ABSTRACT
Inflammation has long been known to play a role in atherogenesis and plaque complication, as well as in some drugs used in therapy for atherosclerotic disease, such as statins, acetylsalicylic acid, and modulators of the renin-angiotensin system, which also have anti-inflammatory effects. Furthermore, inflammatory biomarkers have been demonstrated to predict the incidence of cardiovascular events. In spite of this, and with the exception of acetylsalicylic acid, non-steroidal anti-inflammatory drugs are unable to decrease the incidence of cardiovascular events and may even be harmful to the cardiovascular system. In recent years, other anti-inflammatory drugs, such as canakinumab and colchicine, have shown an ability to reduce the incidence of cardiovascular events in secondary prevention. Colchicine could be a potential candidate for use in clinical practice given its safety and low price, although the results of temporary studies require confirmation in large randomized clinical trials. In this paper, we discuss the evidence linking inflammation with atherosclerosis and review the results from various clinical trials performed with anti-inflammatory drugs. We also discuss the potential use of these drugs in routine clinical settings.
ABSTRACT
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.