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In June 2015, a panel of experts gathered in a consensus conference to plan updating recommendations on the management of the hypertensive patient with elevated heart rate (HR), previously released in 2006. The issues examined during that meeting and further discussed by the participants during the following months involved the assessment of HR, the relevance of HR as a cardiovascular risk factor, the definition of tachycardia and the treatment of the hypertensive patient with high HR. For the measurement of resting HR the panel experts recommended that scientific investigations focusing on HR should report information on length of resting period before measurement, information about temperature and environment, method of measurement, duration of measurement, number of readings, time interval between measurements, body position and type of observer. According to the panellists there is convincing evidence that HR is an important risk factor for cardiovascular disease and they suggest to routinely include HR measurement in the assessment of the hypertensive patient. Regarding the definition of tachycardia, the panellists acknowledged that in the absence of convincing data any threshold used to define tachycardia is arbitrary. Similarly, as there are no outcome studies of HR lowering in tachycardia hypertension, the panellists could not make practical therapeutic suggestions for the management of such patients. However, the experts remarked that absence of evidence does not mean evidence against the importance of tachycardia as a risk factor for cardiovascular disease and that long-term exposure to a potentially important risk factor may impair the patient's prognosis. The main aims of the present document are to alert researchers and physicians about the importance of measuring HR in hypertensive patients, and to stimulate research to clarify unresolved issues.

The evaluation of microvascular structure is, in general, not an easy task. Among the methods that may be applied to humans, plethysmographic evaluation of small arteries and wire or pressure micromyography were extensively used in the last decades. The media-to-lumen ratio of small arteries evaluated by micromyography was demonstrated to possess a strong prognostic significance; however, its extensive evaluation is limited by the local invasiveness of the assessment. Noninvasive approaches were then proposed, including capillaroscopy, which provides information about microvascular rarefaction. Recently, the interest of investigators was focused on the retinal microvascular bed. In particular, a noninvasive measurement of the wall-to-lumen ratio of retinal arterioles using scanning laser Doppler flowmetry has been introduced.

It has been previously demonstrated that dihydropyridine calcium channel blockers may possess antioxidant properties and might improve vascular structure. Combination treatment with an angiotensin-converting enzyme inhibitor may have additional advantages, compared with a thiazide diuretic, in this regard. The aim of the present study was, therefore, to investigate the effects of a short-term treatment with lercanidipine, and to compare two combination treatments: lercanidipine enalapril vs. lercanidipine hydrochlorothiazide on structural alterations in retinal arterioles, on skin capillary density and on large artery distensibility.

The aim of this study is to evaluate the differences in the prevalence of chronic kidney disease (CKD) and of cardiovascular risk factors and diseases between men and women participating in the Italy Developing Education and awareness on MicroAlbuminuria in patients with hyperteNsive Disease (I-DEMAND) study.

Structural alterations of subcutaneous small resistance arteries, as indicated by an increased media-to-lumen ratio, are frequently present in hypertensive andor diabetic patients, and may represent the earliest alteration observed. Furthermore, media-to-lumen ratio of small arteries evaluated by micromyography has a strong prognostic significance; however, its extensive evaluation is limited by the invasivity of the assessment, since a biopsy of subcutaneous fat is needed. Noninvasive measurement of wall-to-lumen of retinal arterioles using scanning laser Doppler flowmetry (SLDF) has recently been introduced. However, this new technique has not yet been compared to micromyographic measurement, generally considered the gold standard approach.

Blood pressure (BP) control is poorly achieved in hypertensive patients, worldwide.

Cardiovascular risk assessment in the clinical practice is mostly based on risk charts, such as Framingham risk score and Systemic Coronary Risk Estimation (SCORE). These enable clinicians to estimate the impact of cardiovascular risk factors and assess individual cardiovascular risk profile. Risk charts, however, do not take into account subclinical organ damage, which exerts independent influence on risk and may amplify the estimated risk profile. Inclusion of organ damage markers in the assessment may thus contribute to improve this process.

