Search

Damià Valero-Bover,1,2 David Monterde,2,3 Gerard Carot-Sans,1,2 Miguel Cainzos-Achirica,4,5 Josep Comin-Colet,6– 8 Emili Vela,1,2 Montse Clèries,1,2 Júlia Folguera,1,2 Sònia Abilleira,9 Miquel Arrufat,3 Yolanda Lejardi,3 Òscar Solans,2,10 Toni Dedeu,11 Marc Coca,1,2 Pol Pérez-Sust,1 Caridad Pontes,1,2,12 Jordi Piera-Jiménez1,2,13 1Catalan Health Service, Barcelona, Spain; 2Digitalization for the Sustainability of the Healthcare System (DS3) – Institut d’Investigacions Biomèdiques de Bellvitge (IDIBELL), Barcelona, Spain; 3Catalan Institute of Health, Barcelona, Spain; 4Center for Outcomes Research, Houston Methodist, Houston, TX, USA; 5Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins Medical Institutions, Baltimore, MD, USA; 6Cardiology Department, Bellvitge University Hospital (IDIBELL), Barcelona, Spain; 7Department of Medicine, University of Barcelona, Hospitalet de Llobregat, Barcelona, Spain; 8CIBER Cardiovascular (CIBERCV), L’Hospitalet de Llobregat, Barcelona, Spain; 9CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain; 10Health Department, eHealth Unit, Barcelona, Spain; 11WHO European Centre for Primary Health Care, Almaty, Kazakhstan; 12Department of Pharmacology, Autonomous University of Barcelona, Barcelona, Spain; 13Faculty of Informatics, Telecommunications and Multimedia, Universitat Oberta de Catalunya, Barcelona, SpainCorrespondence: Jordi Piera-Jiménez, Catalan Health Service, Gran Via de les Corts Catalanes 587, Barcelona, 08007, Spain, Tel +34 93 403 85 85, Email jpiera@catsalut.catPurpose: To assess the contribution of age and comorbidity to the risk of critical illness in hospitalized COVID-19 patients using increasingly exhaustive tools for measuring comorbidity burden.Patients and Methods: We assessed the effect of age and comorbidity burden in a retrospective, multicenter cohort of patients hospitalized due to COVID-19 in Catalonia (North-East Spain) between March 1, 2020, and January 31, 2022. Vaccinated individuals and those admitted within the first of the six COVID-19 epidemic waves were excluded from the primary analysis but were included in secondary analyses. The primary outcome was critical illness, defined as the need for invasive mechanical ventilation, transfer to the intensive care unit (ICU), or in-hospital death. Explanatory variables included age, sex, and four summary measures of comorbidity burden on admission extracted from three indices: the Charlson index (17 diagnostic group codes), the Elixhauser index and count (31 diagnostic group codes), and the Queralt DxS index (3145 diagnostic group codes). All models were adjusted by wave and center. The proportion of the effect of age attributable to comorbidity burden was assessed using a causal mediation analysis.Results: The primary analysis included 10,551 hospitalizations due to COVID-19; of them, 3632 (34.4%) experienced critical illness. The frequency of critical illness increased with age and comorbidity burden on admission, irrespective of the measure used. In multivariate analyses, the effect size of age decreased with the number of diagnoses considered to estimate comorbidity burden. When adjusting for the Queralt DxS index, age showed a minimal contribution to critical illness; according to the causal mediation analysis, comorbidity burden on admission explained the 98.2% (95% CI 84.1– 117.1%) of the observed effect of age on critical illness.Conclusion: Comorbidity burden (when measured exhaustively) explains better than chronological age the increased risk of critical illness observed in patients hospitalized with COVID-19.Keywords: COVID-19, comorbidities, comorbidity burden, risk assessment, hospitalized patients, case-mix tool

