Hypertension and COVID-19: Current Evidence and Perspectives

Abstract

Coronavirus disease 2019 (COVID-19) outbreak, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), represents a real challenge for health-care systems worldwide. Male sex, older age and the coexistence of chronic comorbidities have been described as the most relevant conditions associated with a worse prognosis. Early reports suggested that hypertension might represent a risk factor for susceptibility to SARS-CoV-2 infection, a more severe course of COVID-19 and increased COVID-19-related deaths. Nevertheless, the independent role of hypertension remains under debate, since hypertension is often associated with the older age and other cardiovascular (CV) risk factors in the general population, which may also contribute to the SARS-Cov-2 infection and COVID-19. Moreover, the role of antihypertensive drugs, primarily angiotensin-converting inhibitors (ACEIs) and ARBs (angiotensin receptor blockers) in COVID-19 development and outcome appears controversial. Indeed, preclinical studies using these classes of drugs have suggested a potential upregulation of angiotensin-converting-enzyme 2 (ACE2) which is the key binding receptor promoting cell entry of SARS-CoV-2 in the organism. Renin–angiotensin system (RAS) blockers may potentially upregulate ACE2, hence, it has been initially hypothesized that these agents might contribute to a higher risk of SARS-CoV-2 infection and progressive course of COVID-19. However, several clinical reports do not support a detrimental role of RAS blockers in COVID-19, and an intense debate about the withdrawal or maintenance of chronic therapy with ACEi/ARB has been developed. In this review we will discuss the available evidence on the role of hypertension and antihypertensive drugs on SARS-CoV-2 infection and COVID-19 development.

The impact of COVID-19 on populations living at high altitude: Role of hypoxia-inducible factors (HIFs) signaling pathway in SARS-CoV-2 infection and replication

“…Hypertension is a major risk factor for endothelial dysfunction and atherosclerosis. In this regard, uncontrolled high blood pressure values might lead to the development of vascular remodeling and vascular rigidity, which may predispose to heart left ventricular hypertrophy and fibrosis, acute kidney injury, and extensive microthrombosis in coronary and pulmonary circulation ( Gallo et al, 2022a ). The accumulation of such physiological disorders may severely impact on the prognosis of COVID-19 patients and increase risk of death.…”

Angiotensin Receptor Blockers in the Management of Hypertension: A Real-World Perspective and Current Recommendations

“…Atherosclerosis: decrease of PAI-1 in the vessel wall, reduced atherosclerosis progression and reduced instability of atherosclerotic plaque 39,40 MACE: reduced occurrence of stroke, MI, HF, CV mortality, death from any cause [41][42][43][44][45][46][47] Metabolic diseases: increased urinary uric acid excretion, activation of PPAR-γ, reduction of adipose tissue weight and of adipocyte size 14,31,32 Diabetes: reduction of the occurrence of new-onset diabetes, improvement of insulin sensitivity and HOMA-IR index 29,33 Chronic kidney disease: protective role toward the development of microalbuminuria, overt proteinuria, and the progression to end-stage renal disease [31][32][33][34][35][36] Side effects: reduced incidence of angioedema, cough, hypotension, syncope, and electrolyte abnormalities 52,[56][57][58] COVID-19: potential beneficial effects through vasodilatation, anti-inflammatory, anti-oxidative, and antiproliferative properties [60][61][62][63][64][65][66] Abbreviations: ACEi, angiotensin converting enzyme inhibitors; ARBs, angiotensin receptor blockers; CV, cardiovascular; HF, heart failure; HOMA-IR, homeostasis model assessment; LVH, left ventricular hypertrophy; MI, myocardial infarction; PAI-1, plasminogen activator inhibitor type-I; PPAR-γ, peroxisome proliferator-activated receptor.…”

“…Indeed, the ACE2 counteracts the ACE pathway by cleaving angiotensin-II to angiotensin-(1-7), thereby reducing angiotensin-II availability to the AT1R. 63 Of interest, angiotensin-(1-7), through its MAS-receptor, plays vasodilatation, anti-inflammatory, anti-oxidative, and antiproliferative actions which may contribute to reduce the severity of COVID-19 disease and to improve prognosis [64][65][66][67][68] (Table 2).…”

Preparation of angiotensin I- converting enzyme (ACE) inhibitory peptides from Tieguanyin tea residue protein using two-step enzymatic hydrolysis

“…Research shows that hypertension affects about 25% of the adult population in the world (Zhao et al, 2020). Hypertension is a kind of cardiovascular disease syndrome which is often accompanied by other diseases, such as atherosclerosis, myocardial infarction and stroke (Gallo, Calvez, & Savoia, 2022).…”