RESUMEN
While polygenic risk scores (PRSs) enable early identification of genetic risk for chronic obstructive pulmonary disease (COPD), predictive performance is limited when the discovery and target populations are not well matched. Hypothesizing that the biological mechanisms of disease are shared across ancestry groups, we introduce a PrediXcan-derived polygenic transcriptome risk score (PTRS) to improve cross-ethnic portability of risk prediction. We constructed the PTRS using summary statistics from application of PrediXcan on large-scale GWASs of lung function (forced expiratory volume in 1 s [FEV1] and its ratio to forced vital capacity [FEV1/FVC]) in the UK Biobank. We examined prediction performance and cross-ethnic portability of PTRS through smoking-stratified analyses both on 29,381 multi-ethnic participants from TOPMed population/family-based cohorts and on 11,771 multi-ethnic participants from TOPMed COPD-enriched studies. Analyses were carried out for two dichotomous COPD traits (moderate-to-severe and severe COPD) and two quantitative lung function traits (FEV1 and FEV1/FVC). While the proposed PTRS showed weaker associations with disease than PRS for European ancestry, the PTRS showed stronger association with COPD than PRS for African Americans (e.g., odds ratio [OR] = 1.24 [95% confidence interval [CI]: 1.08-1.43] for PTRS versus 1.10 [0.96-1.26] for PRS among heavy smokers with ≥ 40 pack-years of smoking) for moderate-to-severe COPD. Cross-ethnic portability of the PTRS was significantly higher than the PRS (paired t test p < 2.2 × 10-16 with portability gains ranging from 5% to 28%) for both dichotomous COPD traits and across all smoking strata. Our study demonstrates the value of PTRS for improved cross-ethnic portability compared to PRS in predicting COPD risk.
Asunto(s)
Enfermedad Pulmonar Obstructiva Crónica , Transcriptoma , Humanos , Pulmón , National Heart, Lung, and Blood Institute (U.S.) , Enfermedad Pulmonar Obstructiva Crónica/genética , Factores de Riesgo , Estados Unidos/epidemiologíaRESUMEN
Persistent albuminuria (PA) is common in sickle cell anaemia (SCA). With the association of chronic kidney disease (CKD) with increased mortality, biomarkers that predict its development or progression are needed. We evaluated the association of select biomarkers with PA in adults with SCA using Kruskal-Wallis rank-sum test and logistic regression models, with adjustment for multiple testing. Of 280 subjects, 100 (35.7%) had PA. Median plasma levels of soluble vascular cell adhesion molecule-1 (VCAM-1) (1176.3 vs. 953.4 ng/mL, false discovery rate [FDR] q-value <0.003), thrombin-antithrombin complex (5.5 vs. 4.7 ng/mL, FDR q-value = 0.04), and urinary angiotensinogen (AGT) (12.2 vs. 5.3 ng/mg, FDR q-value <0.003), urinary nephrin (30.6 vs. 27.2 ng/mg, FDR q-value = 0.04), and urinary kidney injury molecule-1 (KIM-1) (0.8 vs. 0.5 ng/mg, FDR q-value <0.003), normalized to urine creatinine, were significantly higher in subjects with PA. In multivariable analysis, only urinary AGT (odds ratio = 1.058, FDR q-value <0.0001) remained a significant predictor of PA. In addition, soluble VCAM-1 (FDR q-value <0.0001), D-dimer (FDR q-value <0.0001), urinary AGT (FDR q-value <0.0001), KIM-1 (FDR q-value <0.0001), and nephrin (FDR q-value <0.0001) were significantly associated with urine albumin-creatinine ratio in multivariable analyses. Longitudinal studies to evaluate the predictive capacity of biomarkers for the development and progression of CKD in SCA are warranted.
