Effect of Plasma Ceramides on Peripheral Vascular Function
Study Details
Study Description
Brief Summary
The goal of this clinical trial is to determine the effect of elevated plasma ceramides on peripheral vascular function. Subjects will be administered a high fat meal consisting of long chain fatty acids (to increase plasma ceramides) or medium chain fatty acids (control) followed by assessment of their vascular function using brachial artery flow-mediated dilation and reactive hyperemia to measure their large and small artery function, respectively. In addition to these traditional methods, specifically peripheral microvascular endothelial function will be assessed using incident darkfield microscopy (CytoCam).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Detailed Description
Following decades of decline in mortality, death due to heart disease is increasing, and remains the #1 cause of death in the United States. Although acute ischemic events are typically due to obstructive plaque within the coronary conduit arteries, strong evidence suggests that dysfunction within the coronary microvasculature is a more powerful predictor of major adverse cardiac events (MACE) than severity of atherosclerosis. The coronary microvasculature likely also contributes to other forms of cardiovascular disease including heart failure with preserved ejection fraction (HFpEF). While assessment of the coronary microvasculature is highly invasive and expensive, interrogation of the peripheral microvasculature offers a more feasible approach. Recent studies have concluded that peripheral microvascular dysfunction mirrors the functional status of the coronary microvasculature. Further, impaired peripheral microvascular function is associated with increased risk of MACE in patients with stable coronary artery disease (CAD), suggesting that the microvasculature plays a critical role in the pathogenesis of heart disease.
Elevated plasma ceramides are also associated with risk of MACE in otherwise healthy individuals as well as in heart failure both with and without reduced ejection fraction (HFrEF and HFpEF, respectively). Recently it was shown that ceramide levels are increased in patients with early CAD. Exposure to exogenous ceramide causes microvascular endothelial dysfunction in arterioles from healthy individuals.
However the effect of ceramide on human in vivo peripheral microvascular function represents a critical knowledge gap that needs to be addressed. This study will observe how blood vessels respond to acetylcholine and nitroglycerin before and after increased plasma ceramide. Acetylcholine induce endothelial-dependent dilation whereas nitroglycerin is an endothelial-independent dilator. Therefore although both are vasodilators they elicit dilation very differently. The nitroglycerin is used to ensure the subject can dilate even despite endothelial dysfunction. Lack of a response to acetylcholine suggests that the subject may have endothelial dysfunction, which is a precursor to cardiovascular disease. Increased plasma ceramide may evoke peripheral in vivo microvascular dysfunction that mirrors that of the coronary microvasculature thus providing a less invasive means to assess future cardiovascular risk.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: High fat meal and FMD This arm will assess the effect of increased plasma ceramide (high fat meal) on flow-mediated dilation (FMD) in the brachial artery. |
Other: High Saturated Fat
High saturated fat meal
|
| Placebo Comparator: High Fat Meal and peripheral microvascular function This arm will assess the effect of increased plasma ceramide (high fat meal) on peripheral microvascular function. |
Other: High Saturated Fat
High saturated fat meal
|
Outcome Measures
Primary Outcome Measures
- Flow-Mediated Dilation [Year 2]
Assess the percentage of brachial artery flow-mediated dilation
Secondary Outcome Measures
- Reactive Hyperemia [Year 2]
Measure the volume of flow following cuff release
- Endothelial-Dependent Total Vessel Density [Year 2]
Use incident dark field technology to assess endothelial dependent increases in total vessel density
Eligibility Criteria
Criteria
Inclusion Criteria:
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Health adults aged 18-40 years
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English-speaking only
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Not pregnant
Exclusion Criteria:
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Health individuals under 18 years or over 40 years of age
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Non-English speaking
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Pregnant individuals
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Individuals on erectile dysfunction medications within the last 24 hours
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Heart rate <60 or >100
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Systolic blood pressure <100 or >160
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Subjects with visible open sores or wounds in mouth
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Subjects with severe environmental allergies requiring medication as well as subjects with allergies to medications
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Subjects taking nitrates or vasodilating medications
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Lactose intolerant or allergy to dairy products.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Medical College of Wisconsin
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 00041566