Clinical Lipidology

A Companion to Braunwald’s Heart Disease

3rd Edition - January 6, 2023
Author: Christie M. Ballantyne
Language: English
Hardback ISBN:
9 7 8 - 0 - 3 2 3 - 8 8 2 8 6 - 6
eBook ISBN:
9 7 8 - 0 - 3 2 3 - 8 8 2 8 7 - 3

Part of the renowned Braunwald family of references, Clinical Lipidology: A Companion to Braunwald’s Heart Disease provides today’s clinicians with clear, authoritative guidance on… Read more

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Part of the renowned Braunwald family of references, Clinical Lipidology: A Companion to Braunwald’s Heart Disease provides today’s clinicians with clear, authoritative guidance on the therapeutic management of patients with high cholesterol levels and other atherogenic lipid disorders. An invaluable resource for cardiologists, lipidologists, endocrinologists, and internal medicine physicians, this one-stop reference covers everything from basic science and the pathogenesis of atherothrombotic disease to risk assessment and the latest therapy options. Now fully updated from cover to cover, the 3rd Edition offers unparalleled coverage of lipidology in an accessible and user-friendly manner.

Cover image
Title page
Table of Contents
Copyright
Contributors
Foreword
Dedication
Preface
Braunwald’s Heart Disease Family of Books
Section I. Introduction/Basic Mechanisms
1. Overview of Lipids and Atherosclerosis
Introduction
Inflammation: A Final Common Path that Links Many Risk Factors to Atherogenesis
Lipoproteins and the Initiation of Atherosclerosis: Response to Low-Density Lipoprotein Retention and Beyond
High-Density Lipoprotein: An Antiatherogenic Lipoprotein?
Triglycerides and Triglyceride-Rich Lipoproteins: Causal Risk Factors for Atherosclerosis?
Fatty Streak Formation
Links Between Lipids and Lesion Progression
Atherothrombosis: The Complications of the Atherosclerotic Plaque
Effects of Lipid Lowering on the Atherosclerotic Plaque
Perspectives on Links Between Lipoproteins and Mechanisms of Atherosclerosis
Acknowledgments
Conflicts of Interest
Section II. Risk Assessment
2. Overview of Risk Assessment
Introduction
Risk Assessment by Age Group
Risk-Enhancing Features
Risk Reclassification with Coronary Artery Calcium Score
Genetics
Conclusion And Summary
3. Measurement of Low-Density Lipoprotein Cholesterol, Non–High-Density Lipoprotein Cholesterol, Apolipoprotein B, and Low-Density Lipoprotein Particle Concentration
Introduction: The Major Atherogenic Lipids and Lipoproteins
Low-Density Lipoprotein Cholesterol (LDL-C)
Non–High-Density Lipoprotein Cholesterol (Non-HDL-C)
Apolipoprotein B
Low-Density Lipoprotein Particle (LDL-P) Concentration and Cardiovascular Risk
Fasting Versus Nonfasting
Summary of Clinical Recommendations
Conclusion
4. Triglycerides, Triglyceride-Rich Lipoproteins, and High-Density Lipoprotein in Coronary Heart Disease Risk Assessment
Introduction
Assessment of Elevated Triglyceride-Rich Lipoproteins
Population Distribution
Nonfasting Versus Fasting
Risk of Coronary Heart Disease, Atherosclerotic Cardiovascular Disease, and all-Cause Mortality
Genetics DocumentS Causality
Risk of Acute Pancreatitis
High-Density Lipoprotein
Mechanism
Residual Atherosclerotic Cardiovascular Disease Risk
Patient-Centered Clinical Applications
Guidelines/Statements
Future Research
5. Lipoprotein(a) in Cardiovascular Risk Assessment
Overview
How are Lipoprotein(a) Levels Determined?
Evidence for Elevated Lipoprotein(a) as a Risk Factor
Measurement of Lipoprotein(a)
In Whom Should Lipoprotein(a) be Measured?
