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Outcomes of Hematopoietic Cell Transplantation in Patients with Germline SAMD9/SAMD9L Mutations.
Ahmed IA, Farooqi MS, Vander Lugt MT, Boklan J, Rose M, Friehling ED, Triplett B, Lieuw K, Saldana BD, Smith CM, Schwartz JR, Goyal RK
(2019) Biol Blood Marrow Transplant 25: 2186-2196
MeSH Terms: Allografts, Child, Preschool, Disease-Free Survival, Female, Genetic Diseases, Inborn, Germ-Line Mutation, Hematopoietic Stem Cell Transplantation, Humans, Infant, Intracellular Signaling Peptides and Proteins, Male, Myelodysplastic Syndromes, Retrospective Studies, Survival Rate, Syndrome, Tumor Suppressor Proteins
Show Abstract · Added September 19, 2019
Germline mutations in SAMD9 and SAMD9L genes cause MIRAGE (myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital phenotypes, and enteropathy) (OMIM: *610456) and ataxia-pancytopenia (OMIM: *611170) syndromes, respectively, and are associated with chromosome 7 deletions, myelodysplastic syndrome (MDS), and bone marrow failure. In this retrospective series, we report outcomes of allogeneic hematopoietic cell transplantation (HCT) in patients with hematologic disorders associated with SAMD9/SAMD9L mutations. Twelve patients underwent allogeneic HCT for MDS (n = 10), congenital amegakaryocytic thrombocytopenia (n = 1), and dyskeratosis congenita (n = 1). Exome sequencing revealed heterozygous mutations in SAMD9 (n = 6) or SAMD9L (n = 6) genes. Four SAMD9 patients had features of MIRAGE syndrome. Median age at HCT was 2.8 years (range, 1.2 to 12.8 years). Conditioning was myeloablative in 9 cases and reduced intensity in 3 cases. Syndrome-related comorbidities (diarrhea, infections, adrenal insufficiency, malnutrition, and electrolyte imbalance) were present in MIRAGE syndrome cases. One patient with a familial SAMD9L mutation, MDS, and morbid obesity failed to engraft and died of refractory acute myeloid leukemia. The other 11 patients achieved neutrophil engraftment. Acute post-transplant course was complicated by syndrome-related comorbidities in MIRAGE cases. A patient with SAMD9L-associated MDS died of diffuse alveolar hemorrhage. The other 10 patients had resolution of hematologic disorder and sustained peripheral blood donor chimerism. Ten of 12 patients were alive with a median follow-up of 3.1 years (range, 0.1 to 14.7 years). More data are needed to refine transplant approaches in SAMD9/SAMD9L patients with significant comorbidities and to develop guidelines for their long-term follow-up.
Copyright © 2019 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.
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Prospective Study of Cardiac Events During Proteasome Inhibitor Therapy for Relapsed Multiple Myeloma.
Cornell RF, Ky B, Weiss BM, Dahm CN, Gupta DK, Du L, Carver JR, Cohen AD, Engelhardt BG, Garfall AL, Goodman SA, Harrell SL, Kassim AA, Jadhav T, Jagasia M, Moslehi J, O'Quinn R, Savona MR, Slosky D, Smith A, Stadtmauer EA, Vogl DT, Waxman A, Lenihan D
(2019) J Clin Oncol 37: 1946-1955
MeSH Terms: Adult, Aged, Aged, 80 and over, Bortezomib, Cardiovascular Diseases, Disease-Free Survival, Electrocardiography, Female, Heart Diseases, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Molecular Targeted Therapy, Multiple Myeloma, Natriuretic Peptide, Brain, Neoplasm Recurrence, Local, Oligopeptides, Prospective Studies, Proteasome Inhibitors, Risk Factors, Time-to-Treatment, Treatment Outcome, Troponin I, Troponin T
Show Abstract · Added November 12, 2019
PURPOSE - Cardiovascular adverse events (CVAEs) can occur during proteasome inhibitor (PI) therapy. We conducted a prospective, observational, multi-institutional study to define risk factors and outcomes in patients with multiple myeloma (MM) receiving PIs.