RESUMEN
Clinical and laboratory correlates of chronic kidney disease (CKD) in sickle cell anaemia remain incompletely defined. In a multicenter cohort study, we evaluated the prevalence of persistent albuminuria (PA) and characteristics associated with PA, albumin-creatinine ratio (ACR) and decreased estimated glomerular filtration rate (eGFR) using logistic, linear and multinomial regression models, respectively. Of 269 participants (median age: 30 years; 57.2% females), the prevalence of PA was 35.7%. Using baseline ACR values of <100 and ≥100 mg/g, the probabilities of PA were 30.0% and 94.6%, respectively. In multivariable logistic regression analyses, male sex (ß = 0.80 [SE = 0.36], p = 0.024) and ACE inhibitors/ARBs use (ß = 1.54 [SE = 0.43], p < 0.001) were associated with higher likelihoods of PA, while higher haemoglobin (ß = -0.33 [SE = 0.13], p = 0.009) and HbF (ß = -0.04 [SE = 0.02], p = 0.041) were associated with lower likelihoods of PA. In multivariable multinomial regression analyses, older age (ß = 0.06 [SE = 0.02], p = 0.004) and higher alkaline phosphatase (ß = 0.01 [SE = 0.00], p = 0.004) were associated with higher odds of having eGFR 60-90 versus eGFR>90 mL/min/1.73 m2 using the cystatin C-based CKD-EPI-2012 equation. Additionally, higher systolic blood pressure (ß = 0.11 [SE = 0.03], p = 0.001) and blood urea nitrogen (ß = 0.45 [SE = 0.12], p < 0.001) were associated with higher odds, while higher haemoglobin (ß = -1.22 [SE = 0.43], p = 0.004) was associated with lower odds of having eGFR<60 versus eGFR>90 mL/min/1.73 m2. PA and decreased eGFR are associated with measures of disease severity and comorbid conditions (Clinicaltrials.gov Identifier: NCT03277547).
RESUMEN
Not available.
Asunto(s)
Anemia de Células Falciformes , Anemia de Células Falciformes/diagnóstico , Tasa de Filtración Glomerular , HumanosRESUMEN
RATIONALE: Chronic lower respiratory diseases (CLRDs), including chronic obstructive pulmonary disease (COPD) and asthma, are the fourth leading cause of death. Prior studies suggest that albuminuria, a biomarker of endothelial injury, is increased in patients with COPD. OBJECTIVES: To test whether albuminuria was associated with lung function decline and incident CLRDs. METHODS: Six U.S. population-based cohorts were harmonized and pooled. Participants with prevalent clinical lung disease were excluded. Albuminuria (urine albumin-to-creatinine ratio) was measured in spot samples. Lung function was assessed by spirometry. Incident CLRD-related hospitalizations and deaths were classified via adjudication and/or administrative criteria. Mixed and proportional hazards models were used to test individual-level associations adjusted for age, height, weight, sex, race/ethnicity, education, birth year, cohort, smoking status, pack-years of smoking, renal function, hypertension, diabetes, and medications. MEASUREMENTS AND MAIN RESULTS: Among 10,961 participants with preserved lung function, mean age at albuminuria measurement was 60 years, 51% were never-smokers, median albuminuria was 5.6 mg/g, and mean FEV1 decline was 31.5 ml/yr. For each SD increase in log-transformed albuminuria, there was 2.81% greater FEV1 decline (95% confidence interval [CI], 0.86-4.76%; P = 0.0047), 11.02% greater FEV1/FVC decline (95% CI, 4.43-17.62%; P = 0.0011), and 15% increased hazard of incident spirometry-defined moderate-to-severe COPD (95% CI, 2-31%, P = 0.0021). Each SD log-transformed albuminuria increased hazards of incident COPD-related hospitalization/mortality by 26% (95% CI, 18-34%, P < 0.0001) among 14,213 participants followed for events. Asthma events were not significantly associated. Associations persisted in participants without current smoking, diabetes, hypertension, or cardiovascular disease. CONCLUSIONS: Albuminuria was associated with greater lung function decline, incident spirometry-defined COPD, and incident COPD-related events in a U.S. population-based sample.
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Albuminuria/epidemiología , Pulmón/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Anciano , Albuminuria/fisiopatología , Estudios de Cohortes , Comorbilidad , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , National Heart, Lung, and Blood Institute (U.S.) , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Pruebas de Función Respiratoria , Factores de Riesgo , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Community trends of acute decompensated heart failure (ADHF) in diverse populations may differ by race and sex. METHODS: The ARIC study (Atherosclerosis Risk in Communities) sampled heart failure-related hospitalizations (≥55 years of age) in 4 US communities from 2005 to 2014 using International Classification of Diseases, Ninth Revision, Clinical Modification codes. ADHF hospitalizations were validated by standardized physician review and computer algorithm, yielding 40 173 events after accounting for sampling design (unweighted n=8746). RESULTS: Of the ADHF hospitalizations, 50% had reduced ejection fraction, and 39% had preserved EF (HFpEF). HF with reduced ejection fraction was more common in black men and white men, whereas HFpEF was most common in white women. Average age-adjusted rates of ADHF were highest in blacks (38.1 per 1000 black men, 30.5 per 1000 black women), with rates differing by HF type and sex. ADHF rates increased over the 10 years (average annual percentage change: black women +4.3%, black men +3.7%, white women +1.9%, white men +2.6%), mostly reflecting more acute HFpEF. Age-adjusted 28-day and 1-year case fatality proportions were ≈10% and 30%, respectively, similar across race-sex groups and HF types. Only blacks showed decreased 1-year mortality over time (average annual percentage change: black women -5.4%, black men -4.6%), with rates differing by HF type (average annual percentage change: black women HFpEF -7.1%, black men HF with reduced ejection fraction -4.7%). CONCLUSIONS: Between 2005 and 2014, trends in ADHF hospitalizations increased in 4 US communities, primarily driven by acute HFpEF. Survival at 1 year was poor regardless of EF but improved over time for black women and black men.
