RESUMEN
Fetal supraventricular tachycardia management is challenging, with consequences for both the fetus and the mother. If left untreated, fetal hydrops may ensue, at which point delivery and treatment of the arrhythmia is preferred. However, if the fetus is not at term nor near-term, significant doses of antiarrhythmics may be needed to achieve adequate transplacental bioavailability. Although digoxin has classically been the mainstay of treatment, the use of flecainide or sotalol as monotherapy or in combination with digoxin is being studied. Interdisciplinary team management and shared decision-making between the physician and patient are key to achieving successful outcomes. Adult cardiologists, particularly inpatient consultation services or through burgeoning cardio-obstetrics programs, may, in some practice settings, be asked to evaluate or comanage pregnant women with fetal arrhythmia.
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Enfermedades Fetales , Taquicardia Supraventricular , Antiarrítmicos/uso terapéutico , Cardiólogos , Femenino , Enfermedades Fetales/tratamiento farmacológico , Humanos , Embarazo , Taquicardia Supraventricular/tratamiento farmacológicoRESUMEN
We present a late presentation of saddle pulmonary embolism and thrombus-in-transit straddle the patent foramen on patient who successfully recovered from severe acute respiratory syndrome coronavirus-2 (COVID-19) pneumonia. Seven days postdischarge (ie, 28 days after initial COVID-19 symptom onset), she was readmitted to hospital for severe dyspnea. Computer tomography angiogram and echocardiography confirmed the diagnosis. Severe pro-inflammatory and pro-thrombotic states with endothelial involvement have been reported associated with severe COVID-19 infection. However, the duration of hypercoagulable state has not yet known. This case highlights the risk of thromboembolic phenomena for prolonged periods of times after recovering from COVID-19 pneumonia.
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Anticoagulantes/uso terapéutico , COVID-19/complicaciones , Ecocardiografía/métodos , Foramen Oval Permeable/diagnóstico por imagen , Embolia Pulmonar/diagnóstico por imagen , Trombosis/diagnóstico por imagen , Anciano , Angiografía por Tomografía Computarizada/métodos , Disnea/etiología , Enoxaparina/análogos & derivados , Enoxaparina/uso terapéutico , Femenino , Heparina/uso terapéutico , Humanos , Readmisión del Paciente , Embolia Pulmonar/tratamiento farmacológico , Embolia Pulmonar/etiología , Trombosis/tratamiento farmacológico , Trombosis/etiologíaRESUMEN
BACKGROUND: The epidemiology of atrial fibrillation (AF) without comorbidities, known as 'lone AF', is uncertain. Although it has been considered a benign condition, we hypothesized that it confers a worse prognosis compared with a matched sample without AF. METHODS: We described the proportion of AF without comorbidities (clinical, subclinical cardiovascular disease and triggers) among the entire AF sample in Framingham Heart Study (FHS). We compared AF without comorbidities with typical AF, and age-, sex- and cohort-matched individuals without AF, using Cox proportional hazards analysis in relation to combined cardiovascular events (stroke, heart failure, myocardial infarction), and mortality. RESULTS: Of 10,311 FHS participants, 1,961 were diagnosed with incident AF, among which 173 individuals had AF without comorbidities (47% women, mean age 71±12 years). AF without comorbidities had a prevalence of 1.7% of the entire cohort, and an annual incidence of 0.5 per 1000 person-years. During a median follow-up of 9.7 years after initial AF, 137 individuals with AF without comorbidities (79.2%) died and 141 individuals developed cardiovascular events (81.5%). AF without comorbidities had significantly lower mortality (HR 0.67, 95%CI 0.55-0.81, P < .001) and total cardiovascular events (HR 0.66, 95% CI 0.55-0.80, P < .001) compared with typical AF. However, mortality (HR1.43, 95% CI 1.18-1.75, P < .001) and risk of total cardiovascular events (HR 1.73, 95% CI 1.39-2.16, P < .001) were higher than age-, sex-, and cohort-matched individuals without AF. CONCLUSIONS: The risk of cardiovascular outcomes and mortality among individuals with AF without comorbidities is lower than typical AF, but is significantly elevated compared with matched individuals without AF.
