scholarly journals Real-world Evidence of Time-varying Effects of Renin-angiotensin System Inhibitors on Pneumonia and Related Deaths: A Territory-wide Cohort Study in 252,616 Patients With Diabetes (2002-2019)

2021 ◽  
Author(s):  
Aimin Yang ◽  
Mai Shi ◽  
Hongjiang Wu ◽  
Eric SH Lau ◽  
Baoqi Fan ◽  
...  
Keyword(s):  
Renin Angiotensin System ◽  
Chinese Patients ◽  
Cumulative Exposure ◽  
Time Varying ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Increased Risk ◽  
Patients With Diabetes ◽  
Reduced Risk

Abstract BackgroundDiabetes is associated with increased risk of respiratory infections. Renin-angiotensin system (RAS) inhibition with anti-fibrotic, anti-inflammatory effects may reduce pneumonia risk. Prior studies did not account for time-varying and cumulative exposure to RAS inhibitors (RASi), with short follow-up periods, nor compared angiotensin converting enzyme inhibitor (ACEi) and angiotensin receptor blocker (ARB) use in Asians. We investigated the association of long-term use of RASi with risk of pneumonia and related death in Chinese people with diabetes using electronic medical record (EMR) data.MethodsThis was a prospective analysis of EMR with overlap propensity-score weighting of a territory-wide cohort (n=252,616, 1.7 million person-years) and a register-based cohort (n=13,017, 0.1 million person-years) in Hong Kong. We compared new-users of RASi (ACEi/ARBs) following baseline assessment with non-RASi users and new-users of calcium-channel blockers as active comparator. The main outcome was first hospitalization and death from pneumonia. ResultsAmongst 252,616 patients with diabetes in the population-based cohort (mean age=61.0 [SD=12.2] years), 73,161 were new-ACEi-only users; 20,907 new-ARBs-only users; 38,778 ACEi/ARBs users; and 119,770 never-ACEi/ARBs users. Over a mean follow-up period of 6.7 years, 5.2% (n=13,057) of patients had pneumonia and 2.2% (n=5,480) died with pneumonia. Compared with non-RASi use, time-varying RASi exposure was associated with reduced risk of pneumonia (hazard ratio, HR, 95% CI): 0.78 (0.75-0.82) and pneumonia-related death (HR=0.49, 0.46-0.53). The respective HRs for ARBs-only were 0.70 (0.62-0.78) and 0.41 (0.33-0.52) and that of ACEi-only were 0.98 (0.91-1.05) and 0.77 (0.68-86). In the Aalen-additive hazards model, the effect of RASi use was time-invariant for pneumonia (P=0.340) and time-varying for related death (P<0.001) with prevention of 0.6 (0.2-0.9) and 1.4 (1.0-1.6) per-1000-person-years pneumonia events and related deaths, respectively.ConclusionsLong-term use of RASi, notably ARB, was associated with reduced risk of pneumonia and related deaths in Chinese patients with diabetes.

Abstract 13174: Sex Differences in Clinical Characteristics, Management and Prognosis in Patients With Heart Failure With Preserved Ejection Faction: Insights From the CHART-2 Study

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Kanako Tsuji ◽  
Yasuhiko Sakata ◽  
Masanobu Miura ◽  
Soichiro Tadaki ◽  
Ryoichi Ushigome ◽  
...  
Keyword(s):  
Heart Failure ◽  
Sex Differences ◽  
Beta Blockers ◽  
Renin Angiotensin System ◽  
Class Iii ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Female Patients ◽  
Increased Risk ◽  
Patients With Heart Failure

