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Purpose: Screening of Cushing Syndrome (CS) and Mild Autonomous Cortisol Secretion (MACS) in hypertensive patients is crucial for proper treatment. The aim of the study was to investigate screening and management of hypercortisolism among patients with hypertension in Italy. Methods: A 10 item-questionnaire was delivered to referral centres of European and Italian Society of Hypertension (ESH and SIIA) in a nationwide survey. Data were analyzed according to type of centre (excellence vsnon-excellence), geographical area, and medical specialty. Results: Within 14 Italian regions, 82 centres (30% excellence, 78.790 patients during the last year, average 600 patients/year) participated to the survey. Internal medicine (44%) and cardiology (31%) were the most prevalent medical specialty. CS and MACS were diagnosed in 313 and 490 patients during the previous 5 years. The highest number of diagnoses was reported by internal medicine and excellence centres. Screening for hypercortisolism was reported by 77% in the presence of specific features of CS, 61% in resistant hypertension, and 38% in patients with adrenal mass. Among screening tests, the 24 h urinary free cortisol was the most used (66%), followed by morning cortisol and ACTH (54%), 1 mg-dexamethasone suppression test (49%), adrenal CT or MRI scans (12%), and late night salivary cortisol (11%). Awareness of referral centres with expertise in management of CS was reported by 67% of the participants, which reduced to 44% among non-excellence centres. Conclusions: Current screening of hypercortisolism among hypertensive patients is unsatisfactory. Strategies tailored to different medical specialties and type of centres should be conceived.

ABSTRACTLimited knowledge exists about rock outcrops in Argentina, especially in the Puna ecoregion. This study investigated small and medium-sized mammal diversity using caves and crevices in Desert Puna’s rocky areas. Three rock outcrop sites, >1 km apart at Don Carmelo Reserve, were equipped with five camera traps each. Monitoring spanned 34 days (dry season) and 22 days (wet season). Five mammal species utilized caves and crevices, with 99% sampling coverage in both seasons. The wet season had slightly higher species richness, while the dry season showed higher diversity. Co-occurrence analysis revealed multiple rodent species sharing caves, indicating substantial species sharing and potential interactions in this habitat. These findings enhance our understanding of mammalian communities and the ecological complexities of the Puna ecoregion.

ABSTRACTThe main driver of biodiversity loss and subsequent decreases in ecosystem functionality is undeniably human interference, destruction and encroachment. The creation and establishment of protected areas serve as tools for guaranteeing biodiversity conservation. In this study, we examined the diversity of medium- and large-sized mammals and flightless walking birds that are supported by a protected area system, the Ischigualasto–Talampaya system, and its area of influence. We set up 106 camera traps and analysed all data with rank–abundance curves and Hill numbers as a measure of diversity. Species richness was lower in protected areas, unlike in the buffer zone, due to the absence of domestic species. Native species were present all over the area, but with variations in their abundances, showing that the presence of domestic species in low densities would not negatively affect the richness of native species, but would indeed affect their abundance.

Measurement of blood pressure (BP) using a brachial cuff sphygmomanometer is universally accepted for the diagnosis of hypertension and prediction of cardiovascular diseases. However, brachial systolic BP does not represent actual systolic BP in the central arteries which encounter cardiac load directly. Due to wave amplification from central to peripheral arteries, a significant difference exists between the two. Central BP measurements also account for arterial stiffness, vessel branching and vascular mechanics, unlike brachial BP. Emerging data suggests that hypertension can be diagnosed more accurately by central pressure indices as compared to brachial BP. Various non-invasive techniques are now available to measure central BP indices owing to recent technological advances. Recently, it has been reported that different classes of anti-hypertensive drugs display differential effects on brachial and central BPs. Nebivolol is a cardio-selective beta-blocker which targets central systolic BP and reduces it significantly along with brachial BP. In this article, we will review the current literature to evaluate the role of central BP to diagnose hypertension in detail. We will also assess the clinical evidence to evaluate the role of nebivolol in the management of elevated central systolic BP. Central BP indices offer better estimation of BP in central arteries and should be considered in routine clinical practice. Nebivolol has shown significant reduction in aortic pressure and wave reflection and improvements in endothelial dysfunction and arterial stiffness in hypertensive patients.

