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Effect of Renin-Angiotensin System Blockade on Mortality in Korean Hypertensive Patients with Proteinuria.

ABSTRACT: Background:Although renin-angiotensin system (RAS) blockade is recommended for hypertensive patients with proteinuria, the effect of RAS blockade on Korean hypertensive patients has not been investigated. Methods:Among individuals who underwent a National Health Examination between 2002 and 2003 in Korea, hypertensive patients with proteinuria (defined as a dipstick test result ?2+) were enrolled in this study. We investigated the outcomes of two groups stratified by RAS blockade prescription (with RAS blockade vs. without RAS blockade). Moreover, Cox proportional hazard regression and Kaplan-Meier analyses were performed to examine the effects of RAS blockade on mortality and end-stage renal disease (ESRD). Results:A total of 8,460 patients were enrolled in this study, of whom 6,236 (73.7%) were prescribed with RAS blockade. The mean follow-up period was 129 months. A total of 1,003 (11.9%) patients died, of whom 273 (3.2%) died of cardiovascular (CV) events. The Kaplan-Meier curves for all-cause or CV mortality showed that the survival probability was significantly higher in the RAS blockade group than in the non-RAS blockade group. Multivariate Cox analysis also revealed RAS blockade significantly reduced the all-cause and CV mortality rates by 39.1% and 33.7%, respectively, compared with non-RAS blockade, even after adjusting for age, sex, and comorbid diseases; however, ESRD was not affected. Conclusion:In this study, we found that RAS blockade was significantly associated with a reduction in mortality but not in the incidence of ESRD. However, 26.3% of the enrolled patients did not use RAS blockade. Physicians need to consider the usefulness of RAS blockade in hypertensive patients with proteinuria.

SUBMITTER: Oh HJ

PROVIDER: S-EPMC6962440 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Effect of Renin-Angiotensin System Blockade on Mortality in Korean Hypertensive Patients with Proteinuria.

Oh Hyung Jung HJ Kim Clara Tammy CT Ryu Dong-Ryeol DR

Electrolyte & blood pressure : E & BP 20191231 2

<h4>Background</h4>Although renin-angiotensin system (RAS) blockade is recommended for hypertensive patients with proteinuria, the effect of RAS blockade on Korean hypertensive patients has not been investigated.<h4>Methods</h4>Among individuals who underwent a National Health Examination between 2002 and 2003 in Korea, hypertensive patients with proteinuria (defined as a dipstick test result ≥2+) were enrolled in this study. We investigated the outcomes of two groups stratified by RAS blockade ...[more]

PMID: 31969921

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Project description:BackgroundTaiwan has the highest renal disease incidence and prevalence in the world. We evaluated the association of statin and renin-angiotensin system inhibitor (RASI) use with dialysis risk in hypertensive patients.MethodsOf 248,797 patients who received a hypertension diagnosis in Taiwan during 2001-2012, our cohort contained 110,829 hypertensive patients: 44,764 who used RASIs alone; 7,606 who used statins alone; 27,836 who used both RASIs and statins; and 33,716 who used neither RASIs or statins. We adjusted for the following factors to reduce selection bias by using propensity scores (PSs): age; sex; comorbidities; urbanization level; monthly income; and use of nonstatin lipid-lowering drugs, metformin, aspirin, antihypertensives, diuretics, and beta and calcium channel blockers. The statin and RASI use index dates were considered the hypertension confirmation dates. To examine the dose-response relationship, we categorized only statin or RASI use into four groups in each cohort: <28 (nonusers), 28-90, 91-365, and >365 cumulative defined daily doses (cDDDs).ResultsIn the main model, PS-adjusted hazard ratios (aHRs; 95% confidence intervals [CIs]) for dialysis risk were 0.57 (0.50-0.65), 0.72 (0.53-0.98), and 0.47 (0.41-0.54) in the only RASI, only statin, and RASI + statin users, respectively. RASIs dose-dependently reduced dialysis risk in most subgroups and in the main model. RASI use significantly reduced dialysis risk in most subgroups, regardless of comorbidities or other drug use (P < 0.001). Statins at >365 cDDDs protected hypertensive patients against dialysis risk in the main model (aHR = 0.62, 95% CI: 0.54-0.71), regardless of whether a high cDDD of RASIs, metformin, or aspirin was used.ConclusionStatins and RASIs independently have a significant dose-dependent protective effect against dialysis risk in hypertensive patients. The combination of statins and RASIs can additively protect hypertensive patients against dialysis risk.

