Manuel Iglesias

Blood Pressure Patterns in Normal Pregnancy, Gestational Hypertension, and Preeclampsia

Abstract —With the aim to describe the daily pattern of blood pressure during the trimesters of pregnancy in clinically healthy women as well as in pregnant women who developed gestational hypertension or preeclampsia, we analyzed 1494 blood pressure series systematically sampled by ambulatory monitoring for 48 hours every 4 weeks after the first obstetric visit in 124 women with uncomplicated pregnancies, 55 with gestational hypertension, and 23 with a final diagnosis of preeclampsia. The circadian pattern of blood pressure variation for each group and trimester of gestation was established by population multiple-component analysis. A highly statistically significant circadian pattern represented by a linear model that includes components with periods of 24 and 12 hours is demonstrated for systolic and diastolic blood pressure for all groups of pregnant women in all trimesters ( P P P P =0.022) but not for diastolic blood pressure ( P =0.986). In the third trimester, the difference in circadian mean is highly statistically significant for both variables ( P

Blood Pressure Excess for the Early Identification of Gestational Hypertension and Preeclampsia

We have examined prospectively whether the combined approach of establishing tolerance intervals for the circadian variability of blood pressure (BP) as a function of gestational age, and then determining the so-called hyperbaric index (area of BP excess above the upper limit of the tolerance interval) by comparison of any patients BP profile (obtained by ambulatory monitoring) with those intervals provides a high sensitivity test for the early detection of pregnant women who subsequently will develop gestational hypertension or preeclampsia. We analyzed 657 BP series from 92 women with uncomplicated pregnancies and 378 series from 60 women who developed gestational hypertension or preeclampsia. BP was sampled for about 48 hours once every 4 weeks after the first obstetric consultation. Circadian 90% tolerance limits were determined as a function of trimester of gestation from 497 series previously sampled from a reference group of 189 normotensive pregnant women. The hyperbaric index was then determined for each individual BP series in the validation sample. Sensitivity of this test for diagnosing gestational hypertension was 93% for women sampled during the first trimester of gestation and increased up to 99% in the third trimester. The positive and negative predictive values were above 96% in all trimesters. Despite the limitations of ambulatory monitoring, the approach presented here, now validated prospectively, represents a reproducible, noninvasive, and high sensitivity test for the very early identification of subsequent gestational hypertension and preeclampsia, on the average, 23 weeks before the clinical confirmation of the disease.

Predictable Blood Pressure Variability in Healthy and Complicated Pregnancies

With the aim of describing the predictable pattern of blood pressure (BP) variability during gestation, we analyzed 2430 BP series systematically sampled by ambulatory monitoring for 48 consecutive hours every 4 weeks from the first obstetric visit (usually within the first trimester of pregnancy) until delivery in 235 normotensive women, 128 women who developed gestational hypertension, and 40 women who had a final diagnosis of preeclampsia. The pattern of variation along gestation of the 24-hour means of BP and heart rate was established for each group of women by polynomial regression analysis. For normotensive women, results indicate a steady decrease in BP up to 20 weeks of pregnancy, followed by an increase in BP up to the day of delivery, with an average 8% BP increase between the middle of gestation and delivery. In complicated pregnancies, BP is stable until the 22nd week of gestation and then increases linearly for the remainder of the pregnancy. Complicated pregnancies are characterized by a 9% and 13% increase in systolic and diastolic BPs, respectively, during the second half of gestation. Results also indicate that during the first half of pregnancy, systolic but not diastolic BP is slightly elevated in women who developed preeclampsia compared with those who developed gestational hypertension. During the second half of gestation, the linear trend of increasing BP for women who developed preeclampsia has a significantly higher slope than the trend for women with gestational hypertension. For both healthy and complicated pregnancies, heart rate increases until the end of the second trimester and slightly decreases thereafter. This study of women systematically sampled by 48-hour ambulatory BP monitoring throughout gestation confirms the predictable pregnancy-associated variability in BP and provides proper information for the establishment of reference limits for BP to be used in the early diagnosis of hypertensive complications in pregnancy. Those limits should be developed as a function of gestational age, taking into account the trends in BP throughout pregnancy demonstrated here.

