Management of transient loss of consciousness of suspected syncopal cause, after the initial evaluation in the Emergency Department

The recommendations enclosed in the present document have been developed by a group of experts appointed by the Gruppo Multidisciplinare per lo Studio della Sincope (Multidisciplinary Group for the Study of Syncope; GIMSI) and Academy of Emergency Medicine and Care (AcEMC). The aim is to define the diagnostic pathway and the management of patients referred to the Emergency Department (ED) for transient loss of consciousness of suspected syncopal cause, which is still unexplained after the initial evaluation. The risk stratification enables the physician to admit, discharge or monitor shortly the patient in the intensive short-stay Syncope Observation Unit (SOU). There are three risk levels of life-threatening events or serious complications (low, moderate, high). Low risk patients can be discharged, while high risk ones should be monitored and treated properly in case of worsening. Moderate risk patients should undergo clinical and instrumental monitoring in SOU, inside the ED. In all these three cases, patients can be subsequently referred to the Syncope Unit for further diagnostic investigations

11ß-hydroxysteroid dehydrogenase type 2 activity is associated with left ventricular mass in essential hypertension

Aims: Left ventricular mass (LVM) is under the control of aldosterone and angiotensin II in experimental hypertension, but the effect of aldosterone on LVM is controversial in essential hypertension (EH). Some EH patients show a mild impairment of 11ß-hydroxysteroid dehydrogenase type 2 (11ß-HSD2) activity without clinical features of the syndrome of apparent mineralocorticoid excess, where the incomplete cortisol-to-cortisone conversion leads to glucocorticoid-mediated mineralocorticoid effects. The mineralocorticoid receptor and 11ß-HSD2 are co-expressed in human heart. We investigated whether LVM may be regulated by glucocorticoids in EH patients. Methods and results: The ratio between 24 h urinary tetrahydro derivatives of cortisol and cortisone (THFs/THE), plasma renin activity, 24 h urinary aldosterone, blood pressure, and LVM indexed for height2.7 (LVMh2.7) were analysed in 493 never-treated hypertensives and 98 normotensives. THFs/THE was associated with LVMh2.7 in hypertensives and normotensives (r=0.32, P<0.001, and r=0.17, P=0.04, respectively) and persisted after adjusting for confounders (multiple regression analysis). Body mass index, sex, recumbent plasma renin activity, and THFs/THE accounted for 26.1% of LVMh2.7 variation. Urinary aldosterone was not correlated with LVMh2.7. Conclusion: We suggest that glucocorticoids may take part in the regulation of LVM in EH patients as a function of 11ß-HSD2 activity, and contribute to the target organ damage associated with essential hypertension

A Kallikrein-like enzyme in the aorta of normotensive and hypertensive rats

We evaluated whether vascular kallikrein is altered in rats with genetic or experimental hypertension. Group 1 was infused intraperitoneally with angiotensin II (Ang II) or vehicle for 4 weeks; group 2 was injected subcutaneously with deoxycorticosterone (75 mumol/kg once a week) or vehicle for 4 weeks; group 3 consisted of uninephrectomized rats on high sodium intake given deoxycorticosterone or vehicle; and group 4 consisted of spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. Active and total kallikrein activity was measured in abdominal aortic homogenates using an amidolytic assay. Ang II increased systolic blood pressure at a dose of 400 nmol/kg per day (146 +/- 6 versus 123 +/- 3 mm Hg in controls, P < .01) but not at 80 nmol/kg per day. Deoxycorticosterone did not increase blood pressure except in uninephrectomized rats on high salt (173 +/- 6 versus 135 +/- 4 mm Hg in controls, P < .01). Blood pressure averaged 194 +/- 2 mm Hg in SHR and 123 +/- 3 mm Hg in WKY rats. Vascular kallikrein was similar in rats given Ang II or vehicle. In deoxycorticosterone-treated rats total kallikrein was higher than in controls (9.2 +/- 0.8 versus 3.5 +/- 0.1 pkat/mg protein, P < .05), whereas active kallikrein did not differ (0.09 +/- 0.04 versus 0.09 +/- 0.03 pkat/mg protein, P = NS). A similar pattern was observed in uninephrectomized deoxycorticosterone-treated rats (active, 0.09 +/- 0.03 versus 0.10 +/- 0.04, P = NS; total, 7.4 +/- 0.7 versus 4.1 +/- 0.2 pkat/mg protein, P < .05). Kallikrein activity was higher in SHR compared with WKY rats (active, 0.34±0.04 versus 0.10±0.03; total, 9.5 + 1.2 versus 4.6±0.3 pkat/mg protein, P<.05). In conclusion, a kallikrein-like enzyme is present in rat aorta. The activity of this enzyme is elevated in rats with genetic hypertension, and it may be regulated by mineralocorticoids

