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2.
J Card Fail ; 2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-32205188

RESUMO

BACKGROUND: Exercise oscillatory ventilation (EOV) is a consequence of ventilatory control system instability frequently observed in advanced heart failure (HF) patients and is associated with adverse prognosis. The goal of this study was to evaluate the effect of cardiac resynchronization therapy (CRT) on oscillatory ventilation as quantified by a proposed EOV score. METHODS AND RESULTS: Consecutive HF patients (n=35) who underwent clinically-indicated CRT, cardiopulmonary exercise testing (CPET) and carbon dioxide (CO2) chemosensitivity by re-breathe before and 4-6 months after CRT were included in this post-hoc analysis. EOV score improved in 22 patients (63%) with CRT. In these patients, left ventricular ejection fraction (LVEF), left atrial volume, brain natriuretic peptide concentration and CO2 chemosensitivity significantly improved post-CRT (p<0.05). Furthermore, VE/VCO2 significantly decreased and end-tidal CO2 increased at rest and peak exercise post-CRT. Multiple regression analysis showed only the change of CO2 chemosensitivity to be significantly associated with the improvement of EOV score (b=0.64; F=11.3; p=0.004). In the EOV score non-improvement group (n=13), though LVEF significantly increased with CRT (p=0.015), no significant changes in ventilation or gas exchange were observed. CONCLUSION: EOV score was mitigated by CRT and associated with decreased CO2 chemosensitivity.

3.
Eur Heart J ; 41(12): 1273-1282, 2020 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-32047900

RESUMO

AIMS: Right ventricular dysfunction (RVD) is an important determinant of functional status and survival in various diseases states. Data are sparse on the epidemiology and outcome of patients with severe RVD. This study examined the characteristics, aetiology, and survival of patients with severe RVD. METHODS AND RESULTS: Retrospective study of consecutive patients with severe RVD diagnosed by transthoracic echocardiography (TTE) between 2011 and 2015 in a single tertiary referral institution. Patients with prior cardiac surgery, mechanical assist devices, and congenital heart disease were excluded. Primary endpoint was all-cause mortality. In 64 728 patients undergoing TTE, the prevalence of ≥mild RVD was 21%. This study focused on the cohort of 1299 (4%) patients with severe RVD; age 64 ± 16 years; 61% male. The most common causes of severe RVD were left-sided heart diseases (46%), pulmonary thromboembolic disease (18%), chronic lung disease/hypoxia (CLD; 17%), and pulmonary arterial hypertension (PAH; 11%). After 2 ± 2 years of follow-up, 701 deaths occurred, 66% within the first year of diagnosis. The overall probability of survival at 1- and 5 years for the entire cohort were 61% [95% confidence interval (CI) 58-64%] and 35% (95% CI 31-38%), respectively. In left-sided heart diseases, 1- and 5-year survival rates were 61% (95% CI 57-65%) and 33% (95% CI 28-37%), respectively; vs. 76% (95% CI 68-82%) and 50% (95% CI 40-59%) in PAH, vs. 71% (95% CI 64-76%) and 49% (95% CI 41-58%) in thromboembolic diseases, vs. 42% (95% CI 35-49%) and 8% (95% CI 4-15%) in CLD (log-rank P < 0.0001). Presence of ≥moderate tricuspid regurgitation portended worse survival in severe RVD. CONCLUSION: One-year mortality of patients with severe RVD was high (∼40%) and dependent on the aetiology of RVD. Left-sided heart diseases is the most common cause of severe RVD but prognosis was worst in CLD.

