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1.
Diabetes Obes Metab ; 2020 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-32227432

RESUMO

AIM: To investigate the association of the Thrombolysis In Myocardial Infarction (TIMI) Risk Score for Heart Failure in Diabetes (TRS-HFDM ) with mortality using data from the EMPA-REG OUTCOME trial. MATERIALS AND METHODS: In EMPA-REG OUTCOME, patients with type 2 diabetes and atherosclerotic cardiovascular (CV) disease (N = 7020) received the sodium-glucose co-transporter-2 inhibitor, empagliflozin, 10 or 25 mg or placebo. Post hoc, patients were stratified into risk categories (low-intermediate, high, very-high risk scores) using baseline TRS-HFDM . Cox regression analyses evaluated the association of TRS-HFDM categories with all-cause mortality (ACM), CV death, hospitalization for heart failure (HHF) and CV death (excluding fatal stroke) or HHF, and whether empagliflozin reduced the risk of CV outcomes across these risk categories. RESULTS: In placebo patients, increasing risk category was associated with a higher risk of ACM, CV death, and HHF. Empagliflozin reduced the risk of ACM (low-intermediate HR 0.68 [95% CI 0.48, 0.97] and very-high 0.69 [0.52, 0.91]), CV death (0.75 [0.48, 1.18] and 0.56 [0.41, 0.78]), HHF (0.53 [0.28, 1.01] and 0.67 [0.48, 0.96]), and CV death or HHF (0.69 [0.46, 1.03]) and (0.64 [0.49, 0.82]) across all risk categories versus placebo. Higher absolute risk reductions (ARRs) were observed for CV death in the very-high versus low-intermediate category (P = 0.01). CONCLUSIONS: Applied to EMPA-REG OUTCOME, higher TRS-HFDM was associated with increased HHF and mortality risk. Empagliflozin reduced CV outcomes across TRS-HFDM categories. Higher ARRs were associated with higher risk scores.

2.
J Med Genet ; 2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32161151

RESUMO

BACKGROUND: Fabry disease (α-galactosidase deficiency) is an X-linked genetic disease caused by a variety of pathogenic GLA variants. The phenotypic heterogeneity is considerable, with two major forms, classic and later-onset disease, but adjudication of clinical phenotype is currently lacking for many variants. We aimed to determine consensus phenotypic classification for previously unclassified GLA variants from the GLA-specific fabry-database.org database. METHODS: A Fabry disease genotype-phenotype workgroup developed a five-stage iterative system based on expert clinical assessment, published literature and clinical evidence of pathogenicity using a 2-point scoring system based on clinical hallmarks of classic disease. Kaplan-Meier (KM) analysis of severe clinical event-free survival was used as final validation. Results were compared with those from web-based disease databases and in silico pathogenicity prediction programmes. RESULTS: Final consensus on classifications of 'pathogenic' was achieved for 32 of 33 GLA variants (26 'classic' phenotype, 171 males; 6 'later-onset' phenotype, 57 males). One variant remained of uncertain significance. KM curves were similar for the known fabry-database.org database phenotypes and when workgroup consensus classifications were added, and the curves retained the same separation between 'classic' and 'later-onset' phenotypes. CONCLUSION: The iterative system implemented by a Fabry disease genotype-phenotype workgroup achieved phenotypic classifications for variants that were previously unclassified. Clinical pathogenicity associated with a particular GLA variant defined in affected males appears to have predictive value and also generally correlates with risk for affected females. The newly established classifications can be of benefit to the clinical care of Fabry patients harbouring these variants.

