9P21 – 9P21 is also known as “the heart attack gene.” 9P21 is a location on the 9th chromosome. It was initially associated with cancers, then heart attack, then diabetes. There are multiple specific points (SNPs) and numerous genetic variations leading to diabetes as well as weak artery walls. 9P21 is very common.
ABI – Ankle Brachial Index – The ABI is a comparison of the ankle and arm blood pressure. If the ankle pressure is low compared to the arm, this implies obstructive plaque in the arteries. This test is simple in concept but requires robust quality systems.
ABIM – American Board of Internal Medicine
ACC – American College of Cardiology
ACC/AHA Guidelines – The ACC/AHA Clinical practice guidelines were written by the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. For purposes of this book, the primary guideline will be the 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease. MEMBERS are volunteer scientists and healthcare professionals appointed by the leadership of the ACC and AHA.
Agatston Score – The Agatston score is a standardized scoring system for the calcium score.
AHA – American Heart Association
ACP (American College of Physicians) – The ACP is a national organization of internists, who specialize in the diagnosis, treatment, and care of adults
Angiography, angiogram – Angiography is the process. An angiogram is an image. Same as cardiography or coronary angiogram.
Angioplasty – Angioplasty is the reconstruction of an artery. The term angiogram usually refers to using a coronary cath to clear a narrowed artery. This is also called PCI. See PCI.
Apolipoprotein – An apolipoprotein is the protein portion of a lipoprotein. Usually, lipoproteins consist of lipids and proteins bound together. Apolipoproteins are the protein portions without the lipid. See lipoprotein, LDL, and HDL.
Arteriography, arteriogram – Arteriography is the process or imaging an artery to understand the anatomy. This is most often done for cv disease. The purpose is to assess the distribution of plaque. Arteriogram is the image. It’s the same as angiography, angiogram. See cardiography, cardiogram, or coronary angiogram.
Atherosclerosis – Atherosclerosis is the condition of having plaque in the artery walls. It is also sometimes called arteriosclerosis.
Autophagy – This is a cellular biology term. It refers to the cell disgesting and recycling deteriorated cellular materials for building blocks and energy. This first involves digesting these cellular parts into proteins, carbohydrates, and fats. The deteriorated (or senescent) materials include broken-down cell parts, such as mitochondria. (See Senescent and Mitochondria)
Biomarkers – Biomarkers are measurable substances in an organism whose presence is indicative of some phenomena such as disease, infection, or environmental exposure.
BMI (Body Mass Index) – BMI is an estimate of body fat based on height and weight. Many criticize BMI since it does not account for muscle. The risk factor is body fat, not muscle. The BMI typically underestimates fat mass in women and overestimates it in men. Arnold Schwarzenegger had a BMI of 30. His height was 6’2,” and he weighed 235 pounds when he won the Mr. Olympia award. His body fat was only 8%. The “Schwarzenegger adjustment” of the BMI incorporates waist size. Some have proposed RFM (Relative Fat Mass) as a better estimate. It’s not very well known. See RFM.
Cardiovascular (CV or cv) – Cardiovascular is a conflated term. The roots of the word imply heart and vascular disease. But the real driver is arterial health. Arterial disease causes the vast majority of heart attacks, stroke, kidney, and eye disease. In other words, arterial health drives chronic diseases. Chronic diseases and aging are arterial health problems. Arterial disease of the heart causes most deaths. Arterial disease impacting the brain causes most strokes (and maybe most dementia). So cv disease is the biggest killer and disabler in the world. The vast majority of arterial disease is caused in turn by insulin resistance (prediabetes or metabolic syndrome).
CAD (Coronary Atherosclerotic Disease) – CAD is the condition of having plaque in the arteries of the heart
Carotid Artery Sonography – See Carotid Ultrasound
Carotid B mode Ultrasound – Carotid B mode ultrasound is a CIMT. It uses ultrasound and information technology software to analyze the carotid artery wall.
Carotid Duplex Ultrasound – A Carotid Duplex includes both B mode (CIMT) and Doppler studies.
