Andrea Verhovez

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.

LXR-activating oxysterols induce the expression of inflammatory markers in endothelial cells through LXR-independent mechanisms

AIMS Liver X receptors alpha and beta (LXRalpha, LXRbeta) are key regulators of cholesterol homeostasis. The effects of LXR ligands on endothelial cells are largely unknown. While oxysterol LXR agonists can increase the endothelial-leukocyte interaction, synthetic LXR agonists are anti-atherogenic and anti-inflammatory. Mechanistic differences may underlie such findings. METHODS AND RESULTS LXRalpha and LXRbeta were found to be expressed in human endothelial cells. While synthetic LXR agonists could blunt the LPS-induced up-regulation of adhesion molecules (ICAM-1, VCAM-1, E-Selectin), 22-hydroxycholesterol and 24,25-epoxycholesterol enhanced such response. Microarray profiling further showed that the endothelial gene expression fingerprints of 22-hydroxycholesterol and T0901317 largely differed and unexpectedly shared only a restricted number of genes. Indeed, 22-hydroxycholesterol down-regulated eNOS and up-regulated a vast cohort of inflammatory mediators such as adhesion molecules, cytokines, enzymes and transcription factors. Other LXR-activating oxysterols such as 24,25-epoxycholesterol, 25-hydroxycholesterol and 27-hydroxycholesterol could also stimulate the endothelial expression of inflammatory markers, although significant differences were observed. These effects persisted in LXR-silenced cells, confirming the mechanistic dissociation of oxysterol and LXR pathways. Furthermore, the oxysterol-induced expression of inflammatory markers was not secondary to cell apoptosis and may relate to oxidative stress. CONCLUSIONS LXR-activating oxysterols comprehensively activate the expression of endothelial inflammation markers independently from LXRs. At proper dosage, synthetic LXR agonists are safe on endothelial cells and may even transrepress inflammatory reactions.

Diagnosis and treatment of low‐renin hypertension

Plasma renin levels can be used to classify hypertension. A significant proportion of hypertensive individuals display a low‐renin profile and thus low‐renin hypertension (LRH) requires appropriate diagnosis and treatment. LRH includes essential, secondary and genetic forms, the most common of which are low‐renin essential hypertension and primary aldosteronism. Several studies have investigated the relationship between PRA status and clinical response to different antihypertensive therapies. The present review will discuss the differential diagnosis of LRH subtypes and the most appropriate treatment options based on the pathophysiological background of this condition.

Captopril Test Can Give Misleading Results in Patients With Suspect Primary Aldosteronism

To the Editor: Primary aldosteronism (PA) has emerged as the most common form of secondary hypertension.1 The widespread use of the plasma aldosterone/plasma renin activity ratio as a screening test for both hypokalemic and normokaliemic hypertensive subjects has allowed the demonstration of a high prevalence of this disease, with PA accounting for up to 5% to 10% of all hypertensive patients.1,2 The diagnosis of PA is of particular importance for the clinician, because it has been demonstrated recently that patients with PA are more prone to cardiovascular and cerebrovascular complications, and to target organ damage compared with essential hypertensive subjects with similar risk profiles.3 A positive plasma aldosterone concentration/plasma renin activity ratio should always be followed by a suppression test to definitively confirm the diagnosis. The confirmatory diagnosis is usually made with a saline load test (SLT; oral or intravenous) or with the fludrocortisone suppression test (FST).1 Confirmation of the diagnosis of PA should subsequently undergo a …

Cognitive Decline and Low Blood Pressure: The Other Side of the Coin

Low blood pressure has been found to be associated with cognitive decline and dementia in cross-sectional studies. Two mechanisms have been proposed to interpret this association: blood pressure levels decrease during the course of the dementia process, and low blood pressure induces or accelerates cognitive decline by lowering cerebral blood flow. Results of the prospective studies are contradictory. Low blood pressure and orthostatic hypotension have been found to predict cognitive impairment in the elderly population in some studies only. While hypotension may play a protective role in healthy elderly people, low blood pressure levels in frail elderly patients with associated diseases may cause cerebral hypoperfusion and accelerate cognitive decline.

Relationship between QT interval and cardiovascular risk factors in healthy young subjects

A prolongation of QT interval increases the risk for coronary heart disease, ventricular arrhythmias, and sudden death in diabetic patients, after myocardial infarction, and in the elderly. An association between QT prolongation and cardiovascular risk factors has been demonstrated in middle-aged and elderly subjects. Aims of this study were to evaluate the prevalence of a prolonged corrected QT interval (QTc) in a healthy young population (n=170, age 22–25 years, 84 males) and to investigate the association of QTc and QT dispersion (QTd) with cardiovascular risk factors (body mass index, blood pressure, fasting blood glucose and cholesterol, smoking habits, and hypertensive familiarity). A prolonged QTc was observed in 10% of female and 5% of male subjects; in multiple regression analysis, QTc showed a significant positive relationship with blood glucose in females (P=0.04) and systolic blood pressure in male subjects (P=0.03), while QTd was not significantly related with any of the factors. In conclusion, the association between QTc length, glucose levels, and blood pressure is present also in young healthy subjects. QT measurement may represent a useful marker in the screening of young subjects for cardiovascular prevention.

Primary aldosteronism (PA) and endothelial progenitor cell (EPC) bioavailability

Objective  Patients with primary aldosteronism (PA) experience more cardiovascular events than patients with essential hypertension matched for risk factor profile. Endothelial progenitor cells (EPC) represent a bone marrow‐derived cell population implicated in vascular healing whose number correlates to the cardiovascular risk factor profile. Aldosterone has been reported to decrease EPC proliferation in rats.

Aldosterone as an Independent Factor in Cerebrovascular Damage

Aldosterone is produced not only in the adrenal gland but also in other tissues, including the brain, where it plays an important role in the control of blood pressure and water and electrolyte homeostasis. Aldosterone has also been demonstrated to be a major factor in target organ damage independent of its effects on blood pressure. Herein we review the pathophysiology of aldosterone action in the brain and the clinical and experimental studies on the detrimental effects of aldosterone in the brain.

Is Renin-Based Treatment a Reasonable Strategy to Treat Essential Hypertension?

Plasma renin activity (PRA) levels have been used to define two categories of essential hypertensive patients differing for the basic pathophysiological mechanisms sustaining high blood pressure and for the responsiveness to different antihypertensive agents. In particular, patients with low-renin hypertension should respond better to antisodium-volume drugs and patients with normal- to high-renin hypertension should respond better to renin angiotensin aldosterone system-targeted drugs. Although the experimental verification of this treatment algorithm in both retrospective and prospective analyses of several clinical trials has led to mixed results, the recommendations from the British Hypertension Society can be interpreted in the light of this approach by substituting the direct determination of PRA with the use of demographic parameters (such as race and age), which have been demonstrated to be strictly correlated to PRA levels. Furthermore, the use of PRA screening has also been advocated in cases of resistant hypertension.

Controversies on the Diagnosis of Primary Aldosteronism

Primary aldosteronism (PA) is the most common secondary form of hypertension. The diagnosis of PA is of particular importance since aldosterone has been shown to play a pathological role in target organs that is partly independent from effects on blood pressure levels and electrolyte balance. Patients with PA display a higher rate of target organ damage than patients with essential hypertension. As a consequence, PA patients experience a higher rate of cardiovascular events such as stroke and myocardial infarction. The diagnosis of PA is also important as one subgroup of PA should be treated with specific medical therapy, whereas the other can be cured or considerably ameliorated by adrenalectomy. In this review we discuss the current controversies on the diagnostic work-up of PA and its subtypes.