Heparin-induced antibodies and cardiovascular risk in patients on dialysis

SummaryThe clinical relevance of heparin-induced antibodies (HIA) in the absence of thrombocytopenia remains to be defined. The aims of this study were (i) to determine the prevalence of HIA in patients treated by dialysis, (ii) to determine the prevalence of thrombocytopenia and heparin-induced thrombocytopenia (HIT), and (iii) to test whether HIA are associated with adverse outcomes. Sera from 740 patients treated by hemodialysis (HD, n=596) and peritoneal dialysis (PD, n=144) were tested for HIA (IgG, IgA or IgM) by masked investigators at approximately six months after enrolment in the Choices for Healthy Outcomes in Caring for End-Stage Renal Disease (CHOICE) study. We assessed, with time-to-event Cox proportional hazards models, whether the presence of HIA predicted any of four clinical outcomes: arterial cardiovascular events, venous thromboembolism, vascular access occlusion and mortality. HIA prevalence was 10.3% overall. HIA positivity did not predict development of thrombocytopenia or any of the four clinical outcomes over a mean follow-up of 3.6 years, with hazard ratios for arterial cardiovascular events of 0.98 (95% confidence interval 0.70–1.37), venous thromboembolism 1.39 (0.17–11.5), vascular access occlusion 0.82 (0.40–1.71), and mortality 1.18 (0.85–1.64). Chronic intermittent heparin exposure was associated with a high seroprevalence of HIA. In dialysis patients these antibodies were not an independent risk factor for cardiovascular events and mortality. Our data do not suggest that dialysis patients should be monitored for HIA antibodies in the absence of thrombocytopenia.

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Added value of cardiovascular calcifications for prediction of recurrent cardiovascular events and cardiovascular interventions in patients with established cardiovascular disease

The International Journal of Cardiovascular Imaging ◽

10.1007/s10554-021-02164-9 ◽

2021 ◽

Author(s):

Cilie C. van ’t Klooster ◽

◽

Yolanda van der Graaf ◽

Hendrik M. Nathoe ◽

Michiel L. Bots ◽

...

Keyword(s):

Cardiovascular Disease ◽

Heart Valve ◽

Cardiovascular Events ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Added Value ◽

Cvd Risk ◽

Major Cardiovascular Events ◽

Cox Proportional Hazards Models ◽

Cardiovascular Interventions

AbstractThe purpose is to investigate the added prognostic value of coronary artery calcium (CAC), thoracic aortic calcium (TAC), and heart valve calcium scores for prediction of a combined endpoint of recurrent major cardiovascular events and cardiovascular interventions (MACE +) in patients with established cardiovascular disease (CVD). In total, 567 patients with established CVD enrolled in a substudy of the UCC-SMART cohort, entailing cardiovascular CT imaging and calcium scoring, were studied. Five Cox proportional hazards models for prediction of 4-year risk of MACE + were developed; traditional CVD risk predictors only (model I), with addition of CAC (model II), TAC (model III), heart valve calcium (model IV), and all calcium scores (model V). Bootstrapping was performed to account for optimism. During a median follow-up of 3.43 years (IQR 2.28–4.74) 77 events occurred (MACE+). Calibration of predicted versus observed 4-year risk for model I without calcium scores was good, and the c-statistic was 0.65 (95%CI 0.59–0.72). Calibration for models II–V was similar to model I, and c-statistics were 0.67, 0.65, 0.65, and 0.68 for model II, III, IV, and V, respectively. NRIs showed improvement in risk classification by model II (NRI 15.24% (95%CI 0.59–29.39)) and model V (NRI 20.00% (95%CI 5.59–34.92)), but no improvement for models III and IV. In patients with established CVD, addition of the CAC score improved performance of a risk prediction model with classical risk factors for the prediction of the combined endpoint MACE+ . Addition of the TAC or heart valve score did not improve risk predictions.

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A Pediatric Approach to Ventilator-Associated Events Surveillance

Infection Control and Hospital Epidemiology ◽

10.1017/ice.2016.277 ◽

2016 ◽

Vol 38 (3) ◽

pp. 327-333 ◽

Cited By ~ 18

Author(s):

Noelle M. Cocoros ◽

Gregory P. Priebe ◽

Latania K. Logan ◽

Susan Coffin ◽

Gitte Larsen ◽

...

