Search

Hypertension is responsible for a relevant burden of cardiovascular morbidity and mortality worldwide. Although several appropriate and integrated pharmacological strategies are available, blood pressure control still remains largely unsatisfactory. Failure to achieve effective blood pressure control in treated hypertensive patients may have a substantial impact on overall cardiovascular risk, since it significantly increases the risk of both macrovascular and microvascular complications. Hypertension is arbitrarily defined as "resistant" or "refractory" when recommended blood pressure goals (clinic blood pressure <140/90 mmHg, or <130/80 mmHg in patients with type 2 diabetes mellitus) are not achieved, despite changes in lifestyle and treatment with adequate doses of at least three antihypertensive drugs from different classes, including a diuretic. A new non-pharmacological option for the treatment of patients with resistant hypertension has recently become available. Renal sympathetic denervation is a minimally invasive procedure performed via femoral access that uses radiofrequency catheter ablation to disable renal sympathetic afferent and efferent nerves. It results in isolation of renal parenchymal and juxtaglomerular cells from the abnormal enhancement of renal adrenergic nerve activity. The present position paper of the Italian Society of Hypertension provides a diagnostic and therapeutic approach to the early identification and effective clinical management of patients with resistant hypertension, who may be candidates for renal denervation. These indications may have important implications not only from a clinical viewpoint but also from an economic perspective. The accurate identification of patients with resistant hypertension and the appropriate selection of patients eligible for this procedure may help improve blood pressure control and reduce the risk of cardiovascular and cerebrovascular complications in these patients.

Observational studies demonstrate that the proportion of treated hypertensive patients who attain the recommended blood pressure goals (140/90 mmHg) does not exceed 30-40%. Conversely, clinical trials have consistently shown that effective blood pressure control within the recommended targets can be achieved in 70-80% of treated hypertensive patients with different cardiovascular risk profile, especially when appropriate, effective and well tolerated combination therapies are used. In order to bridge the gap between current and optimal blood pressure control rates and to achieve a more effective cardiovascular prevention, the Italian Society of Hypertension has recently developed an interventional strategy that aims to approximate 70% of treated controlled patients by 2015. This ambitious goal can be realistically achieved by the appropriate use of modern aids and tools, also including the implementation of combination therapy, especially if this approach can be simplified into a single pill, now available in Italy. At present, 70-80% of hypertensive patients require combination therapies based on at least two classes of antihypertensive drugs to achieve the recommended blood pressure goals. It is therefore of paramount importance to implement this strategy in routine clinical practice. Among the different combination therapies, the use of combination strategies based on drugs inhibiting the renin-angiotensin system, such as angiotensin receptor blockers and angiotensin-converting enzyme inhibitors, combined with diuretics and/or calcium-channel blockers, have demonstrated to significantly reduce the rates of major cardiovascular events and discontinuations from prescribed therapies, resulting in higher antihypertensive efficacy and better tolerability than monotherapy. The present document of the Italian Society of Hypertension aims to provide main indications for implementing combination therapy in the clinical management of hypertension in order to improve blood pressure control in Italy.

Aim: Calcitonin is a hormone secreted by thyroid C-cells. Its primary effect seems to be a direct inhibition of bone degradation, but the physiological function of calcitonin in humans is still uncertain. The role of this hormone in the development of osteoporosis is unknown, but few authors have shown bone mass reduction in thyroidectomy patients., Methods: To investigate the influence of calcitonin deficiency on bone turnover, 9 males (age 31 to 66 years) submitted to total thyroidectomy in 1996 for non-toxic goitre have been studied. These patients received thyroxine treatment at individual dose but never with suppressed TSH levels. Moreover 8 sex-, age- and Body Mass Index-matched normal subjects have also been studied as control group., Results: Calcitonin was undetectable in thyroidectomized patients, while the mean value was 7.1+/-3.2 pg/ml in the control group. At bone ultrasonography 50% of patients showed osteopenia, while only 1 subject showed osteopenia in the control group. The mean calcium serum level of patients was significant lower than in the control group (p<0.001). Calcium urinary level was increased in patients than controls. PTH serum levels were statistically decreased (p<0.001) in patients more than in controls. Osteocalcin showed a significantly (p<0.05) lower bone formation in patients than in controls, while the markers of resorption, deoxypyridinoline and N-terminal telopeptide of type I collagen, suggested an increased bone turnover in calcitonin-deficiency patients., Conclusion: The results of this study show that the chronic lack of calcitonin in total thyroidectomized patients may play a role in increased bone degradation and osteopenia with a higher risk of bone fracture.

