Chronic kidney disease and undiagnosed atrial fibrillation in individuals with diabetes
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ABSTRACT:
SUBMITTER: Heo N
PROVIDER: S-EPMC7528591 | biostudies-literature | 2020 Jan
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND:Cardiological societies recommend, in their guidelines, that patients with atrial fibrillation and an intermediate (or higher) risk of stroke and systemic embolization should be treated with oral anticoagulant drugs. For patients who do not have mitral valve stenosis or a mechanical valve prosthesis, non-vitamin-K dependent oral anticoagulants (NOAC) are preferred over vitamin K antagonists (VKA) for this purpose. It is unclear, however, whether patients with chronic kidney disease and atrial fibrillation benefit from oral anticoagulation to the same extent as those with normal kidney function. It is also unclear which of the two types of anti - coagulant drug is preferable for patients with chronic kidney disease; NOAC are, in part, renally eliminated. METHODS:This review is based on pertinent publications retrieved by a selective literature search, and on international guidelines. RESULTS:Current evidence suggests that patients with atrial fibrillation who have chronic kidney disease with a glomerular filtration rate (GFR) above 15 mL/ min/1.73 m² should be treated with an oral anticoagulant drug if they have an at least intermediate risk of embolization, as assessed with the CHA2DS2-VASc score. For patients with advanced chronic kidney disease (GFR from 15 to 29 mL/ min/1.73 m²), however, this recommendation is based only on registry studies. For dialysis patients with atrial fibrillation, decisions whether to give oral anticoagulant drugs should be taken on an individual basis, in view of the elevated risk of hemorrhage and the unclear efficacy of such drugs in these patients. The subgroup analyses of the NOAC approval studies show that, for patients with atrial fibrillation and chronic kidney disease with a creatinine clearance of >25-30 mL/min, NOAC should be given in preference to VKA, as long as the patient does not have mitral valve stenosis or a mechanical valve prosthesis. For those whose creatinine clearance is less than 25 mL/min, the relative merits of NOAC versus VKA are still debated. CONCLUSION:The cardiological societies' recommendation that patients with atrial fibrillation should be given oral anticoagulant drugs applies to the majority of such patients who also have chronic kidney disease.
| S-EPMC5974258 | biostudies-literature
Project description:Chronic kidney disease (CKD) is associated with a higher risk of atrial fibrillation (AF). The mechanistic link between CKD and AF remains elusive. IL-1β, a main effector of NLR family pyrin domain-containing 3 (NLRP3) inflammasome activation, is a key modulator of conditions associated with inflammation, such as AF and CKD. Circulating IL-1β levels were elevated in patients with CKD who had AF (versus patients with CKD in sinus rhythm). Moreover, NLRP3 activity was enhanced in atria of patients with CKD. To elucidate the role of NLRP3/IL-1β signaling in the pathogenesis of CKD-induced AF, Nlrp3-/- and WT mice were subjected to a 2-stage subtotal nephrectomy protocol to induce CKD. Four weeks after surgery, IL-1β levels in serum and atrial tissue were increased in WT CKD (WT-CKD) mice versus sham-operated WT (WT-sham) mice. The increased susceptibility to pacing-induced AF and the longer AF duration in WT-CKD mice were associated with an abbreviated atrial effective refractory period, enlarged atria, and atrial fibrosis. Genetic inhibition of NLRP3 in Nlrp3-/- mice or neutralizing anti-IL-1β antibodies effectively reduced IL-1β levels, normalized left atrial dimensions, and reduced fibrosis and the incidence of AF. These data suggest that CKD creates a substrate for AF development by activating the NLRP3 inflammasome in atria, which is associated with structural and electrical remodeling. Neutralizing IL-1β antibodies may be beneficial in preventing CKD-induced AF.
