High blood pressure (HTA) is a particularly high frequency condition.
Its satellite is a major increase in cardiovascular risk, which should be remembered as the leading cause of death in our country. These considerations underline the major public health problem of this pathology, and also its heavy financial implications, which sometimes alter the scientific quality of the debates.
Essential hypertension is by far the most frequent hypertension, since its frequency is between 89 and 95% of the cases following the studies. It is a complex condition, at the crossroads of genetics and many environmental factors. His physiopathology keeps a large part of his mystery. As for its treatment, although the codification has evolved well in the last 10 years, many unknowns persist on its indications and modalities.
DEFINITIONS AND CLASSIFICATION:
Since blood pressure is a continuous variable, the definition of a threshold characterizing the pathological condition “hypertension” is necessarily arbitrary. Conceptually, it has long been known that subjects with high blood pressure have a greater risk of cardiovascular morbidity and mortality than others. The American life insurance companies have, since the beginning of the century, established patterns for reducing life expectancy as a function of blood pressure. The so-called “operational” definitions of hypertension have come from the major international organizations, and we will retain that of the World Health Organization (WHO) in its latest versions. In order to try to escape from arbitrariness, it admits that such a definition can only be based on intervention studies demonstrating the benefit of reducing blood pressure. On this basis, the threshold defined as a definition of hypertension is 140/90 mmHg, provided that these figures have been confirmed by iterative measures over several weeks or even several months. It is also stated in this text that the ambulatory blood pressure measurement (MAPA) is not a diagnostic criterion for hypertension, and that it should be used “only in special cases to supplement to the values measured by the doctor “. A point widely debated was that of a different threshold of hypertension in the elderly. This debate can now be considered closed. The threshold of hypertension is the same in the elderly as in the young, it is the frequency of hypertensive disease that increases with age. This is evidenced by the increased incidence of complications (strokes, heart attacks, deaths) above this threshold and, on the other hand, the particularly clear benefit of the reduction in blood pressure in these subjects.WHO has also established classifications of estimated hypertensive disease by gravity. This approach is also delicate and necessarily very imperfect. The first classification is based on blood pressure alone. Perhaps most relevant is the second classification, based on target organ damage.
The validity of this classification can certainly be debated. But in any event, it is amply demonstrated, as we shall see later, that the existence of left ventricular hypertrophy (HVG) or hypertensive retinopathy is a sign of a much more serious threat to the cardiovascular prognosis of patients. It is no less evident that the complications that characterize stage III are a very serious situation.
Precisely assessing the prevalence of hypertension in a population is actually difficult. The most comprehensive data are from the US National Health and Nutrition Examination Survey (NHANES). In its latest report, published in 1994, it is recognized that 24% of the US population is hypertensive. This frequency of course varies with age, from less than 5% in subjects less than 30 years to more than 60% in excess of 70 years. The frequency is much lower in women, at least up to 60 years. It also varies with ethnicity (32% in Blacks compared with 23% in Whites). There is scarcely such exhaustive data in other countries, where predominantly one-off studies on particular population subgroups have been conducted. Moreover, it can be assumed that the prevalence of hypertension is similar in France and in other Western countries than in the United States. On the other hand, it is not the same in all the countries, and the prevalence of the hypertension varies very widely according to the countries (cf infra).
The incidence of hypertension can be assessed by longitudinal cohort follow-up. Particularly valuable data were provided in this respect by the Framingham study. In a cohort of normotensive subjects, followed from an initial age of 30 to 60 years, the incidence of hypertension is 28% at 10 years and 45% at 20 years in men, values are quite high little different in women. In subjects initially with limiting systolic hypertension, the incidence of permanent hypertension was 61% and 80%, respectively, at 10 and 20 years.
Frequency of hypertension: variations according to regions
Blood pressure levels, as well as the prevalence of hypertension, are roughly divergent between different ethnic groups, and there is little doubt that this divergence is explained, at least in part, by genetic factors.
For example, in the Intersalt study of some 10,000 subjects recruited in 52 centers, the prevalence of hypertension (at a comparable age) ranged from 0% among Yanomamo Indians in Brazil and 33% among black Jackson subjects MS.The adjustment for age makes it possible to exclude the idea that the longevity of the populations is an important factor of these discrepancies. Many other studies have found similar disparities. Fabre et al measured the blood pressure of more than 12,000 subjects of all ethnicities, working in international organizations in Geneva. From 40 years onwards, there is a clear difference in the values of blood pressure according to the ethnic groups. The data were analyzed taking into account age and sex. The prevalence of hypertension among men ranges from 4% (Islamic culture nations) to 28% (Black Africa) between 40 and 49 years, and 16 to 73% between 50 and 59 years. The differences were of the same order in the female sex.
Many studies show that overall the prevalence of hypertension is higher in industrialized countries than in developing countries. There are even some communities (all quite closed and living on the margins of the industrial world) in which hypertension is absent or almost absent.
HTA and ethnicity:
There are also differences in the prevalence of hypertension between ethnic groups living in the same country. This difference between ethnic groups has been the subject of particularly careful study in the United States. According to NHANES studies, hypertension is less common in Hispanic Americans than in Caucasians. Among the Asian groups, hypertension appears to be excessive among Filipinos and Chinese (born in the United States), while it is identical to Caucasians for Japanese and other groups from the Far East. It is in fact in black subjects that hypertension is the most frequent, and associated with an excess of morbimortality in relation. The dramatic difference in the prevalence of hypertension between white and black subjects in the United States has led to a concept of “hypertension of the black subject”, which is the subject of various controversies. The specific characteristics of these hypertensions (frequency of complications, low renin, and susceptibility to diuretics) are well known to clinicians, and seem to confer a substrate consisting of the idea of a homogeneous category. The difference in response to different therapeutic classes has also been well documented in various studies. On the contrary, the opponents of this idea of a specific hypertension of the “black subjects” rely on two orders of arguments: the first is that the level of tension is very different in these subjects according to which the data are collected in the United States, In the United States or in the country from which they originate, some African ethnic groups with even lower blood pressure levels; the second argument (corollary to the first) is that environmental factors can almost always be brought to light, explaining in whole or in part the difference in blood pressure; the more these factors are taken into account, the more it appears that there is no statistical correlation between the blood pressure level and the color of the skin; in addition, the sickle cell disease gene (“black” disease) has been correlated with low blood pressure.
