Practical lipid management : concepts and controversies

Chapter 1 Epidemiology of Lipids, Lipid Management and Risk for Coronary Heart Disease: An Overview 1 1.1 Early History of Cardiovascular Epidemiology 2 1.2 Lipid Risk Factors are Central to Efforts at CHD Prevention 3 1.3 LDL-C and CHD Risk 4 1.4 LDL-C Lowering and CHD Risk Reduction 6 1.5 Other Atherogenic Lipoproteins: Atherogenic Remnants 7 1.6 HDL-C and CHD Risk 9 1.7 Trends in Lipids and Lipid Management in the USA 10 1.8 The National Cholesterol Education Program Evaluation Project Using Novel E-Technology (NEPTUNE) II Survey 10 Controversy: Should a Measure of Atherogenic Lipoprotein Particle Number be used in Risk Assessment And/Or to Evaluate the Response to Lipid Therapy? 12 Chapter 2 Vascular Biology and Atherogenesis 19 2.1 Introduction 20 2.2 Arterial Structure 20 2.3 Endothelial Cell Function and Dysfunction 21 2.4 The Role of Monocytes and Lymphocytes 24 2.5 Atheromatous Plaques 25Chapter 3 Detection, Evaluation, and Treatment Goals for Lipid Disorders in Adults 31 3.1 Matching Aggressiveness of Treatment to Absolute Risk 32 3.2 Screening for Dyslipidemias 32 3.3 Risk Stratification 34 3.4 Steps in the Risk Stratification Process – Major Risk Categories 35 3.5 Tips for Calculating the Framingham Risk Score 36 3.6 Subcategories for Consideration ofMore Aggressive Optional Treatment Goals 39 3.7 Very High Risk Patients, Optional LDL-C Goal <70 mg dl−1 40 3.8 Moderately High Risk Patients, OPTIONAL LDL-C Goal <100 mg dl−1 40 3.9 Treatment Goals for Patients with Elevated Triglycerides 40 3.10 Triglycerides and HDL-C as Targets for Therapy 41 Controversy: Should Treatment Guidelines Include Targets for the Total/HDL Cholesterol Ratio? 41 Chapter 4 Therapeutic Lifestyle Changes in the Management of Lipid Disorders and the Metabolic Syndrome 51 4.1 Nature and Nurture in the Development of CHD Risk Factors 52 4.2 Lifestyle Factors as Determinants of CHD Risk in Populations 53 4.3 Within Country Variations in Lifestyle and CHD Risk 53 4.4 The Metabolic Syndrome 54 4.5 Therapeutic Lifestyle Changes 55 4.6 The TLC Diet 56 4.7 Dietary Adjuncts: Viscous Fibers and Plant Sterol/Stanol Products 58 4.8 Physical Activity and Weight Reduction 59 4.9 Smoking Cessation 59 4.10 Importance of Allied Health Professionals 59Management of Elevated Low-Density Lipoprotein Cholesterol 63 5.1 Relationship between LDL-C and Risk for Cardiovascular Events 64 5.2 Clinical Trial Support for Very Aggressive LDL-C Reduction for Those at Highest Risk 66 5.3 Genetic Disorders Associated with Elevated LDL-C 73 5.4 Atherogenic Impact of LDL-C 73 5.5 Management of Elevated LDL-C 74 5.6 Summary 82 Controversy: How Low Should We Go? 82 Controversy: Risks and Benefits of High-Dose Statin Therapy Versus Combination Lipid Drug Therapy 87 Controversy: Do the Benefits of Low-Density Lipoprotein Cholesterol Reduction Depend Strictly on “How Low You Go” or also on “How You Get There”? 