RAS Blockers Research Articles

Impact of age on eGFR dynamics following sodium-glucose cotransporter 2 inhibitor therapy: A real-world study

AimThe initial decrease in estimated glomerular filtration rate (eGFR), often known as the “initial dip,” associated with sodium-glucose cotransporter 2 inhibitors (SGLT2i) is typically transient but may be more pronounced in older patients. MethodsWe analyzed real-world data from 2,070 patients newly prescribed SGLT2i, tracking eGFR changes at baseline and 3, 6, 9, and 12 months after initiation. We defined a significant initial dip as over 10 % reduction in eGFR at 3 months. In addition, the 1-year change in eGFR after the initial decline was also assessed. ResultsOf the total patients, 34.5 % were aged 60–69 years, 21.1 % were aged 70–79 years, and 11.5 % were aged 80 years or older. About 21.4 % experienced a significant dip at 3 months. The incidence of initial dip increases with age, with the highest incidence (38.7 %) in those aged 80 + . Despite the initial decline, subsequent eGFR was stable over one year in all age groups. Factors such as age, lower hemoglobin, higher uric acid levels, and use of RAS blockers were linked to the initial dip. ConclusionsOlder patients showed a more pronounced initial eGFR decline after starting SGLT2i, but it stabilized for one year without further deterioration, similar to younger patients.

#767 Utility of cystatin C as a predictor for postoperative acute kidney injury in non-cardiac surgeries [S1

Abstract Background and Aims Serum creatinine has been widely utilized to estimate glomerular filtration rate (eGFR), although various biomarkers have been developed to address its limitations. Among these biomarkers, the clinical use of Cystatin C is increasingly gaining recognition. However, there is a lack of evaluation regarding the utility of cystatin C in predicting the risk of postoperative acute kidney injury (PO-AKI) in non-cardiac surgeries. Method A retrospective cohort study was conducted on patients who underwent non-cardiac surgeries more than 1 hour from five departments (general surgery, neurosurgery, obstetrics and gynecology [OBGY], orthopedics, and urosurgery) at Chung-Ang University Hospital between 2018 and 2020. Patients with missing baseline information, including creatinine and cystatin C, and those without follow-up serum creatinine levels were excluded. PO-AKI was defined as KDIGO-AKI criteria occurring within 7 days after surgery. The estimated glomerular filtration rate (eGFR) was calculated from 2012 and 2021 chronic kidney disease-epidemiology collaboration (CKD-EPI) equations. Logistic regression was used to develop a prediction model, and C-statistics and the Delong test were used to compare the performance. Baseline comorbidities (diabetes mellitus [DM] and hypertension), laboratory findings (hypoalbuminemia [serum albumin <3.5 g/dL], anemia [hemoglobin <12 g/dL for female or <13 g/dL for male], and hyponatremia [sodium <135 mEq/L]), medication usage within 90 days of surgery (nonsteroidal anti-inflammatory drug and renin-angiotensin-system [RAS] blocker), and operation information (Anesthesia type, emergency operation, and operation duration) were adjusted. Results Overall, 339 patients were enrolled, with 49 patients (14.5%) developed PO-AKI. The median age was 73.0 [64.0; 80.0]; eGFR-Cr 86.4 [65.5; 99.1] mL/min/1.73 m2, eGFR-Cystatin C 70.0 [45.2; 92.7] mL/min/1.73 m2; eGFR-Cr/Cystatin C 77.2 [54.5; 100.5] mL/min/1.73 m2. Patients who developed AKI had a higher prevalence of diabetes (AKI 49.0%, no AKI 28.3%; p-value 0.006) and prescription of RAS blockers (AKI 63.3%, no AKI 34.5%; p-value <0.001), longer operation duration (AKI 63.3%, no AKI 34.5%; p-value <0.001), and lower eGFR of all types (AKI: eGFR-Cr 69.8, eGFR-Cystatin C 48.0, eGFR-Cr/Cystatin C 57.2; no-AKI: eGFR-Cr 88.0, eGFR-Cystatin C 74.0, eGFR-Cr/Cystatin C 80.5 mL/min/1.73 m2; p-values <0.001). No statistical differences were observed in other laboratory findings between the two groups (Table 1). The model with eGFR-Cystatin C demonstrated the highest area under the curve (AUC) among the three models (eGFR-Cr: AUC 0.78, 95% confidential interval [CI] 0.702‒0.857; eGFR-Cystatin C: AUC 0.81, 95% CI 0.735‒0.877; eGFR-Cr/Cystatin C: AUC 0.80, 95% CI 0.724‒0.871). Only the eGFR-Cystatin C-based model showed significant improvement in prediction compared to the eGFR-Cr-based model in the Delong test (eGFR-Cystatin C vs eGFR-Cr: p-value 0.033; eGFR-Cr/Cystatin C vs eGFR-Cr: p-value 0.055, Fig. 1). Conclusion Our findings suggest the potential usefulness of cystatin C in predicting the risk of PO-AKI non-cardiac surgery in addition to conventional PO-AKI risk factors. Further studies including larger and external cohorts, are needed for validation.

