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Keywords:

  • ambulatory arterial stiffness index;
  • blood pressure;
  • dipping;
  • pregnancy

Summary

  1. Top of page
  2. Summary
  3. Introduction
  4. Material and methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Conflict of interest
  9. References

Background

The study sets out to examine differences in arterial stiffness and nocturnal blood pressure dipping as outcomes in women with gestational hypertension compared with healthy pregnant women during pregnancy and 3 months after delivery.

Methods and results

We prospectively studied a cohort of 60 women during the third trimester of pregnancy; of them, 28 suffered pregnancy-induced hypertension or pre-eclampsia and 32 had uncomplicated singleton pregnancies. Subsequently, 42 of these were re-examined 3 months after delivery. In women with a hypertensive disorder, the nocturnal fall in blood pressure (dipping) was significantly smaller than in the normotensive group (systolic, = 0·031; diastolic, P<0·001), but after pregnancy, this difference disappeared (systolic, P = 0·941; diastolic, P = 0·907).

Ambulatory arterial stiffness index (AASI) assessed after pregnancy correlated inversely with fasting glucose level during pregnancy (= −0·580, P = 0·018), both systolic (r = −0·651, P = 0·012) and diastolic (r = −0·687, P = 0·007) nocturnal dipping and total cholesterol concentration after pregnancy (r = −0·526, P = 0·036).

Conclusions

A hypertensive disorder during pregnancy was associated with a flattened circadian blood pressure response, which was restored after delivery. Higher arterial stiffness predicted the signs of postpartum metabolic syndrome and correlated also with non-dipping, especially postpartum.


Introduction

  1. Top of page
  2. Summary
  3. Introduction
  4. Material and methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Conflict of interest
  9. References

About 15% of all pregnancies are complicated by high blood pressure (James & Nelson-Piercy, 2004). Hypertensive pregnancies include a heterogeneous spectrum of conditions; gestational hypertension, pre-eclampsia, chronic hypertension and superimposed pre-eclampsia. Severe preterm pre-eclampsia is known to be associated with an underlying placental abnormality, but milder hypertensive conditions near term can exist without any placental dysfunction. (Vatten & Skjaerven, 2004)(Valensise et al., 2008)(Phillips et al., 2010)It has been claimed that endothelial dysfunction may be present in pregnancies complicated by high blood pressure (Germain et al., 2007)and in fact, systemic arterial stiffness has also been shown to be increased in hypertensive pregnancies.(Tihtonen et al., 2006)(Ronnback et al., 2005).

Blood pressure displays a circadian pattern, that is, there is a blood pressure reduction (dipping) during the night-time, and this phenomenon also occurs during normal pregnancy. Frequently, a 10% fall has been used as a cut-off for a normal blood pressure daytime–night-time reduction. In many previous studies, a reduction in the decline in the nocturnal blood pressure has been claimed to be a risk factor for cardiovascular disease (Ingelsson et al., 2006; Izzedine et al., 2006; Fagard et al., 2008)and it also has been shown to be associated with arterial stiffness (Lekakis et al., 2005). Pre-eclampsia has been frequently found to be associated with non-dipping (Brown et al., 2001). Nocturnal hypertension in pre-eclampsia has been claimed to be associated with elevated levels of compounds related to endothelial damage (Bouchlariotou et al., 2008), for example, the levels of interleukin-6 have been found to be elevated in pre-eclampsia in several studies (Takacs et al., 2003)(Ouyang et al., 2009). The interleukin-6 concentration has also been found to be associated with measures of arterial stiffness and wave reflection (Schnabel et al., 2008).

Women with a history of hypertensive pregnancy are more likely to suffer from the metabolic syndrome (Mahmud et al., 2008) and overall, a tendency to develop cardiovascular events in later life (Garovic et al., 2010). Some recent studies have postulated that pre-eclampsia is not the determining factor for later cardiovascular risk, instead, the two states may share the same risk factors (Romundstad et al., 2010). However, early identification of the actual risk is challenging because the future risk may or may not be proportional to the severity of the metabolic or vascular abnormality observed during pregnancy. At present, it is unclear how best to assess the degree of the future risk during pregnancy.