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Insuficiencia Cardíaca/terapia , Evaluación de Procesos y Resultados en Atención de Salud/tendencias , Admisión del Paciente/tendencias , Negro o Afroamericano , Factores de Edad , Anciano , Femenino , Disparidades en el Estado de Salud , Insuficiencia Cardíaca/etnología , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/fisiopatología , Mortalidad Hospitalaria/tendencias , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Factores Sexuales , Volumen Sistólico , Factores de Tiempo , Resultado del Tratamiento , Estados Unidos/epidemiología , Función Ventricular Izquierda , Población BlancaRESUMEN
BACKGROUND: A lower prevalence of atrial fibrillation (AF), but paradoxically higher burden of cardiovascular disease risk factors, has been observed among African Americans compared to Whites in studies of AF identified by mostly 12-lead electrocardiograms (ECGs) and clinically. METHODS: We performed 48-hour ambulatory electrocardiography (aECG) in a biracial sample of 1,193 participants in the Atherosclerosis Risk in Communities (ARIC) (mean ageâ¯=â¯78â¯years, 62% African Americans, 64% female). Atrial fibrillation was identified from aECG, study visit ECGs, and discharge codes from cohort hospitalizations. We used covariate-adjusted logistic regression to estimate prevalence odds ratios (ORs) for AF in African Americans versus Whites, with adjustment for sampling and nonresponse. RESULTS: African Americans were more likely than Whites to have hypertension and diabetes but less likely to have coronary heart disease. The prevalence of AF detected by aECG or ARIC study ECG (adjusted for age and coronary heart disease) was lower in African Americans than Whites (2.7% vs 5.0%). White men had a higher (although not significant) AF prevalence of 7.8% compared to the other race and gender groups at 2.3%-2.8%. The adjusted OR for AF was 0.49 (0.24-0.99) comparing African Americans to Whites. Findings were similar when AF was defined to include prior AF hospitalizations (ORâ¯=â¯0.42, 0.25-0.72). There were no significant differences by race for asymptomatic or paroxysmal AF. CONCLUSIONS: Atrial fibrillation was less prevalent in African American than white older adults, regardless of detection method. Although overall detection of new AF cases with aECG was low, future studies should consider longer-term monitoring to characterize AF by race.
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Fibrilación Atrial/epidemiología , Negro o Afroamericano/estadística & datos numéricos , Población Blanca/estadística & datos numéricos , Anciano , Fibrilación Atrial/etnología , Electrocardiografía Ambulatoria/estadística & datos numéricos , Femenino , Humanos , Estudios Longitudinales , Masculino , Oportunidad Relativa , Prevalencia , Factores Sexuales , Factores de Tiempo , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Although heart failure (HF) disproportionately affects older adults, little data exist regarding the prevalence of American College of Cardiology/American Heart Association HF stages among older individuals in the community. Additionally, the role of contemporary measures of longitudinal strain and diastolic dysfunction in defining HF stages is unclear. METHODS: HF stages were classified in 6118 participants in the Atherosclerosis Risk in Communities study (67-91 years of age) at the fifth study visit as follows: A (asymptomatic with HF risk factors but no cardiac structural or functional abnormalities), B (asymptomatic with structural abnormalities, defined as left ventricular hypertrophy, dilation or dysfunction, or significant valvular disease), C1 (clinical HF without prior hospitalization), and C2 (clinical HF with earlier hospitalization). RESULTS: Using the traditional definitions of HF stages, only 5% of examined participants were free of HF risk factors or structural heart disease (Stage 0), 52% were categorized as Stage A, 30% Stage B, 7% Stage C1, and 6% Stage C2. Worse HF stage was associated with a greater risk of incident HF hospitalization or death at a median follow-up of 608 days. Left ventricular (LV) ejection fraction was preserved in 77% and 65% in Stages C1 and C2, respectively. Incorporation of longitudinal strain and diastolic dysfunction into the Stage B definition reclassified 14% of the sample from Stage A to B and improved the net reclassification index (P=0.028) and integrated discrimination index (P=0.016). Abnormal LV structure, systolic function (based on LV ejection fraction and longitudinal strain), and diastolic function (based on e', E/e', and left atrial volume index) were each independently and additively associated with risk of incident HF hospitalization or death in Stage A and B participants. CONCLUSIONS: The majority of older adults in the community are at risk for HF (Stages A or B), appreciably more compared with previous reports in younger community-based samples. LV ejection fraction is robustly preserved in at least two-thirds of older adults with prevalent HF (Stage C), highlighting the burden of HF with preserved LV ejection fraction in the elderly. LV diastolic function and longitudinal strain provide incremental prognostic value beyond conventional measures of LV structure and LV ejection fraction in identifying persons at risk for HF hospitalization or death.
