Effect of early endothelial function improvement on subclinical target organ damage in hypertensives.

Endothelial dysfunction is acknowledged as a marker for subclinical target organ damage (STOD) in hypertension, though its therapeutic potential has not yet been clarified. This study assessed whether early endothelial function improvement (EEFI) reduced STOD in patients with essential hypertension (EH). We conducted a retrospective cohort analysis of 456 EH patients initially free from STOD. Endothelial function was assessed using brachial artery flow-mediated dilation (FMD), with values ≤ 7.1% indicating dysfunction. Patients were initially categorized by endothelial status (dysfunction: n = 180, normal: n = 276), and further divided into improved or unimproved groups based on changes within three months post-enrollment. During a median follow-up of 25 months, 177 patients developed STOD. The incidence of STOD was significantly higher in patients with initial dysfunction compared to those with normal function. Kaplan-Meier analysis indicated that the improved group had a lower cumulative incidence of STOD compared to the unimproved group (p < 0.05). Multivariable Cox regression confirmed EEFI as an independent protective factor against STOD in EH patients (p < 0.05), regardless of their baseline endothelial status, especially in those under 65 years old, non-smokers, and with low-density lipoprotein cholesterol levels ≤ 3.4 mmol/L. In conclusion, EEFI significantly reduces STOD incidence in EH patients, particularly in specific subgroups, emphasizing the need for early intervention in endothelial function to prevent STOD.

The prevalence of metabolic syndrome in primary aldosteronism and essential hypertension: A systematic review and meta-analysis.

It remained debates on metabolic-related disorders in patients with primary aldosteronism (PA) and essential hypertension (EH). A systematic review and meta-analysis was conducted to explore the prevalence of metabolic syndrome (MS) and the related indicators in PA and EH. PubMed, Embase, Web of Science and the Cochrane Central Register of Controlled Trials from their commencement to December 2023 were searched for eligible studies. The meta-analysis was performed by Review Manager 5.3 and STATA 15.1 software. A total of 12 studies were included, revealing that there was no significant difference between PA and EH in the prevalence of MS (1.27[0.92, 1.76], p = 0.14) with higher heterogeneity (I2 = 68%, p = 0.0002), while it became significant different (1.45[1.17, 1.81], p = 0.0008) and lower heterogeneity (I2 = 26%, p = 0.19) in patients who were overweight or obese by subgroup analysis. Higher systolic blood pressure (2.99[0.67, 5.31], p = 0.01; I2 = 43%, p = 0.06) and diastolic blood pressure (2.10[0.82, 3.38], p = 0.001; I2 = 36%, p = 0.11) with lower heterogeneity, and lower triglyceride in PA group with higher heterogeneity (-0.23[-0.37, -0.09], p = 0.001; I2 = 76%, p < 0.0001) were observed. No significant difference was found in other indicators. This study showed a higher prevalence of MS in patients who were overweight or obese with PA. However, it was not the same in these patients who were in normal weight. More researches were needed to explore the relationship between PA and metabolism of glucose and lipid.

Analysis of MTHFR C677T genotype and related factors in H-type hypertension in Tibet, China.

BACKGROUND AND AIMS: H-type hypertension is essential hypertension combined with high homocysteine, and both synergistically increase the risk of cardiovascular and cerebrovascular events. The aim of this study was to investigate the risk factors of H-type hypertension in Tibetan plateau population and correlation with MTHFR C677T gene. METHODS AND RESULTS: A multi-stage cluster random sampling method was used to select the research subjects in Tibet Autonomous Region from June 2020 to November 2021. Among Tibetans, the incidence of H-type hypertension accounted for 84.31% of hypertensive patients. The logistic regression analysis demonstrated that age, uric acid (UA), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) were risk factors for the prevalence of H-type hypertension, the OR (95% CI) was 1.083(1.073-1.094), 1.002(1.001-1.004), 1.240(1.050-1.464) and 2.274(1.432-3.611), respectively. MTHFR C677T TT genotype patients with H-type hypertension OR (95% CI) was 1.629(1.004-2.643). Based on this, a nomogram model was established, and the reliability of the model was proved by area under ROC curve, Brier score and average absolute error. The model's results indicate that for every five years of age, the score increases by 6 points; for a 2mmol/L increase in TG, the score increases by 5.5 points; for a 1mmol/L increase in LDL-C, the score increases by 10 points; and individuals with the TT genotype receive 8 points. The higher the score, the greater the risk of disease. CONCLUSION: The MTHFR C677T TT genotype is a risk locus for Tibetan patients with H-type hypertension, with age, TG, and LDL-C were identified as risk factors for the disease.