Impact of Lipid-Lowering Therapy on Lipoprotein(a) Levels and Lipoprotein(a)-Attributable Risk
6. Clinical Evaluation for Genetic Testing and Secondary Causes of Dyslipidemia
Introduction
Genetic and Secondary Causes of Dyslipidemia: General Considerations
The Genetic Basis of Dyslipidemia is Often Polygenic in Nature
Rare Monogenic Dyslipidemias
Selected Severe Dyslipidemias in more Depth
Secondary Causes of Dyslipidemia
Conclusions
7. Polygenic Risk Scores
Introduction
Early Use of Polygenic Risk Scores
Genome-Wide Polygenic Risk Scores
Evaluation of Polygenic Risk Score Compared with Clinical Risk Scores
Limitations
Future Directions
8. High-Sensitivity C-Reactive Protein
Introduction
Markers of Inflammation: High-Sensitivity C-Reactive Protein
Measurement of High-Sensitivity C-Reactive Protein: cut Points, Laboratory Testing, and Variation
Risks Associated with Elevated Levels of High-Sensitivity C-Reactive Protein
Patient-Centered Clinical Applications
High-Sensitivity C-Reactive Protein and Inflammatory Markers: the Guidelines
Future Directions
Conclusions
9. Emerging Assays for Risk Assessment
Biomarkers as Clinical Tools
Role of Cardiac Biomarkers of Subclinical Cardiac Injury/Disease In Lipid Therapy
Application of -Omic Technologies to Biomarker Development
Systems Biology: An Integrated Approach to Future Biomarker Discovery
Summary/Conclusions
10. Imaging Atherosclerosis for Risk Stratification: Cardiac Computed Tomography and Carotid Ultrasound
Introduction
Coronary Calcium Score
Carotid Ultrasound
Conclusion
Section III. Therapy
11. Overview of General Approach to Management of Dyslipidemias
Introduction
Elevated Low-Density Lipoprotein Cholesterol
Mixed Dyslipidemia
Severely Elevated Triglycerides
Low High-Density Lipoprotein Cholesterol
Elevated Lipoprotein(a)
12. Treatment Guidelines Overview: American Heart Association/American College of Cardiology/Multisociety Guideline and Updates
Evolution of us Lipid Guidelines
Secondary Prevention of Atherosclerotic Cardiovascular Disease
Primary Prevention of Atherosclerotic Cardiovascular Disease
Lipid Management in Selected Groups
Monitoring Response and Adherence to Lipid-Lowering Therapy
13. Treatment Guidelines Overview: European Society of Cardiology/European Atherosclerosis Society Guidelines
Introduction
Defining the Cardiovascular Risk
Evidence for the Causal Effects of Lipids and Lipoproteins on the Risk of Atherosclerotic Cardiovascular Disease
Measuring Lipids and Lipoproteins for Cardiovascular Risk Estimation
Lipid Targets and Goals
Lifestyle Modifications to Improve the Plasma Lipid Profile
Strategies to Control Plasma Lipid Levels
High-Density Lipoprotein Cholesterol–Increasing Therapies
Subgroups of Patients
Inflammation
Conclusions and Challenges
14. Dietary Patterns for the Prevention and Treatment of Cardiovascular Disease
Introduction
Dietary Guidelines and Recommendations
Recommended Dietary Patterns
Strategies for Implementing Healthful Dietary Patterns
The Role of Registered Dietitians/Registered Dietitian Nutritionists or Nutrition Professionals In Nutrition Counseling
The Role of Physicians in Facilitating Behavior Change Toward a Healthful Lifestyle
Resources For Clinical Practice
15. Updated Clinical Guide to Exercise and Lipids
Introduction
Lipid Biomarkers: Pathophysiology and Impact on Cardiovascular Disease Outcomes
Semantics in Exercise
Impact of Exercise on Cardiovascular Disease Outcomes
Impact of Exercise Training on Lipid Biomarkers
Exercise Training and C-Reactive Protein
Mechanisms of Lipid and C-Reactive Protein Attenuation During Aerobic Exercise Training
Baseline and Trajectory Levels in Dyslipidemia
Lipoprotein(a) and Proprotein Convertase Subtilisin/Kexin Type 9
Therapeutic Strategies
Conclusions
Acknowledgment
16. Obesity, Lipids, and Cardiovascular Disease
Definition of Obesity
Effects of Obesity on the Cardiovascular System
Diagnosis
Obesity as a Contributor to Cardiovascular Disease
Heart Failure with Preserved Ejection Fraction
Obesity Paradox
Nutrition
Physical Activity
Pharmacotherapy and Bariatric Surgery
17. Statins
Mechanism of Action
Pharmacokinetics
Drug–Drug Interactions
Lipid-Altering Efficacy
Cardiovascular Effects
Special Populations
Statin Adherence, Intolerance, and Safety
18. Cholesterol Absorption Inhibitors
Introduction
Intestinal Cholesterol Absorption
Agents Affecting Cholesterol Absorption
Conclusions
19. Omega-3 Fatty Acids
Introduction
Definitions and Biochemistry
