scholarly journals 20. Risk Factors for Breakthrough Cytomegalovirus (CMV) Infection and De Novo Resistance in Hematopoietic Cell Transplantation (HCT) Recipients Receiving Letermovir Prophylaxis

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S13-S14
Author(s):  
Danniel Zamora ◽  
Garrett Perchetti ◽  
Melinda Biernacki ◽  
Hu Xie ◽  
Jared L Castor ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cox Regression ◽  
De Novo ◽  
Resistance Testing ◽  
Cmv Infection ◽  
Research Support ◽  
Material Support ◽  
Increased Risk ◽  
Clinically Significant ◽  
Cmv Reactivation

Abstract Background Subclinical CMV reactivation on letermovir prophylaxis may be important for CMV-specific immune reconstitution after HCT (Zamora et al. Blood 2021) but concerns remain regarding the development of antiviral resistance. Here we analyze risk factors associated with breakthrough CMV infection on letermovir and describe the incidence of de novo letermovir resistance. Methods All CMV-seropositive, allogeneic HCT recipients who received letermovir prophylaxis from 10/2018-2020 were analyzed. Weekly proportions and cumulative incidences of CMV reactivation in the first 100 days post-HCT were calculated at different levels. Clinically significant CMV infection was treated preemptively with (val)ganciclovir or foscarnet. Univariable/multivariable Cox regression models for breakthrough CMV reactivation at each viral threshold were performed. Patients with CMV reactivation ≥ 200 IU/mL were tested by UL56 sequencing to identify de novo letermovir resistance. Results Two hundred thirty HCT recipients who received letermovir prophylaxis were identified. Weekly proportions and cumulative incidences of CMV reactivation are shown in Figure 1. Nine of 15 patients with CMV reactivation had sufficient serum for letermovir resistance testing. One C325Y mutation was identified in an umbilical cord blood transplant recipient who developed 4 weeks of CMV DNAemia with a peak of 2512 IU/mL. The patient received 56 days of letermovir prior to reactivation and responded to treatment initially with foscarnet (due to cytopenias) followed by ganciclovir. Greater cumulative steroid exposure was associated with increased risk of CMV reactivation and the association remained statistically significant at any level (adjusted Hazard Ratio [aHR] 10.8 mg/kg*days, 95% confidence interval [CI] 5.18-22.7) and ≥ 150 IU/mL (aHR 15.9 mg/kg*days, 95% CI 7.07-35.6) after adjusting for underlying disease and GVHD prophylaxis (Figure 2). Conclusion Letermovir prophylaxis was effective at preventing clinically significant CMV infection but subclinical reactivation continued to occur. Cumulative steroid exposure was the strongest risk factor for reactivation while on letermovir. Development of de novo letermovir resistance on prophylaxis occurred infrequently. Disclosures Michael Boeckh, MD PhD, AlloVir (Consultant)Ansun Biopharma (Grant/Research Support)Astellas (Grant/Research Support)EvrysBio (Consultant, Other Financial or Material Support, Options to acquire equity, but have not exercised them)Gilead Sciences (Consultant, Grant/Research Support)GlaxoSmithKline (Consultant)Helocyte (Consultant, Other Financial or Material Support, Options to acquire equity, but have not exercised them)Janssen (Grant/Research Support)Kyorin (Consultant)Merck (Consultant, Grant/Research Support)Moderna (Consultant)Symbio (Consultant)Takeda (formerly known as Shire) (Consultant, Grant/Research Support)VirBio (Consultant, Grant/Research Support) Alexander L. Greninger, MD, PhD, Abbott (Grant/Research Support)Gilead (Grant/Research Support)Merck (Grant/Research Support)

FRI0141 CHARACTERIZATION OF SERIOUS INFECTIONS WITH UPADACITINIB IN PATIENTS WITH RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 654-655
Author(s):  
K. Winthrop ◽  
L. Calabrese ◽  
F. Van den Bosch ◽  
K. Yamaoka ◽  
C. Selmi ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Risk Factors ◽  
Cox Regression ◽  
Opportunistic Infections ◽  
Oral Candidiasis ◽  
Univariate Analysis ◽  
Janus Kinase ◽  
Research Support ◽  
Phase 3 ◽  
Increased Risk

