The Effect of Atrasentan on Kidney and Heart Failure Outcomes by Baseline Albuminuria and Kidney Function

2021 ◽  
pp. CJN.07340521
Author(s):  
Simke W. Waijer ◽  
Ron T. Gansevoort ◽  
George L. Bakris ◽  
Ricardo Correa-Rotter ◽  
Fan-Fan Hou ◽  
...  
Keyword(s):  
Heart Failure ◽  
Diabetic Nephropathy ◽  
Relative Risk ◽  
Confidence Interval ◽  
Kidney Failure ◽  
Absolute Risk ◽  
Hazard Ratio ◽  
Baseline Risk ◽  
Heart Failure Hospitalization ◽  
Clinical Trial Registry

Background and objectivesAtrasentan reduces the risk of kidney failure but increases the risk of edema and, possibly, heart failure. Patients with severe CKD may obtain greater absolute kidney benefits from atrasentan but may also be at higher risk of heart failure. We assessed relative and absolute effects of atrasentan on kidney and heart failure events according to baseline eGFR and urinary albumin-creatinine ratio (UACR) in a post hoc analysis of the Study of Diabetic Nephropathy with Atrasentan (SONAR) trial.Design, setting, participants, & measurementsThe effect of atrasentan versus placebo in 3668 patients with type 2 diabetes and CKD with elevated albuminuria was examined in the SONAR trial. We used Cox proportional hazards regression analysis to study effects on the primary kidney outcome (composite of doubling of serum creatinine, kidney failure, or kidney death) and heart failure hospitalization across subgroups of eGFR (<30, ≥30–45, and ≥45 ml/min per 1.73 m2) and UACR (<1000, ≥1000–3000, and ≥3000 mg/g).ResultsAtrasentan reduced the relative risk of the primary kidney outcome (hazard ratio, 0.71; 95% confidence interval, 0.58 to 0.88) consistently across all subgroups of baseline eGFR and UACR (all P interaction >0.21). Patients in the highest UACR and lowest eGFR subgroups, in whom rates of the primary kidney outcome were highest, showed the largest absolute benefit (all P interaction <0.01). The risk of heart failure hospitalization was higher in the atrasentan group (hazard ratio, 1.39; 95% confidence interval, 0.97 to 1.99) and was consistent across subgroups, with no evidence that relative or absolute risks differed across eGFR or UACR subgroups (all P interaction >0.09).ConclusionsAtrasentan reduced the relative risk of the primary kidney outcome consistently across baseline UACR and eGFR subgroups. The absolute risk reduction was greater among patients in the lowest eGFR and highest albuminuria category who were at highest baseline risk. Conversely, the relative and absolute risks of heart failure hospitalization were similar across baseline UACR and eGFR subgroups.Clinical Trial registry name and registration number: Study of Diabetic Nephropathy with Atrasentan (SONAR), NCT01858532

scholarly journals Mortality and Access to Kidney Transplantation in Patients with Sickle Cell Disease–Associated Kidney Failure

2021 ◽  
pp. CJN.02720320
Author(s):  
Sunjae Bae ◽  
Morgan Johnson ◽  
Allan B. Massie ◽  
Xun Luo ◽  
Carlton Haywood ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Sickle Cell Disease ◽  
Confidence Interval ◽  
Sickle Cell ◽  
Kidney Failure ◽  
Absolute Risk ◽  
Hazard Ratio ◽  
Cell Disease ◽  
Control Groups ◽  
And Control

