Four-Volume Series on Four-Volume Series on Cardiovascular Diseases:
Causes, Risks and Management
Dr. Pearlman, MD, PhD, FACC
Editor
Leaders in Pharmaceutical Business Intelligence (LPBI) Group
This Series is positioned as Academic Textbooks for Training Residents in Cardiology and Texts for CEU Courses in Cardiology
[Hardcover, Softcover, e-Books]
- CVD 1: Causes of Cardiovascular Diseases
- CVD 2: Risk Assessment of Cardiovascular Diseases
- CVD 3: Management of Cardiovascular Diseases
- CVD 4: Cardiac Imaging
VOLUME TWO
Risks of Cardiovascular Diseases
Justin D. Pearlman MD ME PhD MA FACC, Editor
Leaders in Pharmaceutical Business Intelligence (LPBI) Group, Boston
Other books on Cardiovascular Diseases by the same Editor
Cardiovascular Diseases: Causes, Risks and Management
VOLUME ONE
Causes of Cardiovascular Diseases
Justin D. Pearlman MD PhD MA FACC, Editor
Leaders in Pharmaceutical Business Intelligence (LPBI) Group, Boston
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VOLUME THREE
Management of Cardiovascular Diseases
Justin D. Pearlman MD ME PhD MA FACC, Editor
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VOLUME FOUR
Cardiac Imaging
Justin D. Pearlman MD ME PhD MA FACC, Editor
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Other e-Books in the BioMedicine e-Series
Series A: e-Books on Cardiovascular Diseases
Content Consultant: Justin D Pearlman, MD, PhD, FACC
Volume One: Perspectives on Nitric Oxide
Sr. Editor: Larry Bernstein, MD, FCAP, Editor: Aviral Vatsa, PhD and Content Consultant: Stephen J Williams, PhD
Available on Kindle Store @ Amazon.com
http://www.amazon.com/dp/B00DINFFYC
Volume Two: Cardiovascular Original Research: Cases in Methodology Design for Content Co-Curation
Curators: Justin D Pearlman, MD, PhD, FACC, Larry H Bernstein, MD, FCAP and
Aviva Lev-Ari, PhD, RN
- Causes
- Risks and Biomarkers
- Therapeutic Implication
Available on Kindle Store @ Amazon.com
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Volume Three: Etiologies of Cardiovascular Diseases: Epigenetics, Genetics and Genomics
Curators: Larry H Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN
- Causes
- Risks and Biomarkers
- Therapeutic Implications
Available on Kindle Store @ Amazon.com
http://www.amazon.com/dp/B018PNHJ84
Volume Four: Regenerative and Translational Medicine: The Therapeutics Promise for Cardiovascular Diseases
Curators: Larry H Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN
- Causes
- Risks and Biomarkers
- Therapeutic Implications
Available on Kindle Store @ Amazon.com
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Volume Five: Pharmaco-Therapies of Cardiovascular Diseases
Volume Curators: Larry H. Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN
- Causes
- Risks and Biomarkers
- Therapeutic Implications
Work-in-Progress
Volume Six: Interventional Cardiology and Cardiac Surgery for Disease Diagnosis and Guidance of Treatment
Volume Curators: Justin D Pearlman, MD, PhD, FACC and Aviva Lev-Ari, PhD, RN
- Causes
- Risks and Biomarkers
- Therapeutic Implications
Work-in-Progress
In addition to the Six Volumes of SERIES A: Cardiovascular Diseases, Not included in SERIES A is a Four Volume Series by Dr. Pearlman, Editor, on Cardiovascular Diseases, positioned as Academic Textbooks for Training Residents in Cardiology and Texts for CEU Courses in Cardiology [Hardcover, Softcover, e-Books].