Carotid Ultrasound – The use of ultrasound technology to examine the carotid artery. This term alone does not differentiate between very different techniques: B mode or CIMT (which looks at artery wall structure) and Doppler (which looks at flow). Duplex includes both B mode (CIMT) and Doppler.
Catabolic Metabolism – Catabolic metabolism breaks down or oxidizes materials. Autophagy is part of catabolic metabolism. Anabolic metabolism builds them up. (See Anabolic metabolism)
Cath angiogram – see coronary angiogram.
Catheter – A catheter is a thin, hollow tube. For purposes of this book, catheters are used for injecting Xray contrast dye into the arteries that supply the heart.
CHL/Quest – CHL(Cleveland Heart Labs) originally left Cleveland Clinic Labs to stand alone as a national lab focusing on specialized cv testing. CHL was purchased three years ago by Quest, a national general medical reference lab.
Cholesterol – Cholesterol is a waxy substance found in the blood. It is a crucial component of cell walls, hormones, vitamin D, brain cells, and bile (materials that help digest food). Cholesterol is a lipid. (See lipid)
Choosing Wisely – an educational campaign that involves contributing health information to Wikipedia. It is part of the Consumer Reports WikiProject and organized by the ABIM (American Board of Internal Medicine ) Foundation. Choosing Wisely seeks to provide consumers and providers of healthcare services with information about health diagnostic procedures, which physicians frequently recommend despite a lack of evidence-based research demonstrating the usefulness of those procedures.
CIMT (Carotid Intima-Media Thickness) – A CIMT is a measurement of plaque in the arteries of the neck using ultrasound technology and software analytics. It’s not invasive, inexpensive, and radiation-free. It’s also the only test that provides critical information on whether plaque is soft, inflamed, and dangerous. The CIMT suffers from a lack of standardization. We discuss how to overcome this disadvantage.
Cochrane Library – The Cochrane Library (named after Archie Cochrane) is a collection of databases in medicine and other healthcare specialties provided by Cochrane and other organizations. At its core is the collection of Cochrane Reviews, a database of systematic reviews and meta-analyses which summarize and interpret the results of medical research. The Cochrane Library aims to make the results of well-conducted controlled trials readily available and is a key resource in evidence-based medicine.
Cohort – A cohort is any group that shares an experience. The term is used to describe studies like Framingham that follow populations through an experience or a period of time.
CAD – CAD is an acronym for Coronary Artery Disease.
Coronary Angiogram – A Coronary Angiogram is a procedure that uses dye injected into the heart’s arteries for Xray imaging. The injection is usually done using a catheter inserted into the femoral artery at the groin and threaded up through the aorta to the heart. Other names include coronary artery angiogram, cath angiogram, heart catheterization, cardiac cath.
Coronary Artery Calcium Score (Calcium Score) – A calcium score is a measurement of calcium in the arteries of the heart using CT imaging. The presence of any calcium indicates there is plaque in these arteries. This test is easily accessible, inexpensive, and well standardized. It’s a great screen. But it’s not great for tracking progress (monitoring).
CRP (C-Reactive Protein) – CRP is a protein made by the liver in reaction to many types of inflammation. Because elevated CRP is consistently associated with cv disease, including heart attack and stroke, it’s a biomarker – or predictor – of heart attacks. But the inflammation measured can start from any type of cell damage, ranging from burns to cuts to flu shots. The biggest problem with CRP is that elevated levels can be due to those injuries. For example, two days after a flu shot, 66% of patients have CRP elevation.
CTA (Computerized Tomography Angiogram) – CTA is a measurement and imaging of plaque and anatomy of the coronary arteries using intravenous Xray dye and CT imaging. Recent studies indicate this could bring much clarity to the usual stress testing. There has been a rapid “learning curve,” resulting in the need to encourage the use of the CTA and the use of the latest equipment to avoid radiation.
CV (also cv, cardiovascular) – CV means relating to the heart and blood vessels. CV is a confusing term. It’s rooted in a conflated concept (cardiac vs. vascular). See cardiovascular.