Hypertension is the most common cardiovascular disorder and atrial fibrillation is the most common clinically significant arrhythmia. Both these conditions frequently coexist and their prevalence increases rapidly with aging. There are different risk factors and clinical conditions predisposing to the development of atrial fibrillation, but due its high prevalence, hypertension is still the main risk factor for the development of atrial fibrillation. Several pathophysiologic mechanisms (such as structural changes, neurohormonal activation, fibrosis, atherosclerosis, etc.) have been advocated to explain the onset of atrial fibrillation. The presence of atrial fibrillation per se increases the risk of stroke but its coexistence with high blood pressure leads to an abrupt increase of cardiovascular complications. Different risk models are available for the risk stratification and the prevention of thromboembolism in patients with atrial fibrillation. In all of them hypertension is present and is an important risk factor. Antihypertensive treatment may contribute to reduce this risk, and it seems some classes are superior to others in the prevention of new-onset atrial fibrillation and prevention of stroke. Antithrombotic treatment with warfarin is effective in the prevention of thromboembolic events, although quite recently, new classes of anticoagulants that do not require international normalized ratio monitoring have been introduced with promising results.

We assessed the relationship between pulse pressure and intermediate cardiovascular phenotypes in a middle-aged cohort with high prevalence of hypertension.

To estimate the prevalence of hypertension–migraine comorbidity; to determine their demographic and clinical characteristics versus patients with hypertension or migraine alone; and to see whether a history of cerebrovascular events was more common in the comorbidity group.

We have previously demonstrated that structural alterations in subcutaneous small resistance arteries of hypertensive patients, as indicated by an increased media to lumen ratio (M/L), are a potent predictor of cardiovascular events, and that a close correlation exists between serum creatinine and M/L. The aim of the present study was to assess whether M/L of subcutaneous small resistance arteries may predict subsequent changes in renal function in hypertensive patients.

Hypertension guidelines underline the importance of quantification of total cardiovascular risk; an extensive evaluation of target organ damage (TOD) may increase the number of patients classified at high-added cardiovascular risk.

In the past years, several risk charts have been created to increase the accuracy of cardiovascular risk stratification. The most widely used and validated algorithms do not included target organ damage as risk prediction. The aim of the present study was to evaluate whether preclinical renal damage is associated with cardiovascular diseases independently of individual risk profile assessed by risk charts.

Italy Developing Education and awareness on MicroAlbuminuria in patients with hyperteNsive Disease is an observational, cross-sectional, multicenter study aimed at determining prevalence and correlates of chronic kidney disease (CKD) among Italian hypertensive patients attending out-patient referral clinics. CKD was defined as glomerular filtration rate (GFR) less than 60 ml/min per 1.73 m2(Modification of Diet in Renal Disease equation) or urine albumin to creatinine ratio of at least 2.5 mg/mmol in men and of at least 3.5 mg/mmol in women or both.

Structural alterations in the microcirculation may be considered an important mechanism of organ damage. An increased media-to-lumen ratio of subcutaneous small resistance arteries has been demonstrated to predict the development of cardiocerebrovascular events in hypertensive patients. Alterations in the structure of small cerebral arteries have been demonstrated in animal models of experimental or genetic hypertension. However, no evaluation with reliable techniques has ever been performed in humans.

To compare the effects of the angiotensin II receptor antagonist candesartan with the angiotensin-converting enzyme inhibitor enalapril on myocardial fibrosis evaluated by echoreflectivity analysis.

Renal abnormalities are strongly associated with cardiac damage in essential hypertension. Detection of preclinical cardiac and renal abnormalities is a key clinical step in hypertension management. This study investigated the relationship between ECG abnormalities and microalbuminuria (MAU) in hypertensive patients without overt cardiovascular disease. This relationship, in fact, has never been extensively studied.

A previous analysis of the ForLife study demonstrated a high estimated risk of stroke, poor blood pressure control and higher cardiovascular risk. Data from a subsequent visit within 6 months, to evaluate the impact of systematic stroke risk assessment, are reported.

A number of patients with chronic heart failure (CHF) have diastolic but not systolic dysfunction. This occurs particularly in the elderly and in hypertension, but the prevalence of diastolic dysfunction in elderly hypertensives without CHF has never been investigated systematically.

It has been previously demonstrated that the morning rise (MoR) of blood pressure (BP) may predict major cardiovascular events in hypertensive patients. Structural alterations of small resistance arteries, as evaluated by the tunica media to internal lumen ratio (M/L) of subcutaneous small resistance arteries, may also predict cardiovascular events. Because an increased M/L may amplify the effect of hypertensive stimuli, the present study aimed to evaluate the possible relationships between MoR and M/L in a population of hypertensive patients.

