Current Hypertension Reviews - Volume 17, Issue 3, 2021

Background: Renin angiotensin system (RAS) is a critical pathway involved in blood pressure regulation. Octapeptide, angiotensin II (Ang II), is a biologically active compound of RAS pathway which mediates its action by binding to either angiotensin II type 1 receptor (AT1R) or angiotensin II type 2 receptor (AT2R). Binding of Ang II to AT1R facilitates blood pressure regulation, whereas AT2R is primarily involved in wound healing and tissue remodeling. Objectives: Recent studies have highlighted the additional role of AT2R to counterbalance the detrimental effects of AT1R. Activation of angiotensin II type 2 receptor using AT2R agonist has shown the effect on natriuresis and release of nitric oxide. Additionally, AT2R activation has been found to inhibit angiotensin converting enzyme (ACE) and enhance angiotensin receptor blocker (ARB) activity. These findings highlight the potential of AT2R as a novel therapeutic target against hypertension. Conclusion: The potential role of AT2R highlights the importance of exploring additional mechanisms that might be crucial for AT2R expression. Epigenetic mechanisms, including DNA methylation and histone modification, have been explored vastly with relation to cancer, but the role of such mechanisms in the expression of AT2R has recently gained interest.

Lifestyle modifications in the form of diet and exercise are generally the first-line approach to reduce hypertensive risk and overall cardiovascular disease (CVD) risk. Accumulating research evidence has revealed that consumption of non- and low-fat dairy products incorporated into the routine diet is an effective means to reduce elevated blood pressure and improve vascular functions. However, the idea of incorporating whole-fat or full-fat dairy products in the normal routine diet as a strategy to reduce CVD risk has been met with controversy. The aim of this review was to evaluate both sides of the argument surrounding saturated fat intake and CVD risk from the standpoint of dairy intake. Throughout the review, we examined observational studies on relationships between CVD risk and dairy consumption, dietary intervention studies using non-fat and whole-fat dairy, and mechanistic studies investigating physiological mechanisms of saturated fat intake that may help to explain increases in cardiovascular disease risk. Currently available data have demonstrated that whole-fat dairy is unlikely to augment hypertensive risk when added to the normal routine diet but may negatively impact CVD risk. In conclusion, whole-fat dairy may not be a recommended alternative to non- or low-fat dairy products as a mean to reduce hypertensive or overall CVD risk.

Approximately half a century has passed since the discovery of beta-blockers. Then, their prime therapeutic purpose was to treat angina and cardiac arrhythmias; nowadays, beta-blockers’ usage and effectiveness are extended to treat other cardiovascular diseases, such as hypertension, congestive heart failure, and coronary artery disease. Safety concerns were raised about beta- blockers and their use for chronic obstructive pulmonary disease (COPD) patients with concurrent cardiovascular disease. After thorough research of the literature, this review summarizes the evidence proving that beta-blockers not only might be well tolerated in COPD patients, but they might also have a beneficial effect in this group of patients.

The new pandemic Coronavirus Disease 2019 (COVID-19) causes a wide range of clinical consequences, from asymptomatic infection to acute respiratory failure, and it is very heterogeneous. The renin-angiotensin system (RAS) is well recognized as a key regulating system in circulatory homeostasis that plays prominent roles in pathophysiological processes in abnormal activation, for instance, renal and cardiovascular diseases, obesity, and stroke. Angiotensin-converting enzyme 2(ACE2) is a component of the RAS system. However, unlike the ACE, its activity is not inhibited by the ACE inhibitors. The major product of ACE2 is Ang1-7, known as a vasodilator peptide and part of the depressant arm of the RAS. There are two forms of ACE2; Transmembrane ACE2 and soluble ACE2. Coronavirus is covered with some proteins in order to help viral attachment to the cell membrane ACE2 as a receptor and then fuse and enter the cells. ACE2 was expressed in the oral cavity, salivary glands of the mouth, esophagus, myocardial cells, kidney, and enterocytes, along with all the respiratory tract, intestine, and blood vessels. In this article, the renin- angiotensin system and its components have been explained. Moreover, the organs involved in COVID-19 disease, and the possible causes of damage to these organs have also been discussed. The probable mechanism of using ACE2 in viral attachment and the probable treatment processes will also be reviewed based on the surface proteins of the virus and ACE2. In addition, we briefly discuss anti-angiotensin drugs and why patients with chronic diseases are more susceptible to COVID-19 infection and show worse progression.

Background: Azilsartan medoxomil (AZM) is the newest representative in the class of angiotensin receptor blockers. Azilsartan medoxomil in combination with the older diuretic chlorthalidone (CLD) in fixed-doses of AZM/CLD 40/12.5 mg and 40/25 mg has been approved by the FDA for use in patients with essential hypertension. We sought to evaluate the safety and tolerability of AZL-M alone and in combination with CLD. Methods: We conducted a search in PubMed using the keywords ‘azilsartan’, ‘azilsartan medoxomil’, ‘chlorthalidone, ‘safety’, ‘tolerability’ in order to find scientific studies evaluating the safety of these drugs. We included studies reporting side effects of these drugs, alone or in combination, in comparison to placebo or other antihypertensive medications. For our systematic review, we followed the PRISMA guidelines. Results: Azilsartan medoxomil is a potent antihypertensive medicine with an acceptable safety profile. The most commonly reported adverse events are dizziness, headache, fatigue, upper respiratory tract infection and urinary tract infection. Chlorthalidone is more potent and has a considerably longer duration of action than the most commonly prescribed diuretic hydrochlorothiazide. Safety and tolerability between these two drugs are similar except higher serum uric acid and lower potassium levels with chlorthalidone. Conclusion: The combination of azilsartan medoxomil with chlorthalidone has been shown to be effective in lowering blood pressure with an acceptable safety and tolerability profile. This fixeddose combination is an attractive treatment option for hypertension management.

