Following the success and great interest in Lipids: Current Perspectives, John Betteridge has created a new book on new developments as well as contentious issues in the field of lipids. This is a comprehensive overview and personal insight into topics of current interest which will stimulate thought and guide the practitioner in his clinical practice.
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[BSc MB BS PhD MD FRCP] - Professor of Endocrinology and Metabolism in the Division of Medicine, Royal Free and University College Medical School, London, UKFrom The New England Journal of Medicine:
The basic sciences, epidemiology, and clinical trials have continued to expand the field of lipid research and preventive cardiology. The goal of Lipids and Vascular Disease is to explore areas of current interest and controversy in this fast-moving field. Most of the book's 18 chapters were written by experts in Europe. In general, the book has been well edited and has a rather uniform format for a multiauthored book. The figures are nicely presented in a standard fashion. The chapters are well referenced, with up-to-date citations.
Two chapters constitute an excellent introduction to new areas of investigation and current controversies, but they are not the initial chapters in the book. Faergeman, in chapter 4, provides an introduction to lipoprotein metabolism and then discusses monogenic and polygenic disorders and gene-environment interactions. Law, in chapter 14, provides an overview of cholesterol lowering on a population basis. Law appropriately points out the contribution of cohort studies in estimating the long-term effects of lipid-lowering drugs, a contribution that the usual clinical trial, with a study period of five to seven years, cannot make.
Several chapters bring together information from large and dispersed areas of research. Postprandial hyperlipidemia probably accounts for coronary risk, in addition to the risk attributed to elevated lipid levels in the fasting state. Foger and Patsch summarize the epidemiologic and clinical-trial data that support this contention. I appreciated the thorough discussion of the peroxisome-proliferator-activated receptor (PPAR) system. Fibric acid derivatives have been used clinically for many years, but their mechanism of action has been unclear. Staels discusses the ability of fibrates to increase hepatic fatty-acid metabolism, to induce the production of lipoprotein lipase, to reduce the production of apolipoprotein C-III, and to increase the production of high-density lipoprotein (HDL) cholesterol -- all of which involve the PPAR system. Davignon and Dufour review the expanding data base on the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins). Although the consistency of data demonstrating their efficacy in reducing coronary events is almost unprecedented, clinicians should also be aware of new evidence that pleiotropic actions of statins may have benefits in the treatment of other disorders, such as cancer, inflammatory diseases, transplant rejection, renal failure, and osteoporosis.
In possibly the most interesting chapter, Koch and Beisiegel discuss the role of lipoproteins in the central nervous system. The brain is one of the most lipid-rich organs, and recent epidemiologic studies of apolipoprotein E polymorphisms suggest a role for lipoproteins in senile dementia and Alzheimer's disease. This chapter contains data from research on lipoproteins, enzymes, and receptors in the cerebrospinal fluid and brain. The reader is left convinced that this new field merits attention from both lipid researchers and neurologists.
The controversy over HDL cholesterol as a target for therapy merits discussion. Unfortunately, the chapter by Mackness and Mackness is largely limited to a discussion of the basic-science mechanisms through which HDL cholesterol prevents atherosclerosis through reverse cholesterol transport and the prevention of oxidation. The considerable epidemiologic evidence in support of raising the HDL cholesterol level is mentioned only briefly, and recent clinical trials, such as the Veterans Affairs Cooperative Studies Program High-Density Lipoprotein Cholesterol Intervention Trial, are not discussed at all.
The molecular discussion should have been extended to the chapter on familial hypercholesterolemia. This chapter is clinical in its orientation, in contrast to the preceding chapters on molecular mechanisms. Familial hypercholesterolemia is the virtual paradigm for molecular medicine.
Three chapters deal with emerging data on risk factors other than lipids or lipoproteins. Although fibrinogen, homocysteine, and chronic infection are of great interest to cardiovascular epidemiologists, it would have been helpful if these interesting factors had been discussed in relation to hyperlipidemia.
The book contains five chapters on subgroups that are often undertreated by clinicians: patients with noncoronary vascular disease, those with hypertension, heart-transplant recipients, patients with diabetes, and women. Each chapter provides a useful update on the special needs of these subgroups.
The final chapter, by Wood, reviews the joint approach of the European Society of Cardiology, the European Atherosclerosis Society, and the European Society of Hypertension to the identification and management of global coronary risk. The main thrust of the guidelines is clearly to reduce overall coronary risk, not just low-density lipoprotein cholesterol levels. Though somewhat different from approaches in the United States, this approach is commendable for its speed and simplicity of risk assessment, reliance on a global risk score rather than on a single risk factor, and use of this global risk score to identify patients in whom lipid-lowering therapy is most likely to be cost effective.
Several other interesting and controversial topics should have been addressed in this book. The role of diet is not covered to any extent, despite the emergence of nutritional supplements with potent cholesterol-lowering effects (e.g., stanol esters) and data from recent clinical trials demonstrating the ability of diets high in certain fatty acids (e.g., linolenic acid) to prevent cardiac events. In addition, controversies over the appropriate treatment of children and elderly persons are not addressed. Finally, there is no discussion of the economics of lipid screening and management, a contentious topic, with health care payers continuing to balk at paying for lipid management even as the evidence of its efficacy mounts.
Lipids and Vascular Disease largely succeeds in identifying and discussing important areas of current lipid research. As with many multiauthored books, the depth of coverage varies from one chapter to another, and some topics that are addressed in more comprehensive textbooks are not included here. On the other hand, this book covers a number of topics in more detail than do the standard endocrinology and cardiology textbooks. I recommend the book for students and teachers in the field of lipid research and for endocrinologists and preventive cardiologists who specialize in the management of lipid disorders, but not for general internists or cardiologists, who would benefit from a broader review of this burgeoning field.
Thomas A. Pearson, M.D., Ph.D.
Copyright © 2001 Massachusetts Medical Society. All rights reserved. The New England Journal of Medicine is a registered trademark of the MMS.
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