4.
J Am Coll Cardiol ; 75(1): 29-39, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31918832

RESUMO

BACKGROUND: The prognostic significance of diastolic blood pressure (DBP) and resting heart rate (RHR) in patients with hemodynamically significant aortic regurgitation (AR) is unknown. OBJECTIVES: This study sought to investigate the association of DBP and RHR with all-cause mortality in patients with AR. METHODS: Consecutive patients with ≥ moderate to severe AR were retrospectively identified from 2006 to 2017. The association between all-cause mortality and routinely measured DBP and RHR was examined. RESULTS: Of 820 patients (age 59 ± 17 years; 82% men) followed for 5.5 ± 3.5 years, 104 died under medical management, and 400 underwent aortic valve surgery (AVS). Age, symptoms, left ventricular ejection fraction (LVEF), LV end-systolic diameter-index (LVESDi), DBP, and RHR were univariable predictors of all-cause mortality (all p ≤ 0.002). When adjusted for demographics, comorbidities, and surgical triggers (symptoms, LVEF, and LVESDi), baseline DBP (adjusted-hazard ratio [HR]: 0.79 [95% confidence interval: 0.66 to 0.94] per 10 mm Hg increase, p = 0.009) and baseline RHR (adjusted HR: 1.23 [95% confidence interval: 1.03 to 1.45] per 10 beat per min [bpm] increase, p = 0.01) were independently associated with all-cause mortality. These associations persisted after adjustment for presence of hypertension, medications, time-dependent AVS, and using average DBP and RHR (all p ≤ 0.02). Compared with the general population, patients with AR exhibited excess mortality (relative risk of death >1), which rose steeply in inverse proportion (p nonlinearity = 0.002) to DBP starting at 70 mm Hg and peaking at 55 mm Hg and in direct proportion to RHR starting at 60 bpm. CONCLUSIONS: In patients with chronic hemodynamically significant AR, routinely measured DBP and RHR demonstrate a robust association with all-cause death, independent of demographics, comorbidities, guideline-based surgical triggers, presence of hypertension, and use of medications. Therefore, DBP and RHR should be integrated into comprehensive clinical decision-making for these patients.

6.
Mayo Clin Proc ; 95(1): 124-133, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31902407

RESUMO

OBJECTIVES: To delineate the impact of diabetes mellitus (DM) on the development of cardiovascular diseases in a community population. PATIENTS & METHODS: Cross-sectional survey of residents randomly selected through the Rochester Epidemiology Project, 45 years or older, of Olmsted County as of June 1, 1997, through September 30, 2000. Responders (2042) underwent assessment of systolic and diastolic function using echocardiography. The current analyses included all participants with DM and were compared with a group of participants without DM matched 1:2 for age, sex, hypertension, and coronary artery disease. Baseline characteristics and laboratory and echocardiography findings between groups were compared along with rates of mortality due to various cardiovascular conditions. RESULTS: We identified 116 participants with DM and 232 matched participants without DM. Those with DM had a higher body mass index and plasma insulin and serum glucose levels. Although left ventricular ejection fractions were similar, E/e' ratio (9.7 vs 8.5; P=.001) was higher in DM vs non-DM. During a follow-up of 10.8 (interquartile range, 7.8-11.7) years, participants with DM had a higher incidence of heart failure (HF); hazard ratio, 2.1; 95% confidence limits, 1.2-3.6; P=.01) and 10-year Kaplan-Meier rate of 21% (22 of 116) vs 12% (24 of 232) compared with those without DM. We also examined the subgroup of participants without diastolic dysfunction. In this subgroup, those with DM had an increased risk for HF; hazard ratio, 2.5; 95% confidence limits, 1.0-6.3; P=.04). CONCLUSION: In this cohort, participants with DM have an increased incidence of HF over a 10-year follow-up period even in the absence of underlying diastolic dysfunction. These findings suggest that DM is an independent risk factor for the development of HF and supports the concept of DM cardiomyopathy.


Assuntos
Diabetes Mellitus , Insuficiência Cardíaca , Volume Sistólico , Função Ventricular Esquerda , Glicemia/análise , Índice de Massa Corporal , Estudos Transversais , Diabetes Mellitus/sangue , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia , Ecocardiografia Doppler/métodos , Ecocardiografia Doppler/estatística & dados numéricos , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/epidemiologia , Humanos , Incidência , Insulina/análise , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Minnesota/epidemiologia , Mortalidade , Sistema de Registros/estatística & dados numéricos , Fatores de Risco
7.
JACC Heart Fail ; 8(1): 70-80, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31392960

