- Foreword / Introduction
This is the first installment of a four-part series covering this important topic. We know, in the developed world, at least 20% of individuals with NO symptoms of cardiovascular disease and NO identified cariovascular risk will be found by the newly developed Soterogram to be at increased risk for atherosclerosis, which is the disease responsible for heart attack, stroke, and peripheral vascular disease. This single disease is the cause of over 50% of ALL deaths in the United States and the Western World. The developers of this new technology fully realize that to identify individuals with increased cardiovascular risk will NOT reduce cardiovascular morbidity and mortality, unless, armed with the Platform information/results, methods to reduce risk factors for atherosclerosis, are aggressively institued. At this point, two facts need to be mentioned. First, atherosclerosis is generally a slow process; for reasons which are not science-based, this produces a sense on non-urgency, which does not work to the benefit of patients. Second, current medical science does not have a single cure for atherosclerosis, as was the case with Polio, which was eliminated with a single-dose of medication. The good news is that current medical science is aware of the most important cardiovascular risk factors and have proven ways to reduce current and future cardiovascular risk. The bad news is that, the patient and the patient’s family, play a major role in reducing this risk. We like to say – “the patient is on the wrong cardiovascular trajectory and changes are needed”. The central missions of this Series are to describe new noninvasive methods of assessing current cardiovascular status, describe the operational cardiovascular risk factors, and illustrate guidelines and treatment protocols, both aggressive and non-aggressive, that CAN reduce risk of future heart attack, stroke, and peripheral vascular disease. This sounds like a tall-order for a short four-part Series, but cardiovascular risk reduction with reduced morbidity and mortality are within our grasp!
- What is Atherosclerosis and how can it be Measured?
Atherosclerosis simply means destruction (sclerosis) of the arterial wall (athero). The Arterial Wall, in addition to the one-cell thick lining (endothelium) between the flowing blood and the wall, is composed of three circular layers: intima (I), media (M), and adventitia (A) [Fig. 1]. The Lumen (L) is the open center portion of the artery in which oxygen-rich blood flows. Smooth Muscle, which is a protein, is primarily located in the media of the arterial wall and provides strength. Atherosclerosis importantly involves the movement of smooth muscle cells from the media of the arterial wall to the intima. In the early stages of this process, the changes can be subtle. In addition to thickening of the intima, disease in the arterial wall develops involving lipid pools, thrombus, necrosis, fibrous caps, calcification, plaque rupture, and disruption of the endothelial surface (interface between the wall and flowing blood). The following plates (Fig. 1) show a normal arterial cross-section on the right with a thin wall and thin intima and smooth endothelial surface. The diseased artery on the left shows a thickened wall, thickened intima, and irregular endothelial surface. This is a clear picture of early atherosclerosis.
It has become clear to cardiovascular specialists and other physicians that the focus of attention in preventing and treating cardiovascular disease must shift toward the arterial wall. The key to reducing cardiovascular risk is understanding endothelial dysfunction and reduced compliance (i.e. reduced elasticity). For illustration purposes, a balloon has a HIGH compliance, where a steel pipe has a LOW compliance.
Soteria Medical, LLC has been working from the tenant that early atherosclerosis increases the thickness of the arterial wall (occurring well in advance of blood flow alterations detected by other diagnostic measures). The major technical challenge was to devise an accurate method to measure local arterial volume change. This was accomplished in 2014 with FDA clearance of the Soteria Cardiac Platform which accurately and noninvasively measures arterial compliance in the lower extremity and closely correlates with coronary and cerebrovascular disease.
- What are the Risk Factors for Atherosclerosis and how can they be Reduced?