In non-pregnant subjects, arterial stiffness is a strong predictor of risk of suffering cardiovascular events. The ambulatory arterial stiffness index (AASI) has been shown to correlate with other techniques of measuring arterial stiffness such as pulse wave velocity and augmentation index, and it has been claimed to be capable of detecting arterial dysfunction at a younger age than is possible with pulse pressure (Li et al., 2006). Ambulatory arterial stiffness index has been shown to predict cardiovascular deaths and strokes more precisely than the classical risk factors, even in normotensive subjects (Dolan et al., 2006)(Kikuya et al., 2007)and to be associated with target organ damage in individuals with arterial hypertension.(Leoncini et al., 2006; Mule et al., 2008). We have previously examined AASI in uncomplicated singleton and twin pregnancies and in pregnancies complicated by gestational diabetes mellitus.(Karkkainen et al., 2011, 2013).

The hypothesis for the present study was that women with gestational hypertension would exhibit changes in vascular function, primarily AASI and dipping, both during and after pregnancy when compared to healthy pregnant women. The main outcomes were AASI and dipping, and they were measured during the third trimester of pregnancy and 3 months after delivery. In particular, AASI has not been studied before in hypertensive pregnancies known to be associated with metabolic abnormalities and inflammation. Hence, the additional research questions were related to whether there would be associations between the main outcomes and maternal metabolism and IL-6.

Material and methods

  1. Top of page
  2. Summary
  3. Introduction
  4. Material and methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Conflict of interest
  9. References

Study population

The design of the study was an observational cohort study; hypertension in pregnancy being the exposure and the main outcomes being AASI and dipping both during and 3 months after pregnancy. The cohort of 60 childbearing women (28 with pregnancy-induced hypertension or pre-eclampsia and 32 with uncomplicated singleton pregnancy) was first prospectively studied during the third trimester of pregnancy. Sixteen women of 28 in the gestational hypertension group were receiving antihypertensive drugs (labetalol and/or nifedipine) at the time of recruitment. Control subjects remained normotensive throughout their pregnancies. Three months after delivery, we studied 42 of these women again (15 from the hypertensive group and 27 from the normotensive group), that is, 18 women did not want to participate in the second examination after delivery. We also divided the 28 women in the hypertensive group into two subgroups: pre-eclampsia (N = 18, after pregnancy N = 10) and gestational hypertension (N = 10, after pregnancy N = 5). The cohort was a convenience sample so that the cases were recruited during years 2002–2007 from the Kuopio University Hospital after they had been admitted due to hypertension in pregnancy to the antenatal department or were being followed at the outpatient clinic, where they were asked to participate and enrolled into the study if their clinical condition was stable enough to undergo the protocol and if adequate research resources were available at the time of enrolment. Controls were selected from women with uncomplicated pregnancies seen at the outpatient clinic for reasons, such as suspected breech presentation and low-lying placenta, where the pregnancy was deemed to be normal after the check-up. The study was approved by the Ethics Committee of the Kuopio University Hospital, and all participants provided informed consent.

The women in both groups had been healthy before pregnancy. Gestational hypertension was defined as a systolic blood pressure level ≥140 mm Hg or a diastolic blood pressure level ≥90 mm Hg after 20 weeks of pregnancy in women with previously normal blood pressure and with or without proteinuria. At admission, the following tests were carried out in the hypertensive/pre-eclamptic group: haemoglobin, platelet count, creatinine, alanine aminotransferase, uric acid and urine analysis. Height and weight were measured, and body mass index (BMI) was calculated (weight/height2).

Blood pressure and ambulatory arterial stiffness index (AASI)

Twenty-four-hour ambulatory blood pressure measurements were conducted using an ambulatory blood pressure system (SpaceLabs 90207; SpaceLabs Medical, Inc., Redmond, Washington, USA.) The cuff was placed in the non-dominant arm at the brachial level. We programmed the recorders to take blood pressure readings at 15-min intervals during the daytime and at 30-min intervals during the night-time. The duration of night-time was defined individually for each participant according to their normal rhythm. The ambulatory arterial stiffness index is defined as 1 minus the regression slope of the diastolic and systolic blood pressure values in individual subjects being determined from non-invasive 24-h ambulatory blood pressure recordings. The normal values of AASI have been proposed to be <0·50 at 20 years and <0·70 at 80 years. (Dolan et al., 2006; Kikuya et al., 2007).

The nocturnal fall in blood pressures (dipping) was defined as the difference between mean daytime systolic value and mean night-time systolic value (systolic dip). The diastolic dip was defined as the difference between the mean daytime and the mean nocturnal diastolic pressures. In our study, non-dippers were defined as individuals with nocturnal systolic blood pressure less than 10 mm Hg lower than the value in daytime.