3.
Artigo em Inglês | MEDLINE | ID: mdl-32040154

RESUMO

BACKGROUND: Cardiovascular disease (CVD) is a major contributor to morbidity and mortality in people on hemodialysis (HD). Cardiovascular outcomes are reported infrequently and inconsistently across trials in HD. This study aimed to identify the priorities of patients/caregivers and health professionals (HPs) for CVD outcomes to be incorporated into a core outcome set reported in all HD trials. METHODS: In an international online survey, participants rated the absolute importance of 10 cardiovascular outcomes (derived from a systematic review) on a 9-point Likert scale, with 7-9 being critically important. The relative importance was determined using a best-worst scale. Likert means, medians and proportions and best-worst preference scores were calculated for each outcome. Comments were thematically analyzed. RESULTS: Participants included 127 (19%) patients/caregivers and 549 (81%) HPs from 53 countries, of whom 530 (78%) completed the survey in English and 146 (22%) in Chinese. All but one cardiovascular outcome ('valve replacement') was rated as critically important (Likert 7-9) by all participants; 'sudden cardiac death', 'heart attack', 'stroke' and 'heart failure' were all rated at the top by patients/caregivers (median Likert score 9). Patients/caregivers ranked the same four outcomes as the most important outcomes with mean preference scores of 6.2 (95% confidence interval 4.8-7.5), 5.9 (4.6-7.2), 5.3 (4.0-6.6) and 4.9 (3.6-6.3), respectively. The same four outcomes were ranked most highly by HPs. We identified five themes underpinning the prioritization of outcomes: 'clinical equipoise and potential for intervention', 'specific or attributable to HD', 'severity or impact on the quality of life', 'strengthen knowledge and education', and 'inextricably linked burden and risk'. CONCLUSIONS: Patients and HPs believe that all cardiovascular outcomes are of critical importance but consistently identify sudden cardiac death, myocardial infarction, stroke and heart failure as the most important outcomes to be measured in all HD trials.

4.
ESC Heart Fail ; 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-32100468

RESUMO

AIMS: Long-term treatment effect studies in large female Fabry patient groups are challenging to design because of phenotype heterogeneity and lack of appropriate comparison groups, and have not been reported. We compared long-term cardiomyopathy and kidney function outcomes after agalsidase beta treatment with preceding treatment-naive outcomes. METHODS AND RESULTS: Self-controlled pretreatment and post-treatment comparison (piecewise mixed linear modelling) included Fabry female patients ≥18 years at treatment initiation who received agalsidase beta (0.9-1.1 mg/kg every other week) for ≥2 years, with ≥2 pretreatment and ≥2 post-treatment outcome measurements during 10-year follow-up. Left ventricular posterior wall thickness (LVPWT)/interventricular septal thickness (IVST) and estimated glomerular filtration rate (eGFR, Chronic Kidney Disease Epidemiology Collaboration creatinine equation) analyses included 42 and 86 patients, respectively, aged 50.0 and 46.3 years at treatment initiation, respectively. LVPWT and IVST increased pretreatment (follow-up 3.5 years) but stabilized during 3.6 years of treatment (LVPWT: n = 38, slope difference [95% confidence interval (CI)] = -0.41 [-0.68, -0.15] mm/year, Ppre-post difference  <0.01; IVST: n = 38, slope difference = -0.32 [-0.67, 0.02] mm/year, Ppre-post difference  = 0.07). These findings were not modified by renal involvement or antiproteinuric agent use. Compared with the treatment-naive period (follow-up 3.6 years), eGFR decline remained modest and stabilized within normal ranges during 4.1 years of treatment (slope difference, 95% CI: -0.13 [-1.15, 0.89] mL/min/1.73m2 /year, Ppre-post difference  = 0.80). CONCLUSIONS: Cardiac hypertrophy, progressing during pretreatment follow-up, appeared to stabilize during sustained agalsidase beta treatment. eGFR decline remained within normal ranges. This suggests that treatment may prevent further Fabry-related progression of cardiomyopathy in female patients and maintain normal kidney function.

