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Background There are limited data on the management strategies, temporal trends and clinical outcomes of patients who present with non–ST‐segment–elevation myocardial infarction and have a prior history of CABG. Methods and Results We identified 287 658 patients with non–ST‐segment–elevation myocardial infarction between 2010 and 2017 in the United Kingdom Myocardial Infarction National Audit Project database. Clinical and outcome data were analyzed by dividing into 2 groups by prior history of coronary artery bypass grafting (CABG): group 1, no prior CABG (n=262 362); and group 2, prior CABG (n=25 296). Patients in group 2 were older, had higher GRACE (Global Registry of Acute Coronary Events) risk scores and burden of comorbid illnesses. More patients underwent coronary angiography (69% versus 63%) and revascularization (53% versus 40%) in group 1 compared with group 2. Adjusted odds of receiving inpatient coronary angiogram (odds ratio [OR], 0.91; 95% CI, 0.88–0.95; P P P =0.44), all‐cause mortality (OR, 0.96; 95% CI, 0.88–1.04; P =0.31), reinfarction (OR, 1.02; 95% CI, 0.89–1.17; P =0.78), and major bleeding (OR, 1.01; 95% CI, 0.90–1.11; P =0.98) were similar across groups. Lower adjusted risk of inpatient mortality (OR, 0.67; 95% CI, 0.46–0.98; P =0.04) but similar risk of bleeding (OR,1.07; CI, 0.79–1.44; P =0.68) and reinfarction (OR, 1.13; 95% CI, 0.81–1.57; P =0.47) were observed in group 2 patients who underwent percutaneous coronary intervention compared with those managed medically. Conclusions In this national cohort, patients with non–ST‐segment–elevation myocardial infarction with prior CABG had a higher risk profile, but similar risk‐adjusted in‐hospital adverse outcomes compared with patients without prior CABG. Patients with prior CABG who received percutaneous coronary intervention had lower in‐hospital mortality compared with those who received medical management.

Background Proteinuria and glomerular segmental fibrosis are inevitable complications of diabetic nephropathy though their mechanisms are poorly understood. Understanding the clinical characteristics and pathogenesis of proteinuria and glomerular segmental fibrosis in diabetic nephropathy is, therefore, urgently needed for patient management of this severe disease. Methods and Results Diabetes mellitus was induced in podocyte‐specific glucocorticoid receptor knockout (GR PKO ) mice and control littermates by administration of streptozotocin. Primary podocytes were isolated and subjected to analysis of Wnt signaling and fatty acid metabolism. Conditioned media from primary podocytes was transferred to glomerular endothelial cells. Histologic analysis of kidneys from diabetic GR PKO mice showed worsened fibrosis, increased collagen deposition, and glomerulomegaly indicating severe glomerular fibrosis. Higher expression of transforming growth factor‐βR1 and β‐catenin and suppressed expression of carnitine palmitoyltransferase 1A in nephrin‐positive cells were found in the kidneys of diabetic GR PKO mice. Podocytes isolated from diabetic GR PKO mice demonstrated significantly higher profibrotic gene expression and suppressed fatty acid oxidation compared with controls. Administration of a Wnt inhibitor significantly improved the fibrotic features in GR PKO mice. The glomerular endothelium of diabetic GR PKO mice demonstrated the features of endothelial‐to‐mesenchymal transition. Moreover, endothelial cells treated with conditioned media from podocytes lacking GR showed increased expression of α‐smooth muscle actin, transforming growth factor‐βR1 and β‐catenin levels. Conclusions These data demonstrate that loss of podocyte GR leads to upregulation of Wnt signaling and disruption in fatty acid metabolism. Podocyte–endothelial cell crosstalk, mediated through GR, is important for glomerular homeostasis, and its disruption likely contributes to diabetic nephropathy.