Systematic assessment of blood pressure (BP) control rates may help to improve the clinical management of hypertension in clinical practice. This approach had limited application in Europe over the last three decades and only recently has been implemented in some countries. The present study is aimed at evaluating hypertension prevalence and control among adult outpatients followed by a large, representative sample of general practitioners (GPs) in Italy. We retrospectively analysed the data derived from the GP Health Search-CSD database in 2013. Hypertension prevalence and control were estimated within the overall population sample and in hypertensive outpatients, respectively, according to age and gender. Hypertension diagnosis was defined according to the International Classification of Diseases 9. Clinic BP levels were measured according to the European guidelines. BP control was defined as systolic/diastolic BP <140/90 mm Hg. Data from 911 753 individuals (52.2% females) were scrutinized. Hypertension was diagnosed in 236 377 (25.9%) patients, being higher in male aged <70 years than age-matched female. Hypertension control was recorded in 60.6% of hypertensive patients, being higher in female than male individuals aged <70 years. Our current analysis demonstrates that about 26% of adult outpatients followed in the GP setting had hypertension and that about 61% had controlled BP levels. Both prevalence and control of hypertension appear to be higher when compared with the data reported from the analysis of the same database in 2005, thus confirming a positive trend in BP control in the GP clinical setting in Italy.

The objective of the present real–world analysis was to evaluate the impact of adherence to lipid–lowering drugs in reaching the lipid target in settings of clinical practice in Italy.The analysis was based on administrative and laboratory database of selected Healthcare Units in Italy covering approximately 10% of Italian population. Adult patients prescribed with statin and with at least a low–density lipoprotein (LDL) determination were included between 2012 and 2019. The index date was defined as the first prescription for statin within the inclusion period. Patients fell into 4 clusters collectively exhaustive and mutually exclusive based on their characteristics assessed during the year prior index date. Patients were considered as adherent if they had a proportion of days covered (PDC)≥80%. Among overall patients prescribed statin and with a LDL determination, 1% was with familial hypercholesterolemia, 28% with previous cardiovascular events, 21% with diabetes and 50% in primary prevention. Regardless their risk profile, the increasing of adherence was related to a higher achievement of LDL–target, with an increment of + 53.2% among familial hypercholesterolemia, +43.1% in diabetes and +30% in previous cardiovascular events and primary prevention clusters while progressing from low (PDC<40%) to high (PDC≥80%) levels of adherence. However, while in diabetes and primary prevention clusters 80% and 86% of adherent patients, respectively, had their cholesterol level under control, in the familial hypercholesterolemia and previous cardiovascular events clusters only 46% of adherent patients achieve the lipid target.The analysis showed adherence to be a key factor for cholesterol control. However, our findings underline a therapeutic need for patients that, although adherent, fail to achieve the lipid target, especially among patients with previous cardiovascular events (that have low level of LDL to achieve) and with familial hypercholesterolemia (that have high LDL basal level), suggesting therapeutic intensification should be applied.

The study aimed to evaluate the proportion of patients not reaching their low–density lipoprotein (LDL)–cholesterol target according to their risk profile in real–world settings of Italian clinical practice.This observational analysis was based on administrative and laboratory databases from a pool of Italian Entities covering around 10% of Italian population. All patients included had at least one laboratory LDL test between 2012 and 2019. Presence of lipid–lowering drugs was analyzed in the 6 months before index date (last LDL test detected), during which time adherence to these therapies was measured as proportion of days covered (PDC). Risk profile was assessed based on ESC guidelines.1 Among patients with LDL tests that received lipid–lowering drugs, 49.7% were deemed as very high–risk (VHR), 38.3% at high risk (HR), 12% with other risks (OR). Overall, 80% of patients did not reach their LDL–cholesterol target: 87.2% in the HR–cohort, 82.9% in the VHR–cohort (LDL level target 70 mg/dl and 55 mg/dl, respectively) and 49.6% in OR–cohort (LDL level target 116 mg/dl). Statin and ezetimibe combination was observed only in 6.5% of HR and OR and 10.3% of VHR patients, while patients were mainly in monotherapy with statins (87.5 VHR, 91.2% HR, 90.6% OR). Furthermore, patients adherent to treatment (PDC≥80%) accounted for the 52% of VHR–cohort, 47.2% of HR–cohort and 39.1% of OR–cohort. Our findings highlight the need to optimize the management of cholesterol control, especially among patients at risk. Despite the high proportion of patients not reaching LDL target, sub–optimal levels of adherence and a low use of combination regimens were observed, thus suggesting LDL–control could be supported by increasing adherence and/or the use of combination therapies and, if the target is not yet achieved, by the utilization of more recent therapies.European Heart Journal (2020) 41, 111–188

