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Background: Limited existing data suggest that the novel COVID-19 may increase risk of VTE, but information from large, ethnically diverse populations with appropriate control participants is lacking.Research Question: Does the rate of VTE among adults hospitalized with COVID-19 differ from matched hospitalized control participants without COVID-19?Study Design and Methods: We conducted a retrospective study among hospitalized adults with laboratory-confirmed COVID-19 and hospitalized adults without evidence of COVID-19 matched for age, sex, race or ethnicity, acute illness severity, and month of hospitalization between February 2020 and August 2020 from two integrated health-care delivery systems with 36 hospitals. Outcomes included VTE (DVT or pulmonary embolism ascertained using diagnosis codes combined with validated natural language processing algorithms applied to electronic health records) and death resulting from any cause at 30 days. Fine and Gray hazards regression was performed to evaluate the association of COVID-19 with VTE after accounting for competing risk of death and residual differences between groups, as well as to identify predictors of VTE in patients with COVID-19.Results: We identified 6,319 adults with COVID-19 and 6,319 matched adults without COVID-19, with mean ± SD age of 60.0 ± 17.2 years, 46% women, 53.1% Hispanic, 14.6% Asian/Pacific Islander, and 10.3% Black. During 30-day follow-up, 313 validated cases of VTE (160 COVID-19, 153 control participants) and 1,172 deaths (817 in patients with COVID-19, 355 in control participants) occurred. Adults with COVID-19 showed a more than threefold adjusted risk of VTE (adjusted hazard ratio, 3.48; 95% CI, 2.03-5.98) compared with matched control participants. Predictors of VTE in patients with COVID-19 included age ≥ 55 years, Black race, prior VTE, diagnosed sepsis, prior moderate or severe liver disease, BMI ≥ 40 kg/m2, and platelet count > 217 k/μL.Interpretation: Among ethnically diverse hospitalized adults, COVID-19 infection increased the risk of VTE, and selected patient characteristics were associated with higher thromboembolic risk in the setting of COVID-19. [ABSTRACT FROM AUTHOR]

Background: Multiple morbidity is the norm in advanced COPD and contributes to high symptom burden and worse outcomes.Research Question: Can distinct comorbidity profiles be identified and validated in a community-based sample of patients with COPD from a large integrated health care system using a standard, commonly used diagnostic code-based comorbidity index and downstream 2-year health care use data?Study Design and Methods: In this retrospective cohort study, we used latent class analysis (LCA) to identify comorbidity profiles in a population-based sample of 91,453 patients with a COPD diagnosis between 2011 and 2015. We included specific comorbid conditions from the Charlson Comorbidity Index (CCI) and accounted for variation in underlying prevalence of different comorbidities across the three study sites. Sociodemographic, clinical, and health-care use data were obtained from electronic health records (EHRs). Multivariate logistic regression analysis was used to compare rates of acute and postacute care use by class.Results: The mean age was 71 ± 11 years, 55% of patients were women, 23% of patients were people of color, and 80% of patients were former or current smokers. LCA identified four distinct comorbidity profiles with progressively higher CCI scores: low morbidity (61%; 1.9 ± 1.4), metabolic renal (21%; 4.7 ± 1.8), cardiovascular (12%; 4.6 ± 1.9), and multimorbidity (7%; 7.5 ± 1.7). In multivariate models, during 2 years of follow-up, a significant, nonoverlapping increase was found in the odds of having any all-cause acute (hospitalizations, observation stays, and ED visits) and postacute care use across the comorbidity profiles.Interpretation: Distinct comorbidity profiles can be identified in patients with COPD using standard EHR-based diagnostic codes, and these profiles are associated with subsequent acute and postacute care use. Population-based risk stratification schemes for end-to-end, comprehensive COPD management should consider integrating comorbidity profiles such as those found in this study. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To determine whether burden of multiple chronic conditions (MCCs) influences the risk of receiving inappropriate vs appropriate device therapies. DESIGN: Retrospective cohort study. SETTING: Seven US healthcare delivery systems. PARTICIPANTS: Adults with left ventricular systolic dysfunction receiving an implantable cardioverter‐defibrillator (ICD) for primary prevention. MEASUREMENTS: Data on 24 comorbid conditions were captured from electronic health records and categorized into quartiles of comorbidity burden (0‐3, 4‐5, 6‐7 and 8‐16). Incidence of ICD therapies (shock and antitachycardia pacing [ATP] therapies), including appropriateness, was collected for 3 years after implantation. Outcomes included time to first ICD therapy, total ICD therapy burden, and risk of inappropriate vs appropriate ICD therapy. RESULTS: Among 2235 patients (mean age = 69 ± 11 years, 75% men), the median number of comorbidities was 6 (interquartile range = 4‐8), with 98% having at least two comorbidities. During a mean 2.2 years of follow‐up, 18.3% of patients experienced at least one appropriate therapy and 9.9% experienced at least one inappropriate therapy. Higher comorbidity burden was associated with an increased risk of first inappropriate therapy (adjusted hazard ratio [HR] = 1.94 [95% confidence interval {CI} = 1.14‐3.31] for 4‐5 comorbidities; HR = 2.25 [95% CI = 1.25‐4.05] for 6‐7 comorbidities; and HR = 2.91 [95% CI = 1.54‐5.50] for 8‐16 comorbidities). Participants with 8‐16 comorbidities had a higher total burden of ICD therapy (adjusted relative risk [RR] = 2.12 [95% CI = 1.43‐3.16]), a higher burden of inappropriate therapy (RR = 3.39 [95% CI = 1.67‐6.86]), and a higher risk of receiving inappropriate vs appropriate therapy (RR = 1.74 [95% CI = 1.07‐2.82]). Comorbidity burden was not significantly associated with receipt of appropriate ICD therapies. Patterns were similar when separately examining shock or ATP therapies. CONCLUSIONS: In primary prevention ICD recipients, MCC burden was independently associated with an increased risk of inappropriate but not appropriate device therapies. Comorbidity burden should be considered when engaging patients in shared decision making about ICD implantation. [ABSTRACT FROM AUTHOR]