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Fibrilación Atrial/epidemiología , Insuficiencia Cardíaca/epidemiología , Mortalidad , Infarto del Miocardio/epidemiología , Accidente Cerebrovascular/epidemiología , Anciano , Anciano de 80 o más Años , Comorbilidad , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Massachusetts/epidemiología , Persona de Mediana Edad , Prevalencia , Pronóstico , Modelos de Riesgos ProporcionalesRESUMEN
INTRODUCTION: Inflammation and inflammatory biomarkers have emerged as integral components and predictors of incident cardiovascular (CV) disease. Omega-3 fatty acids, particularly eicosapentaenoic and docosahexaenoic acids (EPA and DHA) have anti-inflammatory properties, and have been variably associated with lower blood pressure, favorable blood lipid changes, and reduced CV events. METHODS AND RESULTS: We examined the cross-sectional association of red blood cell (RBC) fatty acids, representative of body membrane fatty acid composition, with 10 biomarkers active in multiple inflammatory pathways in 2724 participants (mean age 66 ± 9 years, 54% women, 8% minorities) from the Framingham Offspring and minority Omni Cohorts. After multivariable adjustment, the RBC EPA and DHA content was inversely correlated (all P ≤ 0.001) with 8 biomarkers: urinary isoprostanes (r = -0.16); and soluble interleukin-6 (r = -0.10); C-reactive protein (r = -0.08); tumor necrosis factor receptor 2 (r = -0.08); intercellular adhesion molecule-1 (r = -0.08); P-selectin (r = -0.06); lipoprotein-associated phospholipase-A2 mass (r = -0.11) and activity (r = -0.08). The correlations for monocyte chemoattractant protein-1 was -0.05, P = 0.006 and osteoprotegerin (r = -0.06, P = 0.002) were only nominally significant. CONCLUSION: In our large community-based study, we observed modest inverse associations between several types of inflammatory biomarkers with RBC omega-3 fatty acid levels. Our findings are consistent with the hypothesis that omega-3 fatty acids have anti-inflammatory properties.
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Antiinflamatorios/sangre , Ácidos Docosahexaenoicos/sangre , Ácido Eicosapentaenoico/sangre , Eritrocitos/inmunología , Mediadores de Inflamación/sangre , Inflamación/sangre , Anciano , Biomarcadores/sangre , Estudios Transversales , Femenino , Humanos , Inflamación/diagnóstico , Inflamación/inmunología , Inflamación/prevención & control , Masculino , Persona de Mediana Edad , Análisis Multivariante , Factores Protectores , Factores de RiesgoRESUMEN
AIMS: B-type natriuretic peptide (BNP) and C-reactive protein (CRP) predict atrial fibrillation (AF) risk. However, their risk stratification abilities in the broad community remain uncertain. We sought to improve risk stratification for AF using biomarker information. METHODS AND RESULTS: We ascertained AF incidence in 18 556 Whites and African Americans from the Atherosclerosis Risk in Communities Study (ARIC, n=10 675), Cardiovascular Health Study (CHS, n = 5043), and Framingham Heart Study (FHS, n = 2838), followed for 5 years (prediction horizon). We added BNP (ARIC/CHS: N-terminal pro-B-type natriuretic peptide; FHS: BNP), CRP, or both to a previously reported AF risk score, and assessed model calibration and predictive ability [C-statistic, integrated discrimination improvement (IDI), and net reclassification improvement (NRI)]. We replicated models in two independent European cohorts: Age, Gene/Environment Susceptibility Reykjavik Study (AGES), n = 4467; Rotterdam Study (RS), n = 3203. B-type natriuretic peptide and CRP were significantly associated with AF incidence (n = 1186): hazard ratio per 1-SD ln-transformed biomarker 1.66 [95% confidence interval (CI), 1.56-1.76], P < 0.0001 and 1.18 (95% CI, 1.11-1.25), P < 0.0001, respectively. Model calibration was sufficient (BNP, χ(2) = 17.0; CRP, χ(2) = 10.5; BNP and CRP, χ(2) = 13.1). B-type natriuretic peptide improved the C-statistic from 0.765 to 0.790, yielded an IDI of 0.027 (95% CI, 0.022-0.032), a relative IDI of 41.5%, and a continuous NRI of 0.389 (95% CI, 0.322-0.455). The predictive ability of CRP was limited (C-statistic increment 0.003). B-type natriuretic peptide consistently improved prediction in AGES and RS. CONCLUSION: B-type natriuretic peptide, not CRP, substantially improved AF risk prediction beyond clinical factors in an independently replicated, heterogeneous population. B-type natriuretic peptide may serve as a benchmark to evaluate novel putative AF risk biomarkers.
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Fibrilación Atrial/sangre , Fibrilación Atrial/epidemiología , Proteína C-Reactiva/metabolismo , Péptido Natriurético Encefálico/sangre , Fragmentos de Péptidos/sangre , Anciano , Biomarcadores/sangre , Europa (Continente)/epidemiología , Femenino , Humanos , Incidencia , Masculino , Valor Predictivo de las Pruebas , Medición de Riesgo , Factores de Riesgo , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND AND PURPOSE: Beyond the Framingham Stroke Risk Score, prediction of future stroke may improve with a genetic risk score (GRS) based on single-nucleotide polymorphisms associated with stroke and its risk factors. METHODS: The study includes 4 population-based cohorts with 2047 first incident strokes from 22,720 initially stroke-free European origin participants aged ≥55 years, who were followed for up to 20 years. GRSs were constructed with 324 single-nucleotide polymorphisms implicated in stroke and 9 risk factors. The association of the GRS to first incident stroke was tested using Cox regression; the GRS predictive properties were assessed with area under the curve statistics comparing the GRS with age and sex, Framingham Stroke Risk Score models, and reclassification statistics. These analyses were performed per cohort and in a meta-analysis of pooled data. Replication was sought in a case-control study of ischemic stroke. RESULTS: In the meta-analysis, adding the GRS to the Framingham Stroke Risk Score, age and sex model resulted in a significant improvement in discrimination (all stroke: Δjoint area under the curve=0.016, P=2.3×10(-6); ischemic stroke: Δjoint area under the curve=0.021, P=3.7×10(-7)), although the overall area under the curve remained low. In all the studies, there was a highly significantly improved net reclassification index (P<10(-4)). CONCLUSIONS: The single-nucleotide polymorphisms associated with stroke and its risk factors result only in a small improvement in prediction of future stroke compared with the classical epidemiological risk factors for stroke.