European guidelines for the treatment of arterial hypertension 2023: new trends

The treatment strategy for arterial hypertension is aimed at controlling blood pressure levels, as well as preventing serious cardiovascular complications and affecting the prognosis of the disease. Therefore, pharmacotherapy of arterial hypertension is given great importance as a guide to the treatment of patients in real practice. The new 2023 European Society Guidelines for the diagnosis and treatment of hypertension were developed after a thorough analysis of studies in the field of arterial hypertension, and were not limited to RCTs only, but also included realistic studies (observational, cohort, administrative databases). The 2023 Guidelines support the proven value of five major classes of antihypertensive drugs: thiazide/thiazide-like diuretics, ACEIs, ARBs, calcium antagonists, and β-blockers. New data from meta-analyses support the greater clinical relevance of RAS blockers, calcium channel blockers, and thiazide/thiazide-like diuretics in preventing hypertension-related outcomes, leading to their preferred use in the pharmacotherapy of arterial hypertension, including various combinations of drugs. A new trend in the pharmacotherapy of arterial hypertension has been the inclusion of β-blockers among the main antihypertensive drugs, including their preferred use for a number of clinical conditions. New classes of drugs, such as SGLT2 inhibitors and non-steroidal mineralocorticoid receptor antagonists, are cited as having BP-lowering effects and with strong evidence of reduced cardiovascular and renal outcomes in patients with type 2 diabetes and, in the case of SGLT2 inhibitors, in non-diabetic patients. The 2023 Guidelines significantly updated information on available combination strategies for the treatment of arterial hypertension, and added data on the effectiveness of fixed combinations, including quadropills and polypills.

Treatment characteristics and factors associated with heart failure with improved ejection fraction in the heart failure patient management program at Hanoi Heart Hospital

Background: Many patients with heart failure (HF) with reduced ejection fraction (HFrEF) have improved or restored left ventricular ejection fraction (LVEF). Within context heart failure with recovered or improved ejection fraction (HFiEF) has been proposed as a new category of HF. Data on clinical characteristics, outcomes, and medical, interventional, surgical, or related factors in patients with heart failure with improved ejection fraction (HFiEF) are scarce. Methods: Descriptive analysis study, the period from May 2021 to November 2022 satisfies the criteria for heart failure with reduced or slightly reduced ejection fraction and is hospitalized for inpatient treatment, discharged from the hospital to participate in the patient management program heart failure for at least 3 months. Results: 488 patients were included in the study, the average age of the improved group and the remaining group were 64.35±13.74 and 64.39±13.55, the proportion of women in the improvement group and the remaining group are 50% and 41.6%. The rate of use of RAS system drugs and beta blockers improved by 96.4% and 89.3%, respectively, higher than the other group’s 86.1% and 74.5%, which is statistically significant. The rate of MRA, SGLT2-i in the improved group and the remaining group was 63.1%; 59.5% and 64.9%; 61.9%. The rate of using 2 drugs including RAS and beta blockers in the improvement group (85.7%) was statistically significantly higher than the other group (67.6%). The area under the ROC curve of admission EF, LVEDVi, LVESVi in predicting improvement was 0.687 (95% CI 0.640-0.730; p< 0.001), respectively; 0.531(95% CI 0.462-0.599; p=0.378); 0.543 (95% CI 0.467-0.611; p=0.211). If only calculated on the total number of patients with EF ≤ 40%, the Kaplan Meier chart of CABG, heart valve surgery and percutaneous coronary intervention predicting improvement in heart failure after 3 months are all statistically significant. Conclusion: The rate of heart failure improved in the program was 17.2%. EF at admission, rate of use of RAS system drugs, beta blockers, rate of use of 2 RAS system drugs and beta blockers, percutaneous coronary intervention, CABG surgery or Heart valve surgery is significant in predicting improved heart failure in the heart failure program at Hanoi Heart Hospital.

Abstract 11667: Red Cell Indices and Long-Term Prognosis of Heart Failure Patients

Introduction: It has been demonstrated that some properties of red blood cells also play a role in the etiology of cardiovascular diseases and their complications. Hypothesis: We determined to what extent red blood cell indices observed during hospitalization for heart failure (HF) affect the long-term prognosis of these patients. Methods: We followed 3697 patients [mean age 71.4 years (±SD10.1), 59.1% males] hospitalized for decompensated HF between 2010-20. In the multivariate model, we assessed the five-year all-cause mortality risk associated with red cell distribution width (RDW), mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), and hemoglobin concentration (dichotomized by tertiles). Results: Kaplan-Meier survival curves comparing the tertiles of red cell indices are in Figure. Patients with RDW in the top tertile showed roughly two-fold higher 5-year mortality risk than those in the bottom tertile; increased risk we also observed in the middle tertile of RDW. This association remained significant even after complex adjustments for individual characteristics (age, gender, ejection fraction, HF etiology, history of malignancy, revascularization, hypertension, diabetes, LDL, atrial fibrillation, and glomerular filtration) as well as treatments (furosemide, beta-blockers, RAS blockers, MRA′s, statins). [HRR 1.83 (95% CIs: 1.53-2.18), p<0.0001, 3 rd versus 1 st ; 1.42 (95%CIs: 1.19-1.68), p<0.0001, 2 nd versus 1 st ] Similarly, we observed increased mortality risk in the bottom tertile of MCHC [HRR 1.34 (95%CIs:1.14-1.59), p=0.001, 1 st versus 3 rd ( fully adjusted)] or hemoglobin [HRR 1.37 (95%CIs: 1.15-1.62), p<0.0001]. In contrast, MCV did not show any additive mortality risk. Conclusions: High degree of anisocytosis and low red cell status of hemoglobin represents independent indicators of poor prognosis in heart failure patients, even long-term after an acute manifestation.