Keyword(s):

Blood Cell ◽

White Blood Cell ◽

Neonatal Intensive Care ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Adverse Outcomes ◽

Antimicrobial Use ◽

Cell Counts ◽

Cox Proportional Hazards Models ◽

Neonatal Icu

OBJECTIVEAdult ventilator-associated event (VAE) definitions include ventilator-associated conditions (VAC) and subcategories for infection-related ventilator-associated complications (IVAC) and possible ventilator-associated pneumonia (PVAP). We explored these definitions for children.DESIGNRetrospective cohortSETTINGPediatric, cardiac, or neonatal intensive care units (ICUs) in 6 US hospitalsPATIENTSPatients ≤18 years old ventilated for ≥1 dayMETHODSWe identified patients with pediatric VAC based on previously proposed criteria. We applied adult temperature, white blood cell count, antibiotic, and culture criteria for IVAC and PVAP to these patients. We matched pediatric VAC patients with controls and evaluated associations with adverse outcomes using Cox proportional hazards models.RESULTSIn total, 233 pediatric VACs (12,167 ventilation episodes) were identified. In the cardiac ICU (CICU), 62.5% of VACs met adult IVAC criteria; in the pediatric ICU (PICU), 54.2% of VACs met adult IVAC criteria; and in the neonatal ICU (NICU), 20.2% of VACs met adult IVAC criteria. Most patients had abnormal white blood cell counts and temperatures; we therefore recommend simplifying surveillance by focusing on “pediatric VAC with antimicrobial use” (pediatric AVAC). Pediatric AVAC with a positive respiratory diagnostic test (“pediatric PVAP”) occurred in 8.9% of VACs in the CICU, 13.3% of VACs in the PICU, and 4.3% of VACs in the NICU. Hospital mortality was increased, and hospital and ICU length of stay and duration of ventilation were prolonged among all pediatric VAE subsets compared with controls.CONCLUSIONSWe propose pediatric AVAC for surveillance related to antimicrobial use, with pediatric PVAP as a subset of AVAC. Studies on generalizability and responsiveness of these metrics to quality improvement initiatives are needed, as are studies to determine whether lower pediatric VAE rates are associated with improvements in other outcomes.Infect Control Hosp Epidemiol 2017;38:327–333

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Clinical Outcomes of Patients with Combined Idiopathic Pulmonary Fibrosis and Emphysema in the IPF-PRO Registry

Lung ◽

10.1007/s00408-021-00506-x ◽

2022 ◽

Author(s):

Hyun J. Kim ◽

Laurie D. Snyder ◽

Megan L. Neely ◽

Anne S. Hellkamp ◽

David L. Hotchkin ◽

...

Keyword(s):

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Clinical Outcomes ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Models ◽

Baseline Variable ◽

Former Smokers ◽

The Impact ◽

Baseline Covariates

Abstract Purpose To assess the impact of concomitant emphysema on outcomes in patients with idiopathic pulmonary fibrosis (IPF). Methods The IPF-PRO Registry is a US registry of patients with IPF. The presence of combined pulmonary fibrosis and emphysema (CPFE) at enrollment was determined by investigators’ review of an HRCT scan. Associations between emphysema and clinical outcomes were analyzed using Cox proportional hazards models. Results Of 934 patients, 119 (12.7%) had CPFE. Compared with patients with IPF alone, patients with CPFE were older (median 72 vs 70 years); higher proportions were current/former smokers (88.2% vs 63.7%), used oxygen with activity (49.6% vs 31.9%) or at rest (30.8% vs 18.4%), had congestive heart failure (13.6% vs 4.8%) and had prior respiratory hospitalization (25.0% vs 16.7%); they had higher FVC (median 71.8 vs 69.4% predicted) and lower DLco (median 35.3 vs 43.6% predicted). In patients with CPFE and IPF alone, respectively, at 1 year, rates of death or lung transplant were 17.5% (95% CI: 11.7, 25.8) and 11.2% (9.2, 13.6) and rates of hospitalization were 21.6% (14.6, 29.6) and 20.6% (17.9, 23.5). There were no significant associations between emphysema and any outcome after adjustment for baseline variables. No baseline variable predicted outcomes better in IPF alone than in CPFE. Conclusion Approximately 13% of patients in the IPF-PRO Registry had CPFE. Physiologic characteristics and comorbidities of patients with CPFE differed from those of patients with IPF alone, but the presence of emphysema did not drive outcomes after adjustment for baseline covariates. Trial registration ClinicalTrials.gov, NCT01915511; registered August 5, 2013.