Blood pressure (BP) control is reported to be poor in hypertensive patients worldwide.

Objective: To evaluate if a nodule with shape taller than wide (anteroposterior/transverse diameter ratio, A/T≥ 1) is a good predictor of malignancy independent of the size.Methods: We retrospectively examined the cytological and histological results of 7455 nodules (5198 patients) referred for ultrasound-guided-fine needle aspiration cytology (US-FNAC) in our hospital from January 1991 to September 2004.Results: A suitable FNAC was obtained from 6135 nodules (4495 patients); 34.6% were less than 1 cm in diameter (small nodules, SN). A diagnosis of carcinoma was histologically confirmed in 284/349 suspicious lesions after FNAC. The size of carcinoma nodules was not significantly associated with the occurrence of extracapsular growth (large nodules (LN): 10.5%, SN: 4.9%, NS) and lymph node metastasis (LN: 23.6%, SN: 25.0%, NS). Malignant lesions showed microcalcifications more frequently than benign nodules (72.2 vs 28.7%; P< 0.001; (odds ratio, OR(confidence intervals, CI) = 9.9(7.2–13.4)). Similarly, A/T≥ 1 (76 vs 40%; P< 0.001; OR(CI) = 8.6(5.5–13.1)), blurred margins (52.8 vs 18.8%; P< 0.001; OR(CI) = 7.7(5.6–10.2)), solid hypo-echoic appearance (80.6 vs 52.4%; P< 0.001; OR(CI) = 3.2(2.2–4.3)) and intranodular vascular pattern (type 2) (61.6 vs 49.7%; P< 0.001; OR(CI) = 1.7(1.3–2.3)) were significantly more frequent in malignant than in benign nodules.Conclusions: Our data show that no single parameter, including nodule size, satisfactorily identifies a subset of patients to be electively investigated by FNAC. We concluded that A/T≥ 1 with at least two of US features (microcalcification, blurred margins, hypo-echoic pattern) is today the best compromise between missing cancers and cost–benefit.

The presence of endothelial dysfunction in the coronary circulation or in the brachial artery has been found to be associated with a greater incidence of cardiovascular events. However, no data are presently available about the prognostic role of endothelial dysfunction in human small resistance arteries.

Abstract: Purpose: The incidence and aggressiveness of thyroid cancer associated with hyperthyroidism remains a subject of much controversy. The aim of this study was to analyze the frequency of coexisting hyperthyroidism and thyroid cancer, and to determine whether cancer becomes more aggressive with different forms of hyperthyroidism. Methods: We retrospectively studied 2 449 patients assessed for hyperthyroidism between 1985 and 2001. All patients with a “cold” nodule on scintigraphy, such as those with Graves' disease and a concomitant solid nodule, underwent fine-needle aspiration biopsy (FNAB). Criteria for surgery were cytological findings indicative of malignancy, goiter with signs of tracheal or esophageal compression, side effects of antithyroid drug therapy, or Graves' disease with multiple relapses after therapy withdrawal or responsiveness to antithyroid drugs. Results: Thyroid cancer was diagnosed more frequently in patients with Graves' disease (6.5%) than in those with uninodular toxic goiter (UTG) (4.4%) or multinodular toxic goiter (MTG) (3.9%). Lymph node involvement was found in 56% of the patients with Graves' disease, in 23% of those with MTG, and in none of those with UTG. Distant metastases were found in one patient with Graves' disease. Conclusions: Cancers associated with Graves' disease seems to be more aggressive than those associated with MTG or UTG. Thus, we suggest that patients with Graves' disease be carefully monitored for the detection of thyroid nodules. Ultrasonography seems to be the best modality to detect such nodules.

Stroke has a high prevalence in Italy, and is the third cause of death worldwide. Hypertension is the most important risk factor contributing to the risk of stroke. The aims of this study were to assess the risk of stroke in a large cohort of hypertensive patients, and to determine the percentage with controlled blood pressure, to establish the contribution of this factor to the risk of stroke.

Circulating adhesion molecules may have a prognostic significance as markers of endothelial damage. Drugs which inhibit the renin-angiotensin system may be effective in reducing circulating or tissue adhesion molecules, albeit data available are scarce. The aim of the study was to investigate the effects of an angiotensin-converting enzyme (ACE) inhibitor, enalapril and a highly selective angiotensin receptor blocker, candesartan cilexetil, on circulating adhesion molecules in a large sample of patients with non-insulin-dependent diabetes mellitus (NIDDM). The study was comparative, multicenter, randomized and double blind, with two parallel groups.