RESUMO

BACKGROUND: In heart failure with reduced ejection fraction (HFrEF), elevated soluble neprilysin (sNEP) levels are associated with an increased risk of cardiovascular death, and its inhibition with sacubitril/valsartan has improved survival. OBJECTIVES: This study sought to determine the relevance of sNEP as a biomarker in heart failure with preserved ejection fraction (HFpEF) and to compare circulating sNEP levels in patients with HFpEF with normal controls. METHODS: A case-control study was performed in 242 symptomatic patients with HFpEF previously enrolled in the Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Heart Failure with Preserved Ejection Fraction (RELAX) and Nitrates's Effect on Activity Tolerance in Heart Failure With Preserved Ejection (NEAT-HFpEF) clinical trials and 891 asymptomatic subjects without HF or diastolic dysfunction (confirmed by NT-proBNP levels <200 pg/ml and echocardiography) who were enrolled in the Prevalence of Asymptomatic Left Ventricular Dysfunction study. sNEP was measured using a sandwich enzyme-linked immunosorbent assay (ELISA) in all subjects. RESULTS: Overall, sNEP levels were lower in HFpEF compared with controls (3.5 ng/ml; confidence interval [CI]: 2.5 to 4.8 vs. 8.5 ng/ml; CI: 7.2 to 10.0; p < 0.001). After adjusting for age, gender, body mass index (BMI), and smoking history, mean sNEP levels were also lower in HFpEF compared with controls (4.0 ng/ml [CI: 2.7 to 5.4] vs. 8.2 ng/ml [CI: 6.8 to 9.7]; p = 0.002). The cohorts were propensity matched based on age, BMI, diabetes, hypertension, smoking history, and renal function, and sNEP levels remained lower in HFpEF compared with controls (median 2.4 ng/ml [interquartile range: 0.6 to 27.7] vs. 4.9 ng/ml [interquartile range: 1.2 to 42.2]; p = 0.02). CONCLUSIONS: Patients with HFpEF on average have significantly lower circulating sNEP levels compared with controls. These findings challenge our current understanding of the complex biology of circulating sNEP in HFpEF.

8.
Heart ; 106(4): 280-286, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31439661

RESUMO

OBJECTIVES: To examine the prognostic significance of atrial fibrillation (AF) versus sinus rhythm (SR) on the management and outcomes of patients with severe aortic stenosis (AS). METHODS: 1847 consecutive patients with severe AS (aortic valve area ≤1.0 cm2 and aortic valve systolic mean Doppler gradient ≥40 mm Hg or peak velocity ≥4 m/s) and left ventricular ejection fraction ≥50% were identified. The independent association of AF and all-cause mortality was assessed. RESULTS: Age was 76±11 years and 46% were female; 293 (16%) patients had AF and 1554 (84%) had SR. In AF, 72% were symptomatic versus 71% in SR. Survival rate at 5 years for AF (41%) was lower than SR (65%) (age- and sex-adjusted HR=1.66 (1.40-1.98), p<0.0001). In multivariable analysis, factors associated with mortality included age (HR per 10 years=1.55 (1.42-1.69), p<0.0001), dyspnoea (HR=1.58 (1.33-1.87), p<0.0001), ≥ moderate mitral regurgitation (HR=1.63 (1.22-2.18), p=0.001), right ventricular systolic dysfunction (HR=1.88 (1.52-2.33), p<0.0001), left atrial volume index (HR per 10 mL/m2=1.13 (1.07-1.19), p<0.0001) and aortic valve replacement (AVR) (HR=0.44 (0.38-0.52), p<0.0001). AF was not a predictor of mortality independent of variables strongly correlated HR=1.02 (0.84-1.25), p=0.81). The 1-year probability of AVR following diagnosis of severe AS was lower in AF (49.8%) than SR (62.5%) (HR=0.73 (0.62-0.86), p<0.001); among patients with AF not referred for AVR, symptoms were frequently attributed to AF instead of AS. CONCLUSION: AF was associated with poor prognosis in patients with severe AS, but apparent differences in outcomes compared with SR were explained by factors other than AF including concomitant cardiac abnormalities and deferral of AVR due to attribution of cardiac symptoms to AF.

