The primary objective is to improve the risk of long-term cardiovascular mortality and morbidity.
This goal is:
- the smoke,
-the control of dyslipidemia that underlies atherosclerosis
-abdominal obesity
- diabetes,
- appropriate treatment of the associated clinical conditions
- the treatment of high pressure.
Risk factors
• Systolic and diastolic pressure
• Differential pressure (elderly)
• Age (M> 55 years; F> 65 years)
• Smoking habit
• Dyslipidemia
• C-Tot> 5.0 mmol / l (190 mg / dl) or:
• LDL-C> 3.0 mmol / l (115 mg / dl) or:
• C-HDL: M <1.0 mmol / l (40 mg / dl), F <1.2 mmol / l (46 mg / dl) or:
• TG> 1.7 mmol / l (150 mg / dl)
• Fasting plasma glucose: 5.6-6.9 mmol / l (102/125 mg / dl)
• Altered load blood sugar
• Abdominal obesity [abdominal circumference M> 102 cm, F> 88 cm]
• Early familiarity with the disease (M age <55 years; F age <65 years)
Diabetes mellitus
• Fasting plasma glucose ≥ 7.0 mmol / l (126 mg / dl) (repeated data) or:
• Post-prandial blood sugar> 11.0 mmol / l (198 mg / dl)
The first manifestations of damage due to high blood pressure consist of:
Fixed plate with attached thrombus: it is
an autoptic relief from coronary corpse
Hypertensive retinopathy, rigid and thinned
arterioles at the bottom of the eye
• Electrocardiographic evidence of IVS (Sokolow-Lyon> 38 mm; Cornell> 2440 mm * msec) or:
• Echocardiographic evidence of IVS (IMVS M ≥125 g / m2, F ≥110 g / m2)
• Thickening of the carotid wall (IMI> 0.9 mm) or atheromatous plaques
• Carotid-femoral pulse wave velocity> 12 m / sec
• Lower limb / upper limb pressure index <0.9
• Slight increase in plasma creatinine:
• M 115-133 μmol / l (1.3-1.5 mg / dl); F 107-124 μmol / l (1.2-1.4 mg / dl)
• Reduction of glomerular filtrate (MDRD formula) (<60 ml / min / 1.73m2) or
• Creatinine clearance (Cockroft Gault formula) (<60 ml / min)
• Microalbuminuria 30-300 mg / 24h or albumin-creatinine ratio [mg / g of
creatinine]: M ≥22, F ≥31
• Complete CV or renal disease
• Cerebrovascular diseases: ischemic stroke, cerebral haemorrhage, transient ischemic attack (TIA)
• Heart diseases: myocardial infarction, angina, coronary revascularization, heart failure
• Kidney disease: diabetic nephropathy, renal failure (creatininemia M> 133, F> 124 mmol / l),
• Proteinuria> 300 mg / 24h
• Peripheral vasculopathy
• Advanced retinopathy: haemorrhages or exudates, papilledema
The presence of at least three of the following risk factors: abdominal obesity,
impaired fasting glucose, blood pressure higher than 130/86 mmHg, low levels of
HDL cholesterol, elevated triglycerides, makes a diagnosis of metabolic syndrome.
M: male; F: female; CV: cardiovascular; IVS: left ventricular hypertrophy; PA: arterial pressure; TG: triglycerides; CTot: total cholesterolemia; C-LDL: LDL
cholesterol; C-HDL: HDL cholesterol; IMI: mean intimal thickening.
It is recommended that in all hypertensive patients the blood pressure is reduced to values below 140/90 mmHg and that lower values may be a therapeutic target to be pursued, if tolerated by the patient. Antihypertensive treatment should be more aggressive in the diabetic patient in order to reduce blood pressure to values below 130/80 mmHg. Similar pressure targets should also be pursued in patients with a history of cerebrovascular events and at least considered in patients with coronary artery disease. While bearing in mind a certain variability of effects between subjects, the risk of hypoperfusion of vital organs is actually low. An exception is orthostatic hypotension which should be avoided especially in elderly patients and diabetics. The existence of a J curve between events and pressure values in therapy was postulated on the basis of retrospective analyzes that showed that the incidence of events increases in the presence of particularly reduced diastolic values.
It has also been suggested that the curve J phenomenon affects pressure values well below those that represent the therapeutic target even in patients with a previous myocardial infarction or heart failure. In these patients, in fact, beta-blockers and ACE inhibitors have made it possible to obtain a reduction in the incidence of cardiovascular events even when the blood pressure was lower, due to the treatment, to the already low pre-treatment values. However, it must be remembered that, despite the use of a combination therapy, in many trials the systolic blood pressure remains higher than 140 mmHg. Even in the trials in which this objective has been achieved, the finding of adequate blood pressure control does not affect more than 60-70% of the patients enrolled. With the exception of ABCD, which has recruited patients with normal or high-normal blood pressure, no trial has allowed patients with diabetic patients to reach pressures below 130 mmHg. It is therefore difficult to reach the blood pressure target recommended by the Guidelines, especially when blood pressure pretreatment is high, or in elderly subjects in whom the increase in systolic values depends on altered aortic distensibility and vascular fibrosis. Trial data show that even when combination therapy is used, it is more difficult to reach the desired pressure target in diabetic subjects than non-diabetics.