Time-Dependent Effects of Low-Dose Aspirin Administration on Blood Pressure in Pregnant Women

This study investigated the effects of low-dose acetylsalicylic acid (aspirin) on blood pressure in pregnant women who were at risk of developing gestational hypertension or preeclampsia and who received aspirin at different times of the day according to their rest-activity cycle. A double-blind, randomized, controlled trial was conducted in 100 pregnant women. Blood pressure for each subject was automatically monitored for 2 days every 4 weeks from the day of recruitment until delivery. Women were randomly assigned to one of six groups according to treatment (placebo, 50 subjects or aspirin, 100 mg/d, starting at 12 to 16 weeks of gestation) and the time of treatment: on awakening (time 1), 8 hours after awakening (time 2), or before bedtime (time 3). Results indicated that there was (1) no effect on blood pressure from placebo at any time (P>.212) and (2) a highly statistically significant (P<.001) time-dependent effect on blood pressure from aspirin. There was no effect of aspirin on blood pressure at time 1 (compared with placebo), but the blood pressure reduction was highly statistically significant after time 2 and, to a greater extent, after time 3 (mean reduction of 12 and 8 mm Hg in 24 hours for systolic and diastolic blood pressure, respectively, at the time of delivery compared with placebo given at the same time). These time-dependent effects of aspirin on blood pressure should be taken into account for the optimization of long-term aspirin administration at low doses for prevention of preeclampsia. In any meta-analysis of aspirin effects, inquiries about the time when the subjects took the drug are indicated and may account for discrepancies in the literature.

Administration Time–Dependent Influence of Aspirin on Blood Pressure in Pregnant Women

Abstract—This study prospectively investigates the potential influence of low-dose aspirin on blood pressure in pregnant women who were at a higher risk of developing preeclampsia than that of the general obstetric population and who received aspirin at different times of the day according to their rest-activity cycle. A double-blind, randomized, controlled trial was conducted in 341 pregnant women (181 primipara) randomly assigned to 1 of 6 possible groups according to treatment (either placebo or aspirin, 100 mg/day, starting at 12 to 16 weeks of gestation) and the time of treatment: on awakening (time 1), 8 hours after awakening (time 2), or before bedtime (time 3). Blood pressure was automatically monitored for 48 consecutive hours every 4 weeks from the day of recruitment until delivery, as well as at puerperium. There was no effect of aspirin on blood pressure at time 1 (compared with placebo). A blood pressure reduction was highly statistically significant when aspirin was given at time 2 and, to a greater extent, at time 3 (mean reductions of 9.7/6.5 mm Hg in 24-hour mean for systolic/diastolic blood pressure at the time of delivery as compared with placebo given at bedtime). Differences in blood pressure among women receiving aspirin at different circadian times disappeared at puerperium (P >0.096). Results indicate a highly significant effect of aspirin on blood pressure that is markedly dependent on the time of aspirin administration with respect to the rest-activity cycle. Timed use of aspirin at low dose effectively contributes to blood pressure control in women at high risk for preeclampsia.