Background Emerging evidence links acute kidney injury (AKI) in patients with COVID‐19 with higher mortality and respiratory morbidity, but the relationship of AKI with cardiovascular disease outcomes has not been reported in this population. We sought to evaluate associations between chronic kidney disease (CKD), AKI, and mortality and cardiovascular outcomes in patients hospitalized with COVID‐19. Methods and Results In a large multicenter registry including 8574 patients with COVID‐19 from 88 US hospitals, data were collected on baseline characteristics and serial laboratory data during index hospitalization. Primary exposure variables were CKD (categorized as no CKD, CKD, and end‐stage kidney disease) and AKI (classified into no AKI or stages 1, 2, or 3 using a modification of the Kidney Disease Improving Global Outcomes guideline definition). The primary outcome was all‐cause mortality. The key secondary outcome was major adverse cardiac events, defined as cardiovascular death, nonfatal stroke, nonfatal myocardial infarction, new‐onset nonfatal heart failure, and nonfatal cardiogenic shock. CKD and end‐stage kidney disease were not associated with mortality or major adverse cardiac events after multivariate adjustment. In contrast, AKI was significantly associated with mortality (stage 1 hazard ratio [HR], 1.72 [95% CI, 1.46–2.03]; stage 2 HR, 1.83 [95% CI, 1.52–2.20]; stage 3 HR, 1.69 [95% CI, 1.44–1.98]; versus no AKI) and major adverse cardiac events (stage 1 HR, 2.17 [95% CI, 1.74–2.71]; stage 2 HR, 2.70 [95% CI, 2.07–3.51]; stage 3 HR, 3.06 [95% CI, 2.52–3.72]; versus no AKI). Conclusions This large study demonstrates a significant association between AKI and all‐cause mortality and, for the first time, major adverse cardiovascular events in patients hospitalized with COVID‐19.

Background The frequency of the initial short‐term decline in estimated glomerular filtration rate (eGFR), eGFR dip, following initiation of sodium‐glucose cotransporter‐2 inhibitors (SGLT2i) and its clinical implications in real‐world practice are not clear. Methods and Results We built a cohort of 36 638 new users of SGLT2i and 209 025 new users of other antihyperglycemics. Inverse probability weighting was used to estimate the excess rate of eGFR dip, risk of the composite cardiovascular outcome of nonfatal myocardial infarction, nonfatal stroke, hospitalization for heart failure, or all‐cause mortality, and risk of the composite kidney outcome of eGFR decline >50%, end‐stage kidney disease, or all‐cause mortality. In the first 6 months of therapy, compared with other antihyperglycemics, excess rates of eGFR dip >10% and eGFR dip >30% were 9.86 (95% CI: 8.83–11.00) and 1.15 (0.70–1.62) per 100 SGLT2i users, respectively. In mediation analyses that accounted for eGFR dipping, SGLT2i use was associated with reduced risk of cardiovascular and kidney outcomes (hazard ratio, 0.92 [0.84–0.99] and 0.78 [0.71–0.87], respectively); the magnitude of the association reduced by eGFR dipping was small for both outcomes. SGLT2i was associated with reduced risk of both outcomes in those with higher than average probability of eGFR dip >10% or 30%. Compared with discontinuation, continued use of SGLT2i at 6 months was associated with reduced risk of cardiovascular and kidney outcomes in those with no eGFR dip or eGFR dip ≤10%, in those with eGFR dip >10%, and in those with eGFR dip >30%. Conclusions The salutary association of SGLT2i with cardiovascular and kidney outcomes was maintained regardless of eGFR dipping; concerns about eGFR dipping should not preclude use, and occurrence of eGFR dip after SGLT2i initiation may not warrant discontinuation.

Background We compared different methods of estimated glomerular filtration rate (eGFR) and their association with cardiovascular death and major bleeding in 14 980 patients with atrial fibrillation in the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial. Methods and Results eGFR was calculated using equations based on creatinine (Cockcroft‐Gault, Modification of Diet in Renal Disease, and Chronic Kidney Disease Epidemiology Collaboration [CKD‐EPI]) and/or cystatin C (CKD‐EPI CysC and CKD‐EPI CysC+Creatinine ). These 5 eGFR equations, as well as the individual variables that are used in these equations, were assessed for correlation and discriminatory ability for cardiovascular death and major bleeding. The median age was 70.0 years, and 35.6% were women. The median eGFR was highest with Cockcroft‐Gault (74.1 mL/min) and CKD‐EPI CysC (74.2 mL/min), and lowest with Modification of Diet in Renal Disease (66.5 mL/min). Correlation between methods ranged from 0.49 (Cockroft‐Gault and CKD‐EPI CysC ) to 0.99 (Modification of Diet in Renal Disease and CKD‐EPI). Among the eGFR equations, those based on cystatin C yielded the highest C indices for cardiovascular death and major bleeding: 0.628 (CKD‐EPI CysC ) and 0.612 (CKD‐EPI CysC+Creatinine ), respectively. A model based on the variables within the different eGFR equations (age, sex, weight, creatinine, and cystatin C) yielded the highest discriminatory value for both outcomes, with a C index of 0.673 and 0.656, respectively. Conclusions In patients with atrial fibrillation on anticoagulation, correlation between eGFR calculated using different methods varied substantially. Cystatin C–based eGFRs seem to provide the most robust information for predicting death and bleeding. A model based on the individual variables within the eGFR equations, however, provided the highest discriminatory value. Our findings may help refine risk stratification in patients with atrial fibrillation and define how renal function should be determined in future atrial fibrillation studies. Registration URL: https://www.clini​caltr​ials.gov ; Unique identifier: NCT00412984.