Objective: Patients with chronic kidney disease (CKD) have higher risk of sudden cardiac death; however, they may not receive implantable cardioverter defibrillators (ICDs), in part due to higher risk of complications. We evaluated whether CKD is associated with greater risk of device-delivered shocks/antitachycardia pacing (ATP) therapies among patients receiving a primary prevention ICD.Methods: We studied participants in the observational Cardiovascular Research Network Longitudinal Study of Implantable Cardioverter Defibrillators. CKD was defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. Outcomes included all delivered shocks/ATPs therapies and type of shock/ATP therapies (inappropriate or appropriate, determined by physician adjudication) within the 3 years. We evaluated the associations between CKD and time to first device therapy, burden of device therapy, and inappropriate versus appropriate device therapy, adjusting for demographics, comorbidity, laboratory values and medication use.Results: Among 2161 participants, 1066 (49.3%) had CKD (eGFR 44±11 mL/min/1.73 m2) at ICD implantation. During mean of 2.26±0.89 years, 9.8% and 18.5% of participants had at least one inappropriate and appropriate shock/ATP therapies, respectively. CKD was not associated with time to first shock/ATP therapies (adjusted HR 0.87, 95% CI 0.73 to 1.05), overall burden of shock/ATP therapies (adjusted relative rate 0.93, 95% CI 0.74 to 1.17) or inappropriate versus appropriate shock/ATP therapies (adjusted relative risk 0.88, 95% CI 0.68 to 1.14) compared with not having CKD.Conclusions: In adults receiving a primary prevention ICD, mild-to-moderate CKD was not associated with the timing, burden or appropriateness of subsequent device therapy. Potential concern for inappropriate ICD-delivered therapies should not preclude ICDs among eligible patients with CKD. [ABSTRACT FROM AUTHOR]

Background: The accuracy of the 2013 American College of Cardiology/American Heart Association (ACC/AHA) Pooled Cohort Risk Equation for atherosclerotic cardiovascular disease (ASCVD) events in contemporary and ethnically diverse populations is not well understood.Objectives: The goal of this study was to evaluate the accuracy of the 2013 ACC/AHA Pooled Cohort Risk Equation within a large, multiethnic population in clinical care.Methods: The target population for consideration of cholesterol-lowering therapy in a large, integrated health care delivery system population was identified in 2008 and followed up through 2013. The main analyses excluded those with known ASCVD, diabetes mellitus, low-density lipoprotein cholesterol levels <70 or ≥190 mg/dl, prior lipid-lowering therapy use, or incomplete 5-year follow-up. Patient characteristics were obtained from electronic medical records, and ASCVD events were ascertained by using validated algorithms for hospitalization databases and death certificates. We compared predicted versus observed 5-year ASCVD risk, overall and according to sex and race/ethnicity. We additionally examined predicted versus observed risk in patients with diabetes mellitus.Results: Among 307,591 eligible adults without diabetes between 40 and 75 years of age, 22,283 were black, 52,917 were Asian/Pacific Islander, and 18,745 were Hispanic. We observed 2,061 ASCVD events during 1,515,142 person-years. In each 5-year predicted ASCVD risk category, observed 5-year ASCVD risk was substantially lower: 0.20% for predicted risk <2.50%; 0.65% for predicted risk 2.50% to <3.75%; 0.90% for predicted risk 3.75% to <5.00%; and 1.85% for predicted risk ≥5.00% (C statistic: 0.74). Similar ASCVD risk overestimation and poor calibration with moderate discrimination (C statistic: 0.68 to 0.74) were observed in sex, racial/ethnic, and socioeconomic status subgroups, and in sensitivity analyses among patients receiving statins for primary prevention. Calibration among 4,242 eligible adults with diabetes was improved, but discrimination was worse (C statistic: 0.64).Conclusions: In a large, contemporary "real-world" population, the ACC/AHA Pooled Cohort Risk Equation substantially overestimated actual 5-year risk in adults without diabetes, overall and across sociodemographic subgroups. [ABSTRACT FROM AUTHOR]

