Plasma ceramide is increased and associated with proteinuria in women with pre-eclampsia and HELLP syndrome.

OBJECTIVES: Ceramide is a sphingolipid with anti-angiogenic and pro-apoptotic properties that has shown to be increased in plasma of women with pre-eclampsia. We aimed to compare plasma and placental sphingolipid content among normotensive pregnant women and pre-eclamptic women with and without HELLP syndrome and we aimed to assess whether ceramide is related to hypertension and proteinuria in pre-eclampsia. STUDY DESIGN: Case-control study. Participants were recruited from the Department of Obstetrics at the Academic Medical Center in Amsterdam, The Netherlands. In total 48 pregnant women were included: 24 with pre-eclampsia and 24 normotensive controls. Of the 24 pre-eclamptic women, 11 had HELLP syndrome. MAIN OUTCOME MEASURES: Plasma and placental ceramide content and correlation with blood pressure and protein excretion in pre-eclampsia. RESULTS: Total plasma, but not placental, ceramide was higher in pre-eclamptic women with HELLP syndrome (11200 95% CI 9531-12870 nmol/ml, n = 11) compared to pre-eclamptic women without HELLP (7413 95% CI 5928-8898 nmol/ml, n = 13, p < 0.001) and normotensive pregnant women (7404 95% CI 6695-8112 nmol/ml, n = 24, p < 0.001). Maternal circulating ceramide levels were strongly associated with proteinuria (r = 0.621, n = 24, p = 0.001) in pre-eclamptic women and inversely correlated with gestational age at delivery (r = 0.771, p < 0.01) in pre-eclamptic women with HELLP syndrome. Plasma ceramide was not correlated with blood pressure. CONCLUSION: Plasma but not placental ceramide content is increased in women with pre-eclampsia and HELLP syndrome. The strong positive correlation with proteinuria and the inverse correlation with gestational age at delivery indicate that excess plasma ceramide may contribute to the pathophysiology of pre-eclampsia and HELLP.

ESC Council on hypertension position document on the management of hypertensive emergencies.

Hypertensive emergencies are those situations where very high blood pressure (BP) values are associated with acute organ damage, and therefore, require immediate, but careful, BP reduction. The type of acute organ damage is the principal determinant of: (i) the drug of choice, (ii) the target BP, and (iii) the timeframe in which BP should be lowered. Key target organs are the heart, retina, brain, kidneys, and large arteries. Patients who lack acute hypertension-mediated end organ damage do not have a hypertensive emergency and can usually be treated with oral BP-lowering agents and usually discharged after a brief period of observation.

Organic matter degradation in a greywater recycling system using a multistage moving bed biofilm reactor (MBBR).

Greywater is an important non-conventional water resource which can be treated and recycled in buildings. A decentralized greywater recycling system for 223 inhabitants started operating in 2006 in Berlin, Germany. High load greywater undergoes advanced treatment in a multistage moving bed biofilm reactor (MBBR) followed by sand filtration and UV disinfection. The treated water is used safely as service water for toilet flushing. Monitoring of the organic matter degradation was pursued to describe the degradation processes in each stage and optimize the system. Results showed that organic matter reduction was achieved for the most part in the first three reactors, whereas the highest reduction rate was observed in the third reactor in terms of COD (chemical oxygen demand), dissolved organic carbon and BOD7 (biological oxygen demand). The results also showed that the average loading rate entering the system was 3.7 kg COD/d, while the removal rate was 3.4 kg COD/d in a total bioreactor volume of 11.7 m³. In terms of BOD, the loading rate was 2.8 kg BOD/d and it was almost totally removed. This system requires little space (0.15 m²/person) and maintenance work of less than one hour per month and it shows operational stability under peak loads.

SFlt-1 elevates blood pressure by augmenting endothelin-1-mediated vasoconstriction in mice.

OBJECTIVE: Scavenging of vascular endothelial growth factor (VEGF) elevates blood pressure (BP) in patients receiving anti-angiogenic therapy. Similarly, inhibition of circulation VEGF by its soluble receptor fms-like tyrosine kinase-1 (sFlt-1) underlies BP elevation in pre-eclampsia. Both phenotypes are characterized by augmented production of endothelin-1 (ET-1), suggesting a role for ET-1 in anti-angiogenic hypertension. We aimed to assess the effect of VEGF inhibition on ET-1-induced contractility and downstream ET-1 signaling. APPROACH AND RESULTS: Male C57BL/6N mice were treated with either sFlt-1 or vehicle and BP was assessed via tail-cuff. Mean arterial pressure of sFlt-1-treated mice markedly increased compared to vehicle-treated controls (N = 11-12, p<0.05). After sacrifice, carotid and mesenteric arteries were isolated for isometric tension measurements. ET-1-induced contractions were similar in mesenteric arteries of vehicle and sFlt-1-treated mice, but augmented in carotid segments of sFlt-1-treated mice compared to controls (N = 9-10, p<0.05). The increased contraction in carotid segments could be completely abrogated by the cyclooxygenase (COX) inhibitor indomethacin (N = 9-10, p<0.05), indicating heightened prostaglandin-mediated vasoconstriction. This was associated with a shift towards procontractile ETB signaling in sFlt-1-treated mice, possibly explaining the increased ET-1-induced prostaglandin-mediated vasoconstriction. In line with the ex vivo findings, sFlt-1-induced BP elevation could be prevented in vivo by oral treatment with either a high-dose of the COX inhibitor aspirin (N = 7) or with picotamide (N = 9), a dual thromboxane A2 synthase inhibitor and receptor antagonist. CONCLUSIONS: VEGF inhibition augments the pressor response to ET-1. The cyclooxygenase-thromboxane signaling route downstream of ET-1 might be a possible target to prevent BP elevation during VEGF inhibition.