The study aimed to evaluate the healthcare direct costs for Italian National Health System of patients treated with lipid–lowering drugs that do not achieve the low–density lipoprotein (LDL)–cholesterol target compared to those reaching their targets, and to analyze costs according to the distance from LDL target by using real–world data.An observational analysis was performed on administrative and laboratory data from selected Italian Healthcare Departments. Patients were included if they presented at least one laboratory LDL test between 2012 and 2019 and if they were prescribed lipid–lowering drugs during 6 months prior the last LDL detection (index date). Mean annual direct costs were evaluated in the 12 months before index date in terms of all drugs prescribed, all–cause hospitalizations and all outpatient services. Distance to LDL target was calculated as difference between the index LDL level and LDL target. Total mean annual healthcare direct cost for patients that did not reach LDL target was higher compared to total cost of patients achieving LDL target (€3,678 vs €2,906). Costs were mainly driven by hospitalization (€1,330) followed by drugs expenditure (€1,012) and outpatient services (€563). Mean total annual healthcare costs increased with the distance from LDL target, specifically from €3,004 for patients with 10% distance from LDL target up to €4,823 for those 50% or more distance from LDL target. This trend was particularly evident for the cost item related to hospitalization, that went from €1,486 to €2,819 moving from 10% to ≥ 50 distance from LDL target. Results from this real–world study highlighted the higher economic burden for patients that do not reach the therapeutic LDL target, that tend to rise along with increasing distance from the LDL target. Overall, our findings could suggest that reducing the distance from LDL target could have a positive impact also on the economic outcomes for these patients.

Background:Sex hormones and adipokines seem to differently interact in both genders at different ages. Aim:To comparatively evaluate the serum level of adipokines and sex hormones in healthy non-pharmacologically treated premenopausal women, post-menopausal women, and elderly women, and in age-matched men. Subjects:From the historical cohort of the Brisighella Heart Study we selected 199 adult healthy subjects (males: 89; females: 110), aged 62.5±12.4 yr. Men and women included in the age-class subgroups were matched for body mass index (BMI), waist circumference, blood pressure, heart rate, fasting plasma glucose, plasma lipids. Results:Leptin did not differ among various age classes in men, while pre-menopausal women displayed significantly lower serum leptin than post-menopausal women (−6.7±2.2 pg/ml, p=0.036). Post-menopausal women had significantly greater serum leptin when compared with age-matched men (+13.1±2.0 pg/ml, p<0.001); the same was observed for elderly women when compared with elderly men (+11.2±2.3 pg/ml, p<0.001). At any age, women had significantly lower serum testosterone/estrone ratio than age-matched men (p<0.01). Serum DHEAS was inversely proportional to age in both genders. The main predictors of adiponectin level are age in men (p=0.027) and BMI in women (p=0.003). The main predictors of leptin level are BMI and the testosterone/estrone ratio in both sexes (p<0.05). The testosterone/estrone ratio is also the main predictor of ghrelin levels in women (p=0.006). Conclusion:Sex hormones and adipokines show specific interactions in the two genders and in different age-classes in a representative sample of adult healthy subjects.