David Monterde,1,2 Gerard Carot-Sans,2,3 Miguel Cainzos-Achirica,4,5 Sònia Abilleira,1,6 Marc Coca,2,3 Emili Vela,2,3 Montse Clèries,2,3 Damià Valero-Bover,2,3 Josep Comin-Colet,7– 9 Luis García-Eroles,2,3 Pol Pérez-Sust,3 Miquel Arrufat,1 Yolanda Lejardi,1 Jordi Piera-Jiménez2,3,10 1Catalan Institute of Health, Barcelona, Spain; 2Digitalization for the Sustainability of the Healthcare System (DS3), Sistema de Salut de Catalunya, Barcelona, Spain; 3Servei Català de la Salut, Barcelona, Spain; 4Center for Outcomes Research, Houston Methodist, Houston, TX, USA; 5Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins Medical Institutions, Baltimore, MD, USA; 6CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain; 7Department of Cardiology, Hospital Universitari de Bellvitge, L’Hospitalet de Llobregat, Barcelona, Spain; 8Bioheart-Cardiovascular Diseases Research Group (Idibell), L’Hospitalet de Llobregat, Barcelona, Spain; 9Department of Clinical Sciences, School of Medicine, Universität de Barcelona - UB, L’Hospitalet de Llobregat, Barcelona, Spain; 10Open Evidence Research Group, Universitat Oberta de Catalunya, Barcelona, SpainCorrespondence: Jordi Piera-JiménezServei Català de la Salut (CatSalut), Travessera de les Corts, 131-159 (Edifici Olímpia), Barcelona, 08028, SpainTel +34 634283110Email jpiera@catsalut.catBackground: Comorbidity burden has been identified as a relevant predictor of critical illness in patients hospitalized with coronavirus disease 2019 (COVID-19). However, comorbidity burden is often represented by a simple count of few conditions that may not fully capture patients’ complexity.Purpose: To evaluate the performance of a comprehensive index of the comorbidity burden (Queralt DxS), which includes all chronic conditions present on admission, as an adjustment variable in models for predicting critical illness in hospitalized COVID-19 patients and compare it with two broadly used measures of comorbidity.Materials and Methods: We analyzed data from all COVID-19 hospitalizations reported in eight public hospitals in Catalonia (North-East Spain) between June 15 and December 8 2020. The primary outcome was a composite of critical illness that included the need for invasive mechanical ventilation, transfer to ICU, or in-hospital death. Predictors including age, sex, and comorbidities present on admission measured using three indices: the Charlson index, the Elixhauser index, and the Queralt DxS index for comorbidities on admission. The performance of different fitted models was compared using various indicators, including the area under the receiver operating characteristics curve (AUROCC).Results: Our analysis included 4607 hospitalized COVID-19 patients. Of them, 1315 experienced critical illness. Comorbidities significantly contributed to predicting the outcome in all summary indices used. AUC (95% CI) for prediction of critical illness was 0.641 (0.624– 0.660) for the Charlson index, 0.665 (0.645– 0.681) for the Elixhauser index, and 0.787 (0.773– 0.801) for the Queralt DxS index. Other metrics of model performance also showed Queralt DxS being consistently superior to the other indices.Conclusion: In our analysis, the ability of comorbidity indices to predict critical illness in hospitalized COVID-19 patients increased with their exhaustivity. The comprehensive Queralt DxS index may improve the accuracy of predictive models for resource allocation and clinical decision-making in the hospital setting.Keywords: comorbidity, multimorbidity, COVID-19, hospitalization, risk

Santiago Jiménez-Marrero,1,2 Miguel Cainzos-Achirica,1– 4 David Monterde,5 Luis Garcia-Eroles,5 Cristina Enjuanes,1,2 Sergi Yun,1,2,6 Alberto Garay,1,2 Pedro Moliner,1,2 Lidia Alcoberro,1,2 Xavier Corbella,2,6,7 Josep Comin-Colet1,2,8 1Community Heart Failure Program, Department of Cardiology, Bellvitge University Hospital, L’Hospitalet de Llobregat, Barcelona, Spain; 2Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain; 3Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins Medical Institutions, Baltimore, MD, USA; 4School of Medicine and Health Sciences, International University of Catalonia, Barcelona, Spain; 5Healthcare Information and Knowledge Unit, Catalan Health Service, Barcelona, Spain; 6Department of Internal Medicine, Bellvitge University Hospital, L’Hospitalet de Llobregat, Barcelona, Spain; 7Hestia Chair in Integrated Health and Social Care, Faculty of Medicine and Health Sciences, Universitat Internacional de Catalunya, Barcelona, Spain; 8Department of Clinical