PATIENTS AND METHODS - Patients with relapsed MM initiating carfilzomib- or bortezomib-based therapy underwent baseline assessments and repeated assessments at regular intervals over 6 months, including cardiac biomarkers (troponin I or T, brain natriuretic peptide [BNP], and N-terminal proBNP), ECG, and echocardiography. Monitoring occurred over 18 months for development of CVAEs.
RESULTS - Of 95 patients enrolled, 65 received carfilzomib and 30 received bortezomib, with median 25 months of follow-up. Sixty-four CVAEs occurred, with 55% grade 3 or greater in severity. CVAEs occurred in 51% of patients treated with carfilzomib and 17% of those treated with bortezomib ( = .002). Median time to first CVAE from treatment start was 31 days, and 86% occurred within the first 3 months. Patients receiving carfilzomib-based therapy with a baseline elevated BNP level higher than 100 pg/mL or N-terminal proBNP level higher than 125 pg/mL had increased risk for CVAE (odds ratio, 10.8; < .001). Elevated natriuretic peptides occurring mid-first cycle of treatment with carfilzomib were associated with a substantially higher risk of CVAEs (odds ratio, 36.0; < .001). Patients who experienced a CVAE had inferior progression-free survival (log-rank = .01) and overall survival (log-rank < .001). PI therapy was safely resumed in 89% of patients, although 41% required chemotherapy modifications.
CONCLUSION - CVAEs are common during PI therapy for relapsed MM, especially with carfilzomib, particularly within the first 3 months of therapy. CVAEs were associated with worse overall outcomes, but usually, discontinuation of therapy was not required. Natriuretic peptides were highly predictive of CVAEs; however, validation of this finding is necessary before uniform incorporation into the routine management of patients receiving carfilzomib.
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Plasma apoM and S1P levels are inversely associated with mortality in African Americans with type 2 diabetes mellitus.
Liu M, Frej C, Langefeld CD, Divers J, Bowden DW, Carr JJ, Gebre AK, Xu J, Larsson B, Dahlbäck B, Freedman BI, Parks JS
(2019) J Lipid Res 60: 1425-1431
MeSH Terms: African Americans, Apolipoproteins M, Biomarkers, Diabetes Mellitus, Type 2, Disease-Free Survival, Female, Humans, Lysophospholipids, Male, Middle Aged, Sphingosine, Survival Rate
Show Abstract · Added January 10, 2020
apoM is a minor HDL apolipoprotein and carrier for sphingosine-1-phosphate (S1P). HDL apoM and S1P concentrations are inversely associated with atherosclerosis progression in rodents. We evaluated associations between plasma concentrations of S1P, plasma concentrations of apoM, and HDL apoM levels with prevalent subclinical atherosclerosis and mortality in the African American-Diabetes Heart Study participants (N = 545). Associations between plasma S1P, plasma apoM, and HDL apoM with subclinical atherosclerosis and mortality were assessed using multivariate parametric, nonparametric, and Cox proportional hazards models. At baseline, participants' median (25th percentile, 75th percentile) age was 55 (49, 62) years old and their coronary artery calcium (CAC) mass score was 26.5 (0.0, 346.5). Plasma S1P, plasma apoM, and HDL apoM were not associated with CAC. After 64 (57.6, 70.3) months of follow-up, 81 deaths were recorded. Higher concentrations of plasma S1P [odds ratio (OR) = 0.14, = 0.01] and plasma apoM (OR = 0.10, = 0.02), but not HDL apoM ( = 0.89), were associated with lower mortality after adjusting for age, sex, statin use, CAC, kidney function, and albuminuria. We conclude that plasma S1P and apoM concentrations are inversely and independently associated with mortality, but not CAC, in African Americans with type 2 diabetes after accounting for conventional risk factors.