Background:Upadacitinib (UPA) is a selective and reversible Janus kinase (JAK) inhibitor with an approved dose of 15 mg once daily (QD) for the treatment of rheumatoid arthritis (RA). Patients (pts) receiving JAK inhibitors have been reported to be at increased risk of developing serious infection events (SIE) and opportunistic infections (OI).Objectives:To evaluate the incidence of SIEs and OIs in pts with RA receiving UPA and active comparators in the Phase 3 SELECT clinical trial program.Methods:The exposure-adjusted event rate (EAER) per 100 patient-years (E/100 PY) of SIEs and OIs was determined in pts receiving UPA in five randomized Phase 3 trials (SELECT-EARLY, SELECT-MONOTHERAPY, SELECT-NEXT, SELECT-COMPARE, and SELECT-BEYOND), of which four evaluated both UPA 15 mg and 30 mg QD doses and one (SELECT-COMPARE) evaluated only UPA 15 mg QD. Incidences of SIEs and OIs were also determined in pts receiving adalimumab (ADA) + methotrexate (MTX) in SELECT-COMPARE and MTX monotherapy in SELECT-EARLY. Data were analyzed descriptively, with no statistical comparisons between groups or doses. Risk factors for SIEs were determined using a univariate Cox regression model. The data cut-off was June 30, 2019.Results:Overall, 2629 pts who received UPA 15 mg, 1204 pts who received UPA 30 mg, 579 pts who received ADA + MTX, and 314 pts who received MTX monotherapy were included in this analysis. The EAERs (E/100 PYs [95% CI]) of SIEs were 3.2 (2.7–3.7) in the UPA 15 mg group, 5.7 (4.8–6.8) in the UPA 30 mg group, 3.9 (2.6–5.6) in pts receiving ADA + MTX, and 3.1 (1.7–5.2) in pts receiving MTX monotherapy. Pneumonia was the most common SIE, with EAERs (E/100 PYs [95% CI]) of 0.7 (0.5–1.0), 1.3 (0.9–1.9), 0.7 (0.2–1.5), and 0.7 (0.1–1.9) in the UPA 15 mg, UPA 30 mg, ADA + MTX, and MTX monotherapy groups, respectively. Rates of OIs (including oral candidiasis and disseminated herpes zoster [HZ]) (E/100 PYs [95% CI]) were 0.7 (0.5–1.0), 1.3 (0.9–1.9), 0.4 (0.1–1.1), and 0 (0–0) in the UPA 15 mg, UPA 30 mg, ADA + MTX, and MTX monotherapy groups, respectively. Oral candidiasis was the most frequent OI with EAERs (E/100 PYs [95% CI]) of 0.4 (0.2–0.6) in the UPA 15 mg group, 0.6 (0.3–1.0) in the UPA 30 mg group, 0.4 (0.1–1.1) in the ADA + MTX group, and 0 (0–0) in the MTX monotherapy group. Serious adverse events of HZ were only reported in the UPA groups (0.2 E/100 PYs [95% CI: 0.1–0.3] and 0.6 E/100 PYs [95% CI: 0.4–1.1] in the UPA 15 mg and 30 mg groups, respectively). Overall, there were 3 (4 coded events), 3, 1, and 0 pts who had active tuberculosis events in the UPA 15 mg, UPA 30 mg, ADA + MTX, and MTX monotherapy groups, respectively. Risk factors for SIEs are shown in the Figure. For both UPA doses, age ≥75 years and smoking were noted to have hazard ratios >1.Conclusion:The incidence rate of SIEs and OIs was higher in the UPA 30 mg group than the UPA 15 mg group. SIEs observed with UPA 15 mg were similar to that seen with ADA although the rates of HZ were higher on UPA. Pts with RA who are ≥75 years old and/or smokers may be at higher risk than other pts with RA for SIEs while receiving UPA.Figure.Univariate analysis of SIE risk factorsDisclosure of Interests:Kevin Winthrop Grant/research support from: Bristol-Myers Squibb, Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly, Galapagos, Gilead, GSK, Pfizer Inc, Roche, UCB, Leonard Calabrese Consultant of: AbbVie, GSK, Bristol-Myers Squibb, Genentech, Janssen, Novartis, Sanofi, Horizon, Crescendo, and Gilead, Speakers bureau: Sanofi, Horizon, Crescendo, Novartis, Genentech, Janssen, and AbbVie, Filip van den Bosch Consultant of: AbbVie, Celgene Corporation, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, and UCB, Speakers bureau: AbbVie, Celgene Corporation, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, and UCB, Kunihiro Yamaoka Speakers bureau: AbbVie GK, Astellas Pharma Inc., Bristol-Myers Squibb, Chugai Pharmaceutical Co. Ltd, Mitsubishi-Tanabe Pharma Corporation, Pfizer Japan Inc., and Takeda Pharmaceutical Company Ltd, Carlo Selmi Grant/research support from: AbbVie, Janssen, MSD, Novartis, Pfizer, Celgene, and Leo Pharma, Consultant of: Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Roche, and Sanofi-Regeneron, Speakers bureau: AbbVie, Aesku, Alfa-Wassermann, Bristol-Myers Squibb, Biogen, Celgene, Eli-Lilly, Grifols, Janssen, MSD, Novartis, Pfizer, Roche, Sanofi-Genzyme, UCB Pharma, Yanna Song Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Barbara Hendrickson Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Ivan Lagunes-Galindo Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Iain McInnes Grant/research support from: Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Janssen, and UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Gilead, Janssen, Novartis, Pfizer, and UCB

scholarly journals 1104. Risk Factors and Outcomes of Refractory and/or Resistant Cytomegalovirus (CMV) Infection after Allogeneic Hematopoietic Stem Cell Transplantation

