Recent advances in the diagnosis and management of obstructive sleep apnea.

Affecting a large number of middle-aged, frequently overweight subjects, obstructive sleep apnea (OSA) is the most common sleep related breathing disorder. Partial or complete upper airway (UA) collapse during sleep causing repeated apneic episodes, which is the leading pathophysiological mechanism underlying the disorder, results in arterial oxygen desaturation and recurrent arousals from sleep to re-establish airway patency. Untreated OSA is commonly associated with a range of adverse consequences, including cardiovascular complications, such as arterial and/or pulmonary hypertension, arrhythmias, stroke, as well as diabetes mellitus and metabolic syndrome, and motor vehicle accidents. Evidence-based guidelines are presently available for the diagnosis and management of OSA, and a variety of updated testing and treatment procedures and devices including some that are able to identify the site and degree of airway obstruction are becoming increasingly available. As the "one size fits all" approach falls to the wayside, a tailored personal therapeutic strategy is becoming increasingly popular in the field of sleep medicine. The aim of this review is to provide an overview for practicing clinicians on recent advances in the evaluation and management of obstructive sleep apnea in adults.

Calcitonin gene-related peptide, heme oxygenase-1, endothelial progenitor cells and nitric oxide-dependent vasodilation relationships in a human model of angiotensin II type-1 receptor antagonism.

OBJECTIVE: An increased number of endothelial progenitor cells (EPCs), which correlated with heme oxygenase-1 gene expression and nitric oxide-mediated vasodilation [flow-mediated dilation (FMD)], has been recently reported by us in Bartter/Gitelman syndromes, rare diseases that represent a human model of endogenous angiotensin (Ang) II type-1 receptor antagonism and depicting an opposite picture of hypertension. Calcitonin gene-related peptide (CGRP), which prevents circulating EPCs senescence and reverses Ang II-induced EPCs senescence is reduced in hypertensive patients, its level is stimulated by heme oxygenase-1 and is related with stimulation of nitric oxide. This study reports on CGRP concentration and heme oxygenase-1 protein level in Bartter/Gitelman syndrome's patients compared with healthy individuals and analyzes their relationships with EPCs [CD34⁺kinase insert domain receptor (KDR⁺), CD133⁺KDR⁺, CD34⁺CD133⁺KDR⁺) as well as FMD. METHODS AND RESULTS: CGRP concentration (ELISA) and heme oxygenase-1 protein level (sandwich immunoassay) were higher in Bartter/Gitelman syndrome : 38.20 ± 8.23 pg/ml vs. 25.07 ± 3.51, P < 0.002 and 9.44 ± 3.1 ng/ml vs. 5.52 ± 1.1, P < 0.007, respectively. CD133⁺KDR⁺ and CD34⁺CD133⁺KDR⁺ (direct three-color flow cytometry analysis) and FMD (B-mode echo scan of brachial artery) were confirmed higher in Bartter/Gitelman syndrome. CGRP and heme oxygenase-1 strongly correlated (P < 0.0001) and did not differ by group. In Bartter/Gitelman syndrome, both CGRP and heme oxygenase-1 were strongly correlated with both EPCs and FMD. CONCLUSIONS: Using a human model opposite to hypertension, this study provides information on the relationships between CGRP, heme oxygenase-1, FMD, major clinical and biochemical factors involved in cardiovascular disease, and EPC-specific populations and may also serve to confirm the utility of Bartter/Gitelman syndrome patients in delineating EPCs and related factors roles in the pathophysiology of cardiovascular remodeling in humans.

Mild hyperparathyroidism: a novel surgically correctable feature of primary aldosteronism.