Background The aim of this study was to compare the predictive accuracy of acute kidney injury (AKI) after cardiac surgery using cardiopulmonary bypass for the largest area under the curve (AUC) below the oxygen delivery (DO 2 ) threshold and the cumulative AUC below the DO 2 threshold. Methods and Results From March 2017 to October 2019, 202 patients who had undergone cardiac surgery with cardiopulmonary bypass were enrolled. The perfusion parameters were recorded every 20 seconds, and the DO 2 (10×pump flow index [L/min per m 2 ]×[hemoglobin (g/dL)×1.36×arterial oxygen saturation (%)+partial pressure of arterial oxygen (mm Hg)×0.003]) threshold of 300 mL/min per m 2 was considered to define sufficient DO 2 . The nadir DO 2 , the cumulative AUC below the , and the largest AUC below the were used to predict the incidence of AKI. Postoperative AKI was observed in 12.4% of patients (25/202). By multivariable analysis, the largest AUC below the ≥880 (odds ratio [OR], 4.9; 95% CI, 1.2–21.5 [ P =0.022]), preoperative hemoglobin concentration ≤11.6 g/dL (OR, 7.6; 95% CI, 2.0–32.3 [ P =0.004]), and red blood cell transfusions during cardiopulmonary bypass ≥2 U (OR, 3.3; 95% CI, 1.0–11.1 [ P =0.041]) were detected as independent risk factors for AKI. Receiver operating curve analysis revealed that the largest AUC below the was more accurate to predict postoperative AKI compared with the nadir DO 2 and the cumulative AUC below the (differences between areas, 0.0691 [ P =0.006] and 0.0395 [ P =0.001]). Conclusions These data suggest that a high AUC below the is an important independent risk factor for AKI after cardiopulmonary bypass, which could be considered for risk prediction models of AKI.

Background Recommendations have not yet been established for statin therapy in patients on maintenance dialysis. In this study, we aimed to evaluate the effects of statin therapy on all‐cause mortality in patients undergoing maintenance hemodialysis. Methods and Results This retrospective cohort study analyzed data from adults, aged ≥30 years, who were on maintenance hemodialysis for end‐stage renal disease. Data on statin use, along with other clinical information between 2007 and 2017, were extracted from the Health Insurance Review and Assessment Service database in Korea. In total, 65 404 patients were included, and 41 549 (73.2%) patients had received statin therapy for a mean duration of 3.6±2.6 years. Compared with statin nonusers before and after the initiation of hemodialysis (entry), patients who initiated statin therapy after entry and patients who continued statins from the pre–end‐stage renal disease to post–end‐stage renal disease period had a lower risk of all‐cause mortality; the adjusted hazard ratios (95% CIs) were 0.48 (0.47–0.50; P P 75 years, and were maintained even after propensity score matching. Conclusions Our results showed that in adult patients undergoing maintenance hemodialysis, statin therapy, preferably combined with ezetimibe, was associated with a lower risk of all‐cause mortality.

Background Defects in the renal fatty acid β‐oxidation pathway have been implicated in the development of renal fibrosis. Our group has developed a therapeutic vaccine targeting PCSK 9 (proprotein convertase subtilisin/kexin type 9), named PCSK 9Qβ‐003. In this study, we investigated the potential effectiveness of the PCSK 9Qβ‐003 vaccine on hypercholesterolemia with renal fibrosis. Methods and Results The low‐density lipoprotein receptor +/− male mice fed with a high‐cholesterol (1%) Western diet were randomly assigned into 4 groups: the sham group (or the control group), the phosphate‐buffered saline group, the Qβ virus‐like particles group and the PCSK 9Qβ‐003 vaccine group. Mice of the PCSK 9Qβ‐003 group were injected with the PCSK 9Qβ‐003 vaccine (100 μg/time) every 2 or 4 weeks. The mice were administered with either unilateral ureteral obstruction for 2 weeks or N‐nitro‐ l ‐arginine methyl ester (50 mg/kg per day) for 6 weeks to establish a renal fibrosis model. Compared with the other 3 groups, the PCSK 9Qβ‐003 vaccine obviously decreased total cholesterol and low‐density lipoprotein cholesterol in low‐density lipoprotein receptor +/− mice with hypercholesterolemia. Compared with the phosphate‐buffered saline and Qβ virus‐like particles groups, the PCSK 9Qβ‐003 vaccine improved hepatic steatosis and renal function. Histology analysis showed that the PCSK 9Qβ‐003 vaccine significantly ameliorated renal lipid accumulation and renal fibrosis. Moreover, the PCSK 9Qβ‐003 vaccine obviously upregulated the expression of low‐density lipoprotein receptor, very‐low‐density lipoprotein receptor, sterol‐regulatory element binding protein 2, and fatty acid β‐oxidation–related factors, and ameliorated renal fibrosis‐related molecules both in the unilateral ureteral obstruction and N‐nitro‐ l ‐arginine methyl ester models. Conclusions This study suggested that the PCSK 9Qβ‐003 vaccine improved renal lipid accumulation and renal fibrosis by regulating fatty acid β‐oxidation, which may provide a promising method for treating hypercholesterolemia with renal fibrosis.

