Preeclampsia
Conditions
Keywords
preeclampsia, microvascular, inflammation, angiotensin II
Brief summary
Women who develop preeclampsia during pregnancy are more likely to develop cardiovascular disease later in life, even if they are otherwise healthy. The reason why this occurs is unclear but may be related to blood vessel damage and increased inflammation that occurs during the preeclamptic pregnancy and persists postpartum. The purpose of this investigation is to 1) determine the mechanisms contributing to this lasting blood vessel damage and chronic inflammation, and to 2) identify factors (both physiological and pharmacological) that mitigate these negative effects in order to inform better clinical management of cardiovascular disease risk in women who have had preeclampsia.
Interventions
1500mg twice daily for 4 days prior to experimental testing
DRUGPlacebo Oral Tablet
Placebo oral table twice daily for 4 days prior to experimental testing
Sponsors
Penn State University
University of Iowa
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Post-partum women who have delivered within two years and who have had a preeclamptic pregnancy diagnosed by their obstetrician before 34 weeks of gestation and confirmed according to the American College of Obstetricians and Gynecologists criteria for severe preeclampsia. \[This information will be self-reported by the subjects.\] * Post-partum women who have delivered within two years and who have had a normal pregnancy. * 18 years and older.
Exclusion criteria
* skin diseases * current tobacco use * diagnosed or suspected hepatic or metabolic disease * statin or other cholesterol-lowering medication * history of hypertension prior to pregnancy * history of gestational diabetes * current pregnancy * allergy to aspirin or NSAIDs or known allergy to materials used during the experiment (e.g. latex) * renal disease, bleeding disorders and history of gastrointestinal bleeding. * Known allergies to study drugs * Taking blood thinners, aspirin or NSAIDS. * Women who choose to breastfeed will not participate in any parts of the project that include salsalate.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Microvascular Endothelial Function (Cutaneous Conductance, %Maximum) | immediately following the 4 days or oral treatment (salsalate or placebo) | Endothelium-dependent vasodilation assessed as cutaneous conductance response (cutaneous conductance = local red blood cell flux/mean arterial pressure; %maximum) to exogenous acetylcholine delivered via intradermal microdialysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Peripheral Blood Mononuclear Cell Inflammatory Response to Ang II | at the completion of 4 days of oral (placebo or salsalate) treatment | inflammatory cytokine (TNFalpha) release by peripheral blood mononuclear cells isolated from fresh whole blood collected via venipuncture and stimulated with angiotensin II ex vivo. |
Countries
United States
Participant flow
Pre-assignment details
this is a crossover study design - all participants (23 total) completed each arm of the study in a randomized placebo controlled study design
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants All participants were randomized to received both interventions. | 23 |
| Total | 23 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Continuous | 30 years STANDARD_DEVIATION 5 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 22 Participants |
| Sex: Female, Male Female | 23 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 23 | 0 / 23 |
| other Total, other adverse events | 0 / 23 | 2 / 23 |
| serious Total, serious adverse events | 0 / 23 | 0 / 23 |
Outcome results
Primary
Microvascular Endothelial Function (Cutaneous Conductance, %Maximum)
Endothelium-dependent vasodilation assessed as cutaneous conductance response (cutaneous conductance = local red blood cell flux/mean arterial pressure; %maximum) to exogenous acetylcholine delivered via intradermal microdialysis.
Time frame: immediately following the 4 days or oral treatment (salsalate or placebo)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oral Salsalate | Microvascular Endothelial Function (Cutaneous Conductance, %Maximum) | 95 % of maximal cutaneous conductance | Standard Deviation 6 |
| Oral Placebo | Microvascular Endothelial Function (Cutaneous Conductance, %Maximum) | 77 % of maximal cutaneous conductance | Standard Deviation 8 |
Secondary
Peripheral Blood Mononuclear Cell Inflammatory Response to Ang II
inflammatory cytokine (TNFalpha) release by peripheral blood mononuclear cells isolated from fresh whole blood collected via venipuncture and stimulated with angiotensin II ex vivo.
Time frame: at the completion of 4 days of oral (placebo or salsalate) treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oral Salsalate | Peripheral Blood Mononuclear Cell Inflammatory Response to Ang II | 2.37 ng/ml | Standard Deviation 1.28 |
| Oral Placebo | Peripheral Blood Mononuclear Cell Inflammatory Response to Ang II | 2.77 ng/ml | Standard Deviation 1.01 |