Hypertension 1996 : One Medicine, Two Cultures

Primary and secondary prevention of arterial hypertension

A. De Francesco
Division of Intensive Coronary Therapy at “Addolorata” Hospital, manager of Division Cardiology of Sport - Rome.

Introduction

Arterial hypertension is a clinical condition characterized by increased systolic/diastolic tensive values, by definition higher than 140/80-mmHg (1).
Within such wide limits, however, several individual variations may occur, which are used to define a necessarily rigid and schematic classification of the different hypertension types. Based on the criteria established by the World Health Organization (W.H.O.), all individuals with arterial hypertension values ranging from 140/90 to 160/95 mmHg in at least two measurements out of three, performed at five-minute intervals, may be defined as “borderline hypertensive patients” (2).
The importance of such surveying method derives from a precise fact: a random pressure increase may be observed in some individuals as a consequence of an abnormally strong emotional reaction occurring as soon as the physician approaches, but is lower in the presence of a nurse and decreases, or even disappears, at self-measurement; indeed, tensive values in these patients fall within a normal range at automatic 24-hour monitoring. These factors define the so-called “white-coat hypertension”, the outbreak of a clear alarm condition experienced by some individuals who actually do not seem to be exposed to a true hypertensive risk: indeed the quad vitam prognosis for these individuals fully corresponds to that of normotensive people (3,4, 5).
The tensive condition characterized by systolic values equal to or exceeding 160 mmHg, combined with normal or reduced diastolic values, i.e. equal to or lower than 90 mmHg, is defined as “isolated systolic hypertension”. This type of hypertension is typically observed in elderly patients, or anyway aged over 55, and derives from a reduced flexibility and stretching ability of large arterial vessels (1, 6, 7, 8).
Unlike systolic hypertension, the diastolic form, characterized by tensive values equal to or higher than 90 mmHg, progressively increases, in the general population, up to the age of approximately 55, and remains more or less unchanged thereafter (9).
The above definitions are obviously limited to primary or "basic" arterial hypertension, while we will not dwell in this context on the "secondary arterial hypertension" conditions due to other causes, discussed in the appropriate internal medicine books.
After generally defining “arterial hypertension”, it is worth stressing the need to adopt a scale of severity based on pressure values for all hypertensive conditions. Starting from the lowest level, which coincides with “borderline hypertension” (>140/90 and <160/95 mmHg), this scale moves gradually up to “mild” (same as the “borderline” form in America) or “moderate” arterial hypertension (160/95 and <180/110 mmHg), to the “moderate-severe” (>180/110 and <210/120 mmHg) and up to the “severe” form (>210/120 mmRg); the so-called “malignant arterial hypertension”, now hardly ever observed, was characterized in the past by even higher values (5).
After outlining the importance of the severity of hypertension, a further classification is now required based on the age of the patient and/or of the population examined, since arterial hypertension represents an important "risk factor" for the development of cardiovascular diseases in general and atherosclerotic ones in particular. In this respect, this classification is based on the so-called "time/dose product" resulting from the patient's age and/or the dating of the hypertensive condition multiplied by the latter's severity (1).
The term “risk factor”, introduced by the creators and performers of the Framingham Study and by now universally employed, is meant to fill in the logical gap between the concepts of association and cause referring to at least two phenomena that are assumed to be interrelated; it is better defined as a “factor associated with a disease or clinical condition, which is suspected to contribute to the pathogenesis of the latter” (1).
The hypothesis was formulated that the necessary conditions for the development of atheromas at systolic pressure values as low as 120-140 mmHg be established at an endothelial level: this assumption supports the aphorism by which “the lower pressure values, the better; unless the individual faints every time he/she stands up”.
On the other hand, the epidemiological data provided by the different trials showed that a progressively higher risk of vascular accidents corresponds to increasing arterial pressure values, even in case of an isolated increase in systolic arterial pressure; in addition, high diastolic pressure values seem to involve an increased relative risk of both stroke and coronary disease (1, 2, 5, 6, 7, 9, 10).
In the light of the above, the wish to carry out “primary prevention” of arterial hypertension implies pursuing the preservation of good health conditions in order to reduce, or even eliminate, the risk of observing increased tensive values in individual patients or, even more, in the whole population in time.
On the other hand, once pressure values have started increasing, the need emerges to reduce as much as possible the relative and/or even the absolute risk of cardiovascular complications that may result from any hypertensive condition: thus "secondary prevention" of arterial hypertension may be carried out (11, 12).
In order to put all this into practice, it should be considered that different problems may affect paediatric patients compared to young adults and, even more, aged or elderly patients, and that therefore different therapeutic approaches should be adopted.
The problems and therapeutic approaches will therefore be different for a young patient, for an adult patient or for an elderly patient.