Sources of Omega-3 Fatty Acids
Effects on Lipids and Lipoproteins
Effects on Lipids in Patients with Hyperlipidemia
Effects on Cardiovascular Events
Nonlipid Mechanisms
Comparison of Omega-3 Fatty Acids
Omega-3 Index
Safety And Tolerability
Recommended Intake
Clinical Guidelines
Case Discussion
Future Directions
Conclusions
20. Proprotein Convertase Subtilisin/Kexin Type 9 Inhibition
Introduction
Discovery of Proprotein Convertase Subtilisin/Kexin Type 9
Mechanism of Action
Dosing and Pharmacokinetics
Lipid-Lowering Effects
Cardiovascular Outcomes Trials
Achieving Very low low-Density Lipoprotein Cholesterol
Safety and Tolerability
Additional Cardiovascular end Points
Populations of Special Interest
Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors in the Guidelines
Future Directions
Summary
21. Inclisiran
Introduction
Mode of Action
Effect on Lipids, Apolipoproteins, and Atherosclerotic Cardiovascular Disease Biomarkers
Safety, Tolerability, and Contraindications
Indication
Efficacy in Patients With Atherosclerotic Cardiovascular Disease and Atherosclerotic Cardiovascular Disease Risk Equivalents
Efficacy in Patients With Heterozygous Familial Hypercholesterolemia
Efficacy in Patients With Homozygous Familial Hypercholesterolemia
Cost-Effectiveness
Potential Opportunities for Patient Management and Population Health
22. Bempedoic Acid
Introduction
Impact of Acly Gene Variants on Lipid Profile and Cardiovascular Risk
Pharmacokinetics of Bempedoic Acid
Preclinical Studies
Clinical Studies
Conclusions
23. Pemafibrate: A New Selective Peroxisome Proliferator–Activated Receptor–α Modulator for Hypertriglyceridemia Management
Introduction
Mechanism of Action of Peroxisome Proliferator–Activated Receptor Agonists, Including Pemafibrate
Pharmacokinetics and Metabolism Of Pemafibrate
Safety and Tolerability of Pemafibrate
Comparison of Pemafibrate With Fenofibrate
Combination of Pemafibrate with a Statin
Use of Pemafibrate in Patients with Comorbidities
Lipid-Lowering Effects of Pemafibrate
Nonlipoprotein Effects of Pemafibrate
Clinical Application
Ongoing Trials of Pemafibrate
Summary and Conclusion
Conflicts of Interest
24. Anti-inflammatory Therapy for Cardiovascular Disease
Introduction: The Evolving Clinical Paradigm of “Residual Inflammatory Risk”
The Relationship of High-Sensitivity C-Reactive Protein Levels to Future Vascular Risk, Metabolic Syndrome, and Diabetes
When Should High-Sensitivity C-Reactive Protein Test be Ordered and How Should High-Sensitivity C-Reactive Protein Test Results be Interpreted?
Primordial Prevention: Diet, Exercise, and Smoking Cessation all Reduce Inflammation and Lower Cardiovascular Event Rates
Pharmacological Interventions, Part I: Statins are a “Two-Fer” Therapy that Reduces Both Cholesterol and High-Sensitivity C-Reactive Protein
Pharmacological Interventions, Part II: What do the CANTOS, CIRT, COLCOT, and LoDoCo2 Trials Teach US?
Other Available Pharmacological Approaches to High-Sensitivity C-Reactive Protein Lowering: Ezetimibe, Bempedoic Acid, and Glucagon-Like Peptide–1 Analogs
Are There Other Useful Biomarkers for Systemic Vascular Inflammation?
What is the Future for Inflammation Inhibition and Atherosclerosis?
25. Nutraceuticals and Functional Foods for Cholesterol Reduction
Introduction
Plant Sterols
Viscous Fiber
Soy Protein
Pulses (Non-Oilseed Legumes)
Nuts
Other Foods or Food Components with Cholesterol-Lowering Properties
The Need to Improve the Effectiveness of Diet
The “Combination,” or “Dietary Portfolio,” Approach to Cholesterol Reduction
Portfolio: Practical Application
Similar Combination Approaches
Conclusion
Section IV. New and Evolving Therapeutic Targets and Platforms
26. Evolving Therapeutic Targets: Lipoprotein(a)
Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors
Outcomes Studies
RNA Therapy
Conclusion
27. Inhibition of ANGPTL3 as a Target for Treating Dyslipidemias
Introduction: Context
Biology of Angptl3
Rationale for Angptl3 as a Therapeutic Target
Clinical Pharmacology of Angptl3 Inhibitors
Clinical Trials
Putative Mode of Action of Angptl3 Inhibition on Plasma Lipids and Lipoproteins
Therapeutic Perspectives
Conclusion: Research Questions
Conflicts of Interest
Acknowledgment
28. Evolving Therapeutic Targets: Apolipoprotein C-III
Introduction: Background
Structure and Role of Apolipoprotein C-Iii In Human Biology
Rationale for Apolipoprotein C-Iii as a Therapeutic Target
Pharmacotherapy Targeting Apolipoprotein C-Iii
Conclusion
