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Book Details
Abstract
This issue of Cardiology Clinics, edited by Dr. Stephen Nicholls, focuses on Lipidology. Topics include, but are not limited to: Impact of lipoproteins on atherobiology; Lessons from genomic studies; Lipids and lipoproteins in risk prediction; Optimizing statins and ezetimibe in guideline focused management; Statin intolerance; Lipid lowering agents and diabetes risk; PCSK9 inhibitors; Bempedoic Acid; Triglyceride rich lipoproteins; Omega 3 Fatty Acids; Lipoprotein; CETP inhibitors; HDL infusions; and Targeting HDL functionality.
Table of Contents
| Section Title | Page | Action | Price |
|---|---|---|---|
| Front Cover | Cover | ||
| Lipidology\r | i | ||
| Copyright\r | ii | ||
| Contributors | iii | ||
| EDITORIAL BOARD | iii | ||
| EDITOR | iii | ||
| AUTHORS | iii | ||
| Contents | vii | ||
| Preface: Lipidology | vii | ||
| Impact of Lipoproteins on Atherobiology: Emerging Insights | vii | ||
| Causal Effect of Lipids and Lipoproteins on Atherosclerosis: Lessons from Genomic Studies | vii | ||
| Lipids and Lipoproteins in Risk Prediction | vii | ||
| Optimizing Statins and Ezetimibe in Guideline-Focused Management | vii | ||
| Statin Intolerance: Some Practical Hints | viii | ||
| Treating Dyslipidemia in Type 2 Diabetes | viii | ||
| Proprotein Convertase Subtilisin Kexin 9 Inhibitors | viii | ||
| Bempedoic Acid (ETC-1002): A Current Review | viii | ||
| Triglyceride-Rich Lipoproteins | ix | ||
| Evolution of Omega-3 Fatty Acid Therapy and Current and Future Role in the Management of Dyslipidemia | ix | ||
| Is Lipoprotein(a) Ready for Prime-Time Use in the Clinic? | ix | ||
| Cholesteryl Ester Transfer Protein Inhibitors as Agents to Reduce Coronary Heart Disease Risk | ix | ||
| High-Density Lipoprotein Infusions | ix | ||
| High-Density Lipoproteins: Effects on Vascular Function and Role in the Immune Response | x | ||
| Intravascular Ultrasound Studies of Plaque Progression and Regression: Impact of Lipid-Modifying Therapies | x | ||
| CARDIOLOGY CLINICS\r | xi | ||
| FORTHCOMING ISSUES | xi | ||
| August 2018 | xi | ||
| November 2018 | xi | ||
| RECENT ISSUES | xi | ||
| February 2018 | xi | ||
| November 2017 | xi | ||
| Preface:\rLipidology | xiii | ||
| Impact of Lipoproteins on Atherobiology | 193 | ||
| Key points | 193 | ||
| INTRODUCTION | 193 | ||
| FOCUS ON THE ATHEROBIOLOGY OF APOLIPOPROTEIN B–CONTAINING LIPOPROTEINS | 194 | ||
| LIPOPROTEINS | 195 | ||
| BIOLOGICAL ACTIVITIES OF HIGH-DENSITY LIPOPROTEIN RELEVANT TO PROTECTION OF THE ENDOTHELIUM AND ARTERIAL WALL | 196 | ||
| INTERRELATIONSHIPS BETWEEN THE BIOLOGICAL ACTIVITIES AND INTRAVASCULAR METABOLISM OF HIGH-DENSITY LIPOPROTEIN | 196 | ||
| PROTEINS AND LIPIDS IN HIGH-DENSITY LIPOPROTEIN ASSOCIATED WITH ATHEROPROTECTIVE ACTIVITIES | 197 | ||
| DEFECTIVE HIGH-DENSITY LIPOPROTEIN BIOLOGICAL ACTIVITIES IN DYSLIPIDEMIAS ASSOCIATED WITH PREMATURE ATHEROSCLEROTIC CARDIOV ... | 197 | ||
| WHICH FACTORS CAN UNDERLIE SUBNORMAL OR ELEVATED LEVELS OF HIGH-DENSITY LIPOPROTEIN CHOLESTEROL? | 198 | ||
| SUMMARY | 198 | ||
| REFERENCES | 199 | ||