Paediatric age: primary prevention

Some authors point out to the possibility to start preventing the onset of arterial hypertension even immediately after conception, during intrauterine life, based on the observation that a low weight at birth, combined with the large size of the placenta, seems to be often associated, in adults, with a high mortality rate due to cardiovascular diseases, with glucose intolerance and, particularly, with a true hypertensive condition (13, 14, 15).
As a consequence, physicians should be encouraged to adopt a more careful primary prevention, especially if cardiovascular diseases and/or hypertension may have a familial origin (13, 16). However, even if more attention is devoted to the prevention of possible hypertensive conditions in new-born babies, physicians should never forget that “children are not little adults”: no drugs may and should be used for them, but rather strong and effective hygienic and feeding principles aimed at altering, as far as possible, the so-called familial pattern, to which both inheritance, which may not be modified, and the environment, which instead may be thoroughly modified, contribute in various ways and to different degrees (1, 17).
Diet control, aimed at reducing at least two of the three main cardiovascular risk factors - hypercholesteraemia and arterial hypertension - should start in the first two years of life, focusing on breast feeding at birth and on delayed weaning with solid food at 4/6 months of age, while trying to avoid adding sugar to the baby's milk, as well as cooking salt and/or seasonings in food preparation at weaning (1).
A delayed introduction of packaged food into the feeding scheme of all babies is also strongly recommended: indeed, such food formulas involve a four-fold increase in sodium intake compared to normal conditions; in addition, the energy they provide is often higher than needed as well as unbalanced in terms of nutrients, since it involves a considerable intake of sucrose and cholesterol along with a low polyunsaturated to saturated fats ratio. These observations add up to the fact that the consumption of packaged food is usually combined with a reduced intake of fruits and vegetables: the possible integration with vitamins and mineral salts in the package does not really change the fact that those kinds of food will hardly ever find the place they are entitled to within the feeding schemes of adults-to-be (1).
In the first two years of life, the adoption of healthy feeding habits should focus on moderation rather than on the elimination of some types of food, and a wide range of nutritionally balanced food products should be introduced while basing the energy intake on the growth requirements that allow to preserve the desired body weight (1).
Starting from the age of 2, a maximum 30% of calories should be provided by fats and most of the rest should be obtained from vegetal proteins and complex carbohydrates: as for adults, saturated, polyunsaturated and monounsaturated fatty acids should provide 10% of the total calories each, with less than 300 mg/day of cholesterol and less than 5 gr./day of sodium chloride, while the intake of fibres, including soluble ones, should be increased (1).
In order to reduce the intake of saturated fats in children's diet schemes, the main targets to be focused on in view of the primary prevention of atherosclerosis and hypertension should be represented by whole milk, various kinds of sweets and packaged snacks: the latter, like all fatty sweets, are rich in single carbohydrates and able to provide at least twice as many calories as fruits and vegetables at equal weight.
The main source of sodium, whose quantity may hardly be assessed, is rather represented by grains and derived products (bread and pasta), while vegetables rank second. The shift to sodium-free or low-sodium feeding schemes (when used, sodium and its quantity should be indicated on the appropriate package), a reduced use of packaged food products, the purchase of fresh rather than canned vegetables, and the use of spices instead of salt for cooking or eating should allow a significant reduction in sodium intake with food. In Italy, charcuterie products and sausages as well as cheese, also represent a considerable source of sodium: such kinds of food, due often to uninformed parents, sometimes account for a large share of daily food intake (1, 9).