Introduction: The Kaiser Permanente ASCVD Risk Estimator (KPARE) was developed to address the systematic overestimation of actual ASCVD risk by the ACC/AHA ASCVD Pooled Cohort Equation (ACC/AHA PCE) in contemporary populations. We evaluated the accuracy and generalizability of KPARE for estimating 10-year ASCVD risk in eligible primary prevention, community-based populations in the U.S. and Canada, as compared with the ACC/AHA PCE. Methods: We identified adults 40-79 years old in 3 contemporary U.S. populations (Kaiser Permanente Northern California (KPNC), Southern California (KPSC) and Northwest (KPNW), as well as adults 66-79 years old in Ontario, Canada who had LDL-C 70-189 mg/dL, no known ASCVD, diabetes or lipid-lowering therapy and had complete follow-up. Non-fatal and fatal ASCVD events were ascertained from health system electronic health records and death certificates using validated algorithms. We examined observed ASCVD event rates within deciles of predicted 10-year risk using the KPARE vs. the ACC/AHA PCE predicted risk, and calculated metrics of discrimination and calibration. Results: In eligible primary prevention validation cohorts of KPNC (N=151,409), KPSC (N=246,815), KPNW (N=46,784), and Ontario, Canada (N=60,612 adults), the KPARE showed both better discrimination and calibration (Figure) compared to the ACC/AHA PCE to predict 10-year risk of ASCVD events, with c-statistics of 0.78, 0.78, 0.79, and 0.65, respectively. Categorical net reclassification index showed the KPARE improved ASCVD risk prediction over the ACC/AHA PCE by 23% in the KPNC validation cohort, 24% in KPSC, 33% in KPNW, and 25% in Ontario, Canada. Results were similar when stratified by race-gender subgroups. Conclusions: The new Kaiser Permanente ASCVD Risk Estimator provides more accurate ASCVD risk estimates in various community populations than the ACC/AHA PCE and may provide greater utility in shared decision-making for primary prevention strategies. [ABSTRACT FROM AUTHOR]

Low transferrin saturation (TSAT) or reduced serum ferritin level are suggestive of iron deficiency but the relationship between iron parameters and outcomes has not been systematically evaluated in older adults with heart failure (HF) and anemia. We identified a multicenter cohort of adults age ≥ 65 years with HF and incident anemia (hemoglobin <13 g/dL [men] or < 12 g/dL [women]) between 2005 and 2012. Patients were included if ferritin (ng/mL) and TSAT (%) were evaluated within 90 days of incident anemia. HF hospitalizations and all-cause death were ascertained from electronic health records. Among 4103 older adults with HF and incident anemia, 47% had TSAT <20% and the median (IQR) ferritin was 126 (53, 256) ng/mL. In multivariable analyses, compared with TSAT ≥20%, patients with TSAT <20% were at increased risk of HF hospitalization for serum ferritin <100 ng/mL (adjusted HR [aHR] 1.40, 95% CI:1.16–1.70) and 100–300 ng/mL (aHR 1.24, 95% CI:1.01–1.52) but not for a ferritin >300 ng/mL (aHR 0.89, 95% CI 0.65–1.23). In addition, TSAT <20% was independently associated with an increased risk of all-cause death regardless of serum ferritin level (<100 ng/mL: aHR 1.42, 95% CI:1.20–1.68; 100–300 ng/mL: aHR 1.18, 95% CI:1.00–1.38; >300 ng/mL: aHR 1.33, 95% CI:1.06–1.69). Among older adults with HF and incident anemia who had iron studies tested, nearly half had a TSAT <20%, which was independently associated with higher rates of morbidity and death. • Among older adults with HF, ~55% of patients were found to have iron deficiency (i.e., ferritin <100 ng/mL or ferritin 100–300 ng/mL and TSAT <20%). • A TSAT <20% was independently associated with HF hospitalizations and all-cause death. • These findings remained unchanged in sensitivity analyses stratified by degree of systolic dysfunction (i.e., reduced vs. mid-range vs. preserved). [ABSTRACT FROM AUTHOR]