Background: The number of the patients with heart failure with preserved ejection fraction (HFpEF) has been rapidly increasing worldwide. However, sex differences in patients with HFpEF remain to be elucidated. Methods and Results: We examined sex differences in 3,124 consecutive patients with HFpEF (EF≥50%, mean 69.4years, 34.7% female) registered in our Chronic Heart Failure Analysis and Registry in the Tohoku District-2 (CHART-2) Study (N=10,219). Female patients, as compared with male patients, were characterized by higher age (72 vs. 68 years, P<0.01), higher LVEF (67 vs. 64%, P<0.01), higher heart rate (74 vs. 70bpm, PNYHA class III (14.1 vs. 7.0%, P<0.01), higher BNP levels (106 vs. 73pg/mL, P<0.01), lower prevalence of coronary artery disease (30 vs. 53%, P<0.01) and lower prescription rates of renin angiotensin system inhibitors (64.7 vs. 71.8%, P<0.01) and beta-blockers (37.8 vs. 43.9%, P<0.01). During the median 3.2-year follow-up, 147 female patients and 245 males died. Although there was no sex difference in all-cause mortality (13.6 vs. 12.0%, P=0.11), female patients more frequently died due to cardiovascular causes (53.7 vs. 39.2%, hazard ratio (HR): 1.62, 95% CI 1.20-2.18, P<0.01), and experienced more HF admissions (12.6 vs. 9.8%, HR: 1.35, 95% CI 1.08-1.68, P<0.01). Use of beta-blockers or renin-angiotensin system inhibitors was not associated with decreased incidence of death or HF admission in both sexes. In contrast, use of statins was associated with reduced incidence of all-cause death in both sexes (males and females; adjusted HR, 0.59 and 0.57; 95% CI 0.46-0.77 and 0.47-0.70, respectively, both P<0.01) and was also associated with reduced incidence of HF admission in males (adjusted HR: 0.67, 95%CI 0.53-0.85, P<0.01) but not in females (adjusted HR: 0.83, 95% CI 0.63-1.10, P=0.19). Conclusions: As compared with males, female patients with HFpEF were characterized by severer condition of HF and increased risk of cardiovascular death and HF admission. Although statin use was equally associated with improved mortality in both sexes, female patients with HFpEF may benefit from statins less than males in terms of reduction of HF admission.

scholarly journals Proteinuria in frasier syndrome

2013 ◽  
Vol 141 (9-10) ◽  
pp. 685-688
Author(s):  
Amira Peco-Antic ◽  
Fatih Ozaltin ◽  
Vojislav Parezanovic ◽  
Gordana Milosevski-Lomic ◽  
Verica Zdravkovic
Keyword(s):  
Renin Angiotensin System ◽  
Suppressor Gene ◽  
Tumour Suppressor Gene ◽  
Frasier Syndrome ◽  
Angiotensin System ◽  
Increased Risk ◽  
Risk Of Malignancy ◽  
End Stage ◽  
Ras Inhibitors

Introduction. Frasier syndrome (FS) is a genetic form of glomerulopathy, which results from mutations in the Wilms? tumour suppressor gene (WT1). Proteinuria in FS has been traditionally considered unresponsive to any medication and FS inevitably progresses to end stage renal failure. Case Outline. We present a patient with FS who had atypical clinical manifestation and unusual beneficial antiproteinuric response to renin-angiotensin system (RAS) inhibitors given in combination with indomethacin. After 13 years of follow-up, the patient is now 17-year old with normal renal functions and no proteinuria. Conclusion. RAS inhibitors combined with indomethacin showed beneficial effect in our patient. Thus, this combination might be the initial treatment of patients with FS. If this treatment strategy was not satisfied for at least 3 months, then CsA would be considered to be administered taking account of the nephrotoxicity and the increased risk of malignancy. Further prospective study is required to clarify this issue.

MS555 GENETIC INTERACTIONS IN THE RENIN–ANGIOTENSIN SYSTEM CONFER INCREASED RISK OF STROKE

2010 ◽  
Vol 11 (2) ◽  
pp. 221
Author(s):  
A. Bazina ◽  
T. Bozina ◽  
J. Lovric ◽  
Z. Poljaković ◽  
N. Bozina ◽  
...  
Keyword(s):  
Renin Angiotensin System ◽  
Genetic Interactions ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Increased Risk

scholarly journals The Identikit of Patient at Risk for Severe COVID-19 and Death: The Dysregulation of Renin-Angiotensin System as the Common Theme

2021 ◽  
Vol 10 (24) ◽  
pp. 5883
Author(s):  
Riccardo Sarzani ◽  
Massimiliano Allevi ◽  
Federico Giulietti ◽  
Chiara Di Pentima ◽  
Serena Re ◽  
...  
Keyword(s):  
Renin Angiotensin System ◽  
Adverse Outcomes ◽  
Virus Binding ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Renin Angiotensin ◽  
Increased Risk ◽  
Metabolic Conditions ◽  
Patient At Risk

Since the first months of the coronavirus disease 2019 (COVID-19) pandemic, several specific physiologic traits, such as male sex and older age, or health conditions, such as overweight/obesity, arterial hypertension, metabolic syndrome, and type 2 diabetes mellitus, have been found to be highly prevalent and associated with increased risk of adverse outcomes in hospitalized patients. All these cardiovascular morbidities are widespread in the population and often coexist, thus identifying a common patient phenotype, characterized by a hyper-activation of the “classic” renin-angiotensin system (RAS) and mediated by the binding of angiotensin II (Ang II) to the type 1-receptor. At the same time, the RAS imbalance was proved to be crucial in the genesis of lung injury after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, where angiotensin-converting-enzyme-2 (ACE2) is not only the receptor for SARS-CoV-2, but its down-regulation through internalization and shedding, caused by the virus binding, leads to a further dysregulation of RAS by reducing angiotensin 1-7 (Ang 1-7) production. This focused narrative review will discuss the main available evidence on the role played by cardiovascular and metabolic conditions in severe COVID-19, providing a possible pathophysiological link based on the disequilibrium between the two opposite arms of RAS.