Objective: Spontaneous parathyroid hormone (PTH) secretory dynamics include tonic and pulsatile components. It is not known how glucocorticoids might alter these secretory dynamics.Design: The aim of our study was to evaluate spontaneous fluctuations in serum PTH levels in six adult male patients (aged 31–64 years) receiving chronic (>6 months) therapy with glucocorticoids (daily dosage >7.5 mg of prednisone or dose equivalent of other corticosteroid) as compared with a control group of 10 age- and sex-matched normal subjects.Methods: Peripheral venous blood sampling was performed every 3 min for 6 h from 0900 to 1500 h. Plasma PTH release profiles were subjected to deconvolution analysis, a method that resolves measured hormone concentrations into secretion and clearance components, and to an approximate entropy (ApEn) estimate, that in turn provides an integrated measure of the serial regularity or orderliness of the release process.Results: In the glucocorticoid-treated group, the PTH tonic secretory rate was reduced (4.3±0.74 vs 8.8±1.4 pg/ml per min in controls, P= 0.017). There was, however, an increase in the fractional pulsatile PTH secretion (42±8.2 vs 18.3±3.9 pg/ml per min, P= 0.006) in glucocorticoid-treated vs normal subjects. Mean overall PTH concentration, as well as mean integrated area, was similar among normal and glucocorticoid-treated subjects.Conclusions: These results demonstrate, for the first time, that chronic glucocorticoid treatment induces a redistribution of spontaneous PTH secretory dynamics by reducing the amount released in tonic fashion and increasing the amount released as pulses.

Vascular structural alterations in small resistance arteries of patients with essential hypertension (EH) are mostly characterized by inward eutrophic remodeling. In fact, no difference in the smooth muscle cell volume (CV) between normotensive subjects (NT) and essential hypertensive patients was observed. However, experimental models of hypertension with chronic infusion of agonists of adrenergic receptors were characterized by the presence of smooth muscle cell hypertrophy or hyperplasia. Recently, we have observed the presence of vascular smooth muscle cell hypertrophy in patients with renovascular hypertension.

Arterial hypertension is frequently associated with the presence of structural alterations in small arteries. Moreover, a reduced coronary flow reserve and vasodilator capacity has been observed in essential hypertensive patients, possibly due, at least in part, to microangiopathy of small coronary vessels. The aim of the present study was to evaluate a possible relationship between subcutaneous small artery structure and coronary flow reserve or vasodilator capacity in patients with essential hypertension.

Arterial hypertension is frequently associated with the presence of endothelial dysfunction in human subcutaneous small resistance arteries, as evaluated by responses to acetylcholine or bradykinin; however it is not known whether patients with diabetes mellitus show similar alterations. Therefore, we have investigated endothelial function in subcutaneous arteries of normotensive subjects (NT), of patients with essential hypertension (EH), of patients with non-insulin-dependent diabetes mellitus (NIDDM), as well as of patients with both essential hypertension and non-insulin-dependent diabetes mellitus (NIDDM EH).

It has recently been demonstrated that the smoothness index (SI) (the ratio between the average of the blood pressure changes computed for each hour of the recording and its standard deviation), a new and reproducible measure of the homogeneity of blood pressure reduction by antihypertensive treatment, has evident advantages over trough-to-peak ratio (T/P) in the prediction of the regression of left ventricular hypertrophy. Therefore we considered it to be worthwhile to compare the ability of SI and T/P to predict changes of the carotid artery intima–media thickness (IMT) during pharmacological treatment in patients with essential hypertension.

In the conscious rat, sympathectomy (6-hydroxydopamine pretreatment, 100 mg/kg intraperitoneally, twice in the previous 5–6 days) induces, among various homeostatic modifications, the frequent occurrence of sudden and wide oscillations of blood pressure. Since one of the mechanisms underlying this, as yet unexplained, phenomenon may be an enhanced vascular reactivity, we tested the hypothesis that sympathectomized rats exhibit such a hyper-reactivity. We examined the response to a variety of vasoactive agents both in vivo(chronically instrumented conscious animals) and in vitro(small isolated resistance arteries).