Association between circulatory complement activation and hypertensive renal damage: a case-control study.

OBJECTIVE: The aim of this study was to investigate the potential importance of complement system activation, with particular emphasis on the complement alternative pathway (AP), in the pathogenesis of hypertensive renal damage. METHODS: Serum complement C3, complement Factor H (CFH) and AP activation were assessed in 66 participants with established essential hypertension with renal damage (RD). Fifty-nine patients with age- and sex-matched essential hypertension without renal damage (NRD) and 58 healthy participants (normal) were selected. RESULTS: Our study revealed that C3 and AP50 continuously increased from normal to NRD to RD (p < 0.05, respectively), while CFH was significantly lower than that in NRD and healthy participants (p < 0.05, respectively). After multifactorial logistic regression analysis corrected for confounders, elevated serum C3 (p = 0.001) and decreased CFH (p < 0.001) were found to be independent risk factors for hypertension in healthy participants; elevated serum C3 (p = 0.034), elevated AP50 (p < 0.001), decreased CFH (p < 0.001), increased age (p = 0.011) and increased BMI (p = 0.013) were found to be independent risk factors for the progression of hypertension to hypertensive renal damage; elevated serum C3 (p = 0.017), elevated AP50 (p = 0.023), decreased CFH (p = 0.005) and increased age (p = 0.041) were found to be independent risk factors for the development of hypertensive renal damage in healthy participants. CONCLUSION: Abnormal activation of complement, particularly complement AP, may be a risk factor for the development and progression of hypertensive renal damage.

Association of T-cell receptor repertoires and arterial stiffness in patients with essential hypertension.

BACKGROUND: Abnormal immune responses, particularly T-cell activity, are linked to vascular complications in hypertension, but mechanisms remain unknown. Our study aims to explore the association between arterial stiffness, assessed by brachial-ankle pulse wave velocity (baPWV), and T-cell receptor (TCR) repertoires in essential hypertension patients, focusing on understanding the role of T cells in the development of arterial stiffness in this population. METHODS: The study included 301 essential hypertension patients and 48 age-matched normotensive controls. Essential hypertension patients were stratified into high (baPWV ≥1400 cm/s, n = 213) and low (baPWV <1400 cm/s, n = 88) baPWV groups. High-throughput sequencing analyzed peripheral TCRß repertoires. RESULTS: Significant TCRß repertoire differences were observed between essential hypertension and normotensive groups, as well as between high and low baPWV essential hypertension subgroups. Specifically, patients in the high baPWV group exhibited notable variations in the utilization of specific TCR beta joining (TRBJ) and variable (TRBV) genes compared to the low baPWV group. These alterations were accompanied by reduced TCRß diversity (represented by diversity 50 s), increased percentages of the largest TCRß clones, and a higher number of TCRß clones exceeding 0.1%. The presence of specific TCRß clones was detected in both groups. Furthermore, reduced diversity 50s and elevated percentages of the largest TCRß clones were independently correlated with baPWV, emerging as potential risk factors for increased baPWV in essential hypertension patients. CONCLUSION: TCR repertoires were independently associated with arterial stiffness in patients with essential hypertension, implicating a potential role for dysregulated T-cell responses in the pathogenesis of arterial stiffness in this patient population.Trial registration: ChiCTR2100054414.

Self-Performed Dietary Sodium Reduction and Blood Pressure in Patients With Essential Hypertension: A Randomized Clinical Trial.

