Therapeutic Lipidology (eBook)

Preface 7
Contents 10
Contributors 12
Acknowledgments 14
Foreword 15
Lipoprotein Metabolism and Vascular Biology 18
Brian G. Choi, 1MD, 1MBA, Juan J. Badimon, 1P1HD, Pedro R. Moreno, 1MD, and Valentin Fuster, 1MD, 1P1HD 18
Introduction 18
Lipoprotein Classification 19
Apolipoprotein Classification 20
Lipid Metabolism 22
Exogenous Pathway 22
Endogenous Pathway 25
HDL Metabolism 26
Lipoprotein Metabolism Regulation 27
Lipids in Vascular Biology and Atherothrombosis 27
Atherothrombosis Phases 27
Pathogenesis of Phase 1: Endothelial Dysfunction 29
Progression into Phase 2: Lipid Influx 30
Phase 2 Reversal: Lipid Efflux 32
Phase 3: Plaque Rupture 32
Exacerbants of Phase 3 and 4 Complications: Vulnerable Blood 33
Key Points 34
References 35
Genetic Disorders of Lipoprotein Metabolism 40
Marina Cuchel, 1MD, 1P1HD, Atif Qasim, 1MD, and Daniel J. Rader, 1MD 40
Introduction 40
Inherited Disorders of ApoB-ContainingLipoproteins 40
Lipid Disorders Involving Elevated Triglycerides 40
Inherited Syndromes of Elevated LDL-C 44
Inherited Syndromes of Low LDL-C 46
Inherited Disorders of HDL 47
Inherited Syndromes of Low HDL-C 47
Inherited Syndromes of Elevated HDL-C Levels 49
Familial Hyperalphalipoproteinemia 50
References 50
International Guidelines for Dyslipidemia Management 53
Cathleen E. Maki, 1RN, 1MSN, 1NP 53
Introduction 53
The Canadian Guidelines 54
Introduction 54
Risk Assessment 54
Lifestyle Therapy 55
Combination Therapy 55
Metabolic Syndrome 55
Apolipoprotein B 57
Lipoprotein (a) 58
Homocysteine 58
High-Sensitivity C-Reactive Protein 59
The European Guidelines 59
Introduction 59
Risk Assessment 60
Management of CVD Risk Factors 60
Joint British Society Guidelines 63
Conclusion 68
References 68
Pathophysiology and Management of Dyslipidemias Associated with Obesity, Type 2 Diabetes, and Other Insulin-Resistant States 70
Kevin C. Maki, 1P1HD 70
Introduction 71
Obesity and Type 2 Diabetes Mellitus 71
Cardiometabolic Risk Syndrome 72
Lipid Abnormalities Associated with IR 72
Functions of Insulin 72
Excessive Production of Very Low-Density Lipoproteins (VLDL1s): The Primary Lipid Abnormalityin the Insulin-Resistant State 73
Reasons for Elevated FFA Levels in Insulin-Resistant States 73
Formation of Small, Dense LDL Particles 74
Mechanisms Linking IR to Low HDL-C 76
Activities of Lipoprotein and Hepatic Lipases and their Relationships with Atherogenic Dyslipidemia 76
Lifestyle Management for Atherogenic Dyslipidemia 76
Drug Therapies for Atherogenic Dyslipidemia 77
Intensification of Efforts to Lower LDL-C as a Meansof Achieving the Non-HDL-C Goal 78
Targeting TG-Rich Lipoprotein Reduction as a Meansof Achieving Non-HDL-C Goal 79
Management of Diabetic Dyslipidemia 80
Summary 81
References 81
C-Reactive Protein and Other Inflammatory Markers in Cardiovascular Disease 84
Natalie Khuseyinova, 1MD, and Wolfgang Koenig, 1MD, 1P1HD 84
Introduction 84
C-Reactive Protein 85
Cytokines 90
Interleukin-6 90
Interleukin-18 92
Tumor Necrosis Factor- 93
Markers of Hemostasis That are Also Acute-Phase Reactants 94
Fibrinogen 94
Plasminogen Activator Inhibitor-1 96
D-Dimer 98
