Acute Coronary Syndrome, Thrombosis
Conditions
Keywords
acute coronary syndrome, clotting, hormones, women
Brief summary
The investigators are attempting to determine if the response to aspirin in women is related to the level of estrogen and progesterone that a woman has.
Detailed description
Thrombosis plays a significant role in both acute coronary syndromes (ACS) and early saphenous vein graft (SVG) failure. Women with coronary heart disease have higher levels of the inflammatory mediator thromboxane, which is produced by platelets, monocytes, macrophages and the endothelium. Data show that higher levels of urinary thromboxane (UTXB2) are associated with SVG failure 6 months after Coronary Artery Bypass Graft (CABG). Women in the study cohort had higher levels of UTXB2 and higher odds of graft failure when compared to men. The elevated urinary thromboxane seen in the women in our study cohort may represent a marker and/or an etiology of thrombosis. Are the levels of UTXB2 higher in women due to hormonal differences? In a prior pilot study we investigated whether hormonal levels are associated with changes in urinary thromboxane. We looked at hormonal and urinary thromboxane levels in 48 postmenopausal and 52 premenopausal women. We found that postmenopausal women had higher levels of UTXB2 than did premenopausal women (2495 vs. 2299, p=.02) and that in premenopausal women a higher estrogen/progesterone ratio was associated with the highest levels of urinary thromboxane. The goal of the current study is to measure the response to seven days of aspirin administration as it relates to urinary thromboxane levels in pre and post-menopausal women. With this study we will be able to examine the change in UTXB2 comparing the premenopausal to post menopausal women. We will also be able to see if the change in UTXB2 in response to aspirin is affected by hormone levels in the premenopausal women. Lastly this study will provide reference data for more far-reaching studies exploring how global changes in hormonal balance (as seen in pregnancy or menopause) or in the level of inflammation (as seen in aging or with Coronary Artery Disease (CAD) risk factors), affect UTXB2 and platelet hyperreactivity.
Interventions
DRUGAspirin 81 mg
Aspirin 81 mg orally daily for 7 days
Sponsors
Johns Hopkins University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
1. Women age 18-80 2. Signed informed consent.
Exclusion criteria
1. History of CAD, Cerebrovascular Accident (CVA) or Peripheral Artery Disease (PAD), 2. On chronic aspirin therapy, 3. On chronic NSAID therapy. 4. Chronic anticoagulation with coumadin, 5. Known thrombocytopenia (Platelet count \< 100,000), 6. Pregnancy (self-report), 7. Currently on any type of contraceptive or hormone replacement therapy, 8. Hysterectomy and/or oophorectomy. 9. Recent GI bleeding 10. Bleeding diathesis 11. Chronic Systemic Infection
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Level of Urinary Thromboxane (UTXB2) in pg/mg Creatinine | Baseline | Urinary thromboxane (pg/mg creatinine) will be measured in premenopausal and postmenopausal women at baseline and then after taking on aspirin for 7 days. |
| The Change in the Level of UTXB2 in pg/mg Creatinine: Estrogen and Progesterone | baseline to 7 days | Measurement of urinary thromboxane (pg/mg creatinine) in relation to estrogen to progesterone level in premenopausal women on aspirin for 7 days. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Level of UTXB2 in pg/mg Creatinine | baseline | Comparing premenopausal women to postmenopausal women, the level of urinary thromboxane (pg/mg creatinine) in response to aspirin |
| Relative Change of UTXB2 in pg/mg Creatinine in Response to Aspirin | change from baseline to 7 days | Comparing premenopausal women to postmenopausal women, the level of urinary thromboxane (pg/mg creatinine) in response to aspirin |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Premenopausal Aspirin 81 mg PO daily x 7 days | 52 |
| Postmenopausal Aspirin 81 mg PO daily x 7 days | 48 |
| Total | 100 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | study was terminated | 52 | 48 |
Baseline characteristics
| Characteristic | Total | Premenopausal | Postmenopausal |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 48 Participants | 0 Participants | 48 Participants |
| Age, Categorical Between 18 and 65 years | 52 Participants | 52 Participants | 0 Participants |
| Region of Enrollment United States | 100 Participants | 52 Participants | 48 Participants |
| Sex: Female, Male Female | 100 Participants | 52 Participants | 48 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 52 | 0 / 48 |
| other Total, other adverse events | 0 / 52 | 0 / 48 |
| serious Total, serious adverse events | 0 / 52 | 0 / 48 |
Outcome results
Primary
Level of Urinary Thromboxane (UTXB2) in pg/mg Creatinine
Urinary thromboxane (pg/mg creatinine) will be measured in premenopausal and postmenopausal women at baseline and then after taking on aspirin for 7 days.
Time frame: Baseline
Population: Data was only collected at baseline. The study was terminated prior to initiation of intervention (Aspirin) and therefore no follow-up data was collected to calculate the change from baseline.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Premenopausal | Level of Urinary Thromboxane (UTXB2) in pg/mg Creatinine | 2495 pg/mg |
| Postmenopausal | Level of Urinary Thromboxane (UTXB2) in pg/mg Creatinine | 2299 pg/mg |
Primary
The Change in the Level of UTXB2 in pg/mg Creatinine: Estrogen and Progesterone
Measurement of urinary thromboxane (pg/mg creatinine) in relation to estrogen to progesterone level in premenopausal women on aspirin for 7 days.
Time frame: baseline to 7 days
Population: Data was only collected at baseline. The study was terminated prior to obtaining study data.
| Arm | Measure | Group | Value |
|---|---|---|---|
| Unknown | The Change in the Level of UTXB2 in pg/mg Creatinine: Estrogen and Progesterone | UTX | — |
| Unknown | The Change in the Level of UTXB2 in pg/mg Creatinine: Estrogen and Progesterone | Progesterone | — |
Secondary
Level of UTXB2 in pg/mg Creatinine
Comparing premenopausal women to postmenopausal women, the level of urinary thromboxane (pg/mg creatinine) in response to aspirin
Time frame: baseline
Population: Data was only collected at baseline. The study was terminated prior to initiation of intervention (Aspirin) and therefore no follow-up data was collected to calculate the change from baseline.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Premenopausal | Level of UTXB2 in pg/mg Creatinine | 2299 pg/mg |
| Postmenopausal | Level of UTXB2 in pg/mg Creatinine | 2824 pg/mg |
Secondary
Relative Change of UTXB2 in pg/mg Creatinine in Response to Aspirin
Comparing premenopausal women to postmenopausal women, the level of urinary thromboxane (pg/mg creatinine) in response to aspirin
Time frame: change from baseline to 7 days
Population: No data was collected for this outcome measure, as the study was terminated prematurely