Background Cardiac biomarkers may signal mechanistic pathways involved in heart failure ( HF ), a leading complication in chronic kidney disease. We tested the associations of NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide), high‐sensitivity troponin T (hsTnT), galectin‐3, growth differentiation factor‐15 ( GDF ‐15), and soluble ST 2 ( sST 2) with incident HF in chronic kidney disease. Methods and Results We examined adults with chronic kidney disease enrolled in a prospective, multicenter study. All biomarkers were measured at baseline. The primary outcome was incident HF . Secondary outcomes included HF with preserved ejection fraction (EF≥50%) and reduced ejection fraction (EFHF , adjusting for demographics, kidney function, cardiovascular risk factors, and medication use. Among 3314 participants, all biomarkers, with the exception of galectin‐3, were significantly associated with increased risk of incident HF (hazard ratio per SD higher concentration of log‐transformed biomarker): NT ‐pro BNP (hazard ratio, 2.07; 95% CI , 1.79–2.39); hsTnT (hazard ratio, 1.38; 95% CI , 1.21–1.56); GDF ‐15 (hazard ratio, 1.44; 95% CI , 1.26–1.66) and sST 2 (hazard ratio, 1.19; 95% CI, 1.05–1.35). Higher NT ‐pro BNP , hsTnT, and GDF ‐15 were also associated with a greater risk of HF with reduced EF ; while higher NT ‐pro BNP GDF ‐15 and sST 2 were associated with HF with preserved EF . Galectin‐3 was not associated with either HF with reduced EF or HF with preserved EF. Conclusions In chronic kidney disease, elevations of NT ‐pro BNP , hsTnT, GDF ‐15, sST 2 were associated with incident HF . There was a borderline association of galectin‐3 with incident HF . NT ‐pro BNP and hsTnT were more strongly associated with HF with reduced EF , while the associations of the newer biomarkers GDF ‐15 and sST 2 were stronger for HF with preserved EF.

Background Although recommended in the guidelines, the safety of chronic P2Y 12 inhibitor therapy in patients with chronic kidney disease ( CKD ) after an acute myocardial infarction ( MI ) is not well studied. Methods and Results The TRANSLATE ‐ACS (Treatment with ADP Inhibitors: Longitudinal Assessment of Treatment Patterns and Events After Acute Coronary Syndrome) study included 11 108 MI patients treated with percutaneous coronary intervention and discharged alive on a P2Y 12 inhibitor from 233 US hospitals. We compared rates of GUSTO (Global Use of Strategies to Open Occluded Arteries) severe/moderate bleeding and premature discontinuation of P2Y 12 inhibitor by 1 year after MI among patients with varying CKD severity. The majority of MI patients treated with percutaneous coronary intervention had CKD : 42% had stage 2 (mild), 27% had stage 3 (moderate), and 4% had stage ≥4 (severe/end stage). Higher potency P2Y 12 inhibitors (prasugrel or ticagrelor) were prescribed at discharge in 39%, 35%, 23%, and 15% ( P GUSTO severe/moderate bleeding rates were higher with each stage of CKD : 1% in patients with CKD stage 1 or no CKD , 2% with an adjusted hazard ratio of 1.61 (95% CI, 1.05–2.35) for CKD stage 2, 4% with an adjusted hazard ratio of 1.92 (95% CI, 1.21–3.02) for CKD stage 3, and 10% with an adjusted hazard ratio of 2.44 (95% CI, 1.40–4.23) for patients with CKD stage ≥4. By 1 year after MI , 16% of patients overall had prematurely discontinued P2Y 12 inhibitor therapy; however, this rate was not largely affected by CKD stage. Premature P2Y 12 inhibitor–discontinuation rates were higher for patients discharged on higher potency P2Y 12 inhibitors in patients with CKD stage ≥2 ( P Conclusions CKD severity was associated with a higher bleeding risk among those with acute MI treated with a P2Y 12 inhibitor. Patients with more advanced CKD were not significantly more likely than those with less advance CKD to prematurely discontinue P2Y 12 inhibitor therapy.