BACKGROUND: Hypertension is the leading risk factor for cardiovascular disease worldwide. Patients with blood pressure (BP) response to dietary sodium reduction are referred to as "salt sensitive." Salt sensitivity (SS) might be due to differences in sodium storage capacity and the erythrocyte SS examines this capacity of the red blood cells. This study aimed to test the effect of a self-performed sodium reduced diet on BP in patients with essential hypertension and examine whether erythrocyte SS predicts SS. METHODS AND RESULTS: Seventy-two patients with hypertension were included and randomized 2:1 to either sodium reduction or a control group for 4 weeks. Blood samples, 24-hour BP measurement, and 24-hour urine collection were performed before and after. The intervention group received advice on how to lower sodium intake. Urinary sodium excretion decreased 66 mmol (95% CI, -96 to -37 mmol) in the intervention group compared with the control group. Systolic 24-hour BP decreased 9 mm Hg after low-sodium diet compared with the control group (95% CI, -13 to -4 mm Hg). Similarly, the difference in reduction in diastolic BP between the groups was 5 mm Hg (95% CI, -8 to -1 mm Hg). We found no correlation between erythrocyte SS at baseline and decrease in 24-hour BP, neither systolic nor diastolic (P=0.66 and P = 0.84). CONCLUSIONS: Self-performed sodium reduction was feasible and led to decrease in 24-hour BP of 9/5 mm Hg compared with a control group. The erythrocyte SS did not correlate to the change in BP after lowering sodium intake. REGISTRATION: URL: https://clinicaltrials.gov; Unique Identifier: NCT05165823.

Heart rate deceleration and acceleration capacities associated with circadian rhythm of blood pressure in essential hypertension.

BACKGROUND: This study aimed to investigate the potential association between the circadian rhythm of blood pressure and deceleration capacity (DC)/acceleration capacity (AC) in patients with essential hypertension. METHODS: This study included 318 patients with essential hypertension, whether or not they were being treated with anti-hypertensive drugs, who underwent 24-hour ambulatory blood pressure monitoring (ABPM). Patients were categorized into three groups based on the percentage of nocturnal systolic blood pressure (SBP) dipping: the dipper, non-dipper and reverse dipper groups. Baseline demographic characteristics, ambulatory blood pressure monitoring parameters, Holter recordings (including DC and AC), and echocardiographic parameters were collected. RESULTS: In this study, the lowest DC values were observed in the reverse dipper group, followed by the non-dipper and dipper groups (6.46 ± 2.06 vs. 6.65 ± 1.95 vs. 8.07 ± 1.79 ms, P < .001). Additionally, the AC gradually decreased (-6.32 ± 2.02 vs. -6.55 ± 1.95 vs. -7.80 ± 1.73 ms, P < .001). There was a significant association between DC (r = .307, P < .001), AC (r=-.303, P < .001) and nocturnal SBP decline. Furthermore, DC (ß = 0.785, P = .001) was positively associated with nocturnal SBP decline, whereas AC was negatively associated with nocturnal SBP (ß = -0.753, P = .002). By multivariate logistic regression analysis, deceleration capacity [OR (95% CI): 0.705 (0.594-0.836), p < .001], and acceleration capacity [OR (95% CI): 1.357 (1.141-1.614), p = .001] were identified as independent risk factors for blood pressure nondipper status. The analysis of ROC curves revealed that the area under the curve for DC/AC in predicting the circadian rhythm of blood pressure was 0.711/0.697, with a sensitivity of 73.4%/65.1% and specificity of 66.7%/71.2%. CONCLUSIONS: Abnormal DC and AC density were correlated with a blunted decline in nighttime SBP, suggesting a potential association between the circadian rhythm of blood pressure in essential hypertension patients and autonomic nervous dysfunction.

The association between blood pressure variability and renal damage in patients with primary aldosteronism.