Paediatric age: secondary prevention

After expressing these general introductory considerations, which apply to any one, two possible strategies for the control of cardiovascular diseases, even at a paediatric age, should be described: one of them concerns the population, while the other one is defined as the "high risk" strategy. The former, which we have been outlining so far, provides for an approach to public health, involving both individuals at prospective risk of coronary disease (e.g. familial origin) and people that are not deemed at risk; such approach is adopted in view of a downward shift of risk-factor distribution throughout the whole population. In the treatment of the paediatric and teen-age population, efforts should focus on the onset of correct life styles, including on-going physical exercise to be introduced into behavioural patterns, while turning individuals accountable for their own health. The adoption of these correct habits should also spread to include the third major cardiovascular risk factor, i.e. cigarette smoking; in addition, nowadays, measures should be taken against the intake of light and/or heavy drugs and the consumption and/or excess of alcohol (1).
The "high-risk strategy", on the other hand, applies to individuals who are subject to precise and clearly defined cardiovascular risk factors, such as, in our case, arterial hypertension: in high-risk individuals, subject to overt hypertensive conditions during their paediatric and/or teen-age, a priority measure may provide for the use of drugs. In these infrequent situations, not including secondary arterial hypertension cases due to other causes, calcium-antagonists, ACE-inhibitors and, for the forms akin to the so-called “hyperkinetic heart syndrome”, Beta-blockers are the least harmful drugs that may be used: the three groups, and the latter in particular, may benefit from a correct aerobic exercise schedule, whose effects may add up to those provided by the drug, sometimes allowing a dose reduction: the above-described hygienic and feeding principles will represent a correct and inevitable integration (1, 5, 11, 12).