- CVD 1: Causes of Cardiovascular Diseases
- CVD 2: Risk Assessment of Cardiovascular Diseases
- CVD 3: Management of Cardiovascular Diseases
- CVD 4: Cardiac Imaging
Series B: e-Books on Genomics & Medicine
Content Consultant: Larry H Bernstein, MD, FCAP
Volume One: Genomics Orientations for Personalized Medicine
Sr. Editor: Stephen J Williams, PhD
Editors: Larry H Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN
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Volume Two: Latest in Genomics Methodologies for Therapeutics: Gene Editing, NGS & BioInformatics, Simulations and the Genome Ontology
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Volume Three: Institutional Leadership in Genomics
Editors: Aviva Lev-Ari, PhD, RN and TBA
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Content Consultant: Larry H Bernstein, MD, FCAP
Volume One: Cancer Biology & Genomics for Disease Diagnosis
Sr. Editor: Stephen J Williams, PhD
Editors: Ritu Saxena, PhD, Tilda Barliya, PhD
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Volume Two: Cancer Therapies: Metabolic, Genomics, Interventional, Immunotherapy and Nanotechnology in Therapy Delivery
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Larry H Bernstein, MD, FCAP and Stephen J Williams, PhD
Guest Authors:
Dror Nir, PhD and Tilda Barliya, PhD, Demet Sag, PhD, Ziv Raviv, PhD and Aviva Lev-Ari, PhD, RN
2017
Volume Three: Cancer Patients’ Resources on Therapies
Sr. Editor: TBA
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Content Consultant: Larry H Bernstein, MD, FCAP
Volume One: Metabolic Genomics and Pharmaceutics
Author, Curator and Editor: Larry H Bernstein, MD, FCAP
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Volume Three: Immunology and Therapeutics
Authors, Curators and Editors: Larry H Bernstein, MD, FCAP and TBA
Series E: Patient-centered Medicine
Content Consultant: Larry H Bernstein, MD, FCAP
Volume One: The VOICES of Patients, HealthCare Providers, Care Givers and Families: Personal Experience with Critical Care and Invasive Medical Procedures
Author, Curator and Editor: Larry H Bernstein, MD, FCAP and Co-Editor: Gail Thornton, PhD (c)
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About Editor of the Three-Volume Series and Series A: Six e-Books on Cardiovascular Diseases – Content Consultant Justin D. Pearlman MD ME PhD MA FACC
Dr. Pearlman has many different perspectives developed during the years, including:
- Chief of Cardiology
- Vice Chair and Chair of Medicine
- Chair of IRB
- Director of non-invasive imaging
- molecular biology
- mathematics
- imaging research
contributed a number of firsts:
- non-endemic Chagas diagnosis,
- intensity projection angiography,
- magnetization tagging,
- myocardial injury mapping by magnetic resonance contrast retention,
- myocardial viability by MRI,
- atheroma lipid liquid crystal characterization,
- outpatient inotropic infusion therapy,
- angiogenesis imaging,
- multimodal in vivo stem cell imaging,
- real-time velocity beam MRI,
- in vivo microscopic MRI,
- dobutamine stress echocardiography for low gradient valve disease,
- alternative stress tests,
- diagnostic electrocardiography in magnetic environments,
- statistical methods to solve error propagation of large array genomics,
- discovery of monocyte role in native coronary collateral development,
- image tracked stem cell treatment of heart attacks,
- singularity editing in differential topology.
Cover image: [STORY]
List of Contributors
Justin D. Pearlman MD ME PhD MA FACC, Editor and Author of the
- Introduction to the Three-Volume Series
- Introduction to each Volume
- Introduction and key words to Each Chapter
- Summary to each Chapter
- Summary and Epilogue to each volume
- Summary for the Three-Volume Series
Articles: 2.8
1.4, 2.4, 2.5, 2.6, 2.7, 3.1, 3.9, 3.10, 3.12, 3.13, 3.14, 3.15, 3.16, 3.28
Aviva Lev-Ari, PhD, RN, Editor-in-Chief, BioMed e-Books Series
1.1, 1.2, 1.3, 1.5, 2.1, 2.2, 2.8, 2.9, 2.10,2.11,2.12, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, 3.10, 3.17, 3.18, 3.19, 4.1, 4.2, 4.3, 4.4
3.11
3.16
McNally E, MacLeod H, Dellefave L
2.3
List of Videos by Chapter
VIEW VIDEOS – Courtesy of YouTube as well as the individual sponsors of the links cited below.
