Elsevier S & T

The Cholesterol Wars: The Skeptics vs the Preponderance of Evidence

Steinberg, Daniel

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Table of contents
  • Contentsv
  • Forewordxi
  • Prefacexv
  • Acknowledgmentsxix
  • Chapter 1. Overview1
  • On the nature of medical controversy1
  • An overview of the cholesterol wars4
  • Where we stand today9
  • References10
  • Chapter 2. Animal Models of Atherosclerosis15
  • Nikolai N. Anitschkow and the cholesterol-fed rabbit15
  • Why wasn't Anitschkow's lead followed up?20
  • What led Anitschkow to feed rabbits cholesterol?23
  • Atherosclerosis in other species24
  • Notes25
  • References25
  • Chapter 3. Hypercholesterolemia and Atherosclerosis in Humans: Causally Related?27
  • The clinical and genetic evidence27
  • Do more modest degrees of hypercholesterolemia, such as are found in a general population, confer ri31
  • The epidemiologic evidence33
  • Dietary fat, blood cholesterol, and coronary heart disease37
  • Do diets rich in saturated fats really raise blood cholesterol?38
  • Experimental findings39
  • Observational studies46
  • The contribution of dietary cholesterol intake47
  • Early clinical trials of dietary intervention48
  • Additional pre-1970 studies52
  • Overview of all of the pre-1970s diet intervention studies55
  • A brief wrap-up of the case against cholesterol as of 197056
  • Note58
  • References58
  • Chapter 4. Building the Basic Science Foundation63
  • The biosynthesis of cholesterol and its metabolic regulation64
  • The rate-limiting step, HMGCoA reductase69
  • The birth of the lipoproteins and the John W. Gofman story70
  • Unraveling the complex metabolism and interactions of the plasma lipoproteins76
  • Which lipoproteins are proatherogenic?77
  • The National Heart Institute story79
  • Bringing the lipoprotein package concept into clinical practice83
  • Moving from phenotype to genotype85
  • References85
  • Chapter 5. In Search of a Pathogenesis89
  • The importance of understanding mechanism in gaining acceptance of a hypothesis89
  • Early attempts to define the pathogenesis of atherosclerosis90
  • The response-to-injury hypothesis and the monoclonal hypothesis93
  • Understanding the role of HDL as an atheroprotective factor95
  • An update on HDL as a target for intervention98
  • Discovery of the LDL receptor: the remarkable partnership of Brown and Goldstein99
  • Goldstein and Brown start their search for the faulty gene in familial hypercholesterolemia101
  • Discovery of the scavenger receptor on macrophages105
  • Oxidatively modified LDL and atherogenesis106
  • Inflammation in the pathogenesis of atherosclerosis110
  • Weighing the relative importance of inflammation and hyperlipidemia113
  • Regression of atherosclerosis113
  • Status of the lipid hypothesis in the 1980s117
  • Note117
  • References117
  • Chapter 6. The Search for Cholesterol-lowering Drugs125
  • Hypocholesterolemic drugs as a target: cons and pros Nicotinic acid125
  • Bile acid-binding resins129
  • Clofibrate131
  • Probucol134
  • Another blow: the somewhat messy Coronary Drug Project137
  • The cholesterol controversy at its height138
  • References139
  • Chapter 7. The 1984 Coronary Primary Prevention Trial143
  • The National Institutes of Health goes into high gear143
  • Reception by the profession and by the press153
  • The 1984 NIH Consensus Development Conference on lowering Blood Cholesterol to prevent Heart Disease155
  • Reception by the profession and the press162
  • The position of the Food and Drug Administration164
  • The National Cholesterol Education Program165
  • Where we stood in 1985166
  • Notes167
  • References168
  • Chapter 8. Inhibition of Cholesterol Biosynthesis, the Discovery of the Statins, and a Revolution in171
  • Lowering plasma cholesterol levels by inhibiting endogenous cholesterol biosynthesisv171
  • The MER/29 (triparanol) scandal: a setback in the quest for drugs inhibiting cholesterol biosynthesi172
  • Impact of the triparanol debacle on the war against cholesterol173
  • The birth of the statins: Akira Endo176
  • How we almost lost the statins180
  • The implications if lovastatin had been dropped182
  • Was compactin indeed carcinogenic?183
  • The miraculous power of the statins to prevent heart attacks and save lives184
  • What can we expect in the future with the statins?188
  • Notes190
  • References190
  • Chapter 9. Summing up195
  • The long, uphill road for the lipid hypothesis195
  • Why did the controversy last so long?195
  • Some thoughts on hypothesis testing197
  • Have we gone as far as we can go with LDL lowering?198
  • Statins for everyone?199
  • New preventive measures on the horizon200
  • A bold proposal for a long-term approach to controlling hyper-cholesterolemia in the United States a201
  • Note203
  • References203
  • Appendix. Frequently cited criticisms205
  • "Lowering cholesterol levels with drugs may be dangerous"205
  • "Having an innately low cholesterol level is dangerous"206
  • "Dietary fat intake is irrelevant to coronary heart disease risk"208
  • "Dietary cholesterol intake is irrelevant to coronary heart disease risk"209
  • "Most heart attacks occur in people with normal cholesterol levels"210
  • "Blood cholesterol level doesn't matter any longer in old age"210
  • "Not all scientists accept the lipid hypothesis"210
  • "Atherosclerosis in rabbits and other animal models has no relevance to the human disease"211
  • "Lowering your blood cholesterol level will not increase your longevity"211
  • References211
  • Glossary215
  • Index221
Book details
  • Vendor Elsevier S & T
  • SKU 9780123739797
  • ISBN-13 9780080556192
  • Author Steinberg, Daniel
  • Category Medical
  • Subject History

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Today, in the era of the statins (cholesterol lowering drugs), there is no longer any doubt about the value of lowering blood cholesterol levels. This book chronicles the controversy that swirled around the 'lipid hypothesis' of atherosclerosis for so many years. In fact, 'the lower the better' is the position of many clinicians. However, getting to this point has been a long uphill battle marked by heated debate and sometimes violent disagreement. The history of this controversy is told here for its own sake and because remembering it may help us avoid similar mistakes in the future.

* Dr. Steinberg and his colleagues have published over 400 papers relating to lipid and lipoprotein metabolism and atherosclerosis reflecting the prominence these authors have in the community.
* Chronicles the miraculous power of the statins to prevent heart attacks and save lives, of great interest to the many manufacturers of these drugs
* Discusses new targets for intervention based on a better understanding of the molecular basis of atherosclerosis