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S582-S583
Author(s):  
Eleni Karantoni ◽  
Yiqi Su ◽  
Anat Stern ◽  
Phaedon D Zavras ◽  
Sergio Giralt ◽  
...  
Keyword(s):  
Risk Factors ◽  
Overall Survival ◽  
T Cell ◽  
Panel Member ◽  
Multivariable Model ◽  
Research Support ◽  
Review Panel ◽  
Material Support ◽  
Advisory Boards ◽  
Research Grant

Abstract Background The epidemiology of CMV end-organ disease (EOD) after Hematopoietic Cell Transplant (HCT) in the era of preemptive therapy (PET) is defined. In contrast, less data exists on refractory and/or resistant (R/R) CMV. We report on 1) the incidence; 2) risk factors and outcomes of R/R CMV by 1-year post HCT. Methods Retrospective review of 167 CMV seropositive (R+) recipients of first marrow or peripheral blood HCT from 1/2014 - 12/2017 managed by PET. Refractory CMV was defined as failure to achieve >1 log10 decrease in CMV viral load (VL) and having VL >1,000 IU/mL after ≥14 day of PET. Resistant CMV required genotypic confirmation of resistance mutation(s) in UL54 and/or UL97 genes. End organ disease (EOD) was defined by standard criteria. Patients (pts) were followed through 1-year post HCT and were categorized in two mutually exclusive groups as R/R and no R/R. Demographics, clinical characteristics and outcomes were extracted from medical records and hospital databases. Univariable and multivariable logistic models were used to identify risk factors for R/R CMV. Results Of 167 PET recipients, 91 (54.5%) received ex vivo T cell depleted (TCD) HCT; 40 (24.0%) had mismatched donor; and 26 (15.6%) had multiple myeloma. 66/167 (39.5%) pts developed refractory CMV (6 pts also had resistant CMV). Time from HCT to CMV viremia was shorter in R/R group: median (IQR) 21.5 (17.2-27.8) days compared to no R/R group: 26 (19-32) days (p=0.031). Maximum VL was higher for R/R compared to no R/R: median (IQR) 9,118 (2,849-18,456) and 868 (474-1,908), respectively (p< 0.001). In multivariable model, risk factors for R/R included TCD HCT (p< 0.0001) and higher VL at PET initiation (p=0.0002). In contrast, CMV seropositive donor (p=0.035) was protective (Figure 1). CMV EOD developed in 28.2% of R/R and 16.2% of no R/R groups (p=0.085) (Figure 2). Overall survival at 1 year was 59.1% for R/R compared to 83.1% for no R/R group (p=0.00027) (Figure 3). Figure 1. Adjusted odds ratio (OR) and 95% confidence interval (CI) from multivariable model evaluating risk factors of refractory/resistant (R/R) CMV. Figure 2. Cumulative incidence curves of CMV end-organ disease (EOD) at 1-year post HCT Figure 3. Kaplan-Meier survival curves of overall survival (OS) at 1-year post HCT Conclusion 1) Refractory and/or resistant CMV occurred in 39,5% of PET recipients. 2) T-cell depletion and higher CMV VL at PET initiation were risk factors for R/R CMV in multivariable models. 3) R/R CMV was associated with more EOD and worse overall survival. Disclosures Sergio Giralt, MD, Amgen (Advisor or Review Panel member, Research Grant or Support, Served an advisory board for Amgen, Actinuum, Celgene, Johnson & Johnson, JAZZ pharmaceutical, Takeda, Novartis, KITE, and Spectrum pharma and has received research support from Amgen, Actinuum, Celgene, Johnson & Johnson, and Miltenyi, Takeda.) Miguel-Angel Perales, MD, Abbvie (Other Financial or Material Support, Honoraria from Abbvie, Bellicum, Celgene, Bristol-Myers Squibb, Incyte, Merck, Novartis, Nektar Therapeutics, Omeros, and Takeda.)ASTCT (Other Financial or Material Support, Volunteer member of the Board of Directors of American Society for Transplantation and Cellular Therapy (ASTCT), Be The Match (National Marrow Donor Program, NMDP), and the CIBMTR Cellular Immunotherapy Data Resource (CIDR) Committee)Cidara Therapeutics (Advisor or Review Panel member, Other Financial or Material Support, Serve on DSMBs for Cidara Therapeutics, Servier and Medigene, and the scientific advisory boards of MolMed and NexImmune.)Kite/Gilead (Research Grant or Support, Other Financial or Material Support, Received research support for clinical trials from Incyte, Kite/Gilead and Miltenyi Biotec.) Genovefa Papanicolaou, MD, Chimerix (Research Grant or Support)Merck&Co (Research Grant or Support, Investigator and received funding and consulting fees from Merck, Chimerix, Shire and Astellas)

scholarly journals Risk Factors for Disability Pension among Young Adults Diagnosed with Attention-deficit Hyperactivity Disorder (ADHD) in Adulthood