Background and objectivesPatients with sickle cell disease–associated kidney failure have high mortality, which might be lowered by kidney transplantation. However, because they show higher post-transplant mortality compared with patients with other kidney failure etiologies, kidney transplantation remains controversial in this population, potentially limiting their chance of receiving transplantation. We aimed to quantify the decrease in mortality associated with transplantation in this population and determine the chance of receiving transplantation with sickle cell disease as the cause of kidney failure as compared with other etiologies of kidney failure.Design, setting, participants, & measurementsUsing a national registry, we studied all adults with kidney failure who began maintenance dialysis or were added to the kidney transplant waiting list in 1998–2017. To quantify the decrease in mortality associated with transplantation, we measured the absolute risk difference and hazard ratio for mortality in matched pairs of transplant recipients versus waitlisted candidates in the sickle cell and control groups. To compare the chance of receiving transplantation, we estimated hazard ratios for receiving transplantation in the sickle cell and control groups, treating death as a competing risk.ResultsCompared with their matched waitlisted candidates, 189 transplant recipients with sickle cell disease and 220,251 control recipients showed significantly lower mortality. The absolute risk difference at 10 years post-transplant was 20.3 (98.75% confidence interval, 0.9 to 39.8) and 19.8 (98.75% confidence interval, 19.2 to 20.4) percentage points in the sickle cell and control groups, respectively. The hazard ratio was also similar in the sickle cell (0.57; 95% confidence interval, 0.36 to 0.91) and control (0.54; 95% confidence interval, 0.53 to 0.55) groups (interaction P=0.8). Nonetheless, the sickle cell group was less likely to receive transplantation than the controls (subdistribution hazard ratio, 0.73; 95% confidence interval, 0.61 to 0.87). Similar disparities were found among waitlisted candidates (subdistribution hazard ratio, 0.62; 95% confidence interval, 0.53 to 0.72).ConclusionsPatients with sickle cell disease–associated kidney failure exhibited similar decreases in mortality associated with kidney transplantation as compared with those with other kidney failure etiologies. Nonetheless, the sickle cell population was less likely to receive transplantation, even after waitlist registration.

scholarly journals Fibroblast Growth Factor 23 and Incident Cardiovascular Disease and Mortality in Middle‐Aged Adults

2021 ◽  
Author(s):  
Shejuti Paul ◽  
Mandy Wong ◽  
Ehimare Akhabue ◽  
Rupal C. Mehta ◽  
Holly Kramer ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiovascular Disease ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 23 ◽  
Hazard Ratio ◽  
Fibroblast Growth ◽  
Heart Failure Hospitalization ◽  
Middle Aged ◽  
Middle Aged Adults

Background Higher circulating fibroblast growth factor 23 (FGF23) associates with greater risk of cardiovascular disease (CVD) and mortality in older adults. The association of FGF23 with cardiovascular outcomes in younger populations has been incompletely explored. Methods and Results We measured C‐terminal FGF23 (cFGF23) and intact FGF23 (iFGF23) in 3151 middle‐aged adults (mean age, 45±4) who participated in the year 20 examination of the CARDIA (Coronary Artery Risk Development in Young Adults) study. We used separate Cox proportional hazards models to examine the associations of cFGF23 and iFGF23 with incident CVD and mortality, adjusting models sequentially for sociodemographic, clinical, and laboratory factors. A total of 157 incident CVD events and 135 deaths occurred over a median 7.6 years of follow‐up (interquartile range, 4.1–9.9). In fully adjusted models, there were no statistically significant associations of FGF23 with incident CVD events (hazard ratio per doubling of cFGF23: 1.14, 95%CI 0.97,1.34; iFGF23: 0.76, 95%CI 0.57,1.02) or all‐cause mortality (hazard ratio per doubling of cFGF23, 1.17; 95% CI, 1.00–1.38; iFGF23, 0.86; 95% CI, 0.64–1.17). In analyses stratified by CVD subtypes, higher cFGF23 was associated with greater risk of heart failure hospitalization (hazard ratio per doubling of cFGF23, 1.52; 95% CI, 1.18–1.96) but not coronary heart disease or stroke, whereas iFGF23 was not associated with CVD subtypes in any model. Conclusions In middle‐aged adults with few comorbidities, higher cFGF23 and iFGF23 were not independently associated with greater risk of CVD events or death. Higher cFGF23 was independently associated with greater risk of heart failure hospitalization.

scholarly journals Exercise-based cardiac rehabilitation in patients with reduced left ventricular ejection fraction: The Cardiac Rehabilitation Outcome Study in Heart Failure (CROS-HF): A systematic review and meta-analysis

2019 ◽  
Vol 27 (9) ◽  
pp. 929-952 ◽  
Author(s):  
Birna Bjarnason-Wehrens ◽  
R Nebel ◽  
K Jensen ◽  
M Hackbusch ◽  
M Grilli ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Heart Failure ◽  
Relative Risk ◽  
Left Ventricular Ejection Fraction ◽  
Confidence Interval ◽  
Cardiac Rehabilitation ◽  
Left Ventricular ◽  
Left Ventricular Ejection