Background The prognostic impact of jeopardized myocardium ( JM ) in patients with advanced ischemic cardiomyopathy ( ICM ) is unclear. We hypothesized that JM is an independent predictor of mortality in patients with advanced ICM . Methods and Results Patients with ICM who underwent cardiac magnetic resonance imaging between January 2002 and January 2013 were included in our study. JM was identified as a vascular territory with 70% stenosis in a major coronary vessel that was not subsequently revascularized. A propensity score was developed for revascularization. A multivariable Cox proportional hazards model was used to evaluate the association of JM with all‐cause mortality. We evaluated 631 patients over a mean follow‐up of 5.1 years. Overall, 336 patients underwent subsequent revascularization during the follow‐up period, among whom 23% had remaining JM , while 295 patients were medically treated (57% with JM ). There were 204 deaths (32%). On multivariable analysis, JM (hazard ratio, 1.88; 95% confidence interval, 1.38–2.55 [ P JM increased by 5% for every 10‐unit increase in left ventricular end‐systolic volume index. Conclusions JM is an independent and incremental predictor of mortality in patients with advanced ICM . Patients undergoing revascularization with residual JM had similar risk of mortality compared with medically treated patients with JM . The risk associated with JM significantly increased in the presence of worsening adverse left ventricular remodeling. Cardiac magnetic resonance viability assessment may provide important risk stratification in patients with ICM .

Background Our objective was to determine patterns of antihypertensive agent use by stage of chronic kidney disease (CKD) and to evaluate the association between different classes of antihypertensive agents with nonrenal outcomes, especially in advanced CKD . Methods and Results We studied 3939 participants of the CRIC (Chronic Renal Insufficiency Cohort) study. Predictors were time‐dependent angiotensin‐converting enzyme inhibitor or angiotensin receptor blocker , β‐blocker, and calcium channel blocker use (versus nonuse of agents in each class). Outcomes were adjudicated heart failure events or death. Adjusted Cox models were used to determine the association between predictors and outcomes. We also examined whether the associations differed based on the severity of CKD (early [stage 2–3 CKD ] versus advanced disease [stage 4–5 CKD ]). During median follow‐up of 7.5 years, renin‐angiotensin‐aldosterone system inhibitor use plateaued during CKD stage 3 (75%) and declined to 37% by stage 5, while β‐blocker, calcium channel blocker, and diuretic use increased steadily with advancing CKD . Renin‐angiotensin‐aldosterone system inhibitor use was associated with lower risk of heart failure (hazard ratio, 0.79; 95% confidence interval, 0.67–0.97) and death (hazard ratio, 0.78; 95% confidence interval, 0.67–0.90), regardless of severity of CKD . Calcium channel blocker use was not associated with risk of heart failure or death, regardless of the severity of CKD . β‐Blocker use was associated with higher risk of heart failure (hazard ratio, 1.62; 95% confidence interval, 1.29–2.04) and death (hazard ratio, 1.22; 95% confidence interval, 1.03–1.43), especially during early CKD ( P Conclusions Angiotensin‐converting enzyme inhibitor and angiotensin receptor blocker use decreased, while use of other agents increased with advancing CKD . Use of agents besides angiotensin‐converting enzyme inhibitors or angiotensin receptor blockers may be associated with suboptimal outcomes in patients with CKD .

