Cortisol Awakening Reaction and Anxiety in Depressed Coronary Artery Disease Patients.

Disturbances of HPA axis functioning as represented by cortisol awakening reaction (CAR) belong to the mediating pathways linking psychosocial distress and cardiovascular risk. Both depression and anxiety have been confirmed as independent risk factors for coronary artery disease (CAD). However, data on anxiety and cortisol output in CAD patients are scarce. Based on previous data, we hypothesized that anxiety would be associated with higher cortisol output and a more pronounced morning increase in moderately depressed CAD patients. 77 patients (60 y, 79% male) underwent saliva sampling (+0, +30, +45, +60 min after awakening, midday and late-night sample). Anxiety was measured using the Hospital Anxiety and Depression Scale (HADS) and patients were grouped into anxious versus non anxious subjects based upon the recommended score (≥11). A repeated measures ANOVA yielded a significant time and quadratic time effect referring to the typical CAR. Anxious patients showed a significantly steeper 30 min increase, higher AUCi, lower waking and late-night cortisol levels. The steeper cortisol increase in the anxious group is in line with previous data and may be interpreted as a biological substrate of affect regulation. The lower basal and late-night levels coupled with greater AUCi mirror a more dynamic reactivity pattern compared to depressed subjects without anxiety.

Relevance of maternal sodium level for preeclampsia-associated adverse pregnancy outcomes.

OBJECTIVE: To evaluate maternal sodium levels in women with preeclampsia (PE) or at high risk for preeclampsia and their relevance for severe PE-associated adverse pregnancy outcome and remaining pregnancy duration. STUDY DESIGN: In a retrospective cohort of 198 patients presenting with signs and symptoms of preeclampsia (PE), we investigated maternal sodium level and the sFlt-1/PlGF-ratio within 14 days prior to delivery. MAIN OUTCOME MEASURES: In total, 88 patients (44.4%) developed a maternal and/or fetal and neonatal preeclampsia-associated adverse outcome (AO). The median sodium level was lower in the cohort with vs. without AO (136 vs. 137 mmol/l) and correlated negatively with the sFlt-1/PlGF-ratio (r = -0.19, 95% CI: -0.31 to -0.05) in both groups. Logistic regression revealed a significant association of the maternal sodium level with the development of an AO (+1 mmol/l reduced the odds by 21%, [Odds ratio (OR) of 0.79 (95% CI 0.67-0.93), p < 0.01], whereas the sFlt-1/PlGF showed a contrary effect (+10 units OR of 1.05 (95% CI: 1.02-1.08, p < 0.01)). Linear mixed effects models showed consistent results, with sodium level positively associated with the remaining pregnancy duration. CONCLUSIONS: Our results confirm the relevance of decreased maternal sodium level as a severity marker for PE-associated adverse outcomes.

Prediction of Preeclampsia-Related Adverse Outcomes With the sFlt-1 (Soluble fms-Like Tyrosine Kinase 1)/PlGF (Placental Growth Factor)-Ratio in the Clinical Routine: A Real-World Study.

This retrospective real-world study investigated the clinical use of the sFlt-1 (soluble fms-like tyrosine kinase 1)/PlGF (placental growth factor) ratio alone or in combination with other clinical tests to predict an adverse maternal (maternal death, kidney failure, hemolysis elevated liver enzymes low platelets-syndrome, pulmonary edema, disseminated intravascular coagulation, cerebral hemorrhage, or eclampsia) or fetal (delivery before 34 weeks because of preeclampsia and/or intrauterine growth restriction, respiratory distress syndrome, necrotizing enterocolitis, intraventricular hemorrhage, placental abruption or intrauterine fetal death or neonatal death within 7 days post natum) pregnancy outcome in patients with signs and symptoms of preeclampsia. We evaluated the sFlt-1/PlGF-ratio cutoff values of 38 and 85 and evaluated its integration into a multimarker model. Of 1117 subjects, 322 (28.8%) developed an adverse fetal or maternal outcome. Patients with an adverse versus no adverse outcome had a median sFlt-1/PlGF-ratio of 177 (interquartile range, 54-362) versus 14 (4-64). Risk-stratification with the sFlt-1/PlGF cutoff values into high- (>85), intermediate- (38-85), and low-risk (<38) showed a significantly shorter time to delivery in high- and intermediate- versus low-risk patients (4 versus 8 versus 29 days). When integrating all available clinical information into a multimarker model, an area under the curve of 88.7% corresponding to a sensitivity, specificity, positive and negative predictive value of 80.0%, 87.3%, 75.0%, and 90.2% was reached. The sFlt-1/PlGF-ratio alone was inferior to the full model with an area under the curve of 85.7%. As expected, blood pressure and proteinuria were significantly less accurate with an area under the curve of 69.0%. Combining biomarker measurements with all available information in a multimarker modeling approach increased detection of adverse outcomes in women with suspected disease.

Diagnosis of preeclampsia and fetal growth restriction with the sFlt-1/PlGF ratio: Diagnostic accuracy of the automated immunoassay Kryptor®.