Antihypertensive treatment is useful in reducing cardiovascular morbidity and mortality. The possibility of preventing cardiac events is mainly related to the effect of antihypertensive drugs on the occurrence of hypertensive heart disease, i.e. on the anatomic and functional abnormalities of the left ventricle that represent the direct consequence of blood pressure increase. Hypertensive heart disease is associated with the concomitant occurrence of structural and functional changes in large arteries and small resistance arteries. Left ventricular hypertrophy represents the sign of preclinical disease in hypertensive heart disease. The use of antihypertensive treatment may induce the regression of left ventricular hypertrophy and determine a significant improvement of functional and clinical consequences of cardiac hypertrophy, and more importantly the regression of left ventricular hypertrophy is associated with an improvement of cardiovascular prognosis in hypertensive patients. It remains to be established whether some antihypertensive drugs are more effective, or only faster, in determining left ventricular hypertrophy regression. Antihypertensive treatment is extremely useful not only in the primary prevention of cardiac events and hypertrophy, but also in the reduction of cardiac complications in patients already presenting with cardiac disease; in fact these patients are at higher cardiovascular risk and therefore the benefit from blood pressure reduction may be even more evident.

The prognosis of myocardial infarction has considerably and favourably changed over the last decades thanks to new procedures in the hospital and post-discharge management. The identification of high-risk patients exposed to recurrent coronary events allows more appropriate treatment of these subjects and significantly contributes to the observed improvement in the general prognosis. In this short review, we examine different procedures for prognostic assessment in myocardial infarction and discuss a strategy for a favourable cost/benefit ratio in their utilization.

The development of hypertension is associated with the presence of cardiovascular structural alterations. The principal target organs of hypertensive disease are the heart, brain, kidney and eye. Although left ventricular hypertrophy is an initially useful and well tolerated adaptive mechanism because it tends to reduce wall stress, it may subsequently lead to impaired cardiac function and even heart failure. Vascular structural alterations include reduced compliance, the appearance of atheromatous lesions in the large arteries, and hypertrophy or remodelling of small artery walls, and may be involved in the onset of retinal, renal and brain lesions. Technological progress now enables us to evaluate cardiovascular structural alterations early on as well as to monitor their natural history and the modifications induced by antihypertensive therapy. There is no question as to capacity of antihypertensive therapy to reduce the incidence of stroke, heart failure, renal failure and severe hypertensive retinopathy. Although a number of drugs are able to lower blood pressure, ACE-inhibitors and calcium entry blockers more effectively bring about the regression of left ventricular hypertrophy and, probably, also the retrocession of structural alterations in small resistance arteries; they seem to have a beneficial effect on structural alterations in large arteries as well. Although the regression of left ventricular hypertrophy could be associated with an improved prognosis, no data are available yet on the prognostic significance of the presence and regression of vascular structural alterations.

Aim of recent experimental and clinical studies has been to evaluate the important role of the renin-angiotensin system in the development of cardiac hypertrophy, of vascular hypertrophy and of left ventricular fibrosis and remodelling in essential hypertension and ischemic heart disease. It has been suggested that ACE-inhibitors are the class of antihypertensive drugs more effective in reducing left ventricular hypertrophy (LVH) in hypertensive patients. The possible mechanisms are, beyond the decrease in blood pressure, the possibility of interfering not only with the renin-angiotensin system activity, but also with the sympathetic nervous system activity as well as with aortic distensibility, all factors that can influence the development of LVH. Vascular changes in essential hypertension are complex and depend not only on the severity of blood pressure levels, but are related to diameter and structure of the vessels and to the presence of other atherosclerosis risk factors. ACE-inhibitors are effective in inducing the regression of structural changes in resistance arterioles and furthermore can increase arterial compliance in large arteries; new studies are undergoing in order to assess the effects of these drugs on atherosclerotic plaque progression/regression. The results of large clinical trials have shown the efficacy of ACE-inhibitors in the treatment of heart failure, in addition, after it has been demonstrated that ACE-inhibitors can influence the structural remodelling process after myocardial infarction, their use has been extended to patients with ischaemic heart disease.