When necessary, lifestyle changes should be established in all patients, including subjects with normal-high blood pressure and patients requiring pharmacological treatment. The aim is to reduce blood pressure and to modulate the other risk factors and associated clinical conditions, reducing the number and dosage of antihypertensive drugs to be used. However, lifestyle changes have not been proven in hypertensive patients to prevent cardiovascular complications and it is often difficult to maintain non-pharmacological intervention over time. The adoption of these measures should not delay drug treatment, especially in subjects at very high risk.
The overwhelming majority of randomized clinical trials, aimed at comparing active treatment to placebo or different types of active treatment, confirm what was already highlighted in the ESH / ESC 2003 Guidelines, ie, whether the main benefits of antihypertensive therapy depend by reducing the high blood pressure values per se and only partly by the type of drug used, whether thiazide diuretics (as well as chlorthalidone and indapamide), beta-blockers, calcium antagonists, ACE inhibitors and receptor blockers of angiotensin II are all drugs with well documented antihypertensive efficacy and can significantly reduce the incidence of fatal cardiovascular events.It is therefore possible to conclude that the main classes of antihypertensive drugs are all indicated as a therapeutic choice to start with and continue treatment, both in monotherapy and in combination. However, it has been shown that the five classes of drugs can differentiate between themselves for some therapeutic properties and specific characteristics.
Choice of antihypertensive drug. The results of two large trials and a meta-analysis showed that beta-blockers have no effect on cerebrovascular protection, despite the favorable effects on morbid and fatal coronary events. Therefore, beta-blocker therapy should be reserved for patients with history of angina pectoris, heart failure and recent myocardial infarction, ie the major complications of the hypertensive state. Beta-blockers, therefore, can still today be considered as a therapeutic option to start and / or continue the antihypertensive treatment. Beta-blockers should not be prescribed in hypertensive patients with metabolic syndrome or in the presence of abdominal obesity, impaired fasting glucose, carbohydrate intolerance or high diabetogenic risk, as they induce an increase in body weight, have unfavorable effects on glycolipid metabolism and favor more often, compared to other classes of antihypertensive drugs, the development of diabetes. Similar conclusions apply to thiazide diuretics. In most clinical trials, in which there was a high incidence of new cases of diabetes, the therapeutic strategy involved a combination therapy between a thiazide diuretic and a beta-blocker, making it difficult to discriminate which of the two drugs was the main responsible of the metabolic effects. However, these considerations do not necessarily concern new generation beta-blockers (such as carvedilol and nebivolol) which, compared to classical beta-blockers, show a lower diabetogenic effect. Since beta-blockers, ACE inhibitors and angiotensin II receptor blockers are less effective in black patients, it is preferable to use diuretics and calcium channel blockers in this case. Trials that analyzed the effects of intermediate onendpoint therapy revealed other differences between the various classes of drugs for some therapeutic effects or in some specific groups of patients. For example, ACE inhibitors and angiotensin receptor antagonists have been shown to favor regression of left ventricular hypertrophy (including fibrotic component), to reduce microalbuminuria and proteinuria, and to slow down the progression of renal dysfunction. The calcium antagonists were more effective in slowing the progression of the atherogenic process and vascular hypertrophy at the carotid level.
(see also The hypertensive patient)
The metabolic syndrome is an extremely negative prognostic factor because it can increase the cardiovascular risk of patients, both directly and indirectly, predisposing to major diseases such as arterial hypertension, diabetes mellitus and dyslipidemia. The treatment of arterial hypertension in patients with metabolic syndrome is particularly challenging because some classes of drugs, such as beta-blockers and diuretics, promote obesity, diabetes and dyslipidemia, therefore in subjects at risk for such diseases should be avoided or used with extreme caution. Calcium antagonists, on the other hand, are among the main classes of antihypertensive drugs available to physicians to achieve an effective reduction in blood pressure and organ protection. If we consider the antihypertensive efficacy on organ damage and on cardiovascular events, we can state that it is an underused drug class in the treatment of arterial hypertension.