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Characteristics and outcomes of an international cohort of 400,000 hospitalised patients with Covid-19

10.1101/2021.09.11.21263419 ◽

2021 ◽

Author(s):

◽

Christiana Kartsonaki

Keyword(s):

Clinical Outcomes ◽

Proportional Hazards ◽

Invasive Mechanical Ventilation ◽

Case Fatality ◽

Cox Proportional Hazards ◽

Risk Of Death ◽

Cox Proportional Hazards Models ◽

Hospitalised Patients ◽

Male Sex ◽

Viable Model

Background: Policymakers need robust data to respond to the COVID-19 pandemic. We describe demographic features, treatments and clinical outcomes in the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) COVID-19 cohort, the world's largest international, standardised cohort of hospitalised patients. Methods: The dataset analysed includes COVID-19 patients hospitalised between January 2020 and May 2021. We investigated how symptoms on admission, comorbidities, risk factors, and treatments varied by age, sex, and other characteristics. We used Cox proportional hazards models to investigate associations between demographics, symptoms, comorbidities, and other factors with risk of death, admission to intensive care unit (ICU), and invasive mechanical ventilation (IMV). Findings: 439,922 patients with laboratory-confirmed (91.7%) or clinically-diagnosed (8.3%) SARS-CoV-2 infection from 49 countries were enrolled. Age (adjusted hazard ratio [HR] per 10 years 1.49 [95% CI 1.49-1.50]) and male sex (1.26 [1.24-1.28]) were associated with a higher risk of death. Rates of admission to ICU and use of IMV increased with age up to age 60, then dropped. Symptoms, comorbidities, and treatments varied by age and had varied associations with clinical outcomes. Tuberculosis was associated with an 86% higher risk of death, and HIV with an 87% higher risk of death. Case fatality ratio varied by country partly due to differences in the clinical characteristics of recruited patients. Interpretation: The size of our international database and the standardized data collection method makes this study a reliable and comprehensive international description of COVID-19 clinical features. This is a viable model to be applied to future epidemics.

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Vascular Access and Clinical Outcomes in Underserved Hemodialysis Patients in Mexico

Blood Purification ◽

10.1159/000519878 ◽

2021 ◽

pp. 1-8

Author(s):

Pablo Maggiani-Aguilera ◽

Jochen G. Raimann ◽

Jonathan S. Chávez-Iñiguez ◽

Guillermo Navarro-Blackaller ◽

Peter Kotanko ◽

...

Keyword(s):