Adult age: primary prevention

Up to 40% of adult hypertensive patients show a cholesteraemia >240 mg % and an approximately double incidence of obesity and diabetes compared to normotensive people: a reduction, possibly targeted, of any of these risk factors may turn out to be a spontaneous cause for the relevant failure in the prevention of coronary heart diseases (18), which usually have a multiple-factor origin.
Recent epidemiological and clinical data confirm that metabolic risk factors and arterial hypertension may have a common origin, at least in some individuals: indeed, an insulin excess is potentially able to raise pressure values by stimulating sodium re-absorption by the kidneys, by activating the adrenergic nervous system, by stimulating the proliferation of smooth muscle cells of the mean arteriolar, by altering transmembrane ion exchange, by raising triglyceridaemia, by reducing HDL cholesterol, etc. (12, 13, 18).
In addition, the plasma concentration of insulin in each individual may be the result of an integration of 1) an excessive current and past food intake, 2) an androgenic hormone pattern encouraging the accumulation of a fat excess in the trunk, 3) a sedentary lifestyle, and 4) chronic stress conditions, also including cigarette smoking which is suspected to cause a repeated stimulation to the sympathetic nervous system. A chronically increased insulin rate in blood brings about a downward adjustment of this hormone's action, while chronic hyperglycaemia may reduce glucose-induced insulin secretion. The overall effect of this homeostatic system is such that the two variables, insulinaemia and glycaemia, will always vary proportionally, provided that insulin secretion continues.
However, since an on-going insulin excess is not compatible with survival, the body develops an insulin-resistance which may be either primary (of unknown origin) or secondary (puberty, traumas, any kind of stress), in order to mitigate the harmful effects of hyperinsulinism (12, 13, 18).
The insulin-resistance observed in basic arterial hypertension is of the primary kind, i.e. of unknown origin, and mostly located in the skeletal muscles, where it specifically affects glycogen synthesis causing a subsequent endogenous hypertriglycaeridaemia and a triglyceride deposit in the fatty tissue, especially in the abdominal region. The term insulin-resistance derived syndrome, or polymetabolic syndrome, or X syndrome thus seems to point out to a “risk” syndrome rather than to a true pathological condition, which identifies an association between obesity, arterial hypertension, hypertriglycaeridaemia, carbohydrate intolerance and hyperinsulinaemia and/or insulin resistance, and may represent an important warning sign of diseases that may cause accelerated atherosclerosis or ischaemic heart diseases (12, 13, 18).
This combination of several risk factors, including at least hypertension and a metabolic disorder and/or obesity, heavily affects the medical record of hypertensive patients, while encouraging the quicker development of ischaemic coronary disease and/or an enlargement of the left ventricular mass: this is why it should always be pursued, in view of correct diagnostic and therapeutic approaches which should always include non-pharmacological remedies as well (18).
Thus, before issuing any drug treatment, it may be quite useful to adopt non-pharmacological measures to control tensive values, especially in borderline and mild arterial hypertensive patients, but in all other patients too. However, once it is issued, this treatment should not exclude a combination with the hygienic and feeding principles previously recommended and implemented (2).
A weight loss in obese patients, a decreased alcohol consumption down to a maximum 20-30 gr. of ethanol per day, a low-sodium (allowing for a maximum 5 gr. of sodium chloride per day), low-calorie diet, with a high fibre content (at least 30 gr./day including 50% of soluble and 50% of insoluble fibres), regular aerobic exercise (at least 2-3 times per week with 1-hour or longer sessions, while carefully keeping a regular heart rate of 70 to 85% of the theoretic age-related maximum rate); discontinuing or at least sharply reducing cigarette smoking, possibly replacing it with pipe smoking: all these measures together may result into an outstanding fall in tensive values, at least in some patients (2, 12). Other feeding measures, such as reduced coffee consumption down to a maximum two cups per day, the intake of potassium, calcium or magnesium-rich substances (i.e. some types of fruits and legumes and hard mineral water), the increased intake of polyunsaturated fats (mainly contained in white meat and sea fish), and a reduced saturated-fat intake (mainly due to all animal-derived products) could be useful, even though this has not been demonstrated for sure (1, 2, 10, 11, 12). The control of a possibly associated diabetes or lipoidoproteinosis by means of dietary and therapeutic measures and the discontinuing of any oestroprogestinic contraceptive treatments represent other related measures required for hypertensive patients of both sexes.
Adults should avoid eating afternoon snacks; if this is impossible, it could be useful to eat season fruits or raw vegetables (cucumbers, carrots, and fennel), while only consuming sherbets and ice-lolls occasionally and alternatively in the summer period. The physician's and dietician's effort is very hard, though, since it is not aimed at establishing a correct lifestyle, but rather at encouraging behavioural changes that are often hard to achieve by individuals who follow established bad hygienic and feeding patterns, and sometimes even harmful, if not correctly implemented. In some rather uncommon successful cases, especially with respect to the achievement and/or preservation of an ideal or even just acceptable body weight, the effort required to keep it unchanged is often even harder and stronger. However it is worth stressing that general behavioural norms in adults may not be deemed equally important for all types of hypertension: indeed, they represent almost all of the possible therapeutic measures in mild and/or borderline forms, but they gradually lose importance as more severe hypertensive conditions are observed; notwithstanding this, even a simple weight loss in obese patients is likely to induce a sometimes steady fall in tensive values (20, 21, 22).
The Tohms study, carried out on 902 patients with mild arterial hypertension, of both sexes and aged 45 to 69, highlighted the need to adopt an aggressive therapeutic approach to any degree of arterial hypertension, while stressing that a combination of drug treatment and general behavioural norms is more effective in achieving pressure values control as well as in preventing the clinical signs of hypertensive heart diseases and abnormal ultrasound-scanning results (6, 9, 18, 20).
Indeed, even if the absolute ictus and coronary disease risk in mild hypertensive patients may not appear as high as in moderate and severe hypertensive patients, clinical studies suggest that, whenever mild pressure increases are not monitored, arterial pressure values are very likely to shift from moderate to considerably high in the relatively short term (10).

