Prediction of Incident Atrial Fibrillation in Chronic Kidney Disease: The Chronic Renal Insufficiency Cohort Study

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SAMe-TT2R2 Score,Time in Therapeutic Range,and Outcomes in Anticoagulated Patients with Atrial Fibrillation

BackgroundOral anticoagulation is highly effective in preventing stroke and mortality in nonvalvular atrial fibrillation patients. However, the efficacy and safety of vitamin K antagonists (the main oral anticoagulation drug used) strongly depends upon the quantity of anticoagulation control, as reflected by the average percentage of the time in therapeutic range of international normalized ratio 2.0-3.0. An easy, simple prediction of which atrial fibrillation patients are likely to do well on vitamin K antagonists (with good average time in therapeutic range) could guide decision-making between using vitamin K antagonists (eg, warfarin) and non-vitamin K antagonist oral anticoagulants.Methods and ResultsIn a consecutive cohort of nonvalvular atrial fibrillation patients attending our anticoagulation clinic, we tested the hypothesis that the new Sex, Race, Medical history, Tobacco use, Race (SAMe-TT₂R₂) score was a predictor for good average time in therapeutic range, and second, this would translate into adverse events in a “real world” cohort of patients with nonvalvular atrial fibrillation. The incidence of bleeding, adverse cardiovascular events (including stroke/thromboembolism), and mortality during the follow-up was higher with increasing SAMe-TT₂R₂ score. The SAMe-TT₂R₂ score was predictive for the composite of all adverse events (hazard ratio 1.32 [95% Confidence Interval 1.17-1.50]; P <.001), adverse cardiovascular events (1.52 [1.28-1.83]; P <.001), and all-cause mortality (1.41 [1.16-1.67]; P = .001). A trend was also observed for major bleeding events (1.23 [0.99-1.53]; P = .059).ConclusionIn a “real world” cohort of consecutive patients with nonvalvular atrial fibrillation, a high SAMe-TT₂R₂ score (reflecting poor anticoagulation control with poor time in therapeutic range) was associated with more bleeding, adverse cardiovascular events, and mortality during follow-up.     

Prevalence of Atrial Fibrillation and Its Predictors in Nondialysis Patients with Chronic Kidney Disease

Background and objectives: Chronic kidney disease (CKD) increases systemic inflammation, which is implicated in development and maintenance of atrial fibrillation (AF); therefore, we hypothesized that the prevalence of AF would be increased among nondialysis patients with CKD. This study also reports independent predictors of the presence of AF in this population.Design, setting, participants, & measurements: A retrospective, cross-sectional analysis of 1010 consecutive nondialysis patients with CKD from two community-based hospitals was conducted. Estimated GFRs (eGFRs) were calculated using the Modification of Diet in Renal Disease (MDRD) equation. Multivariate logistic regression was used to determine independent predictors.Results: Of 1010 nondialysis patients with CKD, 214 (21.2%) had AF. Patients with AF were older than patients without AF (76 ± 11 versus 63 ± 15 yr). The prevalence of AF among white patients (42.7%) was higher than among black patients (12.7%) or other races (5.7%). In multivariate analyses, age, white race, increasing left atrial diameter, lower systolic BP, and congestive heart failure were identified as independent predictors of the presence of AF. Although serum high-sensitivity C-reactive protein levels were elevated in our population (5.2 ± 7.4 mg/L), levels did not correlate with the presence of AF or with eGFR. Finally, eGFR did not correlate with the presence of AF in our population.Conclusions: The prevalence of AF was increased in our population, and independent predictors were age, white race, increasing left atrial diameter, lower systolic BP, and congestive heart failure.Atrial fibrillation (AF) is the most common arrhythmia in clinical practice (1). Cardiac comorbidities that are associated with AF include hypertension, coronary artery disease (CAD), valvular heart disease (VHD), congestive heart failure (CHF), cardiomyopathy, pericarditis, congenital heart disease (CHD), and cardiac surgery (2–9). Noncardiac comorbidities that are associated with AF include acute pulmonary embolism, chronic obstructive pulmonary disease (COPD), obstructive sleep apnea, hyperthyroidism, and obesity (10–14).Evidence suggests that inflammation is involved in the pathogenesis of AF (15–20). For example, AF after cardiac surgery is associated with proinflammatory cytokine and complement activation (16,19). Moreover, patients with refractory lone AF have inflammatory infiltrates, myocyte necrosis, and fibrosis on biopsy (18). Several studies also reported elevated serum high-sensitivity C-reactive protein (hsCRP) levels in patients with AF (15–17,20).Evidence suggests that inflammation is associated with renal dysfunction (21–24). Proposed mechanisms include decreased proinflammatory cytokine clearance, endotoxemia, oxidative stress, and reduced antioxidant levels (23,24). Moreover, hsCRP levels are higher among elderly patients with renal insufficiency (24). In hemodialysis (HD) patients with ESRD, hsCRP, IL-6, and fibrinogen levels are elevated (21,22).HD patients with ESRD have an increased prevalence of AF; however, prevalence among nondialysis patients with CKD has not been investigated (25–30). Because CKD promotes inflammation, which promotes AF, we hypothesized the prevalence of AF would be increased among nondialysis patients with CKD. This study reports the prevalence and independent predictors of the presence of AF in a nondialysis population with CKD.     