Chapter 1: Cardiovascular Risks
VIDEO: Prevalence of Heart Disease Women Heart Disease Women & Heart Disease: What Women Don’t Know About Their Hearts – Everyday Health, J van Amburgh, TODAY’STMJ4 Channel
VIDEO: Heart Valve Disease Definition and Prevalence — BestDoctorsTV
VIDEO: Rheumatic Heart Disease – Forgotten Not Gone — Jofenable
VIDEO: Adult Smoking Prevalence and Secondhand Smoke Exposure — Center for Disease Control
VIDEO: OBESITY for HMI 7544: Managerial Epidemiology — Garbonzon311
Chapter 2: Testing for Cardiovascular Risk
VIDEO: Risk Factors – Causes of Atherosclerosis — PeaceHealth
VIDEO: Risking It – What Are the Risk Factors for Heart Disease? — British Heart Foundation Channel
VIDEO: Risk Factors for Coronary Heart Disease — NoteworthyExperts
VIDEO: Heart Disease Risk Factors — National Heart Lung and Blood Institute (NHLBI)
VIDEO: Cholesterol and Risk Factor Primer: How to Avoid Heart Disease and Stroke — Duke Medicine
VIDEO: Risk Factors for Heart Disease~ Different Types of Fat — CardioSmart
VIDEO: MedicalHorizon: Added Sugars Increase Heart Disease Risk Factors — Emory University
VIDEO: Risk Factors for Heart Disease~Smoking — CardioSmart
VIDEO: Gum Disease Is A Risk Factor For Heart Disease — Delta Dental of NJ
VIDEO: Part 1 Depression As Risk Factor For Heart Disease — ShrinkPod
VIDEO: Part 2 of 3 Depression As Risk Factor For Heart Disease — ShrinkPod
VIDEO: Part 3 of 3 Depression As Risk Factor For Heart Disease — ShrinkPod
VIDEO: Stress Is a Potent Heart Disease Risk Factor — Health.com
VIDEO: Rheumatic Disease as a Novel Risk Factor for Cardiovascular Disease — Lupus Foundation of America, Inc.
VIDEO: Personalized Genetics — RocketBoom
VIDEO: Advancing Health Care: Personalized Genetic Medicine Genetic testing and personalized medicine – PartnersHealtchCare – pcpgm.partners.org
Chapter 3: Cardiovascular Biomarkers
VIDEO: Prognostic Biomarkers for Cardiovascular Disease — Emory University
[SOUND PROBLEM after 4:34 minutes]
VIDEO: Biomarkers for Heart Disease in African American Women with Lupus — Lupus Foundation of America, Inc.
VIDEO: Novel Biomarkers for Risk Stratifying Patients for Cardiovascular Risk
– (Part 1)— Cleveland Heart Lab
VIDEO: Novel Biomarkers (Part 2) — Cleveland Heart Lab
VIDEO: Biomarker Series: Lipoprotein A — WellnessFX
VIDEO: BioMarker Series: Apolipoprotein B — WellnessFX
VIDEO: Ensuring Effective Diagnostic Biomarkers l Thermo Scientific Global Medical Affairs — Thermo Scientific
VIDEO: Ruling Out Myocardial Ischemia in Low Risk Chest Pain Patients-Ischemia Biomarkers — jchanmeister
VIDEO: Implementing Biomarker Programs – Paul Ridker — GenomeTV
Chapter 4
The Roles of Imaging in Risk Assessment
Introduction
All the Sections in italics below represent the voice of the Editor, Justin D. Pearlman MD ME PhD MA FACC
This volume presents fascinating new data relating to the risks of and from cardiovascular diseases. Causes and management of cardiovascular diseases are addressed in volume 1 and volume 3. These categories have significant overlap: the causes stimulate methods of risk assessment, which in turn influence management. Therefore, these volumes are cross-linked, with the organizing theme of this volume the causes of cardiovascular diseases. As cardiovascular diseases remain the leading causes of death and disability, there is intense effort expanding and correcting the current concepts and evidence basis for best practices in research and clinical applications. The unique format of this series enables continual updates and feedback from experts world wide.