2021 ◽  
pp. 108705472110256
Author(s):  
Lingjing Chen ◽  
Ellenor Mittendorfer-Rutz ◽  
Emma Björkenstam ◽  
Syed Rahman ◽  
Klas Gustafsson ◽  
...  
Keyword(s):  
Risk Factors ◽  
Young Adults ◽  
Disability Pension ◽  
Cox Regression ◽  
Related Factors ◽  
Adult Age ◽  
Work Related ◽  
Hyperactivity Disorder ◽  
Increased Risk ◽  
Similar Risk

Objective: To investigate risk factors of disability pension (DP) in young adults diagnosed with ADHD in Sweden. Method: In total, 9718 individuals diagnosed with incident ADHD in young adult age (19–29 years) 2006 to 2011, were identified through national registers. They were followed for 5 years and Cox regression models were applied to analyze the DP risk (overall and by sex), associated with socio-demographics, work-related factors, and comorbid disorders. Results: Twenty-one percent of all received DP. Being younger at diagnosis (hazard ratio [HR] = 1.54; 95%confidence interval [CI] 1.39–1.71); low educational level (HR = 1.97; 95%CI 1.60–2.43 for <10 years); work-related factors at baseline (no income from work [HR = 2.64; 95%CI 2.35–2.98] and sickness absence >90 days [HR = 2.48; 95%CI2.17–2.83]); and schizophrenia/psychoses (HR = 2.16; 95%CI 1.66–2.80), autism (HR = 1.87; 95%CI 1.42–2.46), anxiety (HR = 1.34; 95%CI 1.22–1.49) were significantly associated with an increased risk of DP. Similar risk patterns were found in men and women. Conclusion: Work-related factors and comorbid mental disorders need to be highlighted in early vocational rehabilitation for individuals with ADHD.

scholarly journals THU0417 READMISSION RISK AND QUALITY OF CARE IN PATIENTS PRESENTING TO THE EMERGENCY DEPARTMENT WITH GOUT FLARES

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 446.2-446
Author(s):  
L. Brunetti ◽  
J. Vekaria ◽  
P. Lipsky ◽  
N. Schlesinger
Keyword(s):  
Risk Factors ◽  
Emergency Department ◽  
Economic Burden ◽  
Hospital Admissions ◽  
Medical Center ◽  
Research Support ◽  
Increased Risk ◽  
Comorbidity Index ◽  
Anti Inflammatory ◽  
Gout Flares

Background:Gout is the most common form of inflammatory arthritis and its economic burden is substantial, with estimates for the overall cost exceeding $20 billion (US) annually. Contributing to the economic burden are hospital admissions and iatrogenic events associated with pharmacotherapy. Identification of modifiable risk factors would be an important contribution to clinical practice.Objectives:The aim of this study was to identify opportunities for enhancing gout care in patients presenting to the Emergency Department (ED) with gout flares.Methods:This retrospective cohort study used data from electronic medical records (EMR) at a large community hospital. All consecutive patients visiting the medical center ED with a primary diagnosis of gout from 1/1/2016 to 7/1/2019 were included. Patients were then followed for 90 days to determine whether they were readmitted to the ED for any reason. A chart review identified whether they were on appropriate medications in terms of gout flare management. All data were summarized using descriptive statistics. A multiple logistic regression was constructed to identify risk factors for ED utilization within 90 days of the index visit.Results:A total of 214 patients were included in the analysis. Most patients were male (79%), mean age was 59.4 ± 15.6 years, and mean Charlson comorbidity index was 0.5 ± 1.14. The most common medications prescribed during the ED visit included NSAIDs (41.6%), opioids (28%), corticosteroids (26.6%), and colchicine (21%). Allopurinol and febuxostat were initiated in the ED in 4.7% and 0.9%, respectively. Discharge medications for the management of gout included NSAIDs (37%), corticosteroids (34.6%), opioids (23.8%), colchicine (14%), febuxostat (7%), and allopurinol (6.5%). Of the patients sent home with an opioid, 40% were newly prescribed. An anti-inflammatory medication was not prescribed in 29.6% of patients discharged from the ED. Readmission within 90 days was recorded in 16.8% of patients. Of these readmissions, 33.3% were gout-related and 11.1% were cardiac related.After adjusting for age and comorbidity index, patients receiving colchicine were 2.8 times more likely (OR, 2.81; 95% CI, 1.12 to 7.02; p=0.027) to return to the ED within 90 days. The most common cause of readmission in this subset was gout-related (54.5%).Conclusion:Nearly 30% of patients were discharged from the ED without an anti-inflammatory medication, whereas initiation of urate lowering therapy was rare. Opiates were used frequently, but the indication was uncertain. Only 5.6% of subjects revisited the ED for gout-related diagnoses in the subsequent 3 months. Colchicine prescription was associated with an increased risk of gout-related ED utilization within 90 days. Treatment of gout in the ED is sub-optimal and often does not follow established guidelines.Disclosure of Interests: :Luigi Brunetti Grant/research support from: Astellas Pharma, CSL Behring, Consultant of: Horizon Foundation of New Jersey, Janaki Vekaria: None declared, Peter Lipsky Consultant of: Horizon Therapeutics, Naomi Schlesinger Grant/research support from: Pfizer, AMGEN, Consultant of: Novartis, Horizon Pharma, Selecta Biosciences, Olatec, IFM Therapeutics, Mallinckrodt Pharmaceuticals, Speakers bureau: Takeda, Horizon