The lead author of this Series (jr) was involved in vascular surgery for 40 years and kept careful records as to the presenting cardiovascular risk factors in patients requiring vascular surgery. Other investigators, who have practiced cardiology and other cardiovascular-related specialities, over the same period, believe this presented material regarding risk factors, is similar to their experience. Table 1 illustrates in 600 consecutive patients undergoing vascular surgery, the percentage of those patients presenting with the six major cardiovascular risk factors. Each Risk Factor is discussed separately in subsequent sections. The Second Installment will cover Tobacco Use, Hypertension, and Diabetes. The Third Installment will discuss Elevated Blood Lipids, Obesity, and Lack of Exercise.
|Cardiovascular Risk Factor||Prevalence in Vascular Surgical Patients (%)|
|Tobacco Use (Current and Prior)||75|
|Hypertension (Per Current AHA Guidelines)||42|
|Diabetes (Fasting Glucose >126 mg/dl x 2 Samples||23|
|Elevated Blood Lipids (Per Current AHA Guidelines)||22|
|Obesity (Body Mass Index > 25)||25|
|Lack of Exercise (< 20 minutes per week)||40|
- Soterogram Results
The Soterogram is the flagship module of the Soteria Cardiac Platform (includes 5 Modules). The other Platform modules are: (i) Registration, (ii) Framingham Risk Profiling and Body Mass Index, (iii) Ankle / Brachial Index (ABIgram), and (iv) Multilevel Lower Extremity Pressure Measurements for evaluation of lower extremity peripheral arterial disease (PADogram). These modules will be briefly discussed in other Sections of this series.
The Soterogram has been developed to provide physicians with information that will be helpful with both Primary and Secondary Prevention of Cardiovascular Disease. Early-onset atherosclerosis is known to cause the arterial wall to thicken and become stiffer. This increased stiffness has been referred to as loss of elasticity and/or loss of viscoelastic properties. Actually, in pathophysiology, this is also referred to as Loss of Compliance, where Compliance is technically defined as (Δ volume / Δ pressure).
The Soterogram is the first medical device cleared by the FDA to accurately and noninvasively measure local Arterial Compliance. Due to the prominance of Smooth Muscle Cells in the coronary arteries, the coronary arteries, more than other arterial bed, develop early atherosclerosis. The arterial wall distribution of Smooth Muscle Cells, in addition to Elastin and Collagen, associated with the distal abdominal aorta, femoral arteries (common and superficial), and popliteal artery, mirror the protein distribution in the coronary arteries. The Soterogram measures Arterial Compliance in the Femoral and Popliteal Arteries and uses this data to predict the status of the Coronary Arteries, as regards atherosclerosis.
- Blood Pressure: The measurement of Brachial Blood Pressure is taken by the Platform using the FDA cleared SP-10 Oscillographic Method of determining Systolic Pressure, Diastolic Pressure, Pulse Pressure, Mean Pressure and Heart Rate. The SP-10 technology has been shown to exceed the accuracy of Korotkoff Sounds and Continuous–Wave Doppler Ultrasound. The Soterogram takes at least three separate complete measurements of Blood Pressure over a period of 12 to 15 minutes. One measurement is taken at Registration; the other two measurements are taken at the beginning (1st BP) and end of Soterogram testing (2nd BP). These measurements are averaged to set Pulse Pressure (Mean PP).
The physician interpretating this report should note the absolute level of blood pressure and heart rate, as well as, the variation of these parameters in the three measurements. Since these are repeated-measures, the combined accuracy is high. It is assumed each physician has personal Criteria for Normal and Abnormal Blood Pressure and Heart Rate. The American Heart Association (AHA), in general terms, believes that a Systolic Pressure > 140 mmHg is abnormal. The abnormal level for Diastolic Pressure is > 90 mmHg. The AHA and many physicians believe tachycardia is present when Heart Rate is > 90 bpm and that bradycardia is present when Heart Rate is < 60 bpm. Clearly, normotension is better than hypertension; further, hypertension is a sensitive parameter when dealing with atherosclerosis.
It has been shown that hypertension is present in 42% of individuals with significant atherosclerosis. This frequency is only exceeded by past and current cigarette smoking. Further, reduced Heart Rate is often associated with satisfactory cardiovascular tone.
- Cuff Pressures [Pcuff (1-5)]: The first measurement of Blood Pressure (1st BP), sets the pressures to be used in the lower extremity cuffs during the Arterial Volume measurements. Essentially, the patient’s Mean Pressure (1st Pmean) is determined. The five cuff pressures are: (i) 10 mmHg below Pmean, (ii) 5 mmHg below Pmean, (iii) Pmean, (iv) 5 mmHg above Pmean, and (v) 10 mmHg above Pmean. This mosaic of pressures is needed for accuracy (repeated-measures) and to account for arterial wall mechanics (i.e. expansion and collapse).