Blood and urine samples

Venous blood samples were collected after an overnight fast. Serum was allowed to clot at room temperature for 30 min. The blood samples were centrifuged at 2000 × g for 10 min, and serum was separated and stored frozen at −70°C until analysis. Subjects were also asked to provide a 24-h urine collection.

Measurements

Clinical assays were performed from serum or urine samples by Konelab 60i Clinical Chemistry Analyzer (Thermo Electron Co, Finland) with Konelab Clinical Chemistry reagents. From serum samples, the creatinine concentration was measured by the Jaffe kinetic method, the uric acid concentration was measured by enzymatic uricase–peroxidase assay, the alanine aminotransferase concentration was measured by the kinetic IFCC method with pyridoxal phosphate addition, and the lactate dehydrogenase concentration was assayed by the kinetic IFCC method. Plasma glucose level was determined by the hexokinase method. All lipid analyses were performed with standard methods. The triglyceride concentration was determined by the GPO-PAP enzymatic, photometric assay, and the total serum cholesterol concentration was analysed by an enzymatic, photometric assay. Concentrations of high-density lipoprotein (HDL) cholesterol and low-density lipoprotein (LDL) cholesterol were determined by a direct, enzymatic, photometric method. The urine analysis was first performed by a dipstick measurement and if being positive, then a 24-h urine sample was collected.

The estimated glomerular filtration rate (GFR) was calculated by Cockcroft–Gault formula (Cockcroft & Gault, 1976).

Interleukin-6 concentrations were measured with a commercially available solid-phase enzyme-linked immunosorbent assay (ELISA) according to the protocol supplied by the manufacturer (Quantikine HS Human IL-6 Kit, R&D Systems, Minneapolis, USA). The working range was 0·156–10 pg ml−1 for IL-6. Calibrators for IL-6 assays were analysed in duplicate, but the samples were assayed as single measurements. The absorbances in ELISA tests were measured at a wavelength of 490 nm using a microplate reader (Tecan SPECTRAFluor, Tecan Group Ltd., Maennedorf, Switzerland).

Statistical analysis

The normality of the distribution of the data was examined with the Kolmogorov–Smirnov test. All data management and analyses were carried out using SPSS for Windows (Version 14.0) on a standard PC. Differences between groups were analysed with the Mann–Whitney U-test or Student t-test according to the normality of the distribution. Paired t-test and ANOVA with Bonferroni's post-tests were used in analysing changes during vs. after pregnancy. Relationships among variables were assessed using Pearson's correlation coefficient. The results are expressed as means ± SD of the mean. Differences were considered significant if P was <0·05.

A post hoc power calculation with an alpha of 0·05 and at a statistical power of 0·80 indicated that we would have needed 500 women; 250 in each group, to detect statistically significant differences in AASI values between the two groups or between the time points during and after the pregnancy.

Results

  1. Top of page
  2. Summary
  3. Introduction
  4. Material and methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Conflict of interest
  9. References

The clinical characteristics of the two study groups are shown in Table 1.

Table 1. Clinical characteristics of the 60 subjects
VariablePregnancy≥3 months after delivery
Normotensive(= 32) (mean ± SD)Hypertonia or pre-eclampsia (N = 28)P-valueNormotensive (N = 27)Hypertonia or pre-eclampsia (N = 15)P-value
  1. BP, blood pressure; AASI, ambulatory arterial stiffness index.

  2. *P<0·05, **P<0·01, ***P<0·001.