This research examines the association between blood pressure variability (BPV) and renal damage in a cohort of 129 primary aldosteronism (PA) patients, employing ambulatory blood pressure monitoring (ABPM) for comparative analysis with individuals diagnosed with essential hypertension (EH). The study reveals that PA patients exhibited significantly elevated levels of cystatin C and urine microalbumin/creatinine ratio (UACR). Additionally, a higher prevalence of non-dipping blood pressure patterns in PA patients suggests an increased risk of circadian blood pressure regulation disturbances. Notably, while most BPV indices were comparable between the two groups, the standard deviation of 24-h weighted diastolic blood pressure was markedly lower in the PA cohort, distinguishing it as a unique variable. Through multiple linear regression analysis, the duration of hypertension, angiotensin II concentrations, and daytime systolic blood pressure standard deviation emerged as significant determinants of estimated glomerular filtration rate (eGFR) in PA patients. Furthermore, UACR was significantly influenced by variables including the 24-h weighted standard deviation (wSD) of systolic BP, glycosylated hemoglobin levels, nocturnal systolic BP peaks, aldosterone-renin ratio (ARR), and total cholesterol, with the most pronounced association observed with the 24-h wSD of systolic BP (ß = 0.383).The study also found significant correlations between the 24-h wSD of systolic BP, ARR, HbA1c, serum potassium levels, and 24-h urinary microalbumin, underscoring the critical role of the 24-h wSD of systolic BP (ß = 0.267). These findings underscore the imperative of an integrated management strategy for PA, addressing the intricate interconnections among metabolic abnormalities, blood pressure variability, and renal health outcomes.

'Essential' arterial hypertension: time for a paradigm change.

The exclusion of causes of hypertension is not systematically exploited in clinical practice. Therefore, essential hypertension is consistently presented as the most prevalent 'cause'. The paradox of a condition with unknown causes being described as a common cause of hypertension translates into a diagnosis of essential hypertension in most patients, which precludes the detection of a curable cause of hypertension. The aim of this review is to investigate how the notion of essential hypertension has developed and whether scientific evidence still support the notion of its high prevalence by examining the most recent studies. These studies provided solid scientific evidence that, when systematically sought for, secondary hypertension is quite common and that secondary hypertension is highly prevalent. The increased awareness should lead to a systematic search for, with the goal of curing or achieving a better control of high blood pressure, and ultimately improving patients' quality of life.

Mediating Effect of the NLR on the Relationship Between HbA1c and Left Atrial Stiffness in Overweight Patients With Hypertension.

BACKGROUND: We aimed to investigate the association between hemoglobin A1c (HbA1c) and left atrial (LA) stiffness in patients with hypertension and to explore the mediating effect of the neutrophil/lymphocyte ratio (NLR) on this association. METHODS: Essential hypertensive patients (n = 292) aged 18-83 years were enrolled and divided into two groups based on the LA stiffness index (LASI): Group I (LASI ≤ 0.32, n = 146) and Group II (LASI > 0.32, n = 146). The LASI was defined as the ratio of early diastolic transmitral flow velocity/lateral mitral annulus myocardial velocity (E/e') to LA reservoir strain. Multivariate linear regression analysis was performed to determine the independent predictors of the LASI. RESULTS: Age, BMI, SBP, HbA1c, CRP, and NLR were significantly greater in Group II than in Group I (P < 0.05). Additionally, Group II had a greater LA volume index (LAVI), left ventricular mass index (LVMI), and early diastolic transmitral flow velocity/lateral mitral annulus myocardial velocity (E/e') and lower LA reservoir, conduit, and booster pump strains than Group I (P < 0.001). Univariate and multivariate linear regression models revealed that age, SBP, HbA1c, and the NLR were independently associated with the LASI. Further mediation analysis was performed to determine the mediating effect of the NLR on the association between HbA1c and the LASI and revealed that the NLR had a mediating role only in overweight hypertensive patients, and the proportion of the mediating effect was 21.9%. CONCLUSIONS: The NLR was independently correlated with the LASI and played a mediating role in the relationship between HbA1c and the LASI in overweight hypertensive patients.

Homocysteine, hyperhomocysteinemia, and H-type hypertension.

