Macro- and Micro Circulation in Hypertension
Michel E. Safar, ed
151 pages. London, UK: Lippincott Williams & Wilkins; 2006. ISBN: 0-7817-8178-7
This book outlines contributions to the field of systemic arterial hypertension by Professor Michel Safar, his students in France, and his colleagues abroad throughout the past 25 years. During this period, Dr Safar has taken a lead in studies of pulsatile pressure in the large arteries and has played a major role in directing attention from “diastolic hypertension” (characterized by increased peripheral resistance and mean pressure) to “systolic hypertension” in older subjects (characterized by increased arterial stiffness and pulse pressure, with early wave reflection and normal resistance and mean pressure). This Gallic mechanistic approach has dovetailed with epidemiological studies such as the Framingham Heart Study, therapeutic trials such as the Systolic Hypertension in the Elderly Program (SHEP) in 1990, and those that have followed. The approach has been complemented by measures of pulsatile phenomena—pulse pressure and systolic pressure in central and peripheral arteries, aortic pulse-wave velocity as a measure of stiffness, and augmentation as an index of early wave reflection. Safar has shown that these phenomena are highly predictive of adverse events, initially in high-risk subjects (patients with end-stage renal disease) and subsequently in elderly and hypertensive subjects, all independently of traditional blood pressure measures. His evidence supports century-old observations in the life insurance industry and very recent observations in normal population cohorts. This work has transformed the clinical approach to patients with hypertension, providing a scientific rationale for its modern management.
The book begins with Safar’s beguilingly simple approach. Diastolic hypertension, largely a disease of the past, is characterized by increases in peripheral resistance and mean pressure and is caused by abnormalities in the microcirculation. This disease causes elevation of all arterial pressures—diastolic, mean, systolic, and pulse pressures—as consequences of secondary distention and passive stiffening of large arteries. Complications such as cardiac failure, coronary atherosclerosis, myocardial infarction, and stroke are principally attributable to this condition. Safar contrasts this condition with systolic hypertension in the elderly, where there is initially no microvascular disease and no increase in mean pressure—just age-related arterial stiffening, though with increases in systolic and pulse pressure—but where there are the very same ultimate clinical outcomes of cardiac failure, heart attack, and stroke as seen in diastolic hypertension.
The book then goes into detailed consideration of macrocirculation and microcirculation, though not to the most recent of Safar’s contributions: the secondary changes to microcirculation in the brain and kidneys that result from arterial stiffening, and the microvascular events that accompany this. Safar and Struijker-Boudier provide a framework on small and large blood vessels that is expanded by Bernard Levy, with stress on the renin-angiotensin-aldosterone system. Benetos discusses gene polymorphisms of the system in “diastolic” and “systolic” hypertension phenotypes, Blacher and colleagues discuss cardiovascular risk and macrocirculation, and Agabiti-Rosei and Rizzoni (Italy) discuss cardiovascular risk and microcirculation, with attention to the studies that led to Heagerty’s award of the 2006 European Society of Hypertension prize on behalf of Danish, Italian, and UK scientists. Gosse and Safar discuss the heart in relation to macro- and microcirculation, and Amar and Chamontin discuss inflammation. The conclusion is by Safar and Smulyan. The segments on sodium and hypertension and on therapy seem dated and unsatisfactory. The attention is focused here on direct drug effects on arterial stiffness and pulse-wave velocity; in recent studies such as Conduit Artery Function Evaluation (CAFÉ) and Regression of Arterial Stiffness with perindOpril/iNdapamide fixed low dose combination (REASON), predominant effects seemed to be on wave reflection from smaller muscular arteries rather than stiffness of the aorta and elastic arteries.
The book is an incomplete tribute to Professor Safar and his contributions. Perhaps these are better showcased in the Handbook of Hypertension 2006, 23rd volume on Arterial Stiffness, which he coedited, and which includes much of the same material presented here, but with less emphasis on angiotensin-converting enzyme inhibitors and their use with low-dose diuretics. The Handbook takes up the other issue described by Safar: the association between aortic stiffening with age and small-vessel disease in the brain and kidneys. This can now be explained by the extension of high pressure and flow pulsations in the dilated blood vessels of these well-perfused organs and by the damage such pulsations create in their microcirculation.
In the book under review, Safar describes his shift of interest from microcirculation to macrocirculation—that is, from diastolic hypertension to systolic hypertension. The book does not satisfactorily cover his most recent major area of study: why small vessel disease occurs in the brain and kidneys of older persons, causing dementia and renal failure, and how this can be explained, prevented, or delayed. Perhaps this book appeared too soon. The next edition will likely be more complete and more satisfying.
Michael O’Rourke is founding director of AtCor Medical Pty Ltd, manufacturer of systems for analyzing the arterial pulse.