Myocardial Infarction
Conditions
Keywords
Myocardial infarction, Platelet aggregation, cold pressor test, Genetics
Brief summary
The aim of the study is to test whether genetic variation in the alpha 2A adrenergic receptor affects diurnal variation in platelet aggregation.
Detailed description
There is a marked diurnal fluctuation in the occurrence of acute myocardial infarction and sudden death, with peak incidences occurring in the early morning. Platelet aggregation has also been shown to increase in the early morning. The investigators will test the hypothesis that alpha 2a-adrenergic receptor (ADRA2A) genetic variation, specifically haplotype 4, affects platelet aggregation. The investigators will compare diurnal platelet aggregation in haplotype 4 subjects with subjects in the other haplotype families. In addition, the investigators will compare platelet aggregation after the cold pressor test in haplotype 4 with the other haplotype families. If there are no differences among haplotypes, then the haplotypes will be combined to analyze.
Interventions
None listed
Sponsors
Vanderbilt University
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Men and women aged 18 - 45 years inclusive. * Women of the above age will be studied between day 1 and day 14 of a normal menstrual cycle. * Subjects must be willing to give informed consent for the study and able to adhere to the study diet and study procedures. * Subjects and immediate extended family up till grandparents will be Caucasians or African Americans only. * Subjects will be free of any clinically significant disease. * Clinical laboratory test (CBC, blood chemistry) will be within acceptable limits.
Exclusion criteria
* Subjects who have taken any antiplatelet, anticoagulant or procoagulant medicines within the last three weeks preceding the study. * Subjects who have taken medications (including over the counter medications) other than oral contraceptives in the past two weeks. * Subjects who smoke or have smoked in the past 3 months. * Subjects who are presently or were formerly a narcotic addict or alcoholic. * Females with a positive pregnancy test. * Females who are breast feeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| LogEC50 Platelet Aggregation | at 6am and 930am | EC50 represents the epinephrine concentration that produced 50% of maximal platelet aggregation (representing sensitivity to epinephrine) EC50 values were not normally distributed and were log-transformed for analyses. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage, Adenosine Diphosphate (ADP) Induced Platelet Aggregation | at 6am and 930am | Blood samples were taken from participants and centrifuged. Adenosine Diphosphate (ADP) at a fixed concentration of 2.5 uM was added. Agonist-induced platelet aggregation was expressed as the percentage aggregation after 6 minutes of stimulation. |
| Percentage, Collagen Induced Platelet Aggregation | at 6am and 930am | Blood samples were taken from participants and centrifuged. Collagen at a fixed concentration of 2.5 ug/ml was added. Agonist-induced platelet aggregation was expressed as the percentage aggregation after 6 minutes of stimulation. |
Countries
United States
Participant flow
Recruitment details
Healthy normotensive, non-smokers Caucasians and African-Americans aged 18-45 years were recruited via flyers and word of mouth from 2012-2015. No medications except oral contraceptives within two weeks and no antiplatelet medications within three weeks of the study. Women were studied in the first 14 days of their menstrual cycle.
Participants by arm
| Arm | Count |
|---|---|
| Healthy Volunteers Normal healthy volunteers | 117 |
| Total | 117 |
Baseline characteristics
| Characteristic | Healthy Volunteers |
|---|---|
| Age, Continuous | 29.5 years STANDARD_DEVIATION 5.7 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 37 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 | 80 Participants |
| Region of Enrollment United States | 117 participants |
| Sex: Female, Male Female | 83 Participants |
| Sex: Female, Male Male | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 117 |
| serious Total, serious adverse events | 1 / 117 |
Outcome results
Primary
LogEC50 Platelet Aggregation
EC50 represents the epinephrine concentration that produced 50% of maximal platelet aggregation (representing sensitivity to epinephrine) EC50 values were not normally distributed and were log-transformed for analyses.
Time frame: at 6am and 930am
Population: outcome data could not be collected on all subjects, since unable to draw enough blood at a particular timepoint
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Healthy Volunteers | LogEC50 Platelet Aggregation | LogEC50 at 6am | 2.65 nM | Standard Deviation 0.49 |
| Healthy Volunteers | LogEC50 Platelet Aggregation | LogEC50 at 930am | 2.62 nM | Standard Deviation 0.44 |
Secondary
Percentage, Adenosine Diphosphate (ADP) Induced Platelet Aggregation
Blood samples were taken from participants and centrifuged. Adenosine Diphosphate (ADP) at a fixed concentration of 2.5 uM was added. Agonist-induced platelet aggregation was expressed as the percentage aggregation after 6 minutes of stimulation.
Time frame: at 6am and 930am
Population: some outcome data could not be collected for all subjects, unable to draw enough blood for a particular timepoint
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Healthy Volunteers | Percentage, Adenosine Diphosphate (ADP) Induced Platelet Aggregation | % aggregation at 930am | 75.8 percentage of aggregation | Standard Deviation 12.8 |
| Healthy Volunteers | Percentage, Adenosine Diphosphate (ADP) Induced Platelet Aggregation | % aggregation at 6am | 72.8 percentage of aggregation | Standard Deviation 14.9 |
Secondary
Percentage, Collagen Induced Platelet Aggregation
Blood samples were taken from participants and centrifuged. Collagen at a fixed concentration of 2.5 ug/ml was added. Agonist-induced platelet aggregation was expressed as the percentage aggregation after 6 minutes of stimulation.
Time frame: at 6am and 930am
Population: Some outcome date could not be collected for all subjects, unable to draw enough blood at a particular time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Healthy Volunteers | Percentage, Collagen Induced Platelet Aggregation | % platelet aggregation at 6am | 84.3 percentage of platelet aggregation | Standard Deviation 7.9 |
| Healthy Volunteers | Percentage, Collagen Induced Platelet Aggregation | % platelet aggregation at 930am | 83.5 percentage of platelet aggregation | Standard Deviation 7.1 |