Identifying Subclinical Cardiovascular Disease

Hello, everyone, and thank you for joining me today for this very important and exciting topic identifying subclinical cardiovascular disease. I'm Gina Pritchard, Cardiovascular acute Care Nurse Practitioner. I'm the owner and founder of the PREVENT! Clinic with locations in Frisco, Texas and Franklin, Tennessee. And I'm a speaker for the Bale Doneen Method/Bale Doneen Practice and for the Cleveland HeartLab as well. The objectives today are to discuss and compare current methods to diagnose cardiovascular disease, to discuss methods that identify subclinical atherosclerosiss, to compare and contrast the disease based model and risk factor model of cardiovascular risk assessment, and to explore methods combining subclinical atherosclerosis assessment with biological testing to diagnose and treat patients to prevent disease progression. As many of you may know, heart attack and stroke all cause cardiovascular disease, is the number one cause of death in the United States and worldwide, and has been so since the year 1919. Approximately 2100 Americans die daily from cardiovascular disease, one every 43 seconds. Cardiovascular disease is responsible for 1 in 3 deaths, and claims more lives than all cause cancer combined. The lifetime risk for developing cardiovascular disease at age 40 for men is 2 in 3, and women 1 in 2. So why aren't we making better headway in heart attack and stroke prevention or in the death rate? So if we are making any improvements and we are, it's occurring in the area of acute care. In other words, we have much improved our stenting procedures, minimally invasive coronary artery bypass graft surgery, improvements in cardiac transplant, and in opportunities for left ventricular assist devices. So our acute care has improved tremendously. The time from presentation of symptoms to arrival to the cardiac catheterization laboratory for stent implantation has decreased. And so these areas of accomplishments have definitely made improvement in saving lives in the acute care setting. However, the 2020 impact goals for the American Heart Association are to improve the cardiovascular health of all Americans by 20% while reducing deaths from cardiovascular diseases and stroke by 20%. So in the previous slide, we showed some areas in which we are making headway in reducing the death rate, but we're not improving overall the cardiovascular health of Americans by 20%. And we're doing still continuing to do a very poor job at primary prevention and at keeping patients from encountering the first heart attack or stroke in the first place. A Community of Heart Attack and Stroke Prevention Specialists of 2020 Impact Goal is to eradicate cardiovascular disease as the number one killer by the year 2020. So these are very lofty goals. I want to talk today about how this might be possible. Traditionally, we focus on the risk factor model of prevention and obviously since heart attack and stroke have been the number one killer since the year 1990, 1919 rather, the risk factor model is not effective. Currently, widespread use of prevention methods based on the risk factor model evaluate a patient based on Framingham Risk Score and Reynolds Risk scoring system and then risk factor modification. So when a person's age, gender and risk factors such as blood pressure, cholesterol levels, etc. are plugged into the Framingham Risk Score and Reynolds Risk scoring system, the patient is identified as low risk, intermediate risk, or high risk and appropriate aggressiveness, if you will, of the risk factor modification is in place. Diagnostic imaging isn't suggested until symptoms occur. Occasionally when a patient is older or has multiple risk factor or is found to be in a high risk category based on the Framingham and Reynolds risk scoring system, then diagnostic imaging might be considered. Certainly if the Framingham Risk score or the Reynolds Risk score identifies the patient as high risk, these scoring systems have great positive predictive value. However, if a patient is placed into a low or intermediate risk category, they are oftentimes mis-categorized and the appropriate level of treatment is not recommended. So these current methods that are symptom driven. First, perhaps order labs to evaluate the symptoms and then order imaging to determine the extent of the disease. An example is the patient in which heart failure is expected, labs such as the NT-proBNP is ordered an elevated and then an echocardiogram ordered to visualize heart structure. Just as an example. So let's compare this risk factor model waiting for diagnostic imaging once the patient has symptoms or is in a high risk category, Let's compare that to a disease based model. In the disease based model, which allows for early opportunities for screening for subclinical atherosclerosis, the patient is evaluated thoroughly before they ever have their first symptom. Instead of focusing