HTA and family:
Whether hypertension is a genetically transmitted disease is a well-known and undisputed fact. On the other hand, it can not be said to be a “genetic disease”, in the sense of a monogenic disease with a Mendelian transmission. The familial aggregation of cases of hypertension is indisputable. Subjects with close relatives of at least two hypertensive individuals before age 50 are 3.8 times more likely to become hypertensive themselves before age 50. Various studies have shown that the correlation of arterial pressure is greater in monozygotic twins than in dizygotic twins. It is stronger in dizygotic twins than in non-twin sibs. She is finally stronger (both mother-child and sibling) for natural children than for adopted children. These twin and adoption studies have estimated the genetic share of blood pressure variability in a population from 20 to 60%. Other segregation studies, insofar as the adjustment is made for major variables such as age, sex, sodium intake, body weight, etc., have resulted in similar figures, estimating the contribution to 50% in the variance of blood pressure between individuals in subjects 50 years of age and older.
Primitive populations, living apart from the industrialized world, are often little or no hypertensive. Moreover, in these populations, blood pressure does not increase with age. They are referred to as “low blood pressure populations”.Many such populations have been duly registered (Eskimo, Australian or Chinese aborigines, nomad tribes of Kenya, Pygmies of the Congo, Melanesian and Polynesian tribes, South American Indians, etc.). These populations, when migrating to industrialized areas, are mostly hypertensive. The hypertension which then appears in them is possibly of greater frequency and severity than that of the host country. The opposite demonstration, which would be the same methodological elegance, was not made, for reasons historically and sociologically understandable …
The black population living in the United States is a striking example of these transplanted groups. Its blood pressure is higher than that of subjects living in sub-Saharan Africa, the region of which the majority of the population is born.Black Americans raise their blood pressure more than white people for an identical sodden charge, and they have a lower renin. From a finalist point of view, this trait, probably genetic, is obviously useful in terms of survival for populations living in hot climates and with limited access to sodium. On the contrary, it may be harmful in populations living in a temperate climate and with free access to sodium, since any sodium intake is therefore a source of expansion of the liquids Blackburn and Prineas have raised the interesting hypothesis known as l ‘slavery. Black Americans, originally from Africa, were transferred to the American continent at the mercy of the slave market. They were subjected to a painful journey, and tried by rationing, diarrhea, vomiting, etc. Such trips were likely to involve high mortality. It is tempting to think that subjects with good sodium preservation have survived these tests better than others. Thus, the harsh conditions of the journey would have been responsible for a kind of genetic selection, bringing only those who best retained sodium to the American continent. It would therefore be logical for the incidence of hypertension to be particularly high among them, since sodium was abundant. This theory has been largely controversial.
Genes of high blood pressure:
Whether it is in humans or in the various strains of genetically hypertensive animals used in the laboratory, the quest for the “hypertension gene” has been active since the accelerated development of molecular genetics. Candidate genes have not lacked and the inventiveness of researchers is great. In fact, there is little chance of a “hypertension gene”. The probability is rather that of a mosaic of genes (and functions) involved, which does not facilitate the research insofar as the statistical weight of each individual taken can not be major. These genes probably do not control the blood pressure level itself, but rather intermediate phenotypes (renin-angiotensin system, membrane ionic “pumps”, sympathetic activity, salt sensitivity …), which are expressed in certain environments better than in d ‘other.The intensive search for polymorphisms of one of the genes controlling the renin-angiotensin system has not been very successful. If a polymorphism of the conversion enzyme gene seems to correlate well with the vascular risk, it is hardly correlated with the level of blood pressure. The situation is similar for the AT1 receptor gene. Only a polymorphism of the angiotensinogen gene (mutation M235T) is correlated with the blood pressure level.
At least three mutations alone responsible for hypertension have been identified which allow us to explain rare disorders: hyperaldosteronism suppressible by dexamethasone (chimeric gene between 11β-hydroxylase and aldosterone synthetase), the apparent excess of (or AME, linked to a mutation of the 11β-hydoxysteroid dehydrogenase gene), and lately Liddle’s syndrome (a mutation in the epithelial sodium channel subunit gene).Indirect arguments suggest that certain essential hypertensions may be minor forms of one of these syndromes, so the search for other, less “mutilating” mutations in these genes is active.
The essential role of the kidney:
The regulation of blood pressure is a highly complex phenomenon, using many distinct though converging processes.Each of these mechanisms has its own action time and its own “gain”, that is, its maximum power of action. One of these mechanisms nevertheless appears to have a place apart, it is the “pressure natriuresis”. When blood pressure rises, natriuresis increases, decreasing extracellular volume and bringing pressure back to normal. In the scheme proposed by Guyton et al for thirty years, the “gain” of this mechanism would be virtually unlimited, which would make pressure natriuresis the main long-term regulator of blood pressure. If we accept this hypothesis, we must therefore admit its corollary, that there can be no permanent hypertension without the pressure natriuresis being defective.Numerous studies This alteration of renal function finds its most dramatic arguments in renal transplant experiments.For example, in Dahl rats, if the kidney of a resistant donor is transplanted to a sensitive recipient, the latter sees its blood pressure normalize. Similar findings have been made in humans, where hypertension is more common in kidney recipients of a hypertensive donor than a normotensive donor. What can be the origin of this anomaly? Brenner and his team, based on anatomical arguments, supported the hypothesis of a reduction in the number of nephrons and / or the filtering surface. Such an abnormality would explain a defective sodium renal excretion, generating glomerular hypertension and then systemic hypertension.