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Ecocardiografía/métodos , Insuficiencia Cardíaca/fisiopatología , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Humanos , Masculino , Pronóstico , Estudios Prospectivos , Factores de RiesgoRESUMEN
Chronic lower respiratory diseases (CLRDs) are the fourth leading cause of death in the United States. To support investigations into CLRD risk determinants and new approaches to primary prevention, we aimed to harmonize and pool respiratory data from US general population-based cohorts. Data were obtained from prospective cohorts that performed prebronchodilator spirometry and were harmonized following 2005 ATS/ERS standards. In cohorts conducting follow-up for noncardiovascular events, CLRD events were defined as hospitalizations/deaths adjudicated as CLRD-related or assigned relevant administrative codes. Coding and variable names were applied uniformly. The pooled sample included 65,251 adults in 9 cohorts followed-up for CLRD-related mortality over 653,380 person-years during 1983-2016. Average baseline age was 52 years; 56% were female; 49% were never-smokers; and racial/ethnic composition was 44% white, 22% black, 28% Hispanic/Latino, and 5% American Indian. Over 96% had complete data on smoking, clinical CLRD diagnoses, and dyspnea. After excluding invalid spirometry examinations (13%), there were 105,696 valid examinations (median, 2 per participant). Of 29,351 participants followed for CLRD hospitalizations, median follow-up was 14 years; only 5% were lost to follow-up at 10 years. The NHLBI Pooled Cohorts Study provides a harmonization standard applied to a large, US population-based sample that may be used to advance epidemiologic research on CLRD.
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Enfermedades Pulmonares Obstructivas/epidemiología , Enfermedades Pulmonares Obstructivas/fisiopatología , National Heart, Lung, and Blood Institute (U.S.)/organización & administración , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Pesos y Medidas Corporales , Bronquiectasia/epidemiología , Bronquiectasia/fisiopatología , Enfermedad Crónica , Estudios de Cohortes , Etnicidad/estadística & datos numéricos , Femenino , Hispánicos o Latinos/estadística & datos numéricos , Hospitalización/estadística & datos numéricos , Humanos , Indígenas Norteamericanos/estadística & datos numéricos , Exposición por Inhalación/estadística & datos numéricos , Enfermedades Pulmonares Obstructivas/etnología , Enfermedades Pulmonares Obstructivas/mortalidad , Masculino , Persona de Mediana Edad , National Heart, Lung, and Blood Institute (U.S.)/normas , Fenotipo , Grupos Raciales/estadística & datos numéricos , Pruebas de Función Respiratoria , Factores de Riesgo , Fumar/epidemiología , Factores Socioeconómicos , Estados Unidos/epidemiología , Población Blanca/estadística & datos numéricos , Adulto JovenAsunto(s)
Anemia de Células Falciformes , Enfermedades Renales , Humanos , Femenino , Masculino , Caracteres Sexuales , Riñón , Progresión de la EnfermedadRESUMEN
BACKGROUND: Patient-reported outcomes and epidemiological studies in adults with tetralogy of Fallot are lacking. Recruitment and longitudinal follow-up investigation across institutions is particularly challenging. Objectives of this study were to assess the feasibility of recruiting adult patients with tetralogy of Fallot for a patient-reported outcomes study, describe challenges for recruitment, and create an interactive, online tetralogy of Fallot registry. METHODS: Adult patients living with tetralogy of Fallot, aged 18-58 years, at the University of North Carolina were identified using diagnosis code query. A survey was designed to collect demographics, symptoms, history, and birth mother information. Recruitment was attempted by phone (Part I, n=20) or by email (Part II, n=20). Data analysis included thematic grouping of recruitment challenges and descriptive statistics. Feasibility threshold was 75% for recruitment and for data fields completed per patient. RESULTS: In Part I, 60% (12/20) were successfully contacted and eight (40%) were enrolled. Demographics and birth mother information were obtained for all enrolled patients. In Part II, 70% (14/20) were successfully contacted; 30% (6/20) enrolled and completed all data fields linked to REDCap database; the median time for survey completion was 8 minutes. Half of the patients had cardiac operations/procedures performed at more than one hospital. Automatic electronic data entry from the online survey was uncomplicated. CONCLUSIONS: Although recruitment (54%) fell below our feasibility threshold, enrolled individuals were willing to complete phone or online surveys. Incorrect contact information, privacy concerns, and patient-reported time constraints were challenges for recruitment. Creating an online survey and linked database is technically feasible and efficient for patient-reported outcomes research.
