Metabolic Syndrome X
Conditions
Keywords
Fibrolytic Dysfunction, Obesity, PAI-1
Brief summary
The combination of high blood pressure and having central obesity is an increasing important factor for heart disease in men and women. It can also lead to the early development of hardening of the arteries and increased risk of a stroke. This study will analyze patients' genetic make up to identify who may be at greater risk for heart disease and strokes in relationship to high blood pressure and central obesity.
Detailed description
Obesity is an increasingly important risk factor for cardiovascular disease in men and women and is associated with the premature development of atherosclerosis, and increased risk of stroke. A classical perspective of cardiovascular risk does not adequately explain all of the cardiovascular events associated with obesity. Elevated plasma levels of plasminogen activator inhibitor type I (PAI-1) are one of the biochemical hallmarks for obesity and likely contribute the increased risk of atherothrombotic events in patients with obesity. The central hypothesis of this proposal is that the increased risk of atherothrombotic events in patients with obesity. The central hypothesis of this proposal is that vascular PAI-1 excess promotes the development of intravascular thrombosis. We will test the hypothesis that secreted factors from adipocytes have autocrine, paracrine and endocrine effects that have a deleterious effect on the fibrinolytic system, either by enhancing PAI-1 production or impairing endothelial t-PA release. From a public health perspective, there is no greater threat to America's cardiovascular health than the epidemic of obesity. It is anticipated that this study will provide new insights nto the molecular mechanisms that contribute to the development of fibrinolytic dysfunction and cardiovascular disease in obesity.
Interventions
DRUGEplerenone
5 mg x 1 week followed by 10 mg x 9 weeks.
DRUGRamipril
Ramipril 5mg qd x 1 week f/b Ramipril qd x 9 weeks.
Sponsors
Vanderbilt University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Male or females between the ages of 18 to 65 years of age. * Documented diagnosis for the metabolic syndrome: * Subjects with hypertension (SP\>130mmHg) * Subjects with central obesity (females waist \>35; males waist \>40) * Subjects with dyslipidemia (HDL \<40mg/dl, triglycerides \> 150 mg/dl) * Subjects who are insulin resistance (fasting glucose \>100mg/dl)
Exclusion criteria
* Subjects who smoke * Women who are pregnant (confirmed by urine beta-HCG). * Women who are breast feeding * Subjects with documentation of the following health risk: * Subjects with serum creatinine \>2.0 mg/dl (males), \>1.8 mg/dl (females) * Subjects whose creatinine clearance \< 50 mls/min * Subjects with serum potassium \>5.5mEql * Subjects with Type 2 diabetes with microalbuminuria (spot urine protein/creatinine ration \>0.2) * Subjects who are currently taking the following medications: * Warfarin
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secreted Factors From Adipocytes Have Autocrine, Paracrine and Endocrine Effects That Have a Deleterious Effect on the Fibrinolytic System, Either by Enhancing PAI-1 Production or Impairing Endothelial t-PA Release | 10-Week period |
| This Study Will Analyze Patients' Genetic Make up to Identify Who May be at Greater Risk for Heart Disease and Strokes in Relationship to High Blood Pressure and Central Obesity. | 10-weeks |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Patients The study was never unblinded as enrollment was never completed. | 4 |
| Total | 4 |
Baseline characteristics
| Characteristic | All Patients |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants |
| Region of Enrollment United States | 4 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 4 |
| serious Total, serious adverse events | 0 / 4 |
Outcome results
Primary
Secreted Factors From Adipocytes Have Autocrine, Paracrine and Endocrine Effects That Have a Deleterious Effect on the Fibrinolytic System, Either by Enhancing PAI-1 Production or Impairing Endothelial t-PA Release
Time frame: 10-Week period
Population: Enrollment was never completed so study was never unblinded and data was never analyzed
Primary
This Study Will Analyze Patients' Genetic Make up to Identify Who May be at Greater Risk for Heart Disease and Strokes in Relationship to High Blood Pressure and Central Obesity.
Time frame: 10-weeks
Population: Enrollment was never completed so study was never unblinded and data was never analyzed