scholarly journals Profile of Diabetic Nephropathy in Southern Morocco

2021 ◽  
Author(s):  
SANAA BENBRIA ◽  
Abdelaali BAHADI ◽  
Youssef ZORKANI ◽  
MOUNIA AZIZI ◽  
yassir zajjari ◽  
...  
Keyword(s):  
Renal Failure ◽  
Renal Function ◽  
Diabetic Nephropathy ◽  
Renin Angiotensin System ◽  
Biological Data ◽  
Diabetic Patients ◽  
Early Management ◽  
Angiotensin System ◽  
Renin Angiotensin

Abstract Diabetic nephropathy (DN) has a steadily increasing prevalence, particularly because of the increase in sedentary lifestyle and obesity. It is defined as the persistent presence of albuminuria in a diabetic patient and requires early management to prevent progression to end-stage renal failure. The purpose of this work is to describe the epidemiologic profile and the progression of DN for the first time in a southern Moroccan region: Guelmim Oued noun - Moroccan Sahara.Patients and methods: It is a retrospective study conducted at the 5th military hospital in Guelmim and including all diabetic patients seen in nephrology consultation between January 2015 and December 2018. We collected the following parameters of our patients: demographics, comorbidities, prescribed treatments and biological data (Albuminuria, renal function and glycated hemoglobin) during their nephrology follow-up.Résults: During the study period 267 diabetic patients were included among 1042 patients, which represented 25.9% of the nephrology consultation activity. Their average age was 64.3 years with a slight male predominance (60%) and only two patients had type 1 diabetes. At the first nephrology consultation the average duration of diabetes was 14.6 years, 61 (22.8%) patients were on diet alone, 95 (35.5%) on oral antidiabetic drugs (OADs), 94 (35.2%) on insulin and 35 (13%) on OAD and insulin. Half the patients were hypertensive and 107 (40%) already had a cardiovascular complication (arterial disease, coronary artery disease or stroke). The average initial albuminuria was 388 mg/24h and the average glomerular filtration rate (GFR) was 67 ml/min ; 115 (43%) patients being in renal failure. 46 (17%) patients had no renal function assessment during their previous follow-up and only 139 (52%) were on renin-angiotensin system inhibitors (RASIs). After 12-month-follow-up in nephrology, the average GFR was 70 ml/min and 64 ml /min after two years.Conclusion: Diabetic nephropathy accounts for at least a quarter of nephrology consultation activity in the region of Guelmim Oued Noun. It is characterized in this context by the delay in treatment using renin angiotensin system inhibitors and late nephrology referral hence the need to strengthen preventive strategies in this region especially continuous training.

Abstract 320: Cardiovascular Outcomes Associated with Combination of Renin Angiotensin System Drugs and Amlodipine

2012 ◽  
Vol 5 (suppl_1) ◽  
Author(s):  
Sumeet Panjabi ◽  
Jason Swindle ◽  
Paul Buzinec ◽  
Serban Iorga ◽  
Carlos M Ferrario
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Renin Angiotensin System ◽  
Cox Proportional Hazards ◽  
Cardiovascular Outcomes ◽  
Cox Proportional Hazards Model ◽  
Cox Models ◽  
Angiotensin System ◽  
Renin Angiotensin