OBJECTIVE: We aimed to characterize the diagnostic accuracy of the Kryptor® assay for sFlt-1 and PlGF in maternal serum samples of uneventful singleton pregnancies and subjects with preeclampsia (PE) and PE-related outcomes such as fetal growth restriction (FGR). Longitudinal reference ranges of the sFlt-1 and PlGF level in the course of normal pregnancies were generated. METHODS: A cohort of subjects with PE and PE-related outcomes including FGR in the third trimester was compared to a cohort of women with uneventful outcome. Serum levels of sFlt-1, PlGF level as well as the sFlt-1/PlGF ratio was analysed with the Kryptor® assay and compared between the case- and control groups. Cut-off values were generated and diagnostic accuracy examined. RESULTS: Longitudinal reference ranges of the sFlt-1 and PlGF level in healthy pregnancies were in line with those levels measured with other immunoassays. Comparison of the sFlt-1/PlGF ratio between PE-related outcomes including FGR or PE and healthy controls showed a high diagnostic accuracy with an area under the curve (AUC) of 0.917 for PE-related outcomes and 0.919 for PE.

[C reactive protein in women with coronary heart disease and its association with depression]. / C-reaktives Protein bei Frauen mit koronarer Herzkrankheit und Zusammenhange mit Depressivitat.

OBJECTIVES: Depression is associated with increased risk and poor outcome of coronary heart disease (CHD), though the mechanisms are largely unknown. Low-grade inflammation offers a possible biological pathway, which has been confirmed in men but not in women. METHODS: We studied the association of C reactive protein (CRP), a biomarker of inflammation, with depressive symptoms in 292 women with CHD and 300 healthy age-matched controls, considering confounder variables (BMI, age, HDL cholesterol, triglycerides, menopausal status). CRP was measured by a high sensitivity assay. RESULTS: In the overall sample no significant association was found between depressive symptoms and CRP, whereas in the control group women with 2 or more versus 0-1 depressive symptoms showed heightened CRP (p = 0.005); there was no significant difference in CRP levels between CHD patients with 0-1 versus 2 or more depressive symptoms. Women with CHD had higher serum levels of CRP and more depressive symptoms than did controls. CONCLUSIONS: Contrary to men and healthy controls there was no link between CRP and depressive symptoms in women with CHD. More research is needed on how the harmful effects of depression are mediated, especially in women.

The genetic deletion of Mas abolishes salt induced hypertension in mice.

The G protein-coupled receptor Mas is a physiological antagonist of the angiotensin II type 1 receptor and is associated with angiotensin-(1-7) signaling. We investigated the effect of Mas-deficiency on blood pressure regulation under physiological conditions and salt load using radiotelemetry. Mas-knockout mice and their wild-type controls received a telemetry implant in the carotid artery. One week after surgery, animals were monitored for 3 days receiving normal diet (0.6% NaCl) followed by one-week high-salt diet (8% NaCl). Under same high-salt diet, another set of mice was placed in individual metabolic cages for 4 days. Basal mean arterial pressure, heart rate and locomotor activity displayed normal day-night rhythm in Mas-deficient mice. Mas-knockout mice were normotensive. High dietary NaCl ingestion did not alter heart rate or locomotor activity in both groups, but significantly increased night time mean arterial pressure in control mice whereas this increase was blunted in Mas-deficient mice. Baseline food and water intake and urine osmolality were not different between both genotypes. Under high-salt diet, water consumption and food intake were equally increased in wild-type controls and Mas-knockout, but urinary electrolytes and osmolality were significantly higher in Mas-knockout. Taken together, basal hemodynamic parameters are unchanged in Mas-knockout mice. In contrast to wild-type controls, telemetric mean arterial pressure measurement revealed salt resistance in Mas-deficient animals, probably due to their higher urinary NaCl excretion. This is the first direct proof that Mas blockade might be a new option in the treatment of salt-sensitive hypertension.

Thoracic epidural anesthesia attenuates endotoxin-induced impairment of gastrointestinal organ perfusion.

BACKGROUND: Systemic inflammation can be associated with a redistribution of organ blood flow and a decrease in gastrointestinal perfusion. Regional sympathetic blockade by means of thoracic epidural anesthesia (TEA) has been shown to improve intestinal microcirculation during systemic inflammation. This study tests the hypothesis that during systemic inflammation, TEA attenuates the impairment of gastrointestinal organ perfusion without compromising blood flow to vital organs. METHODS: Eighteen rats were anesthetized, hemodynamically monitored, and mechanically ventilated with room air. By using fluorescent microspheres, organ perfusion was quantified at baseline, 30 min after the start of epidural infusion of either 2% lidocaine (TEA) or normal saline (control), and after 60 and 120 min of intravenous Escherichia coli lipopolysaccharide infusion in TEA and control animals. RESULTS: Blood pressure initially was lower in TEA animals, but it was comparable to controls during endotoxemia. Gastrointestinal organ perfusion significantly decreased after 120 min of endotoxemia in the controls but not in the TEA animals (-23 +/- 27% vs. -6 +/- 26%, mean +/- SD, P < 0.05). Perfusion of the vital organs such as the heart, brain, liver, and kidneys was comparable between controls and TEA after 120 min of endotoxemia. CONCLUSIONS: TEA attenuates the impairment of gastrointestinal organ perfusion during endotoxemia. Hence, the protective effects of TEA on intestinal microcirculation during endotoxemia may be due to a higher total organ blood flow compared with endotoxemic control animals. Furthermore, in the course of endotoxemia, TEA provides hemodynamic stability and does not compromise blood flow to vital organs.

