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The purpose of the study is to test the hypothesis that a short course of atorvastatin can improve vascular function in women with a history of preeclampsia, compared to placebo.
Women with a history of preeclampsia (high blood pressure/protein in the urine during pregnancy) are at increased risk of developing high blood pressure and heart problems in the 10-15 years after their baby is born. At present we do not know how to reduce this risk. Lowering blood pressure and blood lipid (fats) levels are common strategies for primary prevention of cardiovascular problems. However, most women with a history of preeclampsia in the 5-10 years after pregnancy, will have normal blood pressure readings, blood sugar and cholesterol levels.
Atorvastatin, a type of "statin", is widely used in lowering lipids and preventing cardiovascular disease. This drug has beneficial actions other than lipid-lowering, that may also help prevent cardiovascular problems, including improving function in the lining of blood vessels. We know that impairment in blood vessel function is evident in women in the years after a preeclamptic pregnancy and may contribute to the risk of women after preeclampsia going on to develop cardiovascular disease.
We would like to know if giving a short course of atorvastatin to women with a history of preeclampsia improves their blood vessel function. To do this, ex-preeclamptic women will be invited to take either a atorvastatin or placebo ("dummy") tablet daily for 4 weeks, then no tablets for 4 weeks, then "crossover" to receive the alternative tablet (placebo or atorvastatin) daily for 4 weeks. Blood vessel function would be measured using specialised noninvasive scans and taking a blood test at the beginning and end of each treatment period. The study will be jointly run by the Departments of Cardiovascular Medicine and Obstetrics & Gynaecology at the John Radcliffe Hospital, Oxford.
We anticipate this study will provide valuable data to support larger clinical trials to determine whether improving blood vessel function ultimately reduces the risk of developing early-onset cardiovascular disease after preeclampsia.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Atorvastatin first | Experimental | Participants receive 4 week treatment with atorvastatin 20mg/day, followed by 4 week washout, followed by 4 week treatment with placebo. |
|
| Placebo first | Experimental | Participants receive 4 week treatment with placebo, followed by 4 weeks washout, followed by 4 weeks treatment with atorvastatin 20mg/day. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Atorvastatin | Drug | 4 week treatment, 20mg/day taken orally in tablet form |
|
| Measure | Description | Time Frame |
|---|---|---|
| Alteration in brachial artery flow-mediated dilatation | After 4 weeks treatment with atorvastatin or placebo |
| Measure | Description | Time Frame |
|---|---|---|
| Microvascular endothelial function as measured by laser doppler flowmetry | After 4 weeks treatment with atorvastatin or placebo | |
| Resistance vessel endothelial function as measured by venous occlusion plethysmography | After 4 weeks treatment with atorvastatin or placebo |
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Inclusion Criteria:
Exclusion Criteria:
Participants must not be
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| Name | Affiliation | Role |
|---|---|---|
| Paul Leeson, PhD MRCP FESC | University of Oxford | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Oxford Department of Cardiovascular Medicine | Oxford | OX3 9DU | United Kingdom |
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| ID | Term |
|---|---|
| D011225 | Pre-Eclampsia |
| ID | Term |
|---|---|
| D046110 | Hypertension, Pregnancy-Induced |
| D011248 | Pregnancy Complications |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
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| ID | Term |
|---|---|
| D000069059 | Atorvastatin |
| ID | Term |
|---|---|
| D011758 | Pyrroles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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| Indices of arterial stiffness as measured by arterial tonometry and carotid artery distensibility | After 4 weeks treatment with atorvastatin or placebo |
| Plasma biomarkers of inflammation and endothelial function | After 4 weeks treatment with atorvastatin or placebo |
| Endothelial glycocalyx as measured by sublingual Microscan | After 4 weeks treatment with atorvastatin or placebo |
| D006538 |
| Heptanoic Acids |
| D005227 | Fatty Acids |
| D008055 | Lipids |