Alberto Milan

Drug Effects on Aldosterone/Plasma Renin Activity Ratio in Primary Aldosteronism

Primary aldosteronism is a specifically treatable and potentially curable form of secondary hypertension. The aldosterone/plasma renin activity ratio (ARR) is routinely used as a screening test. An...

Long-Term Cardio- and Cerebrovascular Events in Patients With Primary Aldosteronism

BACKGROUND Aldosterone plays a detrimental role on the cardiovascular system and PA patients display a higher risk of events compared with EH. OBJECTIVES The objectives of the study were to compare cardio- and cerebrovascular events in patients with primary aldosteronism (PA) and matched essential hypertension (EH). METHODS We retrospectively compared the percentage of patients experiencing events at baseline and during a median follow-up of 12 years in 270 PA patients case-control matched 1:3 with EH patients and in PA subtypes [aldosterone-producing adenoma (n = 57); bilateral adrenal hyperplasia (n = 213)] vs matched EH. RESULTS A significantly higher number of PA patients experienced cardiovascular events over the entire period of the study (22.6% vs 12.7%, P < .001). At the diagnosis of PA, a higher number of patients had experienced total events (14.1% vs 8.4% EH, P = .007); furthermore, during the follow-up period, PA patients had a higher rate of events (8.5% vs 4.3% EH, P = .008). In particular, stroke and arrhythmias were more frequent in PA patients. During the follow-up, a higher percentage of PA patients developed type 2 diabetes. Parameters that were independently associated with the occurrence of all events were age, duration of hypertension, systolic blood pressure, presence of diabetes mellitus, and PA diagnosis. After division into PA subtypes, patients with either aldosterone-producing adenoma or bilateral adrenal hyperplasia displayed a higher rate of events compared with the matched EH patients. CONCLUSIONS This study demonstrates in a large population of patients the pathogenetic role of aldosterone excess in the cardiovascular system and thus the importance of early diagnosis and targeted PA treatment.

Echocardiographic Indexes for the Non-Invasive Evaluation of Pulmonary Hemodynamics

Ultrasound imaging has continuously developed over recent years, leading to the development of several novel echocardiographic indexes. Among these, of particular interest are those that focus on pulmonary hemodynamics, because they not only improve both sensitivity and specificity in the echocardiographic evaluation of pulmonary pressures (systolic, mean, and diastolic), but can also be used to estimate other pulmonary hemodynamic parameters, such as pulmonary vascular resistance, pulmonary capillary wedge pressure, and pulmonary capacitance and impedance. Such parameters can provide important diagnostic and prognostic information in patients with heart failure, chronic obstructive pulmonary disease, and pulmonary arterial hypertension and in every patient with suspected pulmonary impairment. In this review, the authors present a comprehensive overview of the echocardiographic indexes involved in pulmonary hemodynamic evaluation and discuss the applications of these indexes in the clinical setting.

Roles of clinical criteria, computed tomography scan, and adrenal vein sampling in differential diagnosis of primary aldosteronism subtypes.

CONTEXT In patients with primary aldosteronism (PA), it is fundamental to distinguish between subtypes that benefit from different therapies. Computed tomography (CT) scans lack sensitivity and specificity and must be followed by adrenal venous sampling (AVS). Because AVS is not widely available, a list of clinical criteria that indicate the presence of an aldosterone-producing adenoma (APA) has been suggested. OBJECTIVE AND DESIGN The objective of the study was to test the sensitivity and specificity of the last generation CT scans, test prospectively the usefulness of clinical criteria in the diagnosis of APA, and develop a flow chart to be used when AVS is not easily available. SETTING Hypertensive patients referred to our hypertension unit were included in our study. PATIENTS Seventy-one patients with confirmed PA participated in our study. INTERVENTION All patients had a CT scan and underwent AVS. MAIN OUTCOME MEASURE Final diagnosis of APA was the main measure. RESULTS A total of 44 and 56% of patients were diagnosed as having an APA and a bilateral adrenal hyperplasia (BAH), respectively. Twenty percent of patients with PA displayed hypokalemia. CT scans displayed a sensitivity of 0.87 and a specificity of 0.71. The posture test displayed a lower sensitivity and specificity (0.64 and 0.70, respectively). The distribution grades of hypertension were not significantly different between APA and BAH. Biochemical criteria of high probability of APA displayed a sensitivity of 0.32 and a specificity of 0.95. CONCLUSIONS This study underlines the central role of AVS in the subtype diagnosis of PA. The use of the clinical criteria to distinguish between APA and BAH did not display a satisfactory diagnostic power.