| Causal Effect of Lipids and Lipoproteins on Atherosclerosis | 203 | ||
| Key points | 203 | ||
| INTRODUCTION | 203 | ||
| MENDELIAN RANDOMIZATION | 204 | ||
| LOW-DENSITY LIPOPROTEIN CHOLESTEROL | 204 | ||
| What is the Causal Effect of Lowering Low-Density Lipoprotein Cholesterol by Inhibiting HMG-CoA Reductase? | 205 | ||
| What is the Causal Effect of Lowering Low-Density Lipoprotein Cholesterol by Inhibiting NPC1L1? | 205 | ||
| What is the Causal Effect of Lowering Low-Density Lipoprotein Cholesterol by Inhibiting PCSK9? | 206 | ||
| Does the Mechanism of Lowering Low-Density Lipoprotein Cholesterol Matter? | 206 | ||
| Is Atherosclerosis Caused by Low-Density Lipoprotein Cholesterol or Low-Density Lipoprotein Particles? | 207 | ||
| TRIGLYCERIDE-RICH VERY LOW-DENSITY LIPOPROTEINS AND THEIR REMNANTS | 207 | ||
| HIGH-DENSITY LIPOPROTEINS | 208 | ||
| LIPOPROTEIN(A) | 209 | ||
| SUMMARY | 210 | ||
| REFERENCES | 210 | ||
| Lipids and Lipoproteins in Risk Prediction | 213 | ||
| Key points | 213 | ||
| INTRODUCTION | 213 | ||
| TRADITIONAL LIPID RISK FACTORS | 215 | ||
| Non–High-Density Lipoprotein Cholesterol | 215 | ||
| Triglycerides | 215 | ||
| High-Density Lipoprotein Cholesterol | 216 | ||
| Total Cholesterol to High-Density Lipoprotein Cholesterol Ratio | 216 | ||
| EMERGING RISK FACTORS | 216 | ||
| Apolipoproteins | 216 | ||
| Lipoprotein(a) | 217 | ||
| Lipoprotein Particles | 217 | ||
| SUMMARY | 217 | ||
| REFERENCES | 218 | ||
| Optimizing Statins and Ezetimibe in Guideline-Focused Management | 221 | ||
| Key points | 221 | ||
| INTRODUCTION | 221 | ||
| DISCUSSION | 222 | ||
| SUMMARY | 223 | ||
| REFERENCES | 223 | ||
| Statin Intolerance | 225 | ||
| Key points | 225 | ||
| DEFINITION AND PREVALENCE | 225 | ||
| SYMPTOMS AND CAUSALITY | 226 | ||
| FOUR-STEP DIAGNOSIS | 227 | ||
| TREATMENT CHALLENGES | 228 | ||
| SUMMARY | 229 | ||
| REFERENCES | 229 | ||
| Treating Dyslipidemia in Type 2 Diabetes | 233 | ||
| Key points | 233 | ||
| INTRODUCTION | 233 | ||
| DYSLIPIDEMIA IN DIABETES | 233 | ||
| STATINS AND DIABETES | 234 | ||
| ADDITIONAL LOW-DENSITY LIPOPROTEIN CHOLESTEROL-LOWERING AGENTS AND DIABETES | 234 | ||
| FIBRIC ACID DERIVATIVES | 235 | ||
| ADDITIONAL TRIGLYCERIDE-LOWERING STRATEGIES | 235 | ||
| HIGH-DENSITY LIPOPROTEIN TARGETED THERAPIES | 236 | ||
| SUMMARY | 236 | ||
| REFERENCES | 236 | ||
| Proprotein Convertase Subtilisin Kexin 9 Inhibitors | 241 | ||
| Key points | 241 | ||
| INTRODUCTION | 241 | ||
| PROPROTEIN CONVERTASE SUBTILISIN KEXIN 9 | 242 | ||
| CLINICAL STUDIES ON EVOLOCUMAB AND ALIROCUMAB | 242 | ||
| Evolocumab | 243 | ||
| Alirocumab | 247 | ||
| OTHER MONOCLONAL ANTIBODIES TO PROPROTEIN CONVERTASE SUBTILISIN KEXIN 9 | 251 | ||
| Bococizumab | 251 | ||
| LY3015014 | 251 | ||
| NEW APPROACHES FOR THE INHIBITION OF PROPROTEIN CONVERTASE SUBTILISIN KEXIN 9 | 252 | ||
| Adnectins | 252 | ||
| Inclisiran | 252 | ||
| Anti–Proprotein Convertase Subtilisin Kexin 9 Vaccines | 252 | ||
| SUMMARY | 253 | ||
| REFERENCES | 253 | ||
| Bempedoic Acid (ETC-1002) | 257 | ||
| Key points | 257 | ||
| INTRODUCTION | 257 | ||
| MECHANISM OF ACTION | 258 | ||