BACKGROUND: The parathyroid hormone (PTH) stimulates aldosterone secretion and cell proliferation in human adrenocortical cells; moreover, in rats hyperaldosteronism was associated with hyperparathyroidism. Hence, PTH could drive aldosterone excess in human primary aldosteronism. METHOD: To test this hypothesis, we recruited 105 consecutive hypertensive patients, of whom 44 had primary aldosteronism due to an aldosterone-producing adenoma (APA) and 61 had primary (essential) hypertension. We measured the plasma levels of (1-84)-PTH, 25(OH)D, 1,25(OH)2D, and serum Ca (total and ionized), inorganic P, Mg, K, and the 24-h urinary excretion of Ca, P, and deoxypyridinoline. In primary aldosteronism patients, these measurements were repeated after adrenalectomy or mineralocorticoid receptor blockade. We also sought for PTH receptor (PTHR-1) mRNA and protein in APA tissue. RESULTS: Compared with primary (essential) hypertension patients, those with primary aldosteronism showed significantly higher plasma PTH (+31%), despite comparable urinary Ca excretion and similarly deficient 25(OH) vitamin D levels. In APA patients, who showed the PTHR-1 transcript and protein in tumor tissue, adrenalectomy normalized PTH levels (from 118 ±â€Š13 to 76 ±â€Š12 ng/l; P = 0.002) and increased ionized Ca(from 1.17 ±â€Š0.04 to 1.22 ±â€Š0.03 mmol/l; P < 0.001). The slope of the inverse PTH/ionized Ca relationship was steeper in primary aldosteronism than in primary (essential) hypertension, but normalized after adrenalectomy. CONCLUSION: Hence, in primary aldosteronism an increased sensitivity of parathyroid cells to Ca lowering leads to an increase of PTH. This subtle hyperparathyroidism by acting on PTHR-1 in APA might contribute to maintaining hyperaldosteronism despite suppression of angiotensin II formation.

Drug-related hypertension and resistance to antihypertensive treatment: a call for action.

Several drugs can cause hypertension and/or blunt the effect of antihypertensive treatment. They can exacerbate a previously well controlled hypertension and/or render it resistant to therapy. Accordingly, drugs represent a common cause of resistance of hypertension to treatment. Identification of drug-related hypertension can be achieved with a thorough medical history targeted to ascertain concurrent therapies that are prescribed for conditions other than cardiovascular diseases. This can avoid prescribing a more aggressive antihypertensive treatment and may prevent embarking in costly and sometimes invasive diagnostic procedures. Drugs that commonly raise blood pressure include NSAIDs, steroids, oestroprogestinic agents, immunosuppressants, erythropoietin, inhibitors of angiogenesis, anti-HIV agents, and also some high-density lipoprotein-raising agents. As withdrawal of the offending drug is often impracticable, knowledge of the mechanism(s) by which each drug exerts its pressor effects may help selecting the most effective treatment. Purpose of this review is to examine the most common causes of resistant hypertension that are due to drugs or abuse of substances along with their underlying pathophysiological mechanisms. The strategy for selecting the most appropriate treatment and the reasons for 'a call of action' of research in this area are also examined.

Secondary hypertension: the ways of management.

The prevalence of secondary hypertension is lower than that of primary (essential) hypertension, but it is likely that it has been underestimated because appropriate tests were not generally performed. Hence, before embarking on a search for secondary hypertension physicians are generally advised to select populations of patients with a high pre-test probability of secondary forms of hypertension in order to maximize the positive predictive value and the gain in "ruling in" of the diagnostic tests. Based on updated information on prevalence and pathophysiology we herein critically review the general diagnostic strategy and the management of the main forms of secondary hypertension. In particular, strategies for identifying primary aldosteronism, the most frequent form of endocrine secondary hypertension, and for determining its unilateral or bilateral causes are discussed in details, because of the differences of treatment that requires adrenalectomy in the unilateral forms and mineralocorticoid receptor blockade in the bilateral forms. The tests available for the diagnosing pheochromocytoma (pheo), which is much rarer but extremely important to identify, as it can be fatal if unrecognized are also discussed, with emphasis on the recent developments in genetic testing. Renovascular hypertension is also a common curable form of hypertension, which should be identified as early as possible to avoid the onset of cardiovascular target organ damage and events, is also discussed.