the majority of our imaging techniques for the identification of late disease, we want to know early if there's evidence of atherosclerosis. As you know, plaque buildup in the artery isn't symptomatic. You don't see all plaque building up in your arteries. You don't feel atherosclerosis. It's not a normal phenomenon. It's incredibly widespread in the United States to find atherosclerosis, but it isn't normal. So if we look for it and identified early, we can recommend appropriate treatment. So it allows for improved accuracy of risk stratification. This has been supported in the literature in many large scale studies, such as the Mason study and others. And if someone is placed in a lower intermediate risk category with the Framingham or Reynolds risk score, adding a screening imaging technique for subclinical atherosclerosis places them in a more accurate category. And then again, appropriate treatment selection. So the presence of atherosclerosis or atherosclerotic disease early instead of after obstruction of the lumen or reduction in blood flow, is the focus of our discussion today. So the arterial system is the most important organ in the body. These blood vessels, the arteries that carry the nourished and oxygenated rich blood to all of the vital organs are the focus of our attention. The first area that we want to look at is the endothelial lining, the 1 to 2 cell layer, the lining of the artery wall, and then the intima media layer underneath. This is where plaque lipid debris accumulate in the presence of atherosclerosis. So if you have blockage or atherosclerosis or narrowing of the blood vessels, any pathologic phenomenon that reduces blood flow to the vital organs, obviously stroke can occur. But also if this occurs chronically over time in the microvasculature, dementia can occur. Heart attack if the blockage occurs in the coronary artery. Heart failure again with the necrosis of cardiac tissue or with chronic microvascular disease. Erectile dysfunction is often the first indication that a patient has vascular disease or atherosclerosis and then peripheral artery disease as well. So let's first just review event reality, meaning what causes a heart attack or stroke in the first place? Most heart attacks and approximately 85% of strokes are caused by plaque eruption and blood clot formation, but not by the plaque itself, meaning the plaque doesn't just grow and continue to accumulate and then ultimately block the flow of blood 100% and immediately a heart attack occurs. That's a chronic accumulation of atherosclerosis. But 85% of strokes and most of ischemic stroke and most heart attacks occur because a smaller lesion, a smaller plaque, if you will, that isn't blocking the flow of blood erupts, the body send in the blood clotting mechanism, and that immediate blockage of blood flow due to the blood clot is what prompts a heart attack or stroke. So the atherosclerotic plaque that is not blocking the flow of blood is dangerous. So it's no wonder and no surprise that 35 to 50% of cardiovascular presentations are sudden cardiac death. Someone could have mild meaning, non flow limiting lesion and never feel it until something as devastating as a heart attack, stroke or sudden cardiac death. On this histology slide, we see the left lipid and debris accumulation in the inflomedia layer. Under the endothelium and on the right slide, you can see the vulnerability of the area in the endothelium, a little crack is beginning to occur. And so should that open up and the debris exposed to the blood flow, then that's when the body sends in the mechanism for blood clotting. So when the lipids and debris start to accumulate in the artery wall, we call that the first failure, meaning the endothelial lining has allowed through permeability, has allowed lipids to get into the wall of the artery. If the body keeps them there, then a heart attack or stroke will not occur. But if a crack, then a second failure or a crack in the endothelium occurs, then we have the problem of a heart attack or stroke. On this post autopsy slide of the coronary artery at the location that did cause this person's demise from a heart attack, we see the area in the wall of the artery where the lipids were residing, if you will. So the first failure had occurred. And then when these two cracks occurred, the second failure in the endothelium and a blood clot formed, it immediately blocked the flow of blood to the coronary artery. This blood clot did fill up the entire lumen and part of it fell out on during the time that they were preparing the artery for the slide, for the picture. This is a drawing of the mechanism we've just talked about the healthy artery in the upper right with uncontrollable risk factors or the modifiable risk factors that are in control or perhaps when inappropriate treatment or less aggressive treatment is implemented, then endothelial damage occurs, which is in the second pictorial. With this