scholarly journals Cytomegalovirus Reactivation in Hematopoietic Stem Cell Transplant Recipients in High Endemic Population

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 23-24
Author(s):  
Muhammad Farhan ◽  
Qamar Un Nisa Chaudhry ◽  
Syed Kamran Mahmood ◽  
Tariq Ghafoor ◽  
Raheel Iftikhar ◽  
...  
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
Viral Load ◽  
High Viral Load ◽  
Transplant Recipients ◽  
Cmv Infection ◽  
Hematopoietic Stem ◽  
Post Transplant ◽  
Endemic Population ◽  
Cmv Reactivation

Background: Cytomegalovirus (CMV) infection is a major cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). It causes end-organ disease, multi-organ dysfunction syndrome, graft failure, increased susceptibility to infections and GVHD. According to the published western data greatest risk of CMV infection is the seropositivity of the recipient, however, in a high endemic population where seropositivity is up to 100%, risk factors for CMV reactivation are different and are analyzed in this study. Methods: It is a prospective descriptive study performed at Armed Forces Bone Marrow Transplant Center, Rawalpindi, Pakistan from January 2017 to March 2020. Consecutive patients who underwent allogeneic HSCT during this period were enrolled. All patients were prospectively monitored for CMV reactivation by weekly or two weekly CMV DNA quantitative PCR, from engraftment till day 100 post-transplant. CMV infection was diagnosed on detection of more than 200 copies/ml on PCR. Threshold for starting preemptive antiviral therapy was kept at 2000 copies/ml. Patients with past history of CMV infection, those who expired before day 14 post-transplant or those with less than 70% of required CMV tests were not included in the study. Factors associated with CMV reactivation, outcome of antiviral therapy and effect of CMV on post-transplant survival were studied. Results: Out of 319 transplants during this period, 230 patients fulfilled the inclusion criteria. Of these, 197 were HLA matched sibling, 18 were matched family donor and 15 were haploidentical transplants. There were 163 males and 67 females. Median age at transplant was 9.5 years (0.5-53). Eighty-three transplants were done in thalassemia, 55 in aplastic anemia, 14 in Fanconi anemia, 27 in acute leukemias, 8 in CML, 9 in MDS, 12 in HLH and 22 in other hematological disorders. All the patients and donor were CMV IgG seropositive when tested before transplantation. CMV reactivation was seen in 152 out of 230 patients (66.1%). Of 152, 95 patients had CMV viral load more than 2000 copies/ml and required antiviral treatment. Median time to reactivation since transplant was 35 days (13-90). In multivariate analysis using binary regression, risk factors for high viral load CMV reactivation included steroid administration (p=0.009), recipient age less than 10 years (p=0.003) and haploidentical transplant (p=0.048). No statistically significant association was found with the use of ATG, GVHD, underlying disease, ABO blood group or gender mismatch. Survival analysis using cox regression showed significant impact of high viral load CMV reactivation on post-transplant survival. Event-free survival (EFS) with and without CMV reactivation was 70.5 % and 89.7% respectively (p=0.004) and overall survival (OS) was 80.0 % and 97.4 % with and without CMV reactivation respectively (p=0.002). Valganciclovir was given in 89 patients and 6patients were treated with ganciclovir. Mean time to clear viremia was 19.8±9 days. Myelosuppression was seen in 41% of patients treated with valganciclovir. Renal impairment was seen in 25% of patients treated with valganciclovir. One patient had resistant disease. One patient had CMV pneumonia and she recovered. One patient died of suspected CMV pneumonia Conclusion: CMV reactivation was seen in 66.1% of the transplant recipients, this is higher compared to the western world due to high CMV seropositivity is this region. Steroids administration in post-transplant period significantly increase the risk of CMV reactivation. Preemptive therapy with valganciclovir effectively treats CMV reactivation. Viral threshold for treatment should be decided considering the regional endemicity. CMV adversely effects the transplant outcome in terms of EFS and OS. Disclosures No relevant conflicts of interest to declare.