| S-EPMC10541185 | biostudies-literature
Project description:Background and objectivesThe efficacy of adjusted-dose warfarin for prevention of stroke in atrial fibrillation patients with stage 3 chronic kidney disease (CKD) is unknown.Design, setting, participants, & measurementsPatients with stage 3 CKD participating in the Stroke Prevention in Atrial Fibrillation 3 trials were assessed to determine the effect of warfarin anticoagulation on stroke and major hemorrhage, and whether CKD status independently contributed to stroke risk. High-risk participants (n = 1044) in the randomized trial were assigned to adjusted-dose warfarin (target international normalized ratio 2 to 3) versus aspirin (325 mg) plus fixed, low-dose warfarin (subsequently shown to be equivalent to aspirin alone). Low-risk participants (n = 892) all received 325 mg aspirin daily. The primary outcome was ischemic stroke (96%) or systemic embolism (4%).ResultsAmong the 1936 participants in the two trials, 42% (n = 805) had stage 3 CKD at entry. Considering the 1314 patients not assigned to adjusted-dose warfarin, the primary event rate was double among those with stage 3 CKD (hazard ratio 2.0, 95% CI 1.2, 3.3) versus those with a higher estimated GFR (eGFR). Among the 516 participants with stage 3 CKD included in the randomized trial, ischemic stroke/systemic embolism was reduced 76% (95% CI 42, 90; P < 0.001) by adjusted-dose warfarin compared with aspirin/low-dose warfarin; there was no difference in major hemorrhage (5 patients versus 6 patients, respectively).ConclusionsAmong atrial fibrillation patients participating in the Stroke Prevention in Atrial Fibrillation III trials, stage 3 CKD was associated with higher rates of ischemic stroke/systemic embolism. Adjusted-dose warfarin markedly reduced ischemic stroke/systemic embolism in high-risk atrial fibrillation patients with stage 3 CKD.
| S-EPMC3359566 | biostudies-literature
Project description:Background and Objectives: Real-world evidence of apixaban treatment in patients with chronic kidney disease remains scarce. This study aimed to compare the relative risk of stroke or systemic embolism (SE) and major bleeding between apixaban and warfarin in atrial fibrillation (AF) patients with different degrees of kidney function. Design, Setting, Participants, and Measurements: We evaluated newly diagnosed AF patients between 2004 and 2018, who were receiving apixaban or warfarin. Electronic medical record data were collected from a large healthcare delivery network in Taiwan. The outcomes of hospitalization for stroke/SE and major bleeding were compared with propensity-score matched apixaban and warfarin cohorts. Stratified analyses according to initial apixaban dose (standard dose of 10 mg/day vs. lower dose of 2.5-5.0 mg/day) and baseline estimated glomerular filtration rate were performed. Results: Each cohort involved 1,625 matched patients. Apixaban was significantly associated with a lower risk of stroke/SE (adjusted hazard ratio [aHR]: 0.74; 95% confidence interval [CI]:0.57-0.97; p = 0.03). The risk of major bleeding was not increased whether in standard doses (aHR: 0.66; 95% CI: 0.45-0.96; p = 0.03) or reduced doses (aHR, 0.84; 95% CI, 0.63-1.12; p = 0.23) of apixaban. Regarding kidney function, apixaban reduced the risk of stroke/SE by 37% in those with an eGFR of <30 ml/min/1.73 m2 (aHR: 0.63; 95% CI: 0.40-0.98; p = 0.04). Conclusions: Compared to warfarin, apixaban is associated with a reduced risk of stroke/SE and is consistent with a subset of AF patients with eGFR <30 ml/min/1.73 m2. Both standard and reduced doses of apixaban showed lower risk of major bleeding than those of warfarin.
| S-EPMC8558356 | biostudies-literature
Project description:Chronic kidney disease (CKD) causes atrial structural remodeling and subsequently increases the incidence of atrial fibrillation (AF). Atrial connexins and inflammatory responses may be involved in this remodeling process. In this study, nephrectomy was used to produce the CKD rat model. Three months post-nephrectomy, cardiac structure, function and AF vulnerability were quantified using echocardiography and electrophysiology methods. The left atrial tissue was tested for quantification of fibrosis and inflammation, and for the distribution and expression of connexin (Cx) 40 and Cx43. An echocardiography showed that CKD resulted in the left atrial enlargement and left ventricular hypertrophy, but had no functional changes. CKD caused a significant increase in the AF inducible rate (91.11% in CKD group vs. 6.67% in sham group, P < 0.001) and the AF duration [107 (0-770) s in CKD vs. 0 (0-70) s in sham, P < 0.001] with prolonged P-wave duration. CKD induced severe interstitial fibrosis, activated the transforming growth factor-?1/Smad2/3 pathway with a massive extracellular matrix deposition of collagen type I and ?-smooth muscle actin, and matured the NLR (nucleotide-binding domain leucine-rich repeat-containing receptor) pyrin domain-containing protein 3 (NLRP3) inflammasome with an inflammatory cascade response. CKD resulted in an increase in non-phosphorylated-Cx43, a decrease in Cx40 and phosphorylated-Cx43, and lateralized the distribution of Cx40 and Cx43 proteins with upregulations of Rac-1, connective tissue growth factor and N-cadherin. These findings implicate the transforming growth factor-?1/Smad2/3, the NLRP3 inflammasome and the connexins as potential mediators of increased AF vulnerability in CKD.