9.
Mayo Clin Proc ; 94(11): 2189-2198, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31668448

RESUMO

OBJECTIVE: To classify subjects in a general population per their renal function and characterize the cardiac biomarker levels, left ventricular function and cardiovascular outcomes over a 10.2 year follow-up period (interquartile range, 5.1-11.4 years). METHODS: This was a retrospective review of a population-based random sample of residents aged ≥45 years. Data were collected between January 1, 1997, and December 31, 2000. One thousand nine hundred eighty-one individuals were classified based on estimated glomerular filtration rate (eGFR) into group I (>90 mL/min/1.73 m2), group II (60 to 89 mL/min/1.73 m2) and group III (<60 mL/min/1.73 m2; chronic kidney disease [CKD]). Age/sex-adjusted baseline characteristics, tertiles of N-terminal pro B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hs-TnT) and their interactions with eGFR were examined. Outcomes measured included incident myocardial infarction (MI), congestive heart failure, stroke, and all-cause mortality. RESULTS: Eight hundred nineteen patients were classified as group I, 1036 as group II, and 126 of 1981 (6.4%) as group III or CKD. Subjects in group III were older and had a higher incidence of hypertension, diabetes, and MI at baseline. Over a 10.2-year follow-up period, CKD was associated with an increased risk of MI (hazard ratio, 1.95; 95% CI, 1.2-3.14; P=.006) and composite cardiovascular outcomes including MI, congestive heart failure, stroke, and all-cause mortality (hazard ratio, 1.38; 95% CI, 1.05-1.83 ;P=.02). Subjects with NT-proBNP or hs-TnT in the third tertile were at greater risk of cardiovascular events without significant interactions between eGFR and levels of NT-proBNP and hs-TnT. CONCLUSION: Subjects with CKD had significantly elevated cardiac biomarkers and were at an increased risk of MI and adverse cardiovascular events. This warrants future studies to investigate whether these cardiac biomarkers could identify high-risk CKD patients for aggressive management of cardiovascular risk factors.


Assuntos
Doenças Cardiovasculares/sangue , Taxa de Filtração Glomerular/fisiologia , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Insuficiência Renal Crônica/sangue , Idoso , Biomarcadores/sangue , Doenças Cardiovasculares/etiologia , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/complicações , Estudos Retrospectivos , Fatores de Risco
11.
J Am Coll Cardiol ; 74(20): 2480-2492, 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31727286

RESUMO

BACKGROUND: The natural history of stage B aortic regurgitation (AR) is unknown. OBJECTIVES: This study sought to examine determinants, rate, and consequences of progression of AR. METHODS: Consecutive patients with ≤moderate chronic AR quantified by effective regurgitant orifice area (EROA) and regurgitant volume (RVol) from 2004 to 2017 who had ≥1 subsequent echocardiogram with quantitation were included. RESULTS: Of 1,077 patients (66 ± 15 years of age), baseline trivial/mild AR was noted in 196 (18%), mild-to-moderate AR in 465 (43%), and moderate AR in 416 (39%); 10-year incidence of progression to ≥moderate-severe AR (stage C/D; progressors) was 12%, 30%, and 53%, respectively. At 4.1-year follow-up (interquartile range: 2.1 to 7.2 years), there were 228 progressors (21%), whose annualized progression rates within 3 years before diagnosis of ≥moderate-severe AR were 4.2 mm2/year for EROA and 9.9 ml/year for RVol. Baseline AR severity and dimensions of sinotubular junction and annulus were associated with progression (all p ≤ 0.007); hypertension and systolic blood pressure were not. Progressors had faster chamber remodeling, functional class decline, and more aortic valve/aortic surgery. At medium-term follow-up, 242 patients (22%) died; poor survival was linked to age, comorbidities, functional class, resting heart rate, and left ventricular (LV) ejection fraction (p ≤ 0.003), not LV end-systolic dimension index. Survival after progression to stage C/D AR was associated with LV end-systolic dimension index (adjusted p = 0.02). CONCLUSIONS: Progression from stage B to stage C/D AR was observed in 21% patients. Repeat echocardiography for trivial/mild, mild-to-moderate, and moderate AR at every 5, 3, and 1 years, respectively, was reasonable. EROA, RVol, annulus, and sinotubular junction should be routinely measured to estimate progression rates and identify patients at high risk of progression, which was associated with adverse consequences.