- Calf and Thigh Segmental Volume Measurements (Vm):
Five meassurements of Total Arterial Volume Change (Vm) under the respective cuffs (Calf and Thigh) are measured and displayed in milliliters (ml) separately for each Cuff Pressure (Pcuff).
These are intermediate measurements and are not used directly by the Interpreting Physician. The Vm versus Pressures Chart is helpful in graphically affirming the expected study results and therefore study integrity.
- Calf Max Vm50 and Thigh Max Vm50: These parameters are calculated by the Platform and refer to the Maximum Volume Change under the Calf Cuff and Thigh Cuff during the patient’s Cardiac Cycle. The value is in ml and is normalized to a Pulse Pressure of 50 mmHg. This normalization is performed to expedite the direct comparison of these parameters between patients.
Since, Arterial Compliance is defined as Δ volume / Δ pressure, the larger the Max Vm50, the greater the Arterial Compliance. Reduced Arterial Compliance is a hallmark of atherosclerosis. Please consider the following cardiovascular physiology. For a standard Cardiac Output of 5 liters/min (5000 ml/min) with a Heart Rate of 70 bpm, the Stroke Volume will be 71 ml (5000 ml / 70 bpm). Blood is essentially an incompressible fluid. This means the Systemic Arterial System must in-total over a Cardiac Cycle accommodate this infused volume (i.e. 71 ml).
Soteria FDA / NIH Alpha, Beta, and Clinical Studies have demonstrated in normal subjects that Calf Max Vm50 averaged 2.0 ml and Thigh Max Vm50 averaged 3.5 ml (Total: 5.5 ml per Combined Calf and Thigh Segments – Two Limbs, therefore would total 11 ml). It is physiologically consistent that 11 ml or approximately 15% of the Stroke Volume would be absorbed by the combined expansion of the Calf and Thigh Arterial Beds.
As will be described, the Calf Max Vm50 and Thigh Max Vm50 will be combined to form a single Soterogram Score.
This ends the first installment of a four-part series. The second installment, scheduled for next month, will begin by illustrating how the above described measurements are used to establish the level of atherosclerosis and continue the discussion in the arena of risk factor reduction.
By Jeffrey K. Raines and Zoraida Catherine Navarro
Professor Jeffrey K. Raines was responsible for the Soteria Cardiac Platform including its design and module development. After attending Harvard Medical School and training in the Surgery Department of Massachusetts General Hospital, Dr. Raines received a PhD in Engineering from MIT. His thesis title was Diagnosis and Analysis of Arteriosclerosis in the Lower Limbs from the Arterial Pressure Pulse; this work outlined the construction and testing of a new medical device called the Pulse Volume Recorder (“PVR”). This device was built and distributed by Life Sciences, Inc. and became a central device in the diagnosis of peripheral vascular disease and in the development of vascular diagnostic laboratories around the world. Dr. Raines was Chief of Research at the University of Miami Department of Surgery until his retirement in 2004 and Director of the Miami Vein Center from 2004 to 2010. Dr. Raines has developed Soteria’s technology over a period of 43 years and now that it has FDA clearance, he looks forward to expanding the use of the Platform worldwide. Dr. Raines is Emeritus Professor of Surgery at Harvard Medical School and the University of Miami. Dr. Raines is a Senior Member of the Society of Vascular Surgery, was elected to American College of Cardiology in 1975 and the Harvard Surgical Society in 2006. Dr. Raines lives in Homestead, Florida with Glo, his wife of many years; they have four children and five grandchildren.
Zoraida Catherine Navarro, MD practices at the Vein Center of the Palm Beaches and Navarro Dermatology Skin & Vein Care. Dr. Navarro earned a B.S. from MIT and medical degrees from Boston University School of Medicine and later, the University of Miami School of Medicine. As a member of the Palm Beach County Medical Society, she helped establish the Women Physicians Medical Society. In 1986, after a year as Director of Medicine for the Wellington Regional Medical Center, Dr. Navarro established the Vein Center of the Palm Beaches in West Palm Beach, an internal medicine solo practice with specialties in varicose vein sclerotherapy, skin care, and holistic approaches.