Microvascular glycocalyx dimension estimated by automated SDF imaging is not related to cardiovascular disease.

OBJECTIVE: The EG regulates vascular homeostasis and has anti-atherogenic properties. SDF imaging allows for noninvasive visualization of microvessels and automated estimation of EG dimensions. We aimed to assess whether microcirculatory EG dimension is related to cardiovascular disease. METHODS: Sublingual EG dimension was estimated by SDF imaging in healthy volunteers and in patients visiting an outpatient clinic for vascular medicine of a university hospital in Amsterdam, the Netherlands. EG dimension was compared among healthy volunteers, patients with CVD, and patients at low (<10%) or high risk (≥ 10%) of CVD according to the Framingham algorithm. RESULTS: In total 120 patients and 30 healthy volunteers were included. Patients had a mean age of 59 ± 14 years, 71 (59%) were men and 24 (20%) were black. Healthy volunteers were on average 28 ± 4 years and 19 (63%) were men. EG dimension was similar in healthy volunteers (2.04 ± 0.23 µm), low-risk patients (2.05 ± 0.24 µm, n = 39), high-risk patients (2.05 ± 0.23 µm, n = 30) and in patients with CVD (2.09 ± 0.21 µm, n = 51, p = 0.79). EG dimension was not correlated with cardiovascular risk factors. CONCLUSIONS: Microcirculatory EG dimension, as estimated by automated SDF imaging, is not associated with CVD, suggesting that this technique may not contribute to cardiovascular risk stratification.

Mortality and cardiovascular risk in patients with a history of malignant hypertension: a case-control study.

The survival of patients with malignant hypertension (MHT) has considerably improved over the past decades. Data regarding the excess risk of mortality and the contribution of conventional cardiovascular risk factors are lacking. The authors retrospectively assessed cardiovascular risk factors and all-cause mortality in 120 patients with a history of MHT and compared them with 120 normotensive and 120 hypertensive age-, sex-, and ethnicity-matched controls. Total cholesterol, low-density lipoprotein cholesterol, and body mass index were lower in MHT patients compared with hypertensive controls, whereas blood pressure, high-density lipoprotein cholesterol, and smoking habit were similar. Median estimated glomerular filtration rate was lower in MHT patients compared with normotensive and hypertensive controls (both P<.01). The annual incidence of all-cause mortality per 100 patient-years was higher in MHT patients (2.6) compared with normotensive (0.2) and hypertensive (0.5) controls (both P<.01). Mortality of patients with a history of MHT remains high compared with normotensive and hypertensive controls. Patients with MHT had a more favorable cardiovascular risk profile compared with hypertensive controls but a higher prevalence of renal insufficiency.

Long-term renal outcome in patients with malignant hypertension: a retrospective cohort study.

BACKGROUND: Malignant hypertension is frequently complicated by renal insufficiency. Although the survival of this hypertensive emergency has improved, recent data on renal outcome and its predictors are lacking. We assessed renal outcome and its predictors in patients with malignant hypertension. METHODS: Retrospective analysis of patients admitted with malignant hypertension in Amsterdam, the Netherlands between August 1992-January 2010. Follow-up data on vital status, renal function and blood pressure (BP) were obtained from the outpatient department and from general practitioners. The primary composite endpoint was end-stage renal disease (ESRD) defined as the start of kidney replacement therapy (KRT) or ≥ 50% decline of estimated glomerular filtration rate (eGFR). The secondary endpoint was all cause mortality. RESULTS: A total of 120 patients admitted with malignant hypertension were included. After a median follow-up period of 67 months (IQR 28 to 108 months) the primary endpoint was reached by 37 (31%) patients, whereas 18 patients (15%) reached the secondary endpoint. Twenty-nine (24%) patients started KRT and 8 patients (7%) had an eGFR decline ≥ 50%. After the acute phase (> 3 months after admission), initial serum creatinine and follow-up BP were the main predictors of future ESRD with hazard ratios of 6.1 (95% CI, 2.2-17) for patients with initial serum creatinine ≥ 175 µmol /L and 4.3 (95% CI, 1.4-14) for patients with uncontrolled hypertension. CONCLUSIONS: Progressive renal function decline leading to ESRD remains a major threat to patients with malignant hypertension. BP control during follow-up was an important modifiable predictor of renal outcome.