| S-EPMC6288485 | biostudies-literature
Project description:Over the past few decades, a series of innovative medicines have been developed in order to optimize anticoagulation therapy for atrial fibrillation (AF). As a result, a number of nonvitamin K antagonist oral anticoagulants (NOAC) that directly target the enzymatic activity of factor II and factor Xa have been successfully licensed providing a more predictable effect and better safety profile compared to conventional anticoagulants (heparins and vitamin K antagonists (VKAs)). However, comparative efficacy and safety data is limited in patients with advanced chronic kidney disease (i.e., CKD stage 4/5 and end stage renal disease) because patients with estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 were actively excluded from landmark trials, thus representing a major clinical limitation for the currently available agents. However, the renal function of AF patients can be altered over time. On the other hand, patients with CKD have an increased risk of developing AF. This review article will provide an overview of current concepts and recent evidence guiding the clinical use of NOACs in patients with CKD requiring chronic anticoagulation, and the associated risks and benefits of treatment in this specific patient population.
| S-EPMC8147111 | biostudies-literature
Project description:Background and objectivesAtrial fibrillation (AF) is common in CKD and associated with poor kidney and cardiovascular outcomes. Prediction models developed using novel methods may be useful to identify patients with CKD at highest risk of incident AF. We compared a previously published prediction model with models developed using machine learning methods in a CKD population.Design, setting, participants, & measurementsWe studied 2766 participants in the Chronic Renal Insufficiency Cohort study without prior AF with complete cardiac biomarker (N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin T) and clinical data. We evaluated the utility of machine learning methods as well as a previously validated clinical prediction model (Cohorts for Heart and Aging Research in Genomic Epidemiology [CHARGE]-AF, which included 11 predictors, using original and re-estimated coefficients) to predict incident AF. Discriminatory ability of each model was assessed using the ten-fold cross-validated C-index; calibration was evaluated graphically and with the Grønnesby and Borgan test.ResultsMean (SD) age of participants was 57 (11) years, 55% were men, 38% were Black, and mean (SD) eGFR was 45 (15) ml/min per 1.73 m2; 259 incident AF events occurred during a median of 8 years of follow-up. The CHARGE-AF prediction equation using original and re-estimated coefficients had C-indices of 0.67 (95% confidence interval, 0.64 to 0.71) and 0.67 (95% confidence interval, 0.64 to 0.70), respectively. A likelihood-based boosting model using clinical variables only had a C-index of 0.67 (95% confidence interval, 0.64 to 0.70); adding N-terminal pro-B-type natriuretic peptide, high-sensitivity troponin T, or both biomarkers improved the C-index by 0.04, 0.01, and 0.04, respectively. In addition to N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin T, the final model included age, non-Hispanic Black race/ethnicity, Hispanic race/ethnicity, cardiovascular disease, chronic obstructive pulmonary disease, myocardial infarction, peripheral vascular disease, use of angiotensin-converting enzyme inhibitor/angiotensin receptor blockers, calcium channel blockers, diuretics, height, and weight.ConclusionsUsing machine learning algorithms, a model that included 12 standard clinical variables and cardiac-specific biomarkers N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin T had moderate discrimination for incident AF in a CKD population.
| S-EPMC8425618 | biostudies-literature
Project description:Background We tested associations of cardiac biomarkers of myocardial stretch, injury, inflammation, and fibrosis with the risk of incident atrial fibrillation (AF) in a prospective study of chronic kidney disease patients. Methods and Results The study sample was 3053 participants with chronic kidney disease in the multicenter CRIC (Chronic Renal Insufficiency Cohort) study who were not identified as having AF at baseline. Cardiac biomarkers, measured at baseline, were NT-proBNP (N-terminal pro-B-type natriuretic peptide), high-sensitivity troponin T, galectin-3, growth differentiation factor-15, and soluble ST-2. Incident AF ("AF event") was defined as a hospitalization for AF. During a median follow-up of 8 years, 279 (9%) participants developed a new AF event. In adjusted models, higher baseline log-transformed NT-proBNP (N-terminal pro-B-type natriuretic peptide) was associated with incident AF (adjusted hazard ratio [HR] per SD higher concentration: 2.11; 95% CI, 1.75, 2.55), as was log-high-sensitivity troponin T (HR 1.42; 95% CI, 1.20, 1.68). These associations showed a dose-response relationship in categorical analyses. Although log-soluble ST-2 was associated with AF risk in continuous models (HR per SD higher concentration 1.35; 95% CI, 1.16, 1.58), this association was not consistent in categorical analyses. Log-galectin-3 (HR 1.05; 95% CI, 0.91, 1.22) and log-growth differentiation factor-15 (HR 1.16; 95% CI, 0.96, 1.40) were not significantly associated with incident AF. Conclusions We found strong associations between higher NT-proBNP (N-terminal pro-B-type natriuretic peptide) and high-sensitivity troponin T concentrations, and the risk of incident AF in a large cohort of participants with chronic kidney disease. Increased atrial myocardial stretch and myocardial cell injury may be implicated in the high burden of AF in patients with chronic kidney disease.