Background In heart failure with reduced left ventricular ejection fraction (HFrEF) patients the effects of exercise-based cardiac rehabilitation on top of state-of-the-art pharmacological and device therapy on mortality, hospitalization, exercise capacity and quality-of-life are not well established. Design The design of this study involved a structured review and meta-analysis. Methods Evaluation of randomised controlled trials of exercise-based cardiac rehabilitation in HFrEF-patients with left ventricular ejection fraction ≤40% of any aetiology with a follow-up of ≥6 months published in 1999 or later. Results Out of 12,229 abstracts, 25 randomised controlled trials including 4481 HFrEF-patients were included in the final evaluation. Heterogeneity in study population, study design and exercise-based cardiac rehabilitation-intervention was evident. No significant difference in the effect of exercise-based cardiac rehabilitation on mortality compared to control-group was found (hazard ratio 0.75, 95% confidence interval 0.39–1.41, four studies; 12-months follow-up: relative risk 1.29, 95% confidence interval 0.66–2.49, eight studies; six-months follow-up: relative risk 0.91, 95% confidence interval 0.26–3.16, seven studies). In addition there was no significant difference between the groups with respect to ‘hospitalization-for-any-reason’ (12-months follow-up: relative risk 0.79, 95% confidence interval 0.41–1.53, four studies), or ‘hospitalization-due-to-heart-failure’ (12-months follow-up: relative risk 0.59, 95% confidence interval 0.12–2.91, four studies; six-months follow-up: relative risk 0.84, 95% confidence interval 0.07–9.71, three studies). All studies show improvement of exercise capacity. Participation in exercise-based cardiac rehabilitation significantly improved quality-of-life as evaluated with the Kansas City Cardiomyopathy Questionnaire: (six-months follow-up: mean difference 1.94, 95% confidence interval 0.35–3.56, two studies), but no significant results emerged for quality-of-life measured by the Minnesota Living with Heart Failure Questionnaire (nine-months or more follow-up: mean difference –4.19, 95% confidence interval –10.51–2.12, seven studies; six-months follow-up: mean difference –5.97, 95% confidence interval –16.17–4.23, four studies). Conclusion No association between exercise-based cardiac rehabilitation and mortality or hospitalisation could be observed in HFrEF patients but exercise-based cardiac rehabilitation is likely to improve exercise capacity and quality of life.

scholarly journals Higher Acceleration/Ejection Time Ratio Predicts Impaired Outcome in Aortic Valve Stenosis

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Eigir Einarsen ◽  
Dana Cramariuc ◽  
Edda Bahlmann ◽  
Helga Midtbo ◽  
John B. Chambers ◽  
...  
Keyword(s):  
Heart Failure ◽  
Aortic Valve ◽  
Ejection Fraction ◽  
Aortic Valve Stenosis ◽  
Cardiovascular Death ◽  
Left Ventricular ◽  
Hazard Ratio ◽  
Left Ventricular Ejection ◽  
Heart Failure Hospitalization ◽  
Ejection Time

Background: Acceleration time (AT)/ejection time (ET) ratio is a marker of aortic valve stenosis (AS) severity and predicts outcome in moderate-severe AS. Methods: We explored the association of increased AT/ET ratio on prognosis in 1530 asymptomatic patients with presumably mild-moderate AS, normal ejection fraction, and without known diabetes or cardiovascular disease. Patients were part of the SEAS study (Simvastatin Ezetimibe Aortic Stenosis). Patients were grouped according to the optimal AT/ET ratio threshold to predict cardiovascular death and heart failure hospitalization. Low-gradient severe AS was identified as combined valve area ≤1.0 cm 2 and mean gradient <40 mm Hg. Outcome was assessed in Cox regression analyses, and results are reported as hazard ratio and 95% CI. Results: Higher AT/ET ratio was significantly associated with lower systolic blood pressure, lower left ventricular ejection fraction, lower stress-corrected midwall shortening, low flow, and with higher left ventricular mass and higher peak aortic jet velocity. AT/ET ratio ≥0.32 provided the optimal cutoff for predicting incident cardiovascular death and heart failure hospitalization in the total study sample. In patients with low-gradient severe AS, this threshold was >0.32. AT/ET ratio ≥0.32 had a 79% higher risk of cardiovascular death and heart failure hospitalization (hazard ratio, 1.79 [95% CI, 1.20–2.68]). In patients with low-gradient severe AS, AT/ET ratio >0.32 was associated with a 2-fold higher risk of cardiovascular death and heart failure hospitalization (hazard ratio, 2.15 [95% CI, 1.22–3.77]). Conclusions: In asymptomatic nonsevere AS and low-gradient severe AS, higher AT/ET ratio was associated with increased cardiovascular morbidity and mortality. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT00092677.