Left ventricular hypertrophy in arterial hypertension can be considered as an adaptive response of the heart to the increased afterload, in order to reduce wall stress; however, cardiac hypertrophy can also represent the first step toward a pathological process that leads to the development of congestive heart failure. Epidemiological studies have documented that left ventricular hypertrophy in essential hypertension represents an independent risk factor for cardiovascular morbidity and mortality. The possibility of reversing, or even preventing, left ventricular hypertrophy through a reduction in elevated blood pressure values and modification of some other pathogenetic factors should represent a major therapeutic need in the treatment of hypertensive patients. It has been demonstrated that different classes of antihypertensive drugs do not have the same effect in reducing left ventricular mass, probably because beyond control of blood pressure, the pharmacological interference with adrenergic system, the renin-angiotensin-aldosterone system or other growth factors can influence the development and the reduction of cardiac hypertrophy. Two recent meta-analyses of the principal regression studies have shown that ACE-inhibitors, followed by calcium antagonists and drugs capable of reducing sympathetic nervous system activity, are more effective in decreasing left ventricular mass. The results of experimental and clinical studies have demonstrated that the reversal of cardiac hypertrophy is associated with an improvement of the functional consequences of an increased left ventricular mass. Further studies are needed in order to verify whether the reversal of left ventricular hypertrophy per se increases survival in essential hypertensive patients.

There are several factors involved in the bronchial muscle tone regulation, such as biochemical, nervous and humoral mechanisms. In general, in chronic obstructive bronchopneumopathy there is a reduction in air flow, due to different physiopathologic factors which, alone or combined, produce these disorders. In particular, according to suggestive hypotheses, it seems that asthma is due to a partial or complete block of beta-receptors with a prevalence of alpha-receptors and subsequent bronchial hypertonicity and hyperactivity, while in patients with allergic asthma a deficiency of beta-2-adrenergic system and an hyperresponsiveness of alpha-adrenergic and/or cholinergic system have been suggested. In relation to this part, alpha-1 antagonist drugs demonstrated to have a bronchodilator effect, thanks to their mechanism of action. Examples of this class of drugs are prazosin, indoramin, and an analogous of prazosin, doxazosin, which has a high antagonist and selective action for post-synaptic alpha-1 adrenergic receptors and a longer half-life. Several and recent observations show that these drugs do not interfere with the respiratory function principal parameters, both in healthy and in asthmatic or chronic bronchopathy subjects, but produce an appreciable improvement of these parameters. Presynaptic alpha-2-adrenergic receptors agonist drugs would mainly act by inhibiting the central nervous system, with a subsequent lower stimulation of post-synaptic alpha-1-adrenergic receptors. Examples of this class of drugs are clonidine, rilmenidine and guanabenz (but, in this case, the effects on the respiratory function are more controversial).(ABSTRACT TRUNCATED AT 250 WORDS)