cholesterol accumulation in the artery wall, there is presence of disease So this is the area where we have the opportunity to image the arteries and identify the presence of disease when it's in this, quote, mild stage. We call it mild because it's not limiting the flow of blood. However, with this, with the presence of chronic inflammation, which can be monitored through blood and urine testing, the the presence of even small lesions, the presence of disease leads to pressure on this endothelial lining. And this plaque can very easily become vulnerable where a mild non flow limiting plaque becomes a vulnerable, dangerous lesion leading to plaque rupture as we see on the left in the clot formation that was identified in the slide previously. So does imaging, some form of testing to look for mild disease or look for the presence of atherosclerosis, help identify patients at risk? We know that this is true based on a study that came out in 2001 called the CAFES-CAVES study. This study was carried out by a group of very forward thinking researchers who said starting in the late 1980s, let's take 10,000 healthy subjects. These were individuals that were relatively young, aged 35 to 65, no diabetes. They were not hypertensive They had to be healthy to get into the study. They said, let's take a look at the femoral arteries and at the carotid arteries using D mode ultrasound. And let's just document what we see and follow these arteries over ten years and demonstrate what occurs. No treatment was allowed for ten years. So the patients were divided into four categories. Class 1 was described as the normal artery. No evidence of early disease, no evidence of pre-atherosclerosis, no thickening of the artery, but normal arterial wall binding. There were nearly 8000 people in that group. In Class 2 wall thickening, meaning an area of intima media thickness that was beyond what was average for that person's age and gender was identified in 930 subjects. In 611 subjects, patients were categorized into the Class 3 presence of disease. So a plaque was found that measured 1.3 millimeters or greater or 50% thicker than the surrounding tissue. That was the presence of disease. Whether it was limiting the flow of blood or not, they would identify them and put them in the Class 3. However, if a person was found to have disease that was stenotic so the presence of plaque that was limiting the flow of blood, then they were placed into the Class 4 category. So followed over ten years. What was the likelihood that the percentage of patients in each category that would go on to have a heart attack or stroke? So what was their ten year risk? Class 1 with the normal artery 0.1%, risk. Class 2 with an increased intima media thickness, 8.7%. And in Class 3, these healthy individuals aged 35 to 65, if a disease was found, albeit mild, non flow, limiting in 611 subjects almost 40%, 39.1% of those individuals went on to have a heart attack or stroke in the next ten years. And of course in the last category, with the presence of late disease or significant atherosclerosis, 81.1% of those went on to have cardiovascular events in the next ten years. So we can see in this Class 3 category, presence of disease, even if it is non flow limiting, is incredibly significant. This allows us to recategorize the patients into a more appropriate risk category. So these people would be the the the patients in whom mild nodular limiting lesions are identified would be placed into a high risk category based on adding our imaging of the artery wall to our Framingham or Reynolds risk score. So since 2001, many more studies have come out to demonstrate the same thing that the presence of disease more appropriately categorizes the patient into a high risk category rather than low or intermediate risk, and early intervention and appropriate treatment can be recommended. So when your risk is 40% of having a heart attack or stroke in the next ten years, it's incredibly significant. Patients are identified as high risk on the Framingham and Risk Reynolds score if they have a 20% risk of developing an event in the next ten years. So screening methods, just simply taking a look to see if there is any asymptomatic subclinical atherosclerosis in an individual, improves the accuracy at risk stratification and allows us to identify appropriate treatments for this patient. Screening, it also allows for screening and early detection. So the presence of atherosclerosis early before an obstruction of the lumen or reduction in blood flow occurs. So can we improve the effectiveness of our efforts to reduce cardiovascular events if we use imaging to screen for subclinical atherosclerosis? Let's explore this a little bit further. How do we currently diagnose disease? So there are a variety of ways. The electrocardiogram, which detects heart rhythm and structural irregularities. That's a global look for clues of heart muscle damage, if you will, and other heart