Effect of the HMG-CoA reductase inhibitors on blood pressure in patients with essential hypertension and primary hypercholesterolemia

Certain hydroxymethylglutaryl coenzyme A reductase inhibitors, ie, statins, may cause vasodilation by restoring the endothelial dysfunction that frequently accompanies hypertension and hypercholesterolemia. Several studies have found that a blood pressure reduction is associated with the use of statins, but conclusive evidence from controlled trials is lacking. After an 8-week placebo and diet run-in period, 30 persons with moderate hypercholesterolemia and untreated hypertension (total cholesterol 6.29±0.52 mmol/L, systolic and diastolic blood pressure 149±6 and 97±2 mm Hg) were randomized in a double-blind manner to placebo or pravastatin (20 to 40 mg/d) in a crossover design. In 25 participants who completed the 32-week trial, pravastatin decreased total and LDL cholesterol (both -1.09 mmol/L, P=0.001), systolic and diastolic blood pressure (-8 and -5 mm Hg, both P=0.001), and pulse pressure (-3 mm Hg, P=0.011) and blunted the blood pressure increase caused by the cold pressor test (-4 mm Hg, P=0.005) compared with placebo. It also reduced the level of circulating endothelin-1 (P=0.001). The blood pressure results were virtually unchanged in stratified analyses according to gender and age and in intention-to-treat analyses that included the 5 patients who dropped out of the study. When the participants were taking either placebo or pravastatin, blood pressure was not significantly correlated with total or LDL cholesterol or with circulating endothelin-1. Pravastatin decreases systolic, diastolic, and pulse pressures in persons with moderate hypercholesterolemia and hypertension. This antihypertensive effect may contribute to the documented health benefits of certain statins

The Role of a-Adducin Polymorphism in Blood Pressure and Sodium Handling Regulation May Not Be Excluded by a Negative Association Study

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Effects of Hoe 140, a bradykinin B₂-receptor antagonist, on renal function in conscious normotensive rats

The present study was designed to determine if endogenous kinins are involved in the regulation of arterial blood pressure and renal function in conscious rats given deoxycorticosterone enantate (DOC, 25 mg kg−1, s.c., weekly) or vehicle for two weeks. The bradykinin B2-receptor antagonist, d-Arg[Hyp3,Thi5,d-Tic7,Oic8]-bradykinin (Hoe 140), at a dose of 300 μg kg−1, s.c., blocked the hypotensive effect of 300 ng kg−1 bradykinin i.a., but it did not alter the blood pressure lowering action of 300 ng kg−1 acetylcholine or prostaglandin E2. Inhibition of the response to bradykinin persisted up to 6 h after the administration of Hoe 140. Administration of 300 μg kg−1 Hoe 140 s.c. four times a day did not alter mean blood pressure, renal blood flow, or renal function in rats given DOC-vehicle. However, it decreased urinary volume by 70% (from 48.2 ± 3.8 to 14.3 ± 3.7 ml 24 h−1, P &lt; 0.01) and urinary secretion of sodium by 54% (from 1.02 ± 0.05 to 0.47 ± 0.16 mmol 24 h−1, P &lt; 0.01) and potassium by 30% (from 2.93 ± 0.15 to 2.04 ± 0.15 mmol 24 h−1, P &lt; 0.05) in DOC-treated rats. Mean blood pressure, glomerular filtration rate and total renal blood flow remained unchanged. Our results suggest that endogenous kinins play a role in the regulation of renal excretion of water and sodium in the presence of elevated levels of DOC.</br