Dabigatran and Warfarin for Secondary Prevention of Stroke in Atrial Fibrillation Patients: A Nationwide Cohort Study

Background

This register-based observational study compares dabigatran to warfarin for secondary stroke prevention in atrial fibrillation patients among both “new starters” on dabigatran and “switchers” to dabigatran from warfarin.

Methods

We identified, in nationwide Danish registries, 2398 patients with atrial fibrillation and a history of stroke/transient ischemic attack, making a first-time purchase of dabigatran 110 mg twice a day (bid; D110) and 150 mg bid (D150). Patients were categorized as either vitamin K antagonist (VKA) naive or experienced. Warfarin controls were identified using a complete (for VKA-naive dabigatran patients) or matched sampling approach (for VKA-experienced dabigatran patients). Subjects were followed for an average of 12.6 months for stroke and transient ischemic attacks. Confounder-adjusted Cox regression models were used to compare event rates between treatments.

Results

Among patients with a history of stroke/transient ischemic attack and prior VKA experience, switching to dabigatran was associated with an increased stroke/transient ischemic attack rate for both dabigatran doses compared with continuing on warfarin (D110 hazard ratio [HR] 1.99; 95% confidence interval [CI], 1.42-2.78; D150 HR 2.34; 95% CI, 1.60-3.41). Among prior stroke/transient ischemic attack patients who were new starters on dabigatran or warfarin, the rate of stroke/transient ischemic attack for both doses of dabigatran was similar to or lower than warfarin (D110 HR 0.64; 95% CI, 0.50-0.80; D150 HR 0.92l; 95% CI, 0.73-1.15).

Conclusions

In this register-based study, VKA-experienced patients with a history of stroke or transient ischemic attack who switched to dabigatran therapy had an increased rate of stroke compared with patients persisting with warfarin therapy.     

非透析慢性肾脏病患者肾小球滤过率的评估值与动脉硬化的相关性

目的 通过测量非透析慢性肾脏病(CKD)患者的踝臂指数(ABI)及肾小球滤过率的评估值(eGFR),分析ABI作为评估CKD患者动脉硬化程度的临床意义.方法 横断面研究诊断明确的非透析CKD(1-5期)患者118例,记录患者性别、年龄、身高、体重、吸烟状况、血压、空腹血糖、高密度脂蛋白胆固醇(HDLC)、低密度脂蛋白胆固醇(LDLC)、肾功能.通过简化的肾脏病膳食改良公式计算eGFR,多普勒血流检测仪测定ABI.结果 按eGFR水平分为CKD1期、CKD2期、CKD3期、CKD4期、CKD5期五个组,与CKD1期组比较,CKD3期组、CKD4期组、CKD5期组ABI值明显降低(P＜0.01),但CKD1期组与CKD2期组间ABI值无统计学差异(P＞0.05).在CKD 2-5期组间随着eGFR降低,ABI值也逐渐下降(P＜0.01).多元线性回归分析显示,年龄、糖尿病、高血压和eGFR为ABI的独立危险因素(P＜0.01).结论 肾功能减退是动脉硬化的独立危险因素,eGFR下降与动脉硬化病变程度密切相关,而ABI可作为评估CKD患者动脉硬化程度的重要临床指标.     