Abstract 16055: Lipoprotein Subclasses, Size, and Statin-Associated Incident Diabetes: An Analysis From the JUPITER Trial

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Sagar Dugani ◽  
Akintunde O Akinkuolie ◽  
Robert J Glynn ◽  
Paul M Ridker ◽  
Samia Mora
Keyword(s):  
Risk Factors ◽  
Cox Regression ◽  
Incident Diabetes ◽  
P Value ◽  
Random Allocation ◽  
Lipoprotein Subclass ◽  
Lipoprotein Subclasses ◽  
Ldl Particles ◽  
Ldl Size ◽  
Increased Risk

Statins reduce CVD events, LDL cholesterol (LDL-C) and triglycerides, with an increased risk of diabetes. The underlying predictors of statin-associated diabetes are unclear. We evaluated lipoprotein subclass and size changes in response to rosuvastatin to identify predictors of diabetes on statin therapy Among 11,918 non-diabetic participants in JUPITER (NCT00239681), lipoprotein subclasses and size were quantified by NMR spectroscopy (LipoScience, NC) prior to and 1 year after randomization to placebo or rosuvastatin (total 370 incident diabetes). Cox regression models were adjusted for diabetes risk factors Compared to baseline, rosuvastatin lowered LDL-C and particles by lowering cholesterol-enriched large LDL (58%) and IDL (46%), with less relative lowering of cholesterol-poor small LDL (22%), resulting in smaller LDL size (1.5%). Rosuvastatin lowered (15%-20%) triglycerides, VLDL triglycerides, and VLDL particles by lowering large (15%), medium (7%), and small (27%) particles, and increasing VLDL size (3%) (all p<0.0001). Among statin-allocated individuals, after adjusting for typical risk factors, incident diabetes was inversely associated with baseline levels of LDL-C, HDL-C, large LDL particles, and LDL size, and positively associated with baseline triglycerides, non-HDL-C, ApoB, LDL particles, VLDL particles, VLDL triglycerides and size (Table). Similar associations were seen in on-treatment rosuvastatin and placebo groups In JUPITER, random allocation to rosuvastatin altered the lipoprotein subclass profile in a manner associated with the development of diabetes Adjusted Hazard Ratios (95% CI) and Risk of Incident Diabetes with Rosuvastatin Baseline parameters HR per 1-SD p value LDL-C .86 (0.76-0.98) .02 HDL-C .69 (0.54-0.87) .002 Triglycerides 1.62 (1.41-1.86) <.0001 Non-HDL-C 1.20 (1.04-1.39) .01 ApoB 1.35 (1.18-1.55) <.0001 Total LDL* 1.32 (1.15-1.51) <.0001 Large LDL* .79 (0.71-0.87) <.0001 Small LDL* 1.71 (1.40-2.08) <.0001 IDL* .97 (0.85-1.11) .69 LDL size .66 (0.58-0.75) <.0001 Total VLDL* 1.16 (1.00-1.34) .046 Large VLDL* 1.78 (1.51-2.10) <.0001 Medium VLDL* 1.35 (1.15-1.58) .0002 Small VLDL* .93 (0.82-1.06) .30 VLDL size 1.58 (1.39-1.80) <.0001 VLDL triglycerides 1.51 (1.31-1.73) <.0001 *particles

Abstract 14541: Incidence, Risk Factors, and Outcomes of Heart Failure in Patients With Graves’ Disease

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Jwan A Naser ◽  
Sorin Pislaru ◽  
Marius N Stan ◽  
Grace Lin
Keyword(s):  
Risk Factors ◽  
Heart Failure ◽  
Cardiovascular Events ◽  
De Novo ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Graves Disease ◽  
Increased Risk ◽  
All Cause Mortality ◽  
Overt Hyperthyroidism