Homocysteine (Hcy) is a sulphur-containing nonessential amino acid derived from the intermediate metabolites of methionine. Methionine is obtained from dietary proteins, such as poultry, meat, eggs, seafood, and dairy products. Abnormalities in Hcy metabolic pathways, deficiencies in dietary methionine, folate, and vitamins B12, B6, and B2 and genetic defects, polymorphisms, or mutations in Hcy metabolism-related enzymes may lead to an increase in plasma Hcy levels. Generally, a plasma Hcy level higher than 10 or 15 µmol/L has been defined as hyperhomocysteinemia (HHcy). An individual with essential hypertension complicated with HHcy is considered to have H-type hypertension (HTH). Currently, HHcy is considered a novel independent risk factor for various cardiovascular diseases. To provide a useful reference for clinicians, the research progress on Hcy, HHcy, and HTH in recent years was systematically reviewed here, with a focus on the source and metabolic pathways of Hcy, plasma Hcy levels and influencing factors, detection methods for plasma Hcy levels, relationship between Hcy concentration and hypertension, pathogenesis of HTH, cardiovascular complications of HTH, and treatment of HTH.

Efficacy and safety of esaxerenone (CS-3150) in primary hypertension: a meta-analysis.

This study aimed to assess the efficacy and safety of esaxerenone (CS-3150) in treating primary hypertension. PubMed (Medline), Cochrane Central Register of Controlled Trials (CENTRAL), and Embase databases were searched for articles published until April 18, 2023. The outcomes included were diastolic blood pressure (DBP), systolic blood pressure (SBP), 24 h DBP, 24 h SBP, and adverse events. The meta-analysis was conducted using RevMan 5.3. This study included three trials. CS-3150 5 mg had a greater effect on lowering the SBP, DBP, 24 h SBP, and 24 h DBP than either CS-3150 2.5 mg or eplerenone 50 mg. In contrast, CS-3150 2.5 mg and eplerenone 50 mg showed no significant difference in lowering DBP, SBP, 24 h DBP, and 24 h SBP. Moreover, adverse events occurred at comparable rates in the three groups. CS-3150 (especially CS-3150 5 mg) is an effective and safe treatment for primary hypertension; which can reduce blood pressure and alleviate hypertensive symptoms.

Efficacy of scraping therapy on blood pressure and sleep quality in stage I and II essential hypertension: A systematic review and meta-analysis.

BACKGROUND: Scraping therapy is widely used in treating stage I and II essential hypertension in China. However, there has been no systematic evaluation of the efficacy of scraping therapy on blood pressure and sleep quality in stage I and II essential hypertension. SEARCH STRATEGY: Seven electronic databases (PubMed, Scopus, Cochrane Library, Web of Science, EBSCO, China National Knowledge Infrastructure and Wanfang Data electronic databases) were searched from inception to December 2022. Based on the principle of combining subject words with text words, the search strategy was constructed around search terms for "scraping therapy," "scraping," "Guasha," "Gua sha," "hypertension," and "high blood pressure" during the database searches. INCLUSION CRITERIA: Randomized controlled trials (RCTs) were included if they recruited patients with stage I and II essential hypertension and included a scraping therapy intervention. The intervention group received antihypertensive drugs and scraping therapy, while the control group only took antihypertensive drugs. DATA EXTRACTION AND ANALYSIS: Review Manager 5.4.0 and STATA 15.1 were used to enter all the relevant outcome variables to conduct the meta-analysis. The quality of the selected RCTs was assessed using the PEDro scale. The sensitivity analysis was carried out by iteratively excluding individual studies and repeating the analysis to determine the stability of the findings and identify any studies with greater influence on the outcome. Subgroup analysis was performed to find the source of heterogeneity. Funnel plots were used to evaluate the publication bias of included studies. RESULTS: Nine RCTs including 765 participants were selected. Meta-analysis showed that scraping therapy combined with medication had an advantage over the use of medication alone in lowering systolic blood pressure (mean difference [MD] = -5.09, 95% confidence interval [CI] = -6.50 to -3.67, P < 0.001) and diastolic blood pressure (MD = -2.66, 95% CI = -3.17 to -2.14, P < 0.001). Subgroup analysis showed that scraping therapy improved sleep quality in middle-aged patients with hypertension, but the efficacy was better in elderly patients (MD = -7.91, 95% CI = -8.65 to -7.16, P < 0.001) than in middle-aged patients (MD = -2.67, 95% CI = -4.12 to -1.21, P = 0.0003). CONCLUSION: The available evidence indicates that scraping therapy has significant effects on patients with stage I and II hypertension, and it improves sleep quality for elderly patients with hypertension better than for middle-aged ones. Scraping therapy can be an adjunctive treatment for stage I and II essential hypertension. However, further high-quality studies are needed to verify its effectiveness and the best therapeutic strategies. Please cite this article as: Zhu, Z, Wang J, Pan, X. Efficacy of scraping therapy on blood pressure and sleep quality in stage I and II essential hypertension: A systematic review and meta-analysis. J Integr Med. 2024; 22(1): 12-21.