29. Evolving Therapeutic Targets: Cholesteryl Ester Transfer Protein Inhibition
Introduction
Cholesteryl Ester Transfer Protein and Plasma Lipoproteins
Evidence Supporting Development of Cholesteryl Ester Transfer Protein Inhibitors
Torcetrapib
Dalcetrapib
Evacetrapib
Anacetrapib
Obicetrapib
Recent Developments
Conclusion
30. Gene Therapy and Therapeutic Genome Editing in Liver for Lipid Disorders
Introduction
Gene Therapy For Lipid Disorders
Therapeutic Genome Editing
Section V. Special Patient Populations
31. Special Patient Populations: Diabetes and Metabolic Syndrome
History of the Metabolic Syndrome
Epidemiology of Metabolic Syndrome and its Relationship to Cardiovascular Disease
The Role of Insulin Resistance in Dyslipidemia of Metabolic Syndrome and Type 2 Diabetes Mellitus
Therapeutic Approaches to Treating the Dyslipidemia of Metabolic Syndrome and Type 2 Diabetes Mellitus
Summary
32. Special Patient Populations: Women and Older Adults
Introduction
Women
Older Adults
Conclusions
33. Special Patient Populations: Children and Adolescents
Introduction
Definition of Dyslipidemia in Childhood
Screening for Dyslipidemia
Differential Diagnosis
Common Genetic Causes of Dyslipidemia in Childhood
Special Population: Combined Dyslipidemia of Obesity
Therapy for Dyslipidemia
Conclusion
34. Special Patient Populations: Familial Hypercholesterolemia and Other Severe Hypercholesterolemias
Introduction
Familial Hypercholesterolemia
Familial Combined Hyperlipidemia
Familial Dysbetalipoproteinemia Syndrome
Lipoprotein X Syndrome
Lipoprotein Apheresis
35. Special Patient Populations: Treatment of Familial Chylomicronemia Syndrome and Sustained Chylomicronemia
Introduction
Principle of Treatment of Sustained Chylomicronemia
Nutritional Management and Use of Medium-Chain Triglyceride Oil
Limits of Fibrates And Traditional Triglyceride-Lowering Agents in The Treatment Of Patients with Sustained Chylomicronemia
Insulin Infusion and Lipoprotein Apheresis in Patients with Sustained Chylomicronemia at Very High Risk of Acute Pancreatitis
Overview of Emerging Therapeutics for Treatment of Sustained Chylomicronemia
Apolipoprotein C-Iii Inhibitors
Angptl3 Inhibitors and Angptl8 Modulators
Angptl3 Versus Apolipoprotein C-III Inhibitors For Treatment of Sustained Chylomicronemia
Apolipoprotein C-II Peptide Mimetics and Dual Apolipoprotein C-II Agonist/Apolipoprotein C-III Antagonist
Agents Affecting Chylomicron Formation in the Enterocyte
Gene-Based Therapeutics
Conclusion
36. Special Patient Populations: Acute Coronary Syndromes
Definition, Scope of Problem, and Risk of Recurrent Events
High-Intensity Statin Therapy in Acute Coronary Syndrome
Ezetimibe
Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors
High-Density Lipoprotein–Based Therapies after Acute Coronary Syndrome
Triglyceride-Rich Lipoproteins
Conflicts of Interest
37. Special Patient Populations: Transplant Recipients
Introduction
Renal Transplantation
Heart Transplantation
Liver Transplantation
Pediatric and Adolescent Transplant Recipients
Conclusions
38. Special Populations: Chronic Kidney Disease
Introduction
Chronic Kidney Disease and Lipid Metabolism
Mechanisms of Dyslipidemia
Altered Enzyme Function
Altered Receptor Function
Cardiovascular Outcomes in People with Chronic Kidney Disease
Impact of Lipid-Lowering Agents on Lipid Markers
Cardiovascular Outcome Trials of Lipid Lowering Specific to Chronic Kidney Disease
Cardiovascular Outcome Trials of Proprotein Convertase Subtilisin/Kexin 9 Inhibitors and Icosapent Ethyl in Subgroups with Chronic Kidney Disease
Effect of Lipid Lowering on Progression of Chronic Kidney Disease
Conclusions
39. Special Patient Populations: Lipid Abnormalities in High-Risk Racial/Ethnic Groups
Introduction
Racial/Ethnic Lipid Abnormalities and Atherosclerotic Cardiovascular Disease Risk Calculation
Heart-Healthy Diet and Statin Therapy
New and Emerging Pharmacotherapies for Lipid Abnormalities
Acknowledgment
40. Persons With Human Immunodeficiency Virus
Introduction
Antiretroviral Therapy, Cardiovascular Disease Risk, and Implications for Management
Cardiovascular Risk Assessments
Current Screening Guidelines
Primary Prevention and Screening for Clinical Practice
Cardiovascular Disease Risk Reduction Interventions in Persons with Human Immunodeficiency Virus
Statin Therapy
Implications for Future Research
Clinical Assessments
Conclusion
Index

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Christie M. Ballantyne