6.
Diabetes Obes Metab ; 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-32030863

RESUMO

In the EMPA-REG OUTCOME trial, we explored the association between pre-randomization uric acid level tertile (<309.30 µmol/L; 309.30 to <387.21 µmol/L; ≥387.21 µmol/L) and cardiovascular (CV) death, hospitalization for heart failure (HHF), HHF or CV death, all-cause mortality, three-point major adverse CV events (MACE), and incident or worsening nephropathy. Patients with type 2 diabetes and CV disease received empagliflozin or placebo. The median baseline plasma uric acid level was 344.98 µmol/L, and patients' baseline characteristics were mainly balanced across tertiles. Baseline uric acid levels were associated with cardio-renal outcomes: in the placebo group, for the highest versus lowest tertile, the multivariable hazard ratios for three-point MACE, HHF or CV death, and incident or worsening nephropathy were 1.22 (95% confidence interval [CI] 0.89-1.67; P = 0.2088), 1.51 (95% CI 1.02-2.23; P = 0.0396) and 1.77 (95% CI 1.33-2.34; P < 0.0001), respectively. When tested as a continuous variable, baseline uric acid was associated with all outcomes in the placebo group. Empagliflozin improved all cardio-renal outcomes across tertiles, with all interaction P values >0.05. Further investigation of these relationships is required.

7.
Eur J Prev Cardiol ; : 2047487320905721, 2020 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-32089004

RESUMO

AIMS: Haemodialysis patients have high cardiovascular disease risk. Although statins reduce this risk in chronic kidney disease, randomised trials in haemodialysis patients show no benefit. Post-hoc analyses of the German Diabetes Dialysis (4D) study identified patient-specific markers associated with heterogeneous treatment effects. We combined these markers to develop a score for predicting individual effects of statins in these patients. METHODS AND RESULTS: We used data from the 4D study, enrolling 1255 haemodialysis patients with type 2 diabetes mellitus, randomised to atorvastatin or placebo and followed for a composite cardiovascular endpoint. We calculated two scores: score 1 based on all 23 predictive markers and score 2 based on 17 clinically accessible markers. Groups stratified by score 1 showed differential treatment effects: for score <26 (458 patients; 36%), the hazard ratio (95% confidence interval) was 1.54 (1.16-2.03), suggesting harm; for 26-31 (331 patients; 26%), it was 1.03 (0.72-1.48), suggesting a neutral effect; and for >31 (466 patients; 38%), it was 0.43 (0.30-0.60), suggesting a benefit. Statins also significantly reduced all-cause mortality in the benefit group. Stratification by score 2 yielded similar results but a smaller group gaining benefit (360 patients). CONCLUSION: Statin effects in haemodialysis patients can be predicted by markers associated with plausible relevant mechanisms including cholesterol metabolism, atherosclerosis, protein energy wasting, or competing risks. In clinical practice, the score could aid in risk stratification, not only to select patients who benefit from statins but also to identify those whom treatment could harm.

8.
Diabetes Obes Metab ; 2020 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-32037653

RESUMO

AIMS: In CARMELINA®, linagliptin demonstrated cardiovascular and renal safety in patients with type 2 diabetes (T2D) with high renal and cardiovascular disease (CVD) risk. We investigated safety and efficacy of this dipeptidyl peptidase-4 inhibitor in older participants. MATERIALS AND METHODS: Subjects aged ≥18 years with T2D and established CVD with urinary albumin-to-creatinine ratio (UACR) >30 mg/g, and/or prevalent kidney disease, were randomized to linagliptin or placebo added to usual care. The primary endpoint (time to first occurrence of 3P-MACE: cardiovascular death, non-fatal myocardial infarction or non-fatal stroke) and other outcomes were evaluated across age groups <65 (n = 2968), 65 to <75 (n = 2800) and ≥75 years (n = 1211). RESULTS: Mean age was 65.9 years (17.4% and 5.9% aged ≥75 and 80, respectively) and median follow-up was 2.2 years. The hazard ratio (HR) for 3P-MACE with linagliptin versus placebo was 1.02 [95% confidence interval (CI) 0.89, 1.17] with no significant interaction between age and treatment effect (P = 0.0937). HRs for participants aged <65, 65 to <75 and ≥75 years were 1.11 (95% CI 0.89, 1.40), 1.09 (0.89, 1.33) and 0.76 (0.57, 1.02), respectively. Linagliptin did not increase the risk of adverse kidney outcomes or hospitalization for heart failure across age groups. The incidence of adverse events, including hypoglycaemia, increased with age but was similar with linagliptin and placebo despite glycated haemoglobin A1c reduction with linagliptin. CONCLUSIONS: Linagliptin did not increase risk for cardiovascular events or hypoglycaemia and kidney function remained stable in older people with T2D and established CVD with albuminuria and/or kidney disease.