Background information
Age (years)31·2 ± 4·731·4 ± 5·60·858   
Nulliparity (%)18 (56)19 (68)0·360   
Height (cm)166·4 ± 6·8164·2 ± 6·50·208   
Weight before pregnancy (kg)63·4 ± 7·867·2 ± 12·10·145   
Body mass index (kg m²)22·9 ± 2·924·9 ± 3·90·031*   
Weight gain (kg)12·8 ± 3·214·9 ± 6·30·090   
Gestational age at 1. measurements (weeks)34·1 ± 3·334·8 ± 3·50·187   
Gestational age at birth (weeks)40·1 ± 0·537·8 ± 1·6<0·001***   
Birth weight (grams)3597 ± 5082908 ± 566<0·001***   
Fasting glucose (mmol l−1)4·4 ± 0·44·5 ± 0·70·2814·8 ± 0·45·0 ± 0·30·043*
Total cholesterol6·7 ± 1·26·4 ± 0·90·4564·6 ± 1·04·9 ± 1·30·298
High-density lipoprotein (mmol l−1)2·0 ± 0·52·0 ± 0·80·9601·6 ± 0·41·4 ± 0·30·119
Low-density lipoprotein (mmol l−1)4·3 ± 1·13·7 ± 0·90·048*2·7 ± 0·83·2 ± 1·10·078
Creatinine (μmol l−1)50 ± 959 ± 120·018*69 ± 962 ± 100·113
Triglycerides (mmol l−1)2·3 ± 0·83·1 ± 0·90·001**0·7 ± 0·41·1 ± 0·60·008**
Interleukin-6 (pmol l−1)2·0 ± 1·32·7 ± 2·00·0571·7 ± 1·31·5 ± 1·01·000
Outcomes
Systolic BP office (mm Hg)109 ± 8134 ± 11<0·001***104 ± 8115 ± 10<0·001***
Diastolic BP office (mm Hg)69 ± 689 ± 9<0·001***70 ± 680 ± 7<0·001***
Systolic BP whole 24 h (mmHg)115 ± 7137 ± 11<0·001***112 ± 7122 ± 8<0·001***
Diastolic BP whole 24 h (mm Hg)71 ± 689 ± 7<0·001***72 ± 680 ± 6<0·001***
Heart rate 24 h (bpm)82 ± 980 ± 70·29169 ± 971 ± 70·507
AASI0·22 ± 0·130·25 ± 0·120·4010·21 ± 0·130·24 ± 0·170·515
Nocturnal systolic dipping(mm Hg)11 ± 47 ± 80·031*9 ± 510 ± 50·941
Nocturnal diastolic dipping (mm Hg)13 ± 48 ± 6<0·001***11 ± 410 ± 40·907

All the blood pressure values differed significantly between groups both during and after pregnancies (Table 1). Ambulatory arterial stiffness index did not differ between these two groups neither during pregnancy nor after delivery. In the hypertensive group, 38·5% of women were classified as dippers and 61·5% as non-dippers and in the normotensive group, the corresponding values were 53·1% and 46·9% (P = 0·266). In women with gestational hypertension or pre-eclampsia, the nocturnal fall in blood pressure was significantly smaller than that observed in the normotensive group (Table 1). When all the groups were pooled, non-dippers had a higher creatinine level during pregnancy, although the creatinine levels were within the normal range (64·3 ± 12·6 mmol l−1 versus 51·3 ± 7·0 mmol l−1, r = 0·532, P = 0·007).

Three months after delivery, there was no longer any difference in the dipping status between the groups; 51·8% women in the normotensive group had a nocturnal systolic blood pressure fall less than 10 mm Hg, the corresponding value in the hypertensive group was 50%.

After we divided the hypertensive group into two subgroups, pre-eclampsia and gestational hypertension, it was found that in the pre-eclamptic patients, nocturnal dipping was less than in the normotensive group and also tended to be less than in the subjects with plain hypertension without proteinuria (Fig. 1). After pregnancy, the dipping values were almost the same in all the subgroups. The use of antihypertensive drugs had no impact on AASI or dipping values (data not shown).

image

Figure 1. (a) Nocturnal systolic and (b) nocturnal diastolic dipping in the subgroups. The significant differences between groups are shown.

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In the pre-eclamptic subgroup, an average value of 3·99 g l−1 proteinuria was observed. The significant differences observed between the pre-eclamptic and hypertensive women are shown in Table 2. The interleukin-6 concentration was significantly higher in the pre-eclamptic group when compared with the normotensive group (3·06 ± 2·34 versus 1·96 ± 1·29 pmol l−1, P = 0·034), whereas the difference was not significant when the pre-eclamptic group was compared with the hypertensive group (3·06 ± 2·34 versus 2·00 ± 0·92 pmol l−1, P = 0·208). Three months after delivery, the interleukin-6 levels had declined in each group. In the pre-eclampsia subgroup, the mean concentration was 1·60 ± 1·17 pmol l−1, the change from the values detected during pregnancy was statistically significant (P = 0·01).

Table 2. Differences between pre-eclampsia and gestational hypertension subgroups, examined during the third trimester of pregnancy
VariablePre-eclampsia (N = 18) (mean ± SD)Gest. hypertension (= 10)P-value
  1. BP, blood pressure.

