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BACKGROUND AND AIMS: The aim of this study was to determine the prognostic value of coronary computed tomography angiography (CCTA)-derived atherosclerotic plaque analysis in ISCHEMIA. METHODS: Atherosclerosis imaging quantitative computed tomography (AI-QCT) was performed on all available baseline CCTAs to quantify plaque volume, composition, and distribution. Multivariable Cox regression was used to examine the association between baseline risk factors (age, sex, smoking, diabetes, hypertension, ejection fraction, prior coronary disease, estimated glomerular filtration rate, and statin use), number of diseased vessels, atherosclerotic plaque characteristics determined by AI-QCT, and a composite primary outcome of cardiovascular death or myocardial infarction over a median follow-up of 3.3 (interquartile range 2.2-4.4) years. The predictive value of plaque quantification over risk factors was compared in an area under the curve (AUC) analysis. RESULTS: Analysable CCTA data were available from 3711 participants (mean age 64 years, 21% female, 79% multivessel coronary artery disease). Amongst the AI-QCT variables, total plaque volume was most strongly associated with the primary outcome (adjusted hazard ratio 1.56, 95% confidence interval 1.25-1.97 per interquartile range increase [559 mm3]; P = .001). The addition of AI-QCT plaque quantification and characterization to baseline risk factors improved the model's predictive value for the primary outcome at 6 months (AUC 0.688 vs. 0.637; P = .006), at 2 years (AUC 0.660 vs. 0.617; P = .003), and at 4 years of follow-up (AUC 0.654 vs. 0.608; P = .002). The findings were similar for the other reported outcomes. CONCLUSIONS: In ISCHEMIA, total plaque volume was associated with cardiovascular death or myocardial infarction. In this highly diseased, high-risk population, enhanced assessment of atherosclerotic burden using AI-QCT-derived measures of plaque volume and composition modestly improved event prediction.
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OBJECTIVE: To perform a detailed characterisation of diabetes burden and pre-diabetes risk in a rural county with previously documented poor health outcomes in order to understand the local within-county distribution of diabetes in rural areas of America. DESIGN, SETTING, AND PARTICIPANTS: In 2021, we prospectively mailed health surveys to all households in Sullivan County, a rural county with the second-worst health outcomes of all counties in New York State. Our survey included questions on demographics, medical history and the American Diabetes Association's Pre-diabetes Risk Test. PRIMARY OUTCOME AND METHODS: Our primary outcome was an assessment of diabetes burden within this rural county. To help mitigate non-response bias in our survey, raking adjustments were performed across strata of age, sex, race/ethnicity and health insurance. We analysed diabetes prevalence by demographic characteristics and used geospatial analysis to assess for clustering of diagnosed diabetes cases. RESULTS: After applying raking procedures for the 4725 survey responses, our adjusted diagnosed diabetes prevalence for Sullivan County was 12.9% compared with the 2019 Behavioural Risk Factor Surveillance System (BRFSS) estimate of 8.6%. In this rural area, diagnosed diabetes prevalence was notably higher among non-Hispanic Black (21%) and Hispanic (15%) residents compared with non-Hispanic White (12%) residents. 53% of respondents without a known history of pre-diabetes or diabetes scored as high risk for pre-diabetes. Nearest neighbour analyses revealed that hotspots of diagnosed diabetes were primarily located in the more densely populated areas of this rural county. CONCLUSIONS: Our mailed health survey to all residents in Sullivan County demonstrated higher diabetes prevalence compared with modelled BRFSS estimates that were based on small telephone samples. Our results suggest the need for better diabetes surveillance in rural communities, which may benefit from interventions specifically tailored for improving glycaemic control among rural residents.
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Diabetes Mellitus , Encuestas Epidemiológicas , Estado Prediabético , Población Rural , Humanos , Masculino , Femenino , New York/epidemiología , Estado Prediabético/epidemiología , Persona de Mediana Edad , Estudios Transversales , Adulto , Población Rural/estadística & datos numéricos , Anciano , Prevalencia , Diabetes Mellitus/epidemiología , Factores de Riesgo , Adulto Joven , AdolescenteRESUMEN
OBJECTIVES: We introduce a widely applicable model-based approach for estimating individual-level Social Determinants of Health (SDoH) and evaluate its effectiveness using the All of Us Research Program. MATERIALS AND METHODS: Our approach utilizes aggregated SDoH datasets to estimate individual-level SDoH, demonstrated with examples of no high school diploma (NOHSDP) and no health insurance (UNINSUR) variables. Models are estimated using American Community Survey data and applied to derive individual-level estimates for All of Us participants. We assess concordance between model-based SDoH estimates and self-reported SDoHs in All of Us and examine associations with undiagnosed hypertension and diabetes. RESULTS: Compared to self-reported SDoHs, the area under the curve for NOHSDP is 0.727 (95% CI, 0.724-0.730) and for UNINSUR is 0.730 (95% CI, 0.727-0.733) among the 329 074 All of Us participants, both significantly higher than aggregated SDoHs. The association between model-based NOHSDP and undiagnosed hypertension is concordant with those estimated using self-reported NOHSDP, with a correlation coefficient of 0.649. Similarly, the association between model-based NOHSDP and undiagnosed diabetes is concordant with those estimated using self-reported NOHSDP, with a correlation coefficient of 0.900. DISCUSSION AND CONCLUSION: The model-based SDoH estimation method offers a scalable and easily standardized approach for estimating individual-level SDoHs. Using the All of Us dataset, we demonstrate reasonable concordance between model-based SDoH estimates and self-reported SDoHs, along with consistent associations with health outcomes. Our findings also underscore the critical role of geographic contexts in SDoH estimation and in evaluating the association between SDoHs and health outcomes.