von Willebrand Factor 99
WBC Count 100
Lipid-Related Biomarkers 102
Myeloperoxidase 102
Oxidized LDL 104
Lipoprotein-associated Phospholipase A2 106
Adiponectin 108
Conclusions 112
Key Points 114
References 114
Dietary Prescriptions to Control Dyslipidemias and CoronaryDisease Risk 128
Margo A. Denke, 1MD 128
Introduction 128
Diet-Enthusiast's Summary of the Evolving Role of Diet 129
Pre-statin Cholesterol Lowering (1960--1987) 129
Early Statin Years: Focus Shifts to LDL Lowering (1987--1994) 129
Landmark Statin Trials, LDL Lowering, and Growth of the Metabolic Syndrome (1994--2004) 130
Lipid Therapy Beyond LDL and CHD Prevention Dietary Therapies Beyond Lipids (2004 to Present) 130
Prescription Pad 1: Dietary Therapy for High LDL Levels 131
Prescription Pad 2: Dietary Therapyfor Hypertriglyceridemia 132
Prescription Pad 3: Dietary Therapy for Combined Elevations in Triglycerides and LDL Cholesterolor Non-HDL Cholesterol Levels (Combined Hyperlipidemia) 133
Prescription Pad 4: Dietary Therapy for Low HDL Cholesterol 133
References 134
Pharmacological Therapy for Cardiovascular Disease 136
Michael H. Davidson, 1MD, 1FACC, 1FACP 136
Introduction 136
Statins 136
Mechanism 137
Pharmacokinetics 141
Efficacy 143
Safety and Drug Interaction 144
Ezetimibe 146
Mechanism 146
Pharmacokinetics 147
Efficacy 148
Safety and Drug Interaction 149
Bile Acid Sequestrants 149
Mechanism and Pharmacokinetics 149
Efficacy 149
Safety and Drug Interaction 149
Niacin 150
Mechanism 150
Pharmacokinetics 150
Efficacy 151
Safety and Drug Interaction 151
Fibrates 152
Mechanism 152
Pharmacokinetics 153
Efficacy 153
Safety and Drug Interaction 155
Omega-3 Fatty Acids 156
Mechanism and Pharmacokinetics 156
Efficacy 156
Safety and Drug Interaction 156
Emerging Drugs 157
CETP Inhibitors 157
Mechanism 158
Efficacy 158
Safety and Drug Interaction 159
Summary 159
References 160
Effects of Thiazolidinediones on Serum Lipoproteins 164
Anjli Maroo, 1MD, 1RVT,and W. H. Wilson Tang, 1MD, 1FACC 164
Introduction 164
Mechanisms of TZD Actions on SerumLipoproteins 164
Clinical Evidence of Lipid-Lowering Effectsof TZDs 165
Meta-Analyses of Pioglitazone and Rosiglitazone Trials 167
Prospective Comparative Clinical Studies 168
Concomitant TZD and Statin Therapy 169
Outcome Studies 170
Future Directions 171
References 171
High-Density Lipoproteins 174
Peter P. Toth, 1MD, 1P1HD 174
Introduction 174
Antiatherogenic Effects of HDL 175
Reverse Cholesterol Transport 175
Prevention of Oxidative Phenomena 180
Effects on Endothelial Cell Function 180
Effects on Thrombotic Phenomena 181
Net Capacity to Affect Atherogenesis 181
Pro-oxidative Activity by HDL 182
Epidemiologic Studies Evaluating the Relationship Between HDL and Risk for Cardiovascular Disease 182
The Definition and Prevalence of Low HDL 186
Effects of Lifestyle Modification on HDL 187
Pharmacologic Therapy for Low Serum HDL-C 188
Niacin 189
Fibrates 197
Statins 200
Thiazolidinediones 202
Estrogen 202
HDL Therapies in Development 203
Apoprotein A-IMilano 203
Liver-X-Receptor- Agonists 203
CETP Inhibitors 203
D4F 204
Acknowledgment 204
References 204
Management of Hypertriglyceridemia 215
