Endothelial Dysfunction: The Silent Trigger
A critical component of personalized, preventive cardiology is diagnostic testing to identify atherosclerotic coronary artery disease (ASCVD) in its earliest stages - this is called subclinical atherosclerosis. One of the earliest signs of coronary artery disease, prior to appearance of plaque in the arteries, is endothelial dysfunction. This refers to the diminished ability of the innermost lining of the vasculature – the endothelium – to perform its essential functions of maintaining vascular tone, regulating inflammation, and providing a barrier to potentially toxic material, including cholesterol containing apoB particles. Endothelial dysfunction in the major coronary arteries (epicardial) and small arteries (microvasculature) is thought to be the initiating step in atherosclerosis leading to obstructive coronary disease. Thus, dysfunctional endothelium is a critical, yet reversible, early indicator of ASCVD - presenting an opportunity to diagnose and treat atherosclerosis in the very earliest stages.
What Is the Endothelium?
The endothelium lines all veins, arteries, and capillaries. It plays a crucial role in regulating vascular tone and controls inflammation through the creation and secretion of vascular-controlling agents. Nitric oxide (NO) is an especially important vasodilator produced by endothelial cells to open blood vessels and increase blood supply in response to increased metabolic demands. The endothelium additionally possesses anticoagulatory and anti-inflammatory effects to slow the formation of blood clots and maintain smooth blood flow as well as serves as an important barrier function.
What Is Endothelial Dysfunction?
Endothelial dysfunction is a disorder of the blood vessel wall lining (endothelium) in which the damaged endothelial cells cannot properly do their job. This results in increased vasoconstriction, heightened oxidative stress, inflammation, and wall permeability - all adverse changes that promote the formation of plaque. Prolonged endothelial dysfunction serves as a precursor to atherosclerosis (plaque buildup in the arteries) and leads to a higher risk of thrombosis (blood clotting), which can eventually result in stroke and heart attack.
In its earliest stages, it does not cause any symptoms. However, with time, it can result in microvascular disease - a disease of the small arteries that causes typical chest pain, or angina, not caused by blockages in the major arteries. Studies have also demonstrated that the presence of endothelial dysfunction is an important predictor of increased risk for mortality and cardiovascular events, independent of traditional risk factors.
The good news - endothelial dysfunction is reversible. Early detection, control of cardiovascular risk factors, and physical exercise can improve endothelial and heart health, thus reducing the risk of ASCVD.
What Causes Endothelial Dysfunction?
Endothelial dysfunction is caused by many of the traditional and nontraditional risk factors for cardiovascular disease, including
aging
poor metabolic health
smoking
high blood pressure
dyslipidemia
a sedentary lifestyle
It’s also more commonly found in those with a history of preeclampsia, prolonged high stress, a family history of heart disease (even without other risk factors), sleep apnea, and autoimmune conditions.
Progression has been correlated with duration of risk factors and with more than one risk factor.
How Is Endothelial Dysfunction Measured?
Invasive coronary angiography is considered the gold standard for measuring endothelial function. This test involves the infusion of acetylcholine to measure changes in the diameter and blood flow of the coronary artery. Given that this technique is invasive, expensive, and occasionally dangerous, it is used only in specific circumstances and not for screening in the general population.
There are several non-invasive approaches, all of which are more appropriate for screening. These include:
Flow Mediated Dilation (FMD) - This test uses a high-resolution ultrasound of the brachial artery, a peripheral artery. A blood pressure cuff is inflated for several minutes, with the blood vessel wall diameter and blood flow measured before and after release of pressure. Studies have shown FMD to be an effective predictor of long-term cardiovascular events, even for healthy patients without heart disease, however it is highly variable and affected by local conditions.
Peripheral Arterial Tonometry - This test is similar to FMD, but instead measures changes in pulse wave amplitude with biosensors following cuff occlusion of the brachial artery.
Cardiopulmonary Exercise Testing (CPET) - This test provides a comprehensive evaluation of the respiratory, circulatory, and metabolic responses to exercise on a treadmill or stationary bike. It is the gold standard to quantify exercise capacity and cardiorespiratory fitness (aka VO2max), as well as risk stratification and determining mechanisms of exercise limitations. By analyzing the heart rate and stroke volume response to exercise, we are also able to assess for early signs of cardiac dysfunction caused by endothelial dysfunction. It is the only non-invasive test that assesses coronary function rather than peripheral arterial function. CPET can also be used to help develop exercise prescriptions and assess response to lifestyle and pharmacotherapy interventions. It is the test of choice here at Whole Heart Cardiology.
Can Endothelial Dysfunction Be Reversed?
Endothelial dysfunction is a reversible disorder! Effective treatment and management are focused on decreasing cardiovascular risk factors through the combination of lifestyle changes and pharmacological interventions as needed to improve vascular function.
Important lifestyle modifications include:
Smoking cessation
Stress reduction
Weight loss if indicated
Healthy diets: The Mediterranean diet rich in whole grains, vegetables, nuts, legumes, fish, and olive oil has been found in several studies to reduce risk of CVD and improve endothelial health. Antioxidants like vitamin C (ascorbic acid), found in plenty of fruits and vegetables, are important to protect endothelial cells from oxidative stress and enhance immune function. Omega-3 and polyphenol-rich foods may also be helpful.
Physical activity: Physical activity of any kind has been demonstrated to reduce risk of cardiovascular disease and improve endothelium. Exercise appears to protect against the natural age-related decline of the endothelium. Some data suggest HIIT (high-intensity interval training), in particular, has shown greater improvement in endothelial function in healthy and heart failure patients compared to moderate exercise.
If medications are required, statins and certain blood pressure medications (ACEI and ARBs) have been shown to improve endothelial dysfunction. There is also some data to support the use of dry sauna, L-arginine supplementation, and insulin sensitizers like metformin.
Takeaways
Endothelial dysfunction is a critical early, but highly manageable, indicator of cardiovascular disease. It is also an independent risk factor for increased cardiovascular mortality. Understanding the importance of proactive detection and treatment of dysfunctional endothelium can significantly reduce the risk of developing more severe cardiovascular complications in all patients, healthy or not, as well as improve overall vascular well-being. As research continues to shed light on the pivotal role of the endothelium, prioritizing its health becomes an essential component of comprehensive heart care.
Interested in discussing your endothelial health with Dr. Harkin?