Central Venous Catheter ◽

Vascular Access ◽

Mortality Risk ◽

Proportional Hazards ◽

Venous Catheter ◽

Cox Proportional Hazards ◽

Adverse Outcomes ◽

Central Venous ◽

Conversion Rates ◽

The Usa

Introduction: Central venous catheter (CVC) as vascular access in hemodialysis (HD) associates with adverse outcomes. Early CVC to fistula or graft conversion improves these outcomes. While socioeconomic disparities between the USA and Mexico exist, little is known about CVC prevalence and conversion rates in uninsured Mexican HD patients. We examined vascular access practice patterns and their effects on survival and hospitalization rates among uninsured Mexican HD patients, in comparison with HD patients who initiated treatment in the USA. Methods: In this retrospective study of incident HD patients at Hospital Civil (HC; Guadalajara, MX) and the Renal Research Institute (RRI; USA), we categorized patients by the vascular access at the first month of HD and after the following 6 months. Factors associated with continued CVC use were identified by a logistic regression model. We developed multivariate Cox proportional hazards models to investigate the effects of access and conversion on mortality and hospitalization over an 18-month follow-up period. Results: In 1,632 patients from RRI, the CVC prevalence at month 1 was 64% and 97% among 174 HC patients. The conversion rate was 31.7% in RRI and 10.6% in HC. CVC to non-central venous catheter (NON-CVC) conversion reduced the risk of hospitalization in both HC (aHR 0.38 [95% CI: 0.21–0.68], p = 0.001) and RRI (aHR 0.84 [95% CI: 0.73–0.93], p = 0.001). NON-CVC patients had a lower mortality risk in both populations. Discussion/Conclusion: CVC prevalence and conversion rates of CVC to NON-CVC differed between the US and Mexican patients. An association exists between vascular access type and hospitalization and mortality risk. Prospective studies are needed to evaluate if accelerated and systematic catheter use reduction would improve outcomes in these populations.

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Matrix Gla Protein, Plaque Stability, and Cardiovascular Events in Patients with Severe Atherosclerotic Disease

Cardiology ◽

10.1159/000493006 ◽

2018 ◽

Vol 141 (1) ◽

pp. 32-36 ◽

Cited By ~ 7

Author(s):

Sabine R. Zwakenberg ◽

Yvonne T. van der Schouw ◽

Cees Vermeer ◽

Gerard Pasterkamp ◽

Hester M. den Ruijter ◽

...

Keyword(s):

Cardiovascular Events ◽

Proportional Hazards ◽

Weighted Kappa ◽

Cox Proportional Hazards ◽

Matrix Gla Protein ◽

Inverse Association ◽

Cvd Risk ◽

Plaque Stability ◽

Cox Proportional Hazards Models ◽

Histological Characteristics

Objective: This study aims to investigate whether plasma matrix Gla protein (MGP) species, desphospho-uncarboxylated (dp-uc) MGP, and total uncarboxylated (t-uc) MGP are associated with plaque levels of uncarboxylated (uc) MGP, markers of plaque stability, and cardiovascular disease (CVD) risk. Methods: From the Athero-Express biobank, we selected carotid plaque samples of 100 patients who underwent carotid endarterectomy. The level of agreement between plasma MGP species and plaque ucMGP levels was assessed using weighted kappa (κ). We analyzed histological characteristics of plaque composition (plaque hemorrhage, lipid and calcification content). Logistic regression analyses were used to assess the association between plasma MGP and plaque characteristics. Furthermore, CVD endpoints (n = 20) were collected over a mean follow-up of 2.6 years. Results: Weighted κ statistics of plasma dp-ucMGP and t-ucMGP and plaque ucMGP were 0.10 (95% CI –0.31 to 0.52) and 0.14 (95% CI –0.20 to 0.48). Higher dp-ucMGP levels tended to be associated with less plaque hemorrhage (ORper 500 nM 0.96; 95% CI 0.92–1.00). No association was found for lipid and calcification content. Cox proportional hazards models showed no association between dp-ucMGP (HRper 200 pM 0.92; 95% CI 0.75–1.11) and an inverse association between t-ucMGP (HRper 500 nM 0.79; 95% CI 0.62–0.99) and cardiovascular events. Conclusions: Plasma dp-ucMGP and t-ucMGP concentrations do not reflect plaque ucMGP levels. Elevated dp-ucMGP levels may be associated with less plaque hemorrhage, suggestive of more stable plaques. T-ucMGP was not related with markers of plaque stability; however, elevated plasma t-ucMGP levels were associated with a reduced CVD risk.

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Effect of altitude on mortality of end-stage renal disease patients on hemodialysis in Peru

Clinical Kidney Journal ◽

10.1093/ckj/sfaa056 ◽

2020 ◽

Author(s):

Katia Bravo-Jaimes ◽

Viky Y Loescher ◽

Carlos Canelo-Aybar ◽

Jose Rojas-Camayo ◽

Christian R Mejia ◽

...