The Atrial Fibrillation Better Care (ABC) Pathway and Clinical Outcomes in Patients with Atrial Fibrillation: the Prospective Murcia AF Project Phase II Cohort

BackgroundThe Atrial fibrillation Better Care (ABC) pathway was proposed for a more holistic or integrated care approach to atrial fibrillation (AF) management. We investigated whether adherence with the ABC pathway reduced the risk of adverse clinical outcomes in real-world AF patients starting vitamin K antagonist (VKAs) therapy.MethodsProspective cohort study including AF outpatients starting VKA therapy from July 2016 to June 2018. Patients were considered as adherent if all ABC pathway criteria (A: Avoid stroke; B: Better symptom control; and C: Cardiovascular risk factors/comorbidities management) were fulfilled. The primary endpoints were all-cause mortality, net clinical outcomes (NCOs), major adverse cardiovascular events (MACE), and composite thrombotic/thromboembolic events at 2 years.ResultsWe enrolled 1045 patients (51.6% female; median age 77 [70–83] years). Of these, 63.0% (658) were adherent to the ABC pathway and 37% (387) were considered non-adherent. Compared to non-adherent patients, those who were ABC adherent had lower event rates for all-cause mortality (13.76 vs. 6.56; p<0.001), NCOs (19.65 vs. 11.94; p<0.001), and MACE (11.88 vs. 7.75; p=0.006) during the follow-up. Adjusted Cox regression analyses demonstrated that the ABC pathway adherent care reduced the risks of all-cause mortality (aHR 0.57, 95% CI 0.42–0.78), NCOs (aHR 0.72, 95% CI 0.56–0.92), and cardiovascular mortality (aHR 0.54, 95% CI 0.32–0.90). Event-free survivals for all-cause mortality, NCOs (both log-rank p-values <0.001), and MACE (log-rank p-value = 0.004) were also higher in ABC pathway adherent patients.ConclusionsIn this real-world prospective cohort of AF patients starting VKA therapy, adherence to the ABC pathway management at baseline significantly reduced the risk of NCOs, all-cause mortality, and cardiovascular death at 2 years.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11606-022-07567-5.KEY WORDS: Atrial fibrillation, ABC pathway, Integrated care, Mortality, MACE     

The Association of Losartan and Ramipril Therapy With Kidney and Cardiovascular Outcomes in Patients With Chronic Kidney Disease: A Chinese Nation-Wide Cohort Study in Taiwan

The aim of this nation-wide cohort study was to assess the association of using an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin II receptor blocker (ARB) therapy on the prognosis of hypertensive patients with chronic kidney disease (CKD).We used Cox''s proportional hazard regression model to estimate hazard ratios (HRs) for the risk of end-stage renal disease (ESRD), all-cause mortality, cardiovascular mortality, and first hospitalization for cardiovascular disease (CVD) for losartan and ramipril versus conventional antihypertensive agents.In total, 136,266 hypertensive patients with CKD in Taiwan were followed up from 2001 to 2008. In an average follow-up of 5.9 years, 7364 (5.40%) patients reached ESRD, 4165 (3.06%) patients died, and 6163 (4.52%) patients had their first hospitalization for CVD. Use of losartan or ramipril was associated with a lower risk of the endpoints compared with the conventional group. In the losartan group, the risks of ESRD, all- and cardiovascular-cause mortality, and first hospitalization for CVD were decreased by 9.2% (P = 0.01), 24.6% (P < 0.001), 12.4% (P = 0.03), and 36.0% (P = 0.01), respectively. In the ramipril group, these risks decreased by 7.6% (P = 0.02) for ESRD, 56.9% (P < 0.001) for all-cause mortality, 7.5% (P = 0.04) for cardiovascular mortality, and 24.7% (P < 0.001) for first hospitalization.This study indicated that losartan and ramipril had distinct association on the prognosis of hypertensive patients with CKD, and was first to disclose that the mean time to reach each endpoint for patients in the losartan, ramipril, and conventional group was not significantly different. However, further study is needed to confirm results of the present study.     