Sciences, School of Medicine, University of Barcelona, Barcelona, SpainCorrespondence: Josep Comin-ColetHospital Universitari de Bellvitge, Department of Cardiology, 19th Floor, Feixa Llarga s/n, 08907 Hospitalet de Llobregat, Barcelona, SpainTel +34932607078Email jcomin@bellvitgehospital.catBackground: The aims of the present analysis are to estimate the prevalence of five key chronic cardiovascular, metabolic and renal conditions at the population level, the prevalence of renin–angiotensin–aldosterone system inhibitor (RAASI) medication use and the magnitude of potassium (K+) derangements among RAASI users.Methods and Results: We used data from more than 375,000 individuals, 55 years of age or older, included in the population-based healthcare database of the Catalan Institute of Health between 2015 and 2017. The conditions of interest were chronic heart failure (CHF), chronic kidney disease (CKD), diabetes mellitus, ischemic heart disease and hypertension. RAASI medications included angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, mineralocorticoid receptor antagonists (MRAs) and renin inhibitors. Hyperkalemia was defined as K+ levels > 5.0 mEq/L and hypokalemia as K+ < 3.5 mEq/L. The prevalence of chronic cardiovascular, metabolic and renal conditions was high, and particularly that of hypertension (prevalence ranging from 48.2% to 48.9%). The use of at least one RAASI medication was almost ubiquitous in these patients (75.2– 77.3%). Among RAASI users, the frequency of K+ derangements, mainly of hyperkalemia, was very noticeable (12% overall), particularly in patients with CKD or CHF, elderly individuals and users of MRAs. Hypokalemia was less frequent (1%).Conclusion: The high prevalence of K+ derangements, and particularly hyperkalemia, among RAASI users highlights the real-world relevance of K+ derangements, and the importance of close monitoring and management of K+ levels in routine clinical practice. This is likely to benefit a large number of patients, particularly those at higher risk.Keywords: chronic heart failure, chronic kidney disease, heart failure, hyperkalemia, hypertension, potassium

David Monterde,1 Miguel Cainzos-Achirica,2,3 Yolima Cossio-Gil,4,5 Luis García-Eroles,6 Pol Pérez-Sust,7 Miquel Arrufat,1 Candela Calle,8 Josep Comin-Colet,3,9 César Velasco4,5 1Catalan Institute of Health, Barcelona, Spain; 2Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins Medical Institutions, Baltimore, MD, USA; 3Bellvitge University Hospital, L’Hospitalet de Llobregat, Barcelona, Spain; 4Vall d’Hebron Hospital, Barcelona, Spain; 5Vall d’Hebron Research Institute (VHIR), Barcelona, Spain; 6Catalan Health Service, Barcelona, Spain; 7Catalan Health Department, Barcelona, Spain; 8Catalan Institute of Oncology (ICO), Barcelona, Spain; 9University of Barcelona, Barcelona, SpainCorrespondence: David MonterdeDepartment of Statistics, Information Systems, Catalan Institute of Health, Gran via De Les Corts Catalanes 587, Barcelona 08007, SpainTel +34 934824642Email dmonterde@gencat.catBackground: Accurate risk adjustment is crucial for healthcare management and benchmarking.Purpose: We aimed to compare the performance of classic comorbidity functions (Charlson’s and Elixhauser’s), of the All Patients Refined Diagnosis Related Groups (APR-DRG), and of the Queralt Indices, a family of novel, comprehensive comorbidity indices for the prediction of key clinical outcomes in hospitalized patients.Material and Methods: We conducted an observational, retrospective cohort study using administrative healthcare data from 156,459 hospital discharges in Catalonia (Spain) during 2018. Study outcomes were in-hospital death, long hospital stay, and intensive care unit (ICU) stay. We evaluated the performance of the following indices: Charlson’s and Elixhauser’s functions, Queralt’s Index for secondary hospital discharge diagnoses (Queralt DxS), the overall Queralt’s Index, which includes pre-existing comorbidities, in-hospital complications, and principal discharge diagnosis (Queralt Dx), and the APR-DRG. Discriminative ability was evaluated using the area under the curve (AUC), and