Keyword(s):

High Altitude ◽

Sea Level ◽

Proportional Hazards ◽

Cox Model ◽

Cox Proportional Hazards ◽

Historical Cohort ◽

Cox Proportional Hazards Models ◽

Low Altitude ◽

Stage Renal Disease ◽

End Stage

Abstract Background In Latin America, the prevalence of end-stage kidney disease (ESKD) has risen tremendously during the last decade. Previous studies have suggested that receiving dialysis at high altitude confers mortality benefits; however, this effect has not been demonstrated at >2000 m above sea level (masl) or in developing countries. Methods This historical cohort study analyzed medical records from six Peruvian hemodialysis (HD) centers located at altitudes ranging from 44 to 3827 masl. Adult ESKD patients who started maintenance HD between 2000 and 2010 were included. Patients were classified into two strata based on the elevation above sea level of their city of residence: low altitude (<2000 masl) and high altitude (≥2000 masl). Death from any cause was collected from national registries and Cox proportional hazards models were built. Results A total of 720 patients were enrolled and 163 (22.6%) resided at high altitude. The low-altitude group was significantly younger, more likely to have diabetes or glomerulonephritis as the cause of ESKD and higher hemoglobin. The all-cause mortality rate was 84.3 per 1000 person-years. In the unadjusted Cox model, no mortality difference was found between the high- and low-altitude groups {hazard ratio [HR] 1.20 [95% confidence interval (CI) 0.89–1.62]}. After multivariable adjustment, receiving HD at high altitude was not significantly associated with higher mortality, but those with diabetes as the cause of ESKD had significantly higher mortality [HR 2.50 (95% CI 1.36–4.59)]. Conclusions In Peru, patients receiving HD at high altitudes do not have mortality benefits.

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Spot Urine Sodium-to-Potassium Ratio Is a Predictor of Stroke

Stroke ◽

10.1161/strokeaha.118.023099 ◽

2019 ◽

Vol 50 (2) ◽

pp. 321-327 ◽

Cited By ~ 6

Author(s):

Michelle M. Averill ◽

Rebekah L. Young ◽

Alexis C. Wood ◽

Emily O. Kurlak ◽

Holly Kramer ◽

...

Keyword(s):

Cardiovascular Events ◽

Proportional Hazards ◽

Routine Care ◽

Cox Proportional Hazards ◽

Urinary Sodium ◽

Dietary Sodium ◽

Urine Sodium ◽

Spot Urine ◽

Cox Proportional Hazards Models ◽

The Impact

Background and Purpose— Dietary sodium reduction with concurrent increase in potassium intake is a current public health priority to reduce risk of cardiovascular events. This study explored associations between the spot urine sodium-to-potassium ratio and cardiovascular events in the MESA (Multi-Ethnic Study of Atherosclerosis) longitudinal cohort. Methods— The MESA is a prospective cohort study of 6814 adults from 4 ethnic groups (European-, Asian-, African- and Hispanic-American) with a mean age of 62 (±10.2) years and an average of 11.7 (±2.2) years of follow-up. Participants were free of clinical cardiovascular disease at baseline. Spot urine sodium and potassium excretion, as a marker of dietary intake, was collected at baseline. The impact of urinary sodium-to-potassium ratio on adjudicated cardiovascular events was assessed using Cox proportional hazards models. Results— Only 39% of MESA participants had a urinary sodium-to-potassium ratio ≤1, and these participants experienced only 74 of the 236 strokes. A sodium-to-potassium ratio >1 was associated with a hazard ratio of 1.47 (95% CI,1.07–2.00) for risk of stroke, adjusting for age, sex, race, cardiovascular risk factors, socio-demographic characteristics, body size, and kidney function. Conclusions— The spot urine sodium-to-potassium ratio (measurable in routine care) is associated with stroke. A urine sodium-to-potassium ratio of ≤1, may be related to a clinically relevant reduction in stroke risk and is a feasible target for health interventions.

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Serum Galectin-3 levels and all-cause and cardiovascular mortality in maintenance hemodialysis patients: a prospective cohort study

BMC Nephrology ◽

10.1186/s12882-021-02636-z ◽

2022 ◽

Vol 23 (1) ◽

Author(s):

Shuxin Liu ◽

Qijun Wu ◽

Shuang Zhang ◽

Zhihong Wang ◽

Hong Liu ◽

...