Copyright © 2019 Liu et al.
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Association between image-defined risk factors and neuroblastoma outcomes.
Phelps HM, Ndolo JM, Van Arendonk KJ, Chen H, Dietrich HL, Watson KD, Hilmes MA, Chung DH, Lovvorn HN
(2019) J Pediatr Surg 54: 1184-1191
MeSH Terms: Disease-Free Survival, Humans, Neoplasm Staging, Neuroblastoma, Retrospective Studies, Risk Factors
Show Abstract · Added November 30, 2020
BACKGROUND - The current neuroblastoma (NBL) staging system employs image-defined risk factors (IDRFs) to assess numerous anatomic features, but the impact of IDRFs on surgical and oncologic outcomes is unclear.
METHODS - The Vanderbilt Cancer Registry identified children treated for NBL from 2002 to 2017. Tumor volume (TV) and IDRFs were measured radiographically at diagnosis and before resection. Perioperative and oncologic outcomes were evaluated.
RESULTS - At diagnosis of 106 NBL, 61% were IDRF positive. MYCN-amplified and undifferentiated NBL had more IDRFs than nonamplified and more differentiated tumors (p = 0.001 and p = 0.01). Of 86 NBLs resected, 43% were IDRF positive, which associated with higher stage, risk, and TV (each p < 0.001). The presence of IDRF at resection was also associated with increased blood loss (p < 0.001), longer operating times (p < 0.001), greater incidence of intraoperative complications (p = 0.03), more frequent ICU admissions postoperatively (p < 0.001), and longer hospital stays (p < 0.001). IDRF negative and positive tumors did not have significantly different rates of gross total resection (p = 0.2). Five-year relapse-free and overall survival was similar for IDRF negative and positive NBL (p = 0.9 and p = 0.8).
CONCLUSIONS - IDRFs at diagnosis were associated with larger, less differentiated, advanced stage, and higher risk NBL and at resection with increased operative difficulty and perioperative morbidity. However, the frequency of gross total resection and patient survival after resection were not associated with the presence of IDRFs.
TYPE OF STUDY - Retrospective cohort study.
Copyright © 2019 Elsevier Inc. All rights reserved.
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Association of tumor-infiltrating lymphocytes with distant disease-free survival in the ShortHER randomized adjuvant trial for patients with early HER2+ breast cancer.
Dieci MV, Conte P, Bisagni G, Brandes AA, Frassoldati A, Cavanna L, Musolino A, Giotta F, Rimanti A, Garrone O, Bertone E, Cagossi K, Sarti S, Ferro A, Piacentini F, Maiorana A, Orvieto E, Sanders M, Miglietta F, Balduzzi S, D'Amico R, Guarneri V
(2019) Ann Oncol 30: 418-423
MeSH Terms: Adult, Aged, Antineoplastic Combined Chemotherapy Protocols, Breast Neoplasms, Chemotherapy, Adjuvant, Disease-Free Survival, Drug-Related Side Effects and Adverse Reactions, Female, Humans, Kaplan-Meier Estimate, Lymphocytes, Tumor-Infiltrating, Middle Aged, Neoplasm Recurrence, Local, Receptor, ErbB-2, Trastuzumab, Treatment Outcome
Show Abstract · Added April 2, 2019
BACKGROUND - There is the need to identify new prognostic markers to refine risk stratification for HER2-positive early breast cancer patients. The aim of this study was to evaluate the association of tumor-infiltrating lymphocytes (TILs) with distant disease-free survival (DDFS) in patients with HER2-positive early breast cancer enrolled in the ShortHER adjuvant trial which compared 9 weeks versus 1-year trastuzumab in addition to chemotherapy, and to test the interaction between TILs and treatment arm.