Lipids and RAS blockers plus CCB combinations. Alternations in prediabetic hypertensive patients, a randomized 12-week open-label comparative study

Lipids and RAS blockers plus CCB combinations. Alternations in prediabetic hypertensive patients, a randomized 12-week open-label comparative study

EFFECTS OF HYPERTENSION ON TAVI OUTCOMES

Objective: Severe aortic stenosis (AS) is the most common valvular disease in elderly and transcatheter aortic valve implantation (TAVI) is the standard of care treatment for AS in patients with high surgical risk. Hypertension accompanies with AS in this population in general. We aimed to evaluate the impact of hypertension on TAVI related outcomes. Design and method: All of the patients who underwent TAVI procedure between January 2010 and March 2020 were screened and patients with eligible datas were included. Datas were obtained from hospital electronic database. Results: A total of 306 cases were enrolled. Mean age of the population was 76.0 ± 10.4 61.4% of the cases were female. Median follow-up was 28.4 (13.0-49.5) months. Age was significantly higher (77.0 ±8.2 vs. 72.7± 14.8; p = 0.018) and diabetes was more frequent (37.6% vs. 16.9%; p = 0.001) in hypertensive patients. Use of RAS blockers (62.0% vs 28.6%; p<0.001) and calcium channel blockers (34.5% vs. 3.9%; p<0.001) were more frequent in hypertensive cases as expected. Baseline characteristics and outcomes were summarized in Table-1. Left ventricular mass index was similar between the two groups (129.5 ± 32.8 vs. 132.7 ± 39.3; p = 0.502). Rates of contrast induced nephropathy, insertion site complications and need of de novo pacemaker implantation due to advanced heart block were not different between the two arms. Stroke rates were distinctly higher in patients with hypertension (7.4% vs 0%; p = 0.009), while all-cause mortality during follow-up was similar between patients with and without hypertension. Conclusions: Left ventricular mass index increases in patients with severe AS and hypertension also leads left ventricular hypertrophy by raising afterload. However, LVMI values were similar between patients with and without hypertension contrary to as expected. Higher proportion of RAS blocker use that has favorable effects on cardiac remodelling can explain this finding. Significantly increased risk of stroke in patients with hypertension is another attractive finding that should be kept in mind.

PS-C27-8: ELIGIBILITY OF FINERENONE INITIATION IN ASIAN CHRONIC KIDNEY DISEASE PATIENTS BY KIDNEY FUNCTION AND DIABETES STATUS

Background: Patients with chronic kidney disease, CK, due to diabetes, DM, and hypertension, HTN, are at risk of rapid progression. The addition of a non-steroidal mineralocorticoid antagonist, finerenone, reduces blood pressure and retards CKD progression. However, it causes a rise in serum potassium, K, of about 0.23 mmol per L. We examined the serum potassium of CKD patients with and without DM by kidney function. Methods: We analyzed data from the Asian Kidney Disease Study. There were 232 CKD patients who underwent measured glomerular filtration rate, GFR, mL per min per 1.73 m2. There were 51 percent male, mean age 58.4, 12.8; 51 percent had DM, 119 of 232, median GFR 47, IQR 29–67. There were 185 of 232 patients using renin-angiotensin system, RAS, blockers. We stratified analyses by groups of K above 4.8, threshold for initiation of finerenone and by GFR above and below 25 where the risks of hyperkalemia is highest. Results: Overall, mean K is 4.35, 0.54. K is negatively associated with GFR; 4.596–0.0048 x GFR; p is 0.0002. There is no difference in serum potassium by use of RAS blockers, 185 of 232. Mean K was higher in DM patients 4.45, 0.58 vs. 4.24, 0.47; P is 0.0023. In patients with GFR below 25, there were 8 of 34 or 23.5 percent with K above 4.8, and 26 of 198 or 13.1% with K above 4.8 and GFR above 25. In DM CKD patients with GFR below 25, 6 of 18 or 33.3 percent had K above 4.8; and 16 of 95 or 16.8 percent had K above 4.8 with GFR above 25. Conclusions: There was 16.8 percent of DM CKD patients with GFR above 25 who had K above 4.8 who would require potassium binders in order to start finerenone.

Effect of the administration of different forms of vitamin D on central blood pressure and aortic stiffness, and its implication in the reduction of albuminuria in chronic kidney disease