measures of goodness of fit were also computed. Subgroup analyses were conducted by principal discharge diagnosis, by age, and type of admission.Results: Queralt DxS provided relevant risk adjustment information in a larger number of patients compared to Charlson’s and Elixhauser’s functions, and outperformed both for the prediction of the 3 study outcomes. Queralt Dx also outperformed Charlson’s and Elixhauser’s indices, and yielded superior predictive ability and goodness of fit compared to APR-DRG (AUC for in-hospital death 0.95 for Queralt Dx, 0.77– 0.93 for all other indices; for ICU stay 0.84 for Queralt Dx, 0.73– 0.83 for all other indices). The performance of Queralt DxS was at least as good as that of the APR-DRG in most principal discharge diagnosis subgroups.Conclusion: Our findings suggest that risk adjustment should go beyond pre-existing comorbidities and include principal discharge diagnoses and in-hospital complications. Validation of comprehensive risk adjustment tools such as the Queralt indices in other settings is needed.Keywords: benchmarking, case-mix, comorbidity, discrimination, multimorbidity, Queralt’s indices, risk

Coronary artery calcium (CAC) measures subclinical atherosclerosis and improves risk stratification. CAC characteristics-including vessel(s) involved, number of vessels, volume, and density-have been shown to differentially impact risk. We assessed how dispersion-either the number of calcified vessels or CAC phenotype (diffuse, normal, and concentrated)-impacted cause-specific mortality. The CAC Consortium is a retrospective cohort of 66,636 participants without coronary heart disease (CHD) who underwent CAC scoring. This study included patients with CAC >0 (n = 28,147). CAC area, CAC density, and CAC phenotypes (derived from the index of diffusion = 1 - [CAC in most concentrated vessel/total Agatston score]) were calculated. The associations between CAC characteristics and cause-specific mortality were assessed. The participant details included (n = 28,147): mean age 58.3 years, 25% female, 89.6% White, and 66% had 2+ calcified vessels. Diabetes, hypertension, and hyperlipidemia were predictors of multivessel involvement (p <0.001). After controlling for the overall CAC score, those with 4-vessel CAC involvement had more CAC area and less dense calcifications than those with 1-vessel. There was a graded increase in all-cause and cardiovascular disease (CVD)- and CHD-specific mortality as the number of calcified vessels increased. Among those with ≥2 vessels involved (n = 18,516), a diffuse phenotype was associated with a higher CVD-specific mortality and had a trend toward higher all-cause and CHD-specific mortality than a concentrated CAC phenotype. Diffuse CAC involvement was characterized by less dense calcification, more CAC area, multiple coronary vessel involvement, and presence of certain traditional risk factors. There is a graded increase in all-cause and CVD- and CHD-specific mortality with increasing CAC dispersion., Competing Interests: Disclosures The authors have no conflicts of interest to declare., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Importance: Atherosclerosis burden and coronary artery calcium (CAC) are associated with the risk for atherosclerotic cardiovascular disease (ASCVD) events, with absence of plaque and CAC indicating low risk. Whether this is true in patients with elevated levels of low-density lipoprotein cholesterol (LDL-C) is not known. Specifically, a high prevalence of noncalcified plaque might signal high risk., Objective: To determine the prevalence of noncalcified and calcified plaque in symptomatic adults and assess its association with cardiovascular events across the LDL-C spectrum., Design, Setting, and Participants: This cohort study included symptomatic patients undergoing coronary computed tomographic angiography from January 1, 2008, to December 31, 2017, from the seminational Western Denmark Heart Registry. Follow-up was completed on July 6, 2018. Data were analyzed from April 2 to December 2, 2021., Exposures: Prevalence of calcified and noncalcified plaque according