Calcium antagonists have the same efficacy as ACE
inhibitors in determining a reduction in IVS, while they are more effective than
this class of drugs in preventing the progression of atherosclerosis. In
contrast, ACE inhibitors are more effective than calcium antagonists in slowing
the progression of renal failure. However, one aspect should be emphasized: the
fact that ACE inhibitors or AT-1 (sartan) antagonists offer better
nephroprotection than calcium antagonists. ACE inhibitors and AT-1 antagonists
block the vasoconstrictive effect of angiotensin II on the efferent arteriole
and, therefore, reduce intraglomerular pressure, which is the main mechanism of
nephroprotection exercised by these classes of drugs. On the contrary, calcium
antagonist drugs act indifferently on both afferent and efferent arterioles,
then expose the glomerulus to systemic pressure. However, to the extent that
calcium antagonists reduce blood pressure, they are in a parallel manner
nephro-protective, being well documented as the reduction of blood pressure is
the main mechanism that determines nefroprotection. As regards the effectiveness
of calcium antagonists on cardiovascular events, they seem to exert a specific
effect in the prevention of stroke, while as regards ischemic heart disease
their effectiveness depends on the extent of the reduction of blood pressure
values. The main limit to the clinical use of calcium antagonists is the
significant incidence of a side effect such as perimalleolar edema. Since in the
vast majority of patients it is necessary to use two or more antihypertensive
drugs in combination to reach the pressure goal, not it is useful on a practical
level to define which class of drugs of first choice is therapeutic. In fact, if
for the long-term therapy it is necessary to resort to the use of two or more
drugs, it is of marginal interest to choose which drug to start treatment with.
However, it has been shown that the various drugs do not have the same
tolerability profile, which can vary from patient to patient. Some specific
classes of drugs may be differentiated for some therapeutic effects on risk
factors, organ damage and specific clinical conditions, or in some specific
groups of patients. Bearing in mind the large amount of data collected so far,
it can be stated that the choice of antihypertensive medication (monotherapy or
combination therapy) will be influenced by numerous factors, including the
experience (favorable or unfavorable) that the patient has accumulated in
Previously using a certain class of antihypertensive drugs in terms of
antihypertensive efficacy and side effects, the effects of the drug on
cardiovascular risk factors in relation to the individual patient's risk profile,
the presence of organ damage and cardiovascular, renal or clinically manifest
diabetes diseases that may benefit from treatment with some medications over
others. Do not overlook the presence of other concomitant diseases that may
favor or limit the use of specific classes of antihypertensive drugs and the
possibility of interaction with drugs that the patient takes for other diseases.
Finally, long-acting drugs or formulations should be preferred, as they are able
to guarantee therapeutic efficacy throughout the 24-hour period once daily.
The simplification of the therapeutic scheme has positive effects on patient compliance with therapy. Moreover, from a prognostic point of view, it is important to obtain good blood pressure control, not only for sphygmomanometry but also during the 24 hours. Lastly, the use of long-acting drugs reduces the pressure variability.
In the ESH / ESC Guidelines there are some innovative aspects regarding factors to be considered in assessing the level of cardiovascular risk, which deserve to be reported. The metabolic syndrome is mentioned because this pathology, rather than an autonomous entity, is a clinical condition characterized by the presence of several risk factors in addition to the hypertensive state, the latter being negatively reflected on the overall cardiovascular risk profile.
- Particular importance has been given to the evaluation of organ damage, whose presence also at the subclinical level considerably increases the risk. A specific section was dedicated to the identification of subclinical organ damage and reference threshold values were proposed for each variable under examination.
- The list of renal organ damage markers has been expanded, which includes the calculation of creatinine clearance using the Cockroft-Gault formula or the glomerular filtration rate estimate using the MDRD formula. The inclusion of these variables depends on the fact that they are reliable markers of cardiovascular risk associated with renal failure. - Microalbuminuria has been considered as an essential parameter for the evaluation of organ damage because its determination is easy and relatively inexpensive. - The concentric ventricular left hypertrophy represents the structural cardiac alteration that significantly increases cardiovascular risk.
- It is recommended to perform assessments of organ damage in different districts (heart, vessels, kidney and brain), as the presence of multi-organ damage is associated with a worse prognosis than the condition characterized by damage of a single organ. -
- In the list of factors influencing the prognosis a variable has been added,
namely the increase of the pulse wave speed as an early index of altered
distensibility of the large arteries, while recognizing the still limited use in
the clinic. - A reduced value of the ratio between upper and lower limb pressure
values (<0.9) has been proposed as an index of atherosclerosis. This parameter
is relatively easy to evaluate in the clinic and is associated with an increase
in overall cardiovascular risk.
- The assessment of organ damage is recommended not only before the therapy is
set (for risk stratification) but also during treatment, as regression of left
ventricular hypertrophy and proteinuria are reliable indices of the protective
effects cardiovascular induced by therapy.
- Elevated heart rate values were included among the risk factors because
their increase is associated with a higher risk of cardiovascular and overall
morbidity and mortality (there is still no threshold value). Furthermore, a high
heart rate was of prognostic value for the risk of developing a hypertensive
state.