AbstractThe term ‘dyslipidemia’ includes a wide family of lipoprotein metabolic defects often related to cardiovascular diseases. Despite the complexity of lipid disorders, current guidelines indicate LDL-C as the single most important therapeutic target; however, other lipido–proteic parameters, such as the concentration of lipoprotein subfractions (e.g., small-dense LDL) or their functional capacity (e.g., HDL reverse cholesterol transport), may display direct pro- or anti-atherogenic properties. Traditional lipid profiles may therefore be inadequate in representing dyslipidemia complexity and may prove to be ineffective in estimating the overall patient’s risk in this context. We designed a research project attempting to provide a coherent framework integrating traditional lipid profiling and advanced diagnostics, to assess qualitative and functional lipoprotein features in relevant clinical conditions and to correlate them with preclinical atherosclerosis.

The term ‘dyslipidemia includes a wide family of lipoprotein metabolic defects often related to cardiovascular diseases. Despite the complexity of lipid disorders, current guidelines indicate LDL-C as the single most important therapeutic target; however, other lipido–proteic parameters, such as the concentration of lipoprotein subfractions (e.g., small-dense LDL) or their functional capacity (e.g., HDL reverse cholesterol transport), may display direct pro- or anti-atherogenic properties. Traditional lipid profiles may therefore be inadequate in representing dyslipidemia complexity and may prove to be ineffective in estimating the overall patients risk in this context. We designed a research project attempting to provide a coherent framework integrating traditional lipid profiling and advanced diagnostics, to assess qualitative and functional lipoprotein features in relevant clinical conditions and to correlate them with preclinical atherosclerosis.

Hypertriglyceridaemia is a common dyslipidaemia encountered in clinical practice. People with hypertriglyceridaemia are frequently obese, insulin-resistant, hypertensive or diabetic, all of which are risk factors for cardiovascular diseases. Hypertriglyceridaemia also contributes to metabolic syndrome, in which an atherogenic diet, sedentary lifestyle, overweight/obesity and genetic factors interact. A multi-factorial intervention for all risk factors is necessary, including weight reduction, dietary modification and increased physical exercise. This review focuses on the influence of diet, sedentary lifestyle and negative habits (such as excessive alcohol intake, smoking and drug addiction) on hypertriglyceridaemia as well as the effects of lifestyle change.

Antihypertensive drugs can differ in target organ protection despite similar blood pressure (BP) control. We compared the effects of losartan (L) and chlorthalidone (C) on renal vascular resistance index (RVRI) in 194 grade I to II, non-diabetic hypertensive patients with increased RVRI (>0.68 m/s by echo-Doppler) but normal renal function. Patients were randomly allocated to C 25 mg/d or L 50 mg/d according to a single blind, PROBE study design. After 4 weeks of treatment, 92 patients (48 L/44 C) with BP <140/90 mm Hg were enrolled in the long-term phase of the study. After 12 months a normalization of RVRI was observed in 47 of 48 patients treated with L (97.5%) and only in 14 of 44 of those treated with C (25.8%) despite no differences in BP control. Patients whose RVRI remained elevated during C therapy underwent a 2-week washout period and then were treated with L 50 mg/d for 12 additional months. After that period 28 of 30 (95%) of patients who were nonresponders to C showed a normalization of RVRI despite no differences in BP control. In conclusion, our data suggest that treatment with L can improve renal hemodynamic and exert a protective renal effect beyond BP control in patients with hypertension.

The term ‘idiopathic’ is used to design sudden sensorineural hearing loss when causative factors cannot be identified. In most cases a viral infection or a circulatory defect are considered to play a significant role when an alternative satisfactory explanation cannot be found. However some significant points remain unclear, since the great variability in age and general conditions of the affected people makes it difficult to find a reliable interpretation of the exact nature of this phenomenon which is reasonably considered to have a multifactorial origin. Under these conditions many different therapeutic strategies have been put forward, thus suggesting some degree of uncertainty not only about the pathogenetic mechanisms of the disease but also on the actual effectiveness of the disparate treatment approaches. In this paper the use of statins in sudden sensorineural hearing loss is firstly proposed on the basis of their metabolic and hemodynamic effects, and the possible clinical implications are outlined.