OBESITY AND AUTONOMIC FUNCTION IN ADOLESCENCE

Hypertension and obesity are risk factors for coronary heart diseases in adults. In turn, childhood overweight and high blood pressure increase the risk of subsequent obesity and hypertension in adulthood. Human obesity is characterized by profound alterations of hemodynamic and metabolic states. Whether these alterations involve sympathetic nervous system control on cardiac function is controversial. We report the results of our study, conducted in a sample of obese adolescents by using power spectral analysis of heart rate variability. An increase in sympathetic tone coupled with a reduction in vagal tone was found. This allowed us to hypothesize that autonomic nervous system changes depend on the time course of obesity development. It is still unclear if treatment of obesity in adolescence prevents subsequent autonomic imbalance and hypertension.

Antihypertensive drugs and the sympathetic nervous system.

Hypertension has been associated with several modifications in the function and regulation of the sympathetic nervous system (SNS). Although it is unclear whether this dysfunction is primary or secondary to the development of hypertension, these alterations are considered to play an important role in the evolution, maintenance, and development of hypertension and its target organ damage. Several pharmacological antihypertensive classes are currently available. The main drugs that have been clearly shown to affect SNS function are β-blockers, α-blockers, and centrally acting drugs. On the contrary, the effects of ACE inhibitors (ACE-Is), AT1 receptor blockers (ARBs), calcium channel blockers (CCBs), and diuretics on SNS function remain controversial. These properties are pharmacologically and pathophysiologically relevant and should be considered in the choice of antihypertensive treatments and combination therapies in order to achieve, beyond optimal blood pressure control, a normalization of SNS physiology and the most effective prevention of target organ damage.

AMBULATORY BLOOD PRESSURE MONITORING AND CLINICAL CHARACTERISTICS OF THE TRUE AND WHITE-COAT RESISTANT HYPERTENSION

The resistant hypertension has been differentiated in true resistant hypertension and white-coat resistant hypertension by using ambulatory blood pressure monitoring. White-coat resistant hypertension was defined as high clinic blood pressure, despite triple treatment for at least 3 months, but day-time blood pressure values < 135/85 mmHg. The aim of this study was to evaluate the presence of different clinical characteristics between two types of resistant hypertension. The study group consisted of 49 patients with essential hypertension, resistant to an adequate and appropriate triple-drug therapy, that included a diuretic, with all 3 drugs prescribed in near maximal doses and that had persistently elevated clinic blood pressure (>140/90 mm Hg), for at least 3 months. They represented the 2% of 2500 hypertensive outpatients that referred at our Hypertension Unit. Patients with white-coat resistant hypertension (n=19) were older (p<0.05) than those with true resistant hypertension (n=30). The sodium intake (p<0.05) and alcohol intake (p<0.05) were significantly higher in patients with true resistant hypertension than in those with white-coat resistant hypertension. The renin plasma activity and plasma aldosterone were higher (p<0.05) in patients with true resistant hypertension than in those with white-coat resistant hypertension with normal plasma electrolyte balance. There were no significant differences in mean values of office systolic and diastolic blood pressures between white coat resistant hypertensives and true resistant hypertensives (165+17 vs 172+28 and 98+12 vs 102+14 mmHg). Day-time and night-time ambulatory 24-h-systolic and diastolic blood pressures were significantly higher in the true resistant hypertensive patients when compared with white-coat resistant hypertensives (153+15 vs 124+10 mmHg and 97+9 vs 76+6 mmHg all p<0.001). Day-time and night-time ambulatory 24-h-heart rate were significantly higher in the true resistant hypertensive patients when compared with white-coat resistant hypertensives (79+11 vs 71+9 beats/min;p<0.01; 68+9 vs 60+6 beats/min. p<0.001). The ABP readings were analysed by a Fourier series with 4 harmonics. According to the runs test both two groups of patients showed a circadian rhythm for both systolic and diastolic blood pressure. The nocturnal fall in SBP, DBP and HR was not different in both groups of patients. In conclusion, our findings showed that true resistant hypertensive patients were characterized both by higher heart rate and higher plasma renin activity values as an expression of a possible increased sympathetic activity. Thus, the combination of ABPM with the assessment of the clinical characteristics allow to differentiate better the true drug-resistant hypertension from the white coat resistant hypertension.