12.
Breast Cancer Res ; 21(1): 118, 2019 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-31660981

RESUMO

BACKGROUND: Given that breast cancer and normal dense fibroglandular tissue have similar radiographic attenuation, we examine whether automated volumetric density measures identify a differential change between breasts in women with cancer and compare to healthy controls. METHODS: Eligible cases (n = 1160) had unilateral invasive breast cancer and bilateral full-field digital mammograms (FFDMs) at two time points: within 2 months and 1-5 years before diagnosis. Controls (n = 2360) were matched to cases on age and date of FFDMs. Dense volume (DV) and volumetric percent density (VPD) for each breast were assessed using Volpara™. Differences in DV and VPD between mammograms (median 3 years apart) were calculated per breast separately for cases and controls and their difference evaluated by using the Wilcoxon signed-rank test. To simulate clinical practice where cancer laterality is unknown, we examined whether the absolute difference between breasts can discriminate cases from controls using area under the ROC curve (AUC) analysis, adjusting for age, BMI, and time. RESULTS: Among cases, the VPD and DV between mammograms of the cancerous breast decreased to a lesser degree (- 0.26% and - 2.10 cm3) than the normal breast (- 0.39% and - 2.74 cm3) for a difference of 0.13% (p value < 0.001) and 0.63 cm3 (p = 0.002), respectively. Among controls, the differences between breasts were nearly identical for VPD (- 0.02 [p = 0.92]) and DV (0.05 [p = 0.77]). The AUC for discriminating cases from controls using absolute difference between breasts was 0.54 (95% CI 0.52, 0.56) for VPD and 0.56 (95% CI, 0.54, 0.58) for DV. CONCLUSION: There is a small relative increase in volumetric density measures over time in the breast with cancer which is not found in the normal breast. However, the magnitude of this difference is small, and this measure alone does not appear to be a good discriminator between women with and without breast cancer.

13.
Circulation ; 140(15): 1251-1260, 2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31589485

RESUMO

BACKGROUND: Mitral stenosis frequently coexists in patients with severe aortic stenosis. Mitral stenosis severity evaluation is challenging in the setting of combined aortic stenosis and mitral stenosis because of hemodynamic interactions between the 2 valve lesions. The impact of aortic valve replacement (AVR) for severe aortic stenosis on mitral stenosis is unknown. This study aimed to assess the effect of AVR on mitral stenosis hemodynamics and the clinical outcomes of patients with severe aortic stenosis with and without mitral stenosis. METHODS: We retrospectively investigated patients who underwent surgical AVR or transcatheter AVR for severe aortic stenosis from 2008 to 2015. Mean transmitral gradient by Doppler echocardiography ≥4 mm Hg was identified as mitral stenosis; patients were then stratified according to mitral valve area (MVA, by continuity equation) as >2.0 cm2 or ≤2.0 cm2. MVA before and after AVR in patients with mitral stenosis were evaluated. Clinical outcomes of patients with and without mitral stenosis were compared using 1:2 matching for age, sex, left ventricular ejection fraction, method of AVR (surgical AVR versus transcatheter AVR) and year of AVR. RESULTS: Of 190 patients with severe aortic stenosis and mitral stenosis (age 76±9 years, 42% men), 184 were matched with 362 with severe aortic stenosis without mitral stenosis. Among all mitral stenosis patients, the mean MVA increased after AVR by 0.26±0.59 cm2 (from 2.00±0.50 to 2.26±0.62 cm2, P<0.01). MVA increased in 105 (55%) and remained unchanged in 34 (18%). Indexed stroke volume ≤45 mL/m2 (odds ratio [OR] 2.40; 95% CI, 1.15-5.01; P=0.020) and transcatheter AVR (OR, 2.36; 95% CI, 1.17-4.77; P=0.017) were independently associated with increase in MVA. Of 107 with significant mitral stenosis (MVA ≤2.0 cm2), MVA increased to >2.0 cm2 after AVR in 52 (49%, pseudo mitral stenosis) and remained ≤2.0 cm2 in 55 (51%, true mitral stenosis). During follow-up of median 2.9 (0.7-4.9) years, true mitral stenosis was an independent predictor of all-cause mortality (adjusted hazard ratio, 1.88; 95% CI, 1.20-2.94; P<0.01). CONCLUSIONS: MVA improved after AVR in nearly half of patients with severe aortic stenosis and mitral stenosis. MVA remained ≤2.0 cm2 (true mitral stenosis) in nearly half of patients with severe aortic stenosis and significant mitral stenosis; this was associated with worse survival among patients undergoing AVR for severe aortic stenosis.