rhythm issues. That EKG is not specific and sensitive enough in all cases. This is why we have additional tests, but it can provide some clues, not enough. Echocardiogram, the chest type ultrasound, evaluating heart structure and function abnormalities. Again, this can identify a problem after it's occurred, but isn’t helpful at identifying problems related to arterial disease early on. The stress test with or without imaging of the heart, tells us if the heart is getting adequate blood flow during a high demand stress, say. So, arterial disease has to be blocking the flow of blood 70% or greater to show an abnormality with the stress test. So again, this test is focusing on late disease. Patients who have normal stress test frequently have extensive atherosclerosis. I think anyone who's been in the medical field very long certainly knows of a case or has a patient or in the cardio cardiology world, we have patients far too frequently who have normal stress tests. Even if it's a stress test with imaging, who end up having a heart attack in the next week, in the next month, in the next six months. So the stress test again is not ideal, particularly for the asymptomatic patients. Certainly we can do coronary angiography to take a look at the coronary arteries with the catheter based, catheter based procedure using contrast dye and viewing the arteries on x-ray. So the benefits of coronary angiography are that you get great temporal and spatial resolution. It establishes the lumen size and pathological changes in the vessels in terms of stenosis. But the drawbacks are that it is invasive. It's a higher complexity than noninvasive outpatient studies performed in the office versus having to go into the hospital, even if it's a day procedure that's still invasive with the risk of complications. And there's still a poor evaluation of the thickness of the wall of the artery, and it's inferior in terms of evaluating plaque composition. This slide tells us some of the problems with coronary angiography and the fact that it isn't three dimensional. So looking from a X-ray standpoint at dye going through the coronary arteries can mislead us. In terms of the area of stenosis, something can appear to be 50% blocking the flow of blood and a 50% type evaluation when indeed the cross-sectional view of the Lumen would show us that actually blocking the flow of blood much, much greater than 50%. Certainly angiography can be coupled with intracoronary ultrasound or intravascular ultrasound, which provides greater information. The benefits of this ultrasound inside the artery wall or inside the lumen of the artery evaluating the artery wall is that it is more accurate. than angiography for visualizing the artery wall and it measures the thickness and the echogenicity of the atherosclerotic plaque, which is incredibly helpful. The drawbacks are, again, that invasive. There is a lot of interest around virtual histology ultrasound, and we'll hear more about that in the in the future. It's a hot topic currently. But there are two methods to identify subclinical atherosclerosis rather than the tests above. If the person is having symptoms or the person is not having symptoms asymptomatic, subclinical, we can use either an ultrasound based method looking at the carotid artery and other artery arterial beds such as the femoral artery using ultrasound techniques. But if we are talking about the carotid artery, we want to measure the intima media thickness. And numerous studies have been done to show the benefit of that. We’ll review these. The second method to identify subclinical atherosclerosis besides the ultrasound giving the ultrasound giving us details of the artery wall, the coronary artery calcium scoring system using computed tomography or CT. And so we'll talk about both of these a little bit more. The ultrasound based method looking at the carotid intima media thickness or even the femoral intima thickness, however, there is more data on the carotid arteries. Uses a ultrasound probe placed on the neck to evaluate the thickening of the artery and stiffening of the artery, perceived lumen occlusion. So if we see that an individual's intima media layer, as you see depicted there at the bottom is thicker than it should be for that person's age and gender, then it can predict more accurately as we saw earlier, the likelihood of any a cardiovascular event in the next ten years. Simply the presence of the intima media thickness tells us that the first failure has occurred, that the endothelium has become permeable and lipids and debris are collected in the artery wall. A common location for plaque buildup that may or may not be limiting the flow of blood is in the bifurcation where the carotid artery divides into the internal and external carotid artery. Due to the shear stresses on the vessel wall in this area of bifurcation oftentimes leads to plaque buildup in the bifurcation area. So when we do the carotid intima