| POTENTIAL MECHANISM OF LOWERING MYOTOXICITY AND ATHEROSCLEROSIS | 259 | ||
| GENETIC DATA ON ATP CITRATE LYASE INHIBITION | 259 | ||
| PHASE 1 AND 2 STUDIES | 259 | ||
| PHASE 3 STUDIES | 261 | ||
| SUMMARY | 262 | ||
| REFERENCES | 262 | ||
| Triglyceride-Rich Lipoproteins | 265 | ||
| Key points | 265 | ||
| INTRODUCTION | 265 | ||
| TRIGLYCERIDE METABOLISM | 265 | ||
| CAUSES OF HYPERTRIGLYCERIDEMIA | 266 | ||
| APPROACH TO THE CONVENTIONAL TREATMENT OF ELEVATED TRIGLYCERIDES | 267 | ||
| OTHER AND NOVEL THERAPIES TARGETING ELEVATED TRIGLYCERIDES | 268 | ||
| Triglycerides Production | 268 | ||
| TARGETING CLEARANCE OF TRIGLYCERIDE-RICH LIPOPROTEINS | 270 | ||
| Lipoprotein Lipase | 270 | ||
| ApolipoproteinCII | 270 | ||
| ApolipoproteinAV | 271 | ||
| ApolipoproteinCIII | 271 | ||
| Angiopoietin-Like Proteins | 271 | ||
| Glycosylphosphatidylinositol-Anchored High-Density Lipoprotein Binding Protein-1 | 272 | ||
| Lipase Maturation Factor-1 | 272 | ||
| SUMMARY | 272 | ||
| REFERENCES | 272 | ||
| Evolution of Omega-3 Fatty Acid Therapy and Current and Future Role in the Management of Dyslipidemia | 277 | ||
| Key points | 277 | ||
| INTRODUCTION | 277 | ||
| AVAILABLE OMEGA-3 FATTY ACID FORMULATIONS | 278 | ||
| OMEGA-3 FATTY ACIDS’ BENEFITS AND MECHANISM OF ACTION | 278 | ||
| DYSLIPIDEMIA SUBGROUPS WITH THE GREATEST ANTICIPATED BENEFIT | 280 | ||
| RESIDUAL RISK DESPITE STATIN THERAPY | 280 | ||
| CURRENT AND FUTURE ROLE OF OMEGA-3 FATTY ACID THERAPY | 280 | ||
| RISKS OF OMEGA-3 FATTY ACID THERAPY | 282 | ||
| SUMMARY | 282 | ||
| REFERENCES | 283 | ||
| Is Lipoprotein(a) Ready for Prime-Time Use in the Clinic? | 287 | ||
| Key points | 287 | ||
| INTRODUCTION | 287 | ||
| BIOLOGY AND EPIDEMIOLOGY OF LIPOPROTEIN(A) | 287 | ||
| CAUSAL ROLE OF LIPOPROTEIN(A) IN ATHEROSCLEROTIC CARDIOVASCULAR DISEASE | 289 | ||
| THERAPEUTIC LOWERING OF LIPOPROTEIN(A): TOWARD WIDER CLINICAL USE OR CLINICAL TRIALS? | 289 | ||
| Niacin, Aspirin, and Estrogen | 290 | ||
| Lipoprotein Apheresis | 290 | ||
| Newer Therapies, Nonspecific Lowering of Lipoprotein(a): Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors, Mipomers ... | 290 | ||
| Proprotein convertase subtilisin/kexin type 9 inhibitors | 290 | ||
| Mipomersen | 291 | ||
| Microsomal triglyceride transfer protein inhibitors | 291 | ||
| Cholesteryl ester transfer protein inhibitors | 291 | ||
| Others agents: thyromimetics, interleukin-6 receptor monoclonal antibodies, and farnesoid X receptor agonists | 291 | ||
| Selective lowering of lipoprotein(a): apolipoprotein(a) antisense and silencing agents | 292 | ||
| PRACTICAL CONSIDERATIONS FOR A FUTURE MODEL OF CARE | 292 | ||
| International Guidelines: Is There Consensus and How Strong Is the Evidence? | 292 | ||
| Detection: Targeted and Systematic Screening | 292 | ||
| Analytical caveats: a thorny issue | 292 | ||
| Risk Assessment: Toward Precision Medicine | 294 | ||
| Lifestyle and Pharmacotherapy: Is It All About Low-Density Lipoprotein Cholesterol? | 294 | ||
| SUMMARY: PRIME-TIME USE? | 295 | ||
| REFERENCES | 296 | ||
| Cholesteryl Ester Transfer Protein Inhibitors as Agents to Reduce Coronary Heart Disease Risk | 299 | ||