Sealey et al proposed another explanatory hypothesis. This hypothesis, called “nephron heterogeneity”, involves a subpopulation of chronically ischemic glomeruli. These would produce inappropriate amounts of renin in the systemic situation, influencing sodium reabsorption by normally filtering nephrons. This anomaly would explain the normal plasma renin activity in most hypertensive patients, whereas hypertension should theoretically be accompanied by complete suppression of renin.
Whatever the hypothesis, hypertensive patients would be subjects “in a state of permanent compensation for a slight excess of extracellular fluid”. This process would assume the permanent activity of volemic control mechanisms, among which, according to De Wardener ‘s scheme, an Na + – K + – ATPase inhibitor could play a major role. This inhibition, ubiquitous, would allow the maintenance of a normal sodium balance, but with as a counterpart systemic hypertension. A strong argument in favor of this idea is the finding of an abnormality of membrane pumps in essential hypertensive patients and in normotensive children of hypertensive parents.
The renin-angiotensin system is probably one of the regulatory factors that has triggered the most work, both pathophysiology and molecular genetics, in hypertension. This system is in fact the key to an important part of the regulation of blood pressure and renal hemodynamics. Angiotensin II is a potent vasoconstrictor. This effect results from the use of the phosphoinositol pathway in the fixation of angiotensin on its vascular receptor, leading to a rapid rise in the intracellular calcium concentration. As such, angiotensin II contributes to the physiological regulation of blood pressure. The fact that it may in itself be responsible for hypertension is attested by certain renal hypertension dependent, such as renascascular hypertension, or better still renin tumors. The fulminant hypertension observed in transgenic rats for another renin gene is also a dramatic argument. Renal hemodynamics is very sensitive to the actions of angiotensin II. This induces vasoconstriction, and therefore decreases the renal blood flow. Angiotensin II receptors exist both in the afferent and efferent arteries and in the glomerular mesangium itself. The effect of angiotensin II involves an increase in the intraglomerular hydrostatic pressure, and therefore an increase in the fraction of filtration, suggesting a predominant effect on efferent arteries. Overall, this results in maintenance of glomerular filtration in the face of decreased renal blood flow. Although these actions are homeostatic, perverse effects are nevertheless known. Brenner et al. Have shown that the increase in filtration pressure leads to glomerular sclerosis. It is accepted that angiotensin is the source, or at least the mediator, of hypertensive nephropathy. Angiotensin II exerts trophic effects on vascular walls. On smooth muscle cell cultures, it increases protein synthesis and induces hypertrophy as well as an increase in the production of collagen. A proliferative effect of angiotensin is more discussed. These actions are accompanied by an increase in the expression of certain proto-oncogens (c-myc, c-fos), and the production of growth factors, in particular the platelet derived growth factor (PDGF). The role of tissue renin-angiotensin systems remains poorly defined. The renin-angiotensin system therefore probably plays a role not only in elevated blood pressure but in the vascular risk associated with hypertension. For example, in a recent prospective study, the incidence of myocardial infarction was 14.7 per 1,000 patients per year in high renin (12% of the population), compared to 5.6 in (56%) and 2.8 in those with low renin (32%). The association with the frequency of strokes was less clear. These observations are corroborated by the association of certain polymorphisms of components of this system with a significant increase in coronary risk.
Sympathetic nervous system
The renin-angiotensin system interferes directly with the sympathetic nervous system, which relays many of its effects.Stress or other factors can act directly on the sympathetic nervous system. The argument in favor of an important role of this system is consequent: numerous studies have established the role of stress, not only on blood pressure and heart rate, but on multiple biological and physiological parameters. In the earliest stages of hypertensive disease, sympathetic hyperactivity can be demonstrated, as well as an increased density of α2 receptors in various tissues. A deregulation of the baroreflex has been widely argued.
It has appeared in the last decade that the endothelium, far from being a simple passive coating of the arterial circuit, has an intense activity of production of various mediators, which actively communicate with the underlying muscle cells. These mediators are produced in response to shear forces, intravascular pressure, circulating hormones, or platelet factors. These interactions concern both the relaxation-contraction state of the cells and their trophicity and growth.
The main endothelial mediators are the endothelium derived relaxing factor (EDRF, later identified as nitric oxide, NO), and endothelium. Many studies have been devoted to possible dysregulations of these systems during human hypertension, without very convincing arguments. But in any case, endothelial functions can only be involved, at least as intermediate mechanisms, in the genesis of hypertension since they manage the pathway of phospho-inositols on one side, that of cyclic guanosine monophosphate (CGMP) on the other, which depend on the intracellular calcium concentration, that is to say the cellular contraction.
Hyperinsulinemia with insulin resistance is present in approximately 50% of non-obese hypertensive patients, and in almost all obese or diabetic type II patients, two conditions commonly associated with essential hypertension. Some authors have attempted to attribute hyperinsulinism to the genesis of these hypertensions. Through multiple studies, the role of hyperinsulinism as a promoter of hypertension and as an independent vascular risk factor has largely been confirmed and led to the concept of “Syndrome X”, unifying the various pathologies concerned. Even if this concept has led to extrapolations which are undoubtedly abusive, it is clear that it has illuminated a large number of observations made in hypertensive patients. This is not another hypothesis, but another intermediate mechanism linking various exogenous factors, the sympathetic nervous system, sodium retention, vascular hypertrophy, and hypertensive disease.
Other endogenous factors:
We shall not go into this brief review on other endogenous factors whose physiopathological importance should not be overlooked: the various natriuretic peptides, prostaglandins, the kallikrein-kinins system, medullipine, vasopressin …
Birth weight: quality of the perinatal environment
Apart from the purely genetic aspect, the innate (in the etymological sense) may also be dependent on prenatal factors. Several studies have shown a link between birth weight and subsequent hypertension.
