evaluating endothelial dysfunction using flow-mediated dilation and subclinical atherogenesis using carotid intima-media thickness for cardiovascular risk assessment

Using Arterial Stiffness and Endothelial Function for Cardiovascular Assessment

Obesity is a major health problem worldwide due to its associated complications, such as hypertension, dyslipidemia, liver disease, atherosclerosis, insulin resistance, and type 2 diabetes mellitus (T2DM), as well as an increased risk of cardiovascular diseases (CVD)1.
The constellation of these conditions, known as Metabolic Syndrome (MS), has been reported to be a major cause of CVD pathogenesis, which is one of the leading causes of death, accounting for up to 30% of all deaths worldwide2. Obese individuals have a higher requirement for oxygen and nutrients throughout the body due to an increased blood supply demand, leading to significant hemodynamic changes. These changes can result in decreased nitric oxide (NO) availability, increased oxidative stress, and vascular endothelial dysfunction3,4,5.
Atherosclerotic diseases are major cardiovascular conditions and represent the leading cause of death worldwide. This is a clinical manifestation of multiple possible factors, including genetic and environmental factors6. People with metabolic abnormalities, such as insulin resistance or prediabetes, have been shown to have a significantly higher prevalence and incidence of coronary atherosclerosis than healthy people. Furthermore, congested blood vessels with highly lipidic plaque have been found even before the appearance of clinical manifestations of metabolic dysfunction7,8,9,10.
Arterial stiffness, endothelial dysfunction, and atherogenesis have been described as important factors in the development of cardiovascular diseases. These processes are related to vascular aging and atherogenic plaque formation in critical vessels like coronary, carotid, or limb arteries. Translational research has evidenced that arterial stiffness, endothelial dysfunction, and atherogenesis are related to common vascular damage induced by chronic inflammation, lower NO production, and oxidative stress11,12.
Measurement of Carotid-femoral pulse-wave velocity (cfPWV) represents the gold standard method to measure arterial stiffness. cfPWV can be measured using a carotid tonometer simultaneously with a leg cuff to capture blood pressure waveforms at the carotid and femoral sites. Then, a software can perform velocity calculation by computing D/&#916;t, where D is the transit distance between carotid and femoral pulse sites, and &#916;t is the time delay from the peak ECG R-wave to the foot of the corresponding pressure waveform between the carotid and femoral waveforms. Increased stiffness of central arteries, like the aorta, causes a higher speed of the ejected pulse from the left ventricle through the arteries, as well as a faster return of the reflected pressure, with a consequent elevation of pressure during left ventricular ejection, which potentially decreases coronary artery perfusion. Therefore, cfPWV may be useful as a marker of coronary artery disease, stroke, and cardiovascular diseases13,14.
Likewise, Pulse Wave Analysis (PWA) is a non-invasive vascular parameter that assesses central pressure wave characteristics, where aortic systolic and diastolic blood pressures are the main variables. By measuring arterial stiffness and elastic compliance, PWA reflects arterial distensibility, which is closely related to cardiovascular risk. This method allows for measuring parameters like the Augmentation Index, which has the ability to predict the severity of cardiovascular and coronary artery diseases. The Augmentation Index may be described as follows: an early incident arterial wave is produced after left ventricular ejection, with a subsequent reflected wave originating from the periphery. The velocity of these waves increases according to arterial stiffness, and if the reflected wave arrives at the central aorta early, aortic systolic pressure will increase. This is known as Augmented Pressure (AP), whereas its percentage relative to Pulse Pressure is known as the Augmentation Index. PWA can be measured through the applanation tonometry method, involving a slight compression of the brachial artery so that its transmural pressure is zero. At this point, Mean Arterial Pressure can be measured. After scaling the arterial pressure waveform, the systolic part of the AP waveform is analyzed, also considering biometric and demographic data15,16,17. Particularly, the applanation tonometry method (SphygmoCor) has shown acceptable repeatability and significant correlation with invasive aortic catheterization in determining aortic PWV, as well as good agreement with the Artery Society Guidelines18,19,20.
Other vascular tests like flow-mediated dilation (FMD) and carotid intima-media thickness (CIMT) represent non-invasive techniques performed by ultrasonography with linear transducers. These assessment procedures are useful for evaluating vascular health, specifically endothelial dysfunction and subclinical atherogenesis, respectively. Both have shown prognostic ability for cardiovascular events. FMD is commonly considered a reflection of endothelium-dependent arterial function, primarily mediated by nitric oxide. It serves as a surrogate marker for vascular health and has been utilized non-invasively to compare subject groups and assess the effects of interventions on individuals21.
The aim of the present study is to describe the use of methods that yield the determination of markers reflecting early subclinical vascular aging, endothelial dysfunction, and atherogenic disease. Such information allows risk stratification among populations with obesity and different metabolic profiles. These methods might be useful to determine cardiovascular damage and prognosis, as well as to evaluate vascular and atherogenic responses to pharmacologic and non-pharmacologic interventions, particularly among populations with metabolic risk factors.