The time course of programmed cell death (apoptosis) in the vasculature of spontaneously hypertensive rats (SHRs) is still unclear. Moreover, no data are presently available about the possible interrelationships between apoptosis and vascular remodelling. The aim of this study was to investigate the mesenteric small resistance arteries and large arteries (aortas) of SHRs and normotensive Wistar-Kyoto (WKY) rats at different ages, before and after the development of overt hypertension.

It was previously observed that a significant regression of structural alterations and endothelial dysfunction in mesenteric small arteries of spontaneously hypertensive rats (SHRs) may be obtained after therapy with angiotensin-converting enzyme (ACE) inhibitors. It is not clear whether angiotensin II-type 1 receptor blockers may share this properties. We evaluated the effects of the ACE inhibitor enalapril and of the angiotensin II-receptor blocker candesartan cilexetil on structural alterations of mesenteric small resistance arteries, on cardiac mass, and on endothelial function in SHRs. Seventy-three rats were included in the study. Sixteen SHRs were treated with enalapril and 21 with candesartan cilexetil, whereas 18 Wistar-Kyoto (WKY) and 18 SHRs were untreated. Enalapril and candesartan cilexetil were administered in the drinking water from weeks 4 to 12 of age. Blood pressure was measured noninvasively every week. The rats were killed at the end of the treatment period, after 3 or 4 days of therapeutic washout. Heart weight/body weight ratio (HW/BW) was measured. Mesenteric arterioles were dissected and mounted on a micromyograph (Mulvany's technique). Then the media-to-lumen ratio (M/L) was evaluated. In addition, endothelium-dependent and endothelium-independent relaxation was evaluated by dose-response curves to acetylcholine (in the presence or absence of a bradykinin-receptor blocker and of indomethacin) and sodium nitroprusside. Systolic blood pressure was significantly reduced by both drugs, compared with untreated SHRs, although the hypotensive effect was greater with enalapril than with candesartan cilexetil. A significant reduction of M/L of mesenteric small arteries and of HW/BW was observed in SHRs treated with candesartan cilexetil or enalapril. A significant improvement of endothelial function, as evaluated by a dose-response to acetylcholine, was observed. The acetylcholine-induced vasodilatation was similar after addition to the organ bath of a selective blocker of bradykinin receptors, thus suggesting a minor role (if any) of the increased local availability of bradykinin, as a consequence of inhibition of ACE, in the improvement of endothelial function observed after enalapril treatment. In addition to a satisfactory antihypertensive effect observed with both drugs, candesartan cilexetil and enalapril were proven to be equally effective in reducing structural alterations in mesenteric small resistance arteries, in normalizing cardiac mass, and in improving endothelial function. The inhibition of bradykinin breakdown does not seem to be involved in the improvement of endothelial dysfunction observed with ACE inhibitors.

It is unclear whether the carotid intima–media thickness can be influenced by antihypertensive treatment and whether some antihypertensive agents, such as calcium antagonists, may have a greater effect on this parameter than others, such as diuretics. The present paper reports the principal results of the ultrasound substudy of the randomized, prospective, controlled, Verapamil in Hypertension and Atherosclerosis Study (VHAS).

To evaluate the modifications of the morphology of mesenteric small resistance vessels in spontaneously hypertensive rats (SHR) induced by lacidipine treatment.

Summary:

For the evaluation in humans of structural alterations in resistance arteries, most studies have used an indirect index, the measurement of minimal vascular resistance (mean blood pressure divided by maximal postischaemic blood flow) in suitable vascular beds. A sensitive and specific micromyographic technique was recently made available for the study of human small resistance arteries. Whether a correlation really exists between results obtained with the two techniques has not yet been investigated.

Many experimental observations have demonstrated the presence of spontaneous cyclic vasomotor activity (CVA) in large and small arteries. This study aimed to evaluate the characteristics of spontaneous CVA in rat and human resistance arteries, and to investigate its possible interference with the evaluation of sympathetic activity by means of spectral analysis of blood pressure in vivo.

The Verapamil in Hypertension and Atherosclerosis Study (VHAS) is a prospective randomized study the objective of which was to compare the long-term effects of verapamil and chlorthalidone on the blood pressure, clinical safety, and the progression/regression of carotid wall lesions in members of a large population of hypertensive patients.