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Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/genética , Factores de Edad , Anciano , Anciano de 80 o más Años , Área Bajo la Curva , Estudios de Casos y Controles , Estudios de Cohortes , Femenino , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple/genética , Curva ROC , Análisis de Regresión , Factores de Riesgo , Factores Sexuales , Población BlancaRESUMEN
BACKGROUND: We investigated whether circulating concentrations of soluble ST2, growth differentiation factor-15 (GDF-15), and high-sensitivity troponin I (hsTnI) are associated with incident atrial fibrillation (AF) and whether these biomarkers improve current risk prediction models including AF risk factors, B-type natriuretic peptide (BNP), and C-reactive protein (CRP). METHODS: We studied the relation between soluble ST2, GDF-15, and hsTnI and development of AF in Framingham Heart Study participants without prevalent AF. We used Cox proportional hazard regression analysis to examine the relation of incident AF during a 10-year follow-up period with each biomarker. We adjusted for standard AF clinical risk factors, BNP, and CRP. RESULTS: The mean age of the 3,217 participants was 59 ± 10 years, and 54% were women. During a 10-year follow-up, 242 participants developed AF. In age- and sex-adjusted models, GDF-15 and hsTnI were associated with risk of incident AF; however, after including the AF risk factors and BNP and CRP, only hsTnI was significantly associated with AF (hazard ratio per 1 SD of loge hsTnI, 1.12, 95% CI 1.00-1.26, P = .045). The c statistic of the base model including AF risk factors, BNP, and CRP was 0.803 (95% CI 0.777-0.830) and did not improve by adding individual or all 3 biomarkers. None of the discrimination and reclassification statistics were significant compared with the base model. CONCLUSION: In a community-based cohort, circulating hsTnI concentrations were associated with incident AF. None of the novel biomarkers evaluated improved AF risk discrimination or reclassification beyond standard clinical AF risk factors and biomarkers.
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Fibrilación Atrial/sangre , Biomarcadores/sangre , Proteína C-Reactiva/genética , Factor 15 de Diferenciación de Crecimiento/sangre , Péptido Natriurético Encefálico/genética , Receptores de Superficie Celular/sangre , Anciano , Fibrilación Atrial/epidemiología , Femenino , Humanos , Proteína 1 Similar al Receptor de Interleucina-1 , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Medición de Riesgo , Factores de RiesgoRESUMEN
OBJECTIVE: Based upon evidence in animal and in vitro studies, we tested the hypothesis that higher serum concentrations of the cytokines interleukin-6 (IL-6) and tumor necrosis factor α (TNFα) and the inflammatory marker C-reactive protein (CRP) would be inversely associated with bone mineral density (BMD) in a community-based cohort of men and women, with the strongest associations among postmenopausal women not receiving menopause hormonal therapy (MHT). METHODS: We ascertained fasting serum concentrations of IL-6, TNFα, and CRP and measured BMD at the femoral neck, trochanter, total femur, and spine (L2-L4) using dual x-ray absorptiometry in 2,915 members of the Framingham Offspring Study (1996-2001). We used multivariable linear regression to estimate the difference (ß) in BMD at each bone site associated with a 1-unit increase in log-transformed serum concentrations of IL-6, TNFα, and CRP separately for men (n = 1,293), premenopausal women (n = 231), postmenopausal women receiving MHT (n = 498), and postmenopausal women not receiving MHT (n = 893). RESULTS: Inflammatory biomarkers were not associated with BMD in men. Among premenopausal women, there were statistically significant, modest inverse associations between IL-6 and trochanter BMD (ß = -0.030, P < 0.01) and between CRP and femoral neck (ß = -0.015, P = 0.05) and trochanter BMD (ß = -0.014, P = 0.04). TNFα was positively associated with spine BMD (ß = 0.043, P = 0.01). In postmenopausal women receiving MHT, CRP was positively associated with femoral neck BMD (ß = 0.011, P = 0.04). There were no associations among postmenopausal women not receiving MHT. CONCLUSION: The lack of consistency in our results suggests that elevated circulating concentrations of inflammatory biomarkers may not be a risk factor for low BMD.