9.
Environ Sci Technol ; 54(4): 2295-2303, 2020 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-31909614

RESUMO

U isotope fractionation may serve as an accurate proxy for U(VI) reduction in both modern and ancient environments, if the systematic controls on the magnitude of fractionation (ε) are known. We model the effect of U(VI) reduction kinetics on U isotopic fractionation during U(VI) reduction by a novel Shewanella isolate, Shewanella sp. (NR), in batch incubations. The measured ε values range from 0.96 ± 0.16 to 0.36 ± 0.07‰ and are strongly dependent on the U(VI) reduction rate. The ε decreases with increasing reduction rate constants normalized by cell density and initial U(VI). Reactive transport simulations suggest that the rate dependence of ε is due to a two-step process, where diffusive transport of U(VI) from the bulk solution across a boundary layer is followed by enzymatic reduction. Our results imply that the spatial decoupling of bulk U(VI) solution and enzymatic reduction should be taken into account for interpreting U isotope data from the environment.


Assuntos
Fracionamento Químico , Cromo , Isótopos , Cinética , Oxirredução
11.
Artigo em Inglês | MEDLINE | ID: mdl-31943084

RESUMO

BACKGROUND: Initiation of renal replacement therapy often results from a combination of kidney function deterioration and symptoms related to chronic kidney disease (CKD) progression. We investigated the association between kidney function decline and symptom development in patients with advanced CKD. METHODS: In the European Quality study on treatment in advanced CKD (EQUAL study), a European prospective cohort study, patients with advanced CKD aged ≥65 years and a kidney function that dropped <20 mL/min/1.73 m2 were followed for 1 year. Linear mixed-effects models were used to assess the association between kidney function decline and symptom development. The sum score for symptom number ranged from 0 to 33 and for overall symptom severity from 0 to 165, using the Dialysis Symptom Index. RESULTS: At least one kidney function estimate with symptom number or overall symptom severity was available for 1109 and 1019 patients, respectively. The mean (95% confidence interval) annual kidney function decline was 1.70 (1.32; 2.08) mL/min/1.73 m2. The mean overall increase in symptom number and severity was 0.73 (0.28; 1.19) and 2.93 (1.34; 4.52) per year, respectively. A cross-sectional association between the level of kidney function and symptoms was lacking. Furthermore, kidney function at cohort entry was not associated with symptom development. However, each mL/min/1.73 m2 of annual kidney function decline was associated with an extra annual increase of 0.23 (0.07; 0.39) in the number of symptoms and 0.87 (0.35; 1.40) in overall symptom severity. CONCLUSIONS: A faster kidney function decline was associated with a steeper increase in both symptom number and severity. Considering the modest association, our results seem to suggest that repeated thorough assessment of symptom development during outpatient clinic visits, in addition to the monitoring of kidney function decline, is important for clinical decision-making.