Background: Epidemiological studies have suggested that elevated serum uric acid may contribute to the progression of chronic kidney disease. However, no large prospective study has examined whether hyperuricemia is an independent risk factor for the progression of autosomal dominant polycystic kidney disease (ADPKD). Methods: We measured uric acid in stored serum samples from the 2-year study visit of 671 participants from the HALT PKD multicenter trials. Participants were categorized according to uric acid tertiles. For Study A (participants aged 15-49 years with preserved kidney function, n=350), we used linear mixed effects models to examine the association between uric acid and repeated measures of height-adjusted total kidney volume (htTKV), the primary outcome for Study A. For Study B (participants aged 18-64 with decreased kidney function, n=321), we used Cox proportional hazards models to assess the hazard for the combined endpoint of 50% loss in estimated glomerular filtration rate (eGFR), end-stage kidney disease (ESKD), or death, the primary outcome for Study B. To assess the association of uric acid with the slope of eGFR decline (secondary outcome of HALT A and B), we used linear mixed effects models for the combined population of Study A and B. Results: In the unadjusted model, the annual change in htTKV was 2.7% higher in the highest uric acid tertile compared to the lowest (p<0.001), but this difference became insignificant after adjustment for gender. Men had faster TKV growth than women (p<0.001). There was no difference in eGFR decline between the 3 uric acid tertiles. Hazard ratios for the clinical endpoint were 2.9 (95% confidence interval, 1.9-4.4) and 1.8 (1.1-2.8) respectively in the high and medium uric acid groups in unadjusted and partially adjusted models (p<0.001), but the significance was lost after adjustment for baseline eGFR. Results were similar when uric acid was examined as a continuous variable. Conclusion: Elevated serum uric acid is not an independent risk factor for disease progression in ADPKD.

Background: Pre-eclampsia contributes significantly to both maternal and perinatal morbidities and mortalities. One of the identified pathophysiologies of pre-eclampsia is the deranged serum lipid profile of which some components have been found to be elevated early in pregnancy in women destined to develop pre-eclampsia. Objectives: To compare the serum fasting lipid profiles of pre-eclamptic primigravidas with normal primigravidas at week 20, 28, and 34. Methods: We conducted a nested case-control study at Obafemi Awolowo University, Ile-Ife between November 2016 and April 2018. A cohort of 290 primigravidas was recruited at week 20 and followed up until delivery. Serum fasting lipid profiles were quantified at weeks 20, 28 and 34 for all participants. Twenty four women that developed pre-eclampsia were compared with 48 women that had a normal pregnancy. Data were analyzed with SPSS version 22. We used a linear mixed-effect regression model with random intercept and slope. Significance was established using p<0.05. Results: Serum lipid profiles showed an average weekly increase in both groups. Primigravidas that developed pre-eclampsia had a weekly increase of 0.2(SE0.14) mmol/l in serum total cholesterol more than those with normal pregnancies. (p<0.001) Serum low-density lipoprotein also showed a differential weekly increase of 0.1(SE0.05)mmol/l in primigravidas that developed pre-eclampsia over primigravidas with normal pregnancies. (p<0.001). Conclusion: The average weekly increase in serum total cholesterol and low-density lipoprotein was significantly higher in primigravidas that developed pre-eclampsia when compared to the control group. These findings depicted an association between serum lipid profile and pre-eclampsia among the primigravidas.

Background: Increased arterial stiffness is an independent predictor of cardiovascular morbidity and mortality. It is unknown whether low BMI has any detrimental effect on the arterial wall during young age. Objectives: The present study was aimed to determine if low BMI can increase arterial stiffness in young, healthy individuals. Methods: A cross-sectional study was conducted on young, healthy subjects (n=100) with low BMI <18.5 (n=50) and normal BMI: 18.5-24.9 (n=50) with ages ranging between 15-23 years. BMI, heart rate, blood pressure, and arterial stiffness indices such as regional pulse wave velocity (PWV) between brachial-ankle (baPWV), carotid-femoral (cfPWV), heart-ankle (haPWV), heartbrachial (hbPWV) were measured. Results: A significantly increased pulse pressure (p=0.014), baPWV (1059.2 ± 140.26 cm/s vs 994.66 ± 129.23 cm/s; p=0.019) and cfPWV (641.03 ± 113.83 cm/s vs 583.96 ± 120.48 cm/s; p=0.017) was found in individuals with low BMI than normal BMI group. There was a significant negative correlation between BMI and central arterial PWV. Further multiple regression analysis showed that BMI was robustly associated with cf-PWV (p=0.004) and baPWV (p=0.016) even after multiple adjustments with potential confounders using several models. Conclusion: These findings show a significant increased aortic stiffness and pulse pressure in low BMI subjects compared to those with normal BMI. Low BMI was inversely and independently associated with central arterial or aortic stiffness. These findings suggest that low BMI may be a risk factor for aortic stiffness in young, healthy individuals.