Oral Anticoagulants and Antiplatelet Agents in Patients With Atrial Fibrillation and Concomitant Critical Limb Ischemia: A Nationwide Cohort Study

BackgroundEvidence of clinical outcomes for oral anticoagulants and antiplatelet treatment (APT) in patients with atrial fibrillation (AF) and critical limb ischemia (CLI) is very limited.MethodsIn this nationwide retrospective cohort study collected from Taiwan National Health Insurance Research Database, 1223 patients with AF and CLI taking direct-acting oral coagulants (DOACs), warfarin, or APT were identified from June 1, 2012, to December 31, 2017. We used propensity score stabilized weighting (PSSW) to balance covariates across study groups.ResultsAfter PSSW, DOAC (n = 446) was associated with lower risks of ischemic stroke/systemic embolism (IS/SE), all major adverse limb events, and all major bleeding events compared with warfarin (n = 237). DOAC was associated with lower risks of IS/SE, acute myocardial infarction (AMI), and all major adverse limb events and a comparable risk of major bleeding events compared with APT (n = 540). DOAC has a lower risk of composite net-clinical-benefit outcome (IS/SE, AMI, all major adverse limb events, plus all major bleeding events) compared with warfarin (hazard ratio [HR]: 0.48; 95% confidence interval [CI]: 0.35-0.65; P < 0.0001) or APT (HR: 0.44; 95% CI: 0.34-0.56; P < 0.0001). The composite net-clinical-benefit outcome was comparable for warfarin vs APT. The reduced risk of net-clinical-benefit outcome for DOAC vs warfarin or APT persisted in high subgroups including age > 75 years, presence of diabetes mellitus, or chronic kidney disease.ConclusionsDOAC was associated with a significantly lower risk of composite net-clinical-benefit outcome than either warfarin or APT in patients with AF and concomitant CLI. Further prospective study is necessary to validate the findings in the future.     

Peripheral Arterial Disease in Patients with Atrial Fibrillation: The AFFIRM Study

BackgroundPeripheral arterial disease has been linked with worse outcomes in patients with atrial fibrillation. The aim of this study is to assess the impact of peripheral arterial disease on mortality and stroke in a cohort of patients with atrial fibrillation.MethodsThis was an ancillary analysis of the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial. A comparison of baseline characteristics was made between patients with atrial fibrillation with and without diagnosed peripheral arterial disease. Multivariate cox regression analysis was performed to compare the risk of stroke, death, and cardiovascular death among the two groups.ResultsThe prevalence of peripheral arterial disease in the whole cohort of 4060 patients with atrial fibrillation was 6.7%. Patients with peripheral arterial disease tended to be older; had higher prevalence of diabetes mellitus, hypertension, and smoking; and were more likely to have a history of coronary artery disease, heart failure, cardiac surgery or cardiac intervention, and stroke or transient ischemic attack (all P < .05). After multivariate adjustment, peripheral arterial disease was significantly associated with overall higher mortality (hazard ratio 1.34, 95% confidence interval 1.06-1.70, P = .016) in patients with atrial fibrillation, but the rates of ischemic stroke were similar in the two groups (3.9% vs 3.5%, P = 0.874).Subgroup analysis confined to the patients with non-anticoagulated atrial fibrillation showed that peripheral arterial disease was an independent predictor of ischemic stroke (hazard ratio 3.37, 95% confidence interval 1.25-9.09, P < .016).ConclusionPeripheral arterial disease predicts higher mortality in atrial fibrillation, and was an independent predictor of ischemic stroke in patients with non-anticoagulated atrial fibrillation. Proactive surveillance and optimization of medical management in this group of patients is warranted, given the high risks associated with peripheral arterial disease where atrial fibrillation is also present.     

Influenza Vaccination Reduces Dementia Risk in Chronic Kidney Disease Patients: A Population-Based Cohort Study

Taiwan has the highest prevalence of chronic kidney disease (CKD) worldwide. CKD, a manifestation of vascular diseases, is associated with a high risk of dementia. Here, we estimated the association between influenza vaccination and dementia risk in patients with CKD.Data from the National Health Insurance Research Database of Taiwan were used in this study. The study cohort included all patients diagnosed with CKD (according to International Classification of Disease, Ninth Revision, Clinical Modification codes) at healthcare facilities in Taiwan (n = 32,844) from January 1, 2000, to December 31, 2007. Each patient was followed up to assess dementia risk or protective factors: demographic characteristics of age and sex; comorbidities of diabetes, hypertension, dyslipidemia, cerebrovascular diseases, parkinsonism, epilepsy, substance and alcohol use disorders, mood disorder, anxiety disorder, psychotic disorder, and sleep disorder; urbanization level; monthly income; and statin, metformin, aspirin, and angiotensin-converting enzyme inhibitor (ACEI) use. A propensity score was derived using a logistic regression model for estimating the effect of vaccination by accounting for covariates that predict receiving the intervention (vaccine). A time-dependent Cox proportional hazard model was used to calculate the hazard ratios (HRs) of dementia among vaccinated and unvaccinated CKD patients.The study population comprised 11,943 eligible patients with CKD; 5745 (48%) received influenza vaccination and the remaining 6198 (52%) did not. The adjusted HRs (aHRs) of dementia decreased in vaccinated patients compared with those in unvaccinated patients (influenza season, noninfluenza season, and all seasons: aHRs = 0.68, 0.58, and 0.64; P < 0.0001, P < 0.0001, and P < 0.0001, respectively). In the sensitivity analysis, adjustments were made to estimate the association of age and sex; diabetes, dyslipidemia, hypertension, cerebrovascular diseases, anxiety disorder; and statin, metformin, ACEI, and aspirin use with the incidence of dementia in various models. A stronger protective effect against dementia risk was demonstrated during the noninfluenza season. Regardless of comorbidities or drug use, influenza vaccination was an independent protective factor and dose-dependently reduced the risk of dementia in CKD patients.Influenza vaccination exerts dose–response and synergistic protective effects against dementia in CKD patients with dementia risk factors by reducing the incidence of dementia.     