Mature age: secondary prevention

The absolute risk of cardiovascular complications for male adults is anyway higher than for females at all systolic pressure levels, although the relative risk is the same for both sexes due to the above-mentioned dose/time ratio, which may reasonably be deemed equal for individuals of the same age. However, the absolute risk related to increased pressure values appears much higher in elderly males and becomes even more serious as age increases, irrespective of pressure values.
The biological role hypertension is assumed to play in cardiovascular conditions has been clearly described: a long-term arterial pressure increase causes a greater pressure load on the heart and ultimately produces left ventricular hypertrophy. In addition, high-pressure levels may also cause arteriolar smooth-muscle hypertrophy, which may even result into a functional impairment of the kidneys. Finally, at a brain level, increased pressure values may cause damage to the arterial wall and a subsequent haemorragic ictus. Increased pressure levels then generally result into an accelerated atherosclerosis, especially at a coronary level (9, 10, and 18).
Last but not least, a steady deviation (at night and day) of pressure towards higher values may occur, a disorder, which is potentially able, in time, to cause, left ventricle hypertrophy. This is a concentric hypertrophy due to the addition, by myocytes, of parallel contractile proteins, which may occur at a mere systolic pressure increase. Until recently, left ventricular hypertrophy seemed to reflect the progressive increase of arterial pressure and of the left ventricular post-load, in turn probably linked to a parallel increase in total peripheral resistance; quite recent outcomes, however, seem to point out to a reduced flexibility and stretching ability of large vessels as the main cause for LVH (8, 18). Other authors consider the missing pressure reduction during the night reported by a few patients as a possible cause for LVH; in particular this could be responsible for changes in the shape of cavities and for concentric hypertrophy, both related to an increased rate of cardiovascular complications (24).
Indeed, many studies in very recent years highlighted that pressure levels are not always correlated with the size of the ventricular mass, almost as if other factors, besides pressure overloads, not necessarily of a haemodynamic kind, could play a role in its development: humoral substances (noradrenaline, angiotensin), intramyocyte substances, concurrent diseases, such as exogenous obesity and/or diabetes mellitus, etc., an endothelial damage brought about by high tension (with a subsequent defective synthesis and release of the endothelium-derived releasing factor (EDRF) and of the endothelium-derived constrictor factor (EDCF) or endothelia in) (1, 2, 5, 19, 24).
Whatever its origin, LVH always represents an adjustment aimed at delaying the onset of cardiac decompensation in physiopathological terms. As a consequence, however, the heart is subject to coronary impairment following up an intramural arteriolar rarefaction, a reduced capillary density per heart mass unit, and a mean hypertrophy in small coronary arteries 1 mm and, ultimately, an increased coronary resistance. All this is combined with collagen build-up and subendocardial fibrosis, with subsequent chronic hypoperfusion as well as a higher risk of heart arrhythmia and/or sudden death (18).
The progressive development of atherosclerotic diseases takes a rather long time, often longer than major trials performed in order to ascertain the effectiveness of treatments, but the ictus risk undoubtedly rises more quickly than the coronary disease risk. The high incidence of risk factors related to atherosclerotic diseases in the coronary circle is very likely to reduce the potential impact of decreased pressure values over a composite-risk pathological process. However it is quite clear that a fall in pressure values reduces risk and extends survival, both in mild hypertensive individuals (moderate or borderline) and, even more so, in patients with high or very high pressure levels (severe or serious) (10).
In cases requiring drug treatment, the global clinical conditions of patients and the side effects of drugs should be taken into account: if the patient also shows metabolic disorders, the potential effects on metabolic parameters, on which Beta-blockers and thiazide diuretics seem to exert the strongest effects (5, 18), should be particularly monitored. Administration of the former, especially if they are not heart-selective and have no intrinsic sympatheticomimetic activity, may block the effects of hyperinsulinaemia, so that hypertriglycaeridaemia and a reduced HDL cholesterol value may be observed during chronic treatment (18).
In a strictly metabolic sense, ACE-inhibitors and calcium-antagonists appear as the drugs of choice, since they may also positively affect the development of atheromatous plaques as well as a reduction of the left ventricular mass which, as mentioned, may alone influence the outcome for hypertensive patients (5, 18, 19, 24).
However, based on current knowledge, it does not seem correct to consider the drug-related heart mass reduction as beneficial, at least as long as it is not possible to establish precisely whether this reduction occurs in the collagen-fibrotic part or in the muscular part; therefore it is not acceptable to charge with an increased risk drugs that do not cause a heart mass reduction (19).
Alpha-blockers and the new Alpha-beta-blockers, like carvedilole, show no undesired effects on glycoside and lipid metabolism, just like anti serotoninergic drugs, which however are not even able to reduce the left ventricular mass; especially the former produce positive metabolic effects, such as an HDL increase and a reduced triglyceride and total cholesterol rate. Physicians are responsible for the choice of the most appropriate drug for each case (6,15).