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Cardiometabolic co-morbidities, diabetes (DM), hypertension (HTN), and obesity contribute to cardiovascular disease. Circulating biomarkers facilitate prognostication for patients with cardiovascular disease. We explored the relation between cardiometabolic co-morbidity burden in patients with chronic coronary disease and biomarkers of myocardial stretch, injury, inflammation, and platelet activity. We analyzed participants from the International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) trials biorepository with plasma biomarkers (N-terminal probrain natriuretic peptide, high-sensitivity cardiac troponin T, high-sensitivity C-reactive protein, interleukin-6, soluble CD40 ligand, and growth differentiation factor-15) and clinical risk factors (hemoglobin A1c [HbA1c], systolic blood pressure [SBP], and body mass index [BMI]) at baseline. We defined cardiometabolic co-morbidities as DM, HTN, and obesity at baseline. Co-morbidity burden is characterized by the number and severity of co-morbidities. Controlled co-morbidities were defined as HbA1c <7% for those with DM, SBP <130 mm Hg for those with HTN, and BMI <30 kg/m2. Severely uncontrolled was defined as HbA1c ≥8%, SBP ≥160 mm Hg, and BMI ≥35 kg/m2. We performed linear regression analyses to examine the association between co-morbidity burden and log-transformed biomarker levels, adjusting for age, gender, estimated glomerular filtration rate controlled for hemodialysis, and left ventricular ejection fraction. A total of 752 participants (mean age 66 years, 19% women, 84% White) were included in this analysis. Self-reported Black race, current smokers, history of myocardial infarction, and heart failure had a greater cardiometabolic co-morbidity burden. The presence of ≥1 severely uncontrolled co-morbidity was associated with significantly higher baseline levels of high-sensitivity cardiac troponin T, high-sensitivity C-reactive protein, interleukin-6, and growth differentiation factor-15 than participants with no co-morbidities. In conclusion, increasing cardiometabolic co-morbidity burden in patients with chronic coronary disease is associated with higher levels of circulating biomarkers of myocardial injury and inflammation.
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Biomarcadores , Comorbilidad , Troponina T , Humanos , Femenino , Masculino , Biomarcadores/sangre , Persona de Mediana Edad , Anciano , Troponina T/sangre , Obesidad/epidemiología , Obesidad/complicaciones , Obesidad/sangre , Hipertensión/epidemiología , Hipertensión/sangre , Enfermedad Crónica , Proteína C-Reactiva/metabolismo , Proteína C-Reactiva/análisis , Diabetes Mellitus/epidemiología , Diabetes Mellitus/sangre , Hemoglobina Glucada/metabolismo , Enfermedad Coronaria/epidemiología , Enfermedad Coronaria/sangre , Factores de Riesgo Cardiometabólico , Fragmentos de Péptidos/sangre , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/epidemiología , Interleucina-6/sangre , Péptido Natriurético Encefálico/sangreRESUMEN
OBJECTIVE: To retrospectively compare inter- and intra-reader agreement of abbreviated MRCP (aMRCP) with comprehensive MRI (cMRCP) protocol for detection of worrisome features, high-risk stigmata, and concomitant pancreatic cancer in pancreatic cyst surveillance. METHODS: 151 patients (104 women, mean age: 69[10] years) with baseline and follow-up contrast-enhanced MRIs were included. This comprised 138 patients under cyst surveillance with 5-year follow-up showing no pancreatic ductal adenocarcinoma (PDAC), 6 with pancreatic cystic lesion-derived malignancy, and 7 with concomitant PDAC. The aMRCP protocol used four sequences (axial and coronal Half-Fourier Single-shot Turbo-spin-Echo, axial T1 fat-saturated pre-contrast, and 3D-MRCP), while cMRCP included all standard sequences, including post-contrast. Three blinded abdominal radiologists assessed baseline cyst characteristics, worrisome features, high-risk stigmata, and PDAC signs using both aMRCP and cMRCP, with a 2-week washout period. Intra- and inter-reader agreement were calculated using Fleiss' multi-rater kappa and Intra-class Correlation Coefficient (ICC). 95% confidence intervals (CI) were calculated. RESULTS: Cyst size, growth, and abrupt main pancreatic duct transition had strong intra- and inter-reader agreement. Intra-reader agreement was ICC = 0.93-0.99 for cyst size, ICC = 0.71-1.00 for cyst growth, and kappa = 0.83-1.00 for abrupt duct transition. Inter-reader agreement for cyst size was ICC = 0.86 (aMRCP) and ICC = 0.83 (cMRCP), and for abrupt duct transition was kappa = 0.84 (aMRCP) and kappa = 0.69 (cMRCP). Thickened cyst wall, mural nodule and cyst-duct communication demonstrated varying intra-reader agreements and poor inter-reader agreements. CONCLUSION: aMRCP showed high intra- and inter-reader agreement for most pancreatic cyst parameters that highly rely on T2-weighted sequences.