Fetal hypotrophy is associated with an increased incidence of hypertension in adulthood, especially if the fetal weight was low relative to the weight of the placenta. This relationship, already present in children, is accentuated with age, and in the sixties, 1 kg more birth weight is associated with a lower systolic blood pressure of 5.2 mmHg. There is no relationship between weight gain in the first year (s) and subsequent blood pressure, suggesting that the initiation of the phenomenon is indeed prenatal, not in the early years of life. Prematurity is not, on its own, linked to the subsequent level of blood pressure. It is therefore the process of intrauterine growth retardation itself. Indeed, it can be argued that intrauterine growth retardation is much more common in hypertensive mothers or at least those with a family history of hypertension …
HTA and nutrition:
The association between obesity and hypertension is a very solid fact. Once the coarse bias of the blood pressure measurement, which requires a cuff adapted to the circumference of the arm, is eliminated, hypertension appears 3 to 6 times more frequent in the obese than in the thin subject. Before 30 years, the multiplier factor would even be 30, according to some studies. In the Intersalt study, there was a strong independent correlation between body mass index (BMI) and blood pressure, both systolic and diastolic. In the work of Fabre et al on the staff of international organizations, the prevalence of hypertension, for all ages and ethnic groups, was 20.5% among those weighing 10 kg or more at their ideal weight, 9.7% in thin subjects. The causal relationship between body weight and hypertension is strongly suggested by the decrease in blood pressure associated with weight reduction. It has been suggested that diastolic blood pressure (PAD) would range from 4 mmHg per 10 kg of weight in one direction or the other. The nature of the bond that unites overweight and hypertension has been widely debated. The role of sodium sensitivity appears to be one of the best supported. Chronic alcohol consumption raises blood pressure regardless of body weight. The incidence of hypertension is 2 to 3 times higher in chronic alcohol users than in abstinents. The Framingham study showed a J curve: the blood pressure is somewhat higher in the abstinent than in the small drinkers. On the other hand, after a certain threshold, the increase in alcohol consumption is accompanied by a proportional increase in blood pressure figures. In the Intersalt study, there was a significant correlation between blood pressure and alcohol consumption, between centers, and within centers for 35 of them. Many other studies in Australia, Germany, and other countries have confirmed this relationship. Lang et al, in a cohort of 6,665 French subjects (who were therefore highly exposed to alcohol) also showed a very significant correlation between alcohol consumption and blood pressure. In addition, alcohol appears to be a highly negative factor in adherence to antihypertensive therapy.
In contrast, several intervention studies have shown that reduced alcohol consumption was associated with lower blood pressure.
Tobacco and coffee have also been implicated in an increase in blood pressure.
In fact, these substances increase blood pressure acutely and reversibly, and there is currently no solid argument for considering an effect on the chronic blood pressure level.
HTA, sodium and other cations:
The link between sodium and hypertension is considered to be one of the most crucial links between the environment and the blood pressure level. Population studies show a higher prevalence of hypertension than sodium consumption.At the cost of some mathematical artifices, a positive correlation can be found between sodium consumption and blood pressure level or prevalence of hypertension. It should be noted that in the Intersalt study, this correlation is due only to the existence of four populations with low prevalence of hypertension and low sodium intake on the 52 centers considered. It disappears if these four populations are omitted. Still, low-sodium populations are undoubtedly low in hypertension, and high-consumption populations are much lower. The dramatic difference in blood pressure between northern and southern Japanese is a classic example.
Things become less simple when we consider not a population as a whole but individuals within a population.Therefore, there is no longer any correlation between sodium intake and blood pressure, except unreasonable mathematical artifices. In the Intersalt study, the intracentral correlation between natriuresis and blood pressure disappears when the adjustment is made for BMI and alcohol consumption. Although sodium intake is a major weight factor between populations, but difficult to find between individuals of the same population, it is no doubt a new joke of genetic duality-environment. Hence the concept of sensitivity of blood pressure to sodium, which has given rise to countless studies in that it is probably an essential key. Many factors have been incriminated in this sensitivity, we will not consider them here in detail. It appears mainly that the sensitive subjects have a relative expansion of the extracellular fluids, and a low and unstable stimulus. This sensitivity most likely has a major genetic component.
An antihypertensive role of food potassium has been suspected for a long time, and it is also debated with some passion. It seems clear that hypertensive patients have an average kaliuresis less than normotensive ones. The difference is 15% in the NHANES II study. Various studies have also shown a negative correlation between blood pressure and kaliuresis. This relationship, however, does not appear to be constant in all studies (among others, it is absent in Framingham, and limited in Intersalt), nor very strong.
Experimentally, potassium depletion raises blood pressure while a potassium load lowers it. Things are less clear in the human clinical setting, where the different intervention trials have produced contradictory results, especially in hypertensive patients. However, in a meta-analysis of 19 trials including 412 hypertensive and 174 normotensive subjects, potassium supplementation significantly reduced blood pressure, 8.2 mmHg for systolic and 4.5 mmHg for diastolic. The reason therefore argues in favor of a modest but undeniable role of a high intake of potassium as an antihypertensive factor.
The eager minds of systematization, disappointed by the results of correlation studies between blood pressure and sodium or potassium intake, which are certainly conclusive results, but whose scope is somewhat below expectations, have devised a new marker: the sodium ratio /potassium. The latter would raise the last doubts and would be much better correlated to the level of tension than each parameter taken separately. In the Intersalt study, after adjustments, the correlation was significant for eight out of 52 centers.