Emotional irritation before mental stress is associated with enhanced peripheral norepinephrine.

Research suggests equivocal findings on associations of catecholamines and mood. Our study investigated the associations of emotional state, blood pressure and catecholamines in 55 healthy males undergoing mental stress. We especially checked the reported link between norepinephrine (NE) and emotional irritation. Blood pressure (SBP, DBP) and heart rate (HR) were continuously monitored. NE and epinephrine (EPI) were measured before, after, and 20 minutes after stress. Participants were divided into irritated versus non-irritated and anxious versus non-anxious subjects by median split on their baseline questionnaires. The task elicited significant cardiovascular, hormonal, and psychological stress responses. NE levels were significantly correlated with irritation before stress. Irritated subjects showed significantly higher DBP and NE than non-irritated subjects. The higher NE and DBP levels in the irritated participants suggest detrimental psycho-physiological interrelations promoting the development of stress-mediated cardiovascular diseases. Heightened emotional irritation before stress may be regarded as a psychological risk factor.

Rapid screening test for primary hyperaldosteronism: ratio of plasma aldosterone to renin concentration determined by fully automated chemiluminescence immunoassays.

BACKGROUND: The ratio of plasma aldosterone concentration to plasma renin activity (PAC/PRA) is the most common screening test for primary hyperaldosteronism (PHA), but it is not standardized among laboratories. We evaluated new automated assays for the simultaneous measurement of PAC and plasma renin concentration (PRC). METHODS: We studied 76 healthy normotensive volunteers and 28 patients with confirmed PHA. PAC and PRC were measured immunochemically in EDTA plasma on the Nichols Advantage chemiluminescence analyzer, and PRA was determined by an activity assay. RESULTS: In volunteers, PAC varied from 33.3 to 1930 pmol/L, PRA from 1.13 to 19.7 ng.mL(-1).h(-1) (0.215 ng.mL(-1).h(-1) = 1 pmol.L(-1).s(-1)), and PRC from 5.70 to 116 mU/L. PAC/PRA ratios ranged from 4.35 to 494 (pmol/L)/(ng.mL(-1).h(-1)) and PAC/PRC ratios from 0.69 to 71.0 pmol/mU. In PHA patients, PAC ranged from 158 to 5012 pmol/L, PRA from 0.40 to 1.70 ng.mL(-1).h(-1), and PRC from 0.80 to 11.7 mU/L. PAC/PRA ratios were between 298 and 6756 (pmol/L)/(ng.mL(-1).h(-1)) and PAC/PRC ratios between 105 and 2328 pmol/mU. Whereas PAC or PRC showed broad overlap between PHA patients and volunteers, the PAC/PRC ratio indicated distinct discrimination of these two groups at a cutoff of 71 pmol/mU. CONCLUSION: The PAC/PRC ratio offers several practical advantages compared with the PAC/PRA screening method. The present study offers preliminary evidence that it may be a useful screening test for PHA. Further studies are required to validate these results, especially in hypertensive cohorts.

Functional effects of acute coronary occlusion and catecholinergic stimuli on the isolated normothermic hemoperfused porcine heart.

The aim of this study was to characterize functional parameters in the isolated and normothermic hemoperfused porcine beating heart model after pathophysiological stimuli for extended perfusion periods. Hearts were prepared and connected to a specially developed perfusion equipment, which simultaneously allowed perfusion with warm autologous blood as well as blood dialysis. Two groups were established: group A (12 hearts: no intervention) and group B (6 hearts: occlusion of the ramus circumflexus of the left coronary artery for 2 hours). Blood gas analyses and oxymetry were performed at baseline and every 30 min during a 6 hours perfusion period. Coronary perfusion pressure (CPP) and blood flow (CBF), right and left ventricular pressure, blood and dialyzate pH-values, and temperature were monitored online by a microcontroller. A steady state regarding the CPP and the CBF was achieved after 1 hour of perfusion for both groups. In group B, CPP increased during occlusion. Comparison of both groups showed no significant differences in the bicarbonate and sodium levels in blood and dialyzate. The potassium concentration in blood and dialyzate increased in both groups constantly during the experiments. No clear alteration of the oxygen consumption was observed. Lactate levels in blood and dialyzate increased during occlusion as did the aspartataminotransferase (AST) venous levels (both determined only for group B). Four concentrations of norepinephrine were injected into the stem of the coronary arteries (10, 20, 40, 80 microg). A clear inotropic effect of this hormone on right and left ventricular pressure was observed. It was concluded that longer perfusion periods and simulation of myocardial infarction for a clinically relevant period can be performed using this model. In addition, right and left ventricular function appear to be well preserved in this model, since the isolated porcine heart responded to norepinephrine stimuli.