High serum cholesterol has been frequently reported in patients with arterial hypertension in whom it might influence the blood pressure control. The aim of this study was to compare the extent of blood pressure changes in 41 patients with hypertension and hypercholesterolemia, taking antihypertensive drugs and treated for 3 months with statins (HC-S; pravastatin or simvastatin) and compared with matched controls with high (HC-D; 44) or normal serum cholesterol (NC-D; 45) undergoing antihypertensive treatment combined with dietary treatment alone. After 3 months of follow-up, a greater reduction of systolic (SBP) and diastolic (DBP) blood pressure values was observed in HC-S patients (ΔSBP/DBP, −11.3 ± 3/−10.6 ± 2%) when compared with both HC-D (ΔSBP/DBP, −6.6 ± 2/−6.1 ± 2%; p < 0.05) and NC-D (ΔSBP/DBP, −6.9 ± 2/−6.8 ± 1.5%; p < 0.05). In statin-treated patients, a slight linear relation has been found between the percentage changes in DBP and those in plasma total cholesterol (R = 0.37, p = 0.043), whereas no relation was found with SBP changes (R = 0.11; p = 0.35). In conclusion, the results of this study demonstrate that the use of statins in combination with antihypertensive drugs can improve blood pressure control in patients with uncontrolled hypertension and high serum cholesterol levels. The additional blood pressure reduction observed in patients treated with statins is clinically relevant and only partially related to the lipid-lowering effect.

Summary Two-hundred-and-three female patients (mean age: 58 yrs; SD: 8.2 yrs) suffering from osteoarthritis entered this late phase IV multicentre, stratified according to previous therapy (e.g. ketoprofen, naproxen, aspirin, indomethacin or indoprofen), randomized, double-blind, between within-patient trial of 2-week duration. Each patient received either diclofenac SR 100 mg/day (D), piroxicam 20 mg/day (P), or placebo (P1 by oral route. Clinical evaluation (functional class; pain assessment; osteoarthritic condition; joint motility and stiffness) was performed at entry, as well as after the first and the second week. Patient compliance and reported signs and symptoms were recorded after the first week and at the end of the trial. Patient preference, as regards previous therapy, and global evaluation (both by the physicians and the patients) were checked at the end of the trial. The clinical evaluation showed a superiority of D and P over P1. No difference was seen between the two active drugs. Placebo effect was very strong. Global evaluation was significantly in favour of D and P. Patient compliance was extremely good (⩽95%). Diclofenac was preferred to naproxen, aspirin and indomethacin, while piroxicam and placebo were preferred only to aspirin. The tolerability of the two active drugs was good and comparable. A significantly lower number of patients complaining of unwanted effects (u.e.) was detected in the placebo group. The number of patients withdrawn for u.e. was similar in the three trial groups.

The relationship between intralymphocytic sodium content (ILSC) and blood pressure (BP) was assessed in a group of 18 untreated patients with essential hypertension. BP was recorded with an automatic device at rest and during mental arithmetic and handgrip. When BP was recorded in the presence of the physician patients with very high ILSC values showed significantly higher values than patients with moderately high ILSC values. This difference was no longer detectable when BP was recorded in a quiet room the patients being alone. ILSC and diastolic BP at rest were significantly related (r=0.80) only when the physician was present. The percent increase in diastolic BP induced by stimulation tests was significantly related to ILSC values (r=0.91). These data suggest that pressor response to adrenergic stimulation in patients with essential hypertension is related to intracellular sodium content.

The standard mercury sphygmomanometer (SMS) and two automatic blood pressure recording devices, Dinamap 845 (D) and Sentron (S), were compared by means of a randomized 3-period cross-over experiment. Both devices recorded diastolic BP lower than SMS, on average and for most individual patients. Systolic BP was similar for SMS and S, and slightly lower for D, with variations for individual patients. A second study failed to detect effects of the physician's presence when BP was measured, whereas the difference between D and SMS was substantially confirmed.

