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Coronavirus disease 2019 (COVID-19) is usually more severe and associated with worst outcomes in individuals with pre-existing cardiovascular pathologies, including hypertension or atherothrombosis. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) can differentially infect multiple tissues (i.e., lung, vessel, heart, liver) in different stages of disease, and in an age- and sex-dependent manner. In particular, cardiovascular (CV) cells (e.g., endothelial cells, cardiomyocytes) could be directly infected and indirectly disturbed by systemic alterations, leading to hyperinflammatory, apoptotic, thrombotic, and vasoconstrictive responses. Until now, hundreds of clinical trials are testing antivirals and immunomodulators to decrease SARS-CoV-2 infection or related systemic anomalies. However, new therapies targeting the CV system might reduce the severity and lethality of disease. In this line, activation of the non-canonical pathway of the renin-angiotensin-aldosterone system (RAAS) could improve CV homeostasis under COVID-19. In particular, treatments with angiotensin-converting enzyme inhibitors (ACEi) and angiotensin-receptor blockers (ARB) may help to reduce hyperinflammation and viral propagation, while infusion of soluble ACE2 may trap plasma viral particles and increase cardioprotective Ang-(1–9) and Ang-(1–7) peptides. The association of specific ACE2 polymorphisms with increased susceptibility of infection and related CV pathologies suggests potential genetic therapies. Moreover, specific agonists of Ang-(1–7) receptor could counter-regulate the hypertensive, hyperinflammatory, and hypercoagulable responses. Interestingly, sex hormones could also regulate all these RAAS components. Therefore, while waiting for an efficient vaccine, we suggest further investigations on the non-canonical RAAS pathway to reduce cardiovascular damage and mortality in COVID-19 patients. [ABSTRACT FROM AUTHOR]

Introduction: Vascular endothelial growth factor inhibition (VEGFi) in cancer treatment is associated with hypertension. Imbalance between the renin-angiotensin-aldosterone system (RAAS) and VEGF may contribute to VEGFi associated hypertension. We hypothesized that RAAS blockade at the time of VEGFi attenuates increases in blood pressure. Methods: Using de-identified medical records from 1085 outpatients with cancer on VEGFi, we extracted demographic, oncologic, anti-hypertensive medication exposure and comorbidity data between 2003-2017. Baseline blood pressure was estimated as the average of all outpatient blood pressures collected during 12-6 weeks prior to VEGFi. Response blood pressure was estimated as the average blood pressure collected from 0-6 weeks after VEGFi. We used non-parametric methods and adjusted regression models to assess associations in BP change between patients taking or not taking ACEi/ARB. Results: Patients where 48% male, 88% Caucasian, and had mean age of 64+13 years. Patients using ACEi/ARB therapy were older with a lower GFR, lower prevalence of hypertension, and a higher prevalence of diabetes and hyperlipidemia compared with patients not using ACEi/ARB therapy (Table 1). We observed a 2.6 + 16mmHg reduction in systolic blood pressure among patients exposed to ACEi/ARB prior to VEGFi compared with 1 + 15mmHg reduction in patients not exposed to an ACEi/ARB. ACEi/ARB exposure was associated with a reduction in BP at 6 weeks even after adjusting for age, gender, BMI, GFR, hyperlipidemia, hypertension, and diabetes (-3.3mmHg [95% CI -5.5, -1.1]; p =0.005). Conclusions: Our results suggest a protective effect of pre-VEGFi exposure to ACEi/ARB on blood pressure response. Future studies are warranted to determine whether RAAS blockade should be initiated prophylactically in patients receiving VEGFi. [ABSTRACT FROM AUTHOR]