Influenzaimpfung – Mehr als nur Influenzaschutz [Influenza vaccination – more than just protection against the flu]

Influenza is a severe infectious disease that leads to significant morbidity and mortality worldwide every year. Cardiovascular events, especially within the first 2 weeks after influenza infection, are the main cause of death. Due to immunosenescence, multimorbidity and frailty, older individuals are particularly at risk for severe disease progression. Influenza vaccination is an effective strategy for reducing influenza infections and associated cardiovascular complications. The Standing Committee on Vaccination (STIKO) therefore recommends annual influenza vaccination for individuals aged 60 years and older as well as for certain high-risk groups regardless of age. Standard vaccines are often less effective in older individuals due to declining immune responses. Therefore, various optimization approaches, such as the use of a high-dose influenza vaccine, are being explored to enhance immune response and vaccine efficacy. Due to the high-quality data available for the high-dose vaccine, the STIKO recommends its use from the age of 60 years onwards. Randomized controlled trials and meta-analyses show that the high-dose vaccine improves the efficacy and effectiveness in terms of influenza infections and cardiopulmonary events compared to standard dose influenza vaccines. Individuals with pre-existing heart conditions also benefit from influenza vaccination. Patients should be informed by their treating physicians about the cardiovascular benefits of influenza vaccination

Functional and structural vascular biomarkers in women 1 year after a hypertensive disorder of pregnancy

OBJECTIVES: Women with a previous hypertensive disorder of pregnancy (HDP: gestational hypertension and preeclampsia) have increased long-term cardiovascular disease risk. Recent meta-analyses show adverse levels of non-invasive functional and structural cardiovascular risk markers such as pulse wave velocity (PWV), heart-rate adjusted augmentation index (AIx75), carotid intima-media thickness (CIMT), and reactive hyperemia index (RHI) after HDPs, and suggest using these for cardiovascular risk stratification. However, it is not known if a previous HDP predict levels of these markers beyond classical cardiovascular risk factors. Study design and main outcome measures. We assessed PWV, AIx75, CIMT, RHI, classical cardiovascular risk factors, and pregnancy characteristics in 221 women 1 year postpartum (controls: 95, previous HDP: 126). Uni- and multi- variate regression analysis were conducted to assess associations between previous HDP and PWV, AIx75, CIMT or RHI. We adjusted for classical cardiovascular risk factors and pregnancy characteristics. A p-level < 0.05 was considered statistically significant. RESULTS: PWV was associated with previous HDP on univariate analysis. This effect was confounded by blood pressure and not significant after adjustment. We found no significant associations between AIx75, RHI, CIMT, and a previous HDP, neither before nor after adjustments. CONCLUSIONS: Associations between a previous HDP and PWV, AIx75, CIMT, or RHI 1 year postpartum can largely be explained by adverse levels of classical cardiovascular risk markers in women with a previous HDP. Women with previous HDP should receive primary prevention of cardiovascular disease, but PWV, AIx75, CIMT or RHI are unlikely to aid in cardiovascular risk stratification 1 year postpartum

Inhibition of Trophoblast-Induced Spiral Artery Remodeling Reduces Placental Perfusion in Rat Pregnancy.

Rats harboring the human angiotensinogen and human renin genes develop preeclamptic features in pregnancy. The preeclamptic rats exhibit a deeper trophoblast invasion associated with a reduced resistance index by uterine Doppler. Doxycycline inhibits matrix metalloproteinase activity. We tested the hypothesis that matrix metalloproteinase inhibition reduces trophoblast invasion with subsequent changes in placental perfusion. Preeclamptic and pregnant control Sprague-Dawley rats were treated with doxycycline (30 mg/kg of body weight orally) from gestational day 12 until day 18. Placental perfusion was assessed using a micromarker contrast agent. The animals were euthanized on day 18 of pregnancy; biometric data were acquired, and trophoblast invasion was analyzed. Doxycycline resulted in intrauterine growth retardation and lighter placentas in both groups. Maternal body weight was not affected. As shown earlier, preeclamptic rats exhibited a deeper endovascular trophoblast invasion. However, doxycycline treatment reduced trophoblast invasion in the preeclamptic rats. The physiological spiral artery remodeling, as assessed by the deposition of fibrinoid and α-actin in the spiral artery contour, was significantly reduced by doxycycline. The vascularity index, as assessed by perfusion measurement of the placenta, was reduced after doxycycline treatment in preeclamptic rats. Thus, matrix metalloproteinase inhibition with doxycycline leads to reduced trophoblast invasion and associated reduced placental perfusion. These studies are the first to show that reducing trophoblast-induced vascular remodeling decreases subsequent placental perfusion. Our model allows the study of dysregulated trophoblast invasion and vascular remodeling in vivo to gain important insights into preeclampsia-related mechanisms