Reginald Labossiere, 1MDand Ira J. Goldberg, 1MD 215
Introduction 215
Physiology 215
Causes of Human Hypertriglyceridemia 218
Chylomicronemia 218
Familial Lipoprotein Lipase Deficiency 218
Familial Apoprotein CII Deficiency 219
Elevations of VLDL 219
Familial Combined Hyperlipidemia 219
Dysbetalipoproteinemia 220
Hepatic Lipase Deficiency 220
Hypertriglyceridemia 221
Secondary Causes of Hypertriglyceridemia 222
Hormones 222
Associated Diseases 224
Beverages 224
Medications 225
Treatments/Recommendations 226
Lifestyle Alterations 226
Pharmaceuticals 227
Case 1: Dysbetalipoproteinemia/Type 3Hyperlipidemia 229
Case 2: Lipoprotein Lipase Deficiency 230
Case 3: Hypertriglyceridemia and Retinoic Acid (Accutane®) 230
Case 4: Metabolic Syndrome 231
References 231
Lowering Low-Density Lipoprotein Cholesterol Levels to Reduce Atherosclerotic Coronary Heart Disease Risk 235
Harold E. Bays, 1MD, 1FACP 235
Introduction 235
LDL-C Pathophysiology 236
Benefits of Reducing LDL-C With Lipid-Altering Drugs 236
LDL-C Treatment Goals 236
Statins 238
Ezetimibe 238
Resins and Polymers (3) 244
Combination Cholesterol Absorption Inhibitor and Statin 248
References 253
Lipoprotein(a) as an Emerging Risk Factor for Atherothrombosis 255
Michael B. Boffa, 1P1HD, Santica M. Marcovina, 1P1HD, 1S1CD and Marlys L. Koschinsky, 1P1HD 255
Perspectives 255
Structure of Lipoprotein(a)and Apolipoprotein(a): Functional Implications 256
Determination of Plasma Lp(a) Levels 260
Modulation of Plasma Lipoprotein(a) Levels 261
Lp(a) as an Emerging Risk Factor for Vascular Disease: Clinical Perspectives 262
The Relationship Between Apo(a) Isoform Sizeand Cardiovascular Disease Risk 264
Proposed Mechanisms of Lp(a) Pathogenicity 265
Challenges in Lp(a) Measurement 270
Progress In The Standardization of Lp(a) Measurement 271
Non-Immunologically Based Methods for Lp(a) Measurement 273
The Impact of Lp(a) Method Inaccuracyon the Interpretation of Lp(a) Values 273
Suggested use of Lp(a) in Clinical Practice 274
References 275
Familial Hypercholesterolemia and Lipid Apheresis 281
Patrick M. Moriarty, 1MD,Cheryl A. Gibson, 1P1HD,and Klaus Flechsenhar, 1MD 281
Introduction 281
Familial Hypercholesterolemia 282
Treatment Guidelines 284
LDL Apheresis Methods 285
LDL Apheresis and Lipid-Lowering Therapy 289
Vascular Effects in Addition to LDL Loweringand Plaque Regression 290
Inflammation 290
Lp(a), Small Dense LDL, Oxidized LDL, and Vascular Motion 290
Thrombosis and Fibrinolysis 292
Hemorheology (Blood Viscosity) 293
Alternative Applications of LDL Apheresis 294
Sudden Idiopathic Hearing Loss 294
Renal Disease 294
Cardiac Transplant 295
Ocular Microcirculatory Disturbances 295
Peripheral Vascular Disease 297
Cerebral Vascular Disease 297
Summary 298
References 298
Phytosterolemia 304
Thomas Dayspring, 1MD, 1FACP 304
Introduction 304
Cholesterol 305
Noncholesterol Sterols 306
Stanols 307
Intestinal Absorption of Sterols 307
Pharmacologic Modulation of Sterol Absorption 314
Sterols and Stanols 314
Ezetimibe 317
Statins and Cholesterol Absorption 320
Fibrates 322
Sitosterolemia (Phytosterolemia) 323
References 327
Utilization of Lipoprotein Subfractions 333