90 Chapter 6 Management of Elevated Triglycerides and Non-High-Density Lipoprotein Cholesterol 105 6.1 Clinical Factors Associated with Elevated TG and Non- HDL-C Levels 106 6.2 Disorders of TG-Rich Lipoprotein Clearance 107 6.3 Insulin Resistance and Hypertriglyceridemia 108 6.4 Excessive Production of VLDL: The Primary Lipid Abnormality in the Insulin-Resistant State 108 6.5 Reasons for Elevated Free Fatty Acid Levels in Insulin- Resistant States 109 6.6 Body Fat Distribution and Insulin Resistance 109 6.7 Insulin Resistance in the Nonobese Patient 109 6.8 Hypertriglyceridemia and the Development of Atherogenic Dyslipidemia 110 6.9 Lifestyle Management for the Metabolic Syndrome and Atherogenic Dyslipidemia 111 6.10 Drug Therapies 112 6.11 Intensification of Efforts to Lower LDL-C as a Means of Achieving the Non-HDL-C Goal 112 6.12 Targeting Triglyceride-Rich Lipoprotein Reduction as a Means of Achieving Non-HDL-C Goal 113 6.13 Fibrates 113 6.14 Niacin 1146.15 Omega-3 Fatty Acids 115 6.16 Management of Diabetic Dyslipidemia 115 Controversy: Do we Need a Triglyceride Treatment Target to Insure a Predominance of Larger, More Buoyant LDL Particles? 116 Chapter 7 Management of Depressed High-Density Lipoprotein Cholesterol 127 7.1 The Relationship between HDL and Risk For CVD 128 7.2 Prevalence of Low HDL-C 130 7.3 Goals for HDL Treatment 131 7.4 Antiatherogenic Effects of HDL 132 7.5 HDL and Insulin Resistance 137 7.6 Effects of Lifestyle Modification on Serum HDL 137 7.7 Pharmacologic Management of Low HDL 139 Controversy: Do we Need HDL Treatment Goals? 143 Chapter 8 Lipid Management in Population Subsets: Women, the Elderly, Ethnic Minorities, Children, and Adolescents 155 8.1 Women 156 8.2 Lipids in Women 157 8.3 Treatment of Dyslipidemia in Women 157 8.4 Sex Hormone Therapy, Lipids, and Cardiovascular Risk in Menopausal Women 159 8.5 The Elderly 159 8.6 Special Considerations for LipidManagement in the Elderly 160 8.7 Ethnic Minorities 160 8.8 Risk Factor Incidence and Prevalence in Ethnic Minority Groups 162 8.9 Children and Adolescents 162 Chapter 9 Emerging Risk Factors and Biomarkers of Cardiovascular Disease 167 9.1 Role of Inflammation in the Pathogenesis of Atherosclerosis 168 9.2 Biomarkers of Cardiovascular Disease 168A Primer on Clinical Trials and Critical Review of Clinical Trial Reports for the Clinician 191 10.1 Design Issues Affecting the Validity and Generalizability of Clinical Trial Results 192 10.2 Chance, Bias, and Confounding as Potential Explanations for Trial Results 199 10.3 Efficacy versus Effectiveness 202 10.4 Useful Questions to ask when Evaluating a Published Clinical Trial Report 203 Controversy: Should Lipid Drugs be Approved without Clinical Event Data? 204 Chapter 11 Case Studies 209 Case One: CAD with Recent Acute Coronary Syndrome 211 Case Two: Peripheral Arterial Disease (PAD) 212 Case Three: Patient with Heterozygous Familial Hypercholesterolemia 214 Case Four: Severe Hypertriglyceridemia 214 Case Five: Metabolic Syndrome 216 Case Six: Intolerance of Intermediate-Dose Statin Therapy 217 Case Seven: Patient with Ischemic Stroke 218 Case Eight: Patient with Chest Pain on Gemfibrozil 219 Case Nine: Low HDL-C in a Patient with Stable CHD and Early Carotid Disease 220 Case Ten: Statin Drug Interaction With Hepatotoxicity 221 Case Eleven: Patient with Dyslipidemia and History of Rhabdomyolysis 222 Case Twelve: Statin-Induced Myalgia without Myopathy 223 Index 227