Risk may be expressed as a Hazard Ratio: How frequently is the condition present with a particular marker compared to without the marker? A Hazard Ratio represents instantaneous risk, distinct from Relative Risk, the prevalence of a disease condition across a defined study period if the marker is positive, versus negative. The Hazard Ratio does assume survival until the time of assessment for both groups, known as conditional hazard. A biomarker is usually a blood test that helps identify a disease condition by achieving a Hazard Ratio distinct from unity.
The major benefit of a biomarker is the ability to diagnosis a condition early (“a stitch in time saves nine”) and thereby hopefully improve the number of quality years a person can enjoy (QALY). A biomarker is deemed cost-effective if it is relatively inexpensive for the number of quality life years of expected improvement if the disease is identified and managed properly. Cost-effectiveness may include not only the cost of performing the test, but also the cost of further diagnostic tests and the treatment versus non-treatment (cost of non-treatment includes loss of wage-earning).
Superficially, Troponin-I is considered a cost effective test because it can help diagnosis heart damage (myocardial injury, infarction) as well as mortality risk for less than ten dollars, but the actual expense of the test to healthcare arguably should include all the extended emergency and hospital stays, catheterizations, interventions, stents and bypass surgeries, even though these expenses are not proven to add quality years in the absence of acute ST-elevation, medically resistant persistent and limiting angina, left main equivalent obstruction, and/or impaired systolic heart function.
In distinction, brain naturetic peptide (BNP) is widely used as an “inexpensive” test for heart failure, and it is well established that identification of systolic heart failure and optimal treatment with beta blocker, ACE inhibitor and aldosterone inhibitor (“triple therapy for heart failure”) adds quality life-years.
Similarly, elevated LDL, low HDL, elevated Lp(a), elevated CRP are all markers of “dyslipidemia” for which statin therapy clearly adds quality life-years, as a well established means to curtail risk of heart attack, stroke, renal failure, limb ischemia and limb loss.
Chapter 1
Cardiovascular Risks
Cardiovascular disease is the leading cause of death and disability, affecting more than four times as many people as all forms of cancer combined.
VIEW VIDEOS – Courtesy of YouTube as well as the individual sponsors of the links cited below.
VIDEO: Prevalence of Heart Disease Women Heart Disease Women & Heart Disease: What Women Don’t Know About Their Hearts – Everyday Health, J van Amburgh, TODAY’STMJ4 Channel
VIDEO: Heart Valve Disease Definition and Prevalence — BestDoctorsTV
VIDEO: Rheumatic Heart Disease – Forgotten Not Gone — Jofenable
VIDEO: Adult Smoking Prevalence and Secondhand Smoke Exposure — Center for Disease Control
VIDEO: OBESITY for HMI 7544: Managerial Epidemiology — Garbonzon311
1.1 785,000 people in the U.S. will have a heart attack for the first time and another 470,000 will have a repeat heart attack Comment
Aviva Lev-Ari, PhD, RN
Aviva Lev-Ari, PhD, RN
Aviva Lev-Ari, PhD, RN
1.4 How Might Sleep Apnea Lead to Serious Health Concerns like Cardiac and Cancers?
Larry H Bernstein, MD, FACP
A 200 pound person has 2 to 6 pounds of active bacteria in their gut (1-3% of body mass), representing ~10,000 species and ~100 trillion symbiotic organisms. Now there is evidence the species that co-habitate constitute a risk factor at least from the product of the proatherosclerotic metabolite, trimethylamine-N-oxide (TMAO).