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Atención a la Salud/estadística & datos numéricos , Sistema de Registros , Tetralogía de Fallot/epidemiología , Adolescente , Adulto , Estudios de Factibilidad , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Morbilidad/tendencias , North Carolina/epidemiología , Estudios Retrospectivos , Encuestas y Cuestionarios , Adulto JovenRESUMEN
BACKGROUND: Timing and trajectories of cardiovascular risk factor (CVRF) development in relation to atrial fibrillation (AF) have not been described previously. We assessed trajectories of CVRF and incidence of AF over 25 years in the ARIC study (Atherosclerosis Risk in Communities). METHODS: We assessed trajectories of CVRF in 2456 individuals with incident AF and 6414 matched control subjects. Subsequently, we determined the association of CVRF trajectories with the incidence of AF among 10 559 AF-free individuals (mean age, 67 years; 52% men; 20% blacks). Risk factors were measured during 5 examinations between 1987 and 2013. Cardiovascular events, including incident AF, were ascertained continuously. We modeled the prevalence of risk factors and cardiovascular outcomes in the period before and after AF diagnosis and the corresponding index date for control subjects using generalized estimating equations. Trajectories in risk factors were identified with latent mixture modeling. The risk of incident AF by trajectory group was examined with Cox models. RESULTS: The prevalence of stroke, myocardial infarction, and heart failure increased steeply during the time close to AF diagnosis. All CVRFs were elevated in AF cases compared with controls >15 years before diagnosis. We identified distinct trajectories for all the assessed CVRFs. In general, individuals with trajectories denoting long-term exposure to CVRFs had increased AF risk even after adjustment for single measurements of the CVRFs. CONCLUSIONS: AF patients have increased prevalence of CVRF many years before disease diagnosis. This analysis identified diverse trajectories in the prevalence of these risk factors, highlighting their different roles in AF pathogenesis.
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Aterosclerosis/diagnóstico , Aterosclerosis/epidemiología , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/epidemiología , Características de la Residencia , Anciano , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de RiesgoRESUMEN
BACKGROUND: The purpose of this study was to characterize the repeatability of ectopic beats, defined by premature atrial contractions (PACs) and premature ventricular contractions (PVCs), on ambulatory electrocardiogram (aECG) monitoring and evaluate the effect of length of aECG monitoring on the repeatability estimates. METHODS: This analysis includes 95 randomly selected participants from the Atherosclerosis Risk in Communities Study (ARIC; 2011-2013). The participants wore a Holter monitor for two, 48-hr periods separated by a mean of 38 days following an identical, standardized protocol. We divided each 48-hr recording into 3-, 6-, 12-, and 24-hr recording periods and calculated intraclass correlation coefficients (ICCs) for PACs and PVCs and also as a percentage of the corresponding total of recorded beats per hour among these periods. RESULTS: All participants had ≥1 PAC during the 48-hr recordings, and only two participants had no PVCs. ICCs were >0.83 for all indices and recording lengths ≥12 hrs. ICCs were intermediate for 6-hr recordings (range 0.80-0.83) and lower for 3-hr recordings (range 0.74-0.80). The ratio of the between- to within-participant variation increased with recording length. CONCLUSION: Repeatability of PACs and PVCs was excellent for recording lengths of 6-24 hr and fair for 3 hr. Repeatability varies over shorter duration recordings within the 48-hr recording period, and thus the present results have implications for detection algorithms for ectopic beats and can facilitate epidemiologic and clinical applications in which knowledge of measurement variability and misclassification are needed.