CVD – CVD is an acronym for Coronary Vascular Disease. It also sometimes means the more general term Cardio Vascular Disease.
Doppler Ultrasound – A Doppler ultrasound of an artery which estimates flow based on changes in frequency (pitch). Doppler studies measure flow, not plaque. Most heart attacks occur in individuals with insufficient plaque to detect blood flow abnormalities.
Embolism – An embolism is the process of a blockage-causing piece of material, inside a blood vessel. The embolus may be a blood clot (thrombus), a fat globule (fat embolism), a bubble of air or other gas (gas embolism), or foreign material. (See embolus and thrombus)
Embolus – An embolus is a blood clot, air bubble, piece of fatty deposit, or another object which has been carried in the bloodstream to lodge in a vessel and cause an infarction, or tissue death. (See thrombus)
Endemic – “Stable” or recurring transmission in a population. (See epidemic and pandemic)
Epidemic – More than the usual number of cases of a disease. (See endemic and pandemic)
Epizootic – A disease in a human whose primary host is animal.
Framingham Risk Calculator – a predictive equation developed from the Framingham Heart Study. The ACC/AHA Preventive standards committee recommends that doctors initiate a cv risk evaluation using a Franigham risk estimator. The Framingham equation incorporates demographics such as age, gender, and race. Other cv risk factors are included as well, such as smoking. Different Framingham risk calculators vary in the list of risk factors they include.
HDL (High-Density Lipoprotein) – Some people still call HDL the “good” cholesterol because higher levels are markers for decreased cv risk. HDL carries cholesterol from other parts of the body back to the liver for removal. HDL includes cholesterol and a different carrier protein from LDL.
Haptoglobin 2 – This is a genetic variation of haptoglobin. Usually, haptoglobin clears arteries of deteriorated, oxidized hemoglobin. Haptoglobin 2 is deficient in this vital role. That appears to have created an advantageous resistance to malaria for carriers of haptoglobin 2. The trade-off is accelerated oxidation (inflammation) of tissues like artery walls. The precursor molecule (zonulin) causes other inflammatory diseases, such as leaky gut and Hashimoto’s thyroiditis.
Heart Catheterization – see coronary catheterization.
Hemoglobin A1c (also called A1c or glycated hemoglobin) – Your hemoglobin with glucose attached. The A1c test evaluates the average amount of glucose in the blood over the last 2 to 3 months by measuring the percentage of glycated hemoglobin in the blood.
hsCRP – high sensitivity CRP. An hsCRP is simply a CRP test showing much lower levels of CRP than the original CRP measurement. CRP ranges from 10 to 1,000 mg/L, whereas hsCRP values range from .5 to 10 mg/L. For this book, we use the terms interchangeably.
IF (Intermittent Fasting) – Abstaining from food for various periods. Most people are referring to the practice of skipping breakfast when they use the term Intermittent Fasting. It can also mean TRE. OMAD is also a form of IF. (See OMAD and TRE)
IMT (Intima-Media Thickness) – a shortened, generic form of CIMT (see CIMT)
Infarction – loss of blood supply due to an organ or region of tissue, usually by an embolus or thrombus
Inflammation – Inflammation is a vital part of the immune system’s response to injury and infection. It involves signaling and defense coordinated by multiple immune cell lines, enzymes, and biomarkers. (See Inflammation panel, CRP, LP-PLA2, and MPO)
Inflammation Panel – An inflammation panel is a panel of tests used to measure inflammation. In this book, we’re referring to our preferred panel, developed by CHL, now part of Quest national labs. It includes hsCRP, Lp-PLA2, MPO, and MACR.
Interleukin 6 (IL6) – IL6 is a protein (and gene) associated with inflammation. Rheumatoid arthritis and Kaposi’s sarcoma are associated with increased IL6.IL6 is also a biomarker for cv inflammation.
Invasive angiography, angiogram – See angiogram. The differentiating term here is “invasive.” It means this angiogram was done as part of a cardiac cath procedure, not as a simple CT angiogram.