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Densidad Ósea/fisiología , Proteína C-Reactiva/metabolismo , Interleucina-6/sangre , Osteoporosis/sangre , Factor de Necrosis Tumoral alfa/sangre , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Femenino , Fémur/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Osteoporosis/diagnóstico por imagen , Radiografía , Factores de Riesgo , Columna Vertebral/diagnóstico por imagenRESUMEN
BACKGROUND: The relations between subclinical atherosclerosis and inflammatory biomarkers have generated intense interest but their significance remains unclear. We sought to determine the association between a panel of biomarkers and subclinical aortic atherosclerosis in a community-based cohort. METHODS AND RESULTS: We evaluated 1547 participants of the Framingham Heart Study Offspring cohort who attended the 7th examination cycle and underwent both cardiovascular magnetic resonance imaging (CMR) and assays for 10 biomarkers associated with atherosclerosis: high-sensitivity C-reactive protein, fibrinogen, intercellular adhesion molecule-1, interleukin-6, interleukin-18, lipoprotein-associated phospholipase-A2 activity and mass, monocyte chemoattractant protein-1, P-selectin, and tumor necrosis factor receptor-2. In logistic regression analysis, we found no significant association between the biomarker panel and the presence of aortic plaque (global P=0.53). Using Tobit regression with aortic plaque as a continuous variable, we noted a modest association between biomarker panel and aortic plaque volume in age- and sex-adjusted analyses (P=0.003). However, this association was attenuated after further adjustment for clinical covariates (P=0.09). CONCLUSIONS: In our community-based cohort, we found no significant association between our multibiomarker panel and aortic plaque. Our results underscore the strengths and limitations of the use of biomarkers for the identification of subclinical atherosclerosis and the importance of traditional risk factors.
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Aorta Abdominal/patología , Aorta Torácica/patología , Enfermedades de la Aorta/diagnóstico , Aterosclerosis/diagnóstico , Mediadores de Inflamación/sangre , Imagen por Resonancia Magnética , Factores de Edad , Anciano , Enfermedades de la Aorta/sangre , Enfermedades de la Aorta/patología , Aterosclerosis/sangre , Aterosclerosis/patología , Biomarcadores/sangre , Femenino , Humanos , Masculino , Massachusetts , Persona de Mediana Edad , Placa Aterosclerótica , Valor Predictivo de las Pruebas , Pronóstico , Factores de Riesgo , Factores SexualesRESUMEN
BACKGROUND: Atrial fibrillation (AF) patterns and their relations with long-term prognosis are uncertain, partly because pattern definitions are challenging to implement in longitudinal data sets. We developed a novel AF classification algorithm and examined AF patterns and outcomes in the community. METHODS AND RESULTS: We characterized AF patterns between 1980 and 2005 among Framingham Heart Study participants who survived ≥ 1 year after diagnosis. We classified participants based on their pattern within the first 2 years after detection as having AF without recurrence, recurrent AF, or sustained AF. We examined associations between AF patterns and 10-year survival using proportional hazards regression. Among 612 individuals with AF, mean age was 72.5 ± 10.8 years, and 53% were men. Of these, 478 participants had ≥ 2 electrocardiograms (median, 3; limits 2 to 23) within 2 years after initial AF and were classified as having AF without 2-year recurrence (n = 63, 10%), recurrent AF (n = 162, 26%) or sustained AF (n = 207, 34%), although some (n = 46, 8%) were indeterminate. Of 432 classified participants, 363 died, 75 had strokes, and 110 were diagnosed with heart failure during the next 10 years. Relative to individuals without AF recurrence, the multivariable-adjusted mortality was higher among people with recurrent AF (hazard ratio [HR], 2.04; 95% confidence interval [CI], 1.26 to 3.29) and sustained AF (HR, 2.36; 95% CI, 1.49 to 3.75). CONCLUSIONS: In our community-based AF sample, only 10% had AF without early-term (2-year) recurrence. Compared with individuals without 2-year AF recurrences, the 10-year prognosis was worse for individuals with either sustained or recurrent AF. Our proposed AF classification algorithm may be applicable in longitudinal data sets.