A meta-analysis of the haemodynamics of primary hypertension in children and adults.

We performed a systematic review and meta-analysis to determine the relative contributions of elevated cardiac output and systemic vascular resistance to hypertension in children and adults. This included 27 studies on 11 765 hypertensive and normotensive children and adults in whom cardiac output was measured. Cardiac output but not systemic vascular resistance was elevated in hypertensive compared to normotensive children and young adults (difference in means 1.15 [0.78-1.52] l/min, P < 0.001). In older hypertensive adults, both were elevated compared to normotensive individuals (0.40 [0.26-0.55] l/min, P < 0.001 and 3.21 [1.91-4.51] mmHg min/l, P < 0.001 for cardiac output and systemic vascular resistance, respectively). The main haemodynamic alteration in primary hypertension (including obesity-hypertension) in both children and young to middle-aged adults is an elevation of cardiac output. With longer duration and greater severity of hypertension there may be progression from a 'cardiac' to a 'vascular' phenotype with increased systemic vascular resistance.

Association between Vitamin D Deficiency and Levels of Renin and Angiotensin in Essential Hypertension.

Objective: The present study aims to investigate the relationship between vitamin D deficiency and renin-angiotensin-aldosterone levels in patients with essential hypertension. Methods: The present study observed two groups of patients from Urumqi, Xinjiang, China, from April 2017 to March 2018. There were two subject groups: the hypertension group (80 patients with essential hypertension selected by random cluster sampling) and the control group (76 healthy adults). The 25-hydroxyvitamin D (25(OH)D or vitamin D) levels were measured through electrolytes; fasting blood glucose, blood lipids, and other biochemical indicators were detected using immune chemiluminescence; and plasma renin activity and angiotensin II concentrations were detected with radio-immunity. Results: Comparison between the hypertension group and control group showed statistically significant differences in the systolic pressure and levels of 25(OH)D, renin, and triglycerides (P < 0.05). The correlation analysis showed that 25(OH)D was negatively correlated with renin (r = -0.185; P=0.021) and positively correlated with systolic pressure (r = -0.105; P=0.035). There were no statistically significant differences in diastolic pressure, fasting blood glucose, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides between the two groups. Conclusions: The results of the present study show that vitamin D deficiency is common in Urumqi, Xinjiang, China and vitamin D levels are negatively correlated with renin levels. Vitamin D plays an important role in regulating blood pressure by affecting renin levels through the renin-angiotensin-aldosterone system.

Association of common medical comorbidities with early renal damage in the Chinese tropics with essential hypertension.