Author Spotlight: Assessing the Cardiovascular Profile of Patients with Metabolic Syndrome

Pulse-Wave Velocity, Flow-Mediated Dilation, and Carotid Intima-Media Thickness to Assess Cardiovascular Risk in Population with Metabolic Syndrome

Vascular aging and atherogenesis are key mechanisms promoting cardiovascular diseases, particularly in the presence of risk factors like diabetes, hypertension, and other metabolic dysfunctions, pulse wave velocity, flow-mediated dilation, and carotid intima-media thickness, evolving to arterial stiffness, endothelial dysfunction, and subclinical atherogenesis, providing highly valuable information about patients'cardiovascular profile. Using combined metals to assess vascular health, we found that patient with metabolically unhealthy obesity has lower values of flow-mediated dilation or FMD and than patient with metabolically healthy obesity. This finding provide information leading to prevention, early intervention, and reduction of cardiovascular diseases in population at risk.Determination of vascular elasticity and compliance, as well as mediators of vasodilation and atherosclerosis provide a more comprehensive evaluation of vascular health and disease leading to improve re-stratification and early intervention in the metabolic syndrome population. Our hemodynamic parameters, FMD, and CIMT represent useful diagnostic tools for evaluating cardiovascular risk. Future challenges for these methods include a combined prognostic interpretation where research is still evolving.

Evaluating Endothelial Dysfunction Using Flow-Mediated Dilation and Subclinical Atherogenesis Using Carotid Intima-Media Thickness for Cardiovascular Risk Assessment

evaluating-endothelial-dysfunction-using-flow-mediated-dilation

Research

JoVE Journal

Medicine

Pulse-wave velocity (PWV), flow-mediated dilation (FMD), and carotid intima-media thickness (CIMT) are established methods used in research and clinical settings to assess arterial stiffness, endothelial function, and subclinical atherogenesis. These measurements may reflect vascular disease and atherosclerotic progression, which are major causes of adverse cardiovascular events. These methods are particularly valuable in determining cardiovascular dysfunction among populations with different risk factors, such as diabetes mellitus, hypertension, and other metabolic dysfunction-related conditions. They provide a non-invasive and reliable source of information that complements clinical practice. Early detection, risk assessment, and therapeutic decisions regarding cardiovascular disease can be achieved, ultimately contributing to improved patient outcomes. Traditional tools for evaluating cardiovascular disease do not reveal whether metabolic syndrome affects early subclinical cardiovascular disease in patients with obesity. Recent research has highlighted the importance of including arterial stiffness and endothelial function in a comprehensive cardiovascular assessment. Therefore, the aim of the present study is to describe methods that provide information on early subclinical vascular aging, endothelial dysfunction, and atherogenic disease, enabling vascular-targeted risk stratification among populations with obesity and different metabolic profiles.

Endothelial/vascular aging and atherogenesis are key mechanisms that promote the development of cardiovascular diseases. The present protocol describes methods to evaluate arterial stiffness, endothelial dysfunction, and atherogenesis in patients with related risk factors, which are highly valuable in the cardiovascular research field.

Pulse-wave velocity (PWV), flow-mediated dilation (FMD), and carotid intima-media thickness (CIMT) are established methods used in research and clinical ...

Evaluation of Vascular Aging Using Arterial Stiffness for Assessment of Cardiovascular Risk

To begin, place the patient in a supine position for at least five minutes before beginning the assessment. Place a brachial cuff and secure it around the patient's arm, centered on the brachial artery. Then connect the brachial cuff tube to the SphygmoCor device tube.Press the start button of the device two times for aortic pressure measurement. Obtain pulse wave analysis or PWA by applanation tonometry. After scaling the arterial pressure waveform, analyze the systolic part of the waveform, also considering biometric and demographic data, then obtain an automatic report of the test containing aortic parameters.Proceed to perform carotid femoral pulse wave velocity or cfPWV determination through applanation tonometry method. Place a femoral cuff around the patient's thigh as high as possible, ensuring the tube is centered at the top of the leg. To find the carotid pulse on the patient's neck below the jaw, ask the patient to rotate their head slightly aside.Once the carotid pulse is found at the strongest perceived site, place an indicator mark on the patient's skin. Obtain three measurements. First, the distance between the carotid pulse and the suprasternal notch.Second, the distance between the suprasternal notch and the femoral cuff. And finally, the distance between the femoral artery by palpating the pulse on the patient's groin and the femoral cuff. Then introduce information on the three distances into SphygmoCor Excel software.Now connect the femoral cuff tube to the SphygmoCor device tube. Place the tip of the tonometer on the site where the carotid pulse was previously located, then press the start button and estimate the cfPWV.