1.5 Increased Cardiovascular Risk: Intestinal Microbial Metabolism.
Aviva Lev-Ari, PhD, RN
Chapter 2
Testing for Cardiovascular Risk
Cardiovascular risk estimates your chances of having a heart attack, stroke, fainting spell from change in heart rhythm, blood clot, high blood pressure, heart failure, claudication, limb loss and other issues that may impair your health. If your risks are high, then you should consider taking steps to lower your risks.
VIEW VIDEOS – Courtesy of YouTube as well as the individual sponsors of the links cited below.
VIDEO: Risk Factors – Causes of Atherosclerosis — PeaceHealth
VIDEO: Risking It – What Are the Risk Factors for Heart Disease? — British Heart Foundation Channel
VIDEO: Risk Factors for Coronary Heart Disease — NoteworthyExperts
VIDEO: Heart Disease Risk Factors — National Heart Lung and Blood Institute (NHLBI)
VIDEO: Cholesterol and Risk Factor Primer: How to Avoid Heart Disease and Stroke — Duke Medicine
VIDEO: Risk Factors for Heart Disease~ Different Types of Fat — CardioSmart
VIDEO: MedicalHorizon: Added Sugars Increase Heart Disease Risk Factors — Emory University
VIDEO: Risk Factors for Heart Disease~Smoking — CardioSmart
VIDEO: Gum Disease Is A Risk Factor For Heart Disease — Delta Dental of NJ
VIDEO: Part 1 Depression As Risk Factor For Heart Disease
VIDEO: Part 2 of 3 Depression As Risk Factor For Heart Disease
VIDEO: Part 3 of 3 Depression As Risk Factor For Heart Disease — ShrinkPod
VIDEO: Stress Is a Potent Heart Disease Risk Factor — Health.com
VIDEO: Rheumatic Disease as a Novel Risk Factor for Cardiovascular Disease — Lupus Foundation of America, Inc.
A lipid profile blood test showing LDL>100 mg/dL indicates elevated risk for progressive atherosclerosis, and levels <50-70 dL favor reversal of atherosclerosis. Fasting lipid studies estimate LDL by subtracting HDL and triglycerides/5 from the total cholesterol. Alternatively, LDL can be measured directly, as “direct LDL.” The government guidelines, which are more lenient that most cardiologists, call for treatment if >160 mg/dL, lower if disease is evident. Checking the LDL subtype adds to the risk information: the small denser subtype of LDL is worse.
Aviva Lev-Ari, PhD, RN
A profile of your gene expression can identify what you over or under produce as well as what medications you metabolize (destroy) slowly or very fast. Those factors can be used to build a strategy of treatment option priorities.
VIDEO: Personalized Genetics – RocketBoom
VIDEO: Advancing Health Care: Personalized Genetic Medicine Genetic testing and personalized medicine — RocketBoom
2.2 Personalized Cardiovascular Genetic Medicine at Partners HealthCare and Harvard Medical School
Aviva Lev-Ari, PhD, RN
Some patients with syncope (fainting) have a gene that codes for abnormal fat in the outflow tract (exit channel) of the right ventricle of the heart, which promotes life-threatening arrhythmias.
2.3 Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy, Autosomal Dominant. McNally E, MacLeod H, Dellefave L. 2005 Apr 18 [Updated 2009 Oct 13]. In: Pagon RA, Bird TD, Dolan CR, et al., editors. GeneReviews™
2.4 Accurate Identification and Treatment of Emergent Cardiac Events
Larry H Bernstein, MD, FACP
Larry H Bernstein, MD, FACP
2.5 2.6 Scale‑Free Diagnosis of AMI from Clinical Laboratory Values
Larry H Bernstein, MD, FACP
Larry H Bernstein, MD, FACP
Careful analysis of electrographic (ECG) monitoring may predict atrial fibrillation (AFIB) and thereby clarify risk, providing a surrogate (early marker) for targetted therapy to prevent the arrhythmia.