IR (Insulin Resistance) – The decreased response of the muscle and liver cell membrane to insulin receptors. IR leads to an inability to get sugar out of the blood and into the cell, where it does less damage. The most common cause of CV inflammation and plaque. Also called Prediabetes or Metabolic Syndrome. (There are some slight technical differences, but they are not significant for this book.) IR can lead to diabetes, CV inflammation, plaque, heart attack, stroke, dementia, blindness, erectile dysfunction, and other chronic diseases associated with aging.
IVUS – Intravascular UltraSound. Use of Ultrasound to create images of arterial plaque from inside the artery during a cardiac cath procedure. This procedure is still investigational. It’s beyond the scope of this book.
Insulin Response – this is a term for a test of insulin values added to each glucose measurement in an OGTT. An insulin response study tells the amount of insulin required to achieve a blood sugar level.
Insulin Survey – an OGTT with an Insulin Response. There are different values and forms of these. The two most common for purposes of this book are the Insulin Survey done through Quest labs for Dr. Brewer’s clinic and the Kraft Insulin Survey. Both tests include an OGTT, which is at least 8 hours fasting followed by a glucose challenge and serial measurements of blood glucose and insulin levels. The Quest test uses 75 grams of glucose and measures blood glucose and insulin at 1 and 2 hours. The Kraft insulin survey typically uses 100 grams of glucose followed by blood glucose and insulin tests at 30 minutes and 1, 2, 3, and 4 hours.
Ischemia (or ischaemia) – Ischemia is a restriction in blood supply to tissues, causing a shortage of oxygen. Cell metabolism requires oxygen. Ischemia is generally caused by problems with blood vessels, with resultant damage to or dysfunction of tissue. ISCHEMIA is also the name of a recent randomized clinical trial that demonstrated bypass grafts don’t prevent heart attack.
JACC – Journal of the American College of Cardiology
kDa (kiloDalton) – A measure of molecular weight
Kraft Insulin Survey – The Kraft Insulin Survey is one of the best methods measuring insulin resistance. It’s similar to an OGTT. But it includes insulin measurements at all the blood glucose checks. It also uses 100 grams of glucose instead of 75. And it typically goes three or four hours instead of two. (See OGTT)
LDL (Low-Density Lipoprotein) – LDL is sometimes called “bad” cholesterol because oxidized forms of LDL are the primary component of arterial plaque. Cholesterol is a type of fat or lipid. So it doesn’t mix well with blood serum, which is 90% water. So the body makes proteins to bind lipids for transport in the serum. HDL cholesterol includes cholesterol and a different protein.
Lipid – The term lipid is a class of compounds including fats, waxes, and oils. Lipids are organic, meaning carbon-based. They dissolve in other carbon-based compounds, but not water. But they are major components of the body. Therefore the body has made proteins to transport lipids such as cholesterol within the body. (See lipoproteins, cholesterol, LDL)
Lipoproteins – proteins made by the body to transport lipids
Lp-PLA2 (LipoProtein-associated PhosphoLipase A2) – An enzyme that plays a role in cv inflammation. It is released by a family of immune cells (mast cells, macrophages, T cells, and foam cells) to break down plaque.
For medical scientists – It hydrolyzes oxidized phospholipids in LDL. The PLA2G7 gene codes it. It’s a 45 kDa protein made of 441 amino acids. In the blood, it travels mainly with LDL. Less than 20% is associated with HDL. A meta-analysis involving 29,036 participants in 32 prospective studies found that Lp-PLA2 levels correlate with increased risk of coronary heart disease and stroke. (Thompson 2010)
Lumen – A lumen is an opening, the inside space of a tubular structure. The lumen is the inside of the arterial tube. CV plaque is commonly assumed to be inside the lumen of the artery. Oxidized LDL gets trapped between the inside layer (intima) and the middle layer (media). This specific location is essential because it leads to the inability to predict heart attack and stroke. The mechanism of most heart attacks and strokes involves liquid plaque escaping from the artery wall and causing a clot.