| Key points | 299 | ||
| INTRODUCTION | 299 | ||
| WHAT IS CHOLESTERYL ESTER TRANSFER PROTEIN, AND WHAT DOES IT DO? | 299 | ||
| EFFECTS OF CHOLESTERYL ESTER TRANSFER PROTEIN ON PLASMA LIPOPROTEINS | 300 | ||
| IMPACT OF CHOLESTERYL ESTER TRANSFER PROTEIN ACTIVITY ON ATHEROSCLEROTIC CARDIOVASCULAR DISEASE | 301 | ||
| Studies in Animals | 301 | ||
| Genetic Studies in People | 302 | ||
| EFFECT OF CHOLESTERYL ESTER TRANSFER PROTEIN INHIBITORS IN HUMAN CLINICAL TRIALS | 302 | ||
| Torcetrapib | 302 | ||
| Dalcetrapib | 303 | ||
| Evacetrapib | 303 | ||
| Anacetrapib | 304 | ||
| TA-8995 (AMG-8995) | 307 | ||
| REASONS FOR THE CONFLICTING RESULTS IN HUMAN CLINICAL OUTCOME TRIALS OF CHOLESTERYL ESTER TRANSFER PROTEIN INHIBITORS | 307 | ||
| Harm Caused by Torcetrapib | 307 | ||
| No Reduction in Cardiovascular Events with Dalcetrapib | 307 | ||
| No Reduction in Cardiovascular Events with Evacetrapib | 307 | ||
| EFFECT OF CHOLESTERYL ESTER TRANSFER PROTEIN INHIBITION ON THE RISK OF DEVELOPING DIABETES | 307 | ||
| SUMMARY | 308 | ||
| REFERENCES | 308 | ||
| High-Density Lipoprotein Infusions | 311 | ||
| Key points | 311 | ||
| INTRODUCTION | 311 | ||
| HIGH-DENSITY LIPOPROTEIN AND PROTECTION | 311 | ||
| HIGH-DENSITY LIPOPROTEIN EFFECTS OF EXISTING LIPID THERAPIES | 312 | ||
| APOA-I MILANO | 312 | ||
| CER | 312 | ||
| CSL | 313 | ||
| IMPLICATIONS OF THESE FINDINGS | 313 | ||
| SUMMARY | 313 | ||
| REFERENCES | 313 | ||
| High-Density Lipoproteins | 317 | ||
| Key points | 317 | ||
| HIGH-DENSITY LIPOPROTEIN CHOLESTEROL HYPOTHESIS | 317 | ||
| POTENTIAL ATHEROPROTECTIVE EFFECTS OF HIGH-DENSITY LIPOPROTEIN IN ENDOTHELIAL CELLS | 317 | ||
| POTENTIAL REGULATORY FUNCTIONS OF HIGH-DENSITY LIPOPROTEIN IN INFECTION CONTROL AND (AUTO-) IMMUNE DISORDERS | 318 | ||
| REGULATORY PROPERTIES OF HIGH-DENSITY LIPOPROTEIN IN INNATE AND ADAPTIVE IMMUNITY: THE ROLE OF LIPID RAFTS | 318 | ||
| HIGH-DENSITY LIPOPROTEIN CHOLESTEROL AS THERAPEUTIC TARGET: RESULTS FROM RANDOMIZED, CONTROLLED CLINICAL TRIALS | 319 | ||
| DYSFUNCTIONAL HIGH-DENSITY LIPOPROTEIN IN PATIENTS WITH CARDIOVASCULAR DISEASE | 321 | ||
| ALTERATION AND MODIFICATION OF HIGH-DENSITY LIPOPROTEIN PROTEIN CARGO: A DETERMINANT OF ITS FUNCTIONAL VASCULAR PROPERTIES | 322 | ||
| ALTERED PROPERTIES OF HIGH-DENSITY LIPOPROTEIN UNDER INFLAMMATORY CONDITIONS | 322 | ||
| THE SHIFT IN HIGH-DENSITY LIPOPROTEIN FUNCTION IS LINKED TO INFLAMMATORY PATHWAYS | 322 | ||
| MODIFICATIONS OF HIGH-DENSITY LIPOPROTEIN CONTRIBUTING TO THE SHIFT IN HIGH-DENSITY LIPOPROTEIN FUNCTION IN RESPONSE TO INF ... | 323 | ||
| SUMMARY | 324 | ||
| ACKNOWLEDGMENTS | 324 | ||
| REFERENCES | 324 | ||
| Intravascular Ultrasound Studies of Plaque Progression and Regression | 329 | ||
| Key points | 329 | ||
| INTRODUCTION | 329 | ||
| EARLY IMAGING CLINICAL TRIALS | 329 | ||
| INTRAVASCULAR ULTRASOUND | 330 | ||
| STATIN ADMINISTRATION | 330 | ||
| LOW-DENSITY LIPOPROTEIN LOWERING BEYOND STATINS | 331 | ||
| ADDITIONAL ATHEROGENIC LIPID TARGETS | 331 | ||
| HIGH-DENSITY LIPOPROTEIN AS A THERAPEUTIC TARGET | 331 | ||
| IMPLICATIONS AND FUTURE STEPS | 332 | ||
| SUMMARY | 332 | ||
| REFERENCES | 332 |