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Fibrilación Atrial/complicaciones , Fibrilación Atrial/mortalidad , Insuficiencia Cardíaca/etiología , Accidente Cerebrovascular/etiología , Anciano , Femenino , Humanos , Masculino , PronósticoRESUMEN
STUDY OBJECTIVES: Sleep disordered breathing is associated with cardiovascular disease. The pathophysiologic mechanisms remain unclear, but enhanced vascular inflammation is implicated. We sought to evaluate the association of sleep disordered breathing with biomarkers of inflammation. DESIGN: Cross-sectional, observational. SETTING: Community-based. PARTICIPANTS: There were 900 participants from the Framingham Heart Study site of the Sleep Heart Health Study (52% females, mean age 60 y, 23% ethnic minorities). INTERVENTIONS: None. MEASUREMENTS: We assessed circulating levels of nine inflammatory biomarkers in relation to polysomnographically-derived apnea-hypopnea index and hypoxemia index (% sleep time with oxyhemoglobin saturation < 90%). Multivariable models were adjusted for demographics, smoking, cardiovascular diseases, diabetes, and other potential confounders, without and with adjustment for body mass index. RESULTS: With multivariable adjustment not including body mass index, the apnea-hypopnea index was associated with C-reactive protein, inter-leukin-6, fibrinogen, intercellular adhesion molecule-1, and P-selectin levels and hypoxemia index was associated with C-reactive protein, interleukin-6, and fibrinogen levels. After adjustment for body mass index, only the association of interleukin-6 with sleep disordered breathing remained significant: the adjusted mean serum interleukin-6 level was 2.93, 3.14, 3.34, and 4.62 pg/mL, respectively, in participants with apnea-hypopnea index < 5, 5-14.9, 15-29.9, and ≥ 30 events/h (P = 0.01 for trend) and 2.97, 3.01, 3.35, and 4.85 pg/mL, respectively, in participants with hypoxemia index < 0.5, 0.5-4.9, 5-9.9, and ≥ 10% of sleep time (P = 0.02 for trend). CONCLUSIONS: In a community-based sample, sleep disordered breathing is associated with higher levels of interleukin-6, a marker of myocardial infarction risk and mortality. Adiposity may mediate the increased levels of C-reactive protein, fibrinogen, intercellular adhesion molecule-1, and P-selectin observed in sleep disordered breathing.
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Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/complicaciones , Síndromes de la Apnea del Sueño/sangre , Síndromes de la Apnea del Sueño/complicaciones , Anciano , Biomarcadores/sangre , Índice de Masa Corporal , Proteína C-Reactiva/metabolismo , Estudios de Cohortes , Femenino , Humanos , Inflamación/sangre , Inflamación/etiología , Molécula 1 de Adhesión Intercelular/sangre , Interleucina-6/sangre , Masculino , Persona de Mediana Edad , Selectina-P/sangre , PolisomnografíaRESUMEN
OBJECTIVE: Evidence suggests that chronic low-grade inflammation and oxidative stress are related to cardiovascular disease (CVD) and mortality. APPROACH AND RESULTS: We examined 11 established and novel biomarkers representing inflammation and oxidative stress (C-reactive protein, fibrinogen, interleukin-6, intercellular adhesion molecule-1, lipoprotein-associated phospholipase-A2 [mass and activity], monocyte chemoattractant protein-1, myeloperoxidase, CD40 ligand, P-selectin, and tumor necrosis factor receptor II [TNFRII]) in relation to incident major CVD and mortality in the community. We studied 3035 participants (mean age, 61 ± 9 years; 53% women). During follow-up (median, 8.9 years), 253 participants experienced a CVD event and 343 died. C-reactive protein (hazard ratio [HR] reported per SD ln-transformed biomarker, 1.18; 95% confidence interval [CI], 1.02-1.35; nominal P=0.02) and TNFRII (HR, 1.15; 95% CI, 1.01-1.32; nominal P=0.04) were retained in multivariable-adjusted models for major CVD, but were not significant after adjustment for multiple testing. The biomarkers related to mortality were TNFRII (HR, 1.33; 95% CI, 1.19-1.49; P<0.0001), ICAM-1 (HR, 1.24; 95% CI, 1.12-1.37; P<0.0001), and interleukin-6 (HR, 1.25; 95% CI, 1.12-1.39; P<0.0001). The addition of these markers to the model, including traditional risk factors, increased discrimination and reclassification for risk of death (P<0.0001), but not for CVD. CONCLUSIONS: Of 11 inflammatory biomarkers tumor necrosis factor receptor II was related to cardiovascular disease and mortality in the Framingham Heart Study. The combination of TNFRII with C-reactive protein in relation to CVD and with interleukin-6 to mortality increased the predictive ability in addition to CVD risk factors for total mortality but not for incident CVD.