To examine cardiovascular outcomes for patients medicated with renin angiotensin system (RAS) drugs/amlodipine in fixed (FDC)- and loose-dose (LDC) combinations. Retrospective claims from a large health plan (data from 01 Mar ‘07 to 31 Dec ’09) were used to identify commercial enrollees aged ≥ 18 yrs with hypertension and index claim for FDC olmesartan/amlodipine (FDC-OA), FDC benazepril/amlodipine (FDC-BA), or LDC angiotensin receptor blocker and amlodipine (LDC-AA). Absence of study drug 6 months prior to index claim, and continuous enrollment for ≥12 months post-index were required. The primary outcome of interest was a cardiovascular event (CVE) composite indicative of heart failure, stroke, myocardial infarction (MI), acute ischemic heart disease excluding MI, and MI/IHD-related surgery. Outcomes were identified on the basis of a primary or secondary ICD-9 diagnosis or procedure codes or CPT codes. To ensure cohort comparability, propensity scores assessing likelihood of assignment to FDC-OA were estimated separately, relative to FDC-BA and LDC-AA, and propensity score quintiles (PSQ) were generated. Cox proportional hazards model of time to first CVE controlling for demographics and baseline characteristics were estimated for each PSQ and results aggregated to compare time to first follow-up event between FDC-OA separately with FDC-BA and LDC-AA. A total of 4,864 individuals were identified on FDC-OA, 12,051 on FDC-BA, and 7,748 on LDC-AA. Mean follow-up duration was 543, 625, and 585 days, respectively. Mean proportion of day covered with therapy was higher in FDC-OA (0.63) cohort compared to FDC-BA (0.55, P <0.001) and LDC-AA cohorts (0.34, P <0.001). The proportion of patients who experienced an incident CVE in the follow-up was lower in the FDC-OA cohort versus FDC-BA and LDC-AA cohorts (5.94% vs 7.85%, and 16.85%, respectively). Adjusted Cox models suggested that patients initiated on LDC-AA (Hazard ratio [HR] =1.35, p<.001) but not FDC-BA (HR=1.14, p=0.085) were at greater risk of having a CVE compared to FDC-OA. Hazard ratios for first CVE in every quintile were greater for the LDC-AA compared to FDC-OA. In this large, managed care population, patients initiated with FDC-OA had a lower risk of cardiovascular events versus those initiated on LDC-AA, which may be attributed to the greater adherence associated with FDC therapy.

scholarly journals Role of renin-angiotensin system antagonists in the prevention of bevacizumab- and sunitinib-mediated cardiac dysfunction

2019 ◽  
Vol 316 (3) ◽  
pp. H446-H458 ◽  
Author(s):  
Viktoriya Mozolevska ◽  
Anna Schwartz ◽  
David Cheung ◽  
Vineet Goyal ◽  
Bilal Shaikh ◽  
...  
Keyword(s):  
Cardiac Dysfunction ◽  
Prophylactic Treatment ◽  
Cell Cancer ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Prophylactic Administration ◽  
Increased Risk ◽  
Ras Inhibitors

Although anticancer systemic therapy agents clearly lead to improved survival in patients with cancer, these can come at the cost of serious complications including cardiotoxicity. Two types of targeted systemic therapies currently in use for colorectal cancer (CRC) and renal cell cancer (RCC), respectively, include the vascular endothelial growth factor inhibitor bevacizumab (BVZ) and the tyrosine kinase inhibitor sunitinib (SNT). Despite the beneficial effects of BVZ and SNT in improving clinical outcomes in the settings of CRC and RCC, there is an increased risk of cardiac dysfunction. The aim of the present study was to determine whether prophylactic administration of renin-angiotensin system (RAS) inhibitors would attenuate the cardiotoxic side effects of BVZ or SNT in a chronic in vivo murine model. A total of 194 wild-type C57Bl/6 male mice received: 1) 0.9% saline, 2) BVZ (10 mg·kg−1·wk−1), or 3) SNT (40 mg·kg−1·day−1) for 4 wk. Within each arm, mice received daily prophylactic treatment with hydralazine (0.05 mg/ml), aliskiren (50 mg/kg), perindopril (4 mg/kg), or valsartan (2 mg/kg). Although hydralazine effectively lowered blood pressure in BVZ- or SNT-treated mice, it did not prevent left ventricular systolic dysfunction. Prophylactic administration of aliskiren, perindopril, or valsartan prevented adverse cardiovascular remodeling in mice treated with either BVZ or SNT. The addition of RAS antagonists also downregulated expression of phosphorylated p38 and Bcl-2-like 19-kDa interacting protein 3 in SNT-treated mice. In our chronic in vivo murine model, RAS antagonists partially attenuated the development of BVZ- or SNT-mediated cardiac dysfunction. Future clinical studies are warranted to investigate the cardioprotective effects of prophylactic treatment with RAS inhibitors in the settings of CRC and RCC. NEW & NOTEWORTHY In the evolving field of cardio-oncology, bevacizumab and sunitinib improve clinical outcomes in the settings of metastatic colorectal cancer and renal cell cancer, respectively. These anticancer drugs, however, are associated with an increased risk of cardiotoxicity. The prophylactic administration of renin-angiotensin system antagonists is partially cardioprotective against bevacizumab- and sunitinib-mediated cardiac dysfunction.

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