Justin D Pearlman, MD, PhD and Aviva Lev-Ari, PhD, RN
2.8 Increased Cardiovascular Risk: Intestinal Microbial Metabolism
Aviva Lev-Ari, PhD, RN
Routine fasting blood lipid studies estimate the bad cholesterol (LDL) based on the total and the triglyceride level. Direct LDL measurements are available and inexpensive. The indirect estimate can be off.
Aviva Lev-Ari, PhD, RN
Stiffness of the left ventricle, aorta, and ventricular-arterial coupling can be estimated from blood pressure, stroke volume and ejection fraction.
2.10 iElastance: Calculates Ventricular Elastance, Arterial Elastance and Ventricular-Arterial Coupling using Echocardiographic derived values in a single beat determination.
Aviva Lev-Ari, PhD, RN
High blood pressure in children leads to stiff blood vessels in the adults.
2.11 IF Elevated Pediatric Blood Pressure THEN High Adult Arterial Stiffness
Aviva Lev-Ari, PhD, RN
Chapter 3
Cardiovascular Biomarkers
Simple blood tests can identify disease conditions. For example, brain naturetic peptide (BNP) reports the strain on your heart chambers as an indication of impending or more advanced heart failure. Troponin levels in a blood sample may indicate injury to the heart muscle resulting in spillage of heart muscle proteins into circulation. Each test is capable of false positives (elevations NOT related to the cause it is supposed to represent), and false negatives (failure to report a condition that is present).
VIEW VIDEOS – Courtesy of YouTube as well as the individual sponsors of the links cited below.
VIDEO: Prognostic Biomarkers for Cardiovascular Disease — Emory University
VIDEO: Biomarkers for Heart Disease in African American Women with Lupus — Lupus Foundation of America, Inc.
VIDEO: Novel Biomarkers for Risk Stratifying Patients for Cardiovascular Risk – (Part 1)– Cleveland Heart Lab
VIDEO: Novel Biomarkers (Part 2) — Cleveland Heart Lab
VIDEO: WellnessFX Biomarker Series: Lipoprotein A Apolipoprotein B — WellnessFX
VIDEO: Ensuring Effective Diagnostic Biomarkers l Thermo Scientific Global Medical Affairs — Thermo Scientific
VIDEO: Ruling Out Myocardial Ischemia in Low Risk Chest Pain Patients-Ischemia Biomarkers — jchanmeister
VIDEO: Implementing Biomarker Programs – Paul Ridker — GenomeTV
Biomarkers are chemistry levels (concentrations in the blood) that potentially identify injury or risk for injury.
Biomarkers constitute blood test indicators of genetic predisposition or disease status that may provide diagnosis (flow of knowledge) that can guide therapeutic compensations to prevent or mitigate complications and future adverse events.
3.1 Assessing Cardiovascular Disease with Biomarkers Comments
Larry H Bernstein MD FACP
3.2 Assessing CVD with Biomarkers —Fillingane S Pharmaceutical Intelligence 12/29/12
Chapter 3.1: Atherosclerosis Markers
3.1.2 Artherogenesis: Predictor of CVD – the Smaller and Denser LDL Particles
Aviva Lev-Ari, PhD, RN
Aviva Lev-Ari, PhD, RN
Aviva Lev-Ari, PhD, RN
Chapter 3.2: Vascular and Coagulation Markers
3.2.1 Cardiovascular Risk: C-Reactive Protein BioMarker and Plasma Fibrinogen
Aviva Lev-Ari, PhD, RN
3.2.1 What is the role of plasma viscosity in hemostasis and vascular disease risk?
Larry H Bernstein, MD, FACP and Aviva Lev-Ari, PhD, RN
3.2.2 Special Considerations in Blood Lipoproteins, Viscosity, Assessment and Treatment
Larry H Bernstein, MD, FACP and Aviva Lev-Ari, PhD, RN
Serum Pentraxin 3 Levels, a newly identified inflammatory marker, indicate the complexity and severity of Coronary Artery Disease (CAD), for patients with stable angina.