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Objective: To perform a geospatial analysis of food insecurity in a rural county known to have poor health outcomes and assess the effect of the COVID-19 pandemic. Methods: In 2020, we mailed a comprehensive cross-sectional survey to all households in Sullivan County, a rural county with the second-worst health outcomes among all counties in New York State. Surveys of households included validated food insecurity screening questions. Questions were asked in reference to 2019, prior to the pandemic, and for 2020, in the first year of the pandemic. Respondents also responded to demographic questions. Raking adjustments were performed using age, sex, race/ethnicity, and health insurance strata to mitigate non-response bias. To identify significant hotspots of food insecurity within the county, we also performed geospatial analysis. Findings: From the 28,284 households surveyed, 20% of households responded. Of 4725 survey respondents, 26% of households reported experiencing food insecurity in 2019, and in 2020, this proportion increased to 35%. In 2020, 58% of Black and Hispanic households reported experiencing food insecurity. Food insecurity in 2020 was also present in 58% of unmarried households with children and in 64% of households insured by Medicaid. The geospatial analyses revealed that hotspots of food insecurity were primarily located in or near more urban areas of the rural county. Conclusions: Our countywide health survey in a high-risk rural county identified significant increases of food insecurity in the first year of the COVID-19 pandemic, despite national statistics reporting a stable rate. Responses to future crises should include targeted interventions to bolster food security among vulnerable rural populations.
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Electronic health records (EHRs) contain rich clinical information for millions of patients and are increasingly used for public health research. However, non-random inclusion of subjects in EHRs can result in selection bias, with factors such as demographics, socioeconomic status, healthcare referral patterns, and underlying health status playing a role. While this issue has been well documented, little work has been done to develop or apply bias-correction methods, often due to the fact that most of these factors are unavailable in EHRs. To address this gap, we propose a series of Heckman type bias correction methods by incorporating social determinants of health selection covariates to model the EHR non-random sampling probability. Through simulations under various settings, we demonstrate the effectiveness of our proposed method in correcting biases in both the association coefficient and the outcome mean. Our method augments the utility of EHRs for public health inferences, as we show by estimating the prevalence of cardiovascular disease and its correlation with risk factors in the New York City network of EHRs.
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Registros Electrónicos de Salud , Estado de Salud , Humanos , Sesgo de Selección , Factores de Riesgo , SesgoRESUMEN
INTRODUCTION: Traditional survey-based surveillance is costly, limited in its ability to distinguish diabetes types and time-consuming, resulting in reporting delays. The Diabetes in Children, Adolescents and Young Adults (DiCAYA) Network seeks to advance diabetes surveillance efforts in youth and young adults through the use of large-volume electronic health record (EHR) data. The network has two primary aims, namely: (1) to refine and validate EHR-based computable phenotype algorithms for accurate identification of type 1 and type 2 diabetes among youth and young adults and (2) to estimate the incidence and prevalence of type 1 and type 2 diabetes among youth and young adults and trends therein. The network aims to augment diabetes surveillance capacity in the USA and assess performance of EHR-based surveillance. This paper describes the DiCAYA Network and how these aims will be achieved. METHODS AND ANALYSIS: The DiCAYA Network is spread across eight geographically diverse US-based centres and a coordinating centre. Three centres conduct diabetes surveillance in youth aged 0-17 years only (component A), three centres conduct surveillance in young adults aged 18-44 years only (component B) and two centres conduct surveillance in components A and B. The network will assess the validity of computable phenotype definitions to determine diabetes status and type based on sensitivity, specificity, positive predictive value and negative predictive value of the phenotypes against the gold standard of manually abstracted medical charts. Prevalence and incidence rates will be presented as unadjusted estimates and as race/ethnicity, sex and age-adjusted estimates using Poisson regression. ETHICS AND DISSEMINATION: The DiCAYA Network is well positioned to advance diabetes surveillance methods. The network will disseminate EHR-based surveillance methodology that can be broadly adopted and will report diabetes prevalence and incidence for key demographic subgroups of youth and young adults in a large set of regions across the USA.
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Diabetes Mellitus Tipo 2 , Niño , Humanos , Adolescente , Adulto Joven , Diabetes Mellitus Tipo 2/epidemiología , Registros Electrónicos de Salud , Prevalencia , Incidencia , AlgoritmosRESUMEN
BACKGROUND: Global longitudinal strain (GLS) is a sensitive marker for identifying subclinical myocardial dysfunction in obstructive coronary artery disease (CAD). Little is known about the relationship between GLS and ischemia in patients with myocardial ischemia and no obstructive CAD (INOCA). OBJECTIVES: To investigate the relationship between resting GLS and ischemia on stress echocardiography (SE) in patients with INOCA. METHODS: Left ventricular GLS was calculated offline on resting SE images at enrollment (n = 144) and 1-year follow-up (n = 120) in the CIAO-ISCHEMIA (Changes in Ischemia and Angina over One year in International Study of Comparative Health Effectiveness with Medical and Invasive Approaches trial screen failures with no obstructive CAD on computed tomography [CT] angiography) study, which enrolled participants with moderate or severe ischemia by local SE interpretation (≥3 segments with new or worsening wall motion abnormality and no obstructive (<50% stenosis) on coronary computed tomography angiography. RESULTS: Global longitudinal strain values were normal in 83.3% at enrollment and 94.2% at follow-up. Global longitudinal strain values were not associated with a positive SE at enrollment (GLS = -21.5% positive SE vs GLS = -19.9% negative SE, P = .443) or follow-up (GLS = -23.2% positive SE vs GLS = -23.1% negative SE, P = .859). Significant change in GLS was not associated with positive SE in follow-up (P = .401). Regional strain was not associated with colocalizing ischemia at enrollment or follow-up. Changes in GLS and number of ischemic segments from enrollment to follow-up showed a modest but not clinically meaningful correlation (ß = 0.41; 95% CI, 0.16, 0.67; P = .002). CONCLUSIONS: In this cohort of INOCA patients, resting GLS values were largely normal and did not associate with the presence, severity, or location of stress-induced ischemia. These findings may suggest the absence of subclinical myocardial dysfunction detectable by echocardiographic strain analysis at rest in INOCA.