The role of calcium is also one of the subjects of passionate debate. Dietary intake of calcium is considered by some authors to be lower in hypertensive than normotensive. Hypertensive patients also have higher urinary calcium excretion than normotensive patients, and the association between essential hypercalciuria and hypertension is known. The high rate of parathyroid hormone (PTH) seen in hypertensive patients may therefore be only a homeostatic response to the combined effect of low intake and urinary calcium leakage. This reaction hyperparathyroidism could be responsible for an increase in blood pressure. The use of calcium supplementation has therefore been tested in various studies in hypertensive patients. We will not enter this debate here. If calcium supplementation proves to be ineffective in cohorts of hypertensive patients, it may be accompanied by a decrease in blood pressure in patients with elevated PTH.
Lifestyle adaptation to the genetic heritage:
The influence of the environment on a predetermined genetic field has not escaped the insight of anthropologists: “From a genetic point of view, today’s humans are Stone Age hunter-gatherers , transported by time in a world that differs from that for which our genetic constitution was selected … The human genome has changed little in 10 000 years, but during the same period our culture has been transformed to the point that there exists now an inadequacy between our old biology, genetically determined, and certain essential aspects of our daily lives … This results in “diseases of civilization” which are the cause of 75% of deaths in Western nations but which are rare in populations whose lifestyle is close to our ancestors before agriculture, “writes Eaton.
These authors compared the diet of the contemporary average American, which can be estimated to have been that of the famous hunter-gatherers, on the basis of feeding the most primitive communities (pre-agrarian) that can be encountered Nowadays. It is clear that our ancestors, to the extent that assimilation has any relevance, had a less fat diet and more based on polyunsaturated fats, consumed much less sodium, more potassium, and more fiber.
Thus hypertension is the disease of acculturation, the inevitable consequence of a lifestyle increasingly unsuited to our genetic heritage. The main cause is excessive food, too rich in salt and saturated fats, as well as alcohol, and other perversions of the so-called modern society. This is a guilty and probably reductive vision. It is the image of the good living, obese, red-haired, fat eater and drinker, pointed to as the candidate for a precocious and well-deserved death.The immigrant, unemployed, eating only a little more and a little more salty than in his country of origin would be just as candidate, less guilty. On the contrary, the return to a hunter-gatherer lifestyle, thin, with simple and sober habits, would illustrate the salutary return to the sources.
However, the genetic inheritance is not harmoniously distributed with regard to certain intermediate phenotypes involved in blood pressure, in particular sensitivity to salt. In the same environment, different populations and different subjects have profoundly different levels of blood pressure. This fact emerges very clearly from Fabre et al’s study, since the subjects studied, from the most diverse countries, all lived in Geneva, had lunch at the same canteen, had the same employer, and had all adopted, , a “western” lifestyle. Even if all environmental disparities were not eliminated (in particular, natriuresis had not been measured), the asymmetry between ethnic groups clearly outweighed the differences in lifestyle.
Thus, if one accepts this conflict between genetic predisposition to various intermediate phenotypes and an environment with complex influences, conflict ultimately being negotiated at a variable level of blood pressure, one should return to one of the initial questions. Why, for example, do rural populations have a low prevalence of hypertension in their home environment, and why does this prevalence increase if the environment is altered? Would this not mean that traditions had, among other purposes, to protect each community, with its genetic heritage as it was, against morbid phenomena? In such a scheme, each community would have had its own “adaptive wisdom”. The thousands of years since the hunter-gatherer would then have little importance. Only brutal migrations, on the scale of a very recent history, would have come to undermine the balances patiently maintained until then.
Quality of life:
There is an inverse correlation between educational attainment, income, and blood pressure. Contrary to popular belief that managers and executives pay a heavy burden to hypertension, quite a number of studies have shown that the prevalence of high blood pressure increases inversely at the socio-professional level. In Hypertension Detection and Follow-up Program (HDFP), in white subjects, the prevalence of hypertension was 13.5% for those with higher education compared with 23% for those with less than 10 years of schooling. In France, mortality from coronary heart disease has changed in the last 20 years in a very different way according to socio-professional categories. It was divided by five among senior managers, while it declined only modestly among employees and farmers. Overall, the relative risk of death of an employee relative to a senior manager in Paris is 3.5 for coronary heart disease and 2.93 for stroke. For a worker, this risk is 1.78 and 1.70 respectively.
It is interesting to note that in the Geneva study on the staff of international organizations, there was no difference in the prevalence of hypertension according to socio-professional categories. It is tempting to deduce that the difference lies not in an intrinsic factor related to the level of education or occupation, but rather in a quality of environment in general, and perhaps particularly in the level of education, access to the health care system, which is particularly homogeneous in this study.
Lang et al analyzed these factors, and showed that some categories have a lower level than others of detecting hypertension. Immigrants have a less frequent detection than natives of the country concerned, alcoholics also have a poor detection rate. In France, 35% of natives are unaware of their hypertension, compared with 63% of immigrants.The unemployed would also have less detection. The common feature of these poorly screened groups would be the lack of a regular care system, and the virtually exclusive use made of hospital emergency departments. This inequality contributes not only to the level of income, but also to knowledge of the health care system and access to social counseling.
The importance of this factor is well illustrated in the HDFP study, since in this study, subjects in the stepped care group under strict control of their blood pressure did not have a mortality gradient between the social categories, contrary to the control group referred care, treated more lax.
The idea that an increase in blood pressure is simply linked to the stresses of everyday life, to an emotional situation, or even simply to work perceived as aggressive, is extremely widespread. In other words, hypertension would be little more than the consequence of aggression by society, possibly in a vulnerable subject. This concept is particularly harmful insofar as it allows to deny the existence of a pathology, to retain only the stress, that is to say the exclusive responsibility of an exogenous factor. Consequently, if the pathology is denied, treatment does not need to be and, worse still, various sedatives too often take the place of antihypertensive drugs, with the inefficiency that we know.
It is well established that “stress” (with all the blurring that surrounds this word) is not, on its own, capable of generating a chronic HTA. It is only one of the risk factors involved in a multifactorial pathology. On the other hand, hypertension is often accompanied by an abnormal reactivity to stress. Indeed, an increased response of blood pressure to various laboratory stimuli (mental calculation, video games, psychological tests …) is known in hypertensive subjects, as in normotensive high risk of hypertension (family context).