Background and objectivesVitamin D (vitD) participates in phospho-calcium metabolism and exerts multiple pleiotropic effects. There is tissue 1-α (OH)ase that converts 25-OH cholecalciferol (25 (OH) D) in calcitriol that exerts autocrine and paracrine effects. 25 (OH)D deficiency could limit these tissue effects of vitD. The administration of nutritional vitD and the activator of the vitD receptor, paricalcitol, may promote beneficial effects on vascular and renal function. The objective of this work was to study in subjects with chronic kidney disease (CKD) the effect that the administration of different forms of vitD has on arterial function and albuminuria, and the possible relationship between the modifications of these variables. Patients and methodsWe studied in 97 patients with CKD stages 3–4 the effect of the administration of cholecalciferol (group 2; n: 35) and paricalcitol (n: 31; group 3) on parameters derived from brachial blood pressure, aortic blood pressure and on aortic stiffness studied using carotid-femoral pulse velocity (Vpc-f), and on albuminuria. A group of patients with stages 3–4 CKD who did not receive vitD therapy served as a control group (n: 31; group 1). All parameters were studied at baseline and after the follow-up period which was 7±2 months. ResultsIn the baseline phase, no differences were observed between the groups in brachial systolic blood pressure (bSBP), central systolic blood pressure (SBP), brachial pulse pressure (bPP), and central pulse pressure (pCP) or in aortic stiffness that was increased in all groups with a baseline Vpc-f value of 10.5 (9.2–12.1) m/sec. The baseline albuminuria value in the grouped patients was 229 (43–876) mg/g (median (interquartile range)), with no differences between the groups.Serum calcium and phosphorus increased significantly in those treated with cholecal-ciferol (native vitD) and paricalcitol (active vitD). Parathormone (PTH) values ​​decreased in those treated with paricalcitol. bPP and cPP decreased in all groups treated with native and active vitD. No significant changes in bPP and cPP were observed in the control group.Vpc-f did not change significantly in any of the groups, although the variation was quantitatively greater in group 3 (11.2±2 vs. 10.7±1.6 (p:0.06)). No differences were observed in the changes in Vpc-f between the groups when adjusted to the baseline values ​​of estimated glomerular filtration rate (eGFR), albuminuria, PTH, vitD, brachial and central blood pressure parameters, and their changes with treatment.Those who received treatment with native and active vitD presented a significant decrease in albuminuria of 17% (group 2) and 21% (group 3) compared to a 16% increase in the untreated group (group 1) (p:0 .01). A decrease in albuminuria ≥30% was observed more frequently in the groups treated with some form of vitD (group 2: 23%; group 3: 45%) than in the control group (13%) (p:0.03). The decrease in albuminuria observed in the groups treated with any of the forms of vitD did not vary when the baseline values ​​of the biochemical parameters of phosphorus-calcium metabolism, those of arterial function (PPb, PPc, Vpc-f) or its modifications were introduced as covariates. There was no significant correlation between changes in Vpc-f and albuminuria. In logistic regression, changes in arterial function parameters were also not explanatory for the ≥30% decrease in albuminuria. ConclusionsIn patients with CKD stages 3–4, treated with RAS blockers and with residual albuminuria, the administration of or paricalcitol reduces brachial and aortic pulse pressures, and albuminuria. The decrease in albuminuria does not seem to be mediated, at least not decisively, by changes in central hemodynamics or aortic stiffness.

Efecto de la administración de diferentes formas de vitamina D en la presión arterial y rigidez aórticas, y su implicación en la reducción de la albuminuria en la enfermedad renal crónica

Background and objectivesVitamin D(vitD) participates in phospho-calcium metabolism and exerts multiple pleiotropic effects. There is tissue 1-α (OH)ase that converts 25-OH cholecalciferol (25 (OH) D) in calcitriol that exerts autocrine and paracrine effects. 25 (OH)D deficiency could limit these tissue effects of vitD. The administration of nutritional vitD and the activator of the vitD receptor, paricalcitol, may promote beneficial effects on vascular and renal function. The objective of this work was to study in subjects with chronic kidney disease (CKD) the effect that the administration of different forms of vitD has on arterial function and albuminuria, and the possible relationship between the modifications of these variables. Patients and methodsWe studied in 97 patients with CKD stages 3-4 the effect of the administration of cholecalciferol (group 2; n: 35) and paricalcitol (n: 31; group 3) on parameters derived from brachial blood pressure, aortic blood pressure and on aortic stiffness studied using carotid-femoral pulse velocity (Vpc-f), and on albuminuria. A group of patients with stages 3-4 CKD who did not receive vitD therapy served as a control group (n: 31; group 1). All parameters were studied at baseline and after the follow-up period which was 7 ± 2 months. ResultsIn the baseline phase, no differences were observed between the groups in brachial systolic blood pressure (bSBP), central systolic blood pressure (SBP), brachial pulse pressure (bPP), and central pulse pressure (pCP) or in aortic stiffness that was increased in all groups with a baseline Vpc-f value of 10.5 (9.2-12.1) m/sec. The baseline albuminuria value in the grouped patients was 229 (43-876) mg / g (median (interquartile range)), with no differences between the groups.Serum calcium and phosphorus increased significantly in those treated with cholecal-ciferol (native vitD) and paricalcitol (active vitD). Parathormone (PTH) values decreased in those treated with paricalcitol.bPP and cPP decreased in all groups treated with native and active vitD. No significant changes in bPP and cPP were observed in the control group.Vpc-f did not change significantly in any of the groups, although the variation was quantitatively greater in group 3 (11.2±2 vs. 10.7±1.6 (P=.06)). No differences were observed in the changes in Vpc-f between the groups when adjusted to the baseline values of estimated glomerular filtration rate (eGFR), albuminuria, PTH, vitD, brachial and central blood pressure parameters, and their changes with treatment.Those who received treatment with native and active vitD presented a significant decrease in albuminuria of 17% (group 2) and 21% (group 3) compared to a 16% increase in the untreated group (group 1) (P=.01). A decrease in albuminuria ≥30% was observed more frequently in the groups treated with some form of vitD (group 2: 23%; group 3: 45%) than in the control group (13%) (P=.03). The decrease in albuminuria observed in the groups treated with any of the forms of vitD did not vary when the baseline values of the biochemical parameters of phosphorus-calcium metabolism, those of arterial function (PPb, PPc, Vpc-f) or its modifications were introduced as covariates. There was no significant correlation between changes in Vpc-f and albuminuria. In logistic regression, changes in arterial function parameters were also not explanatory for the ≥30% decrease in albuminuria. ConclusionsIn patients with CKD stages 3-4, treated with RAS blockers and with residual albuminuria, the administration of or paricalcitol reduces brachial and aortic pulse pressures, and albuminuria. The decrease in albuminuria does not seem to be mediated, at least not decisively, by changes in central hemodynamics or aortic stiffness.