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Aterosclerosis/complicaciones , Complejos Atriales Prematuros/diagnóstico , Electrocardiografía Ambulatoria/estadística & datos numéricos , Evaluación Geriátrica/estadística & datos numéricos , Encuestas Epidemiológicas/estadística & datos numéricos , Complejos Prematuros Ventriculares/diagnóstico , Anciano , Complejos Atriales Prematuros/complicaciones , Complejos Atriales Prematuros/fisiopatología , Estudios de Cohortes , Electrocardiografía Ambulatoria/métodos , Femenino , Evaluación Geriátrica/métodos , Encuestas Epidemiológicas/métodos , Humanos , Vida Independiente , Estudios Longitudinales , Masculino , Reproducibilidad de los Resultados , Riesgo , Factores de Riesgo , Factores de Tiempo , Complejos Prematuros Ventriculares/complicaciones , Complejos Prematuros Ventriculares/fisiopatologíaAsunto(s)
Variaciones en el Número de Copia de ADN , ADN Mitocondrial/genética , Insuficiencia Cardíaca/genética , Anciano , Aterosclerosis/genética , Aterosclerosis/metabolismo , ADN Mitocondrial/sangre , Femenino , Estudios de Seguimiento , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/metabolismo , Insuficiencia Cardíaca/fisiopatología , Humanos , Incidencia , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Mitocondrias Cardíacas/metabolismo , Estudios Prospectivos , Volumen SistólicoRESUMEN
Estimates of the numbers and rates of acute decompensated heart failure (ADHF) hospitalization are central to understanding health-care utilization and efforts to improve patient care. We comprehensively estimated the frequency, rate, and trends of ADHF hospitalization in the United States. Based on Atherosclerosis Risk in Communities (ARIC) Study surveillance adjudicating 12,450 eligible hospitalizations during 2005-2010, we developed prediction models for ADHF separately for 3 International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code 428 discharge diagnosis groups: 428 primary, 428 nonprimary, or 428 absent. We applied the models to data from the National Inpatient Sample (11.5 million hospitalizations of persons aged ≥55 years with eligible ICD-9-CM codes), an all-payer, 20% probability sample of US community hospitals. The average estimated number of ADHF hospitalizations per year was 1.76 million (428 primary, 0.80 million; 428 nonprimary, 0.83 million; 428 absent, 0.13 million). During 1998-2004, the rate of ADHF hospitalization increased by 2.0%/year (95% confidence interval (CI): 1.8, 2.5) versus a 1.4%/year (95% CI: 0.8, 2.1) increase in code 428 primary hospitalizations (P < 0.001). In contrast, during 2005-2011, numbers of ADHF hospitalizations were stable (-0.5%/year; 95% CI: -1.4, 0.3), while the numbers of 428-primary hospitalizations decreased by -1.5%/year (95% CI: -2.2, -0.8) (P for contrast = 0.03). In conclusion, the estimated number of hospitalizations with ADHF is approximately 2 times higher than the number of hospitalizations with ICD-9-CM code 428 in the primary position. The trend increased more steeply prior to 2005 and was relatively flat after 2005.
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Insuficiencia Cardíaca/epidemiología , Hospitalización/tendencias , Enfermedad Aguda , Anciano , Estudios de Cohortes , Femenino , Humanos , Clasificación Internacional de Enfermedades/estadística & datos numéricos , Masculino , Maryland/epidemiología , Persona de Mediana Edad , Minnesota/epidemiología , Mississippi/epidemiología , North Carolina/epidemiología , Estudios Prospectivos , Características de la ResidenciaRESUMEN
OBJECTIVE: The aim of this study was to assess the relationship between abnormally increased P-wave terminal force in lead V1 , an electrocardiographic (ECG) marker of left atrial abnormality, and incident ischemic stroke subtypes. We hypothesized that associations would be stronger with nonlacunar stroke, given that we expected left atrial abnormality to reflect the risk of thromboembolism rather than in situ cerebral small-vessel occlusion. METHODS: Our cohort comprised 14,542 participants 45 to 64 years of age prospectively enrolled in the Atherosclerosis Risk in Communities study and free of clinically apparent atrial fibrillation (AF) at baseline. Left atrial abnormality was defined as PTFV1 >4,000µV*ms. Outcomes were adjudicated ischemic stroke, nonlacunar (including cardioembolic) ischemic stroke, and lacunar stroke. RESULTS: During a median follow-up period of 22 years (interquartile range, 19-23 years), 904 participants (6.2%) experienced a definite or probable ischemic stroke. A higher incidence of stroke occurred in those with baseline left atrial abnormality (incidence rate per 1,000 person-years, 6.3; 95% confidence interval [CI]: 5.4-7.4) than in those without (incidence rate per 1,000 person-years, 2.9; 95% CI: 2.7-3.1; p < 0.001). In Cox regression models adjusted for potential confounders and incident AF, left atrial abnormality was associated with incident ischemic stroke (hazard ratio [HR]: 1.33; 95% CI: 1.11-1.59). This association was limited to nonlacunar stroke (HR, 1.49; 95% CI: 1.07-2.07) as opposed to lacunar stroke (HR, 0.89; 95% CI: 0.57-1.40). INTERPRETATION: We found an association between ECG-defined left atrial abnormality and subsequent nonlacunar ischemic stroke. Our findings suggest that an underlying atrial cardiopathy may cause left atrial thromboembolism in the absence of recognized AF.