  2. *P<0·05, **P<0·01, ***P<0·001.

Gravidity1·4 ± 0·72·4 ± 1·40·035*
Parity0·3 ± 0·71·0 ± 1·10·025*
Nulliparity (%)83400·021*
Age30·6 ± 5·932·8 ± 4·90·329
Gestational age at birth (weeks)37·1 ± 1·439·0 ± 0·90·001**
Birth weight (grams)2691 ± 5393298 ± 3860·006**
Woman's height (centimetres)162·2 ± 6·3167·8 ± 5·50·025*
Weight before pregnancy (kg)65·2 ± 11·270·8 ± 13·40·250
Body mass index (kg m²)24·8 ± 3·925·0 ± 4·00·858
Antihypertensive medication(%)10 (56)6 (60)0·823
Uric acid (μmol l−1)378 ± 73342 ± 980·183
Lactate dehydrogenase (u l−1)357 ± 155250 ± 590·095
Alanine aminotransferase (u l−1)24 ± 3228 ± 351·000
Creatinine (μmol l−1)61 ± 1354 ± 100·183
Interleukin-6 (pmol l−1)3·1 ± 2·32·0 ± 0·90·208
Proteinuria (g l−1)3·99 ± 1·91<0·001***
Systolic BP daytime (mm Hg)140 ± 11135 ± 80·183
Diastolic BP daytime (mm Hg)92 ± 789 ± 80·333
Systolic BP night-time (mm Hg)136 ± 13126 ± 100·047*
Diastolic BP night-time (mm Hg)86 ± 1080 ± 90·145

Ambulatory arterial stiffness index was slightly but non-significantly higher in the pre-eclampsia group during pregnancy as compared to the hypertensive and normotensive groups (0·27 ± 0·12 versus 0·21 ± 0·10 and 0·22 ± 0·13, NS, respectively), but it declined after delivery also in the pre-eclampsia subgroup to a similar level as present in the normotensive group (0·22 ± 0·19 and 0·21 ± 0·13, NS, respectively). However, in the plain hypertension subgroup, AASI tended to elevate 3 months postpartum (0·30 ± 0·13, NS).

We performed bivariate correlations in the pooled gestational hypertension/pre-eclampsia group. Ambulatory arterial stiffness index assessed during pregnancy correlated inversely with BMI before pregnancy (Fig. 2a) and also with weight before pregnancy (r = −0·491, P = 0·009). AASI during pregnancy correlated significantly with the renal function after delivery (creatinine (r = 0·765, P = 0·004), glomerular filtration rate (r = −0·584, P = 0·046)) and with the LDL concentration after delivery (Fig. 2b,c). Systolic (r = −0·482, P = 0·013) and diastolic dipping (r = −0·465, P = 0·017) during pregnancy correlated negatively with interleukin 6 levels (Fig. 3). The interleukin-6 concentration correlated positively with nocturnal mean arterial pressure (r = 0·497, = 0·010).

image

Figure 2. Ambulatory arterial stiffness index during pregnancy and some bivariate correlations in the pooled hypertension/pre-eclamptic group.

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image

Figure 3. The bivariate correlation between the nocturnal systolic dipping and the interleukin-6 level during pregnancy in the pooled hypertension/pre-eclamptic group.

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Ambulatory arterial stiffness index assessed after pregnancy correlated inversely with both systolic and diastolic nocturnal dipping after pregnancy (Fig. 4) and with fasting glucose values during pregnancy (r = −0·580, P = 0·018) and total cholesterol level after pregnancy (r = −0·526, P = 0·036).

image

Figure 4. Bivariate correlations between ambulatory arterial stiffness index and (a) systolic (b) diastolic dipping 3 months after delivery in women with pre-eclampsia or gestational hypertension.

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In the normotensive group, significant correlations between BMI and AASI during pregnancy (r = 0·451, P = 0·010) and diastolic dipping and AASI after pregnancy (r = −0·561, P = 0·004) were found, while other of the above correlations were statistically non-significant.

Discussion

  1. Top of page
  2. Summary
  3. Introduction
  4. Material and methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Conflict of interest
  9. References

It was found that hypertensive disorders during pregnancy were associated with a flattened circadian blood pressure response and that this became restored after delivery. The AASI did not significantly differ in either the gestational hypertensive or normotensive groups or in comparison with during pregnancy/after pregnancy values. Higher arterial stiffness as measured by AASI predicted signs of postpartum metabolic syndrome and correlated also with non-dipping, especially postpartum.