to LDL-C strata of less than 77, 77 to 112, 113 to 154, 155 to 189, and at least 190 mg/dL. Severity of coronary artery disease was categorized using CAC scores of 0, 1 to 99, and ≥100, where higher numbers indicate greater CAC burden., Main Outcomes and Measures: Atherosclerotic cardiovascular disease events (myocardial infarction and stroke) and death., Results: A total of 23 143 patients with a median age of 58 (IQR, 50-65) years (12 857 [55.6%] women) were included in the analysis. During median follow-up of 4.2 (IQR, 2.3-6.1) years, 1029 ASCVD and death events occurred. Across all LDL-C strata, absence of CAC was a prevalent finding (ranging from 438 of 948 [46.2%] in patients with LDL-C levels of at least 190 mg/dL to 4370 of 7964 [54.9%] in patients with LDL-C levels of 77-112 mg/dL) and associated with no detectable plaque in most patients, ranging from 338 of 438 (77.2%) in those with LDL-C levels of at least 190 mg/dL to 1067 of 1204 (88.6%) in those with LDL-C levels of less than 77 mg/dL. In all LDL-C groups, absence of CAC was associated with low rates of ASCVD and death (6.3 [95% CI, 5.6-7.0] per 1000 person-years), with increasing rates in patients with CAC scores of 1 to 99 (11.1 [95% CI, 10.0-12.5] per 1000 person-years) and CAC scores of at least 100 (21.9 [95% CI, 19.9-24.4] per 1000 person-years). Among those with CAC scores of 0, the event rate per 1000 person-years was 6.3 (95% CI, 5.6-7.0) in the overall population compared with 6.9 (95% CI, 4.0-11.9) in those with LDL-C levels of at least 190 mg/dL. Across all LDL-C strata, rates were similar and low in those with CAC scores of 0, regardless of whether they had no plaque or purely noncalcified plaque., Conclusions and Relevance: The findings of this cohort study suggest that in symptomatic patients with severely elevated LDL-C levels of at least 190 mg/dL who are universally considered to be at high risk by guidelines, absence of calcified and noncalcified plaque on coronary computed tomographic angiography was associated with low risk for ASCVD events. These results further suggest that atherosclerosis burden, including CAC, can be used to individualize treatment intensity in patients with severely elevated LDL-C levels.

Aims: Non-ischaemic dilated cardiomyopathy (NIDCM) is characterized by left ventricular (LV) chamber enlargement and systolic dysfunction in the absence of coronary artery disease. Left ventricular reverse remodelling (LVRR) is the ability of a dilated ventricle to restore its normal size, shape and function. We sought to determine the frequency, clinical predictors and prognostic implications of LVRR, in a cohort of heart failure (HF) patients with NIDCM., Methods: We conducted a multicentre observational, retrospective cohort study of patients with NIDCM, with prospective serial echocardiography evaluations. LVRR was defined as an increase of ≥15% in left ventricular ejection fraction (LVEF) or as a LVEF increase ≥ 10% plus reduction of LV end-systolic diameter index ≥ 20%. We used multivariable logistic regression analyses to identify the baseline clinical predictors of LVRR and evaluate the prognostic impact of LVRR., Results: LVRR was achieved in 42.5% of 527 patients with NIDCM during the first year of follow-up (median LVEF 49%, median change +22%), Alcoholic aetiology, HF duration, baseline LVEF and the absence of LBBB (plus NT-proBNP levels when in the model), were the strongest predictors of LVRR. During a median follow-up of 47 months, 134 patients died (25.4%) and 7 patients (1.3%) received a heart transplant. Patients with LVRR presented better outcomes, regardless of other clinical conditions., Conclusions: In patients with NIDCM, LVRR was frequent and was associated with improved prognosis. Major clinical predictors of LVRR were alcoholic cardiomyopathy, absence of LBBB, shorter HF duration, and lower baseline LVEF and NT-proBNP levels. Our study advocates for clinical phenotyping of non-ischaemic dilated cardiomyopathy and intense gold-standard treatment optimization of patients according to current guidelines and recommendations in specialized HF units.