Senile age

Primary prevention is not applicable in elderly patients (>60), unless it has been undertaken in the previous years, but secondary prevention is still possible: indeed, arterial hypertension in individuals clearly showing a progression of arteriosclerotic processes, usually only at a systolic level, represents an important risk factor for the onset of brain vascular diseases and of all the major types of stroke. On the other hand, arterial hypertension also seems to be deeply involved in the pathogenesis and development of atheromatous injuries in extracranial vessels and in the hyaline degeneration of arterial walls, along with a subsequent aneurysm dilatation, of the small arteries entering the brain.
Data drawn from the Framingham cardiovascular study seem to confirm that the death risk of long-term hypertensive patients with other important associated cardiovascular risk factors (age, sex, cigarette smoking, cholesterol levels and glucose intolerance), due to any cause, is reportedly 31% lower and the cardiovascular death risk is 60% lower in patients submitted to long-term treatment compared to untreated ones (4, 25, 26).
This is the reason why arterial hypertension and all other possibly related important risk factors should be treated early and in an appropriate manner. In the SHEP (Systolic Hypertension in the Elderly Program) study, chlorthali done alone, even at low doses (12.5 mg/day), turned out effective for a reduction in the percent rate of lethal and non-lethal stroke in patients over 55 suffering from isolated systolic hypertension. Recently introduced drugs of a different kind, such as ACE-inhibitors and calcium-antagonists, are assumed to provide more substantial benefits (4, 6, and 27). However it is a good practice to use great caution in coping with hypertension in elderly patients, both in the isolated systolic and in the systolic-diastolic form, whether or not associated with other cardiovascular risk factors.
Indeed no brain flow self-regulation disorders following up a reduced vascular compliance should be induced, although they may always occur if related to possible changes in the anatomical structure of the vessel wall of elderly hypertensive patients. In this kind of patients there is no need to reach ideal arterial pressure values, but rather a satisfactory and gradual fall in arterial pressure values should be achieved: such results may often be obtained by simply reducing salt intake with the diet. Systolic hypertension in elderly people seems to be highly sensitive to this measure due to a reduced activation of the adrenergic and the renin-aldosterone systems (5, 7, 20, 22, and 27). Sodium restrictions should be combined with reduced alcohol consumption and calorie intake, in order to obtain a non-dramatic weight loss, however sufficient to keep the body weight within values not exceeding 15% of the ideal weight; cigarette smoking should also be reduced, while reduced cholesterol levels have not proved useful. On the other hand, a potentially effective increased potassium and fibre intake with the diet should be achieved through a more frequent consumption of fresh fruits and vegetables (5, 6).
A motor rehabilitation programme, strictly based on aerobic principles and correctly supported by expert staff according to typical heart rehabilitation measures, may also prove effective in these patients to achieve a better tensive value control (6, 27).

At the end of this discussion on such an irksome subject as prevention, which any physician tends to approach with great efforts and somewhat mistrustfully, we hope we have succeeded in contributing, however slightly, to throw light upon such a wide and complicated field as hypertension, in which practitioners tend to get lost if they are not correctly directed and driven: all this in view of an effective co-operation between specialized cardiologists and general practitioners.

References

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