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Enfermedad de la Arteria Coronaria , Isquemia Miocárdica , Humanos , Enfermedad de la Arteria Coronaria/diagnóstico , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Tensión Longitudinal Global , Isquemia Miocárdica/diagnóstico , Isquemia Miocárdica/diagnóstico por imagen , Corazón , Isquemia/complicaciones , Valor Predictivo de las PruebasRESUMEN
IMPORTANCE: Biomarkers may improve prediction of cardiovascular events for patients with stable coronary artery disease (CAD), but their importance in addition to clinical tests of inducible ischemia and CAD severity is unknown. OBJECTIVES: To evaluate the prognostic value of multiple biomarkers in stable outpatients with obstructive CAD and moderate or severe inducible ischemia. DESIGN AND SETTING: The ISCHEMIA and ISCHEMIA CKD trials randomized 5,956 participants with CAD to invasive or conservative management from July 2012 to January 2018; 1,064 participated in the biorepository. MAIN OUTCOME MEASURES: Primary outcome was cardiovascular death, myocardial infarction (MI), or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. Secondary outcome was cardiovascular death or MI. Improvements in prediction were assessed by cause-specific hazard ratios (HR) and area under the receiver operating characteristics curve (AUC) for an interquartile increase in each biomarker, controlling for other biomarkers, in a base clinical model of risk factors, left ventricular ejection fraction (LVEF) and ischemia severity. Secondary analyses were performed among patients in whom core-lab confirmed severity of CAD was ascertained by computed cardiac tomographic angiography (CCTA). EXPOSURES: Baseline levels of interleukin-6 (IL-6), high sensitivity troponin T (hsTnT), growth differentiation factor 15 (GDF-15), N-terminal pro-B-type natriuretic peptide (NT-proBNP), lipoprotein a (Lp[a]), high sensitivity C-reactive protein (hsCRP), Cystatin C, soluble CD 40 ligand (sCD40L), myeloperoxidase (MPO), and matrix metalloproteinase 3 (MMP3). RESULTS: Among 757 biorepository participants, median (IQR) follow-up was 3 (2-5) years, age was 67 (61-72) years, and 144 (19%) were female; 508 had severity of CAD by CCTA available. In an adjusted multimarker model with hsTnT, GDF-15, NT-proBNP and sCD40L, the adjusted HR for the primary outcome per interquartile increase in each biomarker was 1.58 (95% CI 1.22, 2.205), 1.60 (95% CI 1.16, 2.20), 1.61 (95% 1.22, 2.14), and 1.46 (95% 1.12, 1.90), respectively. The adjusted multimarker model also improved prediction compared with the clinical model, increasing the AUC from 0.710 to 0.792 (P < .01) and 0.714 to 0.783 (P < .01) for the primary and secondary outcomes, respectively. Similar findings were observed after adjusting for core-lab confirmed atherosclerosis severity. CONCLUSIONS AND RELEVANCE: Among ISCHEMIA biorepository participants, biomarkers of myocyte injury/distension, inflammation, and platelet activity improved cardiovascular event prediction in addition to risk factors, LVEF, and assessments of ischemia and atherosclerosis severity. These biomarkers may improve risk stratification for patients with stable CAD.
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Aterosclerosis , Enfermedad de la Arteria Coronaria , Infarto del Miocardio , Humanos , Femenino , Anciano , Masculino , Enfermedad de la Arteria Coronaria/diagnóstico , Factor 15 de Diferenciación de Crecimiento , Volumen Sistólico , Función Ventricular Izquierda , Biomarcadores , Pronóstico , Péptido Natriurético Encefálico , Fragmentos de PéptidosRESUMEN
BACKGROUND: The ISCHEMIA trial (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) compared an initial invasive versus an initial conservative management strategy for patients with chronic coronary disease and moderate or severe ischemia, with no major difference in most outcomes during a median of 3.2 years. Extended follow-up for mortality is ongoing. METHODS: ISCHEMIA participants were randomized to an initial invasive strategy added to guideline-directed medical therapy or a conservative strategy. Patients with moderate or severe ischemia, ejection fraction ≥35%, and no recent acute coronary syndromes were included. Those with an unacceptable level of angina were excluded. Extended follow-up for vital status is being conducted by sites or through central death index search. Data obtained through December 2021 are included in this interim report. We analyzed all-cause, cardiovascular, and noncardiovascular mortality by randomized strategy, using nonparametric cumulative incidence estimators, Cox regression models, and Bayesian methods. Undetermined deaths were classified as cardiovascular as prespecified in the trial protocol. RESULTS: Baseline characteristics for 5179 original ISCHEMIA trial participants included median age 65 years, 23% women, 16% Hispanic, 4% Black, 42% with diabetes, and median ejection fraction 0.60. A total of 557 deaths accrued during a median follow-up of 5.7 years, with 268 of these added in the extended follow-up phase. This included a total of 343 cardiovascular deaths, 192 noncardiovascular deaths, and 22 unclassified deaths. All-cause mortality was not different between randomized treatment groups (7-year rate, 12.7% in invasive strategy, 13.4% in conservative strategy; adjusted hazard ratio, 1.00 [95% CI, 0.85-1.18]). There was a lower 7-year rate cardiovascular mortality (6.4% versus 8.6%; adjusted hazard ratio, 0.78 [95% CI, 0.63-0.96]) with an initial invasive strategy but a higher 7-year rate of noncardiovascular mortality (5.6% versus 4.4%; adjusted hazard ratio, 1.44 [95% CI, 1.08-1.91]) compared with the conservative strategy. No heterogeneity of treatment effect was evident in prespecified subgroups, including multivessel coronary disease. CONCLUSIONS: There was no difference in all-cause mortality with an initial invasive strategy compared with an initial conservative strategy, but there was lower risk of cardiovascular mortality and higher risk of noncardiovascular mortality with an initial invasive strategy during a median follow-up of 5.7 years. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04894877.