14.
Circ Arrhythm Electrophysiol ; 12(9): e007284, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31450977

RESUMO

BACKGROUND: Sex and age have long been known to affect the ECG. Several biologic variables and anatomic factors may contribute to sex and age-related differences on the ECG. We hypothesized that a convolutional neural network (CNN) could be trained through a process called deep learning to predict a person's age and self-reported sex using only 12-lead ECG signals. We further hypothesized that discrepancies between CNN-predicted age and chronological age may serve as a physiological measure of health. METHODS: We trained CNNs using 10-second samples of 12-lead ECG signals from 499 727 patients to predict sex and age. The networks were tested on a separate cohort of 275 056 patients. Subsequently, 100 randomly selected patients with multiple ECGs over the course of decades were identified to assess within-individual accuracy of CNN age estimation. RESULTS: Of 275 056 patients tested, 52% were males and mean age was 58.6±16.2 years. For sex classification, the model obtained 90.4% classification accuracy with an area under the curve of 0.97 in the independent test data. Age was estimated as a continuous variable with an average error of 6.9±5.6 years (R-squared =0.7). Among 100 patients with multiple ECGs over the course of at least 2 decades of life, most patients (51%) had an average error between real age and CNN-predicted age of <7 years. Major factors seen among patients with a CNN-predicted age that exceeded chronologic age by >7 years included: low ejection fraction, hypertension, and coronary disease (P<0.01). In the 27% of patients where correlation was >0.8 between CNN-predicted and chronologic age, no incident events occurred over follow-up (33±12 years). CONCLUSIONS: Applying artificial intelligence to the ECG allows prediction of patient sex and estimation of age. The ability of an artificial intelligence algorithm to determine physiological age, with further validation, may serve as a measure of overall health.

15.
J Am Heart Assoc ; 8(15): e012943, 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31345101

RESUMO

Background Neprilysin is a metalloprotease involved in proteolysis of numerous peptides, including natriuretic peptides, and is of prognostic and therapeutic importance in heart failure with reduced ejection fraction. No studies have investigated circulating neprilysin in the community, its clinical correlates, or its relationship to cardiovascular disease in the general population. Methods and Results Plasma neprilysin was measured in 1536 participants from Olmsted County, Minnesota, using a commercially available sandwich ELISA assay. Clinical and echocardiographic correlates and subsequent outcomes were determined. Soluble neprilysin is non-normally distributed in the community (median: 3.9 ng/mL; interquartile range: 1.0-43.0 ng/mL). There was no relationship between plasma neprilysin and age (Spearman correlation: -0.04, P=0.16); body mass index (Spearman correlation: -0.04, P=0.16); glomerular filtration rate (Spearman correlation: -0.007, P=0.8); or A-, B-, or C-type natriuretic peptides (Spearman correlation: 0.03, P=0.22; -0.001, P=0.96; 0.01, P=0.67, respectively). Among tertiles of neprilysin, the lowest tertile group had the highest prevalence of smokers (P<0.001), hypertension (P=0.04), dyslipidemia (P=0.03), and diastolic dysfunction (P=0.02). Soluble neprilysin was not prospectively associated with death or heart failure over a median of 10.7 years. Conclusions In a large community-based cohort, for the first time, we described the distribution of circulating neprilysin in the general community. We observed that neprilysin does not correlate with natriuretic peptide levels and is not independently associated with adverse outcomes. The novel associations observed between low soluble neprilysin levels and an adverse cardiometabolic and smoking profile requires further investigation.