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Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/mortalidad , Mediadores de Inflamación/sangre , Inflamación/sangre , Inflamación/mortalidad , Anciano , Biomarcadores/sangre , Proteína C-Reactiva/metabolismo , Supervivencia sin Enfermedad , Femenino , Encuestas Epidemiológicas , Humanos , Incidencia , Molécula 1 de Adhesión Intercelular/sangre , Interleucina-6/sangre , Masculino , Massachusetts/epidemiología , Persona de Mediana Edad , Análisis Multivariante , Análisis de Componente Principal , Pronóstico , Modelos de Riesgos Proporcionales , Receptores Tipo II del Factor de Necrosis Tumoral/sangre , Medición de Riesgo , Factores de Riesgo , Factores de TiempoRESUMEN
Increased systemic levels of myeloperoxidase (MPO) are associated with the risk of coronary artery disease (CAD). To identify the genetic factors that are associated with circulating MPO levels, we carried out a genome-wide association study (GWAS) and a gene-centric analysis in subjects of European ancestry and African Americans (AAs). A locus on chromosome 1q31.1 containing the complement factor H (CFH) gene was strongly associated with serum MPO levels in 9305 subjects of European ancestry (lead SNP rs800292; P = 4.89 × 10(-41)) and in 1690 AA subjects (rs505102; P = 1.05 × 10(-8)). Gene-centric analyses in 8335 subjects of European ancestry additionally identified two rare MPO coding sequence variants that were associated with serum MPO levels (rs28730837, P = 5.21 × 10(-12); rs35897051, P = 3.32 × 10(-8)). A GWAS for plasma MPO levels in 9260 European ancestry subjects identified a chromosome 17q22 region near MPO that was significantly associated (lead SNP rs6503905; P = 2.94 × 10(-12)), but the CFH locus did not exhibit evidence of association with plasma MPO levels. Functional analyses revealed that rs800292 was associated with levels of complement proteins in serum. Variants at chromosome 17q22 also had pleiotropic cis effects on gene expression. In a case-control analysis of â¼80 000 subjects from CARDIoGRAM, none of the identified single-nucleotide polymorphisms (SNPs) were associated with CAD. These results suggest that distinct genetic factors regulate serum and plasma MPO levels, which may have relevance for various acute and chronic inflammatory disorders. The clinical implications for CAD and a better understanding of the functional basis for the association of CFH and MPO variants with circulating MPO levels require further study.
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Factor H de Complemento/genética , Peroxidasa/sangre , Peroxidasa/genética , Adulto , Negro o Afroamericano/genética , Anciano , Estudios de Casos y Controles , Enfermedad de la Arteria Coronaria/genética , Femenino , Regulación Enzimológica de la Expresión Génica , Estudios de Asociación Genética , Variación Genética , Estudio de Asociación del Genoma Completo , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Población Blanca/genética , Adulto JovenRESUMEN
BACKGROUND: Atrial fibrillation (AF) is a strong risk factor for heart failure (HF); HF onset in patients with AF is associated with increased morbidity and mortality. Risk factors that predict HF in individuals with AF in the community are not well established. METHODS AND RESULTS: We examined clinical variables related to the 10-year incidence of HF in 725 individuals (mean 73.3 years, 45% women) with documented AF in the Framingham Heart Study. Event rates for incident HF (n = 161, 48% in women) were comparable in women (4.30 per 100 person-years) and men (3.34 per 100 person-years). Age, body mass index, ECG LV hypertrophy, diabetes, significant murmur, and history of myocardial infarction were positively associated with incident HF in multivariable models (C-statistic 0.71; 95% confidence interval 0.67-0.75). We developed a risk algorithm for estimating absolute risk of HF in AF patients with good model fit and calibration (adjusted calibration χ2 statistic 7.29; P(χ2) = 0.61). Applying the algorithm, 47.6% of HF events occurred in the top tertile in men compared with 13.1% in the bottom tertile, and 58.4% in women in the upper tertile compared with 18.2% in the lowest category. For HF type, women had a non-significantly higher incidence of HF with preserved EF compared with men. CONCLUSIONS: We describe advancing age, LV hypertrophy, body mass index, diabetes, significant heart murmur, and history of myocardial infarction as clinical predictors of incident HF in individuals with AF. A risk algorithm may help identify individuals with AF at high risk of developing HF.
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Fibrilación Atrial/epidemiología , Insuficiencia Cardíaca/epidemiología , Medición de Riesgo/métodos , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Algoritmos , Índice de Masa Corporal , Estudios de Cohortes , Diabetes Mellitus/epidemiología , Femenino , Soplos Cardíacos/epidemiología , Humanos , Hipertrofia Ventricular Izquierda/epidemiología , Incidencia , Masculino , Persona de Mediana Edad , Análisis Multivariante , Infarto del Miocardio/epidemiología , Sobrepeso/epidemiología , Modelos de Riesgos Proporcionales , Factores de RiesgoRESUMEN
OBJECTIVES: Traditional clinical risk factors are associated with inflammation cross-sectionally, but associations of longitudinal variation in inflammatory biomarkers with corresponding changes in clinical risk factors are incompletely described. We sought to analyze clinical factors associated with change in inflammation in the community. METHODS: We studied 3013 Framingham Offspring (n = 2735) and Omni Cohort (n = 278) participants (mean age 59 years, 55% women, 9% ethnic/racial minority) who attended two consecutive examination cycles (mean 6.7 years apart). We selected ten inflammatory biomarkers representing distinctive biological functions: C-reactive protein (CRP), intercellular adhesion molecule-1, interleukin-6, isoprostanes, lipoprotein-associated phospholipase-2 (Lp-PLA2) activity, Lp-PLA2-mass, monocyte chemoattractant protein-1, osteoprotegerin, P-selectin, and tumor necrosis factor receptor II (TNFRII). We constructed multivariable-adjusted regression models to assess the relations of baseline, follow-up and change in clinical risk factors with change in biomarker concentrations over time. RESULTS: Baseline, follow-up and change in clinical risk factors explain a moderate amount of the variation in biomarker concentrations across 2 consecutive examinations (ranging from r(2) = 0.28 [TNFRII] up to 0.52 [Lp-PLA2-mass]). In multivariable models, increasing body-mass index, smoking initiation, worsening lipid profile, and increasing waist size were associated with increasing concentrations of several biomarkers. Conversely, hypercholesterolemia therapy and hormone replacement cessation were associated with decreasing concentrations of biomarkers such as CRP, Lp-PLA2-mass and activity. CONCLUSION: Cardiovascular risk factors have different patterns of association with longitudinal change in inflammatory biomarkers and explain modest amounts of variability in biomarker concentrations. Nevertheless, a substantial proportion of longitudinal change in inflammatory markers is not explained by traditional risk factors.
