HE REFERENCE METHOD FOR blood pressure (BP) measurement during clinical consultations is the auscultatory method with a mercury sphygmomanometer. This method has been used to demonstrate the relationship between BP and cardiovascular risk. A meta-analysis of individual data from almost 1 million adults participating in 61 prospective studies precisely established the prognostic value of this method of measurement: for each increase of 10 mm Hg in systolic BP (SBP) or 5 mm Hg in diastolic BP (DBP), the average risk of cerebrovascular mortality increases by 40% and the risk of mortality from ischemic heart disease by 30%. 1 The mercury sphygmomanometer, used during clinical consultations, is also the tool that has demonstrated the benefit of antihypertensive treatment. In the first metaanalysis of randomized controlled trials using the sphygmomanometer, a decrease in DBP of 5 mm Hg to 6 mm Hg was associated with a 42% reduction in the risk of stroke syndrome and a 14% reduction in the risk of coronary events. 2

Severe acute respiratory syndrome coronavirus 2 is the cause of the ongoing coronavirus disease-19 (COVID-19) pandemic. Mortality is mainly due to acute respiratory distress syndrome (ARDS) [1]. High blood pressure appeared to be an independent factor for severity in patients with COVID-19 [2, 3]. The renin-angiotensin system (RAS) is a hemodynamic and biological system that regulates blood pressure, plasma potassium, and the stability of pulmonary epithelial membranes (Fig. 1) [4]. In this system, two antagonistic pathways are balanced. The first is the angiotensinogen pathway that transforms angiotensinogen into angiotensin I (by renin), and then converts it into angiotensin II by angiotensin converting enzyme (ACE). Angiotensin II attaches to angiotensin II type 1 receptor (AT1R) and activates the system to induce vasoconstriction, aldosterone secretion stimulation, hypokalemia, and pulmonary epithelium degradation [5]. The second way in which the angiotensin system is balanced involves a second angiotensin converting enzyme (ACE2) [6, 7]. This pathway transforms a part of angiotensin I [1-10] and angiotensin II [1-8] before it attaches to its AT1R receptor. The angiotensin I and II phosphorylation products are angiotensin 1-9 and angiotensin 1-7. They attach to the angiotensin II type 2 receptor receiver, inducing antagonist effects compared with AT1R [8]. In the infection phase (Fig. 2), COVID-19 virus uses the enzymatic receptor of ACE2 to penetrate the host cell [9, 10]. Coronavirus binding with ACE2 has been shown to lead to a downregulation of ACE2 [11], contributing to an increase in

Patients with difficult to control hypertension typically require 2 or more agents to achieve goal blood pressure (BP) levels. Fixed-dose combination therapies with lower doses generally are well tolerated and more effective than higher-dose monotherapy. The authors performed prespecified and post hoc subgroup analyses of 2 double-blind, randomized, placebo-controlled trials that assessed the efficacy and safety of amlodipine and valsartan, alone and in combination, in patients with mild to moderate hypertension. Patients were randomized to amlodipine (study 1: 2.5 or 5 mg/d; study 2: 10 mg/d), valsartan (study 1: 40, 80, 160, or 320 mg/d; study 2: 160 or 320 mg/d), combination therapy across the same dose ranges, or placebo. Analyses were performed on changes from baseline in mean sitting systolic and diastolic BP and the occurrence of adverse events in specific subgroups of patients (ie, those with stage 2 hypertension [post hoc], the elderly [65 years or older], and blacks [both prespecified]). Amlodipine + valsartan combination therapy was associated with greater BP-lowering effects in the subgroups compared with each respective monotherapy and placebo. These findings were consistent with the primary efficacy analysis results from the overall study populations. Combination regimens were generally well tolerated by all patient subgroups.