Objective: Atherosclerotic cardiovascular disease (ASCVD) and chronic obstructive pulmonary disease (COPD) are among the leading causes of morbidity, mortality, and economic burden in the United States (US). While previous reports have shown that an optimal cardiovascular risk factor (CRF) profile is associated with improved outcomes among COPD patients, the impact of ASCVD and CRF on healthcare costs and resource utilization is not well described., Methods: The Medical Expenditure Panel Survey (MEPS) database was used from 2011 to 2016 to study healthcare expenditure for COPD patients with and without ASCVD and across CRF profiles in a nationally representative population of adults in the United States., Results: The study population consisted of 14,807 adults with COPD, representing 28 million cases annually. Presence of ASCVD was associated with higher reported expenditure across the spectrum of CRF profiles among those with COPD. On average, after adjusting for confounders, presence of ASCVD represented a mean difference per capita of $5438 (95% CI $4121 - $6754; p ​< ​0.001). Mean per capita expenditures were significantly higher comparing poor vs optimal CRF profiles, with marginal expenditures of $8552 and $6531 among those with and without ASCVD, respectively. When comparing individuals with ASCVD and poor CRF profile versus individuals without ASCVD and optimal CRF profile, those in the latter group used 13% fewer prescription medications and required 24% fewer hospitalizations. Furthermore, an optimal CRF profile was associated with lower odds of most sources of healthcare utilization regardless of ASCVD status., Conclusion: An absence of ASCVD and a favorable CRF profile was associated with lower healthcare expenditure and resource utilization among patients with COPD. These results provide robust estimates for potential healthcare savings as preemptive strategies continue to become integrated into new healthcare delivery models, for increased awareness and the need for improvement of CRF profiles among high-risk patients., Competing Interests: Dr. Nasir is supported by the Katz Academy for Translational Research., (© 2020 The Authors.)

Background: The effect of chronic hepatitis B virus (HBV) infection on the risk of chronic kidney disease (CKD) is controversial. We examined the prospective association between hepatitis B surface antigen (HBsAg) serology status and incident CKD in a large cohort of men and women., Methods: Cohort study of 299,913 adults free of CKD at baseline who underwent health screening exams between January 2002 and December 2016 in South Korea. Incident CKD was defined as the development of an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73m 2 and/or proteinuria., Results: Over 1,673,701 person-years of follow-up, we observed 13,924 incident cases of CKD (3225 cases of eGFR < 60 ml/min/1.73m 2 and 11,072 cases of proteinuria). In fully adjusted models comparing positive to negative HBsAg participants, the hazard ratio (HR, 95% confidence interval) for incident CKD was 1.11 (1.03-1.21; P = 0.01). The corresponding HR for incident proteinuria and for eGFR < 60 ml/min/1.73m 2 were 1.23 (1.12-1.35; P <  0.001) and 0.89 (0.73-1.07; P = 0.21), respectively. The associations were similar across categories of liver enzyme levels at baseline., Conclusion: In this large cohort, HBsAg positive serology was associated with higher risk of incident CKD, and we provide novel evidence that this association was due to a higher incidence of proteinuria in HBsAg positive participants. Our study adds to the growing body of evidence suggesting that chronic HBV infection may be a contributor to the increasing incidence of CKD.