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Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/metabolismo , Vasculitis/epidemiología , Vasculitis/metabolismo , 1-Alquil-2-acetilglicerofosfocolina Esterasa/sangre , Anciano , Biomarcadores/sangre , Proteína C-Reactiva/metabolismo , Enfermedades Cardiovasculares/inmunología , Quimiocina CCL2/sangre , Femenino , Humanos , Inflamación/epidemiología , Inflamación/inmunología , Inflamación/metabolismo , Molécula 1 de Adhesión Intercelular/sangre , Interleucina-6/sangre , Isoprostanos/sangre , Estudios Longitudinales , Masculino , Massachusetts/epidemiología , Persona de Mediana Edad , Osteoprotegerina/sangre , Selectina-P/sangre , Receptores Tipo II del Factor de Necrosis Tumoral/sangre , Factores de Riesgo , Vasculitis/inmunologíaRESUMEN
BACKGROUND: Tools for the prediction of atrial fibrillation (AF) may identify high-risk individuals more likely to benefit from preventive interventions and serve as a benchmark to test novel putative risk factors. METHODS AND RESULTS: Individual-level data from 3 large cohorts in the United States (Atherosclerosis Risk in Communities [ARIC] study, the Cardiovascular Health Study [CHS], and the Framingham Heart Study [FHS]), including 18 556 men and women aged 46 to 94 years (19% African Americans, 81% whites) were pooled to derive predictive models for AF using clinical variables. Validation of the derived models was performed in 7672 participants from the Age, Gene and Environment-Reykjavik study (AGES) and the Rotterdam Study (RS). The analysis included 1186 incident AF cases in the derivation cohorts and 585 in the validation cohorts. A simple 5-year predictive model including the variables age, race, height, weight, systolic and diastolic blood pressure, current smoking, use of antihypertensive medication, diabetes, and history of myocardial infarction and heart failure had good discrimination (C-statistic, 0.765; 95% CI, 0.748 to 0.781). Addition of variables from the electrocardiogram did not improve the overall model discrimination (C-statistic, 0.767; 95% CI, 0.750 to 0.783; categorical net reclassification improvement, -0.0032; 95% CI, -0.0178 to 0.0113). In the validation cohorts, discrimination was acceptable (AGES C-statistic, 0.664; 95% CI, 0.632 to 0.697 and RS C-statistic, 0.705; 95% CI, 0.664 to 0.747) and calibration was adequate. CONCLUSION: A risk model including variables readily available in primary care settings adequately predicted AF in diverse populations from the United States and Europe.
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Fibrilación Atrial/epidemiología , Medición de Riesgo/métodos , Negro o Afroamericano/estadística & datos numéricos , Factores de Edad , Anciano , Anciano de 80 o más Años , Fibrilación Atrial/etnología , Estudios de Cohortes , Diabetes Mellitus/epidemiología , Femenino , Insuficiencia Cardíaca/epidemiología , Humanos , Hipertensión/epidemiología , Islandia/epidemiología , Incidencia , Masculino , Persona de Mediana Edad , Infarto del Miocardio/epidemiología , Países Bajos/epidemiología , Modelos de Riesgos Proporcionales , Fumar/epidemiología , Estados Unidos/epidemiología , Población Blanca/estadística & datos numéricosRESUMEN
Heart failure, a strong risk factor for atrial fibrillation (AF), is often accompanied by elevated liver transaminases. The aim of this study was to test the hypothesis that elevated transaminases are associated with the risk for incident AF in the community. A total of 3,744 participants (mean age 65 ± 10 years, 56.8% women) from the Framingham Heart Study Original and Offspring cohorts, free of clinical heart failure, were studied. Cox proportional-hazards models adjusted for standard AF risk factors (age, gender, body mass index, systolic blood pressure, electrocardiographic PR interval, antihypertensive treatment, smoking, diabetes, valvular heart disease, and alcohol consumption) were examined to investigate associations between baseline serum transaminase levels (alanine transaminase and aspartate transaminase) and the incidence of AF over up to 10 years (29,099 person-years) of follow-up. During follow-up, 383 subjects developed AF. The 2 transaminases were significantly associated with greater risk for incident AF (hazard ratio expressed per SD of natural logarithmically transformed biomarker: alanine transaminase hazard ratio 1.19, 95% confidence interval 1.07 to 1.32, p = 0.002; aspartate transaminase hazard ratio 1.12, 95% confidence interval 1.01 to 1.24, p = 0.03). The associations between transaminases and AF remained consistent after the exclusion of participants with moderate to severe alcohol consumption. However, when added to known risk factors for AF, alanine transaminase and aspartate transaminase only subtly improved the prediction of AF. In conclusion, elevated transaminase concentrations are associated with increased AF incidence. The mechanisms by which higher mean transaminase concentrations are associated with incident AF remain to be determined.