Personality factors have also been demonstrated through dozens of psychological tests, leading to a concept of “hypertensive personality”.
Hypertension “limit” is often a young, hyper-emotional and anxious subject. This emotional lability goes hand in hand with an accentuation of the sympathetic response (tachycardia, sweating, trembling, moderate erythema) and an increase in plasma catecholamines. The situation is considerably less caricatured in the proved hypertensives, of significantly higher age, in whom catecholamines are less than in younger hypertensive patients. Beyond a well-known caricature of any clinician, it is not easy to identify a personality, according to a classification that is reliable enough to be correlated to objective quantitative variables. The methods and scales are innumerable, the classifications are hardly less so. The elements most often cited as belonging to the structure of hypertensive patients are anxiety and the repression of aggressiveness.
These personality factors are entangled with the response to stress. It has, moreover, been suggested that hypertensive patients who belong to the category of repression of hostility and idealization of social behavior would have a significantly increased coronary risk. These data, legendary and fragile, have been confirmed more recently by longitudinal studies, therefore less biased. Other environmental factors have been well demonstrated: unemployment, residence in “hot” neighborhoods, work with heavy responsibilities (air traffic controllers), noise. In total, it is reasonable to consider that hypertension, especially at its onset, is associated with increased vascular reactivity to “stress” in a broad sense. The intermediate is clearly an increase in sympathetic tone, which has given rise to a multitude of works. This hyperreactivity is often associated with personality factors, which seem to be dominated by a repression of aggressiveness and a strong management of the social image (image of the responsible subject, sociable, dominated emotivity, and unlimited reliability ). It also varies according to ethnicity. Finally, there appears to be a direct influence of a few “stressful” situations such as job loss and exposure to excessive noise levels on the level of blood pressure.
Sedentary lifestyle is another famous cardiovascular risk factor. A low level of physical activity is associated, in many studies, with increased cardiovascular mortality. It is also a direct factor in the prevalence of hypertension. In a cohort of Harvard alumni, non-sport subjects had a 35% higher risk of becoming hypertensive, regardless of their blood pressure level at university, their family history, and body weight. Another study reported a relative risk of hypertension of 1.52 in subjects with low levels of physical activity after 12 years of 6,000 subjects, adjusted for age, sex, blood pressure at the start of study and BMI.
It is clear that the “disease” hypertension is not a new data that appears one day. It is rather a continuum, which begins at birth with subclinical manifestations, the first clinical translations of which appear only at the end of adolescence, and whose symptomatic phase only appears at maturity , with or without visceral complications.
As we have seen, it is possible to reveal a whole series of physiological anomalies in young subjects, normotensive, but whose parents are hypertensive. These abnormalities relate to renal plasma flow, elimination of sodium, membrane pumps, certain natriuretic factors, and insulin sensitivity. They attest to the activity of the morbid process from the earliest age, and before the first clinical symptoms.
These usually appear in adolescence in the form of hypertensive outbreaks, usually short, and mostly related to stress.For these two reasons, they are often not taken into account, and attributed to “nervousness” alone. It is at this stage that screening would be easy, and that lifestyle measures could be taken to reduce cardiovascular risk. The missed opportunities for diagnosis, such as incorporation into the National Service or the monitoring of contraception. In women, it is often during the first pregnancy that hypertension makes it speak louder, causing more sterile panic than reflection. It is in fact only in the forties or fifties that the hypertension actually settles, whether or not symptomatic.Most authors report that hypertensive patients spend most of their lives practically without clinical symptoms and without complications of their disease. It evolves over a period of about 20 years on average without being talked about, before its complications cause the death of patients 15 or 20 years on average before what should have been their normal life expectancy.
The causes of death are largely dominated by cardiac pathologies. These are all the more frequent as the blood pressure figures are high. Patients with severe and resistant hypertension die mostly from stroke. Those with advanced retinopathy and renal impairment have a lower life expectancy.
HYPERTENSION OF ARTISTS AND VASCULAR RISK:
The fact that hypertension is associated with an increased vascular risk is too well known for it to be necessary to dwell on it. It is clear that the frequency of coronary heart disease, stroke, heart failure is greatly increased in hypertensive patients. The presence of left ventricular hypertrophy still heavily increases these risks.
Hypertension is not the only factor that can increase the cardiovascular prognosis of patients. The lipid profile, glucose tolerance, body weight, tobacco consumption, to mention only the main ones, are all risk factors that come to potentiate that generated by (or more precisely associated with) hypertension. We have also discussed the link between these various risk factors, which is evident in both clinical studies (syndrome X) and genetic polymorphisms, the effect of which appears to be relatively ubiquitous (eg insertion- deletion of the enzyme of conversion). The vascular risk is thus a whole, in which the hypertension is only one element of the puzzle, or even simply a marker.
There are a number of tables and formulas published in the literature and available on websites to assess the overall vascular risk of each subject, and this should be a valuable aid for therapeutic indications. The logic thus indicates that the taking into account of only one of the elements of the vascular risk in a patient is an attitude likely to fail. It is the whole of the risk that must be taken into account, but if this laudable principle is unanimously accepted, the modalities and results of such an undertaking are currently very ill-defined.
It is also necessary to remember that the multifactorial intervention studies that have been practiced here and there have not, so far, yielded the expected results.
which we shall not dwell here. This approach is in fact only the strict observance of the WHO recommendations, based on a so-called “operational” definition, that is to say, leading to a therapeutic strategy. Diagnostic problems are not solved by this semantic discipline alone.
It is “false hypertension”. This concept is fragile, and it is prudent to recognize as false hypertension only the circumstances in which the usual sphygmomanometer measurement is in gross discordance with direct measurement by the intra-arterial route, the use of which is certainly not routine. A striking example of this is found in subjects with poorly compressible arteries (for example medacalcosis), where the classical measurement is totally dissociated from the actual blood pressure.