Lastly, resting tachycardia is very frequently associated with metabolic
alterations and metabolic syndrome. - The main diagnostic elements for
stratification in the "high" and "very high" risk categories are indicated.
The risk factors are:
SBP ≥ 180mmHg and / or diastolic blood pressure ≥ 110mmHg, systolic BP>
160mmHg and diastolic BP <70mmHg, diabetes mellitus, metabolic syndrome, three
or more cardiovascular risk factors, one or more marker subclinical organ damage
(ventricular overload or hypertrophy left ventricular concentric thickening of
the carotid artery wall and atherosclerotic plaques, reduced arterial
distensibility, moderate increase in the serum creatinine, decreased glomerular
filtration rate or creatinine clearance, microalbuminuria or proteinuria),
cardiovascular or renal diseases overt.
The presence of multiple risk factors of diabetes or organ damage mean that a subject, even with blood pressure values high-normal, falls within the category of high risk. In recent years, results of observational studies conducted in older individuals have shown that the relationship between cardiovascular risk and blood pressure are complex. This risk is directly proportional to the systolic pressure and, for each value, inversely proportional to the diastolic pressure. In this way particular importance is given, as a predictive factor of events, to the differential pressure.
The predictive value of the latter may vary depending on the characteristics of individuals. Within the wider meta-analysis of observational studies performed so far (61 studies, of which 70% in Europe, with the involvement of more than one million patients without coronary artery disease), the systolic and diastolic results are predictive of coronary mortality and cerebrovascular disease more clearly than differential pressure, especially in subjects aged less than 55 years. In contrast, the predictive role of differential pressure became apparent in middle-aged or elderly hypertensive patients who presented risk factors or comorbidities.
For many years, hypertension guidelines have considered pressure values as the main variable for discriminating the need and the type of therapeutic intervention. However, already the first ESH / ESC Guidelines had emphasized the importance of carrying out a stratification of the total or total cardiovascular risk profile in the diagnosis and management of the hypertensive patient.
This is because only a small percentage of hypertensive individuals presents an "isolated" pressure increase, while the vast majority of patients also show other cardiovascular risk factors, with a close relationship between the severity of the pressure increase and the extent of changes in glycolipid metabolism. Moreover, when present at the same time, the pressure and metabolic alterations are mutually reinforcing, with an impact on the global cardiovascular risk profile of an exponential and not purely additive type.
Finally, numerous evidences have shown that in high-risk individuals, the threshold and objectives of antihypertensive treatment, as well as other therapeutic strategies, are different from those of individuals with a lower risk profile. The main variables examined in risk stratification include, as in previous guidelines, traditional risk factors (demographic, anthropometric, familiarity for cardiovascular disease at a young age, blood pressure levels, smoking habits, lipid and glucose profiles). , the presence of subclinical organ damage, diabetes mellitus and confirmed cardiovascular or renal disease. The definition of hypertension can be flexible because it depends on the level of global CV risk. For cardiovascular risk (low, moderate, high and very high) we mean the risk of incurring fatal and non-fatal CV events at 10 years. The term "added" indicates that in the various categories the risk is above average.
The results of two large trials and a meta-analysis showed that beta-blockers have no effect on cerebrovascular protection, despite the favorable effects on morbid and fatal coronary events. Therefore, beta-blocker therapy should be reserved for patients with history of angina pectoris, heart failure and recent myocardial infarction, ie the major complications of the hypertensive state. Beta-blockers, therefore, can still today be considered as a therapeutic option to start and / or continue the antihypertensive treatment.
Beta-blockers should not be prescribed in hypertensive patients with metabolic syndrome or in the presence of abdominal obesity, impaired fasting glucose, carbohydrate intolerance or high diabetogenic risk, as they induce an increase in body weight, have unfavorable effects on glycolipid metabolism and favor more often, compared to other classes of antihypertensive drugs, the development of diabetes.
Similar conclusions apply to thiazide diuretics. In most clinical trials, in which there was a high incidence of new cases of diabetes, the therapeutic strategy involved a combination therapy between a thiazide diuretic and a beta-blocker, making it difficult to discriminate which of the two drugs was the main responsible of the metabolic effects.
However, these considerations do not necessarily concern new generation beta-blockers (such as carvedilol and nebivolol) which, compared to classical beta-blockers, show a lower diabetogenic effect. Since beta-blockers, ACE inhibitors and angiotensin II receptor blockers are less effective in black patients, it is preferable to use diuretics and calcium channel blockers in this case. Finally, a news out of the bag is that a good cure of diabetes with glyphosine and with the mimics of GLP-1, are the basis of good blood pressure control and cardioprotection in the diabetic patient.
Other link:
What about the ESH-ESC guidelines
Arterial hypertension and organ damage
Arterial hypertension and organ damage: damage markers
Focus on arterial hypertension
The difficult treatment of hypertension