media thickness test using ultrasound, what do we need to know about arterial health? We need to know, as stated before, the intima media thickness and compare and contrast that to the person and that what we know to be normal or healthy or the average individual of the same age and gender. We need to identify the presence of plaque. Anything that measures greater than 1.3 millimeters or greater than 50% thickness of the surrounding tissue is identified as an atherosclerotic plaque. And we need to know the characteristics of the plaque. If it's soft or non-echogenic, this lesion is more vulnerable. If it's echogenic, completely calcified, then the lesion is more stable and less likely to rupture. And if it's heterogeneous, then we treat it like soft because there is evidence of calcium, but it isn't completely calcified over a completely echogenic. And then certainly the last thing we need to know when we're performing ultrasound in any arterial bed is the presence of obstruction of blood flow and, you know, to what degree. This is an example of two different patients and their arterial age. Arterial age is a term that is commonly used in the general public for this test. The CIMT, our ultrasound based test, often referred to as the arterial age test. Meaning if we put your measurement into a comparison to the others of your age, it tells us if you are on average a thickness older than your biological or chronic blood vessel age or younger than your current age. So Patient 1 is 54 years old and intima media thickness is .94 millimeters, which places him in a category that is more normal for a 75 year, 79 year old male patient. The patient below is a 70 patient number 2 is a 75 year old patient, but with an intima media thickness of 0.56, it places this patient more along the lines of an arterial age on average, that's normal for a 35 year old. So this is an example of the intimate media thickness evaluation. You can see the lumen there. Lunenology refers to the study of our becoming expert in the blood flow through the blood vessel. So looking at the area between the white lines there where the blood is flowing tells us how well the lumen patency is. So stress tests, some of the sonograms and cardiac catheterization is looking at patency of the blood flow, patency of the lumen, but totally ignored the arterial wall. Arteriology, a term that was coined by Dr. Amy Doneen is the study of and becoming an expert in the detail related to atherosclerosis in the wall of the artery, regardless of whether it's blocking the flow of blood or not. You can see this area where the first failure has occurred, leading to a 1.3 greater than 1.3 millimeter plaque formation was totally ignored in the previous slide where we were completely focused on luminology or on blood flow. So the presence of plaque as we see on the left and or an evaluation of the intima media layer, which is depicted in the rectangle box on the right to determine if it's thicker than it should be for the person's age and gender are both important determinants from the ultrasound. And we can see from this study and there have been several others that have supported the fact that patients are reclassified to a more appropriate category for risk stratification when a CIMT score is used in connection with the Framingham Risk Score and the Reynolds risk score. As we see on the left, Baseline risk assessment based on the Framingham Risk score, 63.5% of the patients evaluated in this study were placed in the low risk category, 23% placed in an intermediate risk category, and 13.5% placed in a high risk category. However, once these patients were reclassified following an evaluation of the intima media wall, 24.3% was the accurate amount that were placed into the low risk category, 40.5% were placed into an intermediate risk category and 35.1% were placed into the high risk category. So again, if this is the patient that's sitting in front of us today, we can give them a more accurate prediction of their likelihood of suffering a cardiovascular event in the next ten years and make more appropriate next step recommendation. So what about coronary artery calcium scoring? This is the second test, which is also incredibly helpful to screen for subclinical atherosclerosis because calcification is a surrogate measure of atherosclerosis. We know that death of endothelial cells leads to micro calcification and this is identified on coronary artery calcium scoring. Calcification can indicate that there is more extensive disease, that is soft disease that isn't identified by calcification So a higher level of uncalcified plaque is often present when we see presence of calcium. But it's the place to start for sure. The coronary artery calcium score tells us if there is presence of disease or not. So the CT scan is a multi slice computed tomography of 64 slides or even greater for increased imaging quality and the benefits of this test it that it’s low