Risk of Periodontal Diseases in Patients With Chronic Obstructive Pulmonary Disease: A Nationwide Population-based Cohort Study

Several studies have reported an association between chronic obstructive pulmonary disease (COPD) and periodontal diseases. However, a large-scale population-based cohort study was previously absent from the literature. Therefore, we evaluated the risk of periodontal diseases in patients with COPD in a nationwide population.From the National Health Insurance claims data of Taiwan, we identified 22,332 patients with COPD who were newly diagnosed during 2000 to 2010. For each case, two individuals without COPD were randomly selected and frequency matched by age, sex, and diagnosis year. Both groups were followed up till the end of 2011.The overall incidence of periodontal diseases was 1.19-fold greater in the COPD group than in the comparison group (32.2 vs 26.4 per 1000 person-years; 95% confidence interval [CI] 1.15–1.24). Compared with non-COPD patients, the adjusted hazard ratios of patients with COPD increased with the number of emergency room visits (from 1.14 [95% CI 1.10–1.19] to 5.09 [95% CI 4.53–5.72]) and admissions (from 1.15 [95% CI 1.10–1.20] to 3.17 [95% CI 2.81–3.57]). In addition, the adjusted hazard ratios of patients with COPD treated with inhaled corticosteroids (1.22, 95% CI 1.11–1.34) and systemic corticosteroids (1.15, 95% CI 1.07–1.23) were significantly higher than those of patients not treated with corticosteroids.Patient with COPD are at a higher risk of developing periodontal diseases than the general population. Our results also support that the risk of periodontal diseases is proportional to COPD control. In addition, patients who receive corticosteroid treatment are at a higher risk of developing periodontal diseases.     

A Taiwanese Nationwide Cohort Study Shows Interferon-Based Therapy for Chronic Hepatitis C Reduces the Risk of Chronic Kidney Disease

Hepatitis C virus (HCV) infection is a risk factor for chronic kidney disease (CKD). However, it remains unclear whether interferon-based therapy (IBT) for HCV was associated with reduced risk of CKD.From the Taiwan National Health Insurance Research Database, we identified 919 patients who received 3 months or more of IBT as our treated cohort. This cohort was propensity score-matched 1:4 with 3676 controls who had never received IBT for HCV infection (untreated cohort). Cumulative incidences of and hazard ratios (HRs) for CKD were calculated after adjusting for competing mortality.In the matched HCV cohort, the risk of CKD was significantly lower in the treated cohort (7-year cumulative incidence, 2.6%; 95% confidence interval [CI], 0.7%–6.9%) than in the untreated cohort (4%; 95% CI, 3.5%–5.2%) (P < 0.001), with an adjusted HR of 0.42 (95% CI, 0.20–0.92; P = 0.03). The results also held in the overall HCV cohort. The number needed to treat for 1 fewer CKD at 7 years was 58. The reduced risk of CKD was greatest (0.35; 0.14–0.87; P = 0.024) in HCV-infected patients who received 6 months or more of IBT. Multivariable stratified analysis verified that greater risk reduction of CKD was present in HCV-infected patients with hyperlipidemia, diabetes, hypertension, and those without coronary heart disease.In conclusion, IBT, especially for 6 or more months, is associated with reduced risk of CKD in HCV-infected patients. Hyperlipidemia, diabetes, hypertension, and coronary heart disease can modify this association.