17.
Cancer Causes Control ; 30(10): 1103-1111, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31352658

RESUMO

PURPOSE: High mammographic breast density is a strong, well-established breast cancer risk factor. Whether stem cells may explain high breast cancer risk in dense breasts is unknown. We investigated the association between breast density and breast cancer risk by the status of stem cell markers CD44, CD24, and ALDH1A1 in the tumor. METHODS: We included 223 women with primary invasive or in situ breast cancer and 399 age-matched controls from Mayo Clinic Mammography Study. Percent breast density (PD), absolute dense area (DA), and non-dense area (NDA) were assessed using computer-assisted thresholding technique. Immunohistochemical analysis of the markers was performed on tumor tissue microarrays according to a standard protocol. We used polytomous logistic regression to quantify the associations of breast density measures with breast cancer risk across marker-defined tumor subtypes. RESULTS: Of the 223 cancers in the study, 182 were positive for CD44, 83 for CD24 and 52 for ALDH1A1. Associations of PD were not significantly different across t marker-defined subtypes (51% + vs. 11-25%: OR 2.83, 95% CI 1.49-5.37 for CD44+ vs. OR 1.87, 95% CI 0.47-7.51 for CD44-, p-heterogeneity = 0.66; OR 2.80, 95% CI 1.27-6.18 for CD24+ vs. OR 2.44, 95% CI 1.14-5.22 for CD24-, p-heterogeneity = 0.61; OR 3.04, 95% CI 1.14-8.10 for ALDH1A1+ vs. OR 2.57. 95% CI 1.30-5.08 for ALDH1A1-, p-heterogeneity = 0.94). Positive associations of DA and inverse associations of NDA with breast cancer risk were similar across marker-defined subtypes. CONCLUSIONS: We found no evidence of differential associations of breast density with breast cancer risk by the status of stem cell markers. Further studies in larger study populations are warranted to confirm these associations.


Assuntos
Biomarcadores Tumorais/metabolismo , Densidade da Mama , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/metabolismo , Mamografia , Idoso , Mama/diagnóstico por imagem , Mama/metabolismo , Estudos de Casos e Controles , Feminino , Humanos , Pessoa de Meia-Idade , Fatores de Risco , Células-Tronco/metabolismo
18.
Int J Med Inform ; 128: 32-38, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31160009

RESUMO

BACKGROUND: The management of hypertrophic cardiomyopathy (HCM) patients requires the knowledge of risk factors associated with sudden cardiac death (SCD). SCD risk factors such as syncope and family history of SCD (FH-SCD) as well as family history of HCM (FH-HCM) are documented in electronic health records (EHRs) as clinical narratives. Automated extraction of risk factors from clinical narratives by natural language processing (NLP) may expedite management workflow of HCM patients. The aim of this study was to develop and deploy NLP algorithms for automated extraction of syncope, FH-SCD, and FH-HCM from clinical narratives. METHODS AND RESULTS: We randomly selected 200 patients from the Mayo HCM registry for development (n = 100) and testing (n = 100) of NLP algorithms for extraction of syncope, FH-SCD as well as FH-HCM from clinical narratives of EHRs. The clinical reference standard was manually abstracted by 2 independent annotators. Performance of NLP algorithms was compared to aggregation and summarization of data entries in the HCM registry for syncope, FH-SCD, and FH-HCM. We also compared the NLP algorithms with billing codes for syncope as well as responses to patient survey questions for FH-SCD and FH-HCM. These analyses demonstrated NLP had superior sensitivity (0.96 vs 0.39, p < 0.001) and comparable specificity (0.90 vs 0.92, p = 0.74) and PPV (0.90 vs 0.83, p = 0.37) compared to billing codes for syncope. For FH-SCD, NLP outperformed survey responses for all parameters (sensitivity: 0.91 vs 0.59, p = 0.002; specificity: 0.98 vs 0.50, p < 0.001; PPV: 0.97 vs 0.38, p < 0.001). NLP also achieved superior sensitivity (0.95 vs 0.24, p < 0.001) with comparable specificity (0.95 vs 1.0, p-value not calculable) and positive predictive value (PPV) (0.92 vs 1.0, p = 0.09) compared to survey responses for FH-HCM. CONCLUSIONS: Automated extraction of syncope, FH-SCD and FH-HCM using NLP is feasible and has promise to increase efficiency of workflow for providers managing HCM patients.