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Síndrome Coronario Agudo , Enfermedad de la Arteria Coronaria , Humanos , Femenino , Anciano , Masculino , Tratamiento Conservador , Teorema de Bayes , Enfermedad de la Arteria Coronaria/terapia , Síndrome Coronario Agudo/terapia , Resultado del TratamientoRESUMEN
BACKGROUND: The ISCHEMIA and the ISCHEMIA-CKD trials found no statistical difference in the primary clinical endpoint between initial invasive management and initial conservative management of patients with chronic coronary disease and moderate to severe ischemia on stress testing without or with advanced chronic kidney disease (CKD). In ISCHEMIA, there was numerically lower cardiovascular mortality but higher non-cardiovascular mortality with no significant difference in all-cause death with an initial invasive strategy when compared with a conservative strategy. However, an invasive strategy increased peri-procedural myocardial infarction (MI) but decreased spontaneous MI with continued separation of curves over time, which potentially may lead to reduced risk of cardiovascular and all-cause mortality. Thus, the long-term effect of invasive management strategy on mortality remains unclear. In ISCHEMIA-CKD, the treatment and cause-specific mortality rates were similar during follow-up. METHODS: Funded by the National Heart, Lung, and Blood Institute, the ISCHEMIA-EXTEND observational study is the long-term follow-up of surviving participants (projected median of 10 years) with chronic coronary disease from the ISCHEMIA trial. In the ISCHEMIA trial, 5,179 participants with moderate or severe stress-induced ischemia were randomized to initial invasive management with angiography, revascularization when feasible, and guideline-directed medical therapy (GDMT), or initial conservative management with GDMT alone and angiography reserved for failure of medical therapy. ISCHEMIA-CKD EXTEND is the long-term follow-up of surviving participants (projected median of 9 years) from the ISCHEMIA-CKD trial, a companion trial that included 777 patients with advanced CKD. Ascertainment of death will be conducted via direct participant contact, medical record review, and/or vital status registry search. The overarching objective of long-term follow-up is to assess whether there are between-group differences in long-term all-cause, cardiovascular, and non-cardiovascular mortality, and increase precision around the treatment effect estimates for risk of all-cause, cardiovascular, and non-cardiovascular mortality. We will conduct Bayesian survival modeling to take advantage of rich inferences using the posterior distribution of the treatment effect. CONCLUSIONS: The long-term effect of an initial invasive versus conservative strategy on all-cause, cardiovascular, and non-cardiovascular mortality will be assessed. The findings of ISCHEMIA-EXTEND and ISCHEMIA-CKD EXTEND will inform patients, practitioners, practice guidelines, and health policy.
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Enfermedad Coronaria , Infarto del Miocardio , Insuficiencia Renal Crónica , Humanos , Teorema de Bayes , Infarto del Miocardio/terapia , Insuficiencia Renal Crónica/terapia , Prueba de EsfuerzoRESUMEN
BACKGROUND: Patients with chronic kidney disease (CKD) on dialysis (CKD G5D) have worse cardiovascular outcomes than patients with advanced nondialysis CKD (CKD G4-5: estimated glomerular filtration rate <30 mL/[min·1.73m2]). Our objective was to evaluate the relationship between achievement of cardiovascular guideline-directed medical therapy (GDMT) goals and clinical outcomes for CKD G5D versus CKD G4-5. METHODS: This was a subgroup analysis of ISCHEMIA-CKD (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches-Chronic Kidney Disease) participants with CKD G4-5 or CKD G5D and moderate-to-severe myocardial ischemia on stress testing. Exposures included dialysis requirement at randomization and GDMT goal achievement during follow-up. The composite outcome was all-cause mortality or nonfatal myocardial infarction. Individual GDMT goal (smoking cessation, systolic blood pressure <140 mm Hg, low-density lipoprotein cholesterol <70 mg/dL, statin use, aspirin use) trajectory was modeled. Percentage point difference was estimated for each GDMT goal at 24 months between CKD G5D and CKD G4-5, and for association with key predictors. Probability of survival free from all-cause mortality or nonfatal myocardial infarction by GDMT goal achieved was assessed for CKD G5D versus CKD G4-5. RESULTS: A total of 415 CKD G5D and 362 CKD G4-5 participants were randomized. Participants with CKD G5D were less likely to receive statin (-6.9% [95% CI, -10.3% to -3.7%]) and aspirin therapy (-3.0% [95% CI, -5.6% to -0.6%]), with no difference in other GDMT goal attainment. Cumulative exposure to GDMT achieved during follow-up was associated with reduction in all-cause mortality or nonfatal myocardial infarction (hazard ratio, 0.88 [95% CI, 0.87-0.90]; per each GDMT goal attained over 60 days), irrespective of dialysis status. CONCLUSIONS: CKD G5D participants received statin or aspirin therapy less often. Cumulative exposure to GDMT goals achieved was associated with lower incidence of all-cause mortality or nonfatal myocardial infarction in participants with advanced CKD and chronic coronary disease, regardless of dialysis status. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01985360.