The blood pressure level of each subject varies depending on the day and time, and many patients cross the fetal threshold defining hypertension several times a day in one direction and the other. They can not then speak of permanent hypertension. These subjects are often referred to as hypertensive “limit”. Most of them later become permanent hypertensive. If these subjects do not justify medication at this stage, the early introduction of hygiene measures is certainly desirable. Good surveillance is no less.
Some subjects appear to be hypertensive only during the medical consultation. These situations are called “hypertension of the white coat”. MAPA is the best way to detect such a situation, if it attests to a normotension over the 24 hours off medical consultation. However, the hypertension of the white coat should not be classified as “false hypertension” for several reasons: the incidence of permanent hypertension is higher in these subjects than in others;the frequency of cardiovascular complications is also increased; the terrain, familial and metabolic, is usually that of hypertensive.
Rather, it should be regarded as an exaggerated response to stress, which is particularly demanded by the physician, and which may indicate a predisposition to hypertensive disease. However, it is important to make the diagnosis, not only to avoid unnecessary treatment, but also to manage the associated vascular risk. The distinction with “limit hypertension” or “prehypertensive” states is probably only a question of subtle semantics.
Affirming essential hypertension:
If essential hypertension accounts for 90% or more of hypertension, it is essential not to overlook secondary hypertension. Considering the diagnosis here would take us too far. We shall confine ourselves to recalling two simple principles.
The first is that any hypertension must have a minimal etiological balance. In addition to a suitable clinical examination, this should include the following tests: urine test, creatinine, blood glucose and serum potassium, hematocrit, and lipid profile. An electrocardiogram can usefully supplement this minimal balance. The latter, which is particularly simple and inexpensive, makes it possible to detect the majority of secondary hypertension and to have an evaluation of the overall vascular risk. Endocrine explorations (including catecholamines and vanylmandelic acid -VMA-) and renal morphological investigations (including ultrasound) are considered unjustified, at least initially, by the “Opposable Medical References” in La France.
The second principle is that the existence of a particular clinical symptomatology (the symptomatic triad of pheochromocytoma, signs of hypercorticism, a lumbar blast, etc.), or the resistance of hypertension to a properly conducted treatment, the etiological assessment, and to add to it more complete and targeted explorations.
VALIDATION OF TREATMENT: MAJOR STUDIES
The purpose of antihypertensive therapy is not simply to reduce blood pressure to normal. This only makes sense if it reduces the risk of cardiovascular events and mortality from hypertension. As soon as effective antihypertensive drugs have appeared, the utility of treating severe hypertension has become evident: the frequency of strokes, heart failure, nephroangiosclerosis have been reduced dramatically, and the expectation of life of these patients has increased considerably.
The same demonstration was more difficult to provide for moderate hypertension, which nevertheless represents the bulk of hypertensive patients. Large prospective studies were conducted between the 1970s and 1990s. Although their findings were not ambiguous, it was they who validated the antihypertensive treatment and made it possible to refine the recommendations of the international organizations.
Collins et al published a meta-analysis of these studies, involving some 37,000 patients, with a follow-up of 5 years.They showed that the treatment reduced the frequency of strokes by 42%, which corresponds to the gap predicted by the epidemiological data. On the other hand, the frequency of coronary artery disease is reduced by only 14%, which is barely half of what could be expected.
Several meta-analyzes of therapeutic trials in the elderly have produced more convincing results. For Lever and Ramsay who analyzed the six major studies, the incidence of fatal stroke is reduced by 33%, fatal coronary events by 26%, and overall cardiovascular mortality is reduced by 22%. These results have definitively validated the antihypertensive treatment in the elderly.
The relatively disappointing character of the reduction in the incidence of coronary artery disease in the meta-analysis of Collins et al probably reflects the multifactorial nature of the risk. These results can be compared with those of cholesterol-lowering studies, which showed little preventive effect on stroke, and a major effect on the incidence of myocardial infarction.
Studies that have been subjected to these major meta-analyzes have mainly included diuretics and beta-blockers as therapeutic agents. For this reason, the international bodies considered that these therapeutic classes had actually validated a reduction of the risk and should therefore be used as a priority. It is unfairly making little use of more recent medicines, with which long-term studies are still in progress.
In fact, it is not evident that at the same reduction in blood pressure all antihypertensive drugs are equivalent in terms of cardiovascular prevention. If we consider, for example, the reduction of HVG, all the intermediates exist between the direct vasodilators which accentuate it and the inhibitors of the enzyme of conversion which allow the most important regression. It has even been shown that regression of HVG can be achieved with an ACE inhibitor without reduction of blood pressure. Similarly, while it is true that cellular hypertrophy and proliferation play at least as important a role as mechanical stress in the genesis of hypertensive vascular disease, perhaps it is on the mechanisms of cellular trophicity that it is necessary to act even more than on the figures of blood pressure. There remains many studies to be carried out, and perhaps a profound modification of the choice of the target in antihypertensive treatment.
Hypertension is a particularly common condition. Kaplan noted that “a growing enthusiasm, almost unbridled for early and aggressive drug therapy, began in the 1970s, so that in the US the treatment of hypertension is now the first reason for consultation and prescription of ‘a drug. The result is that more than 30% of Americans aged 55 to 64 take an antihypertensive drug, and more than 40% between 65 and 74 years. It is likely that these proportions are still growing. “ This increasing proportion of subjects taking antihypertensive treatment contrasts with the modesty of the percentage of controlled hypertensions. It is also fairly obvious that a large number of subjects are treated without any real justification, and even without a well-established diagnosis. Thus, the international recommendations were aimed at a closer approach to the question: who to deal with, and how? to give a brief summary: two categories of patients justify the early and unconcerned establishment of a drug treatment: “severe” hypertension, that is to say after 180/105 at all consultations , and hypertensions with visceral resonance (HVG, retinopathy, early nephropathy); in other cases, classified as mild hypertension, both in terms of blood pressure and absence of visceral reactions, is initially limited to non-medicinal measures, while monitoring the patient by 3 in 3 months. It is only when there is a persistence of numbers exceeding 160/95 after a fairly long period of observation and hygiene measures that medicinal treatment can be discussed. Finally, the patient with a high overall vascular risk (family history, lipids, tobacco, etc.) could benefit from treatment even with lower figures, of the order of 140/90 or more.