In subjects with borderline(BL)hypertension and in normal subjects with familial hypertension(FH),the increase in diastolic blood pressure(DBP)induced by mental arithmetic,handgrip and bicycle exercise strongly correlates with intralymphocytic sodium concentration(ILSC). In BL subjects with high or normal ILSC basal BP values are identical, but the increase in DBP during stress is significantly greater in BL subjects with high ILSC. The same phenomenon can be found in normal subjects with FH. Four hours after acute salt loading urinary Na+ is significantly higher in BL subjects with high ILSC.ILSC is a test by which one can identify BL and normal subjects with abnormal responsiveness to stimuli and who probably are fated to develop sustained hypertension.

Plasma values of atrial natriuretic factor (ANF) were evaluated in 31 women with pregnancy-induced hypertension (PIH) and 31 normal pregnant women at the same age of gestation. In 27 women with PIH and 27 normal pregnant women forearm venous tone (FVT) was evaluated by Strain Gauge Plethysmography. Forearm vascular resistance (FVR) was measured as the ratio of mean blood pressure (MBP) to forearm blood flow. In addition Cardiac Index (CI) by means of transthoracic electrical bioimpedance and total peripheral vascular resistance (TPR) (with the Frank Equation) were also measured. In comparison with the normal pregnant women, the women with PIH had similar values of hematocrit (as an index of plasma volume) and significantly higher levels of FVR and TPR, while ANF plasma values did not differ significantly. Subdividing the women with PIH in relation to the presence of proteinuria (20.3 g/l), those with proteinuria, in addition to significantly higher levels of FVR and TPR, had significantly higher levels of FVT than normal pregnant women, while ANF plasma values were higher even though the difference was only near the level of significance. Hypertensive women with proteinuria also had higher values of FVT than hypertensive women without proteinuria. By means of multiple regression ANF did not show any significant correlations with hematocrit or sodium excretion. Hypertension with proteinuria seems to represent a more severe form of the disease in which, in addition to the probable influence of other factors such as the renin-angiotensin and prostaglandin systems, a greater increase in peripheral sympathetic tone than in hypertension alone appears to be present, causing a reduction in venous compliance in addition to the elevation in FVR and TPR, with increase in central blood volume and atrial stretch. This may explain the higher ANF plasma levels in these patients in comparison with normal pregnant women, even though the absence of a significant correlation of ANF with hematocrit and the fact that ANF increase was only near the level of significance may suggest a change in the relation between ANF secretion and atrial volume receptors in pregnancy either normal or complicated by hypertension. ANF does not seem to play an important role in water and sodium excretion in PIH probably because of the presence of very high plasma levels of hormones such as aldosterone, progesterone and oestriol which, together with renal prostaglandins, seem to be involved in diuresis and natriuresis in pregnancy.

Essential hypertension, which is common in dentists, has been attributed to mental stress but the importance of working conditions has not been evaluated. The pressor and forearm circulatory response to correct and incorrect working position during dental practice has been evaluated in 10 normotensive dentists and compared with the effects of mental stress. Mental stress elicited a significant increase in blood pressure not observed during correct dental practice despite a comparable forearm vasodilatation during both tests. Conversely incorrect working position, significantly raised blood pressure to an extent comparable to what observed during mental stress but with only a transitory and rapidly abolished forearm vasodilatation. The recordings of blood pressure or peripheral hemodynamic changes per se did not allow to discriminate between a specific response to mental stress and dental practice which, were clearly differentiated by the analysis of combined pressor and hemodynamic measurements. We conclude that odontoiatric practice carried out in an incorrect working position is able to elicit either an increase in blood pressure or abnormalities in peripheral vascular response which may contribute to the high occurrence of systemic hypertension in dentists. The evaluation of peripheral hemodynamic profile during working conditions seems to provide a useful method for a better understanding of the pattern of cardiovascular involvement in dentistry.

Mathematical models for the design of the linear channel of an MHD generator, are described. By means of a quasi-one-dimensional optimization's model the main design parameters of the channel, are calculated. The local phenomena effects are analyzed through a steady state two-dimensional model. This model is based on the description both of the fluid dynamic and of the electrodynamic in the plane containing the channel axis and normal to the magnetic induction. The transients caused by variations of the loading and by faults, are studied by means of a time dependent quasi-one-dimensional model.