Beneficial effects of RAS blockers in prediabetics with a hypertension-An observational cohort study

Hypertensive patients have a high prevalence of prediabetes and type II Diabetes mellitus. As per International Diabetic Federation, it has been estimated that more than 470 million people will have prediabetes by 2030. Approximately 5-10% of prediabetes progresses to overt diabetes mellitus, with the same proportion converting back to normoglycemia. In patients who are on Renin-Angiotensin System [RAS] blockers either an Angiotensin converting enzyme inhibitor (ACEI) or an Angiotensin receptor blocker (ARB) would slow down the progress of prediabetic state to overt or frank diabetes mellitus. This was a prospective, observational cohort study and a total of 125 hypertensive patients with impaired glucose tolerance were included in the study who were either on ACE inhibitor or ARB monotherapy. An oral Glucose Tolerance Test (GTT) was done at baseline for screening prediabetic patients, then a periodical assessment of glycemic indices, (fasting blood sugar, 2 hr postprandial blood sugar, and glycosylated hemoglobin), lipid profile, and complication status during the study period were evaluated every 3 months for18months. At the end of 1½ years, for patients belonging to the age group 18-54 years the FBS, PPBS, and HbA1C levels decreased significantly when the RAS blocking drugs (ACEIs and ARBs) were used continuously for 1 year and then they got stabilized. The beneficial effect was seen more in the younger age group 18-54 years old patients. Male above 54 years and females above 49 were resistant to the beneficial effects. In hypertensive patients with impaired glucose tolerance, the blockade of RAS with either ACE inhibitor or ARB has a significant preventive effect on the progression of Type II DM. It may be concluded from the finding of the present study that younger hypertensive patients (18-54 years) of either sex if found to be pre-diabetic may be administered ACEI or ARB as suitable for them. The treatment should be continued vigorously for one year and then it may be maintained to continue the beneficial effect.

The impact of mTOR inhibitors in the regression of left ventricular hypertrophy in elderly kidney transplant recipients.

End-stage kidney disease is frequently associated with left ventricular hypertrophy (LVH), a condition more prevalent in the elderly, that may increase mortality after renal transplantation (RTx). Previous studies suggested that mTOR inhibitors (mTORi) can improve LVH, but this has never been tested in elderly kidney transplant recipients. In this prospective randomized clinical trial, we analyzed the impact of Everolimus (EVL) on the reversal of LVH after RTx in elderly recipients (≥60 years) submitted to different immunosuppressive regimens: EVL/lowTacrolimus (EVL group, n=53) or mycophenolate sodium/regularTacrolimus (MPS group, n=47). Patients performed echocardiograms (Echo) up to 3 months after RTx and then annually. At baseline, mean age was 65±3 years in both groups and LVH was observed in 63.6% of patients in EVL group and in 61.8% of MPS group. Last Echo was performed at mean time of 47 and 49 months after RTx in EVL and MPS groups, respectively (P=.34). LVH regression was observed in 23.8% (EVL group) and 19% (MPS group) of patients (P=1.00). Mean eGFR, blood pressure, and use of RAS blockers were similar between groups throughout follow-up. EVL did not improve LVH in this cohort, and this lack of benefit may be attributed to concomitant use of TAC, senescence, or both.

TREATMENT WITH BLOCKERS OF THE RENIN-ANGIOTENSIN SYSTEM DOES NOT AFFECT RENAL FUNCTION IN PATIENTS WITH SEVERE COVID-19 ADMITTED TO INTENSIVE CARE UNIT

Objective: Patients with severe COVID-19 admitted to Intensive Care Units (ICU) are often challenging because of the complications related to co-existing diseases. Among these hypertension is highly prevalent and blockers of renin-angiotensin system (RAS-B) are frequently reported as home drug therapy. However the influence of these medications on renal function and mortality is matter of debate. Design and method: We retrospectively analyzed clinical data and drug treatment of 90 patients (F/M 25/65) admitted in our ICU for severe COVID-19, with lung disease severity expressed as pO2/fractional inspired oxygen (P/F) below 300 mmHg. In normotensive (n = 35) and hypertensive patients previously treated with (n = 35) or without (n = 20) RAS-B, we compared systolic and diastolic blood pressure (SBP and DBP, mmHg), serum creatinine (SC, mg/dl) and potassium (SK, mEq/L) baseline and SC peak values reached during the admission in ICU. Rate of renal replacement therapy (RRT) and mortality were also recorded. Results: Baseline mean SBP and DBP were within the normal limits and similar in normotensive and in both groups of hypertensive patients while P/F was 157 ± 71 in normotensives and 137 ± 64 vs. 94 ± 30 respectively in hypertensives with and without RAS-B. In the latter two groups, baseline, SC and SK were similar (respectively 1 ± 0.5 vs. 1 ± 0.8 and 4 ± 0.6 vs. 4 ± 0.6) and peak SC values were similar as well (respectively 1.74 ± 1.3 vs. 1.71 ± 1.7). Among the seven patients who needed RRT three and four respectively were on and off treatment with RAS-B. Overall mortality was slightly but not significantly higher in hypertensive than in normotensive patients (31/55, 56% and 15/35, 43%) but similar in those with and without RAS-B (19/35, 54% and 12/20, 60%). Conclusions: These preliminary data suggest that in patients with severe COVID-19 admitted to ICU, the use of RAS blockers for the treatment of hypertension prior to the infection does not affect renal function, the need of RRT and mortality.