Some hygiene measures must be applied systematically, whether drug therapy is initiated or not. These measures alone are likely to normalize mild hypertension, and in any case promote the activity of antihypertensive therapy. This is mainly a return to ideal weight, decreased consumption of alcohol and sodium, and regular practice of moderate exercise. Increased intakes of calcium and potassium have not proved to be of any real value. As for the cessation of smoking, if it is desirable to reduce the risk of vascular disease, do not expect a result on blood pressure.
In principle, any antihypertensive therapy must first be a monotherapy. We recall here some simple and well-accepted principles.
This monotherapy should be based on one of five major therapeutic classes: diuretics, beta-blockers, ACE inhibitors, calcium channel blockers, and alpha blockers. In large cohort studies, these different classes of antihypertensive drugs have a substantially equivalent effect on blood pressure.
The choice is not indifferent as there are significant differences in effectiveness between classes for subgroups of patients. Thus, young subjects respond better to ACE inhibitors and β-blockers, while elderly patients respond better to diuretics and calcium channel blockers. In the most recent studies, these differences are relatively marginal, but remain indisputable. Irrespective of age, Black subjects respond better to Whiteheads than Calcium Inhibitors and Diuretics.
All antihypertensive agents have side effects, clinical or metabolic, whose profile may be critical in some patients. They also have contraindications that can be decisive in this choice. The different classes of drugs, besides their effectiveness on blood pressure figures, also have “ancillary” effects that can be specifically sought. These may include immediate effects: slowing heart rate under beta-blocker, the hyperkinetic subject of which will experience immediate benefit, the anti-anginal effect of the same drugs, or the remarkable action of ACE inhibitors cardiac insufficiency. On the contrary, they can be long-term effects, that is, prevention of certain complications. Such effects are even more often discounted than actually demonstrated, apart from the undisputed protective effect of ACE inhibitors on diabetic nephropathy or even all renal insufficiency.
The cost of antihypertensive drugs varies by a factor of 20 depending on the class and the product.
This initial monotherapy only normalizes blood pressure in some 50-60% (at best) of patients. In the others, two attitudes are possible: if there is total resistance to treatment, it is legitimate to attempt a monotherapy by another therapeutic class; the choice should be made for a diuretic or calcium channel blocker if failure has occurred with an ACE inhibitor or a beta-blocker and vice versa; if there is a response to the treatment, but partial and considered insufficient, the logic is rather to associate a second component, chosen according to the same criteria as above, which guarantees a suitable synergy between the two products; it can be a fixed combination, which has the merit of limiting the number of tablets, whose psychological impact on the patient is notable.
In any case, increasing the dosage of a drug makes very little gain in efficiency and loses much in terms of side effects. So it’s a bad policy.
A small fringe of hypertensive patients remains desperately rebellious to treatments. The causes of this lack of response can be extremely diverse. The main ones are: poor compliance, or even total absence of medication;overweight, alcohol abuse; excessive sodium intake, or volume overload (nephropathy); poor dosage or incorrect combination of drugs; Secondary HTA;
In the presence of apparently resistant hypertension, first of all it is necessary to ensure compliance, to make a DAPA to ensure the permanence of this hypertension, to check the sodium intake by a 24-hour natriuresis, and check the coherence of the therapeutic association. In any event, hypertension can be considered as refractory only if its treatment includes at least one inhibitor of the conversion enzyme and a diuretic. In this case, it is appropriate to take again the etiological balance, to the much more meticulous search for a secondary hypertension.
It should be remembered that the management of a single vascular risk factor in a patient with multiple risks is doomed to failure, even if the blood pressure is reduced to normal. For example, antihypertensive medications are more effective in preventing stroke, while cholesterol-lowering therapy is particularly important for coronary heart disease, and diabetes and smoking still increase these risks and therapeutic measures. These data mean that the treatment modalities are specific to each individual and adapted to his particular situation.
Some authors currently advocate therapeutic action based not on the level of a risk factor but on the “absolute” risk to the individual (all factors combined) of having a complication within the next five years. The treatment would then be applied only to patients whose absolute risk exceeds 10 to 15%, or else by the inverse, the number of subjects to be treated to avoid an accident. This reasoning is based on considerations more economical than properly medical, and merits evaluation.
Through this chapter, we have tried to highlight the many facets of essential hypertension, rather than dwelling on clinical considerations well known to all. There is no doubt that physiopathological, and probably genetic, knowledge will evolve rapidly. To date, we have definitions and a therapeutic codification which represent a necessary framework.In conclusion, we would like to emphasize the weaknesses of our current knowledge, and to mention a few points which will undoubtedly be of importance in the future.
All our definitions are based on figures of systolic and diastolic pressure, or pulse which does not change anything.However, the shape of the pressure wave varies widely from one subject to another, leading to a very different arterial stress. The reflections of this wave are beginning to be better known and their importance already appears. Our measurement methods, and therefore our definitions, may quickly become obsolete.
The evaluation of antihypertensive treatments is always based on lower blood pressure figures. But we have seen that this is not the most important point, and the criteria of judgment may evolve.
Finally, much remains to be done in the selection of patients who can really benefit from treatment. Even if we put aside the economic constraints, which will undoubtedly weigh heavily, obtaining a favorable relationship between the therapeutic benefit, the number of subjects treated, and the iatrogenic pathology, is an objective major.