BACKGROUND: Urine albumin/creatinine ratio (UACR) is an important marker of early renal damage (ERD) caused by hypertension. Recent studies showed that blood pressure was a significant inverse association with temperature and climate. The purposes of our study were sought to explore the association of common medical comorbidities with ERD, and find independent risk factors to ERD in Chinese tropics with essential hypertension. METHODS: From January 2018 to December 2019, we assessed UACR in a total of 599 hypertensive Chinese Hainan patients. We defined ERD as a UACR between 30 mg/g and 300 mg/g. We analysed differences between qualitative variables using the chi-squared (χ2) test. We calculated correlations between UACR and age, hypertension duration (HD), systolic blood pressure (SBP), and diastolic blood pressure (DBP) using the Spearman's rho test. To determine the odds ratio (OR), we evaluated binary logistic regression models. RESULTS: Among the 599 patients, 281 (46.9%) were found to have ERD. ERD and factors related to sex, body mass index (BMI), and SBP did not differ significantly (all, p>0.05). Our main findings showed that age, HD, and DBP were associated with ERD (p<0.01, respectively). Furthermore, age ≥ 65 years, HD ≥10 years, DBP ≥ 90 mmHg, SBP ≥ 160 mmHg, and diabetes differed significantly according to ERD status (p < 0.05, respectively). In multivariate analysis using stepwise regression, age (OR = 1.468), DBP (OR = 1.853), and diabetes (OR = 2.031) were significant independent predictors of ERD. The area under the receiver operating characteristic (ROC) curve was 0.677, and the sensitivity and specificity of the optimal cut-off value were 44.5 and 81.1%, respectively. CONCLUSIONS: Common medical comorbidities are associated with ERD; age, DBP, and diabetes are independent risk factors for ERD in patients with essential hypertension who live in the Chinese tropics. Early monitoring of the UACR, as well as control of blood glucose and DBP, can effectively delay ERD.

The Crosstalk between SARS-CoV-2 Infection and the RAA System in Essential Hypertension-Analyses Using Systems Approach.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), responsible for the coronavirus disease of 2019 (COVID-19) pandemic, has affected and continues to affect millions of people across the world. Patients with essential arterial hypertension and renal complications are at particular risk of the fatal course of this infection. In our study, we have modeled the selected processes in a patient with essential hypertension and chronic kidney disease (CKD) suffering from COVID-19, emphasizing the function of the renin-angiotensin-aldosterone (RAA) system. The model has been built in the language of Petri nets theory. Using the systems approach, we have analyzed how COVID-19 may affect the studied organism, and we have checked whether the administration of selected anti-hypertensive drugs (angiotensin-converting enzyme inhibitors (ACEIs) and/or angiotensin receptor blockers (ARBs)) may impact the severity of the infection. Besides, we have assessed whether these drugs effectively lower blood pressure in the case of SARS-CoV-2 infection affecting essential hypertensive patients. Our research has shown that neither the ACEIs nor the ARBs worsens the course infection. However, when assessing the treatment of hypertension in the active SARS-CoV-2 infection, we have observed that ARBs might not effectively reduce blood pressure; they may even have the slightly opposite effect. On the other hand, we have confirmed the effectiveness of arterial hypertension treatment in patients receiving ACEIs. Moreover, we have found that the simultaneous use of ARBs and ACEIs averages the effects of taking both drugs, thus leading to only a slight decrease in blood pressure. We are a way from suggesting that ARBs in all hypertensive patients with COVID-19 are ineffective, but we have shown that research in this area should still be continued.

Sex differences in hypertension: lessons from spontaneously hypertensive rats (SHR).

Although numerous clinical and experimental studies have clearly identified a sexual dimorphism in blood pressure control, the mechanism(s) underlying gender differences in blood pressure remain unclear. Over the past two decades, numerous laboratories have utilized the spontaneously hypertensive rats (SHR) as an experimental model of essential hypertension to increase our understanding of the mechanisms regulating blood pressure in males and females. Previous work by our group and others have implicated that differential regulation of adrenergic receptors, the renin-angiotensin system, oxidative stress, nitric oxide bioavailability and immune cells contribute to sex differences in blood pressure control in SHR. The purpose of this review is to summarize previous findings to date regarding the mechanisms of blood pressure control in male versus female SHR.

Low-dose Aspirin prevents hypertension and cardiac fibrosis when thromboxane A2 is unrestrained.