cost, it's easy access, there's a large number of thin slices for great resolution and it is being considered, chest CT is being considered to replace angiography, chest CT that can look at the coronary artery. But the drawbacks of this test are ionizing radiation. Magnetic resonance, magnetic resonance imaging or MRI is used when CT can't be used due to such as renal dysfunction or due to an allergy to the contrast dye. So the benefits of MRI is that it's non-ionizing and better clarity than a CT. But it's expensive. And of course you can't do use MRI when implanted devices are that are a problem or are present in the patient. So and it has a great likelihood of artifact. This is coronary artery calcium scoring in a patient just to show us the presence of coronary artery calcium and what that looks like. Arterial age can also be determined by coronary artery calcium scoring and provides greater predictive value when added to the Framingham risk or the Reynolds risk score. Numerous studies have been done on this. We know this to be true in women. We know this to be true in young adults. So the presence of calcium can modify the predicted risk scores and give us greater predictability, much like the IMP. So between the intima media thickness test and the coronary artery calcium scoring tests, what are the comparisons so the CIMT is reproducible? There is some variability between intra and inner observers. It's availability can be limited across the United States. The cost is generally $200 to $500. I've seen it as high as $650, but it, like coronary artery calcium scoring, is continuing to come down in price, but it's a relatively inexpensive test. But there is no insurance coverage for the imtima media thickness evaluation or the ultrasound based evaluation of for arterial plaque and arterial thickening. Considerations with the use of coronary artery calcium scoring are as follows: The patient is exposed to radiation and the coronary artery calcium score is difficult to monitor the disease process over time due to the fact that coronary artery calcium scoring identifies only calcified plaque as we spoke about earlier, the soft or uncalcified plaque isn't identified on the CT scan. So with coronary artery calcium score is repeated in a year or 2 years, 5 years, data supports the fact that the coronary calcium score will go up because the uncalcified disease that was there will become calcified if the body compensates appropriately. So what we don't know when the coronary calcium score goes up, if the disease state is worsening, if there is more extensive disease or if the disease process that was already occurring at the time of the baseline coronary artery calcium scoring system, I mean scoring the score with CT is simply stabilizing. So the ultrasound based methods provide more ongoing monitoring information. The coronary artery calcium scoring test, however, has been become incredibly affordable. When it first came out the CT coronary artery calcium CT scan costs well over $1,000. But now most areas of the country, it's available for $100 and, even under $100 in some locations of the country. So the cost is very affordable. And just like the ultrasound based evaluation of the artery wall, no insurances insurance plans are covering the CT coronary artery calcium score. It really depends on the availability in your area. It depends on the patient. Coronary artery calcium scoring is not recommended for those under age 40, and it depends on your goal. Certainly coronary artery calcium scoring is a great place to start for any individual over 40. It's more readily available and it will answer the question is there calcification presence of disease in the coronary arteries or not? However, if the coronary artery calcium score comes back as a zero, no evidence of calcium, I would do not just stop there because the patient may well still be misclassified without the opportunity for early intervention. If you put all your confidence in the coronary artery calcium score number of zero. So then move to the ultrasound based evaluation of the carotid wall. The other thing that is important to note about the carotid imtima media thickness test is, again, it can be monitored over time. So if your patient has a coronary calcium score that zero, we would recommend getting an ultrasound based evaluation of the artery wall to see if there’s presence of disease there. Again, look in as many arterial beds as you can to make sure that you don't miss subclinical disease. And then also the benefit of the ultrasound to be able to monitor the disease once it's identified. So when would you use the subclinical imaging tests to identify subclinical disease for implementation of primary prevention efforts? So you might screen all your patients, you might use it as a tool to investigate further those with moderate risk to determine whether or not to use pharmacological therapy and use it as a tool, the ultrasound base.