PATIENTS AND METHODS - Stromal TILs were assessed for 866 cases on centralized hematoxylin and eosin-stained tumor slides. The association of TILs as 10% increments with DDFS was assessed with Cox models. Kaplan-Meier curves were estimated for patients with TILs ≥20% and TILs <20%. Median follow-up was 6.1 years.
RESULTS - Median TILs was 5% (Q1-Q3 1%-15%). Increased TILs were independently associated with better DDFS in multivariable model [hazard ratio (HR) 0.73, 95% confidence interval (CI) 0.59-0.89, P = 0.006, for each 10% TILs increment]. Five years DDFS rates were 91.1% for patients with TILs <20% and 95.7% for patients with TILs ≥20% (P = 0.025). The association between 10% TILs increments and DDFS was significant for patients randomized to 9 weeks of trastuzumab (HR 0.60, 95% CI 0.41-0.88) but not for patients treated with 1 year of trastuzumab (HR 0.89, 95% CI 0.71-1.12; test for interaction P = 0.088). For patients with TILs <20%, the HR for the comparison between the short versus the long arm was 1.75 (95% CI 1.09-2.80, P=0.021); whereas, for patients with TILs ≥20% the HR for the comparison of short versus long arm was 0.23 (95% CI 0.05-1.09, P = 0.064), resulting in a significant interaction (P = 0.015).
CONCLUSIONS - TILs are an independent prognostic factor for HER2-positive early breast cancer patients treated with adjuvant chemotherapy and trastuzumab and may refine the ability to identify patients at low risk of relapse eligible for de-escalated adjuvant therapy.
© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society for Medical Oncology.
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Should Ki67 immunohistochemistry be performed on all lesions in multifocal small intestinal neuroendocrine tumours?
Numbere N, Huber AR, Shi C, Cates JMM, Gonzalez RS
(2019) Histopathology 74: 424-429
MeSH Terms: Adult, Aged, Aged, 80 and over, Biomarkers, Tumor, Disease-Free Survival, Female, Humans, Immunohistochemistry, Intestinal Neoplasms, Intestine, Small, Ki-67 Antigen, Male, Middle Aged, Neoplasm Grading, Neuroendocrine Tumors, Proportional Hazards Models
Show Abstract · Added November 1, 2018
AIMS - Well-differentiated small intestinal neuroendocrine tumours (SI-NETs) are often multifocal, and this has been suggested to impart worse disease-free survival. Practice guidelines have not been established for World Health Organisation (WHO) grading of multiple primary lesions.
METHODS AND RESULTS - We identified 68 patients with ileal/jejunal SI-NET for a combined total of 207 primary lesions. Each case was evaluated for patient age and sex; size of all tumours; presence of lymph node metastases, mesenteric tumour deposits or distant metastases; and disease-specific outcome. Ki67 staining was performed on all 207 primary lesions. The relationship between multifocality and clinicopathological factors was compared using Fisher's exact test. Outcome was tested using Cox proportional hazard regression. Forty-two patients had unifocal disease, and 26 had multifocal disease (median five lesions, range = 2-32). Most tumours were WHO grade 1 (201 of 207, 97%). Of the five patients with grades 2/3 tumours, three patients had unifocal disease, one patient had two subcentimetre grade 2 lesions (including the largest) and eight subcentimetre grade 1 lesions, and one patient had one 1.6-cm grade 3 lesion and one subcentimetre grade 1 lesion. There was a positive correlation between tumour size and Ki67 index (coefficient 0.28; 95% confidence interval 0.05-0.52, P = 0.017). There was no significant association between multifocality and nodal metastases, mesenteric tumour deposits, distant metastases or disease-specific survival.
CONCLUSIONS - In patients with multifocal SI-NET, unless a particular lesion has a high mitotic rate, only staining the largest lesion for Ki67 should serve to grade almost all cases accurately. Multifocality does not appear to significantly impact patient survival.
© 2018 John Wiley & Sons Ltd.