12.
Artigo em Inglês | MEDLINE | ID: mdl-31999317

RESUMO

AIMS: Trial evidence indicates that glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may reduce the risk of cardiovascular events in patients with diabetes and myocardial infarction (MI). We aimed to expand this observation to routine care settings. METHODS: Prospective observational study including all patients with diabetes surviving an MI and registered in the nationwide SWEDEHEART registry during 2010-2017. Multivariable Cox regression analyses was used to estimate the association between GLP-1 RAs use and the study outcome, which was a composite of stroke, heart failure, reinfarction or cardiovascular death. Covariates included demographics, comorbidities, presentation at admission and use of secondary cardiovascular prevention therapies. RESULTS: Total 17,868 patients with diabetes were discharged alive after a first event of MI. Their median age was 71 years, 36% were women and their median eGFR was 75 ml/min/1.73m2. Of those, 365 (2%) were using GLP-1 RAs. During median 3 years of follow-up, 7005 patients experienced the primary composite outcome. Compared to standard of diabetes care, use of GLP-1 RAs was associated with a lower event risk (adjusted HR 0.72; 95% CI: 0.56-0.92), mainly attributed to a lower rate of reinfarction and stroke. Results were similar after propensity score matching or when compared to users of sulfonylurea. There was no suggestion of heterogeneity across subgroups of age, sex, chronic kidney disease and STEMI. CONCLUSIONS: GLP-1 RAs use, compared to standard of diabetes care, was associated with lower risk for major cardiovascular events in healthcare-managed survivors of an MI.

13.
Eur Heart J ; 41(2): 209-217, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31504427

RESUMO

AIMS: Hypoglycaemia, in patients with Type 2 diabetes (T2D) is associated with an increased risk for cardiovascular (CV) events. In EMPA-REG OUTCOME, the sodium-glucose co-transporter-2 inhibitor empagliflozin reduced the risk of CV death by 38% and heart failure hospitalization (HHF) by 35%, while decreasing glycated haemoglobin (HbA1c) without increasing hypoglycaemia. We investigated CV outcomes in patients with hypoglycaemia during the trial and the impact of hypoglycaemia on the treatment effect of empagliflozin. METHODS AND RESULTS: About 7020 patients with T2D (HbA1c 7-10%) were treated with empagliflozin 10 or 25 mg, or placebo and followed for median 3.1 years. The relationship between on-trial hypoglycaemia and CV outcomes, and effects of empagliflozin on outcomes by incident hypoglycaemia [HYPO-broad: symptomatic hypoglycaemia with plasma glucose (PG) ≤70 mg/dL, any hypoglycaemia with PG <54 mg/dL, or severe hypoglycaemia, and HYPO-strict: hypoglycaemia with PG <54 mg/dL, or severe hypoglycaemia] was investigated using adjusted Cox regression models with time-varying covariates for hypoglycaemia and interaction with treatment. HYPO-broad occurred in 28% in each group and HYPO-strict in 19%. In the placebo group, hypoglycaemia was associated with an increased risk of HHF for both HYPO-broad [hazard ratio (HR, 95% confidence interval, CI) 1.91 (1.25-2.93)] and HYPO-strict [1.72 (1.06-2.78)]. HYPO-broad (but not HYPO-strict) was associated with an increased risk of myocardial infarction (MI) [HR 1.56 (1.06-2.29)]. Empagliflozin improved CV outcomes, regardless of occurrence of hypoglycaemia (P-for interactions >0.05). CONCLUSION: In this post hoc exploratory analysis, hypoglycaemia was associated with an increased risk of HHF and MI. Hypoglycaemia risk was not increased with empagliflozin and incident hypoglycaemia did not attenuate its cardio-protective effects.