As we studied whether women with gestational hypertension would display changes in vascular function, we conclude that AASI had no capability to differentiate hypertensive from normotensive pregnancies or to differentiate placental from metabolic phenotypes of hypertensive pregnancies (Chappell & Morgan, 2006)nor could it be used to monitor endothelial recovery postpartum. These conclusions are based on the following findings: first, AASI was within the normal range in all study groups, and no statistically significant differences were found between hypertensive and control women. Second, the classification of the hypertensive syndrome into proteinuric pre-eclampsia and gestational hypertension or into dippers and non-dippers did not change the significance of the AASI values, whereas the concentrations of interleukin-6 were inversely correlated with the degree of nocturnal dipping. Third, AASI did not vary between the groups 3 months postpartum even though women recovering from hypertensive pregnancies had more unfavourable lipid profiles than the normotensive women.

In this study, AASI values during pregnancy correlated negatively with body weight before pregnancy, which suggested that lighter patients had stiffer arteries during pregnancy. Interestingly, in hypertensive pregnancies, both creatinine levels and GFR (glomerular filtration rate) after pregnancy correlated with AASI during pregnancy, revealing some evidence for mild renal dysfunction. In a recent study, AASI has also been shown to be inversely related to GFR in hypertensive patients.(Mule et al., 2008). In our study, the results could be attributable to endothelial dysfunction, and this may indicate that pregnancy-related endothelial dysfunction can affect kidneys for as long as 3 months after delivery.

Ambulatory arterial stiffness index assessed after pregnancy displayed a strong inverse association with both systolic and diastolic dipping postpartum suggesting that the two risk factors for later cardiovascular diseases are connected. In previous studies, AASI has also been shown to be strongly and inversely dependent on the degree of nocturnal blood pressure fall. Nocturnal dipping or non-dipping did not influence AASI during pregnancy, probably because of the high level of oestrogen or some other factors causing increased elasticity of vessel walls (Edouard et al., 1998). This is reminiscent of the situation in our previous studies of AASI which examined uncomplicated singleton and twin pregnancies (Karkkainen et al., 2011).

There are a few weaknesses in our study. First, we had a rather small number of participants. If we had wished to achieve significant differences in AASI between the groups or between the time points during and after pregnancy, we would have needed 250 women in both groups. Therefore, a small risk of type II error was present, but this does not change the conclusion that the clinical applicability was missing in this context. There were also quite a few dropouts; one obvious reason for the considerable number of dropouts was the presence of the newborn baby, who required the mother's fulltime attention. The healthy pregnant controls who consented to participate in the study could be more motivated to continue also after delivery, while the most problematic cases drop out. Second, some selection bias may have occurred because this was a convenience sample, and the patients were recruited over such a long period of time. Third, the disorders in our pre-eclampsia group were not very severe. This is because of the time of recruitment (about 34 ± 3 pregnancy weeks) and by that time; those pregnancies complicated by the most severe preterm pre-eclampsia have already been dealt with by caesarean section or by induction of the labour. However, it is unlikely that the usefulness of AASI during pregnancy would be dramatically different if it was analysed with a larger sample or in a subgroup with a more severe form of pre-eclampsia. Fourth, there can be some criticism against the pooling of gestational hypertension and pre-eclampsia patients. However, pre-eclampsia itself is likely to represent a combination of more than one diseases, even though the clinical outcome can be similar from case to case.

In conclusion, as shown in previous studies, the association between systemic endothelial damage in pre-eclampsia and the lack of circadian rhythm in blood pressure was found also in the present study. The dipping status has been postulated to be a potential pathophysiologic factor in pre-eclampsia(Bouchlariotou et al., 2008). Endothelial damage and the severity of pre-eclampsia were not reflected in the AASI results during pregnancy; after pregnancy, AASI seemed to be an early predictor of cardiovascular disease in conjunction with the dipping status rather than a marker of endothelial recovery. The results imply that methods other than AASI will need to be devised to assess disturbances in endothelial function during pregnancy.

Acknowledgments

  1. Top of page
  2. Summary
  3. Introduction
  4. Material and methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Conflict of interest
  9. References

We acknowledge the financial support of Kuopio University Hospital (EVO-grants 5302419 and 5031316) and Aarne and Aili Turunen's Foundation.

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  2. Summary
  3. Introduction
  4. Material and methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Conflict of interest
  9. References
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