Effects of Circulating and Local Uteroplacental Angiotensin II in Rat Pregnancy.

The renin-angiotensin (Ang) system is important during placental development. Dysregulation of the renin-Ang system is important in preeclampsia (PE). Female rats transgenic for the human angiotensinogen gene crossed with males transgenic for the human renin gene develop the PE syndrome, whereas those of the opposite cross do not. We used this model to study the role of Ang II in trophoblast invasion, which is shallow in human PE but deeper in this model. We investigated the following groups: PE rats, opposite-cross rats, Ang II–infused rats (1000 ng/kg per day), and control rats. Ang II infusion increased only circulating Ang II levels (267.82 pg/mL), opposite cross influenced only uteroplacental Ang II (13.52 fmol/mg of protein), and PE increased both circulating (251.09 pg/mL) and uteroplacental (19.24 fmol/mg of protein) Ang II. Blood pressure and albuminuria occurred in the models with high circulating Ang II but not in the other models. Trophoblast invasion increased in PE and opposite-cross rats but not in Ang II–infused rats. Correspondingly, uterine artery resistance index increased in Ang II–infused rats but decreased in PE rats. We then studied human trophoblasts and villous explants from first-trimester pregnancies with time-lapse microscopy. Local Ang II dose-dependently increased migration by 75%, invasion by 58%, and motility by 282%. The data suggest that local tissue Ang II stimulates trophoblast invasion in vivo in the rat and in vitro in human cells, a hitherto fore unrecognized function. Conceivably, upregulation of tissue Ang II in the maternal part of the placenta represents an important growth factor for trophoblast invasion and migration

Angiotensin II type 1 receptor antibodies in childhood kidney transplantation

Angiotensin II type 1 receptor antibodies (AT1 RAb) have emerged as non-HLA Ab present in patients with acute AMR and risk of graft loss. Furthermore, AT1 RAb have been shown to increase angiotensin II sensitivity which may play a role in the development of CVD and hypertension. Data on AT1 RAb in stable transplant recipients are lacking. The aim of this study was to analyze the levels of AT1 RAb in a cohort of stable patients after kidney transplantation (tx) in childhood. A cross-sectional study of 30 children (median age 14, range 3-19 yr, median time since tx five yr) and 28 adults who were transplanted in childhood (median age 26, range 20-40 yr, median time since tx 18 yr) transplanted between 1993-2006 and 1983-2002, respectively, was performed. Healthy controls were 51 healthy children (5-8 yr) and 199 healthy donors (median age 56.5 yr, range 42-83 yr). Plasma AT1 RAb were analyzed by immunoassay. Median total AT1 RAb IgG concentration was significantly higher in the pediatric-tx group as compared to the adult-tx group (40.0 and 10.95 U/mL, p < 0.0001). For both groups, the tx group showed higher levels: the pediatric-tx group vs. control group (40.0 vs. 13.3 U/mL, p = 0.0006) and the adult-tx group vs. adult control group (10.95 vs. 6.5 U/mL, p < 0.0001). Age was the strongest indicator of high levels of AT1 RAb IgG (p = 0.0003). AT1 RAb total IgG levels are significantly higher in a stable pediatric-tx cohort as compared to adult-tx patients and healthy controls of comparable age groups. The relevance of our findings in relation to age, time since tx, previous or future rejection, and CVD risk merits future studies