Standard-length catheters vs long catheters in ultrasound-guided peripheral vein cannulation

PURPOSE Ultrasound (US) is a useful tool for peripheral vein cannulation in patients with difficult venous access. However, few data about the survival of US-guided peripheral catheters in acute care setting exist. Some studies showed that the survival rate of standard-length catheters (SC) is poor especially in obese patients. The use of longer than normal catheters could provide a solution to low survival rate. The aim of the present study was to compare US-guided peripheral SCs vs US-guided peripheral long catheters inserted with Seldinger technique (LC) in acute hospitalized patients with difficult venous access. METHODS This was a prospective, randomized controlled trial. A total of 100 consecutively admitted subjects in an urban High Dependency Unit were randomized to obtain US-guided intravenous access using either SC or LC after 3 failed blind attempts. Primary outcome was catheter failure rate. RESULTS Success rate was 86% in the SC groups and 84% in the LC group (P=.77). Time requested to positioning venous access resulted to be shorter for SC as opposed to LC (9.5 vs 16.8 minutes, respectively; P=.001). Catheter failure was observed in 45% of patients in the SC group and in 14% of patients in the LC group (relative risk, 3.2; P<.001). CONCLUSIONS Both SC and LC US-guided cannulations have a high success rate in patients with difficult venous access. Notwithstanding a higher time to cannulation, LC US-guided procedure is associated with a lower risk of catheter failure compared with SC US-guided procedure.

Baroreflex sensitivity correlates with left ventricular morphology and diastolic function in essential hypertension

Objectives Arterial hypertension is a common cause of cardiac organ damage, inducing morphological and functional modifications. Spontaneous baroreflex sensitivity (BRS) control of the heart rate is a key mechanism of blood pressure homeostasis, and is impaired in patients with hypertension. This study sought to assess the association between BRS and left ventricular morphology and function. Methods We studied 224 hypertensive patients (125 men; aged 47.8 ± 10.8 years, mean ± SD) compared with 51 normotensive control subjects (25 men, aged 45.7 ± 12.5 years). Left ventricular morphology, systolic and diastolic function were evaluated by echocardiography. Spontaneous BRS was measured using the sequence method. Results BRS was inversely associated with relative wall thickness (R2 = 0.17; P < 0.0001) and left ventricular mass index (R2 = 0.03; P = 0.01); in particular, BRS was significantly impaired in patients with concentric left ventricular remodelling (median [interquartile difference] 9.4 [4.1]) and hypertrophy (9.05 [3.9]) compared with the normal left ventricle (12.3 [5]; P < 0.001). BRS showed a significant association with systolic function evaluated by midwall fractional shortening (r = 0.28; P < 0.001), stroke volume (r = 0.27; P < 0.001), stroke work (r = 0.17; P < 0.05), and fractional shortening (r = 0.17; P < 0.05). BRS was significantly decreased in patients with diastolic dysfunction; it was lower in patients with diastolic dysfunction compared with both the control group and hypertensive patients with normal diastolic function. Conclusion BRS is associated with left ventricular morphology, systolic and diastolic function in hypertensive patients. In particular BRS is impaired in patients with diastolic dysfunction. These findings suggest a role for BRS as a target in arterial hypertension.

Mineralocorticoid receptor blockade in the protection of target organ damage.

Over the last decade a wealth of studies have shed new light on the role of aldosterone in the pathogenesis of cardiovascular diseases. It is now evident that in addition to its classical role in increasing sodium re-absorbtion in the kidney , aldosterone also exhibits several nonepithelial effects such as the induction of inflammation, fibrosis and necrosis in various organs. Herein we review the experimental evidences for the protective effects of mineralocorticoid receptor blockade in the prevention and treatment of target organ damage, both in animals and in humans. We also discuss the pharmacological and clinical differences between the two available mineralocorticoid receptor blockers, spironolactone and eplerenone.