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16 MeSH Terms
Myeloablative Autologous Stem-Cell Transplantation for Severe Scleroderma.
Sullivan KM, Goldmuntz EA, Keyes-Elstein L, McSweeney PA, Pinckney A, Welch B, Mayes MD, Nash RA, Crofford LJ, Eggleston B, Castina S, Griffith LM, Goldstein JS, Wallace D, Craciunescu O, Khanna D, Folz RJ, Goldin J, St Clair EW, Seibold JR, Phillips K, Mineishi S, Simms RW, Ballen K, Wener MH, Georges GE, Heimfeld S, Hosing C, Forman S, Kafaja S, Silver RM, Griffing L, Storek J, LeClercq S, Brasington R, Csuka ME, Bredeson C, Keever-Taylor C, Domsic RT, Kahaleh MB, Medsger T, Furst DE, SCOT Study Investigators
(2018) N Engl J Med 378: 35-47
MeSH Terms: Adolescent, Adult, Aged, Cyclophosphamide, Disease-Free Survival, Female, Follow-Up Studies, Hematopoietic Stem Cell Transplantation, Humans, Immunosuppressive Agents, Infections, Intention to Treat Analysis, Kaplan-Meier Estimate, Male, Middle Aged, Scleroderma, Systemic, Transplantation Conditioning, Transplantation, Autologous, Young Adult
Show Abstract · Added March 25, 2020
BACKGROUND - Despite current therapies, diffuse cutaneous systemic sclerosis (scleroderma) often has a devastating outcome. We compared myeloablative CD34+ selected autologous hematopoietic stem-cell transplantation with immunosuppression by means of 12 monthly infusions of cyclophosphamide in patients with scleroderma.
METHODS - We randomly assigned adults (18 to 69 years of age) with severe scleroderma to undergo myeloablative autologous stem-cell transplantation (36 participants) or to receive cyclophosphamide (39 participants). The primary end point was a global rank composite score comparing participants with each other on the basis of a hierarchy of disease features assessed at 54 months: death, event-free survival (survival without respiratory, renal, or cardiac failure), forced vital capacity, the score on the Disability Index of the Health Assessment Questionnaire, and the modified Rodnan skin score.
RESULTS - In the intention-to-treat population, global rank composite scores at 54 months showed the superiority of transplantation (67% of 1404 pairwise comparisons favored transplantation and 33% favored cyclophosphamide, P=0.01). In the per-protocol population (participants who received a transplant or completed ≥9 doses of cyclophosphamide), the rate of event-free survival at 54 months was 79% in the transplantation group and 50% in the cyclophosphamide group (P=0.02). At 72 months, Kaplan-Meier estimates of event-free survival (74% vs. 47%) and overall survival (86% vs. 51%) also favored transplantation (P=0.03 and 0.02, respectively). A total of 9% of the participants in the transplantation group had initiated disease-modifying antirheumatic drugs (DMARDs) by 54 months, as compared with 44% of those in the cyclophosphamide group (P=0.001). Treatment-related mortality in the transplantation group was 3% at 54 months and 6% at 72 months, as compared with 0% in the cyclophosphamide group.
CONCLUSIONS - Myeloablative autologous hematopoietic stem-cell transplantation achieved long-term benefits in patients with scleroderma, including improved event-free and overall survival, at a cost of increased expected toxicity. Rates of treatment-related death and post-transplantation use of DMARDs were lower than those in previous reports of nonmyeloablative transplantation. (Funded by the National Institute of Allergy and Infectious Diseases and the National Institutes of Health; ClinicalTrials.gov number, NCT00114530 .).
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Adjuvant therapy is associated with improved survival after curative resection for hilar cholangiocarcinoma: A multi-institution analysis from the U.S. extrahepatic biliary malignancy consortium.