Hypertension in response to IL-6 during pregnancy: role of AT1-receptor activation

BACKGROUND: Increases in interleukin 6 (IL-6) and agonistic autoantibodies to the angiotensin II type 1 receptor (AT1-AA) are proposed to be important links between placental ischemia and hypertension in preeclampsia. METHODS: The purpose of this study was to determine whether IL-6 (5 ng/day), infused into normal pregnant (NP) rats, increased mean arterial pressure (MAP) and AT1-AA. MAP was analyzed in the presence and absence of an angiotensin type 1 receptor (AT1R) antagonist, losartan, L. RESULTS: MAP and AT1-AA increased from 102 ± 2 to 118 ± 4 mmHg and 0.7 ± 0.3 NP to 14.1 ± 1.4 chronotropic units with chronic IL-6 infusion. MAP responses to IL-6 were abolished in losartan pretreated rats (85 ± 4 in NP + L vs 85 ± 3 mmHg in IL-6 + L). CONCLUSION: These data indicate that IL-6 stimulates AT1-AA and that activation of the AT1R mediates IL-6 induced hypertension during pregnancy

Impact of stable angina on health status and quality of life perception of currently treated patients. The BRIDGE 2 survey.

OBJECTIVE: to explore 1) the perception of stable angina (SA) - impact on quality of life (QoL) and current condition related to SA; 2) SA burden - symptoms and frequency of anginal episodes; 3) impairment attributable to SA - limitations in daily activities and impact on work; 4) characteristics that might affect the patients' perception." METHOD: a proprietary questionnaire was administered on-line to SA patients selected using a purpose-built screening program from general population panels collaborating with IQVIA in Italy, Germany, Spain, and the UK. Exploratory analyses were performed: descriptive statistics on the total sample and different stratifications (gender, age class, time since diagnosis) were provided; we used Chi-square tests to compare subgroups. RESULTS: of more than 25,000 subjects who accessed the survey, 268 were eligible and completed the questionnaire: mean age was 61 years and women accounted for 30%. Despite being treated, about 40% of patients reported that SA impacted "completely" or "very much" their QoL, 10% rated their condition as "not good", and 45.1% stated that they felt "Fair". The majority of patients were still symptomatic and many of them perceived that SA had a major impact on their working life. Women, younger patients and those with a more recent diagnosis reported a worse self-assessment of their condition, QoL and symptom burden. CONCLUSIONS: the results of our survey provide new insights on how patients with SA perceived their own health status and suggest that any patient with SA deserves a more detailed and accurate evaluation by their physicians

Disproportional decrease in office blood pressure compared with 24-hour ambulatory blood pressure with antihypertensive treatment: dependency on pretreatment blood pressure levels

The long-term relationship between 24-hour ambulatory blood pressure (ABP) and office BP in patients on therapy is not well documented. From a registry we included all patients in whom antihypertensive therapy needed to be uptitrated. Drug treatment included the direct renin inhibitor aliskiren or an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker or drugs not blocking the renin-angiotensin system, alone or on top of an existing drug regimen. In all patients, office BP and 24-hour ABP were obtained at baseline and after 1 year with validated devices. In the study population of 2722 patients, there was a good correlation between the change in office BP and 24-hour ABP (systolic: r=0.39; P<0.001; diastolic: r=0.34; P<0.001). However, the numeric decrease in office BP did not correspond to the decrease in ABP in a 1:1 fashion, for example, a decrease of 10, 20, and 30 mm Hg corresponded to a decrease of ~7.2, 10.5, and 13.9 mm Hg in systolic ABP, respectively. The disproportionally greater decrease in systolic office BP compared with ABP was dependent on the level of the pretreatment BP, which was consistently higher for office BP than ABP. The white coat effect (difference between office BP and ABP) was on average 10/5 mm Hg lower 1 year after intensifying treatment and the magnitude of that was also dependent on pretreatment BP. There was a disproportionally greater decrease in systolic office BP than in ABP, which for both office BP and ABP seemed to depend on the pretreatment BP level