Assuntos
Algoritmos , Cardiomiopatia Hipertrófica/complicações , Morte Súbita Cardíaca/etiologia , Registros Eletrônicos de Saúde/estatística & dados numéricos , Processamento de Linguagem Natural , Morte Súbita Cardíaca/prevenção & controle , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco
19.
Breast Cancer Res ; 21(1): 68, 2019 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-31118087

RESUMO

BACKGROUND: Mammographic breast density, adjusted for age and body mass index, and a polygenic risk score (PRS), comprised of common genetic variation, are both strong risk factors for breast cancer and increase discrimination of risk models. Understanding their joint contribution will be important to more accurately predict risk. METHODS: Using 3628 breast cancer cases and 5126 controls of European ancestry from eight case-control studies, we evaluated joint associations of a 77-single nucleotide polymorphism (SNP) PRS and quantitative mammographic density measures with breast cancer. Mammographic percent density and absolute dense area were evaluated using thresholding software and examined as residuals after adjusting for age, 1/BMI, and study. PRS and adjusted density phenotypes were modeled both continuously (per 1 standard deviation, SD) and categorically. We fit logistic regression models and tested the null hypothesis of multiplicative joint associations for PRS and adjusted density measures using likelihood ratio and global and tail-based goodness of fit tests within the subset of six cohort or population-based studies. RESULTS: Adjusted percent density (odds ratio (OR) = 1.45 per SD, 95% CI 1.38-1.52), adjusted absolute dense area (OR = 1.34 per SD, 95% CI 1.28-1.41), and the 77-SNP PRS (OR = 1.52 per SD, 95% CI 1.45-1.59) were associated with breast cancer risk. There was no evidence of interaction of the PRS with adjusted percent density or dense area on risk of breast cancer by either the likelihood ratio (P > 0.21) or goodness of fit tests (P > 0.09), whether assessed continuously or categorically. The joint association (OR) was 2.60 in the highest categories of adjusted PD and PRS and 0.34 in the lowest categories, relative to women in the second density quartile and middle PRS quintile. CONCLUSIONS: The combined associations of the 77-SNP PRS and adjusted density measures are generally well described by multiplicative models, and both risk factors provide independent information on breast cancer risk.


Assuntos
Biomarcadores Tumorais , Densidade da Mama/genética , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Herança Multifatorial , Adulto , Idoso , Algoritmos , Índice de Massa Corporal , Estudos de Casos e Controles , Feminino , Humanos , Pessoa de Meia-Idade , Modelos Biológicos , Razão de Chances , Polimorfismo de Nucleotídeo Único , Medição de Risco , Fatores de Risco
20.
Breast Cancer Res Treat ; 177(1): 165-173, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31129803

RESUMO

BACKGROUND: Breast density and body mass index (BMI) are used for breast cancer risk stratification. We evaluate whether the positive association between volumetric breast density and breast cancer risk is strengthened with increasing BMI. METHODS: The San Francisco Mammography Registry and Mayo Clinic Rochester identified 781 premenopausal and 1850 postmenopausal women with breast cancer diagnosed between 2007 and 2015 that had a screening digital mammogram at least 6 months prior to diagnosis. Up to three controls (N = 3535) were matched per case on age, race, date, mammography machine, and state. Volumetric percent density (VPD) and dense volume (DV) were measured with Volpara™. Breast cancer risk was assessed with logistic regression stratified by menopause status. Multiplicative interaction tests assessed whether the association of density measures was differential by BMI categories. RESULTS: The increased risk of breast cancer associated with VPD was strengthened with higher BMI for both premenopausal (pinteraction = 0.01) and postmenopausal (pinteraction = 0.0003) women. For BMI < 25, 25-30, and ≥ 30 kg/m2, ORs for breast cancer for a 1 SD increase in VPD were 1.24, 1.65, and 1.97 for premenopausal, and 1.20, 1.55, and 2.25 for postmenopausal women, respectively. ORs for breast cancer for a 1 SD increase in DV were 1.39, 1.33, and 1.51 for premenopausal (pinteraction = 0.58), and 1.31, 1.34, and 1.65 (pinteraction = 0.03) for postmenopausal women for BMI < 25, 25-30 and ≥ 30 kg/m2, respectively. CONCLUSIONS: The effect of volumetric percent density on breast cancer risk is strongest in overweight and obese women. These associations have clinical relevance for informing prevention strategies.


Assuntos
Índice de Massa Corporal , Densidade da Mama , Neoplasias da Mama/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/etiologia , Neoplasias da Mama/patologia , Estudos de Casos e Controles , Suscetibilidade a Doenças , Detecção Precoce de Câncer , Feminino , Humanos , Mamografia , Programas de Rastreamento , Menopausa , Pessoa de Meia-Idade , Vigilância em Saúde Pública , Sistema de Registros , Risco
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