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Aterosclerosis/diagnóstico , Función del Atrio Izquierdo , Electrocardiografía , Accidente Cerebrovascular/diagnóstico , Aterosclerosis/fisiopatología , Isquemia Encefálica/patología , Enfermedades de los Pequeños Vasos Cerebrales/patología , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Medición de Riesgo , Factores de Riesgo , Accidente Cerebrovascular/clasificación , Accidente Cerebrovascular/fisiopatología , Accidente Vascular Cerebral Lacunar/patología , Tromboembolia/patologíaRESUMEN
BACKGROUND: Individuals with peripheral artery disease (PAD) often have reduced physical activity, which may increase the future risk of diabetes mellitus. Although diabetes is a risk factor for PAD, whether low ankle-brachial index (ABI) predates diabetes has not been studied. METHODS: We examined the association of ABI with incident diabetes using Cox proportional hazards models in the ARIC Study. ABI was measured in 12,247 black and white participants without prevalent diabetes at baseline (1987-1989). Incident diabetes cases were identified by blood glucose levels at three subsequent visits (1990-92, 1993-95, and 1996-98) or self-reported physician diagnosis or medication use at those visits or during annual phone interview afterward through 2011. RESULTS: A total of 3305 participants developed diabetes during a median of 21 years of follow-up. Participants with low (≤0.90) and borderline low (0.91-1.00) ABI had 30-40% higher risk of future diabetes as compared to those with ABI of 1.10-1.20 in the demographically adjusted model. The associations were attenuated after further adjustment for other potential confounders but remained significant for ABI 0.91-1.00 (HR = 1.17, 95% CI 1.04-1.31) and marginally significant for ABI ≤ 0.90 (HR = 1.19, 0.99-1.43). Although the association was largely consistent across subgroups, a stronger association was seen in participants without hypertension, those with normal fasting glucose, and those with a history of stroke compared to their counterparts. CONCLUSIONS: Low ABI was modestly but independently associated with increased risk of incident diabetes in the general population. Clinical attention should be paid to the glucose trajectory among people with low ABI but without diabetes.
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Índice Tobillo Braquial , Aterosclerosis/epidemiología , Diabetes Mellitus/epidemiología , Enfermedad Arterial Periférica/epidemiología , Aterosclerosis/diagnóstico , Biomarcadores/sangre , Glucemia/metabolismo , Distribución de Chi-Cuadrado , Comorbilidad , Diabetes Mellitus/sangre , Diabetes Mellitus/diagnóstico , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Dinámicas no Lineales , Enfermedad Arterial Periférica/diagnóstico , Enfermedad Arterial Periférica/fisiopatología , Valor Predictivo de las Pruebas , Modelos de Riesgos Proporcionales , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Reduced low forced expiratory volume in 1 second (FEV1) is reportedly associated with an increased risk of atrial fibrillation (AF). Extant reports do not provide separate estimates for never smokers or for blacks, who incongruously have lower AF incidence than whites. METHODS AND RESULTS: We examined 15 004 middle-aged blacks and whites enrolled in the Atherosclerosis Risk in Communities (ARIC) cohort study. Standardized spirometry data were collected at the baseline examination. Incident AF was identified from the first among the following: International Classification of Diseases codes for AF on hospital discharge records or death certificates or 12-lead ECGs performed during 3 triennial follow-up visits. Over an average follow-up of 17.5 years, a total of 1691 participants (11%) developed new-onset AF. The rate of incident AF was inversely associated with FEV1 in each of the 4 race and sex groups. After multivariable adjustment for traditional cardiovascular disease risk factors and height, hazard ratios of AF comparing the lowest with the highest quartile of FEV1 were 1.37 (95% confidence interval, 1.02-1.83) for white women, 1.49 (95% confidence interval, 1.16-1.91) for white men, 1.63 (95% confidence interval, 1.00-2.66) for black women, and 2.36 (95% confidence interval, 1.30-4.29) for black men. The above associations were observed across all smoking status categories. Moderate/severe airflow obstruction (FEV1/forced vital capacity <0.70 and FEV1 < 80% of predicted value) was also associated with higher AF incidence. CONCLUSIONS: In this large population-based study with a long-term follow-up, reduced FEV1 and obstructive respiratory disease were associated with a higher AF incidence after adjustment for measured confounders.