The purpose of this double blind, cross-over, randomized study was to assess the antihypertensive efficacy and tolerability of ketanserin given at two different doses (i.e. 20 or 40 mg b.i.d.) in a group of patients with essential hypertension aged over 60 years. In addition, we evaluated the effect of ketanserin on some indexes of the sympathetic nervous system activity and the renin-angiotensin-aldosterone system, as well as the pharmacokinetic characteristics of the drug after acute administration per os and during chronic treatment. Twelve hypertensive patients, 6 males and 6 females gave their informed consent to the study. Each patient underwent a non invasive blood pressure monitoring after a wash out period with placebo, after 5 weeks of treatment with ketanserin (20 or 40 mg b.i.d.), after a second wash out period with placebo, and after a second period of treatment (5 weeks) with ketanserin (40 or 20 mg b.i.d.). In addition, we evaluated ketanserin plasma levels during acute and chronic administration. During treatment with ketanserin 20 mg b.i.d. systolic and diastolic blood pressure showed a small, statistically not significant reduction. The higher dose (40 mg b.i.d.) reduced systolic and diastolic blood pressure. Three hours after administration of 40 mg of the drug, ketanserin plasma levels were higher than after administration of 20 mg; this difference disappeared after 24 hours. A statistically significant relationship between mean blood pressure reduction during chronic treatment and ketanserin plasma levels was detected. No adverse effects were detected. In conclusion, ketanserin seems to be well tolerated and useful in antihypertensive therapy in elderly patients, particularly at the dose of 40 mg b.i.d.

The involvement of cardiopulmonary and arterial sinoaortic receptors in the control of antidiuretic hormone (ADH) and atrial natriuretic peptide (ANP) release is still controversial in humans. Moreover, it is not clear if this control may be impaired in hypertensive patients with left ventricular hypertrophy (LVH). We studied 17 male subjects, age 18-58 (6 normotensives and 9 mild hypertensives, 5 without and 4 with LVH). Each subject underwent selective loading and unloading of cardiopulmonary receptors, in a randomized sequence, by application of a positive (LBPP) or negative (LENP) pressure to the lower body (steps: +10, +20, +40, -10, -40 mmHg, each for about 30 min), through a plexyglass-constructed tubular apparatus with a rubber adhesion round the patients' waist. Blood samples were taken at the end of every step for measurement of ADH, ANP, PRA, immunoreactive renin, aldosterone, noradrenaline and adrenaline. Cuff arterial pressure was measured every 5 min, while heart rate was evaluated by continuous ECG recording. Hypertensive subjects underwent right atrial pressure measurement by an iv catheter and forearm blood flow evaluation at rest and during the different steps (venous occlusion plethysmography). During LBNP, ADH plasma levels increased progressively, but the increase became statistically significant only at the step of -40 mmHg. ANP increased significantly during LBPP. Taking into account only hypertensive patients, a consistent reduction in the changes of ADH and ANP plasma levels, respectively during LBNP and LBPP in patients with LVH in respect to those without LVH was found.(ABSTRACT TRUNCATED AT 250 WORDS)

The antihypertensive effect and the tolerability of the cardioselective beta-blocking drug metoprolol, in comparison to methyldopa, were assessed in 119 hypertensive patients (73 WHO stage 1 and 46 WHO stage 2). After 2 weeks of placebo wash-out, the patients were randomly allocated to treatment with either of the two drugs: metoprolol up to 200 mg bid, and methyldopa up to 500 mg bid, for 6 weeks. Periodical clinical, biochemical, haematological, radiological and electrocardiographical measurements were performed. In respect to pre-treatment values, heart rate, both in lying and standing position, was significantly reduced (P less than 0.01) only in the metoprolol group, while systolic and diastolic blood pressures were significantly reduced (P less than 0.01) with both drugs in both positions. Asymptotic regression analysis showed that velocity of blood pressure reduction was comparable with both drugs. In the lying position, the diastolic blood pressure reduction obtained with metoprolol was significantly greater (P less than 0.05) in respect to that obtained with methyldopa. In general, side effects were few and of mild severity: mainly bradycardia in the metoprolol group and dizziness and fatigue in the methyldopa group. After the formal end of the double-blind trial, 36 patients, 14 in the metoprolol group and 22 in the methyldopa group, were treated in open conditions with metoprolol alone; after an average period of 6.5 weeks, diastolic blood pressure was significantly reduced (P less than 0.05) only in the group previously treated with methyldopa. In conclusion, metoprolol is a well tolerated and effective antihypertensive agent, which may be safely used in patients with mild to moderate hypertension.