We now know that atherosclerosis, the buildup of plaques within the walls of the arteries, is caused when the endothelial cells that line the thousands of miles of blood vessels become dysfunctional. We also know that endothelial dysfunction is caused by the same heart risks that initially damage the endothelium.

Based on new clinical findings, many leading cardiac researchers now believe that endothelial dysfunction is a disease unto itself, and that this disease is what causes damage to the vessels of the heart, not atherosclerosis. Furthermore, this dysfunction is triggered by an inflammatory response to the damaged endothelium. Atherosclerosis, and the subsequent plaques and arterial blockages and heart attacks that it causes, are manifestations of this endothelial dysfunction.

Click the above title for a graphic description of the ongoing disease process as it spans the decades.

This novel way of looking at heart disease is beginning to change the way doctors look not only at the blood vessels, but also at the very nature of heart disease, and how it’s detected and treated. And it all starts with understanding that it’s the delicate endothelial cells lining the blood vessels that need to be protected.

The Lifelong Journey From Healthy Endothelium To Heart Attack

The First Decade: The blood vessels of a child who is physically active and eats a healthful diet are smooth and flexible. The endothelium, the inner lining of the vessels, is typically unblemished and oxygenated blood flows readily through it to the tissues.

Atherosclerosis begins early in life, however, and develops slowly over the years. In the first decade, adolescents who consume a typical Western diet and are physically inactive, begin to develop yellowish fatty streaks that appear on smooth blood vessel surfaces. Cholesterol and other risk factors make the endothelium “sticky” and impair the ability of the endothelium to make nitric oxide, or NO. Nitric oxide helps keep the endothelium smooth and slippery so white blood cells and platelets that trigger the clotting process are unable to adhere. 

Unless changes are made in diet and physical activity levels, the delicate endothelium will eventually become damaged by these fatty streaks, which trigger an inflammatory response that causes even more disruption in the endothelium. The earliest manifestations of endothelial dysfunction are seen at this time. 

With the dual obesity and type 2 diabetes epidemic now affecting children worldwide, EndoPAT testing of children and adolescents can be used to detect early manifestations of endothelial dysfunction. We now know that nearly all children have some degree of fatty streaks on their aortas by the age of three, and they increase steadily after the age of eight, with atherosclerotic plaques present in the coronary arteries of many by their teenage years.

The EndoPAT Solution

Non-invasive diagnosis and measurement of early endothelial damage in adolescents is now possible with a 15-minute, in-office EndoPAT test. Using this test, doctors have the real possibility to change how elevated cardiovascular risk is both evaluated and treated in this young but highly vulnerable age group. 

Not only does the EndoPAT predict adverse cardiovascular outcomes in these youngsters, but their low EndoPAT scores correlate with cardiovascular risk factors, including sedentary behavior, type 2 diabetes, obesity, second-hand smoke, elevated LDL levels, and inflammation.

“The emphasis should be on prevention both from a population basis and by better identification of high-risk individuals decades before clinical cardiovascular disease occurs.”

—Elaine M. Urbina, M.D., et al

Noninvasive Assessment of Subclinical Atherosclerosis in Children and Adolescents.

A Scientific Statement From the American Heart Association (2009)

The Third Decade: Three decades of a typical Western diet, which is high in animal fat and processed foods and low in fruit and vegetable consumption, coupled with smoking and lack of physical activity, continues to damage the endothelium and makes more endothelial cells sticky. White blood cells circulating in the bloodstream get caught in this damaged area, move into the lining of the blood vessel, and cause more inflammation.  

As more LDL (low-density lipoprotein) cholesterol particles are trapped beneath the endothelium and become oxidized, increasing numbers of white blood cells are sent to quell the inflammation. But as these cells consume the oxidized LDL and die off, more inflammatory distress signals are sent out in the form of cytokines, accelerating and continuing this dangerous inflammatory cycle. Over time, areas of gooey plaque develop within the endothelium. A dangerous stage has now been set.


The Fourth Decade: The development of well-established fibrous plaques in the arteries of the heart that began in the third decade of life due to LDL accumulation and the addition of fibrin and calcium, continues in the next decade. In more advanced cases, the plaque grows and spreads, with some pushing into the lumen, the open space within the artery through which the blood passes. As the lumen is narrowed by the bumps caused by the plaque accumulation there, it can be detected by an angiogram.

However, most plaque pushes away from the lumen and are undetectable by most diagnostic heart tests, including stress tests and angiograms. And as they enlarge and begin to cover the vessel wall, the scene is now set for impending heart problems that could have lethal consequences.

Although not detectable by angiogram, the endothelial dysfunction caused by this accumulating atherosclerosis is easily noted by EndoPAT testing and low EndoScores. This is oftentimes three to seven years in advance of an eventual heart attack. Study Review

Traditional coronary artery disease diagnosis at this time includes a detailed medical history and a number of exams and tests, including electrocardiogram, exercise stress test, and coronary angiography. Combined with an EndoPAT test, however, the sensitivity and specificity of these tests is enhanced, enabling better identification of patients with coronary endothelial dysfunction.

If lifestyle changes and lipid-lowering and other appropriate medication therapies are not initiated, the endothelium will become further damaged. Atherosclerotic plaques will continue to grow, thicken, narrowing blood vessels and restricting blood flow. Heart tissue can become oxygen starved and symptoms such as angina and legpain may develop. 

When oneof these plaques eventually ruptures or tears within a blood vessel, its contents pour into the bloodstream. The body responds as it would to any cut and special clot-producing blood cells are rushed to seal off the injury, while inflammatory cells go about their work of remodeling and strengthening the plaque. 

But when plaque breaks, the end result is not always that benign. Too often, the plaque damage leads to complete blockage within the artery, and oxygenated blood is unable to get to the heart. This is the classic heart attack, or myocardial infarction. If the clot is not quickly dissolved or removed, heart muscle cells begin to die. Another dangerous stage is now set, this time for future heart failure or death. 

The New Diagnostic Paradigm

With many leading researchers now looking at endothelial dysfunction as the risk of all heart risk factors, with atherosclerosis but a symptom of the ongoing systemic dysfunction, traditional thinking about heart disease—its diagnosis and treatment—is starting to shift. 

Treatments to repair the damage caused by ruptured plaque—stent, medication, angioplasty, CABG—are now viewed as palliative, not curative, in that they don’t heal the damaged endothelium. They only delay the onset of another plaque rupture.

However, by turning the focus to the health of the endothelium at a much earlier stage in life, by assessing it with noninvasive EndoPAT testing, and then initiating regular physical activity and a low-fat diet, and making concerted efforts to control blood sugar, blood pressure, and cholesterol in at-risk individuals, levels of inflammation can be reduced and the health of the endothelium can be improved, oftentimes dramatically. This is evidenced by rising EndoPAT scores.

Each year in the United States, about 785,000 people will have a heart attack for the first time, while 470,000 will have a repeat attack. In about 20% of the cases, death will result. Early diagnosis with EndoPAT, however, offers a real chance to help reduce these figures significantly.