MACR (MicroAlbumin Creatinine Ratio) – a measurement of microscopic amounts of the protein albumin in the urine. Albumin is a major protein usually present in the blood, but virtually no albumin is present in the urine when the kidneys are functioning correctly. MACR is used to screen for kidney disease in people with chronic diseases such as hypertension or diabetes. Microalbuminuria is an independent and robust indicator of increased cv risk among individuals with and without diabetes. (Stehouwer 2006)
MEDLINE® – MEDLINE is the U.S. National Library of Medicine® (NLM) premier bibliographic database that contains more than 25 million references to journal articles in life sciences with a concentration on biomedicine. A distinctive feature of MEDLINE is that the records are indexed with NLM Medical Subject Headings (MeSH®). MEDLINE is the online counterpart to MEDLARS® (MEDical Literature Analysis and Retrieval System) that originated in 1964.
The great majority of journals are selected for MEDLINE based on the recommendation of the Literature Selection Technical Review Committee (LSTRC), an NIH-chartered advisory committee of external experts analogous to the committees that review NIH grant applications.
MESA Score – The Multi-Ethnic Study of Atherosclerosis (MESA) score is a cv risk calculator. You can find it at (https://www.mesa-nhlbi.org/calcium/input.aspx). It incorporates CAC score in addition to the traditional risk factors of demographics, cholesterol, systolic blood pressure, diabetes, smoking, family history of CHD, and the use of hypertension or cholesterol medications. The MESA calculator is a result of the study of the same name. (Budoff 2009)
Meta-analysis – A meta-analysis is a study that looks at many other studies conducted on a particular subject. Meta-analysis papers (also called literature reviews or lit reviews) are systematic reviews regarding the available or published science in a field of study.
Metabolic Syndrome – see Insulin Resistance and Prediabetes.
Mitochondria – Mitochondria are the powerhouses or furnaces of the cell. Mitochondria burn energy sources.
MPO (Myeloperoxidase) – MPO is an enzyme released by a family of immune cells to carry out out antimicrobial activity. It is part of the CHL/Quest cv Inflammation panel, along with CRP, LP-PLA2, and MACR. Myelo means bone marrow, and peroxidase is a type of enzyme. MPO has a green heme pigment component leading to the greenish color of mucus. MPO blood levels indicate the risk of coronary artery disease. (Zhang 2001)
For doctors – MPO is a peroxidase encoded by the MPO gene on chromosome 17. It produces acids to carry out an antimicrobial activity. It’s a 150 kDa protein consisting of two 15 kDa light chains and two glycosylated heavy chains bound to a prosthetic heme group.
MPI (Myocardial Perfusion Imaging) – Myocardial perfusion imaging (MPI) is a non-invasive imaging test that shows how well blood flows through (perfuses) your heart muscle. It can show areas of the heart muscle that aren’t getting enough blood flow. This test is often called a nuclear stress test.
Myocardium – Myocardium is the muscle of the heart. The prefix “myo” means muscle.
NCEP (The National Cholesterol Education Program) – The NCEP is a program managed by the National Heart, Lung, and Blood Institute, a division of the National Institutes of Health. Its goal is “to reduce increased cardiovascular disease rates due to hypercholesterolemia (elevated cholesterol levels) in the United States of America.” The program has been running since 1985.
Nomogram – A nomogram is a graphical calculation tool. The only one used in this book is the standard IMT measurement for men and women by age.
OGTT (Oral Glucose Tolerance Test) – A test for Insulin Resistance. The OGTT is a measurement of Insulin Resistance. There are multiple types. All involve fasting for eight hours, followed by a glucose challenge and then serial measurements of blood glucose. The OGTT measures the body’s ability to metabolize carbohydrates. The most common problem is the resistance of the insulin receptors in the muscle and liver cell membranes. IR leads to prediabetes, diabetes, CV inflammation, plaque, heart attack, stroke, dementia, blindness, erectile dysfunction, and other chronic diseases associated with aging. The Kraft Insulin Survey is a more detailed test, adding insulin levels to all blood sugar tests. Most Kraft Insulin Surveys also use 100 grams of glucose instead of 75. (See also Kraft Insuling Survey)
OMAD – One Meal per Day. A popular method for weight loss. It also closes the feeding or eating window. OMAD tends to decrease caloric intake. It also stimulates the body to switch back and forth between catabolic and anabolic metabolism. Satchin Panda, Valter Longo, and others have recently demonstrated that this switching improves health. (See Catabolic, Anabolic, Autophagy, IF and TRE).