Blood Pressure Variability During Gestation in Healthy and Complicated Pregnancies

The evaluation of predictable variability in blood pressure by the use of ambulatory devices, and the proper processing of the time series thus obtained, can be useful for the early assessment of hypertensive complications in pregnancy. We have used this approach to quantify a predictable pattern of blood pressure and heart rate throughout pregnancy in clinically healthy women as well as in pregnant women who developed gestational hypertension or preeclampsia. We analyzed 503 blood pressure series from 71 healthy pregnant women and 256 series from 42 women who developed gestational hypertension or preeclampsia. Blood pressure monitoring (48-hour) was done once every 4 weeks after the first obstetric consultation. The pattern of variation along gestation of the 24-hour mean of blood pressure for groups of normotensive and hypertensive pregnant women was established by polynomial regression analysis. This method revealed predictable patterns of variation of 24-hour means with gestational age: for normotensive pregnant women, results indicate a steady decrease in blood pressure up to the 21st week of pregnancy, followed by an increase in blood pressure up to the day of delivery. This pattern of variation is not found in pregnancies complicated with gestational hypertension or even preeclampsia: the 24-hour mean of blood pressure is stable until the 22nd week of pregnancy and then correlated with gestational age, indicating a significant linear increase of blood pressure in the second half of pregnancy. For both healthy and complicated pregnancies, heart rate slightly increases until the end of the second trimester, and it is stable thereafter. This study confirms and extends to ambulatory everyday life conditions the predictable pregnancy-associated variability in blood pressure. The differences between uncomplicated and complicated pregnancies offer new end points for an early identification of gestational hypertension and preeclampsia.

Circadian Blood Pressure Variability in Healthy and Complicated Pregnancies

With the aim to describe the circadian pattern of noninvasive ambulatorily monitored blood pressure during the trimesters of pregnancy in clinically healthy women as well as in pregnant women who developed gestational hypertension or preeclampsia, we analyzed 759 blood pressure series sampled by ambulatory monitoring for about 48 hours every 4 weeks after the first obstetric visit in 71 women with uncomplicated pregnancies, 28 with gestational hypertension, and 14 with preeclampsia. The circadian pattern of blood pressure variation for each group (complicated versus uncomplicated pregnancies) and trimester of gestation was established by linear least-squares methods. A highly statistically circadian pattern is demonstrated for systolic and diastolic blood pressure for both groups of pregnant women in all trimesters (P<.001 in all cases). Blood pressure decreases from the first trimester to the second and rises again in the third for healthy pregnant women. For women who developed gestational hypertension or preeclampsia, blood pressure is stable during the first half of pregnancy and then continuously increases until delivery. The differences in circadian rhythm-adjusted mean between complicated and uncomplicated pregnancies are highly statistically significant in all trimesters (always P<.001). This study confirms and extends to ambulatory everyday life conditions the predictable circadian variability in blood pressure during gestation. The differences in blood pressure between healthy and complicated pregnancies can be observed as early as the first trimester of pregnancy. Those differences are found when both systolic and diastolic blood pressures for women with a later diagnosis of gestational hypertension or preeclampsia are well within the accepted normal physiological range of blood pressure variability.

Influence of Aspirin Usage on Blood Pressure: Dose and Administration-Time Dependencies

This study investigates the possible effects of acetylsalicylic acid (ASA; aspirin) on systolic (S) and diastolic (D) blood pressure (BP) in healthy and mildly hypertensive subjects receiving ASA at different times according to their rest-activity cycle. A double-blind, randomized, controlled trial was conducted in 73 healthy young adult volunteers and 18 previously untreated subjects with mild hypertension. The BP of each subject was automatically monitored every 30 minutes for 48h before the trial and at the end of a one-week course of placebo and a one-week course of ASA. Healthy volunteers were randomly assigned to one of six groups, defined according to the dose of ASA (either 500 mg/day, the usual commercial dose; or 100 mg/day) and timing of ASA and placebo (within 2h after awakening, Time 1; 7h to 9h after awakening, Time 2; or within 2h of bedtime, Time 3). Subjects with mild hypertension received the low dose of 100 mg/day ASA, as well as one week of placebo, and were randomly assigned to one of the same three groups defined above according to the time of treatment. A small (approximately 2 mmHg in the 24h mean of SBP), but statistically significant, BP reduction was found when 500 mg/day ASA was given to healthy volunteers at Time 2. With 100 mg/day, the effect of ASA in healthy subjects was comparable to the BP reduction found with the higher dose for Time 2; there was again no effect on BP at Time 1, but we found a statistically significant effect at Time 3 (2.3 mmHg reduction in the 24h mean of SBP), larger than for Time 2. For hypertensive patients, the BP reduction was again statistically significant for Time 2 and, to a greater extent, for Time 3 (approximately 4.5 mmHg for both SBP and DBP); all patients in these two groups showed a BP reduction after one week of ASA. The effect was about three times as large as the BP reduction obtained in healthy subjects treated with 100 mg/day ASA. Results indicate a statistically significant time- and dose-dependent effect of ASA on BP. In any meta-analysis of ASA effects, inquiries about the time when subjects took the drug are indicated and may account for discrepancies in the literature. Moreover, the influence of ASA on BP demonstrated here indicates the need to identify and control for ASA effects in patients using ASA before and during their participation in antihypertension medication trials.