14.
Nephrol Dial Transplant ; 35(2): 222-226, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31598700

RESUMO

In January 2019, the ERA-EDTA surveyed nephrologists with questions on kidney care and kidney research designed to explore comprehension of the impact of alterations to organization of renal care and of advancements in technology and knowledge of kidney disease. Eight hundred and twenty-five ERA-EDTA members, ∼13% of the whole ERA-EDTA membership, replied to an ad hoc questionnaire. More than half of the respondents argued that kidney centres will be increasingly owned by large dialysis providers, nearly a quarter of respondents felt that many medical aspects of dialysis will be increasingly overseen by non-nephrologists and a quarter (24%) also believed that the care and long-term follow-up of kidney transplant patients will be increasingly under the responsibility of transplant physicians caring for patients with any organ transplant. Nearly half of the participants (45%, n = 367) use fully electronic clinical files integrating the clinical ward, the outpatient clinics, the haemodialysis and peritoneal dialysis units, as well as transplantation. Smartphone-based self-management programmes for the care of chronic kidney disease (CKD) patients are scarcely applied (only 11% of surveyed nephrologists), but a substantial proportion of respondents (74%) are eager to know more about the potential usefulness of these apps. Finally, European nephrologists expressed a cautious optimism about the application of omic sciences to nephrology and on wearable and implantable kidneys, but their expectations for the medium term are limited.

15.
J Clin Periodontol ; 47(1): 19-29, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31603565

RESUMO

AIM: To assess the prevalence and severity of periodontitis in patients with moderate chronic kidney disease (CKD) and comparing the results with the self-reported periodontitis awareness of the study subjects. MATERIAL AND METHODS: The periodontal status of 270 patients with moderate CKD randomly selected from a cohort of 5,217 subjects participating in the prospective observational German Chronic Kidney Disease (GCKD) project was analysed by recording bleeding on probing (BOP), probing pocket depth (PPD) and clinical attachment level (CAL). Furthermore, the awareness of the study subjects of their periodontal conditions was evaluated by a self-reported questionnaire. RESULTS: 24.4% of the CKD study patients showed no or only mild signs of periodontal disease, 47.6% displayed moderate and 27% severe periodontitis. Questionnaire data revealed that 62.3% of the study subjects with severe periodontitis were not aware of the presence of the disease, 44.4% denied having received any systematic periodontal therapy so far, although 50% of them indicated to visit their dentist regularly for professional tooth cleanings. CONCLUSION: While the clinical study data confirm an increased prevalence of periodontitis in CKD patients, their self-reported awareness of periodontitis was low.

16.
Eur J Heart Fail ; 22(1): 126-135, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31820559

RESUMO

AIMS: Atrial fibrillation (AF) is common in patients with diabetes and heart failure (HF) and increases the future risk of adverse cardiovascular (CV) outcomes. This analysis from the EMPA-REG OUTCOME trial explores CV and renal outcomes in patients with vs. without AF at baseline and assesses the benefits of empagliflozin. METHODS AND RESULTS: Analyses were conducted on patients distinguished by the presence (n = 389) or absence (n = 6631) of AF at baseline. Outcome events were more frequent in patients with AF than those without AF. Empagliflozin compared to placebo reduced CV death or HF hospitalisation consistently in patients with AF [hazard ratio (HR) 0.58, 95% confidence interval (CI) 0.36-0.92] and without AF (HR 0.67, 95% CI 0.55-0.82, Pinteraction  = 0.56). Similar results were observed for the components of this endpoint, all-cause mortality, new or worsening nephropathy, first introduction of loop diuretics, or occurrence of oedema. The absolute number of prevented events was higher in patients with AF, resulting in larger absolute treatment effects of empagliflozin. New loop diuretics or oedema were associated with increased rates of subsequent events, and rates appeared lower in those randomised to empagliflozin. CONCLUSIONS: In patients with type 2 diabetes mellitus and established CV disease, those with AF at baseline had higher rates of adverse HF outcomes than those without AF. Irrespective of the presence of AF, empagliflozin reduced HF-related and renal events. The absolute number of prevented events is higher in patients with AF than without AF. Patients with diabetes, CV disease and AF may especially benefit from use of empagliflozin.