scholarly journals The impact of frailty and aging on prognosis in patients with heart failure with preserved ejection fraction – insights from PURSUIT-HFpEF registry

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Okada ◽  
K Inoue ◽  
T Onishi ◽  
K Iwakura ◽  
T Yamada ◽  
...  
Keyword(s):  
Heart Failure ◽  
Confidence Interval ◽  
Ejection Fraction ◽  
Hazard Ratio ◽  
Adverse Outcomes ◽  
Funding Source ◽  
Preserved Ejection Fraction ◽  
Clinical Endpoint ◽  
Patients With Heart Failure

Abstract Introduction Frailty and aging are two common conditions both associated with increased vulnerability to stressful events with high risk of adverse outcomes. Purpose To evaluate the association between frailty and aging and their impacts on clinical outcome in patients with heart failure with preserved ejection fraction (HFpEF). Methods Analysis was performed from a prospective multicenter observational registry for HFpEF (PURSUIT-HFpEF Registry) conducted in the Osaka region of Japan. A total of 757 patients hospitalized for acute heart failure (diagnosed by using Framingham criteria) met the inclusion criteria: a left ventricular ejection fraction ≥50% and brain natriuretic peptide ≥100pg/ml. We included 483 patients (age, 80±9 years; men, 45%; atrial fibrillation, 35%) whose follow-up data after survival discharge were available. Patients' frailty and aging were evaluated using the clinical frailty scale (CFS) and age quartiles (Q1: &lt;76 years (n=122), Q2: 76–82 years (n=111), Q3: 82–87 years (n=127), Q4: &gt;87 years (n=123)), respectively. The primary clinical endpoint was defined as the composite of death, re-hospitalization for heart failure, and cerebrovascular accident. Results The median (interquartile range) CFS rating was 3 (2–5), and there was a little correlation between CFS rating and age (r2=0.16, p&lt;0.001). The prevalence of frailty, defined as a CFS rating &gt;4 (n=132), was positively correlated with age quartiles (Q1: 9.0%, Q2: 21.4%, Q3: 29.9%, Q4: 48.0%, p&lt;0.001). During the median follow-up period 396 days (interquartile range, 344–698) after discharge, the clinical endpoint was observed in 172 patients. The incidence was higher in patients with frailty than those without it (49.6% vs. 30.4%, log-rank p&lt;0.001). It was also correlated with age quartiles (Q1: 23.0%, Q2: 34.2%, Q3: 36.2%, Q4: 48.8%, log-rank p=0.001). Multivariate Cox regression analysis revealed that frailty (hazard ratio, 1.52; 95% confidence interval, 1.09–2.10; p=0.013) and age (hazard ratio per quartile increase, 1.24; 95% confidence interval, 1.07–1.43; p=0.004) were both associated with the clinical endpoint. Subgroup analysis in 352 patients without frailty also revealed the significant impact of age on the endpoint (1.26; 1.06–1.51; p=0.008). However, in 131 patients with frailty, there was no significant impact of age on the endpoint (1.16; 0.90–1.51; p=0.25). Conclusions Frailty was common and was associated with aging in HFpEF patients. Although they were both associated with unfavorable events, aging was no longer a significant predictor of adverse outcomes under the frailty conditions. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Roche Diagnostics K.K. and Fuji Film Toyama Chemical Co. Ltd.

scholarly journals Left ventricular longitudinal shortening at cardiac base as a determinant of left atrial reservoir function in cardiac amyloidosis

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
K Inoue ◽  
Y Nakao ◽  
M Saito ◽  
M Kinoshita ◽  
R Higaki ◽  
...  
Keyword(s):  
Heart Failure ◽  
Left Atrial ◽  
Cardiac Amyloidosis ◽  
Longitudinal Strain ◽  
Left Ventricular ◽  
Male Gender ◽  
Hazard Ratio ◽  
Heart Failure Hospitalization ◽  
Reservoir Function ◽  
Lv Ejection Fraction