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Fibrilación Atrial/enzimología , Insuficiencia Cardíaca/epidemiología , Hígado/enzimología , Medición de Riesgo/métodos , Transaminasas/sangre , Anciano , Fibrilación Atrial/complicaciones , Biomarcadores/sangre , Intervalos de Confianza , Femenino , Estudios de Seguimiento , Insuficiencia Cardíaca/enzimología , Insuficiencia Cardíaca/etiología , Humanos , Incidencia , Masculino , Massachusetts/epidemiología , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , Factores de TiempoRESUMEN
BACKGROUND: Prior studies have reported conflicting findings with regard to the association of biomarkers in the prediction of incident type 2 diabetes. We evaluated 12 biomarkers as possible diabetes predictors in the Framingham Heart Study. METHODS AND RESULTS: Biomarkers representing inflammation (C-reactive protein, interleukin-6, monocyte chemoattractant protein-1, tumor necrosis factor receptor 2, osteoprotegerin, and fibrinogen), endothelial dysfunction (intercellular adhesion molecule-1), vascular damage (CD40-ligand, P-selectin, and lipoprotein-associated phospholipase A2 mass and activity), and oxidative stress (urinary isoprostanes) were measured in participants without diabetes attending the Offspring seventh (n=2499) or multiethnic Omni second (n=189) examination (1998-2001). Biomarkers were log(e) transformed and standardized. Multivariable logistic regression tested each biomarker in association with incident diabetes at a follow-up examination (the Offspring eighth and Omni third examination; mean 6.6 years later), with adjustment for age, sex, cohort, body mass index, fasting glucose, systolic blood pressure, high-density lipoprotein cholesterol, triglycerides, and smoking. C statistics were evaluated with and without inflammatory markers. In 2638 participants (56% women, mean age 59 years), 162 (6.1%) developed type 2 diabetes. All biomarkers, excluding osteoprotegerin, were associated with the outcome with adjustment for age, sex, and cohort; however, none remained significant after multivariable adjustment (all P>0.05). The c statistic from the model including only clinical covariates (0.89) did not statistically significantly improve after addition of biomarkers (all P>0.10). CONCLUSIONS: Biomarkers representing different inflammatory pathways are associated with incident diabetes but do not remain statistically significant after adjustment for established clinical covariates. Inflammatory biomarkers might not be an effective resource to predict type 2 diabetes in community-based samples. (J Am Heart Assoc. 2012;1:e000737 doi: 10.1161/JAHA.112.000869.).
RESUMEN
BACKGROUND: Atrial fibrillation is common among older persons. Catheter ablation is increasingly used in patients for whom medical therapy has failed. METHODS AND RESULTS: We conducted a retrospective cohort study of all fee-for-service Medicare beneficiaries ≥65 years of age who underwent catheter ablation for atrial fibrillation between July 1, 2007, and December 31, 2009. The main outcome measures were major complications within 30 days and mortality, heart failure, stroke, hospitalization, and repeat ablation within 1 year. A total of 15 423 patients underwent catheter ablation for atrial fibrillation. Mean age was 72 years; 41% were women; and >95% were white. For every 1000 procedures, there were 17 cases of hemopericardium requiring intervention, 8 cases of stroke, and 8 deaths within 30 days. More than 40% of patients required hospitalization within 1 year; however, atrial fibrillation or flutter was the primary discharge diagnosis in only 38.4% of cases. Eleven percent of patients underwent repeat ablation within 1 year. Renal impairment (hazard ratio, 2.07; 95% confidence interval, 1.66-2.58), age ≥80 years (hazard ratio, 3.09; 95% confidence interval, 2.32-4.11), and heart failure (hazard ratio, 2.54; 95% confidence interval, 2.07-3.13) were major risk factors for 1-year mortality. Advanced age was a major risk factor for all adverse outcomes. CONCLUSIONS: Major complications after catheter ablation for atrial fibrillation were associated with advanced age but were fairly infrequent. Few patients underwent repeat ablation. Randomized trials are needed to inform risk-benefit calculations for older persons with drug-refractory, symptomatic atrial fibrillation.