ACEI and ARB Lower the Incidence of End-Stage Renal Disease among Patients with Diabetic Nephropathy: A Meta-analysis.

Objective This study explores the effects of Angiotensin-Converting Enzyme Inhibitors (ACEI) or Angiotensin Receptor Blockers (ARB) on the incidence of end-stage renal disease (ESRD) in diabetic nephropathy (DN) patients. Methods Literatures were searched in PubMed, Embase, Medline, CENTRAL, and CNKI databases. These literatures included a randomized controlled trial to evaluate the efficacy of ACEI and ARB among patients with DN. The endpoint event included the occurrence of ERSD. Risk ratio (RR) and 95% confidence interval (CI) were used to represent the combined effect size. A fixed-effect model was used to analyze if heterogeneity did not exist between literatures. If heterogeneity exists between literatures, a random-effect model was used to analyze. The source of heterogeneity was explored by subgroup analysis and sensitivity analysis. Results A total of 11 literatures were included in the study. The RR of ESRD was 0.79 (95% CI (0.79, 0.90), Z = 3.58, P = 0.0003) in the patients treated with RAS blockers compared with placebo, and there was no heterogeneity between studies (Chi2 = 5.09, P = 0.88, I2 = 0%). The funnel plot showed that the scatter point was biased to the left with publication bias. The RR of ESRD was 0.63 (95% CI (0.41, 0.95), Z = 2.18, P = 0.03) in the patients treated with ACEI compared with placebo. There was no heterogeneity between studies (Chi2 = 2.23, P = 0.95, I2 = 0%). Compared with placebo, RR of ESRD among patients with ARB intervention was 0.81 (95% CI (0.71, 0.93), Z = 3.00, P = 0.003). There was no heterogeneity between studies (Chi2 = 1.49, P = 0.48, I2 = 0%). Conclusion ACEI and ARB can reduce the risk of ESRD among diabetic nephropathy patients.

Dose Response Relationship of RAS Blockers and Beta-Blockers in Patients with Acute Heart Failure Syndrome: A Nationwide Prospective Cohort Study, on Behalf of KorAHF Investigators

<h3>Purpose</h3> It remains unclear if patients with acute heart failure syndrome (AHFS) need to reach the maximally tolerated doses of renin-angiotensin system blockers (RASBs) or beta-blockers (BBs) to obtain a survival benefit. This study evaluated the dose-response relationship between RASBs or BBs and survival in AHFS patients. <h3>Methods</h3> In total, 5,331 patients in the Korean Acute Heart Failure registry were analyzed based on the doses of RASBs and BBs at discharge. Also, an additional analysis of 4,613 patients with dosage information at the first post-discharge follow-up visit was done. Survival curves were constructed using the Kaplan-Meier method and compared using the log-rank test, and independent predictors of mortality were identified with the multivariable Cox proportional hazards model. <h3>Results</h3> In patients hospitalized with AHFS, RASB use at discharge was associated with a significant reduction in the risk of all-cause mortality. This effect was dose dependent for heart failure with reduced ejection fraction (HFrEF) but did not attain statistical significance for heart failure with preserved ejection fraction (HFpEF). BB use at discharge was associated with a reduction in all-cause mortality in HFrEF but not for HFpEF patients, although this was not dose dependent. At the first post-discharge follow-up visit, a significantly higher risk of all-cause mortality was associated with the maintenance or withdrawal of RASBs compared to up-titration of dose in HFrEF patients. <h3>Conclusion</h3> Using RASBs or BBs at discharge was associated with improved survival. A dose-response relationship between RASB and all-cause mortality was evident in AHFS patients with a reduced ejection fraction but not BBs. It is important to initiate and up-titrate RASBs to the maximally tolerated dose in AHFS patients during the transition period, especially for patients with a reduced ejection fraction.

Serum interleukin-6 levels predict kidney disease progression in diabetic nephropathy.

Inflammation is a main mechanism for the pathogenesis and progression of diabetic kidney disease (DKD). Interleukin-6 (IL-6) is an important inflammatory mediator that is suggested to be involved in the pathogenesis of DKD. The aim of our study was to evaluate the association between IL-6 levels and progression of DKD in patients with type 2 diabetes mellitus. Materials an methods: IL-6 levels were measured at baseline and after 4 and 12 months in 70 patients included in a multi-center, randomized controlled clinical trial designed to compare the effect of RAS blockers in monotherapy to dual blockade for slowing the progression of DKD. The primary composite endpoint was > 50% increase in baseline serum creatinine, end-stage kidney disease (ESKD), or death. The median follow-up was 36 months, during which 27 patients (38.6%) reached the primary endpoint. Baseline IL-6 levels correlated with TNF-α, C-reactive protein, and PTH levels. Survival analysis showed that patients with the highest IL-6 levels (> 4.84 pg/mL) reached the primary endpoint faster than the other two groups. Multivariate Cox regression analysis showed that baseline IL-6 levels > 4.84 pg/mL (HR 4.10, 95% CI 1.36 - 12.31) were a risk factor for reaching the primary endpoint adjusted for eGFR and proteinuria. Generalized linear mixed model analysis showed no effect on subsequent IL-6 levels either with RAS blockade monotherapy or dual blockade. These results suggest that treatment with RAS blockade does not influence IL-6 levels. IL-6 is independently associated with an increased risk for progression of DKD.