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Fibrilación Atrial/etnología , Fibrilación Atrial/epidemiología , Enfermedades Pulmonares Obstructivas/etnología , Enfermedades Pulmonares Obstructivas/fisiopatología , Pulmón/fisiopatología , Población Negra/etnología , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Volumen Espiratorio Forzado/fisiología , Humanos , Incidencia , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Pruebas de Función Respiratoria , Factores de Riesgo , Espirometría , Población Blanca/etnologíaRESUMEN
Many disorders are associated with altered serum protein concentrations, including malnutrition, cancer, and cardiovascular, kidney, and inflammatory diseases. Although these protein concentrations are highly heritable, relatively little is known about their underlying genetic determinants. Through transethnic meta-analysis of European-ancestry and Japanese genome-wide association studies, we identified six loci at genome-wide significance (p < 5 × 10(-8)) for serum albumin (HPN-SCN1B, GCKR-FNDC4, SERPINF2-WDR81, TNFRSF11A-ZCCHC2, FRMD5-WDR76, and RPS11-FCGRT, in up to 53,190 European-ancestry and 9,380 Japanese individuals) and three loci for total protein (TNFRS13B, 6q21.3, and ELL2, in up to 25,539 European-ancestry and 10,168 Japanese individuals). We observed little evidence of heterogeneity in allelic effects at these loci between groups of European and Japanese ancestry but obtained substantial improvements in the resolution of fine mapping of potential causal variants by leveraging transethnic differences in the distribution of linkage disequilibrium. We demonstrated a functional role for the most strongly associated serum albumin locus, HPN, for which Hpn knockout mice manifest low plasma albumin concentrations. Other loci associated with serum albumin harbor genes related to ribosome function, protein translation, and proteasomal degradation, whereas those associated with serum total protein include genes related to immune function. Our results highlight the advantages of transethnic meta-analysis for the discovery and fine mapping of complex trait loci and have provided initial insights into the underlying genetic architecture of serum protein concentrations and their association with human disease.
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Proteínas Sanguíneas/genética , Proteínas Sanguíneas/metabolismo , Sitios Genéticos , Predisposición Genética a la Enfermedad/genética , Adulto , Anciano , Alelos , Animales , Pueblo Asiatico/genética , Mapeo Cromosómico/métodos , Femenino , Estudio de Asociación del Genoma Completo/métodos , Humanos , Desequilibrio de Ligamiento/genética , Masculino , Ratones , Persona de Mediana Edad , Biosíntesis de Proteínas/genética , Proteolisis , Ribosomas/genética , Albúmina Sérica/genética , Población Blanca/genéticaRESUMEN
INTRODUCTION: Structural changes in the heart are known risk factors for atrial fibrillation (AF). An association between high-sensitivity cardiac troponin T (hs-cTnT), a marker of myocardial cell damage measured with a high-sensitivity assay, and the risk of AF could have implications for AF risk stratification. OBJECTIVE: To estimate the association between hs-cTnT and the risk of incident AF in the ARIC study, a prospective cohort of middle-aged adults from 4 US communities. METHODS: Study included 10,584 participants (mean age 62.7 years) free of AF in 1996 to 1998 and followed through 2008. Atrial fibrillation was defined using International Classification of Diseases codes from hospitalizations and death certificates. Participants with undetectable hs-cTnT levels (58%) were assigned the lower limit of measurement (5 ng/L). Net reclassification improvement was used to examine the discriminative ability of hs-cTnT for 10-year AF risk prediction (categories: <5%, 5%-15%, and >15%). RESULTS: A total of 920 incident AF cases were observed for 109,227 person-years. After adjustment, a 1-SD difference in ln(hs-cTnT) was associated with a hazard ratio of 1.16 (95% CI 1.10-1.23). Compared with those with undetectable levels, participants with hs-cTnT ≥14 ng/L had a hazard ratio of 1.78 (95% CI 1.43-2.24). Addition of hs-cTnT to known AF predictors did not increase the c statistic appreciably (0.756 vs 0.758) or improve risk stratification (net reclassification improvement 0.4%, 95% CI -1.4% to 2.3%). CONCLUSIONS: High-sensitivity cTnT level is associated with an increased incidence rate of AF but did not improve risk stratification.