18.
Artigo em Inglês | MEDLINE | ID: mdl-31711188

RESUMO

BACKGROUND: In renal studies, various outcome endpoints are used with variable definitions, making it nearly impossible to perform meta-analyses and deduce meaningful conclusions. Increasing attention is directed towards standardization of renal outcome reporting. METHODS: A working group was formed to produce a unifying definition of renal outcomes that can be used by all investigators. We propose major adverse renal events (MARE) as the term for a standardized composite of hard renal outcomes. We discuss the components for inclusion in MARE from existing evidence. RESULTS: MARE could include three to five items, considered relevant to patients and regulators. New onset of kidney injury, that is persistent albuminuria/proteinuria and/or decreasing glomerular filtration rate (GFR) <60 ml/min/1.73 m2, persistent signs of worsening kidney disease, development of end-stage kidney disease with estimated GFR <15 ml/min/1.73 m2 without or with initiation of kidney replacement therapy, and death from renal cause are core items of MARE. Additionally, patient reported outcomes should be reported in parallel to MARE as a standard set of primary (or secondary) endpoints in studies on kidney disease of diabetic, hypertensive-vascular, or other origin. CONCLUSIONS: MARE as a reporting standard will enhance the ability to compare studies and thus, facilitate meaningful meta-analyses. This will result in standardized endpoints that should result in guideline improvement to better individualize care of patients with kidney disease.

19.
Dtsch Med Wochenschr ; 144(23): 1642-1649, 2019 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-31752037

RESUMO

Due to the associated risk of stroke, non-valvular atrial fibrillation (nvAF) is a major indication for oral anticoagulation. Many patients suffer from chronic kidney disease (CKD), which increases the risk for stroke and for bleeding. Vitamin K antagonists (VKA) receive only cautious recommendations in guidelines for patients with CKD and nvVHF due to heterogeneous study results; their summaries of product characteristics contain contraindications for patients with manifest CKD. Novel oral anticoagulants (NOACs) have been investigated and are approved in CKD patients with a creatinine clearance (CrCl) ≥ 25 or 30 ml/min, factor Xa inhibitors can be used also if CrCl is > 15 ml/min. NOACs show an advantageous benefit-risk profile compared to VKA in reducing stroke, other thromboembolic events and death on the one hand and occurrence of bleedings on the other, and are recommended by the current ESC guidelines.

20.
J Am Heart Assoc ; 8(21): e013091, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31662068

RESUMO

Background People with reduced glomerular filtration rate (GFR) often have elevated cardiac troponin T (cTnT) levels. It remains unclear how cTnT levels develop over time in those with chronic kidney disease (CKD). The aim of this study was to prospectively study the association between cTnT and GFR over time in older advanced-stage CKD patients not on dialysis. Methods and Results The EQUAL (European Quality Study) study is an observational prospective cohort study in stage 4 to 5 CKD patients aged ≥65 years not on dialysis (incident estimated GFR, <20 mL/min/1.73 m²). The EQUAL cohort used for the purpose of this study includes 171 patients followed in Sweden between April 2012 and December 2018. We used linear mixed models, adjusted for important groups of confounders, to investigate the effect of both measured GFR and estimated GFR on high-sensitivity cTnT (hs-cTnT) trajectory over 4 years. Almost all patients had at least 1 hs-cTnT measurement elevated above the 99th percentile of the general reference population (≤14 ng/L). On average, hs-cTnT increased by 16%/year (95% CI, 13-19; P<0.0001). Each 15 mL/min/1.73 m2 lower mean estimated GFR was associated with a 23% (95% CI, 14-31; P<0.0001) higher baseline hs-cTnT and 9% (95% CI, 5-13%; P<0.0001) steeper increase in hs-cTnT. The effect of estimated GFR on hs-cTnT trajectory was somewhat lower than a previous myocardial infarction (15%), but higher than presence of diabetes mellitus (4%) and male sex (5%). Conclusions In CKD patients, hs-cTnT increases over time as renal function decreases. Lower CKD stage (each 15 mL/min/1.73 m2 lower) is independently associated with a steeper hs-cTnT increase over time in the same range as other established cardiovascular risk factors.

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