Abstract Objective To investigate a mechanistic determinant of left atrial (LA) reservoir function in patients presenting left ventricular (LV) hypertrophy, and clarify diagnostic and prognostic values of LA reservoir strain in patients with cardiac amyloidosis (CA). Methods Three-hundred sixty patients (median age: 68 years, male gender: 65%) with left ventricular hypertrophy (LVH) assessed by echocardiography were retrospectively included. The LVH etiologies were diagnosed by any of biopsy, cardiac magnetic resonance imaging or 99mTc-PYP scintigraphy. LV segmental longitudinal strain was estimated from apical three views, and LA reservoir strain was measured from an apical 4-chamber view. Results The LVH etiologies were confirmed with CA in 81 patients, hypertensive heart disease in 87 patients, hypertrophic cardiomyopathy in 143 patients, and miscellaneous disorders in 49 patients. The median (25th, 75th percentile) value of LV ejection fraction was 59% (48–67). LV basal longitudinal strain and LA reservoir strain were significantly reduced in patients with CA compared with those with other etiologies; LV basal strain: 5.4% (3.9–8.7) vs. 11.9% (9.3–14.6), LA reservoir strain: 9.2% (6.3–12.3) vs. 17.5% (11.3–24.1), p&lt;0.01 respectively. LV basal strain was significantly correlated with LA reservoir strain in patients with CA (r=0.57, p&lt;0.01) and in those with other etiologies (r=0.45, p&lt;0.01). The area under the receiver-operating characteristic curves of LA reservoir strain and E/e' (0.78 and 0.74) to identify CA etiology were significantly larger than that of LA volume index (0.62) (p&lt;0.01). During the follow-up period (median 2.9 years), 53 patients experienced heart failure hospitalization. The Cox regression model including age, gender, LV ejection fraction, E/e' and LA reservoir strain showed that male gender (hazard ratio: 0.46, p=0.03), E/e' (hazard ratio: 1.04, p&lt;0.01) and LA reservoir strain (hazard ratio: 0.94, p&lt;0.01) independently predicted heart failure hospitalization. Conclusions The decrease of LV longitudinal shortening at cardiac base could worsen LA reservoir function especially in patients with CA. LA reservoir strain might be an alternative measure to identify CA etiology and have a predictive value of heart failure hospitalization in patients with LV hypertrophy. FUNDunding Acknowledgement Type of funding sources: None.

scholarly journals Expression of B2 Receptor on Circulating CD34-Positive Cells and Outcomes of Myocardial Infarction

2019 ◽  
Vol 2019 ◽  
pp. 1-7
Author(s):  
Cong Fu ◽  
Yuhan Cao ◽  
Yuyu Yao ◽  
Shengxing Tang ◽  
Qun Fan ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Confidence Interval ◽  
Hazard Ratio ◽  
Cell Surface Receptor ◽  
Kaplan Meier ◽  
Surface Receptor ◽  
Poor Outcomes ◽  
Low Expression

Background. Bradykinin B2 receptor (B2R) is a widely expressed cell surface receptor. The relationship between B2R expression on circulating CD34+ cells and prognosis of myocardial infarction remains unknown.Methods. We analyzed the expression of B2R on circulating CD34-positive cells and plasma VEGF concentration in 174 myocardial infarction patients. All involved patients were divided into two groups: high B2R group and low B2R group according to the median B2R expression percentage. 48 months of follow-up was performed. The endpoints were heart failure and revascularization.Results. The plasma level of VEGF in the low B2R group is67±12 pg/mL, whereas the high B2R group has significantly elevated VEGF levels of145±27 pg/mL(P<0.001). The concentration of VEGF has correlated with expression of B2R (r=0.574,P<0.001). During the 48 months of follow-up, low expression of B2 receptor on circulating CD34-positive cells indicates the high incidence of heart failure (hazard ratio: 2.247; 95% confidence interval: 1.110-4.547;P=0.024) and revascularization (hazard ratio: 2.335; 95% confidence interval: 1.075-5.074;P=0.032). Kaplan-Meier survival analysis showed that the cumulative hazard of heart failure (P=0.014) and revascularization (P=0.032) has significant differences between low B2R and high B2R.Conclusion. Low expression of B2R on circulating progenitor cells indicated the poor outcomes of myocardial infarction.

