Hyperlipidemia
Conditions
Brief summary
Severe hypercholesterolemia produced by conditions such as heterozygous familial hypercholesterolemia is associated with multiple complications including premature atherosclerotic disease. There is evidence that microvascular perfusion, particularly flow reserve, in critical organs is limited due to abnormalities in plasma viscosity, abnormal RBC deformability, and an imbalance between vasodilators and vasoconstrictors. There is little is currently known about acute changes in microvascular blood flow and microvascular rheology that occur in response to plasmapharesis which is used in some patients to lower critically elevated cholesterol levels. Our research group has pioneered CEU methods for assessing myocardial and skeletal muscle perfusion, and has previously demonstrated in pre-clinical models that acute hyperlipidemia produces a reduction in microvascular RBC transit rate. In this study, the investigators will assess acute changes in microvascular perfusion in patients undergoing clinically-indicated plasmapharesis.
Detailed description
Subjects who are scheduled to have planned apheresis treatment for severe hypercholesterolemia will be recruited into the study. They will undergo a screening evaluation, including a medical history, physical examination, ECG, and limited echocardiogram to evaluate for exclusion criteria. Before the apheresis procedure, blood samples will be obtained for plasma markers of inflammation, erythrocyte deformability, and plasma viscosity. Contrast enhanced ultrasound perfusion imaging will be performed to evaluate blood flow in the myocardium at rest, as well as in the forearm skeletal muscle before and after mild isometric exercise (50% maximal grip, 0.2 Hz). Flow mediated vasodilation will be performed. The subjects will then undergo their planned apheresis procedure. Within 2 hours of completion of apheresis, blood collection and CEU will be repeated. Plasma lipids will be available as part of the standard apharesis protocol.
Interventions
PROCEDUREPlasmapharesis
Clinically-indicated LDL apheresis
Sponsors
Oregon Health and Science University
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* hypercholesterolemia (LDL \>200 mg/dL) * clinically-indicated aphersis for hyperlipidemia * age \>18 y.o.
Exclusion criteria
* pregnant or lactating females * hypersensitivity to ultrasound contrast agents * evidence for right to left or bidirectional shunt * on anticoagulants
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Myocardial Perfusion at Rest | 10 min | Acoustic intensity data were fit to the following function: y = A(1-e\^-beta\*t) where y is signal intensity at time t, A is the plateau intensity reflecting relative microvascular blood volume (MBV), and beta is the rate constant reflecting microvascular blood flux rate. Microvascular blood flow was quantified by the product of MBV and beta |
| Skeletal Muscle Perfusion at During Exercise | 10 min | Contrast ultrasound assessment of microvascular perfusion of forearm skeletal muscle during contractile exercise. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Plasmapharesis Patients undergoing apheresis for elevated LDL. Patients will undergo contrast ultrasound perfusion imaging at rest and during forearm exercise at before and immediately after apheresis.
Plasmapharesis: Clinically-indicated LDL apheresis | 8 |
| Total | 8 |
Baseline characteristics
| Characteristic | Plasmapharesis |
|---|---|
| Age, Continuous | 56 years STANDARD_DEVIATION 11 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Region of Enrollment United States | 8 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 8 |
| other Total, other adverse events | 0 / 8 |
| serious Total, serious adverse events | 0 / 8 |
Outcome results
Primary
Myocardial Perfusion at Rest
Acoustic intensity data were fit to the following function: y = A(1-e\^-beta\*t) where y is signal intensity at time t, A is the plateau intensity reflecting relative microvascular blood volume (MBV), and beta is the rate constant reflecting microvascular blood flux rate. Microvascular blood flow was quantified by the product of MBV and beta
Time frame: 10 min
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Plasmapharesis | Myocardial Perfusion at Rest | Pre-apheresis | 55 IU/s | Standard Deviation 21 |
| Plasmapharesis | Myocardial Perfusion at Rest | Post apheresis | 135 IU/s | Standard Deviation 65 |
Primary
Skeletal Muscle Perfusion at During Exercise
Contrast ultrasound assessment of microvascular perfusion of forearm skeletal muscle during contractile exercise.
Time frame: 10 min
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Plasmapharesis | Skeletal Muscle Perfusion at During Exercise | Pre-apheresis | 116 IU/s |
| Plasmapharesis | Skeletal Muscle Perfusion at During Exercise | Post apheresis | 118 IU/s |