Background: Graves’ disease (GD) can both aggravate pre-existing cardiac disease and cause de novo heart failure (HF). Due to the rarity of thyrotoxic HF, population-based studies are lacking, and data from smaller studies are widely variable. Methods: We reviewed the medical records of 1371 consecutive patients with GD evaluated at our clinic between 2009 and 2019. HF was defined according to Framingham criteria. GD-related HFrEF was defined by left ventricular ejection fraction of <50%, while HFpEF was defined according to the Heart Failure Association of the European Society of Cardiology. Outcomes of major cardiovascular events, all-cause mortality, and cardiac hospitalizations were analyzed with adjustments for age, gender, and history of coronary artery disease (CAD). 1:1 matching with controls (age, gender, and CAD) was additionally done. Results: HF occurred in 74 patients (31 HFrEF; 43 HFpEF). Incidence of GD-related HF, HFrEF, and HFpEF was 5.4%, 2.3%, and 3.1%, respectively. In HFrEF, atrial fibrillation (AF) (RR 10.05, p <0.001) and thyrotropin receptor antibodies (TRAb) level (RR 1.05 per unit, p=0.005) were independent predisposing factors. In HFpEF, independent risk factors were COPD (RR 5.78, p < 0.001), older age (RR 1.48 per 10 years, p = 0.003), overt hyperthyroidism (RR 5.37, p = 0.021), higher BMI (1.06 per unit, p = 0.003), and HTN (RR 3.03, p = 0.011). Rates of cardiac hospitalizations were higher in HFrEF (41.9% vs 3.2%, p <0.001) and HFpEF (44.2% vs 4.7%, p < 0.001) compared to controls. Furthermore, while both increased risk of strokes (HFrEF: RR 4.12, p = 0.027; HFpEF: RR 4.64, p = 0.009), only HFrEF increased risk of all-cause mortality (RR 3.78, p = 0.045). Conclusion: De novo HF occurs in 5.4% of patients with GD and increases the rate of cardiovascular events. HF occurs more frequently in GD patients with AF, higher TRAb, higher BMI, and overt hyperthyroidism, suggesting that these may be targets for treatment to prevent cardiovascular complications, especially in older multimorbid patients.

scholarly journals Premature Atrial Contractions on the Screening Electrocardiogram and Risk of Ischemic Stroke: The Reasons for Geographic and Racial Differences in Stroke Study

2016 ◽  
Vol 47 (1) ◽  
pp. 53-58 ◽  
Author(s):  
Wesley T. O'Neal ◽  
Hooman Kamel ◽  
Dawn Kleindorfer ◽  
Suzanne E. Judd ◽  
George Howard ◽  
...  
Keyword(s):  
Risk Factors ◽  
Ischemic Stroke ◽  
Racial Differences ◽  
Stroke Risk ◽  
Cox Regression ◽  
Stroke Risk Factors ◽  
Stroke Study ◽  
Increased Risk ◽  
Study Participants ◽  
The Relationship

Background: It is currently unknown if premature atrial contractions (PACs) detected on the routine screening electrocardiogram are associated with an increased risk of ischemic stroke. Methods: We examined the association between PACs and ischemic stroke in 22,975 (mean age 64 ± 9.2; 56% women; 40% black) participants from the Reasons for Geographic and Racial Differences in Stroke study. Participants who were free of stroke at baseline were included. PACs were detected from centrally read electrocardiograms at baseline. Cox regression was used to examine the association between PACs and ischemic stroke events through March 31, 2014. Results: PACs were present in 1,687 (7.3%) participants at baseline. In a Cox regression model adjusted for stroke risk factors and potential confounders, PACs were associated with an increased risk of ischemic stroke (hazards ratio (HR) 1.34, 95% CI 1.04-1.74). The relationship was limited to non-lacunar infarcts (HR 1.42, 95% CI 1.08-1.87), and not lacunar strokes (HR 1.01, 95% CI 0.51-2.03). An interaction by sex was detected, with the association between PACs and ischemic stroke being stronger among women (HR 1.82, 95% CI 1.29-2.56) than men (HR 1.03, 95% CI 0.69-1.52; p-interaction = 0.0095). Conclusion: PACs detected on the routine electrocardiogram are associated with an increased risk for non-lacunar ischemic strokes, especially in women.

scholarly journals Risk factors for myocardial injury and death in patients with COVID-19: insights from a cohort study with chest computed tomography

2020 ◽  
Vol 116 (14) ◽  
pp. 2239-2246 ◽  
Author(s):  
Giuseppe Ferrante ◽  
Fabio Fazzari ◽  
Ottavia Cozzi ◽  
Matteo Maurina ◽  
Renato Bragato ◽  
...  
Keyword(s):  
Risk Factors ◽  
Computed Tomography ◽  
Cohort Study ◽  
Myocardial Injury ◽  
Troponin I ◽  
Cox Regression ◽  
Chest Ct ◽  
Chest Computed Tomography ◽  
Risk Of Death ◽  
Increased Risk