Background Few studies have shown that right ventricular ( RV ) function is independently related to adverse events regardless of left ventricular ( LV ) function in heart failure. We evaluated the prognostic value of global longitudinal strain ( GLS ) of both ventricles in patients with acute heart failure. Methods and Results We measured biventricular strains in 1824 randomly selected patients (973 men, aged 70±14 years) from a strain registry. A total of 799 patients (43.8%) died during the median follow‐up duration of 31.7 months. In univariate analysis, LVGLS and RVGLS were significantly associated with all‐cause mortality. We classified them into 4 strain groups according to LVGLS (≥9%) and RVGLS (≥12%). On Cox proportional hazards analysis, group 4 (LVGLS and RVGLS ) had the worst prognosis, with a hazard ratio ( HR ) of 1.755 (95% confidence interval [ CI ], 1.473–2.091; P LVGLS and ≥12% RVGLS ). After multivariate analysis, both LVGLS (per 1% decrease; HR : 1.057; 95% CI , 1.029–1.086; P RVGLS (per 1% decrease; HR : 1.022; 95% CI , 1.004–1.040; P =0.014) were also significant. The HR of RVGLS LVGLS ( HR : 1.40 [95% CI , 1.11–1.77] versus 1.07 [95% CI , 0.88–1.30] with pulmonary hypertension; interaction, P =0.043). Conclusions In the patients with acute heart failure, RVGLS was significantly associated with all‐cause mortality regardless of LVGLS , and those with decreased biventricular GLS showed the worst prognosis. The predictive power of RVGLS was more prominent in the absence of pulmonary hypertension.

Background Cardiorenal syndrome type 1 ( CRS 1) as a complication of acute myocardial infarction can lead to adverse outcomes, and a method for early detection is needed. This study investigated the individual and integrated effectiveness of amino‐terminal pro–brain natriuretic peptide (Pro‐BNP), estimated glomerular filtration rate (eGFR), and high‐sensitivity C‐reactive protein (CRP) as predictive factors for CRS 1 in patients with acute myocardial infarction. Methods and Results In a retrospective analysis of 2094 patients with acute myocardial infarction, risk factors for CRS 1 were analyzed by logistic regression. Receiver operating characteristic curves were constructed to determine the predictive ability of the biomarkers individually and in combination. Overall, 177 patients (8.45%) developed CRS 1 during hospitalization. On multivariable analysis, all 3 biomarkers were independent predictors of CRS 1 with odds radios and 95% confidence intervals for a 1‐SD change of 1.792 (1.311‐2.450) for log(amino‐terminal pro–brain natriuretic peptide, 0.424 (0.310‐0.576) for estimated glomerular filtration rate, and 1.429 (1.180‐1.747) for high‐sensitivity C‐reactive peptide. After propensity score matching, the biomarkers individually and together significantly predicted CRS 1 with areas under the curve of 0.719 for amino‐terminal pro–brain natriuretic peptide, 0.843 for estimated glomerular filtration rate, 0.656 for high‐sensitivity C‐reactive peptide, and 0.863 for the 3‐marker panel (all P P CRS 1 risk correlated with the number of biomarkers showing abnormal levels. Abnormal measurements for at least 2 biomarkers indicated a greater risk of CRS 1 (odds ratio 36.19, 95% confidence interval 8.534‐153.455, P Conclusions The combination of amino‐terminal pro–brain natriuretic peptide, estimated glomerular filtration rate, and high‐sensitivity C‐reactive peptide at presentation may assist in the prediction of CRS 1 and corresponding risk stratification in patients with acute myocardial infarction.

Background Higher circulatory corin in patients with cardiac diseases is associated with improved cardiovascular outcomes, and chronic cardiac dysfunction is a well‐known cause of progressive renal dysfunction. This study aimed to determine the role of serum corin in predicting short‐term and long‐term renal outcomes after contrast exposure in patients with suspected coronary artery disease. Methods and Results Four hundred one patients who had received coronary angiography were enrolled. Serum corin levels were determined before administration of contrast media. Contrast‐induced nephropathy was defined as a rise in serum creatinine of 0.5 mg/dL or a 25% increase from baseline within 48 hours after the procedure. Progressive renal dysfunction was defined as >50% decrease in estimated glomerular filtration rate after discharge. All patients were followed up for at least 1 year or until the occurrence of death after coronary angiography. Overall, contrast‐induced nephropathy occurred in 23 (5.7%) patients. During a median follow‐up of 529 days, 44 (11.0%) cases had subsequent decline in renal function. After adjustment for demographic characteristics, kidney function, traditional risk factors, and medications, lower corin level was found to be independently associated with higher risk for progressive renal dysfunction (hazard ratio, 0.23; 95% confidence interval, 0.12–0.44) but not for contrast‐induced nephropathy. This inverse correlation remained evident in patients with underlying chronic kidney disease, coronary artery disease, or heart failure. Conclusions Lower baseline serum corin was associated with higher risk of renal function decline in patients undergoing coronary angiography. Further studies are needed to verify these results.