P920The impact of tricuspid regurgitation on patient outcome in early and late heart failure

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
J X Fang ◽  
H F Tse ◽  
K H Yiu
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Cardiovascular Event ◽  
Tricuspid Regurgitation ◽  
Goodness Of Fit ◽  
Major Adverse Cardiovascular Event ◽  
Hazard Ratio ◽  
Heart Failure Hospitalization ◽  
Adverse Cardiovascular Event ◽  
Goodness Of Fit Test

Abstract Background Severe tricuspid regurgitation (TR) is associated with poor outcome, but TR remains poorly understood and under-treated. Purpose To examine the impact of TR at different stages of heart failure. Methods 3275 patients with outpatient echocardiogram done at our Hospital in 2013–15 with a mean follow-up of 1092 days were analyzed retrospectively. TR was graded by a semi-quantitative approach using jet-area on multiple views and inferior vena cava (IVC) flow pattern. Multivariate Cox proportional hazard model assessed for mortality, time-to-first heart failure hospitalization, and major adverse cardiovascular event in 3 years. Results were adjusted for age, sex, left ventricular ejection fraction (LVEF), left atrial enlargement, pre-existing cardiovascular, peripheral vascular and cerebrovascular disease, moderate-to-severe aortic or mitral valve disease, pulmonary hypertension, diabetes, chronic kidney disease, chronic obstructive pulmonary disease, malignancy, and heart failure stages (0=no heart failure, A=risk factor present, B=structural abnormality, C=symptomatic D=advanced). Subgroup analysis stratified by heart failure stage 0, stage A/B and stage C/D was done. Kaplan-Meier function, log-rank test, logistic regression, AURUC, and goodness-of-fit test were done. Results In patients with stage A-B heart failure, severe TR had a hazard ratio of 2.93 for death in 3 years compared to no TR (95% CI 1.11–7.73, p=0.03) and moderate TR had a hazard ratio of 2.35 (95% CI 1.28–4.31, P=0.006). In stage C/D, severe TR had a hazard ratio of 2.17 (95% CI 1.12–4.16, p=0.02) and moderate TR had no significant effect (hazard ratio 1.09, p=077). For heart failure hospitalization, severe TR had no significant association in stage A/B but had a hazard ratio of 3.74 in stage C/D (95% CI 1.81–7.7, p<0.001). TR had no impact on major adverse cardiovascular event in this model. No significant interaction was found between TR and heart failure stage, ejection fraction, and valvular heart disease. The model had C-statistics of 0.82 for 3-year mortality, 0.90 for heart failure hospitalization, and 0.81 for MACE, with insignificant Hosmer-Lemeshow goodness-of-fit test p for each, indicating good fit. Conclusion The association between TR and increased mortality in heart failure is apparent early and attenuated later, whereas that of TR and heart failure symptom decompensation appears late. Acknowledgement/Funding None

Nocturnal Systolic Hypertension and Adverse Prognosis in Patients with CKD

2021 ◽  
pp. CJN.14420920
Author(s):  
Qin Wang ◽  
Yu Wang ◽  
Jinwei Wang ◽  
Luxia Zhang ◽  
Ming-Hui Zhao ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Kidney Failure ◽  
Cardiovascular Events ◽  
Systolic Hypertension ◽  
Cox Regression ◽  
Cardiovascular Outcomes ◽  
Hazard Ratio ◽  
Adverse Outcomes ◽  
Nocturnal Hypertension ◽  
Diastolic Hypertension