Abstract Aims Whether pulmonary artery (PA) dimension and coronary artery calcium (CAC) score, as assessed by chest computed tomography (CT), are associated with myocardial injury in patients with coronavirus disease 2019 (COVID-19) is not known. The aim of this study was to explore the risk factors for myocardial injury and death and to investigate whether myocardial injury has an independent association with all-cause mortality in patients with COVID-19. Methods and Results This is a single-centre cohort study including consecutive patients with laboratory-confirmed COVID-19 undergoing chest CT on admission. Myocardial injury was defined as high-sensitivity troponin I &gt;20 ng/L on admission. A total of 332 patients with a median follow-up of 12 days were included. There were 68 (20.5%) deaths; 123 (37%) patients had myocardial injury. PA diameter was higher in patients with myocardial injury compared with patients without myocardial injury [29.0 (25th–75th percentile, 27–32) mm vs. 27.7 (25–30) mm, P &lt; 0.001). PA diameter was independently associated with an increased risk of myocardial injury [adjusted odds ratio 1.10, 95% confidence interval (CI) 1.02–1.19, P = 0.01] and death [adjusted hazard ratio (HR) 1.09, 95% CI 1.02–1.17, P = 0.01]. Compared with patients without myocardial injury, patients with myocardial injury had a lower prevalence of a CAC score of zero (25% vs. 55%, P &lt; 0.001); however, the CAC score did not emerge as a predictor of myocardial injury by multivariable logistic regression. Myocardial injury was independently associated with an increased risk of death by multivariable Cox regression (adjusted HR 2.25, 95% CI 1.27–3.96, P = 0.005). Older age, lower estimated glomerular filtration rate, and lower PaO2/FiO2 ratio on admission were other independent predictors for both myocardial injury and death. Conclusions An increased PA diameter, as assessed by chest CT, is an independent risk factor for myocardial injury and mortality in patients with COVID-19. Myocardial injury is independently associated with an approximately two-fold increased risk of death.

P1667ANALYSIS OF RISK FACTORS FOR CMV DISEASE IN KIDNEY TRANSPLANT PATIENTS - SINGLE CENTER STUDY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Vladimir Hanzal ◽  
Janka Slatinska ◽  
Petra Hruba ◽  
Ondrej Viklicky
Keyword(s):  
Risk Factors ◽  
Kidney Transplantation ◽  
Multivariable Analysis ◽  
Graft Function ◽  
Kidney Graft ◽  
Cmv Infection ◽  
Post Transplantation ◽  
Increased Risk ◽  
Cmv Disease ◽  
Cmv Prophylaxis

Abstract Background and Aims Cytomegalovirus (CMV) disease and infection negatively influence outcome of kidney transplantation. The aim of this retrospective study was to analyze risk factors for CMV disease and its influence on kidney graft function and survival. Method 1050 patients underwent kidney transplantation from January 2014 to December 2018 and received calcineurin inhibitor, mycophenolate mofetil and steroid-based immunosuppression. Recipients with PRA&gt;20% received rATG while others had received basiliximab as induction. 825 out of 1050 patients (78.6%) received CMV prophylaxis (D+/R-, n=173; R+, n=652). Patients were followed up to 71 months /median 38 months/. Results CMV tissue invasive disease occurred in 49 out of 1050 patients (4.7%), while CMV infection in 87 patients (8.3%). CMV disease, but not CMV infection, had significant negative influence on graft survival at 5 years post transplantation (p=0.0029). Patients with CMV disease had significantly worse graft function at 4 years post transplantation (p&lt;0.0001). CMV disease occurred in 31 out of 173 patients (17.9%) in D+/R- group vs. 18 out of 652 patients (2.8%) in R+ group. Incidence of CMV infection was 30/173 patients (17.3%) in D+/R- group vs. 57/652 patients (8.7%) with induction therapy. Shortening of CMV prophylaxis was found in 82 patients (9.9%). Leukopenia (≤ 2.0 x 109/L) was observed in 97 (11.7%) patients from those who received CMV prophylaxis, Its shortening significantly increased risk for both CMV infection (20,7% vs. 7.2%, p&lt;0,0001) and CMV disease (8,5% vs. 4,2%, p=0,04). Among most significant risk factors for CMV disease in univariable analysis were CMV mismatch (OR 11, 95% CI: 5,9-20,4; p&lt;0,0001), delayed graft function (OR 2,8, 95% CI: 1,6-5,1; p&lt;0,0001, cadaveric donor (OR 6, 95% CI: 1,5-25,1; p=0,00013) and shortening of CMV prophylaxis (OR 2.1, 95% CI: 0,91-4,86; p=0,08). Multivariable analysis revealed as independent significant predictors of CMV disease DGF (OR 2,29, 95% CI: 1,2-4,3; p=0,01) and CMV mismatch (OR 10,8, 95% CI: 5,7-20,6; p&lt;0.0001) in a model adjusted for type of donor, prophylaxis shortening and leukopenia. Conclusion CMV mismatch is the main independent predictor of CMV disease after kidney transplantation in multivariable analysis.

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