William C. Cromwell, 1MD,and James D. Otvos, 1P1HD 333
Introduction 333
Physiologic Origins of Lipoprotein Particle Heterogeneity 334
Lipoprotein Heterogeneity in Exogenous Lipid Transport 335
Lipoprotein Heterogeneity in Endogenous Lipid Transport 336
Lipoprotein Heterogeneity in Reverse Cholesterol Transport 338
Lipoprotein Assay Methods 338
Gradient Gel Electrophoresis 339
Density Gradient Ultracentrifugation 340
Nuclear Magnetic Resonance Spectroscopy 341
Analytic Implications of Lipoprotein Heterogeneity 341
Relationship of LDL Subfractions with CHD Outcomes 345
Relationship of HDL Particle Subclasses and CHD Risk 346
Relationship of TRL Subclasses and CHD Risk 348
Utilization of Lipoprotein Information for Individual Patient Management 349
Case HC 349
Clinical Considerations 351
Intervention 351
Clinical Discussion 353
Conclusion 353
References 353
Cardiovascular Disease in Women 360
Emma A. Meagher, 1MD 360
Introduction 360
Identifying Cardiovascular Risk 360
Awareness 360
Obesity 362
Metabolic Syndrome 362
Diabetes 362
Cardiovascular Risk Assessment 363
Lipoproteins and CVD 365
Treatment 367
Lifestyle and Behavioral Changes 368
Drug Therapy 369
Bile Acid Sequestrants/Cholesterol Absorption Inhibitors 372
Combination Therapy for the Treatment of Dyslipidemia 373
Statin/Fibrate 374
Statin/BAS or Statin/Cholesterol Absorption Inhibitors 374
Niacin/BAS 374
References 375
Management of Lipids in the Elderly 380
Micah J. Eimer, 1MD, and Neil J. Stone, 1MD 380
Introduction 380
Reducing Risk in the Elderly Through Lipid Treatment 380
Review of Relevant Studies Published AfterATP III 381
The Heart Protection Study 381
The Anglo-Scandinavian Cardiac Outcomes Trial---Lipid-Lowering Arm 382
The Prospective Study of Pravastatin in the Elderly at Risk 382
The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial---Lipid-Lowering Trial 383
Pravastatin or Atorvastatin Evaluation and Infection Therapy 383
Treating to New Targets 384
Cholesterol Treatment Trialists' Collaborators 384
Safety Concerns 384
Predicting Risk in the Elderly 387
High-Density Lipoprotein Cholesterol in the Elderly 388
C-Reactive Protein and the Elderly 389
Lipoprotein(a) and the Elderly 391
Lipoprotein-Associated Phospholipase A2 391
Impaired Renal Function 391
Measures of Subclinical CVD in Older Adults 392
Coronary Artery Calcification and the Elderly 392
Carotid Imaging and the Elderly 392
Ankle-Brachial Index and the Elderly 393
Key Points 393
References 394
Elderly Case Histories 396
Patient 1 396
Patient 2 397
Patient 3 397
The Clinical Use of Noninvasive Modalities in the Assessment of Atherosclerosis 399
Atul R. Chugh, 1MD, Samir N. Patel, 1MD, Venkataraman Rajaram, 1MD, Rachel Neems, 1MD, Matt Feinstein, 1BA, Marshall Goldin, 1MD, and Steven B. Feinstein, 1MD 399
Introduction 399
Review of Noninvasive Cardiovascular Imaging Technologies 400
Carotid Artery Intima-Media Thickness 400
Left Ventricular Echocardiography 404
Coronary Computed Tomography Imaging 404
Cardiac Magnetic Resonance Imaging 407
Ankle-Brachial Index 408
Brachial Artery Reactivity Testing 409
Noninvasive Assessment of Coronary Flow Reserve 410
Conclusions 413
