Dataset Information

Associations of Renin-Angiotensin-Aldosterone System Genes With Blood Pressure Changes and Hypertension Incidence.

ABSTRACT: The renin-angiotensin-aldosterone system (RAAS) plays an important role in blood pressure (BP) regulation. The current study uses single-marker and gene-based analyses to examine the association between RAAS genes and longitudinal BP phenotypes in a Han Chinese population.A total of 1,768 participants from the Genetic Epidemiology Network of Salt Sensitivity (GenSalt) follow-up study were included in the current study. Twenty-seven BP measurements were taken using random-zero sphygmomanometers at baseline and 2 follow-up visits. Mixed-effect models were used to assess the additive associations of 106 single-nucleotide polymorphisms (SNPs) in 10 RAAS genes with longitudinal BP changes and hypertension incidence. Gene-based analyses were conducted using the truncated product method. Attempts were made to replicate significant findings among Asian participants of the Multi-ethnic Study of Atherosclerosis (MESA). False discovery rate procedures were used to adjust for multiple testing.During an average of 7.2 years of follow-up, average systolic and diastolic BP increased, and 32.1% (512) of participants free from hypertension at baseline developed hypertension. NR3C2 SNPs rs7694064 and rs6856803 were significantly associated with longitudinal changes in systolic BP (P interaction = 6.9×10(-5) and 8.2×10(-4), respectively). Through gene-based analysis, NR3C2 was found to be significantly associated with longitudinal systolic BP change (P value of 1.00×10(-7)), even after removal of significant markers rs7694064 and rs6856803 from the analysis. The association between NR3C2 and longitudinal systolic BP change was replicated in Asian MESA participants (P value of 1.00×10(-4)).These findings indicate that NR3C2 may play an important role in BP progression and development of hypertension.

SUBMITTER: He WJ

PROVIDER: S-EPMC4715244 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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Associations of Renin-Angiotensin-Aldosterone System Genes With Blood Pressure Changes and Hypertension Incidence.

He William J WJ Li Changwei C Rao Dabeeru C DC Hixson James E JE Huang Jianfeng J Cao Jie J Rice Treva K TK Shimmin Lawrence C LC Gu Dongfeng D Kelly Tanika N TN

American journal of hypertension 20150328 11

<h4>Background</h4>The renin-angiotensin-aldosterone system (RAAS) plays an important role in blood pressure (BP) regulation. The current study uses single-marker and gene-based analyses to examine the association between RAAS genes and longitudinal BP phenotypes in a Han Chinese population.<h4>Methods</h4>A total of 1,768 participants from the Genetic Epidemiology Network of Salt Sensitivity (GenSalt) follow-up study were included in the current study. Twenty-seven BP measurements were taken us ...[more]

PMID: 25820244

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Project description:RationalePatients with idiopathic pulmonary arterial hypertension (iPAH) often have a low cardiac output. To compensate, neurohormonal systems such as the renin-angiotensin-aldosterone system (RAAS) and the sympathetic nervous system are up-regulated, but this may have long-term negative effects on the progression of iPAH.ObjectivesAssess systemic and pulmonary RAAS activity in patients with iPAH and determine the efficacy of chronic RAAS inhibition in experimental PAH.MethodsWe collected 79 blood samples from 58 patients with iPAH in the VU University Medical Center Amsterdam (between 2004 and 2010) to determine systemic RAAS activity.Measurements and main resultsWe observed increased levels of renin, angiotensin (Ang)I, and AngII, which were associated with disease progression (P < 0.05) and mortality (P < 0.05). To determine pulmonary RAAS activity, lung specimens were obtained from patients with iPAH (during lung transplantation, n = 13) and control subjects (during lobectomy or pneumonectomy for cancer, n = 14). Local RAAS activity in pulmonary arteries of patients with iPAH was increased, demonstrated by elevated angiotensin-converting enzyme activity in pulmonary endothelial cells and increased AngII type 1 (AT(1)) receptor expression and signaling. In addition, local RAAS up-regulation was associated with increased pulmonary artery smooth muscle cell proliferation via enhanced AT(1) receptor signaling in patients with iPAH compared with control subjects. Finally, to determine the therapeutic potential of RAAS activity, we assessed the chronic effects of an AT(1) receptor antagonist (losartan) in the monocrotaline PAH rat model (60 mg/kg). Losartan delayed disease progression, decreased right ventricular afterload and pulmonary vascular remodeling, and restored right ventricular-arterial coupling in rats with PAH.ConclusionsSystemic and pulmonary RAAS activities are increased in patients with iPAH and are associated with increased pulmonary vascular remodeling. Chronic inhibition of RAAS by losartan is beneficial in experimental PAH.

Project description:Hypertension is proved to be associated with severity and mortality in coronavirus disease 2019 (COVID-19). However, little is known about the effects of pre-admission and/or in-hospital antihypertension treatments on clinical outcomes. Thus, this study aimed to investigate the association between in-hospital blood pressure (BP) control and COVID-19-related outcomes and to compare the effects of different antihypertension treatments. This study included 2864 COVID-19 patients and 1628 were hypertensive. Patients were grouped according to their BP during hospitalization and records of medication application. Patients with higher BP showed worse cardiac and renal functions and clinical outcomes. After adjustment, subjects with pre-admission usage of renin-angiotensin-aldosterone system (RAAS) inhibitors (HR = 0.35, 95%CI 0.14-0.86, P = .022) had a lower risk of adverse clinical outcomes, including death, acute respiratory distress syndrome, respiratory failure, septic shock, mechanical ventilation, and intensive care unit admission. Particularly, hypertension patients receiving RAAS inhibitor treatment either before (HR = 0.35, 95%CI 0.13-0.97, P = .043) or after (HR = 0.18, 95%CI 0.04-0.86, P = .031) admission showed a significantly lower risk of adverse clinical outcomes than those receiving application of other antihypertensive medicines. Furthermore, consecutive application of RAAS inhibitors in COVID-19 patients with hypertension showed better clinical outcomes (HR = 0.10, 95%CI 0.01-0.83, P = .033) than non-RAAS inhibitors users. We revealed that COVID-19 patients with poor BP control during hospitalization had worse clinical outcomes. Compared with other antihypertension medicines, RAAS inhibitors were beneficial for improving clinical outcomes in COVID-19 patients with hypertension. Our findings provide direct evidence to support the administration of RAAS inhibitors to COVID-19 patients with hypertension before and after admission.

Dataset Information

Associations of Renin-Angiotensin-Aldosterone System Genes With Blood Pressure Changes and Hypertension Incidence.

Publications

Associations of Renin-Angiotensin-Aldosterone System Genes With Blood Pressure Changes and Hypertension Incidence.

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