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Inhibidores de Hidroximetilglutaril-CoA Reductasas , Infarto del Miocardio , Insuficiencia Renal Crónica , Humanos , Diálisis Renal/efectos adversos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/terapia , Infarto del Miocardio/epidemiología , LDL-Colesterol , Aspirina/efectos adversosRESUMEN
Iron deficits have been reported as a risk factor for psychotic spectrum disorders (PSD). However, examinations of brain iron in PSD remain limited. The current study employed quantitative MRI to examine iron content in several iron-rich subcortical structures in 49 young adult individuals with PSD (15 schizophrenia, 17 schizoaffective disorder, and 17 bipolar disorder with psychotic features) compared with 35 age-matched healthy controls (HC). A parametric approach based on a two-pool magnetization transfer model was applied to estimate longitudinal relaxation rate (R1), which reflects both iron and myelin, and macromolecular proton fraction (MPF), which is specific to myelin. To describe iron content, a synthetic effective transverse relaxation rate (R2*) was modeled using a linear fitting of R1 and MPF. PSD patients compared to HC showed significantly reduced R1 and synthetic R2* across examined regions including the pallidum, ventral diencephalon, thalamus, and putamen areas. This finding was primarily driven by decreases in the subgroup with schizophrenia, followed by schizoaffective disorder. No significant group differences were noted for MPF between PSD and HC while for regional volume, significant reductions in patients were only observed in bilateral caudate, suggesting that R1 and synthetic R2* reductions in schizophrenia and schizoaffective patients likely reflect iron deficits that either occur independently or precede structural and myelin changes. Subcortical R1 and synthetic R2* were also found to be inversely related to positive symptoms within the PSD group and to schizotypal traits across the whole sample. These findings that decreased iron in subcortical regions are associated with PSD risk and symptomatology suggest that brain iron deficiencies may play a role in PSD pathology and warrant further study.
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Hierro , Trastornos Psicóticos , Adulto Joven , Humanos , Trastornos Psicóticos/patología , Ganglios Basales/patología , Encéfalo/patología , Tálamo , Imagen por Resonancia MagnéticaRESUMEN
BACKGROUND: ISCHEMIA-CKD (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches-Chronic Kidney Disease) reported an initial invasive treatment strategy did not reduce the risk of death or nonfatal myocardial infarction (MI) compared with a conservative treatment strategy in patients with advanced chronic kidney disease, stable coronary disease, and moderate or severe myocardial ischemia. The cumulative frequency of different MI type after randomization and subsequent prognosis have not been reported. METHODS: MI classification was based on the Third Universal Definition for MI. For procedural MI, the primary MI definition used creatine kinase-MB as the preferred biomarker, whereas the secondary MI definition used cTn (cardiac troponin); both definitions included elevated biomarker-only events with higher thresholds than nonprocedural MIs. The cumulative frequency of MI type according to treatment strategy was determined. The association of MI with subsequent all-cause death and new dialysis initiation was assessed by treating MI as a time-dependent covariate. RESULTS: The 3-year incidence of type 1 or 2 MI with the primary MI definition was 11.2% in invasive treatment strategy and 13.6% in conservative treatment strategy (hazard ratio [HR], 0.66 [95% CI, 0.42-1.02]). Procedural MIs were more frequent in invasive treatment strategy and accounted for 9.8% and 28.3% of all MIs with the primary and secondary MI definitions, respectively. Patients had an increased risk of all-cause death after type 1 MI (adjusted HR, 4.35 [95% CI, 2.73-6.93]) and after procedural MI with the primary (adjusted HR, 2.75 [95% CI, 0.99-7.60]) and secondary MI definitions (adjusted HR, 2.91 [95% CI, 1.73-4.88]). Dialysis initiation was increased after a type 1 MI (HR, 6.45 [95% CI, 2.59-16.08]) compared with patients without an MI. CONCLUSIONS: In ISCHEMIA-CKD, the invasive treatment strategy had higher rates of procedural MIs, particularly with the secondary MI definition, and lower rates of type 1 and 2 MIs. Procedural MIs, type 1 MIs, and type 2 MIs were associated with increased risk of subsequent death. Type 1 MI increased the risk of dialysis initiation. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01985360.