Krasnick BA, Jin LX, Davidson JT, Sanford DE, Ethun CG, Pawlik TM, Poultsides GA, Tran T, Idrees K, Hawkins WG, Chapman WC, Doyle MBM, Weber SM, Strasberg SM, Salem A, Martin RCG, Isom CA, Scoggins C, Schmidt CR, Shen P, Beal E, Hatzaras I, Shenoy R, Maithel SK, Fields RC
(2018) J Surg Oncol 117: 363-371
MeSH Terms: Aged, Bile Duct Neoplasms, Chemoradiotherapy, Adjuvant, Chemotherapy, Adjuvant, Cholangiocarcinoma, Disease-Free Survival, Female, Humans, Male, Middle Aged, Randomized Controlled Trials as Topic, Retrospective Studies, Survival Rate
Show Abstract · Added April 10, 2018
BACKGROUND - Curative-intent treatment for localized hilar cholangiocarcinoma (HC) requires surgical resection. However, the effect of adjuvant therapy (AT) on survival is unclear. We analyzed the impact of AT on overall (OS) and recurrence free survival (RFS) in patients undergoing curative resection.
METHODS - We reviewed patients with resected HC between 2000 and 2015 from the ten institutions participating in the U.S. Extrahepatic Biliary Malignancy Consortium. We analyzed the impact of AT on RFS and OS. The probability of RFS and OS were calculated in the method of Kaplan and Meier and analyzed using multivariate Cox regression analysis.
RESULTS - A total of 249 patients underwent curative resection for HC. Patients who received AT and those who did not had similar demographic and preoperative features. In a multivariate Cox regression analysis, AT conferred a significant protective effect on OS (HR 0.58, P = 0.013), and this was maintained in a propensity matched analysis (HR 0.66, P = 0.033). The protective effect of AT remained significant when node negative patients were excluded (HR 0.28, P = 0.001), while it disappeared (HR 0.76, P = 0.260) when node positive patients were excluded.
CONCLUSIONS - AT should be strongly considered after curative-intent resection for HC, particularly in patients with node positive disease.
© 2017 Wiley Periodicals, Inc.
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Diagnostic value of histone 3 mutations in osteoclast-rich bone tumors.
Nohr E, Lee LH, Cates JM, Perizzolo M, Itani D
(2017) Hum Pathol 68: 119-127
MeSH Terms: Adolescent, Adult, Aged, Alberta, Biomarkers, Tumor, Bone Cysts, Aneurysmal, Bone Neoplasms, Child, Chondroblastoma, DNA Mutational Analysis, Diagnosis, Differential, Disease-Free Survival, Female, Genetic Predisposition to Disease, Giant Cell Tumor of Bone, Histones, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Mutation, Osteoclasts, Phenotype, Predictive Value of Tests, Tennessee, Time Factors, Young Adult
Show Abstract · Added November 1, 2018
Differentiating osteoclast-rich lesions of bone (giant cell tumor of bone [GCTB], chondroblastoma [CBA], and aneurysmal bone cyst [ABC]) can be challenging, especially in small biopsies or fine-needle aspirations. Mutations affecting codons 34 and 36 of either H3 Histone Family Member 3A (H3F3A) and/or 3B (H3F3B) are characteristically seen in GCTB and CBAs. We devised a simple assay to identify these mutations and evaluated its applicability for routine clinical diagnosis. One hundred twenty-four tissue specimens from 108 patients (43 GCTBs, 38 CBAs and 27 ABCs) were collected from the archives of the Calgary Laboratory Services/University of Calgary and Vanderbilt University Medical Center. Histology was reviewed by an expert orthopedic pathologist. A single base extension assay (SNaPshot) is used to interrogate each nucleotide in codons 34 and 36 of H3F3A and codon 36 of H3F3B. Final diagnoses were generated after re-reviewing cases and incorporating molecular findings. Of 43 GCTBs, 38 (88%) had an H3F3A G34W mutation; 35 of 38 CBAs (92%) had a K36M mutation in either H3F3B (N = 31; 82%) or H3F3A (N = 4; 11%); none of 27 ABCs had a tested mutation. Molecular findings changed the histomorphologic diagnosis in 5 cases (3 GCTB changed to ABC, and 2 ABC changed to GCTB). These findings support the diagnostic utility of mutational analysis for this differential diagnosis in certain challenging cases when clinicoradiologic and histomorphologic features are not definitive, particularly for distinguishing cellular ABC versus GCTB with secondary ABC.