3.2.3 15 Novel Risk Loci for Coronary Artery Disease: found by International Consortium
Aviva Lev-Ari, PhD, RN
3.2.4 Telling NO to Cardiac Risk
Stephen J Williams, PhD
3.2.5 Nitric Oxide Function in Coagulation
Larry H Bernstein, MD, FACP
3.2.6 Nitric Oxide, Platelets, Endothelium and Hemostasis
Larry H Bernstein, MD, FACP
Aviva Lev-Ari, PhD, RN
3.2.8 Identification of Biomarkers that are Related to the ActinCytoskeleton
Larry H Bernstein, MD, FACP
Chapter 3.3: Hypertension Markers
3.3.1 A Second Look at the transthyretin (pre-albumin) Nutrition Inflammatory Conundrum
Larry H Bernstein, MD, FACP
Plasma Renin level reports the amount of hormonal vasoconstriction, which, in excess, can cause severe elevation of blood pressure.
3.3.2 An Important Marker of Hypertension in Youth
Manuela Stoicescu, MD, PhD
Aviva Lev-Ari, PhD, RN
3.3.4 Recombinant Human lecithin-cholesterol acyltransferase (rhLCAT): New Biomarker for Atherosclerosis
Aviva Lev-Ari, PhD, RN
3.3.5 Identification of Biomarkers that are Related to the Actin Cytoskeleton
Larry H Bernstein, MD, FCAP
Larry H Bernstein, MD, FACP
Chapter 3.4: Myocardial Markers
New assays can measure cardiac Troponin in the single digit range of nanograms per liter (picograms per milliliter). Troponin is a protein that belongs inside heart muscle cells, so elevated levels in blood implicate heart injury. However, healthy patients may have elevated levels, sometimes explainable from slowed renal clearance or cross-reactive antibodies, but often not explained and yet with no evidence of heart attack. There is a bias: health services reward diagnosis of myocardial injury, and Troponin elevation can be declared a “Non-STEMI” myocardial injury or myocardial infarction to earn such credits. Then a “validation” study that looks at hospital discharge diagnosis will see a high predictive value of elevated Troponin and “myocardial injury” which may be circular.
3.4.1 Dealing with the Use of the High Sensitivity Troponin (hs cTn) Assays.
Larry H Bernstein MD FACP
3.4.2 Identification of Biomarkers that are Related to the Actin Cytoskeleton
Larry H Bernstein, MD, FCAP
Amyloidosis inserts abnormal proteins into tissues – in the heart, that results in an insidious decline cardiac function marked by increased stiffness (requiring high filling pressures that wet the lungs) and decreased contractility or inotropy (pumping ability). resulting in poor circulation of nutrients to tissues and organs. Amyoloidosis is suspected when imaging shows thickened heart muscle and thickened valves with reduced function, but thickened muscle also occurs as a reaction to incomplete control of elevated blood pressures, as well as by other infiltrative disorders.
3.4.2 Amyloidosis with Cardiomyopathy
Larry H Bernstein, MD, FACP
Protein malnutrition lowers the oncotic (partical) pressure that keeps fluid in circulation, resulting in edema unrelated to heart failure. Transthyretin (pre-albumin) is used as a biomarker because its rapid clearance increases the significance of its concentration. However, it is also an “acute phase reactant” which means acute illness can temporary spoil its value as a biomarker of chronic states.
Chapter 4
The Roles of Imaging in Risk Assessment
Calcium scoring from computed tomography (CT) has been promoted as a risk factor independent of blood tests to predict who is at risk for a heart attack. High frequency ultrasound imaging of carotid intimal thickness has been touted as another imaging based risk evaluation. Half of all heart attacks occur from lesions that are unstable but not obstructive (<50% diameter narrowing at recent catheterization) but catheter inverventions and bypass surgery both focus on obstructive lesions. Imaging of coronary lesions may identify plaque characteristics that predict which lesions are unstable (prone to cracking, bleeding, causing thrombus and thus elevating risk of sudden occlusion). Imaging methods for plaque stability include computed tomography, intravascular ultrasound (IVUS), optical coherence intervascular imaging, and near infra-red spectroscopy.