Interaction of α₁-Na,K-ATPase and Na,K,2Cl-cotransporter genes in human essential hypertension

Essential hypertension is a common disease the genetic determinants of which have been difficult to unravel because of its clinical heterogeneity and complex, multifactorial, polygenic etiology. Based on our observations that α1-Na,K-ATPase (ATP1A1) and renal-specific, bumetanide-sensitive Na,K,2Cl-cotransporter (NKCC2) genes interactively increase susceptibility to hypertension in the Dahl salt-sensitive hypertensive (Dahl S) rat model, we investigated whether parallel molecular genetic mechanisms might exist in human essential hypertension in a relatively genetic homogeneous cohort in northern Sardinia. Putative ATP1A1-NKCC2 gene interaction was tested by comparing hypertensive patients (blood pressure [BP] &gt;165/95 mm Hg) with normotensive controls age &gt;60 years with BP &lt;140/85 mm Hg. Genotype analysis with microsatellite markers revealed conformation to Hardy-Weinberg proportions for 6 alleles of both ATP1A1 (D1S453) and NKCC2 (NKCGT7) markers, respectively. Two-by-six χ2 analysis of alleles identified overrepresentation of ATP1A1 No. 4 and NKCC2 No. 4 alleles, respectively, in hypertensives compared with controls. With a qualitative trait framework, single-gene analysis detected association of both the ATP1A1 No. 4 allele (P=0.004, χ2=8.094, df=1) and the NKCC2 No. 4 allele (P=0.0002, χ2=14.279, df=1) with moderate to severe hypertension. Digenic analysis revealed that ATP1A1 No. 4-NKCC2 No. 4 allele interaction increases susceptibility to hypertension (P&lt;0.0001, χ2=22.3, df=1) beyond levels obtained in single-gene analysis. Analysis was also performed in a quantitative trait framework with BP as the continuous trait parameter. Digenic analysis of ATP1A1 No. 4-NKCC2 No. 4 allele interaction revealed significant association with systolic (1-way ANOVA, P=0.000076) and diastolic (P=0.00099) BP. Interaction was corroborated by 232 factorial ANOVA for interaction (systolic BP interaction term, P&lt;0.05, diastolic BP interaction term, P=0.035). The data are compelling that ATP1A1 and NKCC2 genes are candidate interacting hypertension-susceptibility loci in human essential hypertension and affirm gene interaction as an important genetic mechanism underlying hypertension susceptibility. Although corroboration in other cohorts and identification of functionally significant mutations are imperative next steps, the data provide a genotype-stratification scheme, with 4-fold predictive value (odds ratio, 4.28; 95% confidence interval, 2.29 to 8.0), which could help decipher the complex genetics of essential hypertension

The Role of α-adducin polymorphism in blood pressure and sodium handling regulation may not be excluded by a negative association study

The basic requirement for declaring an association study positive is that the "hypertension-favoring" allele is more frequent in hypertensive cases than in normotensive controls. However, both positive and negative associations with hypertension have been found for the same polymorphism when studied in different populations. In the present study, we addressed the question of the possible cause(s) of this discrepancy among populations by using the α-adducin polymorphism as a paradigm. Four hundred ninety hypertensives and 176 normotensives enrolled in Sassari, Italy, and 468 hypertensives and 181 normotensives enrolled in Milano, Italy, were genotyped for the α-adducin Gly460Trp polymorphism. The blood pressure response to 2 months of hydrochlorothiazide therapy could be evaluated in 143 (85 in Sassari and 58 in Milano) hypertensives with and without the 460Trp α-adducin allele. The α-adducin 460Trp allele was not significantly more frequent in hypertensives in the Sassari population but was more frequent in hypertensives than in normotensives in Milano (P=0.019). Basal plasma renin activity was lower and blood pressure fall after diuretic therapy more pronounced (P&lt;0.01) in hypertensives carrying at least one 460Trp allele than in Gly460Gly homozygotes, irrespective of their membership in the Sassari or Milano cohort. The effect of α-adducin genotype in predicting basal plasma renin activity and blood pressure decrease with diuretic treatment is similar in Sassari and Milano, despite the lack of association of the α-adducin genotype with hypertension in Sassari