Lösliche Guanylatzyklase(sGC)-Stimulation mit Vericiguat: Von der pharmakologischen Idee bis zur Therapie der chronischen Herzinsuffizienz [Soluble guanylate cyclase (sGC) stimulation with vericiguat : from the pharmacological idea to the treatment of chronic heart failure]

BACKGROUND: According to the new European Society of Cardiology (ESC) guidelines on the diagnostics and treatment of acute and chronic heart failure, vericiguat (Verquvo®) can be included in the treatment of adult patients with symptomatic chronic heart failure and reduced ejection fraction who, despite standard treatment after a recently occurring decompensation event, were stabilized with the necessary intravenous (i.v.) therapy. OBJECTIVE: This review article summarizes the development of vericiguat, a soluble guanylate cyclase stimulator (sGC stimulator), which is a good example for the stringent implementation of a novel pharmacological therapy approach into treatment of heart failure. It provides valuable approaches for the practical use via the characterization of this patient collective that was investigated for the first time. RESULTS: The two relevant trials in the clinical development program for vericiguat, SOCRATES-Reduced and VICTORIA, have clearly demonstrated the efficacy and safety of vericiguat. The primary efficacy endpoint in the VICTORIA study “cardiovascular death or hospitalization due to heart failure” was significantly reduced in the vericiguat arm compared to placebo. Relevant subgroup analyses as well as safety data confirm this result and support the safe use in this high-risk population. CONCLUSION: The presented data allow the conclusion that vericiguat can be efficaciously and safely added to an existing treatment with a recommended standard medication for heart failure. It can be expected that in the routine practice the target dose of 10 mg can be reliably reached and maintained. Vericiguat should be regarded as a novel, easy and safe treatment option in a vulnerable patient population, for which there was previously hardly any medicinal treatment option

Angiotensin II induced inflammation in the kidney and in the heart of double transgenic rats

BACKGROUND: We are investigating a double transgenic rat (dTGR) model, in which rats transgenic for the human angiotensinogen and renin genes are crossed. These rats develop moderately severe hypertension but die of end-organ cardiac and renal damage by week 7. The heart shows necrosis and fibrosis, whereas the kidneys resemble the hemolytic-uremic syndrome vasculopathy. Surface adhesion molecules (ICAM-1 and VCAM-1) are expressed early on the endothelium, while the corresponding ligands are found on circulating leukocytes. Leukocyte infiltration in the vascular wall accompanies PAI-1, MCP-1, iNOS and Tissue Factor expression. Furthermore we show evidence that Ang II causes the upregulation of NF-{kappa}B in our model. METHODS: We started PDTC-treatment on four weeks old dTGR (200 mg/kg sc) and age-matched SD rats. Blood-pressure- and albuminuria- measurements were monitored during the treatment period (four weeks). The seven weeks old animals were killed, hearts and kidneys were isolated and used for immunohistochemical-and electromobility shift assay analysis. RESULTS: Chronic treatment with the antioxidant PDTC decreased blood pressure (162 plus minus 8 vs. 190 plus minus 7 mm Hg, p = 0.02). Cardiac hypertrophy index was significantly reduced (4.90 plus minus 0.1 vs. 5.77 plus minus 0.1 mg/g, p < 0.001) compared to dTGR. PDTC reduced 24 h albuminuria by 85 % (2.7 plus minus 0.5 vs. 18.0 plus minus 3.4 mg/d, p < 0.001) and prevented death significantly. Vascular injury was ameliorated in small renal and cardiac vessels. PDTC inhibited NF-{kappa}B binding activity in heart and kidney. Immunohistochemical analysis shows increased expression of the p65 NF-{kappa}B subunit in the endothelium, smooth muscles cells of damaged small vessels, infiltrated cells, glomeruli, tubuli and collecting ducts of dTGR. PDTC markedly reduced the immunoreactivity of p65. CONCLUSION: Our data show that inhibition of NF-{kappa}B by PDTC markedly reduces inflammation, iNOS expression in the dTGR most likely leading to decreased cytotoxicity, and cell proliferation. Thus, NF-{kappa}B activation plays an important role in ANG II-induced end-organ damage