze
Role of nitric oxide in the coupling of myocardial oxygen consumption and coronary vascular dynamics during pregnancy in the dog
Am J Physiol Heart Circ Physiol, October 1, 2007; 293(4): H2479 - H2486.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
A. H. James, M. G. Jamison, M. S. Biswas, L. R. Brancazio, G. K. Swamy, and E. R. Myers
Acute Myocardial Infarction in Pregnancy: A United States Population-Based Study
Circulation, March 28, 2006; 113(12): 1564 - 1571.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (22)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Agatisa, P. K.
Right arrow Articles by McLaughlin, M. K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Agatisa, P. K.
Right arrow Articles by McLaughlin, M. K.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online
Copyright © 2004 by the American Physiological Society.