Enhanced platelet activation has been reported in patients with essential hypertension and heart failure. The possible contribution of platelet-derived thromboxane (TX)A2 in their pathophysiology remains unclear. We investigated the systemic TXA2 biosynthesis in vivo and gene expression of its receptor TP in 22 essential hypertension patients and a mouse model of salt-sensitive hypertension. The contribution of platelet TXA2 biosynthesis on enhanced blood pressure (BP) and overload-induced cardiac fibrosis was explored in mice by treating with low-dose Aspirin, resulting in selective inhibition of platelet cyclooxygenase (COX)-1-dependent TXA2 generation. In essential hypertensive patients, systemic biosynthesis of TXA2 [assessed by measuring its urinary metabolites (TXM) reflecting predominant platelet source] was enhanced together with higher gene expression of circulating leukocyte TP and TGF-ß, vs. normotensive controls. Similarly, in hypertensive mice with prostacyclin (PGI2) receptor (IP) deletion (IPKO) fed with a high-salt diet, enhanced urinary TXM, and left ventricular TP overexpression were detected vs. normotensive wildtype (WT) mice. Increased cardiac collagen deposition and profibrotic gene expression (including TGF-ß) was found. Low-dose Aspirin administration caused a selective inhibition of platelet TXA2 biosynthesis and mitigated enhanced blood pressure, cardiac fibrosis, and left ventricular profibrotic gene expression in IPKO but not WT mice. Moreover, the number of myofibroblasts and extravasated platelets in the heart was reduced. In cocultures of human platelets and myofibroblasts, platelet TXA2 induced profibrotic gene expression, including TGF-ß1. In conclusion, our results support tailoring low-dose Aspirin treatment in hypertensive patients with unconstrained TXA2/TP pathway to reduce blood pressure and prevent early cardiac fibrosis.

Incidence of essential hypertension but not echocardiographic abnormalities at four years with a history of preeclampsia with severe features.

INTRODUCTION: Women with preeclampsia are more likely to have abnormal echocardiographic parameters at the time of diagnosis and are more likely to have hypertension and other cardiovascular diseases (CVD) later in life. Screening for future CVD in preeclamptic women would assist in appropriately risk stratifying and identifying high risk women for preventive management; however, the timing of screening and the screening factors are unknown. OBJECTIVE: The objectives of this project are to 1) assess incidence of essential hypertension 4 years after pregnancy in preeclampsia with severe features (PEC) 2) identify predictive echocardiographic variables at the time of PEC diagnosis and 3) assess the rate of echocardiographic abnormalities 4 years after developing PEC. STUDY DESIGN: This is a prospective longitudinal study observing the incidence of essential hypertension in women within 4 years of a pregnancy complicated by PEC. We further looked at echocardiographic variables at the time of PEC diagnosis and at 4 years after PEC pregnancy in women with and without subsequent incident essential hypertension. The primary outcome measure is the incidence of essential hypertension within 4 years of PEC pregnancy, defined as a systolic blood pressure ≥ 130 mmHg or a diastolic blood pressure ≥ 80 mmHg. Secondary imaging outcomes include the persistence of abnormal echocardiographic parameters. Clinical secondary outcomes are new diagnoses of severe CVD, including coronary artery disease, stroke, arrhythmia, heart failure, or inpatient hospital admission for CVD. RESULTS: Of the 33 enrolled women with PEC, 48% (16/33) developed incident essential hypertension within 4 years of delivery. These women had thicker left ventricular posterior walls on their initial antenatal echocardiogram when compared to the 52% (17/33) who did not develop hypertension (1.0 cm [0.9-1.1 cm] vs 0.9 cm [0.7-0.9 cm]. p < 0.016). However, these abnormal echocardiographic variables resolved in the 16 women who underwent 4-year follow-up echocardiography. CONCLUSION: Women who develop PEC have a high incidence of essential hypertension within 4 years of delivery. The group who develops essential hypertension are more likely to have evidence of adverse cardiac remodeling at the time of PEC diagnosis; however, neither group have cardiac echocardiographic abnormalities 4 years postpartum. Because this is a small study, larger long-term cohort studies are needed to confirm these echocardiographic and clinical findings.