ARNI Pre-Operative Use and Vasoplegic Syndrome in Patients Undergoing Heart Transplantation or Left Ventricular Assist Device Surgery.

Background: Vasoplegic syndrome after orthotopic heart transplantation (OHT) or left ventricular assist device (LVAD) implantation is a rare but highly lethal syndrome with complex etiologies. The objective of this study was to assess if the preoperative use of sacubitril-valsartan combination is associated with an increased vasoplegic syndrome (VS) frequency after OHT or LVAD implantation and its relationship with 30-day mortality. Methods: A retrospective review of perioperative data, between January 2016 and December 2017, from 73 consecutive OHT and LVAD surgery adult patients at our institution was performed. VS was defined as normal cardiac output with persistent low systemic resistance requiring a norepinephrine intravenous perfusion > 0.5 µg/kg/min and the absence of sepsis or hemorrhagic shock within 48 h after surgery. Patients were all followed-up for adverse events and all-cause mortality at 30 days. Results: In our cohort of 73 patients (median age 51.7 years, 65% male patients), 25 (34%) patients developed VS. Twenty-two (30.1%) patients were on ARNI at the time of surgery, 31 (42.5%) were on other RAS blockers, 12 (16.4%) were on norepinephrine and 8 (11%) had no pre-operative drug. The pre-operative use of any vasoactive agent, was not significantly associated with VS (OR = 1.36; IC95% [0.78; 2.35]; p = 0.38). The pre-operative use of an ARNI compared to all other groups was not significantly associated with VS (OR = 2.0; IC95% [0.71; 5.62]; p = 0.19). The pre-operative use of an ARNI compared to other RAS blockers was also not significantly associated with VS (OR = 1.25; IC95% [0.37; 4.26]; p = 0.72). At 30 days, 18 (24.7%) patients had died. The pre-operative treatment with ARNI, or other RAS inhibitors was associated with a significantly lower rate of death compared to the absence of treatment (HR = 0.11; IC95% [0.02; 0.55]; p = 0.009 for ARNI and HR = 0.20; IC95% [0.06; 0.69]; p = 0.011 for other RASi). Conclusions: Preoperative use of sacubitril-valsartan was not significantly associated with development of vasoplegic syndrome in patients undergoing OHT or LVAD surgery. Furthermore, our data suggests a significant 30-day survival benefit with efficient renin-angiotensin blockade before surgery.

411-P: Fibroblast Growth Factor 23 and Diabetic Kidney Disease Phenotypes in Type 2 Diabetes

Fibroblast growth factor 23 (FGF23) targets tubular epithelial cells to promote phosphaturia and it has been associated with adverse outcomes in chronic kidney disease (CKD). Emerging data suggest that FGF23 plays a specific role in type 2 diabetes (T2D). We evaluated intact FGF23 (iFGF23) levels (plasma EDTA; chemiluminescence immunoassay) in 182 T2D subjects with no-DKD (n = 46), with albuminuria alone (ACR ≥30 mg/g; DKD stages 1-2, n = 48), with eGFR &amp;lt;60 ml/min/1.73m2 alone (Alb-DKD; n = 42) and with both albuminuria and eGFR &amp;lt;60 (Alb+DKD; n = 46). There was no difference in ACR between DKD stages 1-2 and Alb+DKD (97 [IQR 49-329] and 268 [62-736] mg/g); eGFR (CKD-EPI formula based on creatinine [eGFRcreat = 49 [45-54] and 45 [35-52] ml/min/1.73m2] or based on creatinine and cystatin-C) did not differ between Alb-DKD and Alb+DKD. Age, DD, HbA1c, triglycerides, uric acid and fibrinogen increased across DKD groups, while HDL cholesterol decreased, with no other significant difference in clinical and laboratory parameters. BP-lowering agents, RAS blockers and lipid-lowering drugs were slightly more frequent in albuminuric groups. Alb+DKD had the highest levels of inflammatory biomarkers: uric acid, hs-CRP and fibrinogen. In the whole cohort, iFGF23 was significantly and directly correlated with these 3 biomarkers. iFGF23 increased steeply (p&amp;lt;0.0001) across DKD groups (no DKD: 48.2 [IQR 37.3-61.5] pg/ml; DKD stages 1-2: 53.0 [42.5-61.4]; Alb-DKD: 60.4 [45.1-73.4] and Alb+DKD 76.6 [60.1-96.3]), with iFGF23 of Alb+DKD higher as compared to no-DKD (p&amp;lt;0.0001), DKD stages 1-2 (p&amp;lt;0.0001), and also Alb-DKD (p=0.008). In the whole cohort, iFGF23 was mildly associated with ACR (r = 0.260; p=0.001) and more strongly inversely related with eGFRcreat (r = -0.483, p&amp;lt;0.0001). Our results suggest that, for the same degree of eGFR reduction, higher iFGF23 levels in Alb+DKD as compared to Alb-DKD might be expression of more advanced renal damage and/or of an overwhelming inflammation. Disclosure M. Garofolo: Consultant; Self; Eli Lilly and Company. C. Pelosini: None. D. Lucchesi: None. P. Falcetta: None. M. Sessa: None. S. Del prato: Advisory Panel; Self; Eli Lilly and Company, Novo Nordisk, Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Speaker’s Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Merck Sharp &amp; Dohme Corp., Novartis Pharmaceuticals Corporation, Sanofi. G. Penno: Advisory Panel; Self; Eli Lilly and Company.

