PREDICT 2

The SARS-CoV-2 pandemic has a high burden of morbidity and mortality due to development of the acute respiratory distress syndrome (ARDS). The reninangiotensin-system (RAS) plays an important role in the development of ARDS, with ACE2 (angiotensin-converting enzyme 2) being a key enzyme within this. The virus's spike protein binds to ACE2, facillitating cellular internalization. Downregulation of ACE2 results in the excessive accumulation of angiotensin II, which in turn increases pulmonary vascular permeability through stimulation of the angiotensin II type 1a receptor (AT1R), thereby exacerbating lung pathology associated with decreased ACE2 activity. Currently available AT1R blockers (ARBs) such as valsartan, have shown potential to block this pathological process mediated by angiotensin II. The Focus The primary aim of the PRAETORIAN-COVID trial is to investigate the effect of the ARB valsartan compared to placebo on the composite end point of admission to an intensive care unit, mechanical ventilation, or death of COVID-19 patients. The Research Participants receiving active treatment are administered valsartan at a dosage titrated to blood pressure, with a maximum of 160 mg twice daily. Participants receiving placebo are provided with a matching placebo. The treatment duration was 14 days or until reaching the primary endpoint, or until hospital discharge, if applicable within 14 days.Two complementary mechanisms underpin the potential efficacy of angiotensin II type 1 receptor blockers (ARBs) in preventing acute respiratory distress syndrome (ARDS) and reducing morbidity and mortality: ARBs block excessive angiotensin-mediated activation of the AT1R. ARBs upregulate ACE2 expression, leading to reduced angiotensin II levels and increased production of the protective vasodilator angiotensin 1–7. Given these mechanisms, ARBs show promise in preventing ARDS development, potentially reducing the need for intensive care unit (ICU) admission and mechanical ventilation, and ultimately lowering mortality rates associated with SARS-CoV-2 infection.

Cardiovascular disease (CVD) and dementia are closely intertwined, often resulting in cognitive impairment among individuals with cardiovascular or cerebrovascular conditions. Approximately one-third of dementia cases are linked to vascular injury, emphasizing that vascular cognitive impairment (VCI) is a preventable aspect of cognitive decline. The Focus The Heart-Brain Connection Crossroads (HBCx) consortium investigates hemodynamic alterations as reversible contributors to VCI, seeking to enhance our understanding of the connection between cardiovascular health and cognitive function. The Research HBCx builds upon the foundation laid by HBC1 (CVON 2012-06), which established a national network dedicated to studying, diagnosing, and treating VCI. Clinical investigations within HBC1, focusing on patients with chronic heart failure (CHF), carotid occlusive disease (COD), and clinically evident VCI, emphasized the role of hemodynamics along the heart-brain axis in VCI. These findings underscored significant associations between heart-brain connections and VCI. The HBCx program, launched in 2019, takes a comprehensive approach by investigating hemodynamics in key cardiac conditions such as atrial fibrillation and heart failure, while also exploring vascular factors and their interplay with amyloid pathology. Moreover, HBCx considers modulating factors like age and sex. The program aims to improve early detection, identify treatable targets, and integrate the Heart-Brain Connection approach into routine care. Ultimately, the long-term vision of HBCx is to reduce VCI prevalence among CVD patients through enhanced understanding and innovative treatment strategies. Origin This consortium was funded through the Impulse Grant program by the Dutch Heart Foundation.