Keyword(s):

Cohort Study ◽

Prospective Cohort Study ◽

Prospective Cohort ◽

Proportional Hazards ◽

Multivariable Analysis ◽

Cox Proportional Hazards ◽

Adverse Outcomes ◽

Maintenance Hemodialysis ◽

Galectin 3 ◽

Stage Renal Disease

Abstract Background Higher serum galectin-3 levels are related to adverse outcomes in different disease states. However, the association of galectin-3 with mortality in the maintenance hemodialysis (HD) population has not been fully described. Thus, we aimed to assess the predictive significance of galectin-3 for all-cause and cardiovascular (CV) mortality through a Chinese maintenance HD population. Methods A prospective cohort study was conducted in five hundred and six patients with end-stage renal disease who underwent hemodialysis at Dalian Central Hospital before December 31, 2014. Serum galectin-3 levels were measured at baseline and classified as high (> 8.65 ng/ml) or low (≤ 8.65 ng/ml) according to the “X-tile” program. Primary and secondary outcomes were all-cause and CV mortality, respectively. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated by the Cox proportional hazards regression models. Results During the median follow-up of 60 months, there were 188 all-cause deaths and 125 CV deaths. Compared with maintenance HD population with galectin-3 ≤ 8.65 ng/ml, the adjusted HR for all-cause mortality among those with galectin-3 > 8.65 ng/ml was 1.59 (CI: 0.96–2.65, p = 0.07). Furthermore, multivariable analysis showed that maintenance HD patients with galectin-3 > 8.65 ng/ml had a 2.13-fold higher risk of CV death than those with galectin-3 ≤ 8.65 ng/ml (HR = 2.13, 95% CI 1.07–4.26). Conclusion Galectin-3 is an independent predictor of CV mortality in maintenance HD patients.

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Temporal trends in the management and clinical outcomes of lower extremity arterial thromboembolism within a national Veteran population

Vascular Medicine ◽

10.1177/1358863x18793210 ◽

2018 ◽

Vol 24 (1) ◽

pp. 41-49 ◽

Cited By ~ 2

Author(s):

Andrew F Prouse ◽

Paula Langner ◽

Mary E Plomondon ◽

P Michael Ho ◽

Javier A Valle ◽

...

Keyword(s):

Lower Extremity ◽

Clinical Outcomes ◽

Proportional Hazards ◽

Temporal Trends ◽

Primary Diagnosis ◽

Cox Proportional Hazards ◽

Major Adverse Cardiovascular Events ◽

Arterial Thromboembolism ◽

Endovascular Revascularization ◽

Cox Proportional Hazards Models

Lower extremity arterial thromboembolism is associated with significant morbidity and mortality. We sought to establish temporal trends in the incidence, management and outcomes of lower extremity arterial thromboembolism within the Veterans Affairs Healthcare System (VAHS). We identified patients admitted to VAHS between 2003 and 2014 with a primary diagnosis of lower extremity arterial thromboembolism. Medical and procedural management were ascertained from pharmaceutical and administrative data. Subsequent rates of major adverse limb events (MALE), major adverse cardiovascular events (MACE), and mortality were calculated using Cox proportional hazards models. From 2003 to 2014, there were 10,636 patients hospitalized for lower extremity thromboembolism across 140 facilities, of which 8474 patients had adequate comorbid information for analysis. Age-adjusted incidence decreased from 7.98 per 100,000 patients (95% CI: 7.28–8.75) in 2003 to 3.54 (95% CI: 3.14–3.99) in 2014. On average, the likelihood of receiving anti-platelet or anti-thrombotic therapy increased 2.3% (95% CI: 1.2–3.4%) per year during this time period and the likelihood of undergoing endovascular revascularization increased 4.0% (95% CI: 2.7–5.4%) per year. Clinical outcomes remained constant over time, with similar rates of MALE, MACE and mortality at 1 year after adjustment. In conclusion, the incidence of lower extremity arterial thromboembolism is decreasing, with increasing utilization of anti-thrombotic therapies and endovascular revascularization among those with this condition. Despite this evolution in management, patients with lower extremity thromboembolism continue to experience high rates of amputation and death within a year of the index event.

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