Background and objectivesNocturnal hypertension is associated with adverse outcomes in patients with CKD. However, the individual association of entities of nocturnal hypertension according to achievement of systolic and/or diastolic BP goals with kidney failure and cardiovascular outcomes of CKD is not clear.Design, setting, participants, & measurementsOur study analyzed data from participants in the Chinese Cohort Study of Chronic Kidney Disease. Nocturnal hypertension was categorized into three entities: isolated nocturnal diastolic hypertension with diastolic BP ≥70 mm Hg and systolic BP <120 mm Hg, isolated nocturnal systolic hypertension with systolic BP ≥120 mm Hg and diastolic BP <70 mm Hg, and nocturnal systolic-diastolic hypertension with both systolic BP ≥120 mm Hg and diastolic BP ≥70 mm Hg. Associations of nocturnal hypertension entities with kidney failure and cardiovascular outcomes were evaluated by Cox regression.ResultsIn total, 2024 patients with CKD stages 1–4 were included in our analysis (mean age, 49±14 years; 57% men; eGFR=51±29 ml/min per 1.73 m2; proteinuria: 0.9 [0.4–2.1] g/d). Among them, 1484 (73%) patients had nocturnal hypertension, with the proportions of 26%, 8%, and 66% for isolated nocturnal diastolic hypertension, isolated nocturnal systolic hypertension, and nocturnal systolic-diastolic hypertension, respectively. Three hundred twenty kidney events and 148 cardiovascular events were recorded during median follow-up intervals of 4.8 and 5.0 years for kidney and cardiovascular events, respectively. After adjustment, isolated nocturnal systolic hypertension was associated with a higher risk for cardiovascular events (hazard ratio, 3.17; 95% confidence interval, 1.61 to 6.23). Nocturnal systolic-diastolic hypertension showed a higher risk for both kidney failure (hazard ratio, 1.71; 95% confidence interval, 1.17 to 2.49) and cardiovascular outcomes (hazard ratio, 2.19; 95% confidence interval, 1.24 to 3.86). No association was observed between isolated nocturnal diastolic hypertension with either kidney failure or cardiovascular events.ConclusionsNocturnal systolic hypertension, either alone or in combination with diastolic hypertension, is associated with higher risks for adverse outcomes in patients with CKD.

Efficacy and Safety of Mineralocorticoid Receptor Antagonists in Kidney Failure Patients Treated with Dialysis: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 16 (6) ◽  
pp. 916-925 ◽  
Author(s):  
Kuan-Ting Chen ◽  
Yi-No Kang ◽  
Yen-Chung Lin ◽  
I-Lin Tsai ◽  
Wei-Chiao Chang ◽  
...  
Keyword(s):  
Relative Risk ◽  
Confidence Interval ◽  
Kidney Failure ◽  
Mineralocorticoid Receptor ◽  
Meta Analysis ◽  
Left Ventricular ◽  
Efficacy And Safety ◽  
Mineralocorticoid Receptor Antagonists ◽  
Receptor Antagonists ◽  
Randomized Controlled

Background and objectivesPatients with kidney failure have a high risk of cardiovascular disease due to cardiac remodeling, left ventricular fibrosis, and hyperaldosteronism, all of which can be potentially mitigated by mineralocorticoid receptor antagonists. However, because of the fear of hyperkalemia, the use of mineralocorticoid receptor antagonists in patients with kidney failure is limited in current clinical practice, and few studies have investigated the efficacy and safety. Thus, we aimed to determine the benefits and side effects of mineralocorticoid receptor antagonists in patients with kidney failure treated with dialysis.Design, setting, participants, & measurementsThis is a systematic review and meta-analysis of randomized controlled trials published from 2005 to 2020 that compared the effect of mineralocorticoid receptor antagonists with either placebo or no treatment in patients with kidney failure. Two reviewers independently searched the PubMed, EMBASE, and Cochrane databases for all published studies, extracted data, assessed the risk of bias, and rated the quality of evidence. A meta-analysis was conducted on 14 eligible randomized controlled trials, and a total of 1309 patients were included.ResultsHigh-quality evidence suggested that mineralocorticoid receptor antagonists are associated with lower cardiovascular mortality (relative risk, 0.41; 95% confidence interval, 0.24 to 0.70; P=0.001) and all-cause mortality (relative risk, 0.44; 95% confidence interval, 0.30 to 0.66; P<0.001), and the risk of hyperkalemia was comparable with that of control group (relative risk, 1.12; 95% confidence interval, 0.91 to 1.36; P=0.29). However, no significant decrease in nonfatal cardiovascular events and stroke was observed, and there was no significant improvement in BP or cardiac performance parameters, including left ventricular ejection fraction and left ventricular mass index.ConclusionsOur meta-analysis suggests that mineralocorticoid receptor antagonists might improve clinical outcomes of patients with kidney failure without significant increase in the risk of hyperkalemia.

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