Pandemic – There are multiple definitions, but it includes clusters (or epidemics) in multiple countries and local transmission occurring in these multiple populations. (See endemic and epidemic)
PCI (Percutaneous Coronary Intervention) – A PCI is the process of using a catheter to clear a narrowed artery of the heart. (See Stent or Angioplasty)
Perfusion – Perfusion is the passage of blood, a blood substitute, or other fluid through the blood vessels or other natural channels in an organ or tissue.
PET (Positron Emission Tomography) – A PET scan is a process of using a radioactive tracer to generate images tending to be more detailed than other nuclear imaging tests. See stress tests.
Plaque – A plaque is a distinct region of damage to the intimal lining of the artery resulting from damage or deposits. Plaques are found within the walls of arteries, not in the lumen, or inside of the artery. The term plaque is also often used in related fields of study: dentistry and study of Alzheimer’s dementia. In dentistry, these plaques are made mostly of bacterial residues. In Alzheimer’s dementia, the plaques are made of a protein called beta-amyloid.
Prediabetes – see Insulin Resistance
R0 (R zero, or R naught) – A measure of disease spread. With SARS CoV-2, the R0 has been measured early on at about 2.7 that means that each case has been infecting 2.7 new cases.
RFM (Relative Fat Mass) – RFM is another method of estimating fat mass suggested as a better option than the BMI. It uses only waist circumference and height. It was developed using NHANES data. It avoids the typical BMI errors of underestimating fat mass in women and overestimating it in men.
Sarcopenia – loss of muscle mass. The root “sarco” means muscle, and the root “penia” means loss. Sarcopenia is strongly related to age beyond 65 years, inflammation, prediabetes, and death.
Senescence – the condition or process of deterioration with age.
Sensitivity – Sensitivity is a test characteristic. Sensitivity is the ability to identify those with the disease correctly. It’s also called the true positive rate. That’s the percentage of true positive test results divided by all tested. (See Specificity)
Serum – Serum is the liquid part of the blood.
Specificity – Specificity is a test characteristic. Specificity is the ability to identify those without the disease correctly. It’s also called the true negative rate. That’s the percentage of true negative test results divided by all tested.
SPECT (Single Photon Emission Computerized Tomography) – SPECT is a process of using a radioactive tracer to generate images tending to be more detailed than other nuclear imaging tests. See stress tests.
Stress test – A stress test is a procedure used to measure how the heart works during physical activity. These typically involve assessment heart function while exercising on a treadmill, exercise bike, or during drug-induced heart stress. Stress tests are by far the most common method of looking for cardiovascular risk. They have many problems, such as high false positive and false negative tests when used to predict heart attack and stroke. Even conservative standards bodies like the American College of Cardiology, the Internal Medicine Foundation, and the American College of Family Practitioners agree that doctors and patients are using too many stress tests. Researchers have developed multiple ways of assessing heart function during the test to improve the stress test. Examples include EKG, physical symptoms such as breathlessness and fatigue, echo/ultrasound, and multiple forms involving radiation such as MRI, SPECT, and PET scans.
Study – We use two meanings of this word in this book/blog. The first is a test procedure, such as a nuclear stress test. The second is a research project, such as the COURAGE or ORBITA trials.
Thrombus – A thrombus is a blood clot formed in situ within the vascular system of the body and impeding blood flow.
TRF (Time-Restricted Feeding) or TRE (Time-Restricted Eating) – TRF or TRE are acronyms referring to narrowing the time of day for caloric input. This tends to decreases caloric intake. It also stimulates the body to switch back and forth between catabolic and anabolic metabolism. Satchin Panda, Valter Longo, and others have recently demonstrated that this switching improves health. (Longo 2016).