Project description:There is an ongoing interest in the renin-angiotensin system (RAS) contribution either to pathological mechanisms leading to hypertension (mainly regarding the ACE/AngII/AT1R axis), or, to RAS protective and pro-regenerative actions, primarily ascribed to the mediation of the AT2R and the MAS1 receptor. In the present study, we evaluated the modulation of gene expression and protein levels of "deleterious" (ACE/AngII/AT1R) and "protective" [ACE/AngII/AT2R and ACE2/Ang(1-7)/MAS1 arms] RAS components in parietal and frontal areas of cerebral cortex of spontaneously hypertensive rats (SHRs), after two periods of mandibular extensions (MEs). Blood pressure, BP and heart rate, HR were also measured. While no significant changes in BP and HR were present in the sham operated (SO) group, in rats after two MEs (2-ME rats), BP displayed a marked decrease (p < 0.001) at ME2, and remained then stably low for the subsequent observation period. In gene expression analysis, in SHRs undergoing two MEs, either in parietal or frontal cortex, we did not observe any significant variation of AT2R and ACE2 with respect to SO rats. In contrast, we observed a decrease in Mas1 gene expression in parietal area (p < 0.01) and an increase in frontal region (p < 0.01). AT1R and ACE gene expression was significantly higher in 2-ME rats than SO in parietal cortex (p < 0.05) but no difference was observed in the frontal area. Concerning protein levels, in parietal area, AT1R and AT2R did not change whereas MAS1 significantly decreased in 2-ME rats (p < 0.05). In frontal area, both AT1R and AT2R significantly decreased in 2-ME rats (p < 0.05), whereas MAS1 did not significantly change. Gene expression analysis in normotensive (NT) rats revealed the non-detectability of AT1R in both parietal and frontal zone. In parietal area, AT2R (p < 0.0001) and Mas1 (p < 0.01) were significantly decreased in 2-ME NT rats, when compared to SO, and ACE and ACE2 resulted not detectable whereas there was some expression of these genes after 2-ME procedure. In conclusion, our data in rat models indicated that a 2-ME procedure induced a hypotensive response and that a modulation of gene expression and protein levels of RAS components occurred in different cerebral cortex areas.

Project description:Background and objectivesSoluble Klotho is an anti-aging phosphaturic protein associated with vascular-renal protection. In vitro and in vivo studies have demonstrated that renin-angiotensin system (RAS) blockade increases soluble Klotho levels. The effect of RAS blockers on soluble Klotho in patients with diabetic kidney disease (DKD) is unknown.Design, setting, participants, & measurementsPlasma-soluble Klotho was measured in a secondary analysis of a randomized controlled clinical trial performed at a single university hospital center (ClinicalTrials.gov number NCT001715, from March 2003 to September 2006). Seventy-six patients with type 2 diabetes and DKD (all with albuminuria and serum creatinine <1.7 mg/dl) were studied at baseline and at 24 weeks (study end) after randomization to valsartan/hydrochlorothiazide (n=37) or amlodipine (n=39) treatment. Aortic-pulse wave velocity by applanation tonometry and albuminuria (from three timed urine collections) were also measured at baseline and 24 weeks.ResultsValsartan/hydrochlorothiazide treatment significantly increased mean (± SD) soluble Klotho (from 432.7 ± 179 to 506.4 ± 226.8 pg/ml; P=0.01) and reduced serum phosphate (from 3.25 ± 1.18 to 2.60 ± 0.96 mg/dl; P=0.04) compared with amlodipine (from 430.1 ± 145.8 to 411.9 ± 157.6 pg/ml and from 2.94 ± 0.56 to 2.69 ± 1.52 mg/dl, respectively). There was a significant difference between treatment groups in soluble Klotho (mean 91.9 pg/ml; 95% confidence interval, 19.9 to 162) and serum phosphate levels (mean -0.68 mg/dl; 95% confidence interval, -0.15 to -1.33) with valsartan/hydrochlorothiazide treatment (P=0.03 and P=0.04, respectively). Attained BP was similar in the two groups and levels of soluble Klotho were not associated with aortic-pulse wave velocity and albuminuria, variables that fell significantly only with valsartan/hydrochlorothiazide.ConclusionsTreatment with a RAS blocker, valsartan, is associated with an increase in soluble Klotho, which may contribute to the BP-independent cardiorenal benefits of these drugs in DKD.

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Effect of Renin-Angiotensin System Blockade on Mortality in Korean Hypertensive Patients with Proteinuria.

Publications

Effect of Renin-Angiotensin System Blockade on Mortality in Korean Hypertensive Patients with Proteinuria.

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