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Enfermedad de la Arteria Coronaria , Infarto del Miocardio , Insuficiencia Renal Crónica , Biomarcadores , Enfermedad de la Arteria Coronaria/complicaciones , Humanos , Isquemia/complicaciones , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/epidemiología , Infarto del Miocardio/terapia , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/terapia , Resultado del TratamientoRESUMEN
OBJECTIVE: The aim of the study was to compare the distribution of Prostate Imaging and Reporting Data System (PI-RADS) scores, interreader agreement, and diagnostic performance of PI-RADS v2.0 and v2.1 for transition zone (TZ) lesions. METHODS: The study included 202 lesions in 202 patients who underwent 3T prostate magnetic resonance imaging showing a TZ lesion that was later biopsied with magnetic resonance imaging/ultrasound fusion. Five abdominal imaging faculty reviewed T2-weighted imaging and high b value/apparent diffusion coefficient images in 2 sessions. Cases were randomized using a crossover design whereby half in the first session were reviewed using v2.0 and the other half using v2.1, and vice versa for the 2nd session. Readers provided T2-weighted imaging and DWI scores, from which PI-RADS scores were derived. RESULTS: Interreader agreement for all PI-RADS scores had κ of 0.37 (v2.0) and 0.26 (v2.1). For 4 readers, the percentage of lesions retrospectively scored PI-RADS 1 increased greater than 5% and PI-RADS 2 score decreased greater than 5% from v2.0 to v2.1. For 2 readers, the percentage scored PI-RADS 3 decreased greater than 5% and, for 2 readers, increased greater than 5%. The percentage of PI-RADS 4 and 5 lesions changed less than 5% for all readers. For the 4 readers with increased frequency of PI-RADS 1 using v2.1, 4% to 16% were Gleason score ≥3 + 4 tumor. Frequency of Gleason score ≥3 + 4 in PI-RADS 3 lesions increased for 2 readers and decreased for 1 reader. Sensitivity of PI-RADS of 3 or greater for Gleason score ≥3 + 4 ranged 76% to 90% (v2.0) and 69% to 96% (v2.1). Specificity ranged 32% to 64% (v2.0) and 25% to 72% (v2.1). Positive predictive value ranged 43% to 55% (v2.0) and 41% to 58% (v2.1). Negative predictive value ranged 82% to 87% (v2.0) and 81% to 91% (v2.1). CONCLUSIONS: Poor interreader agreement and lack of improvement in diagnostic performance indicate an ongoing need to refine evaluation of TZ lesions.
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Próstata , Neoplasias de la Próstata , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Clasificación del Tumor , Próstata/diagnóstico por imagen , Próstata/patología , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Estudios RetrospectivosRESUMEN
BACKGROUND: The ISCHEMIA-CKD (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches-Chronic Kidney Disease) trial found no advantage to an invasive strategy compared to conservative management in reducing all-cause death or myocardial infarction (D/MI). However, the prognostic influence of angiographic coronary artery disease (CAD) burden and ischemia severity remains unknown in this population. We compared the relative impact of CAD extent and severity of myocardial ischemia on D/MI in patients with advanced chronic kidney disease (CKD). METHODS: Participants randomized to invasive management with available data on coronary angiography and stress testing were included. Extent of CAD was defined by the number of major epicardial vessels with ≥50% diameter stenosis by quantitative coronary angiography. Ischemia severity was assessed by site investigators as moderate or severe using trial definitions. The primary endpoint was D/MI. RESULTS: Of the 388 participants, 307 (79.1%) had complete coronary angiography and stress testing data. D/MI occurred in 104/307 participants (33.9%). Extent of CAD was associated with an increased risk of D/MI (P < .001), while ischemia severity was not (P = .249). These relationships persisted following multivariable adjustment. Using 0-vessel disease (VD) as reference, the adjusted hazard ratio (HR) for 1VD was 1.86, 95% confidence interval (CI) 0.94 to 3.68, P = .073; 2VD: HR 2.13, 95% CI 1.10 to 4.12, P = .025; 3VD: HR 4.00, 95% CI 2.06 to 7.76, P < .001. Using moderate ischemia as the reference, the HR for severe ischemia was 0.84, 95% CI 0.54 to 1.30, P = .427. CONCLUSION: Among ISCHEMIA-CKD participants randomized to the invasive strategy, extent of CAD predicted D/MI whereas severity of ischemia did not.
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Enfermedad de la Arteria Coronaria , Isquemia Miocárdica , Insuficiencia Renal Crónica , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/complicaciones , Enfermedad de la Arteria Coronaria/diagnóstico , Enfermedad de la Arteria Coronaria/epidemiología , Humanos , Isquemia/complicaciones , Isquemia Miocárdica/complicaciones , Isquemia Miocárdica/epidemiología , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/epidemiología , Factores de RiesgoRESUMEN
RATIONALE AND OBJECTIVES: Asymptomatic COVID-19 carriers and insufficient testing make containment of the virus difficult. The purpose of this study was to determine if unexpected lung base findings on abdominopelvic CTs concerning for COVID-19 infection could serve as a surrogate for the diagnosis of COVID-19 in the community. MATERIALS AND METHODS: A database search of abdominopelvic CT reports from March 1,2020 to May 2,2020 was performed for keywords suggesting COVID-19 infection by lung base findings. COVID-19 status, respiratory symptoms, laboratory parameters and patient outcomes (hospitalization, ICU admission and/or intubation, and death) were recorded. The trend in cases of unexpected concerning lung base findings on abdominopelvic CT at our institution was compared to the total number of confirmed new cases in NYC over the same time period. RESULTS: The trend in abnormal lung base findings on abdominopelvic CT at our institution correlated with the citywide number of confirmed new cases, including rise and subsequent fall in total cases. The trend was not mediated by COVID-19 testing status or number of tests performed. Patients with respiratory symptoms had significantly higher ferritin (median = 995ng/ml vs 500ng/ml, p = 0.027) and death rate (8/24, 33% vs 4/54, 9%, p = 0.018) compared to those without. CONCLUSION: The rise and fall of unexpected lung base findings suggestive of COVID-19 infection on abdominopelvic CT in patients without COVID-19 symptoms correlated with the number of confirmed new cases throughout NYC from the same time period. A model using abdominopelvic CT lung base findings can serve as a surrogate for future COVID-19 outbreaks.