Differences in circadian blood pressure variability during gestation between healthy and complicated pregnancies

BACKGROUND Changes in circadian variation of blood pressure (BP) could be used either to predict preeclampsia or to assess its severity. We examined and compared characteristics of circadian variability in BP in women with both healthy and complicated pregnancies who were systematically monitored throughout gestation. METHODS We analyzed 2430 BP series sampled by ambulatory monitoring for 48 h once every 4 weeks from the first obstetric visit until delivery in 235 women with uncomplicated pregnancies, 128 with gestational hypertension, and 40 with preeclampsia. The circadian pattern of BP variation for each group and trimester of gestation was established by population multiple-components analysis. RESULTS The differences in 24-h mean and amplitude between healthy and complicated pregnancies were highly significant in all trimesters (P < 0.001). Results further indicated similar circadian characteristics between gestational hypertension and preeclampsia in the first trimester of pregnancy. The difference between these two groups in 24-h mean was statistically significant for systolic (P =.002) and diastolic BP (P =.038) in the second trimester and, to a larger extent, in the third trimester (P < 0.001). CONCLUSIONS The differences in BP between healthy and complicated pregnancies that can be observed as early as in the first trimester of pregnancy are found when both systolic and diastolic BP for women with a later diagnosis of gestational hypertension or preeclampsia are well within the accepted range of normotension. These differences offer new end points that may lead to an early identification of hypertensive complications in pregnancy as well as to the establishment of prophylactic intervention.

High sensitivity test for the early diagnosis of gestational hypertension and preeclampsia. I. Predictable variability of cardiovascular characteristics during gestation in healthy and hypertensive pregnant women

The evaluation of predictable variability in blood pressure and heart rate by (a) the use of fully ambulatory devices, and (b) the proper processing of the time series thus obtained, can be useful in assessing early cardiovascular disease risk in pregnancy. We have used this approach to quantify a predictable time structure of blood pressure throughout pregnancy in clinically healthy women as well as in pregnant women who developed gestational hypertension of preeclampsia. We analyzed a total of 745 blood pressure series sampled by ambulatory monitoring for about 48 hours in each of several occasions in 189 women with uncomplicated pregnancies, 71 with gestational hypertension, and 29 with preeclampsia. The pattern of variation along gestation of the 24-hour mean of blood pressure for groups of normotensive and hypertensive pregnant women was established by polynomial regression analysis. Regression analysis revealed predictable patterns of variation of 24-hour means with gestational age: for normotensive pregnant women, results indicate a steady decrease in blood pressure up to the 20th week of pregnancy, followed by an increase in blood pressure up to the day of delivery. Women with gestational hypertension or preeclampsia are characterized, however, by a continuous linear increase of blood pressure with gestational age, starting from the beginning of pregnancy. This study confirms and extends to ambulatory everyday life conditions the predictable pregnancy-associated variability in blood pressure. The differences between uncomplicated and complicated pregnancies offer new endpoints for an early identification of gestational hypertension and preeclampsia.