4.1 Advanced CT Reconstruction: Plaque Estimation Algorithm for Fewer Errors and Semiautomation
Aviva Lev-Ari, PhD, RN
Use of Computed Tomography (CT) exposes patients to xrays, which can be equivalent to over 100 chest xrays, enough to cause cancer in 1/1000 patients over a lifetime. Industry has responded by lowering the radiation hazard by a combination of shielding, reduced exposure times, and improved image quality at lower doses.
Aviva Lev-Ari, PhD, RN
Ultimately (at death) autopsy has been considered the final arbiter of whatever may have been predictable. Some patients accept the joke of reassuring a patient: “the test results are unclear but I am sure we can figure it out at autopsy.” However, visible tissue damage used for post mortem diagnosis actually requires on-going biologic functions – the release of lysozyme tissue destruction enzymes, the development of inflammatory cell infiltrates, fibroblast activation and scar tissue all require that biologic functions continue after the injury to create post mortem evidence. Sudden death from a heart attack or arrhythmia leaves no markers to the naked eye. Imaging as an adjunct to autopsy may improve final diagnosis.
4.3 Sudden Cardiac Death invisible at Autopsy: Forensic Power of Postmortem MRI
Aviva Lev-Ari, PhD RN
Imaging is the primary means to identify aneurysmal dilation of the aorta which poses a risk for sudden death from rupture of the aorta, but there are often no warning symptoms or signs to tell you when to get the imaging.
4.4 No Early Symptoms – An Aortic Aneurysm Before It Ruptures – Is There A Way To Know If I Have it?
Aviva Lev-Ari, PhD RN
Justin D Pearlman, MD, PhD, FACC and Aviva Lev-Ari, PhD, RN
Chapter 5
Predicting Outcomes
Collecting data on death rates and prior lab values can identify associations. Association can be a useful flag, but it does not establish a causal linkage. It is important to consider additional aspects. Causation (A causes B) requires more than just association. The editor has proposed an “ABCDE” test: A=association, B=biologic plausibility, C=controlled trial (a study where other factors are randomized to substantively reduce interference), D=determinism (a bench biology study which shows the mechanism linking A to B occurs if and only if A is present), E=evidence (a series of independent studies preponderantly supporting the causal connection, including in clinical practice).
Aviva Lev-Ari, PhD RN
When different factors can relate to eventual harm, it is helpful to analyze which has stronger impact as a predictor: heaviness of the heart (LV mass), or wall stiffness.
5.2 Prediction of Occurrence of Cardiovascular Events Independently of Left Ventricular Mass in Hypertensive Patients: Monitoring of Timing of Korotkoff Sounds as Indicator of Arterial Stiffness
Aviva Lev-Ari, PhD RN
5.3 Accurate Identification and Treatment of Emergent Cardiac Events
Larry H Bernstein, MD, FACP
Chapter 6:
Translational Medicine for Diagnosis and Risk Assessment
Translational Medicine converts scientific discovery to clinical application plus validated application benefits to everyday practice. The methods are prone to bias, as there is a strong interest in pioneering a success and claiming value. Promotion of translational medicine requires recognition of the translational value of a discovery and of the utility of efforts to bring it to validated improvements in clinical practice. Recognition and promotion of translational research is a difficult task, prone to error, manipulation and bias.
6.1 Assessment of risk of bias in translational science, Journal of Translational Medicine 2013, 11:184 (8 August 2013)
Andre Barkhordarian1, Peter Pellionisz2, Mona Dousti1, Vivian Lam1, Lauren Gleason1, Mahsa Dousti1, Josemar Moura3 and Francesco Chiappelli14*
Summary For Volume 2
This series represents a dynamic collection of articles covering the emerging new knowledge of the causes, risks and management of cardiovascular diseases, based on enormous contribution by many brilliant collaborating scientists. Your comments will promote further advances.
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