Acute heart failure: 24 hours blood pressure pattern correlates with left ventricular ejection fraction depression severity

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Ambulatory blood pressure monitoring (ABPM) is routinely used in hypertension patients. However, its importance in acute heart failure (AHF) patients has been scarcely mentioned. Purpose To analyze possible differences in 24 h BP pattern in patients with AHF and Moderate (VEF 45-30%) or Severe (VEF &amp;lt;30%) Ventricular Ejection Fraction Methods In 154 patients with AHF, an echocardiogram and a 24-hour Ambulatory Blood Pressure Measurement were performed. We comparatively study patients with moderate and severe left ventricular dysfunction (LVD) Results 154 patients (p) included in the study. The baseline characteristics of patients according to ventricular dysfunction: moderate: (82p 23.4% women, mean age 67.9, BMI 29.7 Kg / m2) versus Severe (72 p, 16.6% women, mean age 62 and BMI 30.6 Kg/m2). Prevalence (%) of hypertension (66 vs 56 (*)), diabetes (38.8 vs 34.1 (**)), and dyslipidemia (55.5 vs 31.7 (*),. Regarding the etiology : hypertensive (36.1 vs 31.7 (**)), ischemic (30.5 vs 21.9 (*)), and enolic (11.1 vs 7.3) (**)) were significantly higher ( * = p &amp;lt;.001) (** = p &amp;lt;.05) among patients with severe ventricular dysfunction. Despite the fact that patients with severe ventricular dysfunction received a higher percentage of drugs (p &amp;lt;0.001): RAS blockers, beta-blockers, loop diuretics, and antialdosteronics. The comparative results between patients with moderate and severe ventricular dysfunction: 24h BP (mmHg). Systolic (S): (114.4 (*) 110.8) and Diastolic (D): (64.7 (ns) 64.8); Daytime: PAS (116 (**) 108), and PAD (66 (ns) 66); Nocturnal SBP (111 (*) 108, and DBP (61 (NS) 61.5 mmHg) 24 h Pulse pressure (mmHg) (50 (*) 46) Variability BP systolic (mmHg): (15.3 (*) 12.9) Non-Dipper Patterns (%): 58.1 vs 50 (*); Riser: 19.4 vs. 27 (ns). (*) = P &amp;lt;0.05; (**) = p &amp;lt; 0.001 In the logistic regression analysis, increased risk for severe left ventricular dysfunction were found for: Mean BP &amp;lt; 80 mmHg (OR 2,82; CI 95% 1,104- 7,392) and male gender (OR :3,62, CI 1,130 – 9,447. After correction for confounding variables, such as number antihypertensive agents) Conclusions Patients with severe LVD showed lower 24 hours BP levels. Despite the use of greater number of antihypertensive agents, lower BP levels in these patients seem to be related mainly to functional left ventricular depression. In patients with AHF male gender and lower BP levels could be considered as a marker for severe left ventricular dysfunction.

Nocturnal hypertension in acute heart failure patients: 24 hours blood pressure pattern

Abstract Funding Acknowledgements Type of funding sources: None. Background It is well defined the prognosis value of the abnormalities in the circadian variation in hypertensive patients. In the phisiopathology of heart failure, neurohumoral mechanism plays an important role. Nevertheless, the circadian variation in nonhypertensive heart failure patients has not been well evaluated. Purpose Our aim was to evaluate 24-h blood pressure patterns and the prevalence of nocturnal hypertension in patients admitted with acute heart failure. Methods We studied 122 patients with a clinical diagnosis of AHF. We permormed a 24-h ambulatory blood pressure monitoring as well as an echocardiogram and anaytical test. Results 122 patients. Mean age: 63 ± 10. Males: 75%. Mean BMI: 30 ± 6 Kg/m2. Associated risk factors: 56,6% hypertension, 40 % dyslipidemia, 34,7% Diabetes, 29,3% obesity, 22,9% smoking. The etiology of HF: ischemic 41,2%;hypertensive 22,7%; dilated cardiomyopathy 20,9%;valvular 8,3%; others 6,9%.Therapeutic regimen applied: RAS blockers 93,4%; betablockers 85,7%; loop diuretic 81%; spironolactone 42,3%; statins 68,4%; antiplatelet/anticoagulant drugs 89%. The 24 h ABPM measurements are in table 1 The majority of AHF patients (80,4%) have an abnormal pattern of ABPM: Dipper 19,6%, non-dipper 51,1%, riser 0%.The prevalence of nocturnal hypertension was 22,8%. Conclusions In our area, AHF patients have optimal control of BP , however, the normal circadian variation in blood pressure is altered in most of them. In addition, nocturnal hypertension is very common in heart failure patients. Ambulatory blood pressure monitoring may be helpful in identified this altered patterns (which could be unrecognized) and may be used to optimise heart failure therapy, and could be a prognosis marker in this patient group. Table 124 hoursDaytimeNightimeSysolic BP107,7 ± 13,8109,6 ± 14,2104,5 ± 14,5Diastolic BP64,4 ± 7,866,4 ± 8,860,4 ± 7,6