| S-EPMC6761652 | biostudies-literature
Project description:BACKGROUND:Chronic kidney disease (CKD) is highly prevalent in patients with atrial fibrillation (AF). However, the association between CKD and clinical consequences in AF patients is still under debate. METHODS:We included 19,079 nonvalvular AF patients with available estimated glomerular filtration rate (eGFR) values in the Chinese Atrial Fibrillation Registry from 2011 to 2018. Patients were classified into no CKD (eGFR ≥ 90 mL/min per 1.73 m2), mild CKD (60 ≤ eGFR < 90 mL/min per 1.73 m 2), moderate CKD (30 ≤ eGFR < 60 mL/min per 1.73 m 2), and severe CKD (eGFR < 30 mL/min per 1.73 m 2) groups. The risks of thromboembolism, major bleeding, and cardiovascular mortality were estimated with Fine-Gray regression analysis according to CKD status. Cox regression was performed to assess the risk of all-cause mortality associated with CKD. RESULTS:Over a mean follow-up of 4.1 ± 1.9 years, there were 985 thromboembolic events, 414 major bleeding events, 956 cardiovascular deaths, and 1,786 all-cause deaths. After multivariate adjustment, CKD was not an independent risk factor of thromboembolic events. As compared to patients with no CKD, those with mild CKD, moderate CKD, and severe CKD had a 45%, 47%, and 133% higher risk of major bleeding, respectively. There was a graded increased risk of cardiovascular mortality associated with CKD status compared with no CKD group: adjusted hazard ratio [HR] was 1.34 (95% CI: 1.07-1.68,P = 0.011) for mild CKD group, 2.17 (95% CI: 1.67-2.81,P < 0.0001) for moderate CKD group, and 2.95 (95% CI: 1.97-4.41, P < 0.0001) for severe CKD group, respectively. Risk of all-cause mortality also increased among patients with moderate or severe CKD. CONCLUSIONS:CKD status was independently associated with progressively higher risks of major bleeding and mortality, but didn't seem to be an independent predictor of thromboembolism in AF patients.
| S-EPMC8648544 | biostudies-literature
Project description:Background Chronic kidney disease ( CKD ) is a common comorbidity in patients with atrial fibrillation. The presence of CKD complicates drug selection for stroke prevention and rhythm control. Methods and Results Patients enrolled in ORBIT AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation) with baseline renal function and follow-up data were included (N=9019). CKD was defined as an estimated creatinine clearance <60 mL /min. Patient characteristics were compared by CKD status, and Cox proportional hazards modeling was used to examine the association between oral anticoagulant ( OAC ) use and outcomes and antiarrhythmic drug use and outcomes stratified by CKD stages. At enrollment, 3490 (39%) patients had an estimated creatinine clearance <60 mL /min. Patients with CKD were older and had higher CHA 2 DS 2 VAS c and Anticoagulant and Risk Factors in Atrial Fibrillation (ATRIA) scores. A rhythm control strategy was selected less frequently in patients with CKD , while OAC use was lower among Stage IV and V CKD patients. After adjustment, no significant interaction was noted for OAC and CKD on all-cause mortality ( P=0.5442) or cardiovascular death ( P=0.1233), although a trend for increased major bleeding ( P=0.0608) and stroke, systemic embolism or transient ischemic attack ( P=0.0671) was observed. No interaction was noted for antiarrhythmic drug use and CKD status on all-cause mortality ( P=0.9706), or stroke, systemic embolism or transient ischemic attack ( P=0.4218). Conclusions Patients with atrial fibrillation and CKD are less likely to be treated with rhythm control. Patients with advanced CKD are less likely to receive OAC . Finally, outcomes with OAC in patients with advanced CKD may be materially different with higher rates of both bleeding and stroke.
| S-EPMC6222961 | biostudies-literature