Copyright © 2017 Elsevier Inc. All rights reserved.
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eGFR and Albuminuria in Relation to Risk of Incident Atrial Fibrillation: A Meta-Analysis of the Jackson Heart Study, the Multi-Ethnic Study of Atherosclerosis, and the Cardiovascular Health Study.
Bansal N, Zelnick LR, Alonso A, Benjamin EJ, de Boer IH, Deo R, Katz R, Kestenbaum B, Mathew J, Robinson-Cohen C, Sarnak MJ, Shlipak MG, Sotoodehnia N, Young B, Heckbert SR
(2017) Clin J Am Soc Nephrol 12: 1386-1398
MeSH Terms: Adult, Aged, Aged, 80 and over, Albuminuria, Atrial Fibrillation, Biomarkers, Creatinine, Cystatin C, Disease-Free Survival, Female, Glomerular Filtration Rate, Heart Failure, Humans, Incidence, Kaplan-Meier Estimate, Kidney, Kidney Failure, Chronic, Male, Middle Aged, Myocardial Infarction, Proportional Hazards Models, Risk Assessment, Risk Factors, Time Factors, United States, Young Adult
Show Abstract · Added September 19, 2017
BACKGROUND AND OBJECTIVES - The incidence of atrial fibrillation is high in ESRD, but limited data are available on the incidence of atrial fibrillation across a broad range of kidney function. Thus, we examined the association of eGFR and urine albumin-to-creatinine ratio with risk of incident atrial fibrillation.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS - We meta-analyzed three prospective cohorts: the Jackson Heart Study, the Multi-Ethnic Study of Atherosclerosis, and the Cardiovascular Health Study. Cox regression models were performed examining the association of eGFR and urine albumin-to-creatinine ratio with incident atrial fibrillation adjusting for demographics and comorbidity. In additional analyses, we adjusted for measures of subclinical cardiovascular disease (by electrocardiogram and cardiac imaging) and interim heart failure and myocardial infarction events.
RESULTS - In the meta-analyzed study population of 16,769 participants without prevalent atrial fibrillation, across categories of decreasing eGFR (eGFR>90 [reference], 60-89, 45-59, 30-44, and <30 ml/min per 1.73 m), there was a stepwise increase in the adjusted risk of incident atrial fibrillation: hazard ratios (95% confidence intervals) were 1.00, 1.09 (0.97 to 1.24), 1.17 (1.00 to 1.38), 1.59 (1.28 to 1.98), and 2.03 (1.40 to 2.96), respectively. There was a stepwise increase in the adjusted risk of incident atrial fibrillation across categories of increasing urine albumin-to-creatinine ratio (urine albumin-to-creatinine ratio <15 [reference], 15-29, 30-299, and ≥300 mg/g): hazard ratios (95% confidence intervals) were 1.00, 1.04 (0.83 to 1.30), 1.47 (1.20 to 1.79), and 1.76 (1.18 to 2.62), respectively. The associations were consistent after adjustment for subclinical cardiovascular disease measures and interim heart failure and myocardial infarction events.
CONCLUSIONS - In this meta-analysis of three cohorts, reduced eGFR and elevated urine albumin-to-creatinine ratio were significantly associated with greater risk of incident atrial fibrillation, highlighting the need for further studies to understand mechanisms linking kidney disease with atrial fibrillation.
Copyright © 2017 by the American Society of Nephrology.
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