References 413
Management of Dyslipidemia in Children 419
Stephen R. Daniels, 1MD, 1P1HD 419
Early Atherosclerosis 419
Clinical Approach to Cholesterol Abnormalities in Children 420
The Population Approach 421
Recommended Diet 421
Recommendations for Children Aged 2 Years and Older 422
The Individual Approach 423
Screening 423
Treatment of Elevated Cholesterol: Who Should Be Treated? 424
What is the Target for Treatment? 424
How Should Patients Be Treated? 425
Diet Therapy 425
Other Dietary Approaches to Therapy 426
Pharmacologic Intervention 427
Bile Acid Binding Agents 427
HMG-CoA Reductase Inhibitors 428
Cholesterol Absorption Inhibitors 429
Fibric Acid Derivatives 429
Summary 429
References 430
The Allied Health Professional's Role in the Management of Dyslipidemia 434
Lynne T. Braun, 11P1HD, RN, CNP,and Joan E. Mathien, 1BSN 434
Introduction 434
Lipid Clinic/Prevention Clinic Models 435
Nurse's Role 436
Dietitian's Role 439
Exercise Specialist's Role 442
Clinical Psychologist's Role 445
Conclusions 446
References 447
Development and Management of a Lipid Clinic 449
Carol M. Mason, 1ARNP, 1FAHA 449
Introduction 449
Rationale for a Lipid Clinic 450
The Lipid Clinic Plan 451
The Lipid Clinic Program Committee 451
Developing the Mission Statement 451
Establishing Lipid Clinic Goals 451
Writing Program Objectives 452
Developing the Business Plan 452
Revenue 453
Other Sources of Revenue 454
Expenses 454
``Break-Even Planning'' 456
Estimating Annual Clinic Revenue 457
Lipid Clinic Services 457
Patient Care Services 458
Patient Selection for a Lipid Clinic 458
Laboratory Services 460
Clinical Research 461
Group Visits 461
Other Patient Care Services 461
Becoming a Lipid Specialist 462
Professional Associations 463
Areas of Expertise for the Lipid Specialist 463
Lipid Clinic Resources 464
Lipid Clinic Organization 465
An Overview of Staffing 465
Examples of Lipid Clinic Staff Positions 465
Job Descriptions 466
Scheduling Visits 466
The ``Initial'' or New Patient Visit 467
The Medical History for a Lipid Clinic Patient 468
Physical Examination for a Lipid Clinic Patient 469
Visit Schedules 470
Physical Space 470
Lipid Clinic Equipment 472
Tracking Programs 472
Data Tracking Programs 473
Marketing your Lipid Clinic 473
Market Assessment 473
Marketing to Your Referral Base 473
Demographics and Patient Population 474
Business/Community Wellness Programs 475
Advertising Through Community Media Resources 475
When to Refer 475
Documentation, Coding, and Reimbursement 475
Providers 476
Payors 476
Documentation 478
Communication 480
Resources for Lipid Clinic Providers 482
References 482
The American Board of Clinical Lipidology PhysicianCertification Program 484
Nicola A. Sirdevan, 1MPA 484
Introduction 484
Why is There a Board Certification Programin Clinical Lipidology? 485
Eligibility Criteria 485
Basic Requirements for All Candidates 485
Training Requirements 486
The Certifying Examination 486
Attainment of Designation and Redesignation 487
To Apply 487
Continuing Education and Lifelong Learning 487
Certification for Allied Health Professionals 487
References 487
Index 488
Editors Biography 495