Background Acute kidney injury ( AKI ) after cardiac surgery is associated with increased short‐ and long‐term mortality. Inflammation, oxidative stress, and endothelial dysfunction and damage play important roles in the development of AKI . High‐density lipoproteins ( HDLs ) have anti‐inflammatory and antioxidant properties and improve endothelial function and repair. Statins enhance HDL 's anti‐inflammatory and antioxidant capacities. We hypothesized that a higher preoperative HDL cholesterol concentration is associated with decreased AKI after cardiac surgery and that perioperative statin exposure potentiates this association. Methods and Results We tested our hypothesis in 391 subjects from a randomized clinical trial of perioperative atorvastatin to reduce AKI after cardiac surgery. A 2‐component latent variable mixture model was used to assess the association between preoperative HDL cholesterol concentration and postoperative change in serum creatinine, adjusted for known AKI risk factors and suspected confounders. Interaction terms were used to examine the effects of preoperative statin use, preoperative statin dose, and perioperative atorvastatin treatment on the association between preoperative HDL and AKI . A higher preoperative HDL cholesterol concentration was independently associated with a decreased postoperative serum creatinine change ( P =0.02). The association between a high HDL concentration and an attenuated increase in serum creatinine was strongest in long‐term statin‐using patients ( P =0.008) and was further enhanced with perioperative atorvastatin treatment ( P =0.004) and increasing long‐term statin dose ( P =0.003). Conclusions A higher preoperative HDL cholesterol concentration was associated with decreased AKI after cardiac surgery. Preoperative and perioperative statin treatment enhanced this association, demonstrating that pharmacological potentiation is possible during the perioperative period. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique Identifier: NCT 00791648.

Background Albuminuria is a marker of inflammation and an independent predictor of cardiovascular morbidity and mortality. The current study evaluated whether eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) supplementation attenuates progression of albuminuria in subjects with coronary artery disease. Methods and Results Two‐hundred sixty‐two subjects with stable coronary artery disease were randomized to either Lovaza (1.86 g of EPA and 1.5 g of DHA daily) or no Lovaza (control) for 1 year. Percent change in urine albumin‐to‐creatinine ratio ( ACR ) was compared. Mean ( SD ) age was 63.3 (7.6) years; 17% were women and 30% had type 2 diabetes mellitus. In nondiabetic subjects, no change in urine ACR occurred in either the Lovaza or control groups. In contrast, ACR increased 72.3% ( P ACR , whereas those not receiving Lovaza had a 64.2% increase ( P ACR was directly correlated with change in systolic blood pressure ( r =0.394, P =0.01). Conclusions EPA and DHA supplementation attenuated progression of albuminuria in subjects with type 2 diabetes mellitus and coronary artery disease, most of whom were on an angiotensin‐converting enzyme‐inhibitor or angiotensin‐receptor blocker. Thus, EPA and DHA supplementation should be considered as additional therapy to an angiotensin‐converting enzyme‐inhibitor or angiotensin‐receptor blocker in subjects with type 2 diabetes mellitus and coronary artery disease. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 01624727.

Background Conflicting results have been obtained in trials that have evaluated the prophylactic efficacy of N ‐acetylcysteine ( NAC ) pretreatment in the prevention of contrast‐induced nephropathy ( CIN ). In this meta‐analysis of randomized controlled trials, we aimed to assess the effectiveness of NAC treatment for the prevention of CIN . Methods and Results PubMed, EMBASE , and the Cochrane Library were electronically searched from inception to January 2016 for all relevant studies. The weighted relative risk ( RR ) and corresponding 95% CI for incident CIN were estimated using random effects models. Standard methods for assessing statistical heterogeneity and publication bias were used. The study included 11 480 participants and 1653 cases of CIN . The incidence of CIN was 12.8% in the NAC group versus 16.0% in the control group ( RR : 0.76, 95% CI : 0.66–0.88, P =0.0002). In the patients undergoing coronary angiography, the incidence of CIN in the NAC group versus the control group was 13.7% versus 17.2% ( RR : 0.74, 95% CI : 0.63–0.87, P =0.0002); in those undergoing peripheral angiography, the incidence was 6.4% versus 5.8% ( RR : 1.00, 95% CI : 0.42–2.40, P =1.00); in those undergoing computed tomography, the incidence was 7.7% versus 14.8% ( RR : 0.51, 95% CI : 0.29–0.89, P =0.02). Conclusions Our meta‐analysis showed an inverse and significant association between NAC supplementation and risk of CIN in patients undergoing coronary angiography and computed tomography, while a protective role for NAC in patients undergoing peripheral angiography was not obvious.

Background Chronic kidney disease ( CKD ) increases cardiovascular disease ( CVD ) risk. However, the association of mildly reduced kidney function with CVD risk is unclear. Methods and Results This study investigated the association of estimated glomerular filtration rate ( eGFR ) with prevalent CVDs, 10‐year Framingham risk for coronary heart disease ( CHD ), and 10‐year risk of atherosclerotic cardiovascular diseases ( ASCVD ) in 239 832 participants from the baseline of the Risk Evaluation of cA ncers in Chinese diabeTic Individuals: a lON gitudinal study. With an interviewer‐assisted questionnaire, we collected information on CVD , including reported CHD , stroke, or myocardial infarction. Chronic Kidney Disease–Epidemiology Collaboration ( CKD ‐ EPI ) equation was used to calculate eGFR . Compared with individuals with normal eGFR (≥90 mL/min per 1.73 m 2 ), those with decreased eGFR (75–89, 60–74, and 2 ) had higher risk of prevalent obesity, diabetes mellitus, hypertension, and dyslipidemia in both men and women ( P for trend all CHD and 10‐year risk for ASCVD was observed in both men and women with mildly decreased eGFR (60–89 mL/min per 1.73 m 2 ). Conclusions Even mildly reduced eGFR (under 90 mL/min per 1.73 m 2 ) is associated with elevated 10‐year Framingham risk for CHD and 10‐year ASCVD risk among Chinese adults.

Background N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) has been associated with important risk factors for contrast‐induced nephropathy (CIN). However, few studies have investigated the predictive value of NT‐proBNP itself. This study investigated whether levels of preprocedural NT‐proBNP could predict CIN after elective coronary angiography as effectively as the Mehran CIN score. Methods and Results We retrospectively observed 2248 patients who underwent elective coronary angiography. The predictive value of preprocedural NT‐proBNP for CIN was assessed by receiver operating characteristic and multivariable logistic regression analysis. The 50 patients (2.2%) who developed CIN had higher Mehran risk scores (9.5±5.1 versus 4.8±3.8), and higher preprocedural levels of NT‐proBNP (5320±7423 versus 1078±2548 pg/mL, P P =0.8431). An NT‐proBNP cutoff value of 682 pg/mL predicted CIN with 78% sensitivity and 70% specificity. Multivariable analysis suggested that, after adjustment for other risk factors, NT‐proBNP >682 pg/mL was significantly associated with CIN (odds ratio: 4.007, 95% CI: 1.950 to 8.234; P P =0.0006). Conclusions Preprocedural NT‐proBNP >682 pg/mL was significantly associated with the risk of CIN and death. NT‐proBNP, like the Mehran CIN score, may be another useful and rapid screening tool for CIN and death risk assessment, identifying subjects who need therapeutic measures to prevent CIN.

Background Premature cardiovascular disease limits the duration and quality of life on long‐term hemodialysis. The objective of this study was to define the frequency of fatal and nonfatal cardiovascular events attributable to atherosclerotic and nonatherosclerotic mechanisms, risk factors for these events, and the effects of cinacalcet, using adjudicated data collected during the EValuation of Cinacalcet HC l Therapy to Lower CardioVascular Events ( EVOLVE ) Trial. Methods and Results EVOLVE was a randomized, double‐blind, placebo‐controlled clinical trial that randomized 3883 hemodialysis patients with moderate to severe secondary hyperparathyroidism to cinacalcet or matched placebo for up to 64 months. For this post hoc analysis, the outcome measure was fatal and nonfatal cardiovascular events reflecting atherosclerotic and nonatherosclerotic cardiovascular diseases. During the trial, 1518 patients experienced an adjudicated cardiovascular event, including 958 attributable to nonatherosclerotic disease. Of 1421 deaths during the trial, 768 (54%) were due to cardiovascular disease. Sudden death was the most frequent fatal cardiovascular event, accounting for 24.5% of overall mortality. Combining fatal and nonfatal cardiovascular events, randomization to cinacalcet reduced the rates of sudden death and heart failure. Patients randomized to cinacalcet experienced fewer nonatherosclerotic cardiovascular events (adjusted relative hazard 0.84, 95% CI 0.74 to 0.96), while the effect of cinacalcet on atherosclerotic events did not reach statistical significance. Conclusions Accepting the limitations of post hoc analysis, any benefits of cinacalcet on cardiovascular disease in the context of hemodialysis may result from attenuation of nonatherosclerotic processes. Clinical Trials Registration Unique identifier: NCT00345839. URL: ClinicalTrials.gov .