(Circulation. 1998;98:1039.)
© 1998 American Heart Association, Inc.
Hormonal, Metabolic, and Cellular Influences on Cardiovascular Disease in Women
Trudy M. Forte, PhD. 365 pp. Armonk, NY: Futura Publishing Co Inc;1997. $85.00. ISBN 0-87993-668-1.
Rita F. Redberg, MD, MSc, FACC
Division of Cardiology,
UCSF Medical Center,
Codirector, Center of Excellence for Women,
San Francisco, Calif
A recent survey commissioned by the American Heart Association
found that only 7% of all women identify heart disease as their
greatest health threat, despite the fact that it is actually the
leading cause of death in women. With increasing awareness in the
medical as well as the lay community of the major role
cardiovascular disease plays in morbidity and mortality
of women, there has been mounting attention to gender differences in
cardiovascular disease. It is striking that heart
disease does not begin to appear in noticeable numbers in women until
after menopause, a fact that stimulates discussion and investigation of
the role of estrogen in warding off the ravages of
atherosclerosis. This book is a comprehensive and
scholarly discussion of the current state of knowledge of possible
mechanisms for interaction between estrogen and
cardiovascular disease in women.
Although it has been known for some time that estrogen regulates
lipoprotein binding and clearance by the liver with a favorable effect
on the lipid profile, it has also been clear that the
hypocholesterolemic effect of estrogen accounts for
less than half of its associated cardiac risk reduction. Other possible
mechanisms are explored in fascinating detail in this monograph, such
as the antioxidant properties of estrogen, the effect of estrogen on
the composition of connective tissue molecules, the effect of estrogen
on inhibiting monocyte differentiation into macrophages, and
the role of estrogen in regulating vascular cell proliferation at both
the level of smooth muscle proliferation and collagen and elastin
synthesis. The book begins with a discussion of the pathophysiology of
atherosclerosis, proceeds with data from nonhuman
primates, genetic mechanisms and estrogen receptors, vascular smooth
muscle, the interaction of sex hormones in endothelial
function, vascular calcification, and the effect of estrogen on
lipoprotein metabolism as well as epidemiological data and
a cursory discussion of hormone replacement therapy.
Although the word estrogen is not specifically contained in the title
of the book, it (or the word hormone) is included in the title of 18 of
the 21 chapters, and the monograph serves as an excellent resource on
cellular and molecular mechanisms of estrogen on the
cardiovascular system.
This monograph stems from an AHA conference chaired by Dr Forte in
October 1995, entitled "Hormonal, Metabolic, and Cellular
Influences on Cardiovascular Disease in Women."
The introductory chapter by Michael Rosenfeld is an excellent summary
of the cellular events of atherosclerosis that stands
well on its own as well as providing a thorough background for gaining
an understanding of the possible effects of estrogen at each step of
the atherogenic cascade.
Linda Demer's chapter (chapter 9) presents a fascinating theory
about the paradox of vascular calcification and osteoporosis and the
reason for this dual occurrence as we age as well as the latest
information on mechanisms of vascular calcification. In chapter 11,
David Herrington provides an excellent review of the currently
available data on the effects of estrogen on anatomic and functional
sequelae of coronary atherosclerosis: abnormal
wall thickening and lumenal encroachment, abnormal
endothelial-dependent vasodilator capacity, and
abnormal thrombogenic potential as well as an overview of ongoing
angiographic trials of estrogen replacement.
There is a comprehensive summary of the literature on
hypertriglyceridemia as an independent
cardiac risk factor with attention to gender differences, suggesting
that the relative risk is greater for women than for men. Chapter 17
presents epidemiological data from the Healthy Women's Study on
changes in risk factors 5 years after menopause.
The book's greatest strengths are an exhaustive review of the
pathophysiology of atherosclerosis and the interaction
of estrogen in this pathway, including the mechanisms of regulation of
gene expression by estrogen receptors, effects on
endothelium-derived factors in coronary
arteries and vascular smooth muscle, and a discussion of the
antioxidant effect of estrogen as well as vascular calcification data.
Any reader who seeks to understand the molecular biology of estrogen
and the role that sex hormones play in the atherosclerotic cascade will
be well served by this volume. The numerous diagrams, tables, and
summaries at the end of most chapters are particularly useful. There is
some duplication among chapters. It would be helpful to include a
condensed abstract for each chapter along with the chapter titles in
the table of contents.
The clinician seeking practical advice on how to diagnose and treat
heart disease in women would not be best served by this book. Although
the final chapter gives a brief summary of the current status of
hormone replacement therapy, it is by no means an exhaustive discussion
of the current literature, pros and cons of hormone replacement
therapy, or practical advice on dosing or cyclic versus continuous
regimens. This chapter does mention phytoestrogens, the latest estrogen
to receive much attention, highlighting the complexity of clinical
decision making in this important area. However, I highly recommend
this monograph to any researcher or clinician wanting a better
understanding of hormonal, metabolic, and cellular
influences on cardiovascular disease in women.