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COVID-19 , Prueba de COVID-19 , Brotes de Enfermedades , Humanos , Pulmón , Ciudad de Nueva York/epidemiología , SARS-CoV-2RESUMEN
BACKGROUND: Among patients with diabetes and chronic coronary disease, it is unclear if invasive management improves outcomes when added to medical therapy. METHODS: The ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trials (ie, ISCHEMIA and ISCHEMIA-Chronic Kidney Disease) randomized chronic coronary disease patients to an invasive (medical therapy + angiography and revascularization if feasible) or a conservative approach (medical therapy alone with revascularization if medical therapy failed). Cohorts were combined after no trial-specific effects were observed. Diabetes was defined by history, hemoglobin A1c ≥6.5%, or use of glucose-lowering medication. The primary outcome was all-cause death or myocardial infarction (MI). Heterogeneity of effect of invasive management on death or MI was evaluated using a Bayesian approach to protect against random high or low estimates of treatment effect for patients with versus without diabetes and for diabetes subgroups of clinical (female sex and insulin use) and anatomic features (coronary artery disease severity or left ventricular function). RESULTS: Of 5900 participants with complete baseline data, the median age was 64 years (interquartile range, 57-70), 24% were female, and the median estimated glomerular filtration was 80 mL·min-1·1.73-2 (interquartile range, 64-95). Among the 2553 (43%) of participants with diabetes, the median percent hemoglobin A1c was 7% (interquartile range, 7-8), and 30% were insulin-treated. Participants with diabetes had a 49% increased hazard of death or MI (hazard ratio, 1.49 [95% CI, 1.31-1.70]; P<0.001). At median 3.1-year follow-up the adjusted event-free survival was 0.54 (95% bootstrapped CI, 0.48-0.60) and 0.66 (95% bootstrapped CI, 0.61-0.71) for patients with diabetes versus without diabetes, respectively, with a 12% (95% bootstrapped CI, 4%-20%) absolute decrease in event-free survival among participants with diabetes. Female and male patients with insulin-treated diabetes had an adjusted event-free survival of 0.52 (95% bootstrapped CI, 0.42-0.56) and 0.49 (95% bootstrapped CI, 0.42-0.56), respectively. There was no difference in death or MI between strategies for patients with diabetes versus without diabetes, or for clinical (female sex or insulin use) or anatomic features (coronary artery disease severity or left ventricular function) of patients with diabetes. CONCLUSIONS: Despite higher risk for death or MI, chronic coronary disease patients with diabetes did not derive incremental benefit from routine invasive management compared with initial medical therapy alone. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01471522.
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Diabetes Mellitus/tratamiento farmacológico , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
Introduction: Optimal medical therapy (OMT) is the cornerstone of treatment for stable coronary disease with the ISCHEMIA trial showing similar outcomes using OMT with or without an initial invasive approach. Objectives: To describe OMT goal attainment in Polish ISCHEMIA participants compared with other countries. Patients and methods: Among 5179 trial participants, 333 were randomized in Poland. The median follow-up was 3.2 years. OMT targets were: not smoking, high-intensity statin therapy, low-density lipoprotein cholesterol (LDL-C) of less than 70 mg/dl, systolic blood pressure of less than 140 mm Hg, aspirin therapy, and ACEI / ARB, and ß-blocker therapy if indicated. Results: Compared with 36 other countries, at randomization, patients in Poland were older (67 [6275] y vs 65 [5871] y); P <â 0.001), more often female (30% vs 22%; P = 0.002), with a longer history of angina (3 [19] y vs 1 [03] y; P <â 0.001), and there were more cases of prior myocardial infarction (32% vs 18%; P <â 0.01) and revascularization (PCI, 40% vs 19%; CABG, 11% vs 3%; P <â 0.001 for both). The number of OMT goals attained increased from baseline to follow-up visits (5 [45] vs 6 [56]; P <â 0.001) in Poland and other countries alike (P = 0.89 vs P = 0.14). In Poland, significant improvements were achieved regarding high-intensity statin therapy (27% vs 50%), LDL-C <â 70 mg/dl (29% vs 65%), and systolic blood pressure of less than 140 mm Hg (63% vs 81%) (P <â 0.001 for all), whereas not-smoking (89% vs 89%), aspirin (90% vs 88%), ACEI / ARB (93% vs 95%), and ß-blocker therapy (94% vs 90%) remained high. Conclusions: With regular surveillance and contemporary medical therapy, high OMT goal